U.S. jurisdictions are letting pharmacists dispense more vaccines to younger patients with less direct prescriber oversight but barriers remain.

Since the 1990s, states have made laws to increase access to immunization services by giving pharmacists authority to give vaccines, said Cason D. Schmit, JD, of Texas A&M University at College Station, and Matthew S. Penn, JD, director of the Public Health Law Program at the Centers for Disease Control and Prevention, Atlanta. This has the advantage of pharmacies being open longer hours than most physicians’ offices, in addition to the opportunities for immunizing people in rural locations as well as those people without a regular physician.

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U.S. jurisdictions are letting pharmacists dispense more vaccines to younger patients with less direct prescriber oversight but barriers remain.

Since the 1990s, states have made laws to increase access to immunization services by giving pharmacists authority to give vaccines, said Cason D. Schmit, JD, of Texas A&M University at College Station, and Matthew S. Penn, JD, director of the Public Health Law Program at the Centers for Disease Control and Prevention, Atlanta. This has the advantage of pharmacies being open longer hours than most physicians’ offices, in addition to the opportunities for immunizing people in rural locations as well as those people without a regular physician.

copyright itsmejust/Thinkstock

U.S. jurisdictions are letting pharmacists dispense more vaccines to younger patients with less direct prescriber oversight but barriers remain.

Since the 1990s, states have made laws to increase access to immunization services by giving pharmacists authority to give vaccines, said Cason D. Schmit, JD, of Texas A&M University at College Station, and Matthew S. Penn, JD, director of the Public Health Law Program at the Centers for Disease Control and Prevention, Atlanta. This has the advantage of pharmacies being open longer hours than most physicians’ offices, in addition to the opportunities for immunizing people in rural locations as well as those people without a regular physician.

copyright itsmejust/Thinkstock

SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.

Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.

“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”

He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.

“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.

Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.

Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).

In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.

All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.

Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.

The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.

The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.

Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.

The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.

Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”

Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.

Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.

Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets. 

SOURCE: Bardia A et al. Abstract GS1-07.

SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.

Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.

“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”

He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.

“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.

Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.

Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).

In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.

All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.

Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.

The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.

The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.

Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.

The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.

Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”

Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.

Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.

Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets. 

SOURCE: Bardia A et al. Abstract GS1-07.

SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.

Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.

“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”

He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.

“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.

Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.

Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).

In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.

All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.

Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.

The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.

The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.

Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.

The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.

Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”

Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.

Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.

Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets. 

SOURCE: Bardia A et al. Abstract GS1-07.

Parents generally can take photographs of good enough quality to allow accurate teledermatology diagnoses to be made of many pediatric skin conditions, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.

Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.

copyright/Thinkstock.com

Parents generally can take photographs of good enough quality to allow accurate teledermatology diagnoses to be made of many pediatric skin conditions, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.

Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.

copyright/Thinkstock.com

Parents generally can take photographs of good enough quality to allow accurate teledermatology diagnoses to be made of many pediatric skin conditions, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.

Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.

copyright/Thinkstock.com

Patients with nonradiographic axial spondyloarthritis (nr-axSpA) who enter remission on adalimumab are likely to relapse if the medication is withdrawn – and many won’t attain remission again, even if the drug is restarted.

However, the findings of the ABILITY-3 trial do offer an intriguing potential, Robert Landewé, MD, PhD, said at the annual meeting of the American College of Rheumatology. About 30% of the study group did maintain remission after adalimumab (Humira) withdrawal, suggesting that at least a portion of these patients can stay in good clinical shape off TNF inhibition.

msullivan@frontlinemedcom.com

SOURCE: Landewé R et al. ACR 2017 Abstract 1787.

Patients with nonradiographic axial spondyloarthritis (nr-axSpA) who enter remission on adalimumab are likely to relapse if the medication is withdrawn – and many won’t attain remission again, even if the drug is restarted.

However, the findings of the ABILITY-3 trial do offer an intriguing potential, Robert Landewé, MD, PhD, said at the annual meeting of the American College of Rheumatology. About 30% of the study group did maintain remission after adalimumab (Humira) withdrawal, suggesting that at least a portion of these patients can stay in good clinical shape off TNF inhibition.

msullivan@frontlinemedcom.com

SOURCE: Landewé R et al. ACR 2017 Abstract 1787.

Patients with nonradiographic axial spondyloarthritis (nr-axSpA) who enter remission on adalimumab are likely to relapse if the medication is withdrawn – and many won’t attain remission again, even if the drug is restarted.

However, the findings of the ABILITY-3 trial do offer an intriguing potential, Robert Landewé, MD, PhD, said at the annual meeting of the American College of Rheumatology. About 30% of the study group did maintain remission after adalimumab (Humira) withdrawal, suggesting that at least a portion of these patients can stay in good clinical shape off TNF inhibition.

msullivan@frontlinemedcom.com

SOURCE: Landewé R et al. ACR 2017 Abstract 1787.

There are currently 15 drugs indicated for adverse conditions of the urinary tract. The reported frequency of use in pregnancy and during breastfeeding for most of these agents is very low or completely absent.

The five subclasses of urinary tract agents are analgesics, antispasmodics, urinary acidifiers, urinary alkalinizers, and urinary germicides. With the exception of the three urinary germicides, anti-infectives are not covered in this column.

Analgesics

The analgesic subclass includes pentosan and phenazopyridine. Pentosan (Elmiron), a heparinlike compound, is an oral drug that is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. Systemic absorption is low, at about 6%. Because of the high molecular weight (4,000-6,000), it does not appear to cross the placenta, at least in the first half of pregnancy. A 1975 reference described its use in five women with preeclampsia. Each patient received 100 mg intramuscularly every 8 hours for about 5 days in the last weeks of pregnancy. No maternal benefit from the therapy was observed. There was apparently no fetal harm, but the neonatal outcomes were not described.

There are substantial – more than 900 – human pregnancy exposures in the first trimester with phenazopyridine. The exposures were not related to an increased risk of embryo-fetal harm and so use of the drug in pregnancy can be classified as compatible. However, the low molecular weight (about 214 for the free base) suggests that the drug will cross to the embryo and fetus.
 

Antispasmodics

The eight antispasmodics are darifenacin (Enablex), fesoterodine (Toviaz), flavoxate, mirabegron (Myrbetriq), oxybutynin (Ditropan XL), solifenacin (Vesicare), tolterodine (Detrol LA), and trospium.

These agents are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. The molecular weights range between 342 and 508, suggesting that all will cross the human placenta. There are no human pregnancy data for six of these agents and very limited data for flavoxate and oxybutynin. There is no evidence of embryo-fetal harm from these two drugs, but only one case involved exposure in the first trimester.

In seven of these drugs, the animal data suggested low risk. There was no embryo harm from doses that were equal to or less than 10 times the human dose based on body surface area (BSA) or area under the concentration curve (AUC). Solifenacin did cause embryo toxicity in pregnant mice. There was no embryo toxicity in pregnant rats and rabbits, but the maximum doses used were very low. Overall, the available data suggest that exposure to an antispasmodic in pregnancy is low risk for embryo, fetal, and newborn harm.
 

Urinary acidifiers

Ammonium chloride is a urinary acidifier as well as a respiratory expectorant. There is a large amount of data related to when the drug was used as an expectorant. There was no evidence that this use was associated with large categories of major or minor malformations. However, there were possible associations with three individual defects: inguinal hernia, cataract, and any benign tumor. No reports describing its use as a urinary acidifier have been located. When large amounts are consumed near term, the drug may cause acidosis in the mother and fetus. The molecular weight (about 53) suggests that it will cross the placenta.

Urinary alkalinizers

Potassium citrate (Urocit-K) is indicated for the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate with nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones. The molecular weight (about 307) suggests it will cross the placenta. Only one case of its use in pregnancy has been located. The newborn had an unspecified defect but no other information was provided. The animal data in four species suggest low risk.

Urinary germicides

There are three urinary germicides: methenamine, methylene blue, and nitrofurantoin. Methenamine is available as methenamine mandelate (molecular weight abut 292) and methenamine hippurate (molecular weight about 319). Both are metabolized to formaldehyde (molecular weight about 30), the active agent. The molecular weights suggest that all will cross the placenta. The use of methenamine during pregnancy has been reported in more than 750 pregnancies. There have been no embryo or fetal adverse effects attributed to the drug.

The human data involving oral methylene blue, a weak urinary germicide, is limited to 55 exposures. There were three infants with birth defects (type not specified). Several reports have described the use of intra-amniotic injections to assist in the diagnosis of suspected membrane rupture. This use has resulted in newborns with hemolytic anemia, hyperbilirubinemia with or without Heinz body formation, blue staining of the skin, and methemoglobinemia. Fetal deaths have also been described. Recommendations to avoid the intra-amniotic use of methylene blue were issued more than 10 years ago. Moreover, the use of oral methylene blue as a urinary germicide is no longer recommended.

The low molecular weight (about 238) of nitrofurantoin suggests that it will cross the placenta. It is commonly used in pregnancy for the treatment or prophylaxis of urinary tract infections. The large amount of human data indicates that the risk of drug-induced birth defects is low. Several cohort studies have found no increased risk for birth defects. However, some case-control studies have found increased risks for hypoplastic left heart syndrome and oral clefts. A 2015 review concluded that this difference was due to the increased sensitivity of case-control studies to detect adverse effects (J Obstet Gynaecol Can. 2015 Feb;37[2]:150-6).

Use of the drug close to term may cause hemolytic anemia in newborns who are glucose-6-phosphate dehydrogenase (G6PD) deficient. Although rare, this may also occur in newborns who are not G6PD deficient. The best course is to avoid use of the drug close to delivery. As for use of the drug in the first trimester, ACOG’s Committee on Obstetric Practice stated in Committee Opinion No. 717 that nitrofurantoin was still thought to be appropriate when no other suitable alternative antibiotics were available (Obstet Gynecol. 2017 Sept;130[3]:666-7).
 

Breastfeeding

Except for methenamine and nitrofurantoin, there are no data related to the use of the urinary tract drugs during breastfeeding. Peak levels of methenamine occur at 1 hour, but no reports of adverse effects on nursing infants have been located. Several reports have described the use of nitrofurantoin during breastfeeding. Minor diarrhea was noted in two infants. However, breastfeeding an infant with G6PD deficiency could lead to hemolytic anemia.

Phenazopyridine should be used with caution especially for an infant younger than 1 month or with G6PD deficiency because of the risk for methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia.

Although there have been no reports of the use of mirabegron during lactation, the characteristics of the drug – low molecular weight (about 397), long elimination half life (50 hours), and moderate plasma protein binding (about 71%) – suggest that the drug will be excreted into milk, potentially in clinically significant amounts. There is also concern with use of tolterodine (molecular weight about 476) because both the primary drug and its equipotent metabolite may be excreted into milk.
 

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and an adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.

There are currently 15 drugs indicated for adverse conditions of the urinary tract. The reported frequency of use in pregnancy and during breastfeeding for most of these agents is very low or completely absent.

The five subclasses of urinary tract agents are analgesics, antispasmodics, urinary acidifiers, urinary alkalinizers, and urinary germicides. With the exception of the three urinary germicides, anti-infectives are not covered in this column.

Analgesics

The analgesic subclass includes pentosan and phenazopyridine. Pentosan (Elmiron), a heparinlike compound, is an oral drug that is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. Systemic absorption is low, at about 6%. Because of the high molecular weight (4,000-6,000), it does not appear to cross the placenta, at least in the first half of pregnancy. A 1975 reference described its use in five women with preeclampsia. Each patient received 100 mg intramuscularly every 8 hours for about 5 days in the last weeks of pregnancy. No maternal benefit from the therapy was observed. There was apparently no fetal harm, but the neonatal outcomes were not described.

There are substantial – more than 900 – human pregnancy exposures in the first trimester with phenazopyridine. The exposures were not related to an increased risk of embryo-fetal harm and so use of the drug in pregnancy can be classified as compatible. However, the low molecular weight (about 214 for the free base) suggests that the drug will cross to the embryo and fetus.
 

Antispasmodics

The eight antispasmodics are darifenacin (Enablex), fesoterodine (Toviaz), flavoxate, mirabegron (Myrbetriq), oxybutynin (Ditropan XL), solifenacin (Vesicare), tolterodine (Detrol LA), and trospium.

These agents are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. The molecular weights range between 342 and 508, suggesting that all will cross the human placenta. There are no human pregnancy data for six of these agents and very limited data for flavoxate and oxybutynin. There is no evidence of embryo-fetal harm from these two drugs, but only one case involved exposure in the first trimester.

In seven of these drugs, the animal data suggested low risk. There was no embryo harm from doses that were equal to or less than 10 times the human dose based on body surface area (BSA) or area under the concentration curve (AUC). Solifenacin did cause embryo toxicity in pregnant mice. There was no embryo toxicity in pregnant rats and rabbits, but the maximum doses used were very low. Overall, the available data suggest that exposure to an antispasmodic in pregnancy is low risk for embryo, fetal, and newborn harm.
 

Urinary acidifiers

Ammonium chloride is a urinary acidifier as well as a respiratory expectorant. There is a large amount of data related to when the drug was used as an expectorant. There was no evidence that this use was associated with large categories of major or minor malformations. However, there were possible associations with three individual defects: inguinal hernia, cataract, and any benign tumor. No reports describing its use as a urinary acidifier have been located. When large amounts are consumed near term, the drug may cause acidosis in the mother and fetus. The molecular weight (about 53) suggests that it will cross the placenta.

Urinary alkalinizers

Potassium citrate (Urocit-K) is indicated for the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate with nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones. The molecular weight (about 307) suggests it will cross the placenta. Only one case of its use in pregnancy has been located. The newborn had an unspecified defect but no other information was provided. The animal data in four species suggest low risk.

Urinary germicides

There are three urinary germicides: methenamine, methylene blue, and nitrofurantoin. Methenamine is available as methenamine mandelate (molecular weight abut 292) and methenamine hippurate (molecular weight about 319). Both are metabolized to formaldehyde (molecular weight about 30), the active agent. The molecular weights suggest that all will cross the placenta. The use of methenamine during pregnancy has been reported in more than 750 pregnancies. There have been no embryo or fetal adverse effects attributed to the drug.

The human data involving oral methylene blue, a weak urinary germicide, is limited to 55 exposures. There were three infants with birth defects (type not specified). Several reports have described the use of intra-amniotic injections to assist in the diagnosis of suspected membrane rupture. This use has resulted in newborns with hemolytic anemia, hyperbilirubinemia with or without Heinz body formation, blue staining of the skin, and methemoglobinemia. Fetal deaths have also been described. Recommendations to avoid the intra-amniotic use of methylene blue were issued more than 10 years ago. Moreover, the use of oral methylene blue as a urinary germicide is no longer recommended.

The low molecular weight (about 238) of nitrofurantoin suggests that it will cross the placenta. It is commonly used in pregnancy for the treatment or prophylaxis of urinary tract infections. The large amount of human data indicates that the risk of drug-induced birth defects is low. Several cohort studies have found no increased risk for birth defects. However, some case-control studies have found increased risks for hypoplastic left heart syndrome and oral clefts. A 2015 review concluded that this difference was due to the increased sensitivity of case-control studies to detect adverse effects (J Obstet Gynaecol Can. 2015 Feb;37[2]:150-6).

Use of the drug close to term may cause hemolytic anemia in newborns who are glucose-6-phosphate dehydrogenase (G6PD) deficient. Although rare, this may also occur in newborns who are not G6PD deficient. The best course is to avoid use of the drug close to delivery. As for use of the drug in the first trimester, ACOG’s Committee on Obstetric Practice stated in Committee Opinion No. 717 that nitrofurantoin was still thought to be appropriate when no other suitable alternative antibiotics were available (Obstet Gynecol. 2017 Sept;130[3]:666-7).
 

Breastfeeding

Except for methenamine and nitrofurantoin, there are no data related to the use of the urinary tract drugs during breastfeeding. Peak levels of methenamine occur at 1 hour, but no reports of adverse effects on nursing infants have been located. Several reports have described the use of nitrofurantoin during breastfeeding. Minor diarrhea was noted in two infants. However, breastfeeding an infant with G6PD deficiency could lead to hemolytic anemia.

Phenazopyridine should be used with caution especially for an infant younger than 1 month or with G6PD deficiency because of the risk for methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia.

Although there have been no reports of the use of mirabegron during lactation, the characteristics of the drug – low molecular weight (about 397), long elimination half life (50 hours), and moderate plasma protein binding (about 71%) – suggest that the drug will be excreted into milk, potentially in clinically significant amounts. There is also concern with use of tolterodine (molecular weight about 476) because both the primary drug and its equipotent metabolite may be excreted into milk.
 

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and an adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.

There are currently 15 drugs indicated for adverse conditions of the urinary tract. The reported frequency of use in pregnancy and during breastfeeding for most of these agents is very low or completely absent.

The five subclasses of urinary tract agents are analgesics, antispasmodics, urinary acidifiers, urinary alkalinizers, and urinary germicides. With the exception of the three urinary germicides, anti-infectives are not covered in this column.

Analgesics

The analgesic subclass includes pentosan and phenazopyridine. Pentosan (Elmiron), a heparinlike compound, is an oral drug that is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. Systemic absorption is low, at about 6%. Because of the high molecular weight (4,000-6,000), it does not appear to cross the placenta, at least in the first half of pregnancy. A 1975 reference described its use in five women with preeclampsia. Each patient received 100 mg intramuscularly every 8 hours for about 5 days in the last weeks of pregnancy. No maternal benefit from the therapy was observed. There was apparently no fetal harm, but the neonatal outcomes were not described.

There are substantial – more than 900 – human pregnancy exposures in the first trimester with phenazopyridine. The exposures were not related to an increased risk of embryo-fetal harm and so use of the drug in pregnancy can be classified as compatible. However, the low molecular weight (about 214 for the free base) suggests that the drug will cross to the embryo and fetus.
 

Antispasmodics

The eight antispasmodics are darifenacin (Enablex), fesoterodine (Toviaz), flavoxate, mirabegron (Myrbetriq), oxybutynin (Ditropan XL), solifenacin (Vesicare), tolterodine (Detrol LA), and trospium.

These agents are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. The molecular weights range between 342 and 508, suggesting that all will cross the human placenta. There are no human pregnancy data for six of these agents and very limited data for flavoxate and oxybutynin. There is no evidence of embryo-fetal harm from these two drugs, but only one case involved exposure in the first trimester.

In seven of these drugs, the animal data suggested low risk. There was no embryo harm from doses that were equal to or less than 10 times the human dose based on body surface area (BSA) or area under the concentration curve (AUC). Solifenacin did cause embryo toxicity in pregnant mice. There was no embryo toxicity in pregnant rats and rabbits, but the maximum doses used were very low. Overall, the available data suggest that exposure to an antispasmodic in pregnancy is low risk for embryo, fetal, and newborn harm.
 

Urinary acidifiers

Ammonium chloride is a urinary acidifier as well as a respiratory expectorant. There is a large amount of data related to when the drug was used as an expectorant. There was no evidence that this use was associated with large categories of major or minor malformations. However, there were possible associations with three individual defects: inguinal hernia, cataract, and any benign tumor. No reports describing its use as a urinary acidifier have been located. When large amounts are consumed near term, the drug may cause acidosis in the mother and fetus. The molecular weight (about 53) suggests that it will cross the placenta.

Urinary alkalinizers

Potassium citrate (Urocit-K) is indicated for the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate with nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones. The molecular weight (about 307) suggests it will cross the placenta. Only one case of its use in pregnancy has been located. The newborn had an unspecified defect but no other information was provided. The animal data in four species suggest low risk.

Urinary germicides

There are three urinary germicides: methenamine, methylene blue, and nitrofurantoin. Methenamine is available as methenamine mandelate (molecular weight abut 292) and methenamine hippurate (molecular weight about 319). Both are metabolized to formaldehyde (molecular weight about 30), the active agent. The molecular weights suggest that all will cross the placenta. The use of methenamine during pregnancy has been reported in more than 750 pregnancies. There have been no embryo or fetal adverse effects attributed to the drug.

The human data involving oral methylene blue, a weak urinary germicide, is limited to 55 exposures. There were three infants with birth defects (type not specified). Several reports have described the use of intra-amniotic injections to assist in the diagnosis of suspected membrane rupture. This use has resulted in newborns with hemolytic anemia, hyperbilirubinemia with or without Heinz body formation, blue staining of the skin, and methemoglobinemia. Fetal deaths have also been described. Recommendations to avoid the intra-amniotic use of methylene blue were issued more than 10 years ago. Moreover, the use of oral methylene blue as a urinary germicide is no longer recommended.

The low molecular weight (about 238) of nitrofurantoin suggests that it will cross the placenta. It is commonly used in pregnancy for the treatment or prophylaxis of urinary tract infections. The large amount of human data indicates that the risk of drug-induced birth defects is low. Several cohort studies have found no increased risk for birth defects. However, some case-control studies have found increased risks for hypoplastic left heart syndrome and oral clefts. A 2015 review concluded that this difference was due to the increased sensitivity of case-control studies to detect adverse effects (J Obstet Gynaecol Can. 2015 Feb;37[2]:150-6).

Use of the drug close to term may cause hemolytic anemia in newborns who are glucose-6-phosphate dehydrogenase (G6PD) deficient. Although rare, this may also occur in newborns who are not G6PD deficient. The best course is to avoid use of the drug close to delivery. As for use of the drug in the first trimester, ACOG’s Committee on Obstetric Practice stated in Committee Opinion No. 717 that nitrofurantoin was still thought to be appropriate when no other suitable alternative antibiotics were available (Obstet Gynecol. 2017 Sept;130[3]:666-7).
 

Breastfeeding

Except for methenamine and nitrofurantoin, there are no data related to the use of the urinary tract drugs during breastfeeding. Peak levels of methenamine occur at 1 hour, but no reports of adverse effects on nursing infants have been located. Several reports have described the use of nitrofurantoin during breastfeeding. Minor diarrhea was noted in two infants. However, breastfeeding an infant with G6PD deficiency could lead to hemolytic anemia.

Phenazopyridine should be used with caution especially for an infant younger than 1 month or with G6PD deficiency because of the risk for methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia.

Although there have been no reports of the use of mirabegron during lactation, the characteristics of the drug – low molecular weight (about 397), long elimination half life (50 hours), and moderate plasma protein binding (about 71%) – suggest that the drug will be excreted into milk, potentially in clinically significant amounts. There is also concern with use of tolterodine (molecular weight about 476) because both the primary drug and its equipotent metabolite may be excreted into milk.
 

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and an adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.

SAN ANTONIO – Fully one-third of patients with heavily pretreated metastatic triple-negative breast cancer (TNBC) had a response to therapy with a novel antibody-drug conjugate called sacituzumab govitecan. The conjugate consists of the active metabolites of the topoisomerase I inhibitor irinotecan linked to a humanized monoclonal antibody target Trop-2, a cell-surface glycoprotein expressed in triple-negative breast cancers and most other epithelial malignancies.

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, previously reported results of a phase 1/2 basket trial that resulted in sacituzumab govitecan receiving a breakthrough designation from the Food and Drug Administration.

In this video interview, he discusses the conjugate’s activity in the third-line or greater setting for patients with metastatic TNBC, with an overall response rate of 34%, including some complete responses according to independent reviewers, and describes planned clinical trials pitting the agent against standard-of-care single-drug therapies.

The trial was supported by Immunomedics. Dr. Bardia reported institutional funding from the company, but no other conflicts of interest.

SAN ANTONIO – Fully one-third of patients with heavily pretreated metastatic triple-negative breast cancer (TNBC) had a response to therapy with a novel antibody-drug conjugate called sacituzumab govitecan. The conjugate consists of the active metabolites of the topoisomerase I inhibitor irinotecan linked to a humanized monoclonal antibody target Trop-2, a cell-surface glycoprotein expressed in triple-negative breast cancers and most other epithelial malignancies.

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, previously reported results of a phase 1/2 basket trial that resulted in sacituzumab govitecan receiving a breakthrough designation from the Food and Drug Administration.

In this video interview, he discusses the conjugate’s activity in the third-line or greater setting for patients with metastatic TNBC, with an overall response rate of 34%, including some complete responses according to independent reviewers, and describes planned clinical trials pitting the agent against standard-of-care single-drug therapies.

The trial was supported by Immunomedics. Dr. Bardia reported institutional funding from the company, but no other conflicts of interest.

SAN ANTONIO – Fully one-third of patients with heavily pretreated metastatic triple-negative breast cancer (TNBC) had a response to therapy with a novel antibody-drug conjugate called sacituzumab govitecan. The conjugate consists of the active metabolites of the topoisomerase I inhibitor irinotecan linked to a humanized monoclonal antibody target Trop-2, a cell-surface glycoprotein expressed in triple-negative breast cancers and most other epithelial malignancies.

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, previously reported results of a phase 1/2 basket trial that resulted in sacituzumab govitecan receiving a breakthrough designation from the Food and Drug Administration.

In this video interview, he discusses the conjugate’s activity in the third-line or greater setting for patients with metastatic TNBC, with an overall response rate of 34%, including some complete responses according to independent reviewers, and describes planned clinical trials pitting the agent against standard-of-care single-drug therapies.

The trial was supported by Immunomedics. Dr. Bardia reported institutional funding from the company, but no other conflicts of interest.

WASHINGTON – As a potential add-on therapy to phenobarbital, bumetanide demonstrated acceptable safety and promising antiseizure activity in a phase 1/2 safety study presented at the annual meeting of the American Epilepsy Society.

“This is an early-phase trial, but it did associate bumetanide with an additional reduction in seizure burden relative to phenobarbital alone,” reported Janet S. Soul, MD, director of the fetal-neonatal neurology program at Boston Children’s Hospital. She added, “The adverse events observed were not substantially different in the group that received the experimental agent.”

Ted Bosworth/Frontline Medical News

SOURCE: Soul J Abstract 2.426

WASHINGTON – As a potential add-on therapy to phenobarbital, bumetanide demonstrated acceptable safety and promising antiseizure activity in a phase 1/2 safety study presented at the annual meeting of the American Epilepsy Society.

“This is an early-phase trial, but it did associate bumetanide with an additional reduction in seizure burden relative to phenobarbital alone,” reported Janet S. Soul, MD, director of the fetal-neonatal neurology program at Boston Children’s Hospital. She added, “The adverse events observed were not substantially different in the group that received the experimental agent.”

Ted Bosworth/Frontline Medical News

SOURCE: Soul J Abstract 2.426

WASHINGTON – As a potential add-on therapy to phenobarbital, bumetanide demonstrated acceptable safety and promising antiseizure activity in a phase 1/2 safety study presented at the annual meeting of the American Epilepsy Society.

“This is an early-phase trial, but it did associate bumetanide with an additional reduction in seizure burden relative to phenobarbital alone,” reported Janet S. Soul, MD, director of the fetal-neonatal neurology program at Boston Children’s Hospital. She added, “The adverse events observed were not substantially different in the group that received the experimental agent.”

Ted Bosworth/Frontline Medical News

SOURCE: Soul J Abstract 2.426

ORLANDO – Bariatric surgery significantly linked with increased levels of alcohol use and abuse in a meta-analysis of 28 studies with a total of nearly 16,000 patients.

Following any of several methods of bariatric surgery, patients showed a statistically significant 8% higher rate of new onset alcohol abuse, and a relative 50% increased rate of significant alcohol use, compared with rates before surgery, Prandeet Wander, MD, said at the World Congress of Gastroenterology at ACG 2017.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

SOURCE: Wander P et al. World Congress of Gastroenterology, abstract 10.
 

ORLANDO – Bariatric surgery significantly linked with increased levels of alcohol use and abuse in a meta-analysis of 28 studies with a total of nearly 16,000 patients.

Following any of several methods of bariatric surgery, patients showed a statistically significant 8% higher rate of new onset alcohol abuse, and a relative 50% increased rate of significant alcohol use, compared with rates before surgery, Prandeet Wander, MD, said at the World Congress of Gastroenterology at ACG 2017.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

SOURCE: Wander P et al. World Congress of Gastroenterology, abstract 10.
 

ORLANDO – Bariatric surgery significantly linked with increased levels of alcohol use and abuse in a meta-analysis of 28 studies with a total of nearly 16,000 patients.

Following any of several methods of bariatric surgery, patients showed a statistically significant 8% higher rate of new onset alcohol abuse, and a relative 50% increased rate of significant alcohol use, compared with rates before surgery, Prandeet Wander, MD, said at the World Congress of Gastroenterology at ACG 2017.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

SOURCE: Wander P et al. World Congress of Gastroenterology, abstract 10.
 

Levels of antiphospholipid antibodies were significantly higher in adults with celiac disease compared with healthy controls, and gluten was not a factor, according to a study published in Digestive and Liver Disease (Dig Liver Dis. 2017. doi: 10.1016/j.dld.2017.11.018).

“In inflammatory bowel diseases active prophylaxis and treatment of thromboembolic complications is considered appropriate despite the increased risk of gastrointestinal bleeding,” wrote Outi Laine, MD, of Tampere University, Finland, and colleagues.

Results from previous studies suggest that thrombophilic autoantibodies are increased in celiac disease patients, but data are limited, the researchers wrote. In this study, the researchers measured antiphospholipid antibodies (cardiolipin IgG and M, prothrombin IgG, and aPS/PT IgG) in 179 adults with celiac disease (89 untreated, 90 on long-term gluten-free diets) and 91 nonceliac controls. Demographic characteristics were similar among the groups; the average age of the patients was 48 years in the untreated celiac disease group, 58 years in the treated group, and 45 years in the control group. In addition, the presentation of disease (gastrointestinal symptoms, malabsorption or anemia, and extraintestinal symptoms or screen-detected celiac disease) was similar among the groups.

Overall, the levels of antiphospholipid antibodies were significantly higher among celiac disease patients compared with controls 4.9 U/mL vs. 2.2 U/mL respectively, for anticardiolipin; 2.9 U/mL vs. 2.1 U/mL for antiprothrombin IgG, and 6.9 U/mL vs. 2.3 U/mL for antiphosphatidylserine-prothrombin. All three were higher among the untreated celiac disease patients compared with the treated patients.

“Treated patients with the highest levels of cardiolipin IgG and prothrombin IgG antibodies and aPS/PT were older than the newly diagnosed, untreated patients. This observation suggests that the formation of antibodies is not triggered by gluten but is related to the autoimmune-based celiac disease itself,” the researchers wrote.

The study was not designed to assess the impact of antiphospholipid antibodies on thrombosis, the researchers noted. However, “To guide therapeutic decisions, the optimal predictive biomarkers for thromboembolic episodes in patients with celiac disease should be determined,” and future areas of research should include identifying patients at high risk for thromboembolic episodes, they said.

The researchers had no financial conflicts to disclose. The study was funded in part by organizations including the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital, the Academy of Finland, and the Finnish Association of Hematology.

Levels of antiphospholipid antibodies were significantly higher in adults with celiac disease compared with healthy controls, and gluten was not a factor, according to a study published in Digestive and Liver Disease (Dig Liver Dis. 2017. doi: 10.1016/j.dld.2017.11.018).

“In inflammatory bowel diseases active prophylaxis and treatment of thromboembolic complications is considered appropriate despite the increased risk of gastrointestinal bleeding,” wrote Outi Laine, MD, of Tampere University, Finland, and colleagues.

Results from previous studies suggest that thrombophilic autoantibodies are increased in celiac disease patients, but data are limited, the researchers wrote. In this study, the researchers measured antiphospholipid antibodies (cardiolipin IgG and M, prothrombin IgG, and aPS/PT IgG) in 179 adults with celiac disease (89 untreated, 90 on long-term gluten-free diets) and 91 nonceliac controls. Demographic characteristics were similar among the groups; the average age of the patients was 48 years in the untreated celiac disease group, 58 years in the treated group, and 45 years in the control group. In addition, the presentation of disease (gastrointestinal symptoms, malabsorption or anemia, and extraintestinal symptoms or screen-detected celiac disease) was similar among the groups.

Overall, the levels of antiphospholipid antibodies were significantly higher among celiac disease patients compared with controls 4.9 U/mL vs. 2.2 U/mL respectively, for anticardiolipin; 2.9 U/mL vs. 2.1 U/mL for antiprothrombin IgG, and 6.9 U/mL vs. 2.3 U/mL for antiphosphatidylserine-prothrombin. All three were higher among the untreated celiac disease patients compared with the treated patients.

“Treated patients with the highest levels of cardiolipin IgG and prothrombin IgG antibodies and aPS/PT were older than the newly diagnosed, untreated patients. This observation suggests that the formation of antibodies is not triggered by gluten but is related to the autoimmune-based celiac disease itself,” the researchers wrote.

The study was not designed to assess the impact of antiphospholipid antibodies on thrombosis, the researchers noted. However, “To guide therapeutic decisions, the optimal predictive biomarkers for thromboembolic episodes in patients with celiac disease should be determined,” and future areas of research should include identifying patients at high risk for thromboembolic episodes, they said.

The researchers had no financial conflicts to disclose. The study was funded in part by organizations including the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital, the Academy of Finland, and the Finnish Association of Hematology.

Levels of antiphospholipid antibodies were significantly higher in adults with celiac disease compared with healthy controls, and gluten was not a factor, according to a study published in Digestive and Liver Disease (Dig Liver Dis. 2017. doi: 10.1016/j.dld.2017.11.018).

“In inflammatory bowel diseases active prophylaxis and treatment of thromboembolic complications is considered appropriate despite the increased risk of gastrointestinal bleeding,” wrote Outi Laine, MD, of Tampere University, Finland, and colleagues.

Results from previous studies suggest that thrombophilic autoantibodies are increased in celiac disease patients, but data are limited, the researchers wrote. In this study, the researchers measured antiphospholipid antibodies (cardiolipin IgG and M, prothrombin IgG, and aPS/PT IgG) in 179 adults with celiac disease (89 untreated, 90 on long-term gluten-free diets) and 91 nonceliac controls. Demographic characteristics were similar among the groups; the average age of the patients was 48 years in the untreated celiac disease group, 58 years in the treated group, and 45 years in the control group. In addition, the presentation of disease (gastrointestinal symptoms, malabsorption or anemia, and extraintestinal symptoms or screen-detected celiac disease) was similar among the groups.

Overall, the levels of antiphospholipid antibodies were significantly higher among celiac disease patients compared with controls 4.9 U/mL vs. 2.2 U/mL respectively, for anticardiolipin; 2.9 U/mL vs. 2.1 U/mL for antiprothrombin IgG, and 6.9 U/mL vs. 2.3 U/mL for antiphosphatidylserine-prothrombin. All three were higher among the untreated celiac disease patients compared with the treated patients.

“Treated patients with the highest levels of cardiolipin IgG and prothrombin IgG antibodies and aPS/PT were older than the newly diagnosed, untreated patients. This observation suggests that the formation of antibodies is not triggered by gluten but is related to the autoimmune-based celiac disease itself,” the researchers wrote.

The study was not designed to assess the impact of antiphospholipid antibodies on thrombosis, the researchers noted. However, “To guide therapeutic decisions, the optimal predictive biomarkers for thromboembolic episodes in patients with celiac disease should be determined,” and future areas of research should include identifying patients at high risk for thromboembolic episodes, they said.

The researchers had no financial conflicts to disclose. The study was funded in part by organizations including the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital, the Academy of Finland, and the Finnish Association of Hematology.

The numbers tell a grim story. Nationwide, 43.7 million adult Americans experienced a mental health condition during 2016 – an increase of 1.2 million over the previous year. Mental health issues send almost 5.5 million people to emergency departments each year; nearly 60% of adults with a mental illness received no treatment at all.

If that massive – and growing – need is one side of the story, shrinking resources are the other. Mental health resources had already been diminishing for decades before the recession hit – and hit them especially hard. Between 2009 and 2012, states cut $5 billion in mental health services; during that time, at least 4,500 public psychiatric hospital beds nationwide disappeared – nearly 10% of the total supply. The bulk of those resources have never been restored.

Provider numbers also are falling. “Psychiatry is probably the top manpower shortage among all specialties,” said Joe Parks, MD, medical director of the National Council for Behavioral Health. “We have about a third the number of psychiatrists that most estimates say we need, and the number per capita is decreasing.” A significant percentage of psychiatrists – more than 50% – only accept cash, bypassing the low reimbursement rates even private insurance typically offers.

Providers of last resort

But much of the burden of caring for this population ends up falling on hospitals by default. At Denver Health, Melanie Rylander, MD, medical director of the inpatient psychiatric unit, reports seeing this manifest in three categories of patients. First, there is an influx of people coming into the emergency department with primary mental health issues.

“We’re also seeing an influx of people coming in with physical problems, and upon assessment it becomes very clear very quickly that the real issue is an underlying mental health issue,” she said. Then there are the people coming in for the same physical problems over and over – maybe decompensated heart failure or COPD exacerbations – because mental health issues are impeding their ability to take care of themselves.

Some hospitalists say they feel ill equipped to care for these patients. “We don’t have the facility or the resources many times to properly care for their psychiatric needs when they’re in the hospital. It’s not really part of an internist’s training to be familiar with a lot of the medications,” said Atashi Mandal, MD, a hospitalist and pediatrician in Los Angeles. “Sometimes they get improperly medicated because we don’t know what else to do and the patient’s behavioral issues are escalating, so it’s really a difficult position.”

It’s a dispiriting experience for a hospitalist. “It really bothers me when I am trying to care for a patient who has psychiatric needs, and I feel I’m not able to do it, and I can’t find resources, and I feel that this patient’s needs are being neglected – not because we don’t care, and not because of a lack of effort by the staff. It’s just set up to fail,” Dr. Mandal said.
 

Ending the silo mentality

Encouraging a more holistic view of health across health care would be an important step to begin to address the problem – after all, the mind and the body are not separate.

“We work in silos, and we really have to stop doing that because these are intertwined,” said Corey Karlin-Zysman, MD, FHM, FACP, chief of the division of hospital medicine at Northwell Health. “A schizophrenic will become worse when they’re medically ill. That illness will be harder to treat if their psychiatric illness is active.” This is starting to happen in the outpatient setting, evidenced by the expansion of the integrated care model, where a primary care doctor is the lead physician working in combination with psychologists, psychiatrists, and social workers. Communication among providers becomes simpler, and patients don’t fall through the cracks as often while trying to navigate the system.

Hospitals and communities

It’s axiomatic to say that a better approach to mental health would be based around prevention and early intervention, rather than the less crisis-oriented system we have now. Some efforts are being made in that direction, and they involve, and require, outreach outside the hospital.

“The best hospitals doing work in mental health are going beyond the hospital walls; they’re really looking at their community,” Dr. Nguyen said. “You have hospitals, like Accountable Care Organizations, who are trying to move earlier and think about mental health from a pediatric standpoint: How can we support parents and children during critical phases of brain growth? How can we provide prevention services?” Ultimately, those efforts should help lower future admission rates to EDs and hospitals.

That forward-looking approach may be necessary, but it’s also a challenge. “As a hospital administrator, I would think that you look out at the community and see this problem is not going away – in fact, it is likely going to get worse,” Dr. McHugh said. “A health system may look at themselves and say we have to take the lead on this.” The difficulty is that thinking of it in a sense of value to the community, and making the requisite investments, will have a very long period of payout; a health system that’s struggling may not be able to do it. “It’s the large [health systems] that tend to be more integrated … that are thinking about this much differently,” he said.

Still, the reality is that’s where the root of the problem lies, Dr. Rylander said – not in the hospital, but in the larger community. “In the absence of very basic needs – stable housing, food, heating – it’s really not reasonable to expect that people are going to take care of their physical needs,” she said. “It’s a much larger social issue: how to get resources so that these people can have stable places to live, they can get to and from appointments, that type of thing.”

Those needs are ongoing, of course. Many of these patients suffer from chronic conditions, meaning people will continue to need services and support, said Ron Honberg, JD, senior policy adviser for the National Alliance on Mental Illness. Often, people need services from different systems. “There are complexities in terms of navigating those systems and getting those systems to work well together. Until we make inroads in solving those things, or at least improving those things, the burdens are going to fall on the providers of last resort, and that includes hospitals,” he said.

What a hospitalist can do

One thing hospitalists might consider is starting that practice at their own hospitals, measuring, recording, and sharing that kind of information.

“Hospitalists should measure systematically, and in a very neutral manner, the total burden and frequency of the problem and report it consistently to management, along with their assessment that this impairs the quality of care and creates patient risk,” Dr. Parks said. That information can help hospitalists lobby for access to psychiatric personnel, be that in person or through telemedicine. “We don’t have to lay hands on you. There’s no excuse for any hospital not having a contract in place for on-demand consultation in the ER and on the floors.”

Track outcomes, too, Dr. Mandal suggests. With access to the right personnel, are you getting patients out of the ED faster? Are you having fewer negative outcomes while these patients are in the hospital, such as having to use restraints or get security involved? “Hopefully you can get some data in terms of how much money you’ve saved by decreasing the length of stays and decreasing inadvertent adverse effects because the patients weren’t receiving the proper care,” he said.

As this challenge seems likely to continue to grow, hospitalists might consider finding more training in mental health issues themselves so they are more comfortable handling these issues, Dr. Parks said. “The average mini-psych rotation from medical school is only 4 weeks,” he noted. “The ob.gyn. is at least 8 weeks and often 12 weeks, and if you don’t go into ob.gyn., you’re going to see a lot more mentally ill people through the rest of your practice, no matter what you do, than you are going to see pregnant women.”

Just starting these conversations – with patients, with colleagues, with family and friends – might be the most important change of all. “Even though nobody is above these issues afflicting them, this is still something that is not part of an open dialogue, and this is something that affects our own colleagues,” Dr. Mandal said. “I don’t know how many more trainees jumping out of windows it will take, or colleagues going through depression and feeling that it’s a sign of weakness to even talk about it.

“We need to create safe harbors within our own medical communities and acknowledge that we ourselves can be prone to this,” he said. “Perhaps by doing that, we will develop more empathy and become more comfortable, not just with ourselves and our colleagues but also helping these patients. People get overwhelmed and throw their hands up because it is just such a difficult issue. I don’t want people to give up, both from the medical community and our society as a whole – we can’t give up.”
 

A med-psych unit pilot project

Med-psych units can be a good model to take on these challenges. At Long Island Jewish Medical Center, they launched a pilot project to see how one would work in their community and summarized the results in an SHM abstract.

The hospital shares a campus with a 200-bed inpatient psych hospital, and doctors were seeing a lot of back and forth between the two institutions, said Corey Karlin-Zysman, MD, FHM, FACP, chief of the division of hospital medicine at Northwell Health. “Patients would come into the hospital because they had an active medical issue, but because of their behavioral issues, they’d have to have continuous observation. It would not be uncommon for us to have sometimes close to 30 patients who needed 24-hour continuous observation to make sure they were not hurting themselves.” These PCAs or nurse’s assistants were doing 8-hour shifts, so each patient needed three. “The math is staggering – and with not any better outcomes.”

So the hospital created a 15-bed closed med-psych unit for medically ill patients with behavioral health disorders. They staffed it with a dedicated hospitalist, a nurse practitioner, a psychologist, and a nurse manager.

The number of patients requiring continuous observation fell to single digits. Once in their own unit, these patients caused less disruption and stress on the medical units. They had a lower length of stay compared to their previous admissions in other units, and this became one of the hospital’s highest performing units in terms of patient experience.

The biggest secret of their success, Dr. Karlin-Zysman said, is cohorting. “Instead of them going to the next open bed, wherever it may be, you get the patients all in one place geographically, with a team trained to manage those patients.” Another factor: it’s a hospitalist-run unit. “You can’t have 20 different doctors taking care of the patients; it’s one or two hospitalists running this unit.”

Care models like this can be a true win-win, and her hospital is using them more and more.

“I have a care model that’s a stroke unit; I have a care model that’s an onc unit and one that’s a pulmonary unit,” she said. “We’re creating these true teams, which I think hospitalists really like being part of. What’s that thing that makes them want to come to work every day? Things like this: running a care model, becoming specialized in something.” There are research and abstract opportunities for hospitalists on these units too, which also helps keep them engaged, she said. “I’ve used this care model and things like that to reduce burnout and keep people excited.”
 

The persistent mortality gap

Patients with mental illness tend to receive worse medical care than people without, studies have shown; they die an average of 25 years earlier, largely from preventable or treatable conditions such as cardiovascular disease and diabetes. The World Health Organization has called the problem “a hidden human rights emergency.”

In one in a series of articles on mental health, Lisa Rosenbaum, MD, a cardiologist at Brigham and Women’s Hospital, Boston, raises the question: Might physician attitudes toward mentally ill people contribute to this mortality gap, and if so, can we change them?

She recognizes the many obstacles physicians face in treating these patients. “The medicines we have are good but not great and can cause obesity and diabetes, which contributes to cardiovascular morbidity and mortality,” Dr. Rosenbaum said. “We have the adherence challenge for the psychiatric medications and for medications for chronic disease. It’s hard enough for anyone to take a medicine every day, and to do that if you’re homeless or you don’t have insight into the need for it, it’s really hard.”

Also, certain behaviors that are more common among people with serious mental illness – smoking, substance abuse, physical inactivity – increase their risk for chronic diseases.

These hurdles may foster a sense of helplessness among hospitalists who have just a small amount of time to spend with a patient, and attitudes may be hard to change.

“Negotiating more effectively about care refusals, more adeptly assessing capacity, and recognizing when our efforts to orchestrate care have been inadequate seem feasible,” Dr. Rosenbaum writes. “Far harder is overcoming any collective belief that what mentally ill people truly need is not something we can offer.” That’s why a truly honest examination of attitudes and biases is a necessary place to start.

She tells the story of one mentally ill patient she learned of in her research, who, after decades as the quintessential frequent flier in the ER, was living stably in the community. “No one could have known how many tries it would take to help him get there,” she writes. His doctor told her, “Let’s say 10 attempts are necessary. Someone needs to be number 2, 3 and 7. You just never know which number you are.”
 

Education for physicians

A course created by the National Alliance on Mental Illness addresses mental illness issues from a provider perspective.

“Although the description states that the course is intended for mental health professionals, it can be and has been used to educate and inform other healthcare professionals as well,” said Ron Honberg, JD, senior policy advisor for the National Alliance on Mental Illness. The standard course takes 15 hours; there is an abbreviated 4-hour alternative as well. More information can be found at http://www.nami.org/Find-Support/NAMI-Programs/NAMI-Provider-Education.
 

Sources

1. Szabo L. Cost of Not Caring: Nowhere to Go. USA Today. https://www.usatoday.com/story/news/nation/2014/05/12/mental-health-system-crisis/7746535/. Accessed March 10, 2017.

2. Mental Health America. The State of Mental Health in America. http://www.mentalhealthamerica.net/issues/state-mental-health-america. Accessed March 30, 2017.

3. Karlin-Zysman C, Lerner K, Warner-Cohen J. Creating a Hybrid Medicine and Psychiatric Unit to Manage Medically Ill Patients with Behavioral Health Disorders [abstract]. Journal of Hospital Medicine. 2015; 10 (suppl 2). http://www.shmabstracts.com/abstract/creating-a-hybrid-medicine-and-psychiatric-unit-to-manage-medically-ill-patients-with-behavioral-health-disorders/. Accessed March 19, 2017.

4. Garey J. When Doctors Discriminate. New York Times. http://www.nytimes.com/2013/08/11/opinion/sunday/when-doctors-discriminate.html. August 10, 2013. Accessed March 15, 2017.

5. Rosenbaum L. Closing the Mortality Gap – Mental Illness and Medical Care. N Engl J Med. 2016; 375:1585-1589. doi: 10.1056/NEJMms1610125.

6. Rosenbaum L. Unlearning Our Helplessness – Coexisting Serious Mental and Medical Illness. N Engl J Med. 2016;375:1690-4. doi: 10.1056/NEJMms1610127.

The numbers tell a grim story. Nationwide, 43.7 million adult Americans experienced a mental health condition during 2016 – an increase of 1.2 million over the previous year. Mental health issues send almost 5.5 million people to emergency departments each year; nearly 60% of adults with a mental illness received no treatment at all.

If that massive – and growing – need is one side of the story, shrinking resources are the other. Mental health resources had already been diminishing for decades before the recession hit – and hit them especially hard. Between 2009 and 2012, states cut $5 billion in mental health services; during that time, at least 4,500 public psychiatric hospital beds nationwide disappeared – nearly 10% of the total supply. The bulk of those resources have never been restored.

Provider numbers also are falling. “Psychiatry is probably the top manpower shortage among all specialties,” said Joe Parks, MD, medical director of the National Council for Behavioral Health. “We have about a third the number of psychiatrists that most estimates say we need, and the number per capita is decreasing.” A significant percentage of psychiatrists – more than 50% – only accept cash, bypassing the low reimbursement rates even private insurance typically offers.

Providers of last resort

But much of the burden of caring for this population ends up falling on hospitals by default. At Denver Health, Melanie Rylander, MD, medical director of the inpatient psychiatric unit, reports seeing this manifest in three categories of patients. First, there is an influx of people coming into the emergency department with primary mental health issues.

“We’re also seeing an influx of people coming in with physical problems, and upon assessment it becomes very clear very quickly that the real issue is an underlying mental health issue,” she said. Then there are the people coming in for the same physical problems over and over – maybe decompensated heart failure or COPD exacerbations – because mental health issues are impeding their ability to take care of themselves.

Some hospitalists say they feel ill equipped to care for these patients. “We don’t have the facility or the resources many times to properly care for their psychiatric needs when they’re in the hospital. It’s not really part of an internist’s training to be familiar with a lot of the medications,” said Atashi Mandal, MD, a hospitalist and pediatrician in Los Angeles. “Sometimes they get improperly medicated because we don’t know what else to do and the patient’s behavioral issues are escalating, so it’s really a difficult position.”

It’s a dispiriting experience for a hospitalist. “It really bothers me when I am trying to care for a patient who has psychiatric needs, and I feel I’m not able to do it, and I can’t find resources, and I feel that this patient’s needs are being neglected – not because we don’t care, and not because of a lack of effort by the staff. It’s just set up to fail,” Dr. Mandal said.
 

Ending the silo mentality

Encouraging a more holistic view of health across health care would be an important step to begin to address the problem – after all, the mind and the body are not separate.

“We work in silos, and we really have to stop doing that because these are intertwined,” said Corey Karlin-Zysman, MD, FHM, FACP, chief of the division of hospital medicine at Northwell Health. “A schizophrenic will become worse when they’re medically ill. That illness will be harder to treat if their psychiatric illness is active.” This is starting to happen in the outpatient setting, evidenced by the expansion of the integrated care model, where a primary care doctor is the lead physician working in combination with psychologists, psychiatrists, and social workers. Communication among providers becomes simpler, and patients don’t fall through the cracks as often while trying to navigate the system.

Hospitals and communities

It’s axiomatic to say that a better approach to mental health would be based around prevention and early intervention, rather than the less crisis-oriented system we have now. Some efforts are being made in that direction, and they involve, and require, outreach outside the hospital.

“The best hospitals doing work in mental health are going beyond the hospital walls; they’re really looking at their community,” Dr. Nguyen said. “You have hospitals, like Accountable Care Organizations, who are trying to move earlier and think about mental health from a pediatric standpoint: How can we support parents and children during critical phases of brain growth? How can we provide prevention services?” Ultimately, those efforts should help lower future admission rates to EDs and hospitals.

That forward-looking approach may be necessary, but it’s also a challenge. “As a hospital administrator, I would think that you look out at the community and see this problem is not going away – in fact, it is likely going to get worse,” Dr. McHugh said. “A health system may look at themselves and say we have to take the lead on this.” The difficulty is that thinking of it in a sense of value to the community, and making the requisite investments, will have a very long period of payout; a health system that’s struggling may not be able to do it. “It’s the large [health systems] that tend to be more integrated … that are thinking about this much differently,” he said.

Still, the reality is that’s where the root of the problem lies, Dr. Rylander said – not in the hospital, but in the larger community. “In the absence of very basic needs – stable housing, food, heating – it’s really not reasonable to expect that people are going to take care of their physical needs,” she said. “It’s a much larger social issue: how to get resources so that these people can have stable places to live, they can get to and from appointments, that type of thing.”

Those needs are ongoing, of course. Many of these patients suffer from chronic conditions, meaning people will continue to need services and support, said Ron Honberg, JD, senior policy adviser for the National Alliance on Mental Illness. Often, people need services from different systems. “There are complexities in terms of navigating those systems and getting those systems to work well together. Until we make inroads in solving those things, or at least improving those things, the burdens are going to fall on the providers of last resort, and that includes hospitals,” he said.

What a hospitalist can do

One thing hospitalists might consider is starting that practice at their own hospitals, measuring, recording, and sharing that kind of information.

“Hospitalists should measure systematically, and in a very neutral manner, the total burden and frequency of the problem and report it consistently to management, along with their assessment that this impairs the quality of care and creates patient risk,” Dr. Parks said. That information can help hospitalists lobby for access to psychiatric personnel, be that in person or through telemedicine. “We don’t have to lay hands on you. There’s no excuse for any hospital not having a contract in place for on-demand consultation in the ER and on the floors.”

Track outcomes, too, Dr. Mandal suggests. With access to the right personnel, are you getting patients out of the ED faster? Are you having fewer negative outcomes while these patients are in the hospital, such as having to use restraints or get security involved? “Hopefully you can get some data in terms of how much money you’ve saved by decreasing the length of stays and decreasing inadvertent adverse effects because the patients weren’t receiving the proper care,” he said.

As this challenge seems likely to continue to grow, hospitalists might consider finding more training in mental health issues themselves so they are more comfortable handling these issues, Dr. Parks said. “The average mini-psych rotation from medical school is only 4 weeks,” he noted. “The ob.gyn. is at least 8 weeks and often 12 weeks, and if you don’t go into ob.gyn., you’re going to see a lot more mentally ill people through the rest of your practice, no matter what you do, than you are going to see pregnant women.”

Just starting these conversations – with patients, with colleagues, with family and friends – might be the most important change of all. “Even though nobody is above these issues afflicting them, this is still something that is not part of an open dialogue, and this is something that affects our own colleagues,” Dr. Mandal said. “I don’t know how many more trainees jumping out of windows it will take, or colleagues going through depression and feeling that it’s a sign of weakness to even talk about it.

“We need to create safe harbors within our own medical communities and acknowledge that we ourselves can be prone to this,” he said. “Perhaps by doing that, we will develop more empathy and become more comfortable, not just with ourselves and our colleagues but also helping these patients. People get overwhelmed and throw their hands up because it is just such a difficult issue. I don’t want people to give up, both from the medical community and our society as a whole – we can’t give up.”
 

A med-psych unit pilot project

Med-psych units can be a good model to take on these challenges. At Long Island Jewish Medical Center, they launched a pilot project to see how one would work in their community and summarized the results in an SHM abstract.

The hospital shares a campus with a 200-bed inpatient psych hospital, and doctors were seeing a lot of back and forth between the two institutions, said Corey Karlin-Zysman, MD, FHM, FACP, chief of the division of hospital medicine at Northwell Health. “Patients would come into the hospital because they had an active medical issue, but because of their behavioral issues, they’d have to have continuous observation. It would not be uncommon for us to have sometimes close to 30 patients who needed 24-hour continuous observation to make sure they were not hurting themselves.” These PCAs or nurse’s assistants were doing 8-hour shifts, so each patient needed three. “The math is staggering – and with not any better outcomes.”

So the hospital created a 15-bed closed med-psych unit for medically ill patients with behavioral health disorders. They staffed it with a dedicated hospitalist, a nurse practitioner, a psychologist, and a nurse manager.

The number of patients requiring continuous observation fell to single digits. Once in their own unit, these patients caused less disruption and stress on the medical units. They had a lower length of stay compared to their previous admissions in other units, and this became one of the hospital’s highest performing units in terms of patient experience.

The biggest secret of their success, Dr. Karlin-Zysman said, is cohorting. “Instead of them going to the next open bed, wherever it may be, you get the patients all in one place geographically, with a team trained to manage those patients.” Another factor: it’s a hospitalist-run unit. “You can’t have 20 different doctors taking care of the patients; it’s one or two hospitalists running this unit.”

Care models like this can be a true win-win, and her hospital is using them more and more.

“I have a care model that’s a stroke unit; I have a care model that’s an onc unit and one that’s a pulmonary unit,” she said. “We’re creating these true teams, which I think hospitalists really like being part of. What’s that thing that makes them want to come to work every day? Things like this: running a care model, becoming specialized in something.” There are research and abstract opportunities for hospitalists on these units too, which also helps keep them engaged, she said. “I’ve used this care model and things like that to reduce burnout and keep people excited.”
 

The persistent mortality gap

Patients with mental illness tend to receive worse medical care than people without, studies have shown; they die an average of 25 years earlier, largely from preventable or treatable conditions such as cardiovascular disease and diabetes. The World Health Organization has called the problem “a hidden human rights emergency.”

In one in a series of articles on mental health, Lisa Rosenbaum, MD, a cardiologist at Brigham and Women’s Hospital, Boston, raises the question: Might physician attitudes toward mentally ill people contribute to this mortality gap, and if so, can we change them?

She recognizes the many obstacles physicians face in treating these patients. “The medicines we have are good but not great and can cause obesity and diabetes, which contributes to cardiovascular morbidity and mortality,” Dr. Rosenbaum said. “We have the adherence challenge for the psychiatric medications and for medications for chronic disease. It’s hard enough for anyone to take a medicine every day, and to do that if you’re homeless or you don’t have insight into the need for it, it’s really hard.”

Also, certain behaviors that are more common among people with serious mental illness – smoking, substance abuse, physical inactivity – increase their risk for chronic diseases.

These hurdles may foster a sense of helplessness among hospitalists who have just a small amount of time to spend with a patient, and attitudes may be hard to change.

“Negotiating more effectively about care refusals, more adeptly assessing capacity, and recognizing when our efforts to orchestrate care have been inadequate seem feasible,” Dr. Rosenbaum writes. “Far harder is overcoming any collective belief that what mentally ill people truly need is not something we can offer.” That’s why a truly honest examination of attitudes and biases is a necessary place to start.

She tells the story of one mentally ill patient she learned of in her research, who, after decades as the quintessential frequent flier in the ER, was living stably in the community. “No one could have known how many tries it would take to help him get there,” she writes. His doctor told her, “Let’s say 10 attempts are necessary. Someone needs to be number 2, 3 and 7. You just never know which number you are.”
 

Education for physicians

A course created by the National Alliance on Mental Illness addresses mental illness issues from a provider perspective.

“Although the description states that the course is intended for mental health professionals, it can be and has been used to educate and inform other healthcare professionals as well,” said Ron Honberg, JD, senior policy advisor for the National Alliance on Mental Illness. The standard course takes 15 hours; there is an abbreviated 4-hour alternative as well. More information can be found at http://www.nami.org/Find-Support/NAMI-Programs/NAMI-Provider-Education.
 

Sources

1. Szabo L. Cost of Not Caring: Nowhere to Go. USA Today. https://www.usatoday.com/story/news/nation/2014/05/12/mental-health-system-crisis/7746535/. Accessed March 10, 2017.

2. Mental Health America. The State of Mental Health in America. http://www.mentalhealthamerica.net/issues/state-mental-health-america. Accessed March 30, 2017.

3. Karlin-Zysman C, Lerner K, Warner-Cohen J. Creating a Hybrid Medicine and Psychiatric Unit to Manage Medically Ill Patients with Behavioral Health Disorders [abstract]. Journal of Hospital Medicine. 2015; 10 (suppl 2). http://www.shmabstracts.com/abstract/creating-a-hybrid-medicine-and-psychiatric-unit-to-manage-medically-ill-patients-with-behavioral-health-disorders/. Accessed March 19, 2017.

4. Garey J. When Doctors Discriminate. New York Times. http://www.nytimes.com/2013/08/11/opinion/sunday/when-doctors-discriminate.html. August 10, 2013. Accessed March 15, 2017.

5. Rosenbaum L. Closing the Mortality Gap – Mental Illness and Medical Care. N Engl J Med. 2016; 375:1585-1589. doi: 10.1056/NEJMms1610125.

6. Rosenbaum L. Unlearning Our Helplessness – Coexisting Serious Mental and Medical Illness. N Engl J Med. 2016;375:1690-4. doi: 10.1056/NEJMms1610127.

The numbers tell a grim story. Nationwide, 43.7 million adult Americans experienced a mental health condition during 2016 – an increase of 1.2 million over the previous year. Mental health issues send almost 5.5 million people to emergency departments each year; nearly 60% of adults with a mental illness received no treatment at all.

If that massive – and growing – need is one side of the story, shrinking resources are the other. Mental health resources had already been diminishing for decades before the recession hit – and hit them especially hard. Between 2009 and 2012, states cut $5 billion in mental health services; during that time, at least 4,500 public psychiatric hospital beds nationwide disappeared – nearly 10% of the total supply. The bulk of those resources have never been restored.

Provider numbers also are falling. “Psychiatry is probably the top manpower shortage among all specialties,” said Joe Parks, MD, medical director of the National Council for Behavioral Health. “We have about a third the number of psychiatrists that most estimates say we need, and the number per capita is decreasing.” A significant percentage of psychiatrists – more than 50% – only accept cash, bypassing the low reimbursement rates even private insurance typically offers.

Providers of last resort

But much of the burden of caring for this population ends up falling on hospitals by default. At Denver Health, Melanie Rylander, MD, medical director of the inpatient psychiatric unit, reports seeing this manifest in three categories of patients. First, there is an influx of people coming into the emergency department with primary mental health issues.

“We’re also seeing an influx of people coming in with physical problems, and upon assessment it becomes very clear very quickly that the real issue is an underlying mental health issue,” she said. Then there are the people coming in for the same physical problems over and over – maybe decompensated heart failure or COPD exacerbations – because mental health issues are impeding their ability to take care of themselves.

Some hospitalists say they feel ill equipped to care for these patients. “We don’t have the facility or the resources many times to properly care for their psychiatric needs when they’re in the hospital. It’s not really part of an internist’s training to be familiar with a lot of the medications,” said Atashi Mandal, MD, a hospitalist and pediatrician in Los Angeles. “Sometimes they get improperly medicated because we don’t know what else to do and the patient’s behavioral issues are escalating, so it’s really a difficult position.”

It’s a dispiriting experience for a hospitalist. “It really bothers me when I am trying to care for a patient who has psychiatric needs, and I feel I’m not able to do it, and I can’t find resources, and I feel that this patient’s needs are being neglected – not because we don’t care, and not because of a lack of effort by the staff. It’s just set up to fail,” Dr. Mandal said.
 

Ending the silo mentality

Encouraging a more holistic view of health across health care would be an important step to begin to address the problem – after all, the mind and the body are not separate.

“We work in silos, and we really have to stop doing that because these are intertwined,” said Corey Karlin-Zysman, MD, FHM, FACP, chief of the division of hospital medicine at Northwell Health. “A schizophrenic will become worse when they’re medically ill. That illness will be harder to treat if their psychiatric illness is active.” This is starting to happen in the outpatient setting, evidenced by the expansion of the integrated care model, where a primary care doctor is the lead physician working in combination with psychologists, psychiatrists, and social workers. Communication among providers becomes simpler, and patients don’t fall through the cracks as often while trying to navigate the system.

Hospitals and communities

It’s axiomatic to say that a better approach to mental health would be based around prevention and early intervention, rather than the less crisis-oriented system we have now. Some efforts are being made in that direction, and they involve, and require, outreach outside the hospital.

“The best hospitals doing work in mental health are going beyond the hospital walls; they’re really looking at their community,” Dr. Nguyen said. “You have hospitals, like Accountable Care Organizations, who are trying to move earlier and think about mental health from a pediatric standpoint: How can we support parents and children during critical phases of brain growth? How can we provide prevention services?” Ultimately, those efforts should help lower future admission rates to EDs and hospitals.

That forward-looking approach may be necessary, but it’s also a challenge. “As a hospital administrator, I would think that you look out at the community and see this problem is not going away – in fact, it is likely going to get worse,” Dr. McHugh said. “A health system may look at themselves and say we have to take the lead on this.” The difficulty is that thinking of it in a sense of value to the community, and making the requisite investments, will have a very long period of payout; a health system that’s struggling may not be able to do it. “It’s the large [health systems] that tend to be more integrated … that are thinking about this much differently,” he said.

Still, the reality is that’s where the root of the problem lies, Dr. Rylander said – not in the hospital, but in the larger community. “In the absence of very basic needs – stable housing, food, heating – it’s really not reasonable to expect that people are going to take care of their physical needs,” she said. “It’s a much larger social issue: how to get resources so that these people can have stable places to live, they can get to and from appointments, that type of thing.”

Those needs are ongoing, of course. Many of these patients suffer from chronic conditions, meaning people will continue to need services and support, said Ron Honberg, JD, senior policy adviser for the National Alliance on Mental Illness. Often, people need services from different systems. “There are complexities in terms of navigating those systems and getting those systems to work well together. Until we make inroads in solving those things, or at least improving those things, the burdens are going to fall on the providers of last resort, and that includes hospitals,” he said.

What a hospitalist can do

One thing hospitalists might consider is starting that practice at their own hospitals, measuring, recording, and sharing that kind of information.

“Hospitalists should measure systematically, and in a very neutral manner, the total burden and frequency of the problem and report it consistently to management, along with their assessment that this impairs the quality of care and creates patient risk,” Dr. Parks said. That information can help hospitalists lobby for access to psychiatric personnel, be that in person or through telemedicine. “We don’t have to lay hands on you. There’s no excuse for any hospital not having a contract in place for on-demand consultation in the ER and on the floors.”

Track outcomes, too, Dr. Mandal suggests. With access to the right personnel, are you getting patients out of the ED faster? Are you having fewer negative outcomes while these patients are in the hospital, such as having to use restraints or get security involved? “Hopefully you can get some data in terms of how much money you’ve saved by decreasing the length of stays and decreasing inadvertent adverse effects because the patients weren’t receiving the proper care,” he said.

As this challenge seems likely to continue to grow, hospitalists might consider finding more training in mental health issues themselves so they are more comfortable handling these issues, Dr. Parks said. “The average mini-psych rotation from medical school is only 4 weeks,” he noted. “The ob.gyn. is at least 8 weeks and often 12 weeks, and if you don’t go into ob.gyn., you’re going to see a lot more mentally ill people through the rest of your practice, no matter what you do, than you are going to see pregnant women.”

Just starting these conversations – with patients, with colleagues, with family and friends – might be the most important change of all. “Even though nobody is above these issues afflicting them, this is still something that is not part of an open dialogue, and this is something that affects our own colleagues,” Dr. Mandal said. “I don’t know how many more trainees jumping out of windows it will take, or colleagues going through depression and feeling that it’s a sign of weakness to even talk about it.

“We need to create safe harbors within our own medical communities and acknowledge that we ourselves can be prone to this,” he said. “Perhaps by doing that, we will develop more empathy and become more comfortable, not just with ourselves and our colleagues but also helping these patients. People get overwhelmed and throw their hands up because it is just such a difficult issue. I don’t want people to give up, both from the medical community and our society as a whole – we can’t give up.”
 

A med-psych unit pilot project

Med-psych units can be a good model to take on these challenges. At Long Island Jewish Medical Center, they launched a pilot project to see how one would work in their community and summarized the results in an SHM abstract.

The hospital shares a campus with a 200-bed inpatient psych hospital, and doctors were seeing a lot of back and forth between the two institutions, said Corey Karlin-Zysman, MD, FHM, FACP, chief of the division of hospital medicine at Northwell Health. “Patients would come into the hospital because they had an active medical issue, but because of their behavioral issues, they’d have to have continuous observation. It would not be uncommon for us to have sometimes close to 30 patients who needed 24-hour continuous observation to make sure they were not hurting themselves.” These PCAs or nurse’s assistants were doing 8-hour shifts, so each patient needed three. “The math is staggering – and with not any better outcomes.”

So the hospital created a 15-bed closed med-psych unit for medically ill patients with behavioral health disorders. They staffed it with a dedicated hospitalist, a nurse practitioner, a psychologist, and a nurse manager.

The number of patients requiring continuous observation fell to single digits. Once in their own unit, these patients caused less disruption and stress on the medical units. They had a lower length of stay compared to their previous admissions in other units, and this became one of the hospital’s highest performing units in terms of patient experience.

The biggest secret of their success, Dr. Karlin-Zysman said, is cohorting. “Instead of them going to the next open bed, wherever it may be, you get the patients all in one place geographically, with a team trained to manage those patients.” Another factor: it’s a hospitalist-run unit. “You can’t have 20 different doctors taking care of the patients; it’s one or two hospitalists running this unit.”

Care models like this can be a true win-win, and her hospital is using them more and more.

“I have a care model that’s a stroke unit; I have a care model that’s an onc unit and one that’s a pulmonary unit,” she said. “We’re creating these true teams, which I think hospitalists really like being part of. What’s that thing that makes them want to come to work every day? Things like this: running a care model, becoming specialized in something.” There are research and abstract opportunities for hospitalists on these units too, which also helps keep them engaged, she said. “I’ve used this care model and things like that to reduce burnout and keep people excited.”
 

The persistent mortality gap

Patients with mental illness tend to receive worse medical care than people without, studies have shown; they die an average of 25 years earlier, largely from preventable or treatable conditions such as cardiovascular disease and diabetes. The World Health Organization has called the problem “a hidden human rights emergency.”

In one in a series of articles on mental health, Lisa Rosenbaum, MD, a cardiologist at Brigham and Women’s Hospital, Boston, raises the question: Might physician attitudes toward mentally ill people contribute to this mortality gap, and if so, can we change them?

She recognizes the many obstacles physicians face in treating these patients. “The medicines we have are good but not great and can cause obesity and diabetes, which contributes to cardiovascular morbidity and mortality,” Dr. Rosenbaum said. “We have the adherence challenge for the psychiatric medications and for medications for chronic disease. It’s hard enough for anyone to take a medicine every day, and to do that if you’re homeless or you don’t have insight into the need for it, it’s really hard.”

Also, certain behaviors that are more common among people with serious mental illness – smoking, substance abuse, physical inactivity – increase their risk for chronic diseases.

These hurdles may foster a sense of helplessness among hospitalists who have just a small amount of time to spend with a patient, and attitudes may be hard to change.

“Negotiating more effectively about care refusals, more adeptly assessing capacity, and recognizing when our efforts to orchestrate care have been inadequate seem feasible,” Dr. Rosenbaum writes. “Far harder is overcoming any collective belief that what mentally ill people truly need is not something we can offer.” That’s why a truly honest examination of attitudes and biases is a necessary place to start.

She tells the story of one mentally ill patient she learned of in her research, who, after decades as the quintessential frequent flier in the ER, was living stably in the community. “No one could have known how many tries it would take to help him get there,” she writes. His doctor told her, “Let’s say 10 attempts are necessary. Someone needs to be number 2, 3 and 7. You just never know which number you are.”
 

Education for physicians

A course created by the National Alliance on Mental Illness addresses mental illness issues from a provider perspective.

“Although the description states that the course is intended for mental health professionals, it can be and has been used to educate and inform other healthcare professionals as well,” said Ron Honberg, JD, senior policy advisor for the National Alliance on Mental Illness. The standard course takes 15 hours; there is an abbreviated 4-hour alternative as well. More information can be found at http://www.nami.org/Find-Support/NAMI-Programs/NAMI-Provider-Education.
 

Sources

1. Szabo L. Cost of Not Caring: Nowhere to Go. USA Today. https://www.usatoday.com/story/news/nation/2014/05/12/mental-health-system-crisis/7746535/. Accessed March 10, 2017.

2. Mental Health America. The State of Mental Health in America. http://www.mentalhealthamerica.net/issues/state-mental-health-america. Accessed March 30, 2017.

3. Karlin-Zysman C, Lerner K, Warner-Cohen J. Creating a Hybrid Medicine and Psychiatric Unit to Manage Medically Ill Patients with Behavioral Health Disorders [abstract]. Journal of Hospital Medicine. 2015; 10 (suppl 2). http://www.shmabstracts.com/abstract/creating-a-hybrid-medicine-and-psychiatric-unit-to-manage-medically-ill-patients-with-behavioral-health-disorders/. Accessed March 19, 2017.

4. Garey J. When Doctors Discriminate. New York Times. http://www.nytimes.com/2013/08/11/opinion/sunday/when-doctors-discriminate.html. August 10, 2013. Accessed March 15, 2017.

5. Rosenbaum L. Closing the Mortality Gap – Mental Illness and Medical Care. N Engl J Med. 2016; 375:1585-1589. doi: 10.1056/NEJMms1610125.

6. Rosenbaum L. Unlearning Our Helplessness – Coexisting Serious Mental and Medical Illness. N Engl J Med. 2016;375:1690-4. doi: 10.1056/NEJMms1610127.