OBG Management

Program Director

Steven R. Goldstein, MD, CCD, NCMP, FACOG
Professor of Obstetrics and Gynecology
New York University School of Medicine
Director of Gynecological Ultrasound
Co-Director of Bone Densitometry
Department of Obstetrics and Gynecology
New York University Medical Center
New York, New York

Authors/Editors

Reni S. Butler, MD
Assistant Professor, Diagnostic Radiology
Yale University
New Haven, Connecticut

Bonnie N. Joe, MD, PhD, FSBI
Professor of Radiology and Biomedical Imaging
Chief, Breast Imaging
University of California, San Francisco
San Francisco, California

Bruce A. Porter, MD, FACR
Clinical Associate Professor
Department of Radiology
University of Washington School of Medicine
Seattle, Washington

Michael J. Ulissey, MD, FACR
Adjunct Professor of Radiology
University of Texas
Health Sciences Center
San Antonio, Texas
Breast Diagnostic Centers
Auburn and Federal Way, Washington

Conflict of Interest Disclosure

Steven R. Goldstein, MD, CCD, NCMP, FACOG
Consultant: Cook OB/GYN, fees received
No Disclosures to Declare
Reni S. Butler, MD; Bonnie N. Joe, MD, PhD, FSBI;
Bruce A. Porter, MD, FACR; Michael J. Ulissey, MD, FACR;
Heidi M. Wilson, Course Director

Program Director

Steven R. Goldstein, MD, CCD, NCMP, FACOG
Professor of Obstetrics and Gynecology
New York University School of Medicine
Director of Gynecological Ultrasound
Co-Director of Bone Densitometry
Department of Obstetrics and Gynecology
New York University Medical Center
New York, New York

Authors/Editors

Reni S. Butler, MD
Assistant Professor, Diagnostic Radiology
Yale University
New Haven, Connecticut

Bonnie N. Joe, MD, PhD, FSBI
Professor of Radiology and Biomedical Imaging
Chief, Breast Imaging
University of California, San Francisco
San Francisco, California

Bruce A. Porter, MD, FACR
Clinical Associate Professor
Department of Radiology
University of Washington School of Medicine
Seattle, Washington

Michael J. Ulissey, MD, FACR
Adjunct Professor of Radiology
University of Texas
Health Sciences Center
San Antonio, Texas
Breast Diagnostic Centers
Auburn and Federal Way, Washington

Conflict of Interest Disclosure

Steven R. Goldstein, MD, CCD, NCMP, FACOG
Consultant: Cook OB/GYN, fees received
No Disclosures to Declare
Reni S. Butler, MD; Bonnie N. Joe, MD, PhD, FSBI;
Bruce A. Porter, MD, FACR; Michael J. Ulissey, MD, FACR;
Heidi M. Wilson, Course Director

Program Director

Steven R. Goldstein, MD, CCD, NCMP, FACOG
Professor of Obstetrics and Gynecology
New York University School of Medicine
Director of Gynecological Ultrasound
Co-Director of Bone Densitometry
Department of Obstetrics and Gynecology
New York University Medical Center
New York, New York

Authors/Editors

Reni S. Butler, MD
Assistant Professor, Diagnostic Radiology
Yale University
New Haven, Connecticut

Bonnie N. Joe, MD, PhD, FSBI
Professor of Radiology and Biomedical Imaging
Chief, Breast Imaging
University of California, San Francisco
San Francisco, California

Bruce A. Porter, MD, FACR
Clinical Associate Professor
Department of Radiology
University of Washington School of Medicine
Seattle, Washington

Michael J. Ulissey, MD, FACR
Adjunct Professor of Radiology
University of Texas
Health Sciences Center
San Antonio, Texas
Breast Diagnostic Centers
Auburn and Federal Way, Washington

Conflict of Interest Disclosure

Steven R. Goldstein, MD, CCD, NCMP, FACOG
Consultant: Cook OB/GYN, fees received
No Disclosures to Declare
Reni S. Butler, MD; Bonnie N. Joe, MD, PhD, FSBI;
Bruce A. Porter, MD, FACR; Michael J. Ulissey, MD, FACR;
Heidi M. Wilson, Course Director

Access Dr. Burkman's Webcasts on contraception:

• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use

Access Dr. Burkman's Webcasts on contraception:

• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use

Access Dr. Burkman's Webcasts on contraception:

• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use

Chlorhexidine-alcohol is superior to iodine-alcohol for reducing SSIs after cesarean delivery_{Tuuli Mg, Liu J, Stout Mj, et al. A randomized trial comparing skin antiseptic agents at cesarean delivery. N Engl J Med. 2016;374(7):647-655.}

In the United States, cesarean delivery is the most commonly performed major surgical procedure, with 32.7% of births--or 1.3 million--occurring in this fashion in 2013.^1,2 In general, for all surgical procedures, the SSI rate is 2% to 5%, with the rate rising to 5% to 12% for cesarean delivery, especially in obese patients.^3-6 Not only do SSIs increase morbidity for the patient but they also contribute to high medical costs, with an estimated additional expense of $3,529 per cesarean-associated infection.⁷

Skin pathogens are a major source of SSIs. Choosing the proper antiseptic has the potential to decrease infection risk. While current guidelines recommend use of an antiseptic containing alcohol, it is unclear which disinfectant is the most effective agent to combine with the alcohol.³ 

Most trials evaluating preoperative antiseptic skin preparation have studied patients undergoing general surgery procedures. A well-designed trial by Darouiche and coauthors demonstrated that chlorhexidine was superior to iodine when used as an antiseptic for skin preparation.⁸ Interestingly, however, this trial, like most others, compared chlorhexidine-alcohol to iodine without alcohol. It is therefore unclear whether the chlorhexidine or the alcohol is responsible for the enhanced antiseptic effect.

Details of the studyIn the single-center randomized trial conducted by Tuuli and colleagues, patients were assigned to preoperative skin antisepsis with either chlorhexidine-alcohol (2% chlorhexidine gluconate with 70% isopropyl alcohol) or iodine-alcohol (8.3% povidone-iodine with 72.5% isopropyl alcohol). Antiseptic was applied according to the manufacturer's instructions, with a standard wait time of 3 minutes between application and skin incision. However, wait time was eliminated for patients undergoing emergency cesarean delivery. Additionally, patients received standard, weight-based preoperative antibiotic prophylaxis (agent not specified). 

The authors estimated the necessary sample size for the trial by assuming an 8% baseline SSI rate and an anticipated 50% reduction of infection in the chlorhexidine-alcohol group. Exclusion criteria included a known allergy to chlorhexidine, alcohol, iodine, or shellfish or a preexisting skin infection adjacent to the operative site.

In addition to assessing the primary outcome of SSI with the 2 preparations, the authors conducted 4 prespecified subgroup analyses. These subgroups were based on: type of cesarean delivery (scheduled vs unscheduled), body weight (obese vs nonobese), type of skin closure (subcuticular suture vs staples), and presence or absence of chronic medical conditions (diabetes, hypertension, renal disease). Additionally, a post hoc analysis was performed, comparing women with diabetes (gestational and pregestational) to those without diabetes.
 
A total of 1,636 pregnant women were screened for eligibility. Of these, 489 women were excluded because they did not meet inclusion criteria or declined to participate or because informed consent could not be obtained. Baseline characteristics were similar across both groups.

Patients were followed for 30 days after surgery. A total of 1,082 women (94.3% of sample size) completed the follow-up. Among these patients, the rate of SSI was significantly lower in the chlorhexidine-alcohol group (4.3%) compared with the iodine-alcohol group (7.7%, P = .02).

In the subgroup analyses, the frequency of SSI remained lower for the chlorhexidine-alcohol group than for the iodine-alcohol group. These reductions were not affected by whether the cesarean was scheduled or unscheduled, the presence or absence of obesity, the type of skin closure, the presence of chronic disease, or diabetes status.
 
Several secondary outcomes also were examined in this study. There were no significant differences between the 2 antiseptic groups with respect to rates of endometritis, hospital readmission for infection-related complications, length of hospital stay, use of other health care services (such as emergency department visits, additional wound surgery, and home health services), and rates of other wound complications (seroma, hematoma, and cellulitis). Patients in the chlorhexidine-alcohol group were significantly less likely than those in the iodine-alcohol group to have physician office visits for concerns about possible wound complications (P = .009).

The authors concluded that the use of chlorhexidine-alcohol was superior to iodine-alcohol in preventing SSI after cesarean delivery.

Study strengths and limitations The authors acknowledged that their study had some minor limitations. First, the trial was conducted at a single site, which may limit the generalizability of the findings. However, the study population was racially and economically diverse. Second, the lack of blinding among providers and participants may have introduced bias, although, as the authors explain, we would expect this bias to be largely nondirectional.

A major strength of this study is its randomized design. Another strength is that the authors included emergency cesarean deliveries in their analysis. Emergency procedures represent a substantial proportion of cesarean deliveries, and they place the patient at increased risk for SSIs because of limited time available to prepare the skin before surgery begins. Thus, it is of great interest that chlorhexidine-alcohol was so effective even in the highest-risk patients.
 
Several properties may make chlorhexidine superior to iodine as an antiseptic: high binding affinity for the skin, high antibacterial activity against both gram-positive and gram-negative bacteria, and longer residual effects than iodine. Additionally, iodine is inactivated by organic matter, such as body fluids, whereas chlorhexidine is not.
 
A recent study by Ngai and colleagues⁹ compared chlorhexidine-alcohol with iodine-alcohol for skin preparation before cesarean delivery. These authors found no difference in SSI when comparing the 2 solutions used separately or sequentially, except in morbidly obese women. In these women, sequential application of both solutions reduced the infection rate. However, this study specifically excluded emergency cesarean deliveries, making the generalizability of the results questionable.⁹

What this evidence means for practiceThis large, randomized study found chlorhexidine-alcohol to be superior to iodine-alchol in reducing the risk of SSIs after cesarean delivery. These results confirm those of previous studies from both the obstetric and general surgery literature. Although chlorhexidine-alcohol is more expensive than iodine-alcohol, we strongly recommend its use in patients having cesarean delivery.

Five effective oral and intramuscular antibiotic regimens for treating postpartum endometritis_{Meaney-Delman D, Bartlett LA, Gravett MG, Jamieson DJ. Oral and intramuscular treatment options for early postpartum endometritis in low-resource settings: a systematic review. Obstet Gynecol. 2015;125(4):789-800.}

The authors of this excellent systematic review on antibiotic treatments for early postpartum endometritis conducted their study in 3 phases. Initially, Meaney-Delman and colleagues searched the literature for reports of prospective studies that evaluated the use of oral and intramuscular (IM) antibiotics for treatment of patients who developed endometritis following either cesarean or vaginal delivery. When they discovered that these initial trials were few in number and of relatively poor quality, they reviewed more rigorous trials of intravenous (IV) antibiotics. Finally, they evaluated clinical trials that specifically identified microorganisms isolated from the uterus in patients with endometritis and used this information to help inform their recommendations for treatment options.

Details of the studyIn evaluating the trials of oral and IM antibiotics, the authors set as a standard for effectiveness a cure rate of 85%, a figure comparable to that generally achieved with IV antibiotics. They identified 2 oral antibiotic regimens that met this standard of effectiveness: amoxicillin-clavulanate (100% cure in 36 patients; 95% confidence interval [CI], 90-100) and ampicillin plus metronidazole (97% cure in 37 patients; 95% CI, 86-100).

Two studies demonstrated acceptable levels of cure with single-agent IM antibiotics: aztreonam (100% cure in 16 patients; 95% CI, 81-100) and imipenem (91% cure in 23 patients; 95% CI, 73-98). One additional trial demonstrated an acceptable clinical response rate when IV clindamycin was combined with IM gentamicin (100% cure in 54 patients; 95% CI, 94-100). By contrast, the authors noted, many different IV regimens--either as a single agent or as a drug combination--provided cure rates that equaled or exceeded 85%.

In the study's final phase, the authors provided an excellent overview of the polymicrobial nature of puerperal endometritis. As documented in multiple prior reports, the most common pathogens are the gram-negative anaerobic bacilli, such as Bacteroides and Prevotella species; the anaerobic gram-positive organisms, including Peptococcus and Peptostreptococcus species; aerobic gram-negative bacilli, such as Escherichia coli, Klebsiella pneumoniae, and Proteus species; and aerobic gram-positive cocci, such as group B streptococci, enterococci, and staphylococci.

Recommended regimens. Based on their review of clinical and microbiological studies, the authors proposed 5 oral or combined oral-IM treatment regimens that could be used in low-resource settings:

• oral clindamycin (600 mg every 6 hours)
• plus IM gentamicin (4.5 g every 24 hours)
• oral amoxicillin-clavulanic acid (875 mg every 12 hours)
• IM cefotetan (2 g every 8 hours)
• IM meropenem or imipenem-cilastatin (500 mg every 8 hours)
• oral amoxicillin (500 mg every 8 hours) plus oral metronidazole (500 mg every 8 hours).

Typical endometritis treamentEndometritis is the single most common complication following cesarean delivery. The frequency of its occurrence depends on several factors, including: the socioeconomic characteristics of the patient population, length of labor, length of ruptured membranes, number of internal vaginal examinations, presence of preexisting lower genital tract infection, type of anesthesia, surgical technique, and use of prophylactic antibiotics. Endometritis is much less common after vaginal delivery but still may occur in 3% to 5% of patients.¹⁰

Endometritis is clearly a polymicrobial infection that includes multiple aerobic and anaerobic organisms. Accordingly, antibiotic therapy must target all the major groups of pathogens. The usual standard of care for treatment of early-onset endometritis is IV antibiotics, and patients typically are treated until they have been afebrile and asymptomatic for a minimum of 24 hours. Several different IV regimens provide acceptable treatment¹⁰:

• clindamycin plus gentamicin
• metronidazole plus ampicillin plus gentamicin
• extended-spectrum cephalosporins, such as cefepime, cefotetan, and cefoxitin
• extended-spectrum penicillins, such as ampicillin-sulbactam, piperacillin- tazobactam, and ticarcillin-clavulanic acid
• carbapenems, such as imipenem-cilastatin and meropenem.

What this evidence means for practiceClearly, IV antibiotics, even generic drugs, are more expensive than oral agents. They also are more difficult to administer than oral or IM drugs. The systematic review by Meaney-Delman and co-workers is therefore a very important contribution to the literature and should reassure clinicians practicing in low-resource settings that oral and oral-IM regimens can provide safe and effective treatment for endometritis. Until more rigorous comparative trials are conducted, however, we agree with the authors' caveat that, for now, such treatment should be limited to individuals whose infection occurred after vaginal delivery or who have evidence of only mild postcesarean endometritis.

Treatment options for chlamydia infection: How does azithromycin compare with doxycycline?_{Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med. 2015;373(26):2512-2521.}

The Centers for Disease Control and Prevention recommendations for treatment of chlamydia genital tract infection are either oral doxycycline, 100 mg twice daily for 7 days, or azithromycin, 1,000 mg in a single dose.¹¹ Recent reports have raised questions about the relative effectiveness of single-dose azithromycin compared with the multiple-day doxycycline regimen. Accordingly, Geisler and colleagues conducted an interesting randomized controlled trial to determine if azithromycin is noninferior to doxycycline.

Details of the studyThe study took place in a unique institutional setting--the Los Angeles County youth correctional facilities. Participants were young men and women, aged 12 to 21 years, who tested positive for chlamydia infection by a nucleic acid amplification test on entry to the correctional facility. Participants then were randomly assigned to receive either doxycycline or azithromycin in the doses described above. The primary outcome was the percent of individuals who still tested positive for chlamydia 28 days after treatment.

Of note, all patients took their medication under direct observation of corrections officers and, with rare exceptions, did not engage in sexual activity during the period of observation. Because this was a noninferiority trial, Geisler and colleagues analyzed the outcomes only of the individuals who actually took their medication in accordance with the assigned protocol. A priori, the authors established a 95% CI of <5% difference in effectiveness as indicative of noninferiority.

Overall, 155 patients in each treatment group completed the trial according to the assigned protocol. No treatment failures occurred in the doxycycline group (0%; 95% CI, 0.0-2.4). Five treatment failures occurred in the azithromycin group (3.2%; 95% CI, 0.4-7.4), in 1 female and 4 male participants. Because the 95% CI for the difference in treatment outcome exceeded 5%, the authors were unable to conclude that azithromycin was noninferior to doxycycline.

Consider real-world treatment adherence in these resultsFor several reasons, we do not conclude from this article that ObGyns should now stop using azithromycin to treat patients with chlamydia infection. First, the actual per protocol sample size was still relatively small. If there had been just 2 fewer failures in the azithromycin group, the 95% CI for the difference in outcomes would have been less than 5%, and the authors would have concluded that the 2 drug regimens were noninferior. Second, 4 of the 5 treatment failures in the azithromycin group were in male rather than female participants. Third, the unique study design resulted in almost perfect adherence with the 7-day doxycycline treatment regimen. Such adherence is very unlikely in other practice settings, and patients who do not complete their treatment regimen are significantly more likely to fail therapy. Finally, azithromycin is definitely preferred in pregnancy because we try to avoid maternal/fetal exposure to drugs such as tetracycline and doxycycline.

