As we find ourselves in November, on the heels of yet another exceptional CHEST Annual Meeting, I cannot help but use my last column as CHEST President to reflect on a year well spent.

For the first time since CHEST 2011, when I was the Scientific Program Committee Vice Chair, I was able to return to beautiful Hawaiʻi as the organization’s President, which was such a big coincidence that it felt almost like fate.

During my time on stage at the CHEST 2023 Opening Session, I reflected on the last (at the time) 9 months and shared how truly humbled I have been to lead such a group of leaders and doers. I’m continually amazed at the energy of our members and our staff. In my 25 years as a member, I thought I knew all that CHEST did, but there is so much more happening than any one person realizes. From creating and implementing patient care initiatives to drafting and endorsing statements advocating for better access to health care, there is a tremendous amount accomplished by this organization every year.
 

One notable accomplishment of this particular year is that not only was CHEST 2023 our largest meeting ever, but I’m proud to share that we also had more medical students, residents, and fellows than any other year, with over 2,000 attendees in-training.

This is a great reflection of the work we’ve been doing to expand the CHEST community – both to physicians earlier in their careers and also to the whole care team. We are putting a dedicated focus toward welcoming and creating a sense of belonging for every clinician. The first step toward this inclusion is the creation of the new CHEST interest groups – Respiratory Care, which is dedicated to the field, and Women in Chest Medicine, which is a more inclusive evolution of the previous Women & Pulmonary group.

This year, we also established CHEST organizational values. The result of a tremendous effort from an advisory committee, CHEST leaders, members, and staff, these values – Community, Inclusivity, Innovation, Advocacy, and Integrity – are reflective of the CHEST organization and will guide decisions for years to come.

They also serve to elevate the work we are doing in social responsibility and health equity, within both of which we’ve made great strides. CHEST philanthropy evolved from what was known as the CHEST Foundation, with a new strategic focus, and we continue working to create opportunities to expand diversity within health care, including the new CHEST mentor/mentee sponsorship fellowship in partnership with the Association of Pulmonary and Critical Care Medicine Program Directors.

Though I could go on for eternity describing all we did at CHEST this year, the reality is that at the end of the next month, as we ring in the new year, I will cede the presidency to the incredibly accomplished and capable Jack Buckley, MD, MPH, FCCP, who will take the reins of our great organization.

For now, in my parting words to you, I encourage everyone to stay in touch. I am always reachable by email and would love to hear your thoughts on CHEST – reflections on this past year, ideas about where we’re going, and suggestions for what we’re missing. The role of the President (and, to some extent, the Immediate Past President) is to be a steward of the needs of the CHEST members, and it’s been a true honor being your 2023 CHEST President.

As we find ourselves in November, on the heels of yet another exceptional CHEST Annual Meeting, I cannot help but use my last column as CHEST President to reflect on a year well spent.

For the first time since CHEST 2011, when I was the Scientific Program Committee Vice Chair, I was able to return to beautiful Hawaiʻi as the organization’s President, which was such a big coincidence that it felt almost like fate.

During my time on stage at the CHEST 2023 Opening Session, I reflected on the last (at the time) 9 months and shared how truly humbled I have been to lead such a group of leaders and doers. I’m continually amazed at the energy of our members and our staff. In my 25 years as a member, I thought I knew all that CHEST did, but there is so much more happening than any one person realizes. From creating and implementing patient care initiatives to drafting and endorsing statements advocating for better access to health care, there is a tremendous amount accomplished by this organization every year.
 

One notable accomplishment of this particular year is that not only was CHEST 2023 our largest meeting ever, but I’m proud to share that we also had more medical students, residents, and fellows than any other year, with over 2,000 attendees in-training.

This is a great reflection of the work we’ve been doing to expand the CHEST community – both to physicians earlier in their careers and also to the whole care team. We are putting a dedicated focus toward welcoming and creating a sense of belonging for every clinician. The first step toward this inclusion is the creation of the new CHEST interest groups – Respiratory Care, which is dedicated to the field, and Women in Chest Medicine, which is a more inclusive evolution of the previous Women & Pulmonary group.

This year, we also established CHEST organizational values. The result of a tremendous effort from an advisory committee, CHEST leaders, members, and staff, these values – Community, Inclusivity, Innovation, Advocacy, and Integrity – are reflective of the CHEST organization and will guide decisions for years to come.

They also serve to elevate the work we are doing in social responsibility and health equity, within both of which we’ve made great strides. CHEST philanthropy evolved from what was known as the CHEST Foundation, with a new strategic focus, and we continue working to create opportunities to expand diversity within health care, including the new CHEST mentor/mentee sponsorship fellowship in partnership with the Association of Pulmonary and Critical Care Medicine Program Directors.