What this evidence means for practiceIn this study, both doxycycline and azithromycin were highly effective (100% and 97%, respectively) for treating chlamydia genital tract infection, and they are comparable in cost. In our opinion, the improved adherence that is possible with single-dose azithromycin, the greater safety in pregnancy, and the excellent tolerability of this drug outweigh its slightly deceased rate of microbiologic cure.

Vaccine effective against hepatitis E for 4+ years_{Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015;372(10):914-922.}

This study conducted by Zhang and colleagues in Dongtai, China, is an extended follow-up study of the hepatitis E virus (HEV) vaccine (Hecolin; Xiamen Innovax Biotech). A recombinant vaccine directed against HEV genotype 1, Hecolin has been used in China since 2012.

In the initial efficacy study, healthy adults aged 16 to 65 years were randomly assigned to receive either the hepatitis E vaccine (vaccine group, 56,302 participants) or the hepatitis B vaccine (control group, 56,302 participants). Vaccine administration occurred at 0, 1, and 6 months, and participants were followed for a total of 19 months.

Details of the studyThe follow-up study was designed to assess the efficacy, immunogenicity, and safety of the HEV vaccine up to 4.5 years postvaccination. All health care centers (205 village and private clinics) in the study area were enrolled in the program. The treatment assignments of all patients remained double blinded. Unblinding occurred only after the data on safety, efficacy, and immunogenicity had been locked.

A diagnosis of HEV infection was made if at least 2 of the following markers were present: a positive test for immunoglobulin M antibodies against HEV, a positive test for HEV RNA, or a serum concentration of immunoglobulin G (IgG) antibodies against HEV that was at least 4 times higher than previously measured at any time during the same illness. Vaccine immunogenicity was assessed by testing serum samples for IgG antibodies against HEV at regular intervals after the vaccination was given.

Over the 4.5-year study period, 7 cases of hepatitis E occurred in the vaccine group, and 53 in the control group. Vaccine efficacy was 86.8% (P<.001) in the modified intention-to-treat analysis. Among patients who received 3 doses of HEV vaccine and who were seronegative at the start of the study, 87% maintained antibodies against HEV for 4.5 years. Within the control group, HEV titers developed in 9% of participants. The vaccine and control groups had similar rates of adverse events.

The authors concluded that the HEV vaccine induced antibodies against hepatitis E that lasted up to 4.5 years. Additionally, 2 doses of vaccine induced slightly lower levels of antibody than those produced by 3 doses of the vaccine. Finally, all participants in the vaccine group who developed HEV had antibodies with high or moderate avidity, indicating an anamnestic response from previous immunity. Most participants in the control group who developed HEV, however, had antibodies with low avidity, indicating no previous immunity.
The burden of HEVHepatitis E is a serious infection and is the most common waterborne illness in the world. It occurs mainly in developing countries with limited resources. HEV infection is caused by genotypes 1, 2, 3, or 4, although all 4 genotypes belong to the same serotype. Genotypes 1 and 2 are typically waterborne, and genotypes 3 and 4 are typically transmitted from animals and humans. In general, the case fatality rate associated with HEV infection is 1% to 3%.¹² In pregnancy, this rate increases to 5% to 25%.^13,14 In Bangladesh, for example, hepatitis E is responsible for more than 1,000 deaths per year among pregnant women.¹⁵

Clinical presentation of HEV infection is a spectrum, with most symptomatic patients presenting with acute, self-limited hepatitis. Severe cases may be associated with pancreatitis, arthritis, aplastic anemia, and neurologic complications, such as seizures. Populations at risk for more severe cases include pregnant women, elderly men, and patients with pre‑ existing, chronic liver disease. 

What this evidence means for practiceStandard sanitary precautions, such as clean drinking water, traditionally have been considered the mainstay of hepatitis E prevention. However, as the study authors indicate, recent severe outbreaks of HEV infection in Sudan and Uganda have occurred despite these measures. Thus, an effective vaccine that produces long-standing immunity has great potential for reducing morbidity and mortality in these countries. The present vaccine appears to be highly effective and safe. The principal unanswered question is the duration of immunity.

My patients are asking, "What is the best insect repellent to try to avoid Zika virus?"

With summer upon us we have received questions from colleagues about the best over-the-counter insect repellents to advise their pregnant patients to use.

The preferred insect repellent for skin coverage is DEET (N,N-diethyl-meta-toluamide) (TABLE). Oil of lemon/eucalyptus/para-menthane-diol and IR3535 are also acceptable repellents to use on the skin that are safe for use in pregnancy. In addition, instruct patients to spray permethrin on their clothing or to buy clothing (boots, pants, socks) that has been pretreated with permethrin.^1,2
Anushka Chelliah, MD, and Patrick Duff, MD.

Abbreviation: OTC, over the counter.

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Coming soon to OBG Management
Drs. Chelliah and Duff follow-up on their March 2016 examination of Zika virus infection with:  

• Latest information on Zika virus-associated birth defects
• Ultrasonographic and radiologic evidence of abnormalities in the fetus and newborn exposed to Zika virus infection
• Link between Zika virus infection and serious neurologic complications in adults
• New recommendations for preventing sexual transmission of Zika virus infection 

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Dr. Chelliah is a Maternal Fetal Medicine-Fellow in the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.

Dr. Duff is Associate Dean for Student Affairs and Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, University of Florida College of Medicine.

The author reports no financial relationships relevant to this article.

---

References

1. Peterson EE, Staples JE, Meaney-Delman D, et al. Interim guidelines for pregnant women during a Zika virus outbreak--United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(2):30-33.
2. Centers for Disease Control and Prevention. CDC Features: Avoid mosquito bites. http://www.cdc.gov/Features/stopmosquitoes/index.html. Updated March 18, 2016. Accessed May 10, 2016.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Chlorhexidine-alcohol is superior to iodine-alcohol for reducing SSIs after cesarean delivery_{Tuuli Mg, Liu J, Stout Mj, et al. A randomized trial comparing skin antiseptic agents at cesarean delivery. N Engl J Med. 2016;374(7):647-655.}

In the United States, cesarean delivery is the most commonly performed major surgical procedure, with 32.7% of births--or 1.3 million--occurring in this fashion in 2013.^1,2 In general, for all surgical procedures, the SSI rate is 2% to 5%, with the rate rising to 5% to 12% for cesarean delivery, especially in obese patients.^3-6 Not only do SSIs increase morbidity for the patient but they also contribute to high medical costs, with an estimated additional expense of $3,529 per cesarean-associated infection.⁷

Skin pathogens are a major source of SSIs. Choosing the proper antiseptic has the potential to decrease infection risk. While current guidelines recommend use of an antiseptic containing alcohol, it is unclear which disinfectant is the most effective agent to combine with the alcohol.³ 

Most trials evaluating preoperative antiseptic skin preparation have studied patients undergoing general surgery procedures. A well-designed trial by Darouiche and coauthors demonstrated that chlorhexidine was superior to iodine when used as an antiseptic for skin preparation.⁸ Interestingly, however, this trial, like most others, compared chlorhexidine-alcohol to iodine without alcohol. It is therefore unclear whether the chlorhexidine or the alcohol is responsible for the enhanced antiseptic effect.

Details of the studyIn the single-center randomized trial conducted by Tuuli and colleagues, patients were assigned to preoperative skin antisepsis with either chlorhexidine-alcohol (2% chlorhexidine gluconate with 70% isopropyl alcohol) or iodine-alcohol (8.3% povidone-iodine with 72.5% isopropyl alcohol). Antiseptic was applied according to the manufacturer's instructions, with a standard wait time of 3 minutes between application and skin incision. However, wait time was eliminated for patients undergoing emergency cesarean delivery. Additionally, patients received standard, weight-based preoperative antibiotic prophylaxis (agent not specified). 

The authors estimated the necessary sample size for the trial by assuming an 8% baseline SSI rate and an anticipated 50% reduction of infection in the chlorhexidine-alcohol group. Exclusion criteria included a known allergy to chlorhexidine, alcohol, iodine, or shellfish or a preexisting skin infection adjacent to the operative site.

In addition to assessing the primary outcome of SSI with the 2 preparations, the authors conducted 4 prespecified subgroup analyses. These subgroups were based on: type of cesarean delivery (scheduled vs unscheduled), body weight (obese vs nonobese), type of skin closure (subcuticular suture vs staples), and presence or absence of chronic medical conditions (diabetes, hypertension, renal disease). Additionally, a post hoc analysis was performed, comparing women with diabetes (gestational and pregestational) to those without diabetes.
 
A total of 1,636 pregnant women were screened for eligibility. Of these, 489 women were excluded because they did not meet inclusion criteria or declined to participate or because informed consent could not be obtained. Baseline characteristics were similar across both groups.

Patients were followed for 30 days after surgery. A total of 1,082 women (94.3% of sample size) completed the follow-up. Among these patients, the rate of SSI was significantly lower in the chlorhexidine-alcohol group (4.3%) compared with the iodine-alcohol group (7.7%, P = .02).

In the subgroup analyses, the frequency of SSI remained lower for the chlorhexidine-alcohol group than for the iodine-alcohol group. These reductions were not affected by whether the cesarean was scheduled or unscheduled, the presence or absence of obesity, the type of skin closure, the presence of chronic disease, or diabetes status.
 
Several secondary outcomes also were examined in this study. There were no significant differences between the 2 antiseptic groups with respect to rates of endometritis, hospital readmission for infection-related complications, length of hospital stay, use of other health care services (such as emergency department visits, additional wound surgery, and home health services), and rates of other wound complications (seroma, hematoma, and cellulitis). Patients in the chlorhexidine-alcohol group were significantly less likely than those in the iodine-alcohol group to have physician office visits for concerns about possible wound complications (P = .009).

The authors concluded that the use of chlorhexidine-alcohol was superior to iodine-alcohol in preventing SSI after cesarean delivery.

Study strengths and limitations The authors acknowledged that their study had some minor limitations. First, the trial was conducted at a single site, which may limit the generalizability of the findings. However, the study population was racially and economically diverse. Second, the lack of blinding among providers and participants may have introduced bias, although, as the authors explain, we would expect this bias to be largely nondirectional.

A major strength of this study is its randomized design. Another strength is that the authors included emergency cesarean deliveries in their analysis. Emergency procedures represent a substantial proportion of cesarean deliveries, and they place the patient at increased risk for SSIs because of limited time available to prepare the skin before surgery begins. Thus, it is of great interest that chlorhexidine-alcohol was so effective even in the highest-risk patients.
 
Several properties may make chlorhexidine superior to iodine as an antiseptic: high binding affinity for the skin, high antibacterial activity against both gram-positive and gram-negative bacteria, and longer residual effects than iodine. Additionally, iodine is inactivated by organic matter, such as body fluids, whereas chlorhexidine is not.
 
A recent study by Ngai and colleagues⁹ compared chlorhexidine-alcohol with iodine-alcohol for skin preparation before cesarean delivery. These authors found no difference in SSI when comparing the 2 solutions used separately or sequentially, except in morbidly obese women. In these women, sequential application of both solutions reduced the infection rate. However, this study specifically excluded emergency cesarean deliveries, making the generalizability of the results questionable.⁹

What this evidence means for practiceThis large, randomized study found chlorhexidine-alcohol to be superior to iodine-alchol in reducing the risk of SSIs after cesarean delivery. These results confirm those of previous studies from both the obstetric and general surgery literature. Although chlorhexidine-alcohol is more expensive than iodine-alcohol, we strongly recommend its use in patients having cesarean delivery.

Five effective oral and intramuscular antibiotic regimens for treating postpartum endometritis_{Meaney-Delman D, Bartlett LA, Gravett MG, Jamieson DJ. Oral and intramuscular treatment options for early postpartum endometritis in low-resource settings: a systematic review. Obstet Gynecol. 2015;125(4):789-800.}

The authors of this excellent systematic review on antibiotic treatments for early postpartum endometritis conducted their study in 3 phases. Initially, Meaney-Delman and colleagues searched the literature for reports of prospective studies that evaluated the use of oral and intramuscular (IM) antibiotics for treatment of patients who developed endometritis following either cesarean or vaginal delivery. When they discovered that these initial trials were few in number and of relatively poor quality, they reviewed more rigorous trials of intravenous (IV) antibiotics. Finally, they evaluated clinical trials that specifically identified microorganisms isolated from the uterus in patients with endometritis and used this information to help inform their recommendations for treatment options.

Details of the studyIn evaluating the trials of oral and IM antibiotics, the authors set as a standard for effectiveness a cure rate of 85%, a figure comparable to that generally achieved with IV antibiotics. They identified 2 oral antibiotic regimens that met this standard of effectiveness: amoxicillin-clavulanate (100% cure in 36 patients; 95% confidence interval [CI], 90-100) and ampicillin plus metronidazole (97% cure in 37 patients; 95% CI, 86-100).

Two studies demonstrated acceptable levels of cure with single-agent IM antibiotics: aztreonam (100% cure in 16 patients; 95% CI, 81-100) and imipenem (91% cure in 23 patients; 95% CI, 73-98). One additional trial demonstrated an acceptable clinical response rate when IV clindamycin was combined with IM gentamicin (100% cure in 54 patients; 95% CI, 94-100). By contrast, the authors noted, many different IV regimens--either as a single agent or as a drug combination--provided cure rates that equaled or exceeded 85%.

In the study's final phase, the authors provided an excellent overview of the polymicrobial nature of puerperal endometritis. As documented in multiple prior reports, the most common pathogens are the gram-negative anaerobic bacilli, such as Bacteroides and Prevotella species; the anaerobic gram-positive organisms, including Peptococcus and Peptostreptococcus species; aerobic gram-negative bacilli, such as Escherichia coli, Klebsiella pneumoniae, and Proteus species; and aerobic gram-positive cocci, such as group B streptococci, enterococci, and staphylococci.

Recommended regimens. Based on their review of clinical and microbiological studies, the authors proposed 5 oral or combined oral-IM treatment regimens that could be used in low-resource settings:

• oral clindamycin (600 mg every 6 hours)
• plus IM gentamicin (4.5 g every 24 hours)
• oral amoxicillin-clavulanic acid (875 mg every 12 hours)
• IM cefotetan (2 g every 8 hours)
• IM meropenem or imipenem-cilastatin (500 mg every 8 hours)
• oral amoxicillin (500 mg every 8 hours) plus oral metronidazole (500 mg every 8 hours).

Typical endometritis treamentEndometritis is the single most common complication following cesarean delivery. The frequency of its occurrence depends on several factors, including: the socioeconomic characteristics of the patient population, length of labor, length of ruptured membranes, number of internal vaginal examinations, presence of preexisting lower genital tract infection, type of anesthesia, surgical technique, and use of prophylactic antibiotics. Endometritis is much less common after vaginal delivery but still may occur in 3% to 5% of patients.¹⁰

Endometritis is clearly a polymicrobial infection that includes multiple aerobic and anaerobic organisms. Accordingly, antibiotic therapy must target all the major groups of pathogens. The usual standard of care for treatment of early-onset endometritis is IV antibiotics, and patients typically are treated until they have been afebrile and asymptomatic for a minimum of 24 hours. Several different IV regimens provide acceptable treatment¹⁰:

• clindamycin plus gentamicin
• metronidazole plus ampicillin plus gentamicin
• extended-spectrum cephalosporins, such as cefepime, cefotetan, and cefoxitin
• extended-spectrum penicillins, such as ampicillin-sulbactam, piperacillin- tazobactam, and ticarcillin-clavulanic acid
• carbapenems, such as imipenem-cilastatin and meropenem.

What this evidence means for practiceClearly, IV antibiotics, even generic drugs, are more expensive than oral agents. They also are more difficult to administer than oral or IM drugs. The systematic review by Meaney-Delman and co-workers is therefore a very important contribution to the literature and should reassure clinicians practicing in low-resource settings that oral and oral-IM regimens can provide safe and effective treatment for endometritis. Until more rigorous comparative trials are conducted, however, we agree with the authors' caveat that, for now, such treatment should be limited to individuals whose infection occurred after vaginal delivery or who have evidence of only mild postcesarean endometritis.

Treatment options for chlamydia infection: How does azithromycin compare with doxycycline?_{Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med. 2015;373(26):2512-2521.}

The Centers for Disease Control and Prevention recommendations for treatment of chlamydia genital tract infection are either oral doxycycline, 100 mg twice daily for 7 days, or azithromycin, 1,000 mg in a single dose.¹¹ Recent reports have raised questions about the relative effectiveness of single-dose azithromycin compared with the multiple-day doxycycline regimen. Accordingly, Geisler and colleagues conducted an interesting randomized controlled trial to determine if azithromycin is noninferior to doxycycline.

Details of the studyThe study took place in a unique institutional setting--the Los Angeles County youth correctional facilities. Participants were young men and women, aged 12 to 21 years, who tested positive for chlamydia infection by a nucleic acid amplification test on entry to the correctional facility. Participants then were randomly assigned to receive either doxycycline or azithromycin in the doses described above. The primary outcome was the percent of individuals who still tested positive for chlamydia 28 days after treatment.

Of note, all patients took their medication under direct observation of corrections officers and, with rare exceptions, did not engage in sexual activity during the period of observation. Because this was a noninferiority trial, Geisler and colleagues analyzed the outcomes only of the individuals who actually took their medication in accordance with the assigned protocol. A priori, the authors established a 95% CI of <5% difference in effectiveness as indicative of noninferiority.

Overall, 155 patients in each treatment group completed the trial according to the assigned protocol. No treatment failures occurred in the doxycycline group (0%; 95% CI, 0.0-2.4). Five treatment failures occurred in the azithromycin group (3.2%; 95% CI, 0.4-7.4), in 1 female and 4 male participants. Because the 95% CI for the difference in treatment outcome exceeded 5%, the authors were unable to conclude that azithromycin was noninferior to doxycycline.

Consider real-world treatment adherence in these resultsFor several reasons, we do not conclude from this article that ObGyns should now stop using azithromycin to treat patients with chlamydia infection. First, the actual per protocol sample size was still relatively small. If there had been just 2 fewer failures in the azithromycin group, the 95% CI for the difference in outcomes would have been less than 5%, and the authors would have concluded that the 2 drug regimens were noninferior. Second, 4 of the 5 treatment failures in the azithromycin group were in male rather than female participants. Third, the unique study design resulted in almost perfect adherence with the 7-day doxycycline treatment regimen. Such adherence is very unlikely in other practice settings, and patients who do not complete their treatment regimen are significantly more likely to fail therapy. Finally, azithromycin is definitely preferred in pregnancy because we try to avoid maternal/fetal exposure to drugs such as tetracycline and doxycycline.

What this evidence means for practiceIn this study, both doxycycline and azithromycin were highly effective (100% and 97%, respectively) for treating chlamydia genital tract infection, and they are comparable in cost. In our opinion, the improved adherence that is possible with single-dose azithromycin, the greater safety in pregnancy, and the excellent tolerability of this drug outweigh its slightly deceased rate of microbiologic cure.

Vaccine effective against hepatitis E for 4+ years_{Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015;372(10):914-922.}

This study conducted by Zhang and colleagues in Dongtai, China, is an extended follow-up study of the hepatitis E virus (HEV) vaccine (Hecolin; Xiamen Innovax Biotech). A recombinant vaccine directed against HEV genotype 1, Hecolin has been used in China since 2012.

In the initial efficacy study, healthy adults aged 16 to 65 years were randomly assigned to receive either the hepatitis E vaccine (vaccine group, 56,302 participants) or the hepatitis B vaccine (control group, 56,302 participants). Vaccine administration occurred at 0, 1, and 6 months, and participants were followed for a total of 19 months.

Details of the studyThe follow-up study was designed to assess the efficacy, immunogenicity, and safety of the HEV vaccine up to 4.5 years postvaccination. All health care centers (205 village and private clinics) in the study area were enrolled in the program. The treatment assignments of all patients remained double blinded. Unblinding occurred only after the data on safety, efficacy, and immunogenicity had been locked.

A diagnosis of HEV infection was made if at least 2 of the following markers were present: a positive test for immunoglobulin M antibodies against HEV, a positive test for HEV RNA, or a serum concentration of immunoglobulin G (IgG) antibodies against HEV that was at least 4 times higher than previously measured at any time during the same illness. Vaccine immunogenicity was assessed by testing serum samples for IgG antibodies against HEV at regular intervals after the vaccination was given.

Over the 4.5-year study period, 7 cases of hepatitis E occurred in the vaccine group, and 53 in the control group. Vaccine efficacy was 86.8% (P<.001) in the modified intention-to-treat analysis. Among patients who received 3 doses of HEV vaccine and who were seronegative at the start of the study, 87% maintained antibodies against HEV for 4.5 years. Within the control group, HEV titers developed in 9% of participants. The vaccine and control groups had similar rates of adverse events.

The authors concluded that the HEV vaccine induced antibodies against hepatitis E that lasted up to 4.5 years. Additionally, 2 doses of vaccine induced slightly lower levels of antibody than those produced by 3 doses of the vaccine. Finally, all participants in the vaccine group who developed HEV had antibodies with high or moderate avidity, indicating an anamnestic response from previous immunity. Most participants in the control group who developed HEV, however, had antibodies with low avidity, indicating no previous immunity.
The burden of HEVHepatitis E is a serious infection and is the most common waterborne illness in the world. It occurs mainly in developing countries with limited resources. HEV infection is caused by genotypes 1, 2, 3, or 4, although all 4 genotypes belong to the same serotype. Genotypes 1 and 2 are typically waterborne, and genotypes 3 and 4 are typically transmitted from animals and humans. In general, the case fatality rate associated with HEV infection is 1% to 3%.¹² In pregnancy, this rate increases to 5% to 25%.^13,14 In Bangladesh, for example, hepatitis E is responsible for more than 1,000 deaths per year among pregnant women.¹⁵

Clinical presentation of HEV infection is a spectrum, with most symptomatic patients presenting with acute, self-limited hepatitis. Severe cases may be associated with pancreatitis, arthritis, aplastic anemia, and neurologic complications, such as seizures. Populations at risk for more severe cases include pregnant women, elderly men, and patients with pre‑ existing, chronic liver disease. 

What this evidence means for practiceStandard sanitary precautions, such as clean drinking water, traditionally have been considered the mainstay of hepatitis E prevention. However, as the study authors indicate, recent severe outbreaks of HEV infection in Sudan and Uganda have occurred despite these measures. Thus, an effective vaccine that produces long-standing immunity has great potential for reducing morbidity and mortality in these countries. The present vaccine appears to be highly effective and safe. The principal unanswered question is the duration of immunity.

My patients are asking, "What is the best insect repellent to try to avoid Zika virus?"

With summer upon us we have received questions from colleagues about the best over-the-counter insect repellents to advise their pregnant patients to use.

The preferred insect repellent for skin coverage is DEET (N,N-diethyl-meta-toluamide) (TABLE). Oil of lemon/eucalyptus/para-menthane-diol and IR3535 are also acceptable repellents to use on the skin that are safe for use in pregnancy. In addition, instruct patients to spray permethrin on their clothing or to buy clothing (boots, pants, socks) that has been pretreated with permethrin.^1,2
Anushka Chelliah, MD, and Patrick Duff, MD.

Abbreviation: OTC, over the counter.

---

Coming soon to OBG Management
Drs. Chelliah and Duff follow-up on their March 2016 examination of Zika virus infection with:  

• Latest information on Zika virus-associated birth defects
• Ultrasonographic and radiologic evidence of abnormalities in the fetus and newborn exposed to Zika virus infection
• Link between Zika virus infection and serious neurologic complications in adults
• New recommendations for preventing sexual transmission of Zika virus infection 

---

Dr. Chelliah is a Maternal Fetal Medicine-Fellow in the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.

Dr. Duff is Associate Dean for Student Affairs and Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, University of Florida College of Medicine.

The author reports no financial relationships relevant to this article.

---

References

1. Peterson EE, Staples JE, Meaney-Delman D, et al. Interim guidelines for pregnant women during a Zika virus outbreak--United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(2):30-33.
2. Centers for Disease Control and Prevention. CDC Features: Avoid mosquito bites. http://www.cdc.gov/Features/stopmosquitoes/index.html. Updated March 18, 2016. Accessed May 10, 2016.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Chlorhexidine-alcohol is superior to iodine-alcohol for reducing SSIs after cesarean delivery_{Tuuli Mg, Liu J, Stout Mj, et al. A randomized trial comparing skin antiseptic agents at cesarean delivery. N Engl J Med. 2016;374(7):647-655.}

In the United States, cesarean delivery is the most commonly performed major surgical procedure, with 32.7% of births--or 1.3 million--occurring in this fashion in 2013.^1,2 In general, for all surgical procedures, the SSI rate is 2% to 5%, with the rate rising to 5% to 12% for cesarean delivery, especially in obese patients.^3-6 Not only do SSIs increase morbidity for the patient but they also contribute to high medical costs, with an estimated additional expense of $3,529 per cesarean-associated infection.⁷

Skin pathogens are a major source of SSIs. Choosing the proper antiseptic has the potential to decrease infection risk. While current guidelines recommend use of an antiseptic containing alcohol, it is unclear which disinfectant is the most effective agent to combine with the alcohol.³ 

Most trials evaluating preoperative antiseptic skin preparation have studied patients undergoing general surgery procedures. A well-designed trial by Darouiche and coauthors demonstrated that chlorhexidine was superior to iodine when used as an antiseptic for skin preparation.⁸ Interestingly, however, this trial, like most others, compared chlorhexidine-alcohol to iodine without alcohol. It is therefore unclear whether the chlorhexidine or the alcohol is responsible for the enhanced antiseptic effect.

Details of the studyIn the single-center randomized trial conducted by Tuuli and colleagues, patients were assigned to preoperative skin antisepsis with either chlorhexidine-alcohol (2% chlorhexidine gluconate with 70% isopropyl alcohol) or iodine-alcohol (8.3% povidone-iodine with 72.5% isopropyl alcohol). Antiseptic was applied according to the manufacturer's instructions, with a standard wait time of 3 minutes between application and skin incision. However, wait time was eliminated for patients undergoing emergency cesarean delivery. Additionally, patients received standard, weight-based preoperative antibiotic prophylaxis (agent not specified). 

The authors estimated the necessary sample size for the trial by assuming an 8% baseline SSI rate and an anticipated 50% reduction of infection in the chlorhexidine-alcohol group. Exclusion criteria included a known allergy to chlorhexidine, alcohol, iodine, or shellfish or a preexisting skin infection adjacent to the operative site.

In addition to assessing the primary outcome of SSI with the 2 preparations, the authors conducted 4 prespecified subgroup analyses. These subgroups were based on: type of cesarean delivery (scheduled vs unscheduled), body weight (obese vs nonobese), type of skin closure (subcuticular suture vs staples), and presence or absence of chronic medical conditions (diabetes, hypertension, renal disease). Additionally, a post hoc analysis was performed, comparing women with diabetes (gestational and pregestational) to those without diabetes.
 
A total of 1,636 pregnant women were screened for eligibility. Of these, 489 women were excluded because they did not meet inclusion criteria or declined to participate or because informed consent could not be obtained. Baseline characteristics were similar across both groups.

Patients were followed for 30 days after surgery. A total of 1,082 women (94.3% of sample size) completed the follow-up. Among these patients, the rate of SSI was significantly lower in the chlorhexidine-alcohol group (4.3%) compared with the iodine-alcohol group (7.7%, P = .02).

In the subgroup analyses, the frequency of SSI remained lower for the chlorhexidine-alcohol group than for the iodine-alcohol group. These reductions were not affected by whether the cesarean was scheduled or unscheduled, the presence or absence of obesity, the type of skin closure, the presence of chronic disease, or diabetes status.
 
Several secondary outcomes also were examined in this study. There were no significant differences between the 2 antiseptic groups with respect to rates of endometritis, hospital readmission for infection-related complications, length of hospital stay, use of other health care services (such as emergency department visits, additional wound surgery, and home health services), and rates of other wound complications (seroma, hematoma, and cellulitis). Patients in the chlorhexidine-alcohol group were significantly less likely than those in the iodine-alcohol group to have physician office visits for concerns about possible wound complications (P = .009).

The authors concluded that the use of chlorhexidine-alcohol was superior to iodine-alcohol in preventing SSI after cesarean delivery.

Study strengths and limitations The authors acknowledged that their study had some minor limitations. First, the trial was conducted at a single site, which may limit the generalizability of the findings. However, the study population was racially and economically diverse. Second, the lack of blinding among providers and participants may have introduced bias, although, as the authors explain, we would expect this bias to be largely nondirectional.

A major strength of this study is its randomized design. Another strength is that the authors included emergency cesarean deliveries in their analysis. Emergency procedures represent a substantial proportion of cesarean deliveries, and they place the patient at increased risk for SSIs because of limited time available to prepare the skin before surgery begins. Thus, it is of great interest that chlorhexidine-alcohol was so effective even in the highest-risk patients.
 
Several properties may make chlorhexidine superior to iodine as an antiseptic: high binding affinity for the skin, high antibacterial activity against both gram-positive and gram-negative bacteria, and longer residual effects than iodine. Additionally, iodine is inactivated by organic matter, such as body fluids, whereas chlorhexidine is not.
 
A recent study by Ngai and colleagues⁹ compared chlorhexidine-alcohol with iodine-alcohol for skin preparation before cesarean delivery. These authors found no difference in SSI when comparing the 2 solutions used separately or sequentially, except in morbidly obese women. In these women, sequential application of both solutions reduced the infection rate. However, this study specifically excluded emergency cesarean deliveries, making the generalizability of the results questionable.⁹

What this evidence means for practiceThis large, randomized study found chlorhexidine-alcohol to be superior to iodine-alchol in reducing the risk of SSIs after cesarean delivery. These results confirm those of previous studies from both the obstetric and general surgery literature. Although chlorhexidine-alcohol is more expensive than iodine-alcohol, we strongly recommend its use in patients having cesarean delivery.

Five effective oral and intramuscular antibiotic regimens for treating postpartum endometritis_{Meaney-Delman D, Bartlett LA, Gravett MG, Jamieson DJ. Oral and intramuscular treatment options for early postpartum endometritis in low-resource settings: a systematic review. Obstet Gynecol. 2015;125(4):789-800.}

The authors of this excellent systematic review on antibiotic treatments for early postpartum endometritis conducted their study in 3 phases. Initially, Meaney-Delman and colleagues searched the literature for reports of prospective studies that evaluated the use of oral and intramuscular (IM) antibiotics for treatment of patients who developed endometritis following either cesarean or vaginal delivery. When they discovered that these initial trials were few in number and of relatively poor quality, they reviewed more rigorous trials of intravenous (IV) antibiotics. Finally, they evaluated clinical trials that specifically identified microorganisms isolated from the uterus in patients with endometritis and used this information to help inform their recommendations for treatment options.

Details of the studyIn evaluating the trials of oral and IM antibiotics, the authors set as a standard for effectiveness a cure rate of 85%, a figure comparable to that generally achieved with IV antibiotics. They identified 2 oral antibiotic regimens that met this standard of effectiveness: amoxicillin-clavulanate (100% cure in 36 patients; 95% confidence interval [CI], 90-100) and ampicillin plus metronidazole (97% cure in 37 patients; 95% CI, 86-100).

Two studies demonstrated acceptable levels of cure with single-agent IM antibiotics: aztreonam (100% cure in 16 patients; 95% CI, 81-100) and imipenem (91% cure in 23 patients; 95% CI, 73-98). One additional trial demonstrated an acceptable clinical response rate when IV clindamycin was combined with IM gentamicin (100% cure in 54 patients; 95% CI, 94-100). By contrast, the authors noted, many different IV regimens--either as a single agent or as a drug combination--provided cure rates that equaled or exceeded 85%.

In the study's final phase, the authors provided an excellent overview of the polymicrobial nature of puerperal endometritis. As documented in multiple prior reports, the most common pathogens are the gram-negative anaerobic bacilli, such as Bacteroides and Prevotella species; the anaerobic gram-positive organisms, including Peptococcus and Peptostreptococcus species; aerobic gram-negative bacilli, such as Escherichia coli, Klebsiella pneumoniae, and Proteus species; and aerobic gram-positive cocci, such as group B streptococci, enterococci, and staphylococci.

Recommended regimens. Based on their review of clinical and microbiological studies, the authors proposed 5 oral or combined oral-IM treatment regimens that could be used in low-resource settings:

• oral clindamycin (600 mg every 6 hours)
• plus IM gentamicin (4.5 g every 24 hours)
• oral amoxicillin-clavulanic acid (875 mg every 12 hours)
• IM cefotetan (2 g every 8 hours)
• IM meropenem or imipenem-cilastatin (500 mg every 8 hours)
• oral amoxicillin (500 mg every 8 hours) plus oral metronidazole (500 mg every 8 hours).

Typical endometritis treamentEndometritis is the single most common complication following cesarean delivery. The frequency of its occurrence depends on several factors, including: the socioeconomic characteristics of the patient population, length of labor, length of ruptured membranes, number of internal vaginal examinations, presence of preexisting lower genital tract infection, type of anesthesia, surgical technique, and use of prophylactic antibiotics. Endometritis is much less common after vaginal delivery but still may occur in 3% to 5% of patients.¹⁰

Endometritis is clearly a polymicrobial infection that includes multiple aerobic and anaerobic organisms. Accordingly, antibiotic therapy must target all the major groups of pathogens. The usual standard of care for treatment of early-onset endometritis is IV antibiotics, and patients typically are treated until they have been afebrile and asymptomatic for a minimum of 24 hours. Several different IV regimens provide acceptable treatment¹⁰:

• clindamycin plus gentamicin
• metronidazole plus ampicillin plus gentamicin
• extended-spectrum cephalosporins, such as cefepime, cefotetan, and cefoxitin
• extended-spectrum penicillins, such as ampicillin-sulbactam, piperacillin- tazobactam, and ticarcillin-clavulanic acid
• carbapenems, such as imipenem-cilastatin and meropenem.

What this evidence means for practiceClearly, IV antibiotics, even generic drugs, are more expensive than oral agents. They also are more difficult to administer than oral or IM drugs. The systematic review by Meaney-Delman and co-workers is therefore a very important contribution to the literature and should reassure clinicians practicing in low-resource settings that oral and oral-IM regimens can provide safe and effective treatment for endometritis. Until more rigorous comparative trials are conducted, however, we agree with the authors' caveat that, for now, such treatment should be limited to individuals whose infection occurred after vaginal delivery or who have evidence of only mild postcesarean endometritis.

Treatment options for chlamydia infection: How does azithromycin compare with doxycycline?_{Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med. 2015;373(26):2512-2521.}

The Centers for Disease Control and Prevention recommendations for treatment of chlamydia genital tract infection are either oral doxycycline, 100 mg twice daily for 7 days, or azithromycin, 1,000 mg in a single dose.¹¹ Recent reports have raised questions about the relative effectiveness of single-dose azithromycin compared with the multiple-day doxycycline regimen. Accordingly, Geisler and colleagues conducted an interesting randomized controlled trial to determine if azithromycin is noninferior to doxycycline.

Details of the studyThe study took place in a unique institutional setting--the Los Angeles County youth correctional facilities. Participants were young men and women, aged 12 to 21 years, who tested positive for chlamydia infection by a nucleic acid amplification test on entry to the correctional facility. Participants then were randomly assigned to receive either doxycycline or azithromycin in the doses described above. The primary outcome was the percent of individuals who still tested positive for chlamydia 28 days after treatment.

Of note, all patients took their medication under direct observation of corrections officers and, with rare exceptions, did not engage in sexual activity during the period of observation. Because this was a noninferiority trial, Geisler and colleagues analyzed the outcomes only of the individuals who actually took their medication in accordance with the assigned protocol. A priori, the authors established a 95% CI of <5% difference in effectiveness as indicative of noninferiority.

Overall, 155 patients in each treatment group completed the trial according to the assigned protocol. No treatment failures occurred in the doxycycline group (0%; 95% CI, 0.0-2.4). Five treatment failures occurred in the azithromycin group (3.2%; 95% CI, 0.4-7.4), in 1 female and 4 male participants. Because the 95% CI for the difference in treatment outcome exceeded 5%, the authors were unable to conclude that azithromycin was noninferior to doxycycline.

Consider real-world treatment adherence in these resultsFor several reasons, we do not conclude from this article that ObGyns should now stop using azithromycin to treat patients with chlamydia infection. First, the actual per protocol sample size was still relatively small. If there had been just 2 fewer failures in the azithromycin group, the 95% CI for the difference in outcomes would have been less than 5%, and the authors would have concluded that the 2 drug regimens were noninferior. Second, 4 of the 5 treatment failures in the azithromycin group were in male rather than female participants. Third, the unique study design resulted in almost perfect adherence with the 7-day doxycycline treatment regimen. Such adherence is very unlikely in other practice settings, and patients who do not complete their treatment regimen are significantly more likely to fail therapy. Finally, azithromycin is definitely preferred in pregnancy because we try to avoid maternal/fetal exposure to drugs such as tetracycline and doxycycline.

What this evidence means for practiceIn this study, both doxycycline and azithromycin were highly effective (100% and 97%, respectively) for treating chlamydia genital tract infection, and they are comparable in cost. In our opinion, the improved adherence that is possible with single-dose azithromycin, the greater safety in pregnancy, and the excellent tolerability of this drug outweigh its slightly deceased rate of microbiologic cure.

Vaccine effective against hepatitis E for 4+ years_{Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015;372(10):914-922.}

This study conducted by Zhang and colleagues in Dongtai, China, is an extended follow-up study of the hepatitis E virus (HEV) vaccine (Hecolin; Xiamen Innovax Biotech). A recombinant vaccine directed against HEV genotype 1, Hecolin has been used in China since 2012.

In the initial efficacy study, healthy adults aged 16 to 65 years were randomly assigned to receive either the hepatitis E vaccine (vaccine group, 56,302 participants) or the hepatitis B vaccine (control group, 56,302 participants). Vaccine administration occurred at 0, 1, and 6 months, and participants were followed for a total of 19 months.

Details of the studyThe follow-up study was designed to assess the efficacy, immunogenicity, and safety of the HEV vaccine up to 4.5 years postvaccination. All health care centers (205 village and private clinics) in the study area were enrolled in the program. The treatment assignments of all patients remained double blinded. Unblinding occurred only after the data on safety, efficacy, and immunogenicity had been locked.

A diagnosis of HEV infection was made if at least 2 of the following markers were present: a positive test for immunoglobulin M antibodies against HEV, a positive test for HEV RNA, or a serum concentration of immunoglobulin G (IgG) antibodies against HEV that was at least 4 times higher than previously measured at any time during the same illness. Vaccine immunogenicity was assessed by testing serum samples for IgG antibodies against HEV at regular intervals after the vaccination was given.

Over the 4.5-year study period, 7 cases of hepatitis E occurred in the vaccine group, and 53 in the control group. Vaccine efficacy was 86.8% (P<.001) in the modified intention-to-treat analysis. Among patients who received 3 doses of HEV vaccine and who were seronegative at the start of the study, 87% maintained antibodies against HEV for 4.5 years. Within the control group, HEV titers developed in 9% of participants. The vaccine and control groups had similar rates of adverse events.

The authors concluded that the HEV vaccine induced antibodies against hepatitis E that lasted up to 4.5 years. Additionally, 2 doses of vaccine induced slightly lower levels of antibody than those produced by 3 doses of the vaccine. Finally, all participants in the vaccine group who developed HEV had antibodies with high or moderate avidity, indicating an anamnestic response from previous immunity. Most participants in the control group who developed HEV, however, had antibodies with low avidity, indicating no previous immunity.
The burden of HEVHepatitis E is a serious infection and is the most common waterborne illness in the world. It occurs mainly in developing countries with limited resources. HEV infection is caused by genotypes 1, 2, 3, or 4, although all 4 genotypes belong to the same serotype. Genotypes 1 and 2 are typically waterborne, and genotypes 3 and 4 are typically transmitted from animals and humans. In general, the case fatality rate associated with HEV infection is 1% to 3%.¹² In pregnancy, this rate increases to 5% to 25%.^13,14 In Bangladesh, for example, hepatitis E is responsible for more than 1,000 deaths per year among pregnant women.¹⁵

Clinical presentation of HEV infection is a spectrum, with most symptomatic patients presenting with acute, self-limited hepatitis. Severe cases may be associated with pancreatitis, arthritis, aplastic anemia, and neurologic complications, such as seizures. Populations at risk for more severe cases include pregnant women, elderly men, and patients with pre‑ existing, chronic liver disease. 

What this evidence means for practiceStandard sanitary precautions, such as clean drinking water, traditionally have been considered the mainstay of hepatitis E prevention. However, as the study authors indicate, recent severe outbreaks of HEV infection in Sudan and Uganda have occurred despite these measures. Thus, an effective vaccine that produces long-standing immunity has great potential for reducing morbidity and mortality in these countries. The present vaccine appears to be highly effective and safe. The principal unanswered question is the duration of immunity.

My patients are asking, "What is the best insect repellent to try to avoid Zika virus?"

With summer upon us we have received questions from colleagues about the best over-the-counter insect repellents to advise their pregnant patients to use.

The preferred insect repellent for skin coverage is DEET (N,N-diethyl-meta-toluamide) (TABLE). Oil of lemon/eucalyptus/para-menthane-diol and IR3535 are also acceptable repellents to use on the skin that are safe for use in pregnancy. In addition, instruct patients to spray permethrin on their clothing or to buy clothing (boots, pants, socks) that has been pretreated with permethrin.^1,2
Anushka Chelliah, MD, and Patrick Duff, MD.

Abbreviation: OTC, over the counter.

---

Coming soon to OBG Management
Drs. Chelliah and Duff follow-up on their March 2016 examination of Zika virus infection with:  

• Latest information on Zika virus-associated birth defects
• Ultrasonographic and radiologic evidence of abnormalities in the fetus and newborn exposed to Zika virus infection
• Link between Zika virus infection and serious neurologic complications in adults
• New recommendations for preventing sexual transmission of Zika virus infection 

---

Dr. Chelliah is a Maternal Fetal Medicine-Fellow in the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.

Dr. Duff is Associate Dean for Student Affairs and Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, University of Florida College of Medicine.

The author reports no financial relationships relevant to this article.

---

References

1. Peterson EE, Staples JE, Meaney-Delman D, et al. Interim guidelines for pregnant women during a Zika virus outbreak--United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(2):30-33.
2. Centers for Disease Control and Prevention. CDC Features: Avoid mosquito bites. http://www.cdc.gov/Features/stopmosquitoes/index.html. Updated March 18, 2016. Accessed May 10, 2016.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

On April 17, 2014, the US Food and Drug Administration (FDA) released a safety communication that discouraged the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids. This recommendation was based mainly on the premise that fibroids may contain an underlying malignancy (in 1 in 350 women) that laparoscopic power morcellation could spread, thereby potentially worsening a cancer prognosis.¹ Whether we liked it or not, minimally invasive gynecologic surgery as we knew it had changed forever on that fateful day.

During the last 2 years, the implications of that initial safety communication, along with its update in November of 2014,² have been far reaching. From a health care industry perspective, the largest manufacturer of power morcellators, Johnson & Johnson, completely pulled its device out of the market within months of the initial FDA safety communication.³ Although several other companies remained in the market, health insurers such as Highmark and Aetna took the stance of not paying for the routine use of a power morcellator.^4,5 Soon government officials became involved in the campaign against power morcellators and trial lawyers made this surgical device the latest “hot target.”^6,7

The power morcellator’s absence impactFor clinicians, the narrative painted had moved the pendulum so far against power morcellation that it did not come as a surprise that practice patterns were significantly impacted. Harris and colleagues recently measured that impact by evaluating practice patterns and postoperative complications before and after the FDA safety communication on power morcellation. In their retrospective cohort study of patients within the Michigan Surgical Quality Collaborative, utilization of minimally invasive hysterectomy decreased and major surgical, nontransfusion complications and 30-day hospital readmission rates increased after release of the safety communication.⁸

Further support of this change in practice patterns was demonstrated in a recent survey conducted by the AAGL and American College of Obstetricians and Gynecologists Collaborative Ambulatory Research Network (ACOG CARN). In this survey study, Lum and colleagues were able to show that power morcellation use decreased among AAGL and ACOG CARN members after the FDA warnings, and rates of laparotomy increased.⁹

Critical to the discussion, yet apparently overlooked during the formulation of the initial FDA warning, was the potential clinical significance of the downstream impact of converting minimally invasive surgical cases to more invasive laparotomies. A decision-tree analysis published by Siedhoff and colleagues highlighted this point by predicting fewer overall deaths for laparoscopic hysterectomy with morcellation compared with abdominal hysterectomy.¹⁰ An ability to weigh the benefits and risks of procedure-related complications that are associated with laparotomy, including death, should have been part of the conversation from the beginning.

There is a silver lining emergingBased on this domino effect, it would seem that the damage done to minimally invasive gynecologic surgery over the past 2 years is irreparable. So is there any silver lining to the current state of affairs in tissue extraction? I would argue yes.

We have updated estimates for incidence of unsuspected leiomyosarcoma. First of all, discussions surrounding the FDA’s estimated 1 in 350 risk of encountering an unsuspected uterine sarcoma during the treatment of fibroids prompted a more critical evaluation of the scientific literature. In fact, Parker and colleagues, in a commentary published in Obstetrics & Gynecology, summarized very nicely the flawed methodology in the FDA’s determination of risk and in turn presented several updated calculations and studies that placed the prevalence somewhere in the range of 2 in 8,720 (0.023%) to 1 in 1,550 (0.064%).¹¹

We are speaking with the FDA. Channels of communication with the FDA have since been developed and societies such as the AAGL were invited by the Center for Devices and Radiological Health (CDRH) at the FDA to serve in their Network of Experts. This Network of Experts is an FDA-vetted group of non−FDA affiliated scientists, clinicians, and engineers who provide the CDRH at the FDA with rapid access to scientific, engineering, and medical expertise when it is needed to supplement existing knowledge and expertise within the CDRH. By developing these lines of communication, the CDRH is able to broaden its exposure to scientific viewpoints without the influence of external, or non−FDA, policy advice or opinions.

We have been innovating our techniques. Clinicians also began to develop innovative techniques for tissue extraction that also included contained, in-bag power morcellation. Vargas and colleagues showed similar perioperative outcomes when comparing open power morcellation with contained power morcellation within an insufflated isolation bag. The mean operative time was prolonged by only 26 minutes with in-bag morcellation.¹²

Although the initial experience of surgeons involved various containment systems that were off label in their usage and not designed to be paired with a power morcellator, it allowed for the identification of potential limitations, such as the risk of leakage. Cohen and colleagues, in their published experience, demonstrated a 9.2% spillage in 76 patients who underwent contained power morcellation.¹³

Could a new FDA approval turn the tide?In an interesting turn of events, the FDA, on April 7, 2016, nearly 2 years after their initial warning about power morcellation, gave de novo classification clearance to Advanced Surgical Concepts for its PneumoLiner device.¹⁴ This first-of-a-kind medical device was developed for the purpose of completely containing fluid, cells, and tissue fragments during laparoscopic power morcellation, isolating uterine tissue that is not suspected to contain cancer (FIGURES 1 and 2). It is important to note, however, that it has not been shown to reduce the risk of spreading cancer during this procedure. Although a surprise to some, the approval of such a product is in keeping with the FDA’s safety communication update in November 2014 that encouraged the development of containment systems designed specifically for gynecologic surgery.
 

FIGURE 1 PneumoLiner tissue containment device		FIGURE 2 PneumoLiner device placement

Currently, the PneumoLiner is not yet available for purchase until Olympus, who will be the exclusive distributor, finalizes its formal training program rollout for ensuring safe and effective use of the device by gynecologic surgeons. As part of the FDA approval process, a training protocol was validated in a laboratory setting by surgeons with varying levels of experience in order to demonstrate that adherence to this process showed no damage to any of the containment systems used during the study.

As I look forward to the opportunity to learn more about this new containment system and potentially incorporate it into my surgical armamentarium, several questions immediately come to mind.

• Will hospitals, many of which pulled morcellators off their shelves in the wake of the FDA safety communication, be willing to embrace such innovative new containment technology and make it available to their surgeons?
• Will the litigious landscape painted by trial lawyers prevent surgeons from offering this option to their patients?
• Can surgeons undo much of the misinformation being propagated by the media as it relates to tissue extraction and the risk of encountering a malignancy?

I hope the answer to all of these questions is yes.

I do believe the pendulum can change directionAs surgeons it is our duty to evaluate potentially innovative solutions to the surgical challenges we face in clinical practice while maintaining an evidence-based approach. Most importantly, all of this must be balanced by sound clinical judgment that no technology can replace. With these guiding principles in mind, I believe that the pendulum regarding tissue extraction can change direction.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

On April 17, 2014, the US Food and Drug Administration (FDA) released a safety communication that discouraged the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids. This recommendation was based mainly on the premise that fibroids may contain an underlying malignancy (in 1 in 350 women) that laparoscopic power morcellation could spread, thereby potentially worsening a cancer prognosis.¹ Whether we liked it or not, minimally invasive gynecologic surgery as we knew it had changed forever on that fateful day.

During the last 2 years, the implications of that initial safety communication, along with its update in November of 2014,² have been far reaching. From a health care industry perspective, the largest manufacturer of power morcellators, Johnson & Johnson, completely pulled its device out of the market within months of the initial FDA safety communication.³ Although several other companies remained in the market, health insurers such as Highmark and Aetna took the stance of not paying for the routine use of a power morcellator.^4,5 Soon government officials became involved in the campaign against power morcellators and trial lawyers made this surgical device the latest “hot target.”^6,7

The power morcellator’s absence impactFor clinicians, the narrative painted had moved the pendulum so far against power morcellation that it did not come as a surprise that practice patterns were significantly impacted. Harris and colleagues recently measured that impact by evaluating practice patterns and postoperative complications before and after the FDA safety communication on power morcellation. In their retrospective cohort study of patients within the Michigan Surgical Quality Collaborative, utilization of minimally invasive hysterectomy decreased and major surgical, nontransfusion complications and 30-day hospital readmission rates increased after release of the safety communication.⁸

Further support of this change in practice patterns was demonstrated in a recent survey conducted by the AAGL and American College of Obstetricians and Gynecologists Collaborative Ambulatory Research Network (ACOG CARN). In this survey study, Lum and colleagues were able to show that power morcellation use decreased among AAGL and ACOG CARN members after the FDA warnings, and rates of laparotomy increased.⁹

Critical to the discussion, yet apparently overlooked during the formulation of the initial FDA warning, was the potential clinical significance of the downstream impact of converting minimally invasive surgical cases to more invasive laparotomies. A decision-tree analysis published by Siedhoff and colleagues highlighted this point by predicting fewer overall deaths for laparoscopic hysterectomy with morcellation compared with abdominal hysterectomy.¹⁰ An ability to weigh the benefits and risks of procedure-related complications that are associated with laparotomy, including death, should have been part of the conversation from the beginning.

There is a silver lining emergingBased on this domino effect, it would seem that the damage done to minimally invasive gynecologic surgery over the past 2 years is irreparable. So is there any silver lining to the current state of affairs in tissue extraction? I would argue yes.

We have updated estimates for incidence of unsuspected leiomyosarcoma. First of all, discussions surrounding the FDA’s estimated 1 in 350 risk of encountering an unsuspected uterine sarcoma during the treatment of fibroids prompted a more critical evaluation of the scientific literature. In fact, Parker and colleagues, in a commentary published in Obstetrics & Gynecology, summarized very nicely the flawed methodology in the FDA’s determination of risk and in turn presented several updated calculations and studies that placed the prevalence somewhere in the range of 2 in 8,720 (0.023%) to 1 in 1,550 (0.064%).¹¹

We are speaking with the FDA. Channels of communication with the FDA have since been developed and societies such as the AAGL were invited by the Center for Devices and Radiological Health (CDRH) at the FDA to serve in their Network of Experts. This Network of Experts is an FDA-vetted group of non−FDA affiliated scientists, clinicians, and engineers who provide the CDRH at the FDA with rapid access to scientific, engineering, and medical expertise when it is needed to supplement existing knowledge and expertise within the CDRH. By developing these lines of communication, the CDRH is able to broaden its exposure to scientific viewpoints without the influence of external, or non−FDA, policy advice or opinions.

We have been innovating our techniques. Clinicians also began to develop innovative techniques for tissue extraction that also included contained, in-bag power morcellation. Vargas and colleagues showed similar perioperative outcomes when comparing open power morcellation with contained power morcellation within an insufflated isolation bag. The mean operative time was prolonged by only 26 minutes with in-bag morcellation.¹²

Although the initial experience of surgeons involved various containment systems that were off label in their usage and not designed to be paired with a power morcellator, it allowed for the identification of potential limitations, such as the risk of leakage. Cohen and colleagues, in their published experience, demonstrated a 9.2% spillage in 76 patients who underwent contained power morcellation.¹³

Could a new FDA approval turn the tide?In an interesting turn of events, the FDA, on April 7, 2016, nearly 2 years after their initial warning about power morcellation, gave de novo classification clearance to Advanced Surgical Concepts for its PneumoLiner device.¹⁴ This first-of-a-kind medical device was developed for the purpose of completely containing fluid, cells, and tissue fragments during laparoscopic power morcellation, isolating uterine tissue that is not suspected to contain cancer (FIGURES 1 and 2). It is important to note, however, that it has not been shown to reduce the risk of spreading cancer during this procedure. Although a surprise to some, the approval of such a product is in keeping with the FDA’s safety communication update in November 2014 that encouraged the development of containment systems designed specifically for gynecologic surgery.
 

FIGURE 1 PneumoLiner tissue containment device		FIGURE 2 PneumoLiner device placement

Currently, the PneumoLiner is not yet available for purchase until Olympus, who will be the exclusive distributor, finalizes its formal training program rollout for ensuring safe and effective use of the device by gynecologic surgeons. As part of the FDA approval process, a training protocol was validated in a laboratory setting by surgeons with varying levels of experience in order to demonstrate that adherence to this process showed no damage to any of the containment systems used during the study.

As I look forward to the opportunity to learn more about this new containment system and potentially incorporate it into my surgical armamentarium, several questions immediately come to mind.

• Will hospitals, many of which pulled morcellators off their shelves in the wake of the FDA safety communication, be willing to embrace such innovative new containment technology and make it available to their surgeons?
• Will the litigious landscape painted by trial lawyers prevent surgeons from offering this option to their patients?
• Can surgeons undo much of the misinformation being propagated by the media as it relates to tissue extraction and the risk of encountering a malignancy?

I hope the answer to all of these questions is yes.

I do believe the pendulum can change directionAs surgeons it is our duty to evaluate potentially innovative solutions to the surgical challenges we face in clinical practice while maintaining an evidence-based approach. Most importantly, all of this must be balanced by sound clinical judgment that no technology can replace. With these guiding principles in mind, I believe that the pendulum regarding tissue extraction can change direction.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

On April 17, 2014, the US Food and Drug Administration (FDA) released a safety communication that discouraged the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids. This recommendation was based mainly on the premise that fibroids may contain an underlying malignancy (in 1 in 350 women) that laparoscopic power morcellation could spread, thereby potentially worsening a cancer prognosis.¹ Whether we liked it or not, minimally invasive gynecologic surgery as we knew it had changed forever on that fateful day.

During the last 2 years, the implications of that initial safety communication, along with its update in November of 2014,² have been far reaching. From a health care industry perspective, the largest manufacturer of power morcellators, Johnson & Johnson, completely pulled its device out of the market within months of the initial FDA safety communication.³ Although several other companies remained in the market, health insurers such as Highmark and Aetna took the stance of not paying for the routine use of a power morcellator.^4,5 Soon government officials became involved in the campaign against power morcellators and trial lawyers made this surgical device the latest “hot target.”^6,7

The power morcellator’s absence impactFor clinicians, the narrative painted had moved the pendulum so far against power morcellation that it did not come as a surprise that practice patterns were significantly impacted. Harris and colleagues recently measured that impact by evaluating practice patterns and postoperative complications before and after the FDA safety communication on power morcellation. In their retrospective cohort study of patients within the Michigan Surgical Quality Collaborative, utilization of minimally invasive hysterectomy decreased and major surgical, nontransfusion complications and 30-day hospital readmission rates increased after release of the safety communication.⁸

Further support of this change in practice patterns was demonstrated in a recent survey conducted by the AAGL and American College of Obstetricians and Gynecologists Collaborative Ambulatory Research Network (ACOG CARN). In this survey study, Lum and colleagues were able to show that power morcellation use decreased among AAGL and ACOG CARN members after the FDA warnings, and rates of laparotomy increased.⁹

Critical to the discussion, yet apparently overlooked during the formulation of the initial FDA warning, was the potential clinical significance of the downstream impact of converting minimally invasive surgical cases to more invasive laparotomies. A decision-tree analysis published by Siedhoff and colleagues highlighted this point by predicting fewer overall deaths for laparoscopic hysterectomy with morcellation compared with abdominal hysterectomy.¹⁰ An ability to weigh the benefits and risks of procedure-related complications that are associated with laparotomy, including death, should have been part of the conversation from the beginning.

There is a silver lining emergingBased on this domino effect, it would seem that the damage done to minimally invasive gynecologic surgery over the past 2 years is irreparable. So is there any silver lining to the current state of affairs in tissue extraction? I would argue yes.

We have updated estimates for incidence of unsuspected leiomyosarcoma. First of all, discussions surrounding the FDA’s estimated 1 in 350 risk of encountering an unsuspected uterine sarcoma during the treatment of fibroids prompted a more critical evaluation of the scientific literature. In fact, Parker and colleagues, in a commentary published in Obstetrics & Gynecology, summarized very nicely the flawed methodology in the FDA’s determination of risk and in turn presented several updated calculations and studies that placed the prevalence somewhere in the range of 2 in 8,720 (0.023%) to 1 in 1,550 (0.064%).¹¹

We are speaking with the FDA. Channels of communication with the FDA have since been developed and societies such as the AAGL were invited by the Center for Devices and Radiological Health (CDRH) at the FDA to serve in their Network of Experts. This Network of Experts is an FDA-vetted group of non−FDA affiliated scientists, clinicians, and engineers who provide the CDRH at the FDA with rapid access to scientific, engineering, and medical expertise when it is needed to supplement existing knowledge and expertise within the CDRH. By developing these lines of communication, the CDRH is able to broaden its exposure to scientific viewpoints without the influence of external, or non−FDA, policy advice or opinions.

We have been innovating our techniques. Clinicians also began to develop innovative techniques for tissue extraction that also included contained, in-bag power morcellation. Vargas and colleagues showed similar perioperative outcomes when comparing open power morcellation with contained power morcellation within an insufflated isolation bag. The mean operative time was prolonged by only 26 minutes with in-bag morcellation.¹²

Although the initial experience of surgeons involved various containment systems that were off label in their usage and not designed to be paired with a power morcellator, it allowed for the identification of potential limitations, such as the risk of leakage. Cohen and colleagues, in their published experience, demonstrated a 9.2% spillage in 76 patients who underwent contained power morcellation.¹³

Could a new FDA approval turn the tide?In an interesting turn of events, the FDA, on April 7, 2016, nearly 2 years after their initial warning about power morcellation, gave de novo classification clearance to Advanced Surgical Concepts for its PneumoLiner device.¹⁴ This first-of-a-kind medical device was developed for the purpose of completely containing fluid, cells, and tissue fragments during laparoscopic power morcellation, isolating uterine tissue that is not suspected to contain cancer (FIGURES 1 and 2). It is important to note, however, that it has not been shown to reduce the risk of spreading cancer during this procedure. Although a surprise to some, the approval of such a product is in keeping with the FDA’s safety communication update in November 2014 that encouraged the development of containment systems designed specifically for gynecologic surgery.
 

FIGURE 1 PneumoLiner tissue containment device		FIGURE 2 PneumoLiner device placement

Currently, the PneumoLiner is not yet available for purchase until Olympus, who will be the exclusive distributor, finalizes its formal training program rollout for ensuring safe and effective use of the device by gynecologic surgeons. As part of the FDA approval process, a training protocol was validated in a laboratory setting by surgeons with varying levels of experience in order to demonstrate that adherence to this process showed no damage to any of the containment systems used during the study.

As I look forward to the opportunity to learn more about this new containment system and potentially incorporate it into my surgical armamentarium, several questions immediately come to mind.

• Will hospitals, many of which pulled morcellators off their shelves in the wake of the FDA safety communication, be willing to embrace such innovative new containment technology and make it available to their surgeons?
• Will the litigious landscape painted by trial lawyers prevent surgeons from offering this option to their patients?
• Can surgeons undo much of the misinformation being propagated by the media as it relates to tissue extraction and the risk of encountering a malignancy?

I hope the answer to all of these questions is yes.

I do believe the pendulum can change directionAs surgeons it is our duty to evaluate potentially innovative solutions to the surgical challenges we face in clinical practice while maintaining an evidence-based approach. Most importantly, all of this must be balanced by sound clinical judgment that no technology can replace. With these guiding principles in mind, I believe that the pendulum regarding tissue extraction can change direction.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The use of antenatal corticosteroids for preterm deliveries between 24 and 34 weeks has been standard of care in obstetric practice. But approximately 70% of preterm deliveries in the United States occur after 34 weeks, in the so-called late preterm period (34 weeks 0 days to 36 weeks 6 days). Recently, Gyamfi-Bannerman and colleagues at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network completed a trial that examined the use of antenatal betamethasone in women at risk for delivery in the late preterm period.

Details of the study
The Antenatal Late Preterm Steroids (ALPS) trial was a randomized, double-blind, placebo-controlled study that included women with a singleton gestation between 34 weeks 0 days and 36 weeks 5 days who had a high probability risk of delivery in the late preterm period. The authors defined “high probability of delivery” as spontaneous labor with cervical change (at least 3-cm dilation or 75% effacement), preterm premature rupture of the membranes, or a planned delivery scheduled in the late preterm period for specific obstetric indications, such as oligohydramnios, preeclampsia, gestational hypertension, and intrauterine growth restriction.

Women were excluded from the study if they had previously received a course of steroids or had multiple gestations, pregestational diabetes, chorioamnionitis, or were expected to deliver in less than 12 hours due to advanced labor, vaginal bleeding, or nonreassuring fetal status.

Study participants were randomly assigned to receive 2 doses (12 mg intramuscularly) of betamethasone 24 hours apart (1,429 participants) or identical-appearing placebo (1,402 participants). Tocolysis was not allowed in the protocol.

Positive outcomes for neonates
The use of corticosteroids was associated with a significant reduction in the primary outcome of need for respiratory support in the first 72 hours of life (14.4% in the placebo group vs 11.6% in the betamethasone group; relative risk [RR], 0.80; 95% confidence interval [CI], 0.66–0.97; P = .02). Steroid use also decreased the incidence of severe respiratory complications, the need for resuscitation at birth, the need for surfactant therapy, the incidence of transient tachypnea of the newborn, and the incidence of bronchopulmonary dysplasia. Neonatal hypoglycemia was more frequent among infants exposed to betamethasone (24% vs 15%; RR, 1.6; 95% CI, 1.37–1.87; P<.001).

New guidelines issued
The ALPS study is the largest randomized trial to evaluate the benefit of antenatal steroids during the late preterm period. The study’s findings certainly will change clinical practice. Based on the study’s large sample size, rigorous design and protocol, and a cohort generalizable to the US population, SMFM has issued new recommendations for practitioners on using antenatal steroids in the late preterm period in women at risk for preterm delivery.

What this EVIDENCE means for practice
In light of the new SMFM recommendations, in my practice, I will adhere to the inclusion criteria used in the ALPS study, and be careful not to apply the same approach used before 34 weeks, when delivery is often delayed intentionally in order to achieve steroid benefit. If considering adoption of this same practice, clinicians should not use tocolytics when administering corticosteroids in the late preterm period. When indicated, such as in women with severe preeclampsia or ruptured membranes, delivery should not be delayed. A patient with high probability of delivery in the late preterm period is eligible for treatment as long as the clinician thinks that she is not going to deliver within 12 hours. On the other hand, clinicians should not overtreat women, and should maintain a high suspicion for delivery in patients with preterm labor (a cervix that is at least 3 cm dilated or 75% effaced).
 
The ALPS trial did not allow the administration of more than one course of steroids. The eligibility criteria for corticosteroid use in the late preterm period should not be extended to include subpopulations that were not studied in the trial (including patients with multiple gestations, pregestational diabetes, or those who already had received a complete course of steroids).
— Luis Pacheco, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The use of antenatal corticosteroids for preterm deliveries between 24 and 34 weeks has been standard of care in obstetric practice. But approximately 70% of preterm deliveries in the United States occur after 34 weeks, in the so-called late preterm period (34 weeks 0 days to 36 weeks 6 days). Recently, Gyamfi-Bannerman and colleagues at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network completed a trial that examined the use of antenatal betamethasone in women at risk for delivery in the late preterm period.

Details of the study
The Antenatal Late Preterm Steroids (ALPS) trial was a randomized, double-blind, placebo-controlled study that included women with a singleton gestation between 34 weeks 0 days and 36 weeks 5 days who had a high probability risk of delivery in the late preterm period. The authors defined “high probability of delivery” as spontaneous labor with cervical change (at least 3-cm dilation or 75% effacement), preterm premature rupture of the membranes, or a planned delivery scheduled in the late preterm period for specific obstetric indications, such as oligohydramnios, preeclampsia, gestational hypertension, and intrauterine growth restriction.

Women were excluded from the study if they had previously received a course of steroids or had multiple gestations, pregestational diabetes, chorioamnionitis, or were expected to deliver in less than 12 hours due to advanced labor, vaginal bleeding, or nonreassuring fetal status.

Study participants were randomly assigned to receive 2 doses (12 mg intramuscularly) of betamethasone 24 hours apart (1,429 participants) or identical-appearing placebo (1,402 participants). Tocolysis was not allowed in the protocol.

Positive outcomes for neonates
The use of corticosteroids was associated with a significant reduction in the primary outcome of need for respiratory support in the first 72 hours of life (14.4% in the placebo group vs 11.6% in the betamethasone group; relative risk [RR], 0.80; 95% confidence interval [CI], 0.66–0.97; P = .02). Steroid use also decreased the incidence of severe respiratory complications, the need for resuscitation at birth, the need for surfactant therapy, the incidence of transient tachypnea of the newborn, and the incidence of bronchopulmonary dysplasia. Neonatal hypoglycemia was more frequent among infants exposed to betamethasone (24% vs 15%; RR, 1.6; 95% CI, 1.37–1.87; P<.001).

New guidelines issued
The ALPS study is the largest randomized trial to evaluate the benefit of antenatal steroids during the late preterm period. The study’s findings certainly will change clinical practice. Based on the study’s large sample size, rigorous design and protocol, and a cohort generalizable to the US population, SMFM has issued new recommendations for practitioners on using antenatal steroids in the late preterm period in women at risk for preterm delivery.

What this EVIDENCE means for practice
In light of the new SMFM recommendations, in my practice, I will adhere to the inclusion criteria used in the ALPS study, and be careful not to apply the same approach used before 34 weeks, when delivery is often delayed intentionally in order to achieve steroid benefit. If considering adoption of this same practice, clinicians should not use tocolytics when administering corticosteroids in the late preterm period. When indicated, such as in women with severe preeclampsia or ruptured membranes, delivery should not be delayed. A patient with high probability of delivery in the late preterm period is eligible for treatment as long as the clinician thinks that she is not going to deliver within 12 hours. On the other hand, clinicians should not overtreat women, and should maintain a high suspicion for delivery in patients with preterm labor (a cervix that is at least 3 cm dilated or 75% effaced).
 
The ALPS trial did not allow the administration of more than one course of steroids. The eligibility criteria for corticosteroid use in the late preterm period should not be extended to include subpopulations that were not studied in the trial (including patients with multiple gestations, pregestational diabetes, or those who already had received a complete course of steroids).
— Luis Pacheco, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The use of antenatal corticosteroids for preterm deliveries between 24 and 34 weeks has been standard of care in obstetric practice. But approximately 70% of preterm deliveries in the United States occur after 34 weeks, in the so-called late preterm period (34 weeks 0 days to 36 weeks 6 days). Recently, Gyamfi-Bannerman and colleagues at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network completed a trial that examined the use of antenatal betamethasone in women at risk for delivery in the late preterm period.

Details of the study
The Antenatal Late Preterm Steroids (ALPS) trial was a randomized, double-blind, placebo-controlled study that included women with a singleton gestation between 34 weeks 0 days and 36 weeks 5 days who had a high probability risk of delivery in the late preterm period. The authors defined “high probability of delivery” as spontaneous labor with cervical change (at least 3-cm dilation or 75% effacement), preterm premature rupture of the membranes, or a planned delivery scheduled in the late preterm period for specific obstetric indications, such as oligohydramnios, preeclampsia, gestational hypertension, and intrauterine growth restriction.

Women were excluded from the study if they had previously received a course of steroids or had multiple gestations, pregestational diabetes, chorioamnionitis, or were expected to deliver in less than 12 hours due to advanced labor, vaginal bleeding, or nonreassuring fetal status.

Study participants were randomly assigned to receive 2 doses (12 mg intramuscularly) of betamethasone 24 hours apart (1,429 participants) or identical-appearing placebo (1,402 participants). Tocolysis was not allowed in the protocol.

Positive outcomes for neonates
The use of corticosteroids was associated with a significant reduction in the primary outcome of need for respiratory support in the first 72 hours of life (14.4% in the placebo group vs 11.6% in the betamethasone group; relative risk [RR], 0.80; 95% confidence interval [CI], 0.66–0.97; P = .02). Steroid use also decreased the incidence of severe respiratory complications, the need for resuscitation at birth, the need for surfactant therapy, the incidence of transient tachypnea of the newborn, and the incidence of bronchopulmonary dysplasia. Neonatal hypoglycemia was more frequent among infants exposed to betamethasone (24% vs 15%; RR, 1.6; 95% CI, 1.37–1.87; P<.001).

New guidelines issued
The ALPS study is the largest randomized trial to evaluate the benefit of antenatal steroids during the late preterm period. The study’s findings certainly will change clinical practice. Based on the study’s large sample size, rigorous design and protocol, and a cohort generalizable to the US population, SMFM has issued new recommendations for practitioners on using antenatal steroids in the late preterm period in women at risk for preterm delivery.

What this EVIDENCE means for practice
In light of the new SMFM recommendations, in my practice, I will adhere to the inclusion criteria used in the ALPS study, and be careful not to apply the same approach used before 34 weeks, when delivery is often delayed intentionally in order to achieve steroid benefit. If considering adoption of this same practice, clinicians should not use tocolytics when administering corticosteroids in the late preterm period. When indicated, such as in women with severe preeclampsia or ruptured membranes, delivery should not be delayed. A patient with high probability of delivery in the late preterm period is eligible for treatment as long as the clinician thinks that she is not going to deliver within 12 hours. On the other hand, clinicians should not overtreat women, and should maintain a high suspicion for delivery in patients with preterm labor (a cervix that is at least 3 cm dilated or 75% effaced).
 
The ALPS trial did not allow the administration of more than one course of steroids. The eligibility criteria for corticosteroid use in the late preterm period should not be extended to include subpopulations that were not studied in the trial (including patients with multiple gestations, pregestational diabetes, or those who already had received a complete course of steroids).
— Luis Pacheco, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE Surgeon accused of operating outside her scope of expertise

A 38-year-old woman (G2 P2002) presented to the emergency department (ED) with acute pelvic pain involving the right lower quadrant (RLQ). The patient had a history of stage IV endometriosis and chronic pelvic pain, primarily affecting the RLQ, that was treated by total laparoscopic hysterectomy with bilateral salpingo-oophorectomy 6 months earlier. Pertinent findings on physical examination included hypoactive bowel sounds and rebound tenderness. The ED physician ordered a computed tomography (CT) scan of the abdomen, which showed no evidence of ureteral injury or other abnormality. The gynecologist who performed the surgery 6 months ago evaluated the patient in the ED.

The gynecologist decided to perform operative laparoscopy because of the severity of the patient’s pain and duration of symptoms. Informed consent obtained in the ED before the patient received analgesics included a handwritten note that said “and other indicated procedures.” The patient signed the document prior to being taken to the operating room (OR). Time out occurred in the OR before anesthesia induction. The gynecologist proceeded with laparoscopic adhesiolysis with planned appendectomy, as she was trained. A normal appendix was noted and left intact. RLQ adhesions involving the colon and abdominal wall were treated with electrosurgical cautery. When the gynecologist found adhesions between the liver and diaphragm in the right upper quadrant (RUQ), she continued adhesiolysis. However, the diaphragm was inadvertently punctured.

As the gynecologist attempted to suture the defect laparoscopically, she encountered difficulty and converted to laparotomy. Adhesions were dense and initially precluded adequate closure of the diaphragmatic defect. The gynecologist persisted and ultimately the closure was adequate; laparotomy concluded. Postoperatively, the patient was given a diagnosis of atelectasis, primarily on the right side; a chest tube was placed by the general surgery team. The patient had an uneventful postoperative period and was discharged on postoperative day 5. One month later she returned to the ED with evidence of pneumonia; she was given a diagnosis of empyema, and antibiotics were administered. She responded well and was discharged after 6 days.

The patient filed a malpractice lawsuit against the gynecologist, the hospital, and associated practitioners. The suit made 3 negligence claims: 1) the surgery was improperly performed, as evidenced by the diaphragmatic perforation; 2) the gynecologist was not adequately trained for RUQ surgery, and 3) the hospital should not have permitted RUQ surgery to proceed. The liability claim cited the lack of qualification of a gynecologic surgeon to proceed with surgical intervention near the diaphragm and the associated consequences of practicing outside the scope of expertise.

Fitz-Hugh Curtis syndrome, a complication of pelvic inflammatory disease that may cause adhesions, was raised as the initial finding at the second surgical procedure and documented as such in the operative report. The plaintiff’s counsel questioned whether surgical correction of this syndrome was within the realm of a gynecologic surgeon. The plaintiff’s counsel argued that the laparoscopic surgical procedure involved bowel and liver; diaphragmatic adhesiolysis was not indicated, especially with normal abdominal CT scan results and the absence of RUQ symptoms. The claim specified that the surgery and care, as a consequence of the RUQ adhesiolysis, resulted in atelectasis, pneumonia, and empyema, with pain and suffering. The plaintiff sought unspecified monetary damages for these results.

What’s the verdict?

The case is in negotiation prior to trial.

Legal and medical considerations

“To err is not just human but intrinsically biological and no profession is exempt from fallibility.”¹

Error and liability

To err may be human, but human error is not necessarily the cause of every suboptimal medical outcome. In fact, the overall surgical complication rate has been reported at 3.4%.² Even when there is an error, it may not have been the kind of error that gives rise to medical malpractice liability. When it comes to surgical errors, the most common are those that actually relate to medications given at surgery that appear to be more common—one recent study found that 1 in 20 perioperative medication administrations resulted in a medication error or an adverse drug event.³

Medical error vs medical malpractice

The fact is that medical error and medical malpractice (or professional negligence) are not the same thing. It is critical to understand the difference.

Medical error is the third leading cause of death in the United States.⁴ It is defined as “the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim,”⁵ or, in the Canadian literature, “an act of omission or commission in planning or execution that contributes or could contribute to an unintended result.”⁶ The gamut of medical errors spans (among others) problems with technique, judgment, medication administration, diagnostic and surgical errors, and incomplete record keeping.⁵

Negligent error, on the other hand, is generally a subset of medical error recognized by the law. It is error that occurs because of carelessness. Technically, to give rise to liability for negligence (or malpractice) there must be duty, breach, causation, and injury. That is, the physician must owe a duty to the patient, the duty must have been breached, and that breach must have caused an injury.⁷

Usually the duty in medical practice is that the physician must have acted as a reasonable and prudent professional would have performed under the circumstances. For the most part, malpractice is a level of practice that the profession itself would not view as reasonable practice.⁸ Specialists usually are held to the higher standards of the specialty. It also can be negligent to undertake practice or a procedure for which the physician is not adequately trained, or for failing to refer the patient to another more qualified physician.

The duty in medicine usually arises from the physician-patient relationship (clearly present here). It is reasonably clear in this case that there was an injury, but, in fact, the question is whether the physician acted carelessly in a way that caused that injury. Our facts leave some ambiguity—unfortunately,a common problem in the real world.

It is possible that the gynecologist was negligent in puncturing the diaphragm. It may have been carelessness, for example, in the way the procedure was performed, or in the decision to proceed despite the difficulties encountered. It is also possible that the gynecologist was not appropriately trained and experienced in the surgery that was undertaken, in which case the decision to do the surgery (rather than to refer to another physician) could well have been negligent. In either of those cases, negligence liability (malpractice) is a possibility.

Proving negligence. It is the plaintiff (the patient) who must prove the elements of negligence (including causation).⁸ The plaintiff will have to demonstrate not only carelessness, but that carelessness is what caused the injuries for which she is seeking compensation. In this case, the injuries are the consequence of puncturing the diaphragm. The potential damages would be the money to cover the additional medical costs and other expenses, lost wages, and noneconomic damages such as pain and suffering.

The hospital’s role in negligence

The issue of informed consent is also raised in this case, with a handwritten note prior to surgery (but the focus of this article is on medical errors). In addition to the gynecologist, the hospital and other medical personnelwere sued. The hospital is responsible for the acts of its agents, notably its employees. Even if the physicians are not technically hospital employees, the hospital may in some cases be responsible. Among other things, the hospital likely has an obligation to prevent physicians from undertaking inappropriate procedures, including those for which the physician is not appropriately trained. If the gynecologist in this case did not have privileges to perform surgery in this category, the hospital may have an obligation to not schedule the surgery or to intraoperatively question her credentials for such a procedure. In any event, the hospital will have a major role in this case and its interests may, in some instances, be inconsistent with the interests of the physician.

Why settlement discussions?

The case description ends with a note that settlement discussions were underway. If the plaintiff must prove all of the elements of negligence, why have these discussions? First, such discussions are common in almost all negligence cases. This does not mean that the case actually will be settled by the insurance company representing the physician or hospital; many malpractice cases simply fade away because the patient drops the action. Second, there are ambiguities in the facts, and it is sometimes impossible to determine whether or not a jury would find negligence. The hospital may be inclined to settle if there is any realistic chance of a jury ruling against it. Paying a small settlement may be worth avoiding high legal expenses and the risk of an adverse outcome at trial.⁹

Reducing medical/surgical error through a team approach

Recognizing that “human performance can be affected by many factors that include circadian rhythms, state of mind, physical health, attitude, emotions, propensity for certain common mistakes and errors, and cognitive biases,”¹⁰ health care professionals have a commitment to reduce the errors in the interest of patient safety and best practice.

The surgical environment is an opportunity to provide a team approach to patient safety. Surgical risk is a reflection of operative performance, the main factor in the development of postoperative complications.¹¹ We wish to broaden the perspective that gynecologic surgeons, like all surgeons, must keep in mind a number of concerns that can be associated with problems related to surgical procedures, including¹²:

• visual perception difficulties
• stress
• loss of haptic perception (feedback using touch), as with robot-assisted procedures
• lack of situational awareness (a term we borrow from the aviation industry)
• long-term (and short-term) memory problems.

Analysis of surgical errors shows that they are related to, in order of frequency ¹:

• surgical technique
• judgment
• inattention to detail
• incomplete understanding of the problem or surgical situation.

Medical errors: Caring for the second victim (you)

Patrice M. Weiss, MD

We use the term “victim” to refer to the patient and her family following a medical error. The phrase “the second victim” was coined by Dr. Albert Wu in an article in the British Medical Journal¹ and describes how a clinician and team of health care professionals also can be affected by medical errors.

 

What signs and symptoms identify a second victim?Those suffering as a second victim may show signs of depression, loss of joy in work, and difficulty sleeping. They also may replay the events, question their own ability, and feel fearful about making another error. These reactions can lead to burnout—a serious issue that 46% of physicians report.²

As colleagues of those involved in a medical error, we should be cognizant of changes in behavior such as excessive irritability, showing up late for work, or agitation. It may be easier to recognize these symptoms in others rather than in ourselves because we often do not take time to examine how our experiences may affect us personally. Heightening awareness can help us recognize those suffering as second victims and identify the second victim symptoms in ourselves.
 

How can we help second victims?One challenge second victims face is not being allowed to discuss a medical error. Certainly, due to confidentiality requirements during professional liability cases, we should not talk freely about the event. However, silence creates a barrier that prevents a second victim from processing the incident.

Some hospitals offer forums to discuss medical errors, with the goal of preventing reoccurrence: morbidity and mortality conferences, morning report, Quality Assurance and Performance Improvement meetings, and root cause analyses. These forums often are not perceived by institutions’ employees in a positive way. Are they really meant to improve patient care or do they single out an individual or group in a “name/blame/shame game”? An intimidating process will only worsen a second victim’s symptoms. It is not necessary, however, to create a whole new process; it is possible to restructure, reframe, and change the culture of an existing practice.

Some institutions have developed a formalized program to help second victims. The University of Missouri has a “forYOU team,” an internal, rapid response group that provides emotional first aid to the entire team involved in a medical error case. These responders are not from human resources and do not need to be sought out; they are peers who have been educated about the struggles of the second victim. They will not discuss the case or how care was rendered; they naturally and instinctively provide emotional support to their colleagues.

At my institution, the Carilion Clinic at the Virginia Tech Carilion School of Medicine, “The Trust Program” encourages truth, respectfulness, understanding, support, and transparency. All health care clinicians receive basic training, but many have volunteered for additional instruction to become mentors because they have experienced second-victim symptoms themselves.

Clinicians want assistance when dealing with a medical error. One poll reports that 90% of physicians felt that health care organizations did not adequately help them cope with the stresses associated with a medical error.³ The goal is to have all institutions recognize that clinicians can be affected by a medical error and offer support.

To hear an expanded audiocast from Dr. Weiss on “the second victim” click here.

---

Dr. Weiss is Professor, Department of Obstetrics & Gynecology, Virginia Tech Carilion School of Medicine, and Chief Medical Officer and Executive Vice President, Carilion Clinic, Roanoke, Virginia.

The author reports no financial relationships relevant to this article.

 

---

References

1. Wu AW. Medical error: the second victim. BMJ. 2000;320(7237):726–727.
2. Peckham C. Medscape Physician Lifestyle Report 2015. Medscape website. http://www.medscape.com/features/slideshow/lifestyle/2015/public/overview#1. Published January 26, 2015. Accessed May 24, 2016.
3. White AA, Waterman AD, McCotter P, Boyle DJ, Gallagher TH. Supporting health care workers after medical error: considerations for health care leaders. JCOM. 2008;15(5):240–247.

“Inadequacy” with regard to surgical proceduresIndication for surgery is intrinsic to provision of appropriate care. Surgery inherently poses the possibility of unexpected problems. Adequate training and skill, therefore, must include the ability to deal with a range of problems that arise in the course of surgery. The spectrum related to inadequacy as related to surgical problems includes “failed surgery,” defined as “if despite the utmost care of everyone involved and with the responsible consideration of all knowledge, the designed aim is not achieved, surgery by itself has failed.”⁵ Of paramount importance is the surgeon’s knowledge of technology and the ability to troubleshoot, as well as the OR team’s responsibility for proper maintenance of equipment to ensure optimal functionality.¹

Aviation industry studies indicate that “high performing cockpit crews have been shown to devote one third of their communications to discuss threats and mistakes in their environment, while poor performing teams devoted much less, about 5%, of their time to such.”^1,13 A well-trained and well-motivated OR nursing team has been equated with reduction in operative time and rate of conversion to laparotomy.¹⁴ Outdated instruments may also contribute to surgical errors.¹

Moving the “learning curve” out of the OR and into the simulation lab remains valuable, which is also confirmed by the aviation industry.¹⁵ The significance of loss of haptic perception continues to be debated between laparoscopic (straight-stick) surgeons and those performing robotic approaches. Does haptic perception play a major role in surgical intervention? Most surgeons do not view loss of haptic perception, as with minimally invasive procedures, as a major impediment to successful surgery. From the legal perspective, loss of haptic perception has not been well addressed.

The American College of Obstetricians and Gynecologists has focused on patient safety in the surgical environment including concerns for wrong-patient surgery, wrong-side surgery, wrong-level surgery, and wrong-part surgery.¹⁶ The Joint Commission has identified factors that may enhance the risk of wrong-site surgery: multiple surgeons involved in the case, multiple procedures during a single surgical visit, unusual time pressures to start or complete the surgery, and unusual physical characteristics including morbid obesity or physical deformity.¹⁶

10 starting points for medical error preventionSo what are we to do? Consider:

Set the stage for best outcomesA true team approach is an excellent modus operandi before, during, and after surgery,setting the stage for best outcomes for patients.

“As human beings, surgeons will commit errors and for this reason they have to adopt and utilize stringent defense systems to minimize the incidence of these adverse events … Transparency is the first step on the way to a new safety culture with the acknowledgement of errors when they occur with adoption of systems destined to establish their cause and future prevention.”¹

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE Surgeon accused of operating outside her scope of expertise

A 38-year-old woman (G2 P2002) presented to the emergency department (ED) with acute pelvic pain involving the right lower quadrant (RLQ). The patient had a history of stage IV endometriosis and chronic pelvic pain, primarily affecting the RLQ, that was treated by total laparoscopic hysterectomy with bilateral salpingo-oophorectomy 6 months earlier. Pertinent findings on physical examination included hypoactive bowel sounds and rebound tenderness. The ED physician ordered a computed tomography (CT) scan of the abdomen, which showed no evidence of ureteral injury or other abnormality. The gynecologist who performed the surgery 6 months ago evaluated the patient in the ED.

The gynecologist decided to perform operative laparoscopy because of the severity of the patient’s pain and duration of symptoms. Informed consent obtained in the ED before the patient received analgesics included a handwritten note that said “and other indicated procedures.” The patient signed the document prior to being taken to the operating room (OR). Time out occurred in the OR before anesthesia induction. The gynecologist proceeded with laparoscopic adhesiolysis with planned appendectomy, as she was trained. A normal appendix was noted and left intact. RLQ adhesions involving the colon and abdominal wall were treated with electrosurgical cautery. When the gynecologist found adhesions between the liver and diaphragm in the right upper quadrant (RUQ), she continued adhesiolysis. However, the diaphragm was inadvertently punctured.

As the gynecologist attempted to suture the defect laparoscopically, she encountered difficulty and converted to laparotomy. Adhesions were dense and initially precluded adequate closure of the diaphragmatic defect. The gynecologist persisted and ultimately the closure was adequate; laparotomy concluded. Postoperatively, the patient was given a diagnosis of atelectasis, primarily on the right side; a chest tube was placed by the general surgery team. The patient had an uneventful postoperative period and was discharged on postoperative day 5. One month later she returned to the ED with evidence of pneumonia; she was given a diagnosis of empyema, and antibiotics were administered. She responded well and was discharged after 6 days.

The patient filed a malpractice lawsuit against the gynecologist, the hospital, and associated practitioners. The suit made 3 negligence claims: 1) the surgery was improperly performed, as evidenced by the diaphragmatic perforation; 2) the gynecologist was not adequately trained for RUQ surgery, and 3) the hospital should not have permitted RUQ surgery to proceed. The liability claim cited the lack of qualification of a gynecologic surgeon to proceed with surgical intervention near the diaphragm and the associated consequences of practicing outside the scope of expertise.

Fitz-Hugh Curtis syndrome, a complication of pelvic inflammatory disease that may cause adhesions, was raised as the initial finding at the second surgical procedure and documented as such in the operative report. The plaintiff’s counsel questioned whether surgical correction of this syndrome was within the realm of a gynecologic surgeon. The plaintiff’s counsel argued that the laparoscopic surgical procedure involved bowel and liver; diaphragmatic adhesiolysis was not indicated, especially with normal abdominal CT scan results and the absence of RUQ symptoms. The claim specified that the surgery and care, as a consequence of the RUQ adhesiolysis, resulted in atelectasis, pneumonia, and empyema, with pain and suffering. The plaintiff sought unspecified monetary damages for these results.

What’s the verdict?

The case is in negotiation prior to trial.

Legal and medical considerations

“To err is not just human but intrinsically biological and no profession is exempt from fallibility.”¹

Error and liability

To err may be human, but human error is not necessarily the cause of every suboptimal medical outcome. In fact, the overall surgical complication rate has been reported at 3.4%.² Even when there is an error, it may not have been the kind of error that gives rise to medical malpractice liability. When it comes to surgical errors, the most common are those that actually relate to medications given at surgery that appear to be more common—one recent study found that 1 in 20 perioperative medication administrations resulted in a medication error or an adverse drug event.³

Medical error vs medical malpractice

The fact is that medical error and medical malpractice (or professional negligence) are not the same thing. It is critical to understand the difference.

Medical error is the third leading cause of death in the United States.⁴ It is defined as “the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim,”⁵ or, in the Canadian literature, “an act of omission or commission in planning or execution that contributes or could contribute to an unintended result.”⁶ The gamut of medical errors spans (among others) problems with technique, judgment, medication administration, diagnostic and surgical errors, and incomplete record keeping.⁵

Negligent error, on the other hand, is generally a subset of medical error recognized by the law. It is error that occurs because of carelessness. Technically, to give rise to liability for negligence (or malpractice) there must be duty, breach, causation, and injury. That is, the physician must owe a duty to the patient, the duty must have been breached, and that breach must have caused an injury.⁷

Usually the duty in medical practice is that the physician must have acted as a reasonable and prudent professional would have performed under the circumstances. For the most part, malpractice is a level of practice that the profession itself would not view as reasonable practice.⁸ Specialists usually are held to the higher standards of the specialty. It also can be negligent to undertake practice or a procedure for which the physician is not adequately trained, or for failing to refer the patient to another more qualified physician.

The duty in medicine usually arises from the physician-patient relationship (clearly present here). It is reasonably clear in this case that there was an injury, but, in fact, the question is whether the physician acted carelessly in a way that caused that injury. Our facts leave some ambiguity—unfortunately,a common problem in the real world.

It is possible that the gynecologist was negligent in puncturing the diaphragm. It may have been carelessness, for example, in the way the procedure was performed, or in the decision to proceed despite the difficulties encountered. It is also possible that the gynecologist was not appropriately trained and experienced in the surgery that was undertaken, in which case the decision to do the surgery (rather than to refer to another physician) could well have been negligent. In either of those cases, negligence liability (malpractice) is a possibility.

Proving negligence. It is the plaintiff (the patient) who must prove the elements of negligence (including causation).⁸ The plaintiff will have to demonstrate not only carelessness, but that carelessness is what caused the injuries for which she is seeking compensation. In this case, the injuries are the consequence of puncturing the diaphragm. The potential damages would be the money to cover the additional medical costs and other expenses, lost wages, and noneconomic damages such as pain and suffering.

The hospital’s role in negligence

The issue of informed consent is also raised in this case, with a handwritten note prior to surgery (but the focus of this article is on medical errors). In addition to the gynecologist, the hospital and other medical personnelwere sued. The hospital is responsible for the acts of its agents, notably its employees. Even if the physicians are not technically hospital employees, the hospital may in some cases be responsible. Among other things, the hospital likely has an obligation to prevent physicians from undertaking inappropriate procedures, including those for which the physician is not appropriately trained. If the gynecologist in this case did not have privileges to perform surgery in this category, the hospital may have an obligation to not schedule the surgery or to intraoperatively question her credentials for such a procedure. In any event, the hospital will have a major role in this case and its interests may, in some instances, be inconsistent with the interests of the physician.

Why settlement discussions?

The case description ends with a note that settlement discussions were underway. If the plaintiff must prove all of the elements of negligence, why have these discussions? First, such discussions are common in almost all negligence cases. This does not mean that the case actually will be settled by the insurance company representing the physician or hospital; many malpractice cases simply fade away because the patient drops the action. Second, there are ambiguities in the facts, and it is sometimes impossible to determine whether or not a jury would find negligence. The hospital may be inclined to settle if there is any realistic chance of a jury ruling against it. Paying a small settlement may be worth avoiding high legal expenses and the risk of an adverse outcome at trial.⁹

Reducing medical/surgical error through a team approach

Recognizing that “human performance can be affected by many factors that include circadian rhythms, state of mind, physical health, attitude, emotions, propensity for certain common mistakes and errors, and cognitive biases,”¹⁰ health care professionals have a commitment to reduce the errors in the interest of patient safety and best practice.

The surgical environment is an opportunity to provide a team approach to patient safety. Surgical risk is a reflection of operative performance, the main factor in the development of postoperative complications.¹¹ We wish to broaden the perspective that gynecologic surgeons, like all surgeons, must keep in mind a number of concerns that can be associated with problems related to surgical procedures, including¹²:

• visual perception difficulties
• stress
• loss of haptic perception (feedback using touch), as with robot-assisted procedures
• lack of situational awareness (a term we borrow from the aviation industry)
• long-term (and short-term) memory problems.

Analysis of surgical errors shows that they are related to, in order of frequency ¹:

• surgical technique
• judgment
• inattention to detail
• incomplete understanding of the problem or surgical situation.

Medical errors: Caring for the second victim (you)

Patrice M. Weiss, MD

We use the term “victim” to refer to the patient and her family following a medical error. The phrase “the second victim” was coined by Dr. Albert Wu in an article in the British Medical Journal¹ and describes how a clinician and team of health care professionals also can be affected by medical errors.

 

What signs and symptoms identify a second victim?Those suffering as a second victim may show signs of depression, loss of joy in work, and difficulty sleeping. They also may replay the events, question their own ability, and feel fearful about making another error. These reactions can lead to burnout—a serious issue that 46% of physicians report.²

As colleagues of those involved in a medical error, we should be cognizant of changes in behavior such as excessive irritability, showing up late for work, or agitation. It may be easier to recognize these symptoms in others rather than in ourselves because we often do not take time to examine how our experiences may affect us personally. Heightening awareness can help us recognize those suffering as second victims and identify the second victim symptoms in ourselves.
 

How can we help second victims?One challenge second victims face is not being allowed to discuss a medical error. Certainly, due to confidentiality requirements during professional liability cases, we should not talk freely about the event. However, silence creates a barrier that prevents a second victim from processing the incident.

Some hospitals offer forums to discuss medical errors, with the goal of preventing reoccurrence: morbidity and mortality conferences, morning report, Quality Assurance and Performance Improvement meetings, and root cause analyses. These forums often are not perceived by institutions’ employees in a positive way. Are they really meant to improve patient care or do they single out an individual or group in a “name/blame/shame game”? An intimidating process will only worsen a second victim’s symptoms. It is not necessary, however, to create a whole new process; it is possible to restructure, reframe, and change the culture of an existing practice.

Some institutions have developed a formalized program to help second victims. The University of Missouri has a “forYOU team,” an internal, rapid response group that provides emotional first aid to the entire team involved in a medical error case. These responders are not from human resources and do not need to be sought out; they are peers who have been educated about the struggles of the second victim. They will not discuss the case or how care was rendered; they naturally and instinctively provide emotional support to their colleagues.

At my institution, the Carilion Clinic at the Virginia Tech Carilion School of Medicine, “The Trust Program” encourages truth, respectfulness, understanding, support, and transparency. All health care clinicians receive basic training, but many have volunteered for additional instruction to become mentors because they have experienced second-victim symptoms themselves.

Clinicians want assistance when dealing with a medical error. One poll reports that 90% of physicians felt that health care organizations did not adequately help them cope with the stresses associated with a medical error.³ The goal is to have all institutions recognize that clinicians can be affected by a medical error and offer support.

To hear an expanded audiocast from Dr. Weiss on “the second victim” click here.

---

Dr. Weiss is Professor, Department of Obstetrics & Gynecology, Virginia Tech Carilion School of Medicine, and Chief Medical Officer and Executive Vice President, Carilion Clinic, Roanoke, Virginia.

The author reports no financial relationships relevant to this article.

 

---

References

1. Wu AW. Medical error: the second victim. BMJ. 2000;320(7237):726–727.
2. Peckham C. Medscape Physician Lifestyle Report 2015. Medscape website. http://www.medscape.com/features/slideshow/lifestyle/2015/public/overview#1. Published January 26, 2015. Accessed May 24, 2016.
3. White AA, Waterman AD, McCotter P, Boyle DJ, Gallagher TH. Supporting health care workers after medical error: considerations for health care leaders. JCOM. 2008;15(5):240–247.

“Inadequacy” with regard to surgical proceduresIndication for surgery is intrinsic to provision of appropriate care. Surgery inherently poses the possibility of unexpected problems. Adequate training and skill, therefore, must include the ability to deal with a range of problems that arise in the course of surgery. The spectrum related to inadequacy as related to surgical problems includes “failed surgery,” defined as “if despite the utmost care of everyone involved and with the responsible consideration of all knowledge, the designed aim is not achieved, surgery by itself has failed.”⁵ Of paramount importance is the surgeon’s knowledge of technology and the ability to troubleshoot, as well as the OR team’s responsibility for proper maintenance of equipment to ensure optimal functionality.¹

Aviation industry studies indicate that “high performing cockpit crews have been shown to devote one third of their communications to discuss threats and mistakes in their environment, while poor performing teams devoted much less, about 5%, of their time to such.”^1,13 A well-trained and well-motivated OR nursing team has been equated with reduction in operative time and rate of conversion to laparotomy.¹⁴ Outdated instruments may also contribute to surgical errors.¹

Moving the “learning curve” out of the OR and into the simulation lab remains valuable, which is also confirmed by the aviation industry.¹⁵ The significance of loss of haptic perception continues to be debated between laparoscopic (straight-stick) surgeons and those performing robotic approaches. Does haptic perception play a major role in surgical intervention? Most surgeons do not view loss of haptic perception, as with minimally invasive procedures, as a major impediment to successful surgery. From the legal perspective, loss of haptic perception has not been well addressed.

The American College of Obstetricians and Gynecologists has focused on patient safety in the surgical environment including concerns for wrong-patient surgery, wrong-side surgery, wrong-level surgery, and wrong-part surgery.¹⁶ The Joint Commission has identified factors that may enhance the risk of wrong-site surgery: multiple surgeons involved in the case, multiple procedures during a single surgical visit, unusual time pressures to start or complete the surgery, and unusual physical characteristics including morbid obesity or physical deformity.¹⁶

10 starting points for medical error preventionSo what are we to do? Consider:

Set the stage for best outcomesA true team approach is an excellent modus operandi before, during, and after surgery,setting the stage for best outcomes for patients.

“As human beings, surgeons will commit errors and for this reason they have to adopt and utilize stringent defense systems to minimize the incidence of these adverse events … Transparency is the first step on the way to a new safety culture with the acknowledgement of errors when they occur with adoption of systems destined to establish their cause and future prevention.”¹

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE Surgeon accused of operating outside her scope of expertise

A 38-year-old woman (G2 P2002) presented to the emergency department (ED) with acute pelvic pain involving the right lower quadrant (RLQ). The patient had a history of stage IV endometriosis and chronic pelvic pain, primarily affecting the RLQ, that was treated by total laparoscopic hysterectomy with bilateral salpingo-oophorectomy 6 months earlier. Pertinent findings on physical examination included hypoactive bowel sounds and rebound tenderness. The ED physician ordered a computed tomography (CT) scan of the abdomen, which showed no evidence of ureteral injury or other abnormality. The gynecologist who performed the surgery 6 months ago evaluated the patient in the ED.

The gynecologist decided to perform operative laparoscopy because of the severity of the patient’s pain and duration of symptoms. Informed consent obtained in the ED before the patient received analgesics included a handwritten note that said “and other indicated procedures.” The patient signed the document prior to being taken to the operating room (OR). Time out occurred in the OR before anesthesia induction. The gynecologist proceeded with laparoscopic adhesiolysis with planned appendectomy, as she was trained. A normal appendix was noted and left intact. RLQ adhesions involving the colon and abdominal wall were treated with electrosurgical cautery. When the gynecologist found adhesions between the liver and diaphragm in the right upper quadrant (RUQ), she continued adhesiolysis. However, the diaphragm was inadvertently punctured.

As the gynecologist attempted to suture the defect laparoscopically, she encountered difficulty and converted to laparotomy. Adhesions were dense and initially precluded adequate closure of the diaphragmatic defect. The gynecologist persisted and ultimately the closure was adequate; laparotomy concluded. Postoperatively, the patient was given a diagnosis of atelectasis, primarily on the right side; a chest tube was placed by the general surgery team. The patient had an uneventful postoperative period and was discharged on postoperative day 5. One month later she returned to the ED with evidence of pneumonia; she was given a diagnosis of empyema, and antibiotics were administered. She responded well and was discharged after 6 days.

The patient filed a malpractice lawsuit against the gynecologist, the hospital, and associated practitioners. The suit made 3 negligence claims: 1) the surgery was improperly performed, as evidenced by the diaphragmatic perforation; 2) the gynecologist was not adequately trained for RUQ surgery, and 3) the hospital should not have permitted RUQ surgery to proceed. The liability claim cited the lack of qualification of a gynecologic surgeon to proceed with surgical intervention near the diaphragm and the associated consequences of practicing outside the scope of expertise.

Fitz-Hugh Curtis syndrome, a complication of pelvic inflammatory disease that may cause adhesions, was raised as the initial finding at the second surgical procedure and documented as such in the operative report. The plaintiff’s counsel questioned whether surgical correction of this syndrome was within the realm of a gynecologic surgeon. The plaintiff’s counsel argued that the laparoscopic surgical procedure involved bowel and liver; diaphragmatic adhesiolysis was not indicated, especially with normal abdominal CT scan results and the absence of RUQ symptoms. The claim specified that the surgery and care, as a consequence of the RUQ adhesiolysis, resulted in atelectasis, pneumonia, and empyema, with pain and suffering. The plaintiff sought unspecified monetary damages for these results.

What’s the verdict?

The case is in negotiation prior to trial.

Legal and medical considerations

“To err is not just human but intrinsically biological and no profession is exempt from fallibility.”¹

Error and liability

To err may be human, but human error is not necessarily the cause of every suboptimal medical outcome. In fact, the overall surgical complication rate has been reported at 3.4%.² Even when there is an error, it may not have been the kind of error that gives rise to medical malpractice liability. When it comes to surgical errors, the most common are those that actually relate to medications given at surgery that appear to be more common—one recent study found that 1 in 20 perioperative medication administrations resulted in a medication error or an adverse drug event.³

Medical error vs medical malpractice

The fact is that medical error and medical malpractice (or professional negligence) are not the same thing. It is critical to understand the difference.

Medical error is the third leading cause of death in the United States.⁴ It is defined as “the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim,”⁵ or, in the Canadian literature, “an act of omission or commission in planning or execution that contributes or could contribute to an unintended result.”⁶ The gamut of medical errors spans (among others) problems with technique, judgment, medication administration, diagnostic and surgical errors, and incomplete record keeping.⁵

Negligent error, on the other hand, is generally a subset of medical error recognized by the law. It is error that occurs because of carelessness. Technically, to give rise to liability for negligence (or malpractice) there must be duty, breach, causation, and injury. That is, the physician must owe a duty to the patient, the duty must have been breached, and that breach must have caused an injury.⁷

Usually the duty in medical practice is that the physician must have acted as a reasonable and prudent professional would have performed under the circumstances. For the most part, malpractice is a level of practice that the profession itself would not view as reasonable practice.⁸ Specialists usually are held to the higher standards of the specialty. It also can be negligent to undertake practice or a procedure for which the physician is not adequately trained, or for failing to refer the patient to another more qualified physician.

The duty in medicine usually arises from the physician-patient relationship (clearly present here). It is reasonably clear in this case that there was an injury, but, in fact, the question is whether the physician acted carelessly in a way that caused that injury. Our facts leave some ambiguity—unfortunately,a common problem in the real world.

It is possible that the gynecologist was negligent in puncturing the diaphragm. It may have been carelessness, for example, in the way the procedure was performed, or in the decision to proceed despite the difficulties encountered. It is also possible that the gynecologist was not appropriately trained and experienced in the surgery that was undertaken, in which case the decision to do the surgery (rather than to refer to another physician) could well have been negligent. In either of those cases, negligence liability (malpractice) is a possibility.

Proving negligence. It is the plaintiff (the patient) who must prove the elements of negligence (including causation).⁸ The plaintiff will have to demonstrate not only carelessness, but that carelessness is what caused the injuries for which she is seeking compensation. In this case, the injuries are the consequence of puncturing the diaphragm. The potential damages would be the money to cover the additional medical costs and other expenses, lost wages, and noneconomic damages such as pain and suffering.

The hospital’s role in negligence

The issue of informed consent is also raised in this case, with a handwritten note prior to surgery (but the focus of this article is on medical errors). In addition to the gynecologist, the hospital and other medical personnelwere sued. The hospital is responsible for the acts of its agents, notably its employees. Even if the physicians are not technically hospital employees, the hospital may in some cases be responsible. Among other things, the hospital likely has an obligation to prevent physicians from undertaking inappropriate procedures, including those for which the physician is not appropriately trained. If the gynecologist in this case did not have privileges to perform surgery in this category, the hospital may have an obligation to not schedule the surgery or to intraoperatively question her credentials for such a procedure. In any event, the hospital will have a major role in this case and its interests may, in some instances, be inconsistent with the interests of the physician.

Why settlement discussions?

The case description ends with a note that settlement discussions were underway. If the plaintiff must prove all of the elements of negligence, why have these discussions? First, such discussions are common in almost all negligence cases. This does not mean that the case actually will be settled by the insurance company representing the physician or hospital; many malpractice cases simply fade away because the patient drops the action. Second, there are ambiguities in the facts, and it is sometimes impossible to determine whether or not a jury would find negligence. The hospital may be inclined to settle if there is any realistic chance of a jury ruling against it. Paying a small settlement may be worth avoiding high legal expenses and the risk of an adverse outcome at trial.⁹

Reducing medical/surgical error through a team approach

Recognizing that “human performance can be affected by many factors that include circadian rhythms, state of mind, physical health, attitude, emotions, propensity for certain common mistakes and errors, and cognitive biases,”¹⁰ health care professionals have a commitment to reduce the errors in the interest of patient safety and best practice.

The surgical environment is an opportunity to provide a team approach to patient safety. Surgical risk is a reflection of operative performance, the main factor in the development of postoperative complications.¹¹ We wish to broaden the perspective that gynecologic surgeons, like all surgeons, must keep in mind a number of concerns that can be associated with problems related to surgical procedures, including¹²:

• visual perception difficulties
• stress
• loss of haptic perception (feedback using touch), as with robot-assisted procedures
• lack of situational awareness (a term we borrow from the aviation industry)
• long-term (and short-term) memory problems.

Analysis of surgical errors shows that they are related to, in order of frequency ¹:

• surgical technique
• judgment
• inattention to detail
• incomplete understanding of the problem or surgical situation.

Medical errors: Caring for the second victim (you)

Patrice M. Weiss, MD

We use the term “victim” to refer to the patient and her family following a medical error. The phrase “the second victim” was coined by Dr. Albert Wu in an article in the British Medical Journal¹ and describes how a clinician and team of health care professionals also can be affected by medical errors.

 

What signs and symptoms identify a second victim?Those suffering as a second victim may show signs of depression, loss of joy in work, and difficulty sleeping. They also may replay the events, question their own ability, and feel fearful about making another error. These reactions can lead to burnout—a serious issue that 46% of physicians report.²

As colleagues of those involved in a medical error, we should be cognizant of changes in behavior such as excessive irritability, showing up late for work, or agitation. It may be easier to recognize these symptoms in others rather than in ourselves because we often do not take time to examine how our experiences may affect us personally. Heightening awareness can help us recognize those suffering as second victims and identify the second victim symptoms in ourselves.
 

How can we help second victims?One challenge second victims face is not being allowed to discuss a medical error. Certainly, due to confidentiality requirements during professional liability cases, we should not talk freely about the event. However, silence creates a barrier that prevents a second victim from processing the incident.

Some hospitals offer forums to discuss medical errors, with the goal of preventing reoccurrence: morbidity and mortality conferences, morning report, Quality Assurance and Performance Improvement meetings, and root cause analyses. These forums often are not perceived by institutions’ employees in a positive way. Are they really meant to improve patient care or do they single out an individual or group in a “name/blame/shame game”? An intimidating process will only worsen a second victim’s symptoms. It is not necessary, however, to create a whole new process; it is possible to restructure, reframe, and change the culture of an existing practice.

Some institutions have developed a formalized program to help second victims. The University of Missouri has a “forYOU team,” an internal, rapid response group that provides emotional first aid to the entire team involved in a medical error case. These responders are not from human resources and do not need to be sought out; they are peers who have been educated about the struggles of the second victim. They will not discuss the case or how care was rendered; they naturally and instinctively provide emotional support to their colleagues.

At my institution, the Carilion Clinic at the Virginia Tech Carilion School of Medicine, “The Trust Program” encourages truth, respectfulness, understanding, support, and transparency. All health care clinicians receive basic training, but many have volunteered for additional instruction to become mentors because they have experienced second-victim symptoms themselves.

Clinicians want assistance when dealing with a medical error. One poll reports that 90% of physicians felt that health care organizations did not adequately help them cope with the stresses associated with a medical error.³ The goal is to have all institutions recognize that clinicians can be affected by a medical error and offer support.

To hear an expanded audiocast from Dr. Weiss on “the second victim” click here.

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Dr. Weiss is Professor, Department of Obstetrics & Gynecology, Virginia Tech Carilion School of Medicine, and Chief Medical Officer and Executive Vice President, Carilion Clinic, Roanoke, Virginia.

The author reports no financial relationships relevant to this article.

 

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References

1. Wu AW. Medical error: the second victim. BMJ. 2000;320(7237):726–727.
2. Peckham C. Medscape Physician Lifestyle Report 2015. Medscape website. http://www.medscape.com/features/slideshow/lifestyle/2015/public/overview#1. Published January 26, 2015. Accessed May 24, 2016.
3. White AA, Waterman AD, McCotter P, Boyle DJ, Gallagher TH. Supporting health care workers after medical error: considerations for health care leaders. JCOM. 2008;15(5):240–247.

“Inadequacy” with regard to surgical proceduresIndication for surgery is intrinsic to provision of appropriate care. Surgery inherently poses the possibility of unexpected problems. Adequate training and skill, therefore, must include the ability to deal with a range of problems that arise in the course of surgery. The spectrum related to inadequacy as related to surgical problems includes “failed surgery,” defined as “if despite the utmost care of everyone involved and with the responsible consideration of all knowledge, the designed aim is not achieved, surgery by itself has failed.”⁵ Of paramount importance is the surgeon’s knowledge of technology and the ability to troubleshoot, as well as the OR team’s responsibility for proper maintenance of equipment to ensure optimal functionality.¹

Aviation industry studies indicate that “high performing cockpit crews have been shown to devote one third of their communications to discuss threats and mistakes in their environment, while poor performing teams devoted much less, about 5%, of their time to such.”^1,13 A well-trained and well-motivated OR nursing team has been equated with reduction in operative time and rate of conversion to laparotomy.¹⁴ Outdated instruments may also contribute to surgical errors.¹

Moving the “learning curve” out of the OR and into the simulation lab remains valuable, which is also confirmed by the aviation industry.¹⁵ The significance of loss of haptic perception continues to be debated between laparoscopic (straight-stick) surgeons and those performing robotic approaches. Does haptic perception play a major role in surgical intervention? Most surgeons do not view loss of haptic perception, as with minimally invasive procedures, as a major impediment to successful surgery. From the legal perspective, loss of haptic perception has not been well addressed.

The American College of Obstetricians and Gynecologists has focused on patient safety in the surgical environment including concerns for wrong-patient surgery, wrong-side surgery, wrong-level surgery, and wrong-part surgery.¹⁶ The Joint Commission has identified factors that may enhance the risk of wrong-site surgery: multiple surgeons involved in the case, multiple procedures during a single surgical visit, unusual time pressures to start or complete the surgery, and unusual physical characteristics including morbid obesity or physical deformity.¹⁶

10 starting points for medical error preventionSo what are we to do? Consider:

Set the stage for best outcomesA true team approach is an excellent modus operandi before, during, and after surgery,setting the stage for best outcomes for patients.

“As human beings, surgeons will commit errors and for this reason they have to adopt and utilize stringent defense systems to minimize the incidence of these adverse events … Transparency is the first step on the way to a new safety culture with the acknowledgement of errors when they occur with adoption of systems destined to establish their cause and future prevention.”¹

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Transvaginal ultrasound: We are gaining a better understanding of its clinical applications

Steven R. Goldstein, MD

In my first book I coined the phrase "sonomicroscopy." We are seeing things with transvaginal ultrasonography (TVUS) that you could not see with your naked eye even if you could it hold it at arms length and squint at it. For instance, cardiac activity can be seen easily within an embryo of 4 mm at 47 days since the last menstrual period. If there were any possible way to hold this 4-mm embryo in your hand, you would not appreciate cardiac pulsations contained within it! This is one of the beauties, and yet potential foibles, of TVUS.

In this excellent pictorial article, Michelle Stalnaker Ozcan, MD, and Andrew M. Kaunitz, MD, have done an outstanding job of turning this low-power "sonomicroscope" into the uterus to better understand a number of unique yet important clinical applications of TVUS.

Tamoxifen is known to cause a slight but statistically significant increase in endometrial cancer. In 1994, I first described an unusual ultrasound appearance in the uterus of patients receiving tamoxifen, which was being misinterpreted as "endometrial thickening," and resulted in many unnecessary biopsies and dilation and curettage procedures.¹ This type of uterine change has been seen in other selective estrogen-receptor modulators as well.^2,3 In this article, Drs. Ozcan and Kaunitz correctly point out that such an ultrasound pattern does not necessitate any intervention in the absence of bleeding. 

Another common question I am often asked is, "How do we handle the patient whose status is post-endometrial ablation and presents with staining?" The scarring shown in the figures that follow make any kind of meaningful evaluation extremely difficult. 

There has been an epidemic of cesarean scar pregnancies when a subsequent gestation implants in the cesarean scar defect.⁴ Perhaps the time has come when all patients with a previous cesarean delivery should have their lower uterine segment scanned to look for such a defect as shown in the pictures that follow. If we are not yet ready for that, at least early TVUS scans in subsequent pregnancies, in my opinion, should be employed to make an early diagnosis of such cases that are the precursors of morbidly adherent placenta, a potentially life-threatening situation that appears to be increasing in frequency.

Finally, look to obgmanagement.com for next month's web-exclusive look at outstanding images of patients who have undergone transcervical sterilization.

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Dr. Goldstein is Professor, Department of Obstetrics and Gynecology, New York University School of Medicine, Director, Gynecologic Ultrasound, and Co-Director, Bone Densitometry, New York University Medical Center. He also serves on the OBG Management Board of Editors.

Dr. Goldstein reports that he has an equipment loan from Philips, and is past President of the American Institute of Ultrasound in Medicine.

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References

1. Goldstein SR. Unusual ultrasonographic appearance of the uterus in patients receiving tamoxifen. Am J Obstet Gynecol. 1994;170(2):447–451.
2. Goldstein SR, Neven P, Cummings S, et al. Postmenopausal evaluation and risk reduction with lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18(1):17–22.
3. Goldstein SR, Nanavati N. Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Am J Obstet Gynecol. 2002;187(3):521–527.
4. Timor-Tritsch IE, Monteagudo A. Unforeseen consequences of the increasing rate of cesarean deliveries: early placenta accreta and cesarean scar pregnancy. A review. Am J Obstet Gynecol. 2012;207(1):14–29.

New technology, minimally invasive surgical procedures, and medications continue to change how physicians manage specific medical issues. Many procedures and medications used by gynecologists can cause characteristic findings on sonography. These findings can guide subsequent counseling and management decisions and are important to accurately interpret on imaging. Among these conditions are Asherman syndrome, postendometrial ablation uterine damage, cesarean scar defect, and altered endometrium as a result of tamoxifen use. In this article, we provide 2 dimensional and 3 dimensional sono‑graphic images of uterine presentations of these 4 conditions.

Asherman syndromeCharacterized by variable scarring, or intrauterine adhesions, inside the uterine cavity following endometrial trauma due to surgical procedures, Asherman syndrome can cause menstrual changes and infertility. Should pregnancy occur in the setting of Asherman syndrome, placental abnormalities may result.¹ Intrauterine adhesions can follow many surgical procedures, including curettage (diagnostic or for missed/elective abortion or retained products of conception), cesarean delivery, and hysteroscopic myomectomy. They may even occur after spontaneous abortion without curettage. Rates of Asherman syndrome are highest after procedures that tend to cause the most intrauterine inflammation, including²:

• curettage after septic abortion
• late curettage after retained products of conception
• hysteroscopy with multiple myomectomies.

In severe cases Asherman syndrome can result in complete obliteration of the uterine cavity.³

Clinicians should be cognizant of the appearance of Asherman syndrome on imaging because patients reporting menstrual abnormalities, pelvic pain (FIGURE 1), infertility, and other symptoms may exhibit intrauterine lesions on sonohysterography, or sometimes unenhanced sonography if endometrial fluid/blood is present. Depending on symptoms and patient reproductive plans, treatment may be indicated.²

FIGURE 1 Asherman syndrome

Postablation endometrial destruction
Surgical destruction of the endometrium to the level of the basalis has been associated with the formation of intrauterine adhesions (FIGURE 2) as well as pockets of hematometra (FIGURE 3). In a large Cochrane systematic review, the reported rate of hematometra was 0.9% following non− resectoscopic ablation and 2.4% following resectoscopic ablation.⁴

FIGURE 2 Intrauterine changes postablation

Loculated fluid collections in the endometrium on transverse (A), sagittal (B), and 3 dimensional images (C) of a 41-year-old patient who presented with dysmenorrhea 3 years after an endometrial ablation procedure. The patient ultimately underwent transvaginal hysterectomy.

FIGURE 3 Postablation hematometrum

2 dimensional sonograms of a 40-year-old patient with a history of bilateral tubal ligation who presented for severe cyclic pelvic pain postablation.