Though I could go on for eternity describing all we did at CHEST this year, the reality is that at the end of the next month, as we ring in the new year, I will cede the presidency to the incredibly accomplished and capable Jack Buckley, MD, MPH, FCCP, who will take the reins of our great organization.

For now, in my parting words to you, I encourage everyone to stay in touch. I am always reachable by email and would love to hear your thoughts on CHEST – reflections on this past year, ideas about where we’re going, and suggestions for what we’re missing. The role of the President (and, to some extent, the Immediate Past President) is to be a steward of the needs of the CHEST members, and it’s been a true honor being your 2023 CHEST President.

As we find ourselves in November, on the heels of yet another exceptional CHEST Annual Meeting, I cannot help but use my last column as CHEST President to reflect on a year well spent.

For the first time since CHEST 2011, when I was the Scientific Program Committee Vice Chair, I was able to return to beautiful Hawaiʻi as the organization’s President, which was such a big coincidence that it felt almost like fate.

During my time on stage at the CHEST 2023 Opening Session, I reflected on the last (at the time) 9 months and shared how truly humbled I have been to lead such a group of leaders and doers. I’m continually amazed at the energy of our members and our staff. In my 25 years as a member, I thought I knew all that CHEST did, but there is so much more happening than any one person realizes. From creating and implementing patient care initiatives to drafting and endorsing statements advocating for better access to health care, there is a tremendous amount accomplished by this organization every year.
 

One notable accomplishment of this particular year is that not only was CHEST 2023 our largest meeting ever, but I’m proud to share that we also had more medical students, residents, and fellows than any other year, with over 2,000 attendees in-training.

This is a great reflection of the work we’ve been doing to expand the CHEST community – both to physicians earlier in their careers and also to the whole care team. We are putting a dedicated focus toward welcoming and creating a sense of belonging for every clinician. The first step toward this inclusion is the creation of the new CHEST interest groups – Respiratory Care, which is dedicated to the field, and Women in Chest Medicine, which is a more inclusive evolution of the previous Women & Pulmonary group.

This year, we also established CHEST organizational values. The result of a tremendous effort from an advisory committee, CHEST leaders, members, and staff, these values – Community, Inclusivity, Innovation, Advocacy, and Integrity – are reflective of the CHEST organization and will guide decisions for years to come.

They also serve to elevate the work we are doing in social responsibility and health equity, within both of which we’ve made great strides. CHEST philanthropy evolved from what was known as the CHEST Foundation, with a new strategic focus, and we continue working to create opportunities to expand diversity within health care, including the new CHEST mentor/mentee sponsorship fellowship in partnership with the Association of Pulmonary and Critical Care Medicine Program Directors.

Though I could go on for eternity describing all we did at CHEST this year, the reality is that at the end of the next month, as we ring in the new year, I will cede the presidency to the incredibly accomplished and capable Jack Buckley, MD, MPH, FCCP, who will take the reins of our great organization.

For now, in my parting words to you, I encourage everyone to stay in touch. I am always reachable by email and would love to hear your thoughts on CHEST – reflections on this past year, ideas about where we’re going, and suggestions for what we’re missing. The role of the President (and, to some extent, the Immediate Past President) is to be a steward of the needs of the CHEST members, and it’s been a true honor being your 2023 CHEST President.

Chest Infections & Disaster Response Network

Disaster Response & Global Health Section

In recent years, the importance of inpatient vaccinations against respiratory viral illnesses has become increasingly clear. As the world grapples with the ever-present threat of contagious diseases like influenza, COVID-19, Respiratory Syncytial Virus (RSV) and other respiratory viruses, the significance of vaccinating individuals during hospital stays cannot be overstated. Notably, the rates of inpatient vaccinations have significantly increased in recent years.

Numerous studies have demonstrated the success of various strategies to boost vaccine delivery to hospitalized patients. These strategies include personalized catch-up plans, electronic medical record (EMR) prompts, visual reminders, staff education and training, and allowing nonphysicians to screen and order vaccines. The implementation of nonphysician protocols has proven effective in increasing inpatient influenza vaccinations in multiple studies (Mihalek AJ, et al. Hosp Pediatr. 2021 Dec 1. doi: 10.1542/hpeds.2021-005924; Skull S, et al. J Paediatr Child Health. 1999;35[5]:472).

Optimizing the delivery of vaccines to hospitalized patients carries substantial public health benefits. This is especially vital for patients who face challenges accessing primary care and during periods of health care systems disruptions, such as those experienced during the COVID-19 pandemic.

In conclusion, inpatient vaccinations against respiratory viral illnesses are supported by a growing body of evidence. These vaccinations not only prevent disease transmission within health care facilities but also protect vulnerable patients, alleviate the burden on health care systems and with the recent approval of the RSV vaccine, we have a new tool to combat respiratory viruses effectively. As we continue to navigate the challenges posed by respiratory viruses, prioritizing inpatient vaccinations is a wise and necessary step toward a healthier, safer future for all.

Stella Ogake, MD – Section Member-at-Large

Chest Infections & Disaster Response Network

Disaster Response & Global Health Section

In recent years, the importance of inpatient vaccinations against respiratory viral illnesses has become increasingly clear. As the world grapples with the ever-present threat of contagious diseases like influenza, COVID-19, Respiratory Syncytial Virus (RSV) and other respiratory viruses, the significance of vaccinating individuals during hospital stays cannot be overstated. Notably, the rates of inpatient vaccinations have significantly increased in recent years.

Numerous studies have demonstrated the success of various strategies to boost vaccine delivery to hospitalized patients. These strategies include personalized catch-up plans, electronic medical record (EMR) prompts, visual reminders, staff education and training, and allowing nonphysicians to screen and order vaccines. The implementation of nonphysician protocols has proven effective in increasing inpatient influenza vaccinations in multiple studies (Mihalek AJ, et al. Hosp Pediatr. 2021 Dec 1. doi: 10.1542/hpeds.2021-005924; Skull S, et al. J Paediatr Child Health. 1999;35[5]:472).

Optimizing the delivery of vaccines to hospitalized patients carries substantial public health benefits. This is especially vital for patients who face challenges accessing primary care and during periods of health care systems disruptions, such as those experienced during the COVID-19 pandemic.

In conclusion, inpatient vaccinations against respiratory viral illnesses are supported by a growing body of evidence. These vaccinations not only prevent disease transmission within health care facilities but also protect vulnerable patients, alleviate the burden on health care systems and with the recent approval of the RSV vaccine, we have a new tool to combat respiratory viruses effectively. As we continue to navigate the challenges posed by respiratory viruses, prioritizing inpatient vaccinations is a wise and necessary step toward a healthier, safer future for all.

Stella Ogake, MD – Section Member-at-Large

Chest Infections & Disaster Response Network

Disaster Response & Global Health Section

In recent years, the importance of inpatient vaccinations against respiratory viral illnesses has become increasingly clear. As the world grapples with the ever-present threat of contagious diseases like influenza, COVID-19, Respiratory Syncytial Virus (RSV) and other respiratory viruses, the significance of vaccinating individuals during hospital stays cannot be overstated. Notably, the rates of inpatient vaccinations have significantly increased in recent years.

Numerous studies have demonstrated the success of various strategies to boost vaccine delivery to hospitalized patients. These strategies include personalized catch-up plans, electronic medical record (EMR) prompts, visual reminders, staff education and training, and allowing nonphysicians to screen and order vaccines. The implementation of nonphysician protocols has proven effective in increasing inpatient influenza vaccinations in multiple studies (Mihalek AJ, et al. Hosp Pediatr. 2021 Dec 1. doi: 10.1542/hpeds.2021-005924; Skull S, et al. J Paediatr Child Health. 1999;35[5]:472).

Optimizing the delivery of vaccines to hospitalized patients carries substantial public health benefits. This is especially vital for patients who face challenges accessing primary care and during periods of health care systems disruptions, such as those experienced during the COVID-19 pandemic.

In conclusion, inpatient vaccinations against respiratory viral illnesses are supported by a growing body of evidence. These vaccinations not only prevent disease transmission within health care facilities but also protect vulnerable patients, alleviate the burden on health care systems and with the recent approval of the RSV vaccine, we have a new tool to combat respiratory viruses effectively. As we continue to navigate the challenges posed by respiratory viruses, prioritizing inpatient vaccinations is a wise and necessary step toward a healthier, safer future for all.

Stella Ogake, MD – Section Member-at-Large

Chest Infections & Disaster Response Network

Chest Infections Section

November 12 marks World Pneumonia Day, and while it has long been recognized that viruses play a significant role in causing pneumonia, awareness has surged due to the COVID-19 pandemic. Furthermore, with the advent of rapid molecular diagnostics, the contribution of respiratory viral pathogens in pneumonia has become clearer (Seema J, et al. N Engl J Med. 2015 Jul 30;373[5]:415-27). Despite COVID-19 remaining a substantial threat, infection rates with other respiratory viruses are on the rise and will continue to increase during colder months. Here, we will provide an update on influenza and RSV:
 

Currently, influenza activity in the United States is low (National Center for Immunization and Respiratory Diseases. FluView. 2023 Oct 4. https://www.cdc.gov/flu/weekly/index.htm). Vaccination coverage for US adults during the previous influenza season stood at 47% (Centers for Disease Control and Prevention. FluVaxView Vaccination Dashboard. 2023 Oct 4. https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html). Hospitalizations were estimated to range between 300,000 and 650,000, a significant increase from the 2021-2022 season, which saw about 100,000 hospitalizations (Centers for Disease Control and Prevention. Preliminary In-Season Estimates of Influenza Burden. 2023 Oct 4. https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm). Data from the Southern Hemisphere’s recent influenza season indicates a 52% vaccine efficacy in preventing influenza-associated hospitalizations (Fowlkes AL, et al. MMWR Morb Mortal Wkly Rep. 2023 Sep 15;72[37]:1010-5). Influenza hospitalization rates are likely returning to higher pre-COVID-19 levels.

Respiratory Syncytial Virus (RSV) is a seasonal pathogen causing substantial morbidity and mortality. This year, two new vaccines have become available to prevent RSV-associated lower respiratory tract diseases, boasting a vaccine effectiveness of over 80% for the first and over 70% for the second season post-administration (Melgar M, et al. MMWR Morb Mortal Wkly Rep. 2023 Jul 21;72[29]:793-801). The CDC’s Advisory Committee on Immunization Practices recommends a single dose for adults over 60, and one vaccine is FDA-approved for pregnant individuals (32-36 weeks gestation) to provide passive infant immunity.

In summary, both the current influenza vaccine and the new RSV vaccines demonstrate effectiveness and are strongly recommended, alongside an updated COVID-19 vaccine.

John Huston, MD

Jamie Felzer, MD, MPH – Section Fellow-in-Training

Charles Dela Cruz, MD – Section Member-at-Large

Sebastian Kurz, MD, FCCP – Network Member-at-Large

Chest Infections & Disaster Response Network

Chest Infections Section

November 12 marks World Pneumonia Day, and while it has long been recognized that viruses play a significant role in causing pneumonia, awareness has surged due to the COVID-19 pandemic. Furthermore, with the advent of rapid molecular diagnostics, the contribution of respiratory viral pathogens in pneumonia has become clearer (Seema J, et al. N Engl J Med. 2015 Jul 30;373[5]:415-27). Despite COVID-19 remaining a substantial threat, infection rates with other respiratory viruses are on the rise and will continue to increase during colder months. Here, we will provide an update on influenza and RSV:
 

Currently, influenza activity in the United States is low (National Center for Immunization and Respiratory Diseases. FluView. 2023 Oct 4. https://www.cdc.gov/flu/weekly/index.htm). Vaccination coverage for US adults during the previous influenza season stood at 47% (Centers for Disease Control and Prevention. FluVaxView Vaccination Dashboard. 2023 Oct 4. https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html). Hospitalizations were estimated to range between 300,000 and 650,000, a significant increase from the 2021-2022 season, which saw about 100,000 hospitalizations (Centers for Disease Control and Prevention. Preliminary In-Season Estimates of Influenza Burden. 2023 Oct 4. https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm). Data from the Southern Hemisphere’s recent influenza season indicates a 52% vaccine efficacy in preventing influenza-associated hospitalizations (Fowlkes AL, et al. MMWR Morb Mortal Wkly Rep. 2023 Sep 15;72[37]:1010-5). Influenza hospitalization rates are likely returning to higher pre-COVID-19 levels.

Respiratory Syncytial Virus (RSV) is a seasonal pathogen causing substantial morbidity and mortality. This year, two new vaccines have become available to prevent RSV-associated lower respiratory tract diseases, boasting a vaccine effectiveness of over 80% for the first and over 70% for the second season post-administration (Melgar M, et al. MMWR Morb Mortal Wkly Rep. 2023 Jul 21;72[29]:793-801). The CDC’s Advisory Committee on Immunization Practices recommends a single dose for adults over 60, and one vaccine is FDA-approved for pregnant individuals (32-36 weeks gestation) to provide passive infant immunity.

In summary, both the current influenza vaccine and the new RSV vaccines demonstrate effectiveness and are strongly recommended, alongside an updated COVID-19 vaccine.

John Huston, MD

Jamie Felzer, MD, MPH – Section Fellow-in-Training

Charles Dela Cruz, MD – Section Member-at-Large

Sebastian Kurz, MD, FCCP – Network Member-at-Large

Chest Infections & Disaster Response Network

Chest Infections Section

November 12 marks World Pneumonia Day, and while it has long been recognized that viruses play a significant role in causing pneumonia, awareness has surged due to the COVID-19 pandemic. Furthermore, with the advent of rapid molecular diagnostics, the contribution of respiratory viral pathogens in pneumonia has become clearer (Seema J, et al. N Engl J Med. 2015 Jul 30;373[5]:415-27). Despite COVID-19 remaining a substantial threat, infection rates with other respiratory viruses are on the rise and will continue to increase during colder months. Here, we will provide an update on influenza and RSV:
 

Currently, influenza activity in the United States is low (National Center for Immunization and Respiratory Diseases. FluView. 2023 Oct 4. https://www.cdc.gov/flu/weekly/index.htm). Vaccination coverage for US adults during the previous influenza season stood at 47% (Centers for Disease Control and Prevention. FluVaxView Vaccination Dashboard. 2023 Oct 4. https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html). Hospitalizations were estimated to range between 300,000 and 650,000, a significant increase from the 2021-2022 season, which saw about 100,000 hospitalizations (Centers for Disease Control and Prevention. Preliminary In-Season Estimates of Influenza Burden. 2023 Oct 4. https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm). Data from the Southern Hemisphere’s recent influenza season indicates a 52% vaccine efficacy in preventing influenza-associated hospitalizations (Fowlkes AL, et al. MMWR Morb Mortal Wkly Rep. 2023 Sep 15;72[37]:1010-5). Influenza hospitalization rates are likely returning to higher pre-COVID-19 levels.

Respiratory Syncytial Virus (RSV) is a seasonal pathogen causing substantial morbidity and mortality. This year, two new vaccines have become available to prevent RSV-associated lower respiratory tract diseases, boasting a vaccine effectiveness of over 80% for the first and over 70% for the second season post-administration (Melgar M, et al. MMWR Morb Mortal Wkly Rep. 2023 Jul 21;72[29]:793-801). The CDC’s Advisory Committee on Immunization Practices recommends a single dose for adults over 60, and one vaccine is FDA-approved for pregnant individuals (32-36 weeks gestation) to provide passive infant immunity.

In summary, both the current influenza vaccine and the new RSV vaccines demonstrate effectiveness and are strongly recommended, alongside an updated COVID-19 vaccine.

John Huston, MD

Jamie Felzer, MD, MPH – Section Fellow-in-Training

Charles Dela Cruz, MD – Section Member-at-Large

Sebastian Kurz, MD, FCCP – Network Member-at-Large

Residual excessive daytime sleepiness (REDS) is defined as the urge to sleep during the day despite an intention to remain alert after optimal treatment of obstructive sleep apnea (OSA). This is a distressing outcome with an estimated prevalence of 9% to 22% among patients with OSA (Pépin JL, et al. Eur Respir J. 2009;33[5]:1062). The pathophysiology of the condition is complex, and experimental studies conducted on animal models have demonstrated that chronic sleep fragmentation and chronic intermittent hypoxia can result in detrimental effects on wake-­promoting neurons. Additionally, there is evidence of heightened oxidative stress and alterations in melatonin secretion, with the severity and duration of the disease playing a significant role in the manifestation of these effects (Javaheri S, et al. Chest. 2020;158[2]:776). It is considered a diagnosis of exclusion, with the assessment being mostly subjective. Prior to diagnosing REDS, it is crucial to optimize positive airway pressure (PAP) therapy and nocturnal ventilation, ensure sufficient adherence to sleep hygiene practices, and exclude the presence of other sleep disorders. The Epworth Sleepiness Scale (ESS) score is widely utilized as a primary clinical tool in the assessment of sleepiness. To enhance the precision of this score, it is advantageous to take input from both family members and friends. Additional objective assessments that could be considered include the utilization of the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT).

Due to the socioeconomic and public health considerations of REDS, pharmacological therapy is crucial to its management after exhausting conservative measures. Off-label use of traditional central nervous system stimulants, like amphetamine or methylphenidate, in these patients is almost extinct. The potential for abuse and negative consequences outweighs the potential benefits. FDA-approved medications for treatment of REDS in OSA include modafinil, armodafinil, and solriamfetol in the United States.

Historically, modafinil and armodafinil are the first-line and most commonly used wake-promoting agents. Both agents bind to the dopamine transporter and inhibit dopamine reuptake. They have demonstrated efficacy in reducing EDS and improving wakefulness in patients with OSA treated with CPAP. A meta-analysis of 10 randomized, placebo-controlled trials of modafinil and armodafinil found that they were better than placebo by 2.2 points on the ESS score and 3 minutes on the MWT (Maintenance of Wakefulness Test) (Chapman JL, et al. Eur Respir J. 2016;47[5]:1420). Both drugs have common adverse effects of headache, nausea, nervousness, insomnia, dizziness, rhinitis, and diarrhea. Drug interaction with CYP3A4/5 substrates and oral contraceptives is a concern with these medications. In 2010, the European Medicines Agency restricted the use of modafinil only to patients with narcolepsy, considering its cardiovascular and neuropsychiatric risks (European Medicines Agency website; press release, July 22, 2010).

Solriamfetol is the newest medication being utilized for EDS in OSA and is approved in both the United States and Europe for this indication. It is a dopamine and norepinephrine reuptake inhibitor with a simultaneous effect on both transporters. It has been effective in improving wakefulness and reducing sleepiness in patients with residual OSA. In the landmark trial TONES 3, dose-dependent (37.5, 75, 150, and 300 mg/day) effects were observed, with improvements in ESS scores of –1.9 to –4.7 points and sleep latency in MWT by 4.5 to 12.8 minutes (Schweitzer PK, et al. Am J Respir Crit Care Med. 2019;199[11]:1421). The current recommended dosing for REDS in OSA is to start with the lowest dose of 37.5 mg/day and increase to the maximum dose of 150 mg/day by titrating up every 3 days if needed. A recent meta-analysis showed an indirect treatment comparison between efficacy and safety among the medications solriamfetol, modafinil, and armodafinil (Ronnebaum S, et al. J Clin Sleep Med. 2021;17[12]:2543). Six parallel-arm, placebo-controlled, randomized, controlled trials were looked at. The ESS score, MWT20 sleep latency, and CGI-C (Clinical Global Impression of Change) all got better in comparison to the placebo. Relative to the comparators and placebo at 12 weeks, solriamfetol at 150 mg and 300 mg had the highest degree of improvement in all the outcomes studied. Common adverse effects of solriamfetol include headache, nausea, decreased appetite, insomnia, dry mouth, anxiety, and minimal increase in blood pressure and heart rate. The adverse effects in terms of blood pressure and heart rate change have a dose-dependent relationship, and serial vitals monitoring is recommended for patients every 6 months to a year. This medication is contraindicated in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of an MAOI because of the risk of hypertensive reactions. Solriamfetol is renally excreted, so dose adjustment is needed in patients with moderate to severe renal impairment. It is not recommended for use in end-stage renal disease (eGFR <15 mL/min/1.73 m²) (SUNOSI. Full prescribing information. Axsome; revised 06/2023. https://www.sunosihcp.com/assets/files/sunosi.en.uspi.pdf. Accessed: Sept 24, 2023). Solriamfetol demonstrates a comparatively shorter half-life when compared with traditional pharmaceuticals like modafinil and armodafinil, implying the possibility of a decreased duration of its effects. The effect in question may exhibit interpersonal diversity in its impact on quality of life when applied in a therapeutic setting.

Pitolisant is another potential medication to treat REDS in patients with OSA. While only approved for treating EDS and cataplexy in adult US patients with narcolepsy, it is currently approved for REDS in OSA in Europe (Ozawade. European Medicines Agency. Last updated 12/05/2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ozawade#product-information-­section. Accessed: Oct 2, 2023). It is a selective histamine H3 receptor antagonist and an inverse agonist of the presynaptic H3 receptor. The fact that this medication is not scheduled and has a negligible or nonexistent risk of abuse is one of its advantages. It is dosed once daily, and the most frequent adverse effects include headaches and insomnia. A prolonged QT interval was observed in a few patients; caution is needed with concomitant use of other medications with known similar effects. Dosage modification is recommended in patients with moderate hepatic impairment and moderate to severe renal impairment. Drug interactions are also observed with the concomitant use of CYP2D6 inhibitors and CYP3A4 inducers. Pitolisant may reduce the efficacy of hormonal contraception, including up to 21 days after its discontinuation (WAKIX. Full prescribing information. Harmony biosciences; revised 12/2022.https://wakixhcp.com/pdf/wakix-­tablets-pi.pdf. Accessed: Sept 24, 2023).
 

Dr. Mechineni is Sleep Attending Physician, Ascension Illinois, Alexian Brothers Medical Center, Chicago. Dr. Sahni is Assistant Professor of Clinical Medicine, Associate Program Director, Sleep Medicine Fellowship; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago.

Residual excessive daytime sleepiness (REDS) is defined as the urge to sleep during the day despite an intention to remain alert after optimal treatment of obstructive sleep apnea (OSA). This is a distressing outcome with an estimated prevalence of 9% to 22% among patients with OSA (Pépin JL, et al. Eur Respir J. 2009;33[5]:1062). The pathophysiology of the condition is complex, and experimental studies conducted on animal models have demonstrated that chronic sleep fragmentation and chronic intermittent hypoxia can result in detrimental effects on wake-­promoting neurons. Additionally, there is evidence of heightened oxidative stress and alterations in melatonin secretion, with the severity and duration of the disease playing a significant role in the manifestation of these effects (Javaheri S, et al. Chest. 2020;158[2]:776). It is considered a diagnosis of exclusion, with the assessment being mostly subjective. Prior to diagnosing REDS, it is crucial to optimize positive airway pressure (PAP) therapy and nocturnal ventilation, ensure sufficient adherence to sleep hygiene practices, and exclude the presence of other sleep disorders. The Epworth Sleepiness Scale (ESS) score is widely utilized as a primary clinical tool in the assessment of sleepiness. To enhance the precision of this score, it is advantageous to take input from both family members and friends. Additional objective assessments that could be considered include the utilization of the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT).

Due to the socioeconomic and public health considerations of REDS, pharmacological therapy is crucial to its management after exhausting conservative measures. Off-label use of traditional central nervous system stimulants, like amphetamine or methylphenidate, in these patients is almost extinct. The potential for abuse and negative consequences outweighs the potential benefits. FDA-approved medications for treatment of REDS in OSA include modafinil, armodafinil, and solriamfetol in the United States.

Historically, modafinil and armodafinil are the first-line and most commonly used wake-promoting agents. Both agents bind to the dopamine transporter and inhibit dopamine reuptake. They have demonstrated efficacy in reducing EDS and improving wakefulness in patients with OSA treated with CPAP. A meta-analysis of 10 randomized, placebo-controlled trials of modafinil and armodafinil found that they were better than placebo by 2.2 points on the ESS score and 3 minutes on the MWT (Maintenance of Wakefulness Test) (Chapman JL, et al. Eur Respir J. 2016;47[5]:1420). Both drugs have common adverse effects of headache, nausea, nervousness, insomnia, dizziness, rhinitis, and diarrhea. Drug interaction with CYP3A4/5 substrates and oral contraceptives is a concern with these medications. In 2010, the European Medicines Agency restricted the use of modafinil only to patients with narcolepsy, considering its cardiovascular and neuropsychiatric risks (European Medicines Agency website; press release, July 22, 2010).

Solriamfetol is the newest medication being utilized for EDS in OSA and is approved in both the United States and Europe for this indication. It is a dopamine and norepinephrine reuptake inhibitor with a simultaneous effect on both transporters. It has been effective in improving wakefulness and reducing sleepiness in patients with residual OSA. In the landmark trial TONES 3, dose-dependent (37.5, 75, 150, and 300 mg/day) effects were observed, with improvements in ESS scores of –1.9 to –4.7 points and sleep latency in MWT by 4.5 to 12.8 minutes (Schweitzer PK, et al. Am J Respir Crit Care Med. 2019;199[11]:1421). The current recommended dosing for REDS in OSA is to start with the lowest dose of 37.5 mg/day and increase to the maximum dose of 150 mg/day by titrating up every 3 days if needed. A recent meta-analysis showed an indirect treatment comparison between efficacy and safety among the medications solriamfetol, modafinil, and armodafinil (Ronnebaum S, et al. J Clin Sleep Med. 2021;17[12]:2543). Six parallel-arm, placebo-controlled, randomized, controlled trials were looked at. The ESS score, MWT20 sleep latency, and CGI-C (Clinical Global Impression of Change) all got better in comparison to the placebo. Relative to the comparators and placebo at 12 weeks, solriamfetol at 150 mg and 300 mg had the highest degree of improvement in all the outcomes studied. Common adverse effects of solriamfetol include headache, nausea, decreased appetite, insomnia, dry mouth, anxiety, and minimal increase in blood pressure and heart rate. The adverse effects in terms of blood pressure and heart rate change have a dose-dependent relationship, and serial vitals monitoring is recommended for patients every 6 months to a year. This medication is contraindicated in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of an MAOI because of the risk of hypertensive reactions. Solriamfetol is renally excreted, so dose adjustment is needed in patients with moderate to severe renal impairment. It is not recommended for use in end-stage renal disease (eGFR <15 mL/min/1.73 m²) (SUNOSI. Full prescribing information. Axsome; revised 06/2023. https://www.sunosihcp.com/assets/files/sunosi.en.uspi.pdf. Accessed: Sept 24, 2023). Solriamfetol demonstrates a comparatively shorter half-life when compared with traditional pharmaceuticals like modafinil and armodafinil, implying the possibility of a decreased duration of its effects. The effect in question may exhibit interpersonal diversity in its impact on quality of life when applied in a therapeutic setting.

Pitolisant is another potential medication to treat REDS in patients with OSA. While only approved for treating EDS and cataplexy in adult US patients with narcolepsy, it is currently approved for REDS in OSA in Europe (Ozawade. European Medicines Agency. Last updated 12/05/2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ozawade#product-information-­section. Accessed: Oct 2, 2023). It is a selective histamine H3 receptor antagonist and an inverse agonist of the presynaptic H3 receptor. The fact that this medication is not scheduled and has a negligible or nonexistent risk of abuse is one of its advantages. It is dosed once daily, and the most frequent adverse effects include headaches and insomnia. A prolonged QT interval was observed in a few patients; caution is needed with concomitant use of other medications with known similar effects. Dosage modification is recommended in patients with moderate hepatic impairment and moderate to severe renal impairment. Drug interactions are also observed with the concomitant use of CYP2D6 inhibitors and CYP3A4 inducers. Pitolisant may reduce the efficacy of hormonal contraception, including up to 21 days after its discontinuation (WAKIX. Full prescribing information. Harmony biosciences; revised 12/2022.https://wakixhcp.com/pdf/wakix-­tablets-pi.pdf. Accessed: Sept 24, 2023).
 

Dr. Mechineni is Sleep Attending Physician, Ascension Illinois, Alexian Brothers Medical Center, Chicago. Dr. Sahni is Assistant Professor of Clinical Medicine, Associate Program Director, Sleep Medicine Fellowship; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago.

Residual excessive daytime sleepiness (REDS) is defined as the urge to sleep during the day despite an intention to remain alert after optimal treatment of obstructive sleep apnea (OSA). This is a distressing outcome with an estimated prevalence of 9% to 22% among patients with OSA (Pépin JL, et al. Eur Respir J. 2009;33[5]:1062). The pathophysiology of the condition is complex, and experimental studies conducted on animal models have demonstrated that chronic sleep fragmentation and chronic intermittent hypoxia can result in detrimental effects on wake-­promoting neurons. Additionally, there is evidence of heightened oxidative stress and alterations in melatonin secretion, with the severity and duration of the disease playing a significant role in the manifestation of these effects (Javaheri S, et al. Chest. 2020;158[2]:776). It is considered a diagnosis of exclusion, with the assessment being mostly subjective. Prior to diagnosing REDS, it is crucial to optimize positive airway pressure (PAP) therapy and nocturnal ventilation, ensure sufficient adherence to sleep hygiene practices, and exclude the presence of other sleep disorders. The Epworth Sleepiness Scale (ESS) score is widely utilized as a primary clinical tool in the assessment of sleepiness. To enhance the precision of this score, it is advantageous to take input from both family members and friends. Additional objective assessments that could be considered include the utilization of the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT).

Due to the socioeconomic and public health considerations of REDS, pharmacological therapy is crucial to its management after exhausting conservative measures. Off-label use of traditional central nervous system stimulants, like amphetamine or methylphenidate, in these patients is almost extinct. The potential for abuse and negative consequences outweighs the potential benefits. FDA-approved medications for treatment of REDS in OSA include modafinil, armodafinil, and solriamfetol in the United States.

Historically, modafinil and armodafinil are the first-line and most commonly used wake-promoting agents. Both agents bind to the dopamine transporter and inhibit dopamine reuptake. They have demonstrated efficacy in reducing EDS and improving wakefulness in patients with OSA treated with CPAP. A meta-analysis of 10 randomized, placebo-controlled trials of modafinil and armodafinil found that they were better than placebo by 2.2 points on the ESS score and 3 minutes on the MWT (Maintenance of Wakefulness Test) (Chapman JL, et al. Eur Respir J. 2016;47[5]:1420). Both drugs have common adverse effects of headache, nausea, nervousness, insomnia, dizziness, rhinitis, and diarrhea. Drug interaction with CYP3A4/5 substrates and oral contraceptives is a concern with these medications. In 2010, the European Medicines Agency restricted the use of modafinil only to patients with narcolepsy, considering its cardiovascular and neuropsychiatric risks (European Medicines Agency website; press release, July 22, 2010).

Solriamfetol is the newest medication being utilized for EDS in OSA and is approved in both the United States and Europe for this indication. It is a dopamine and norepinephrine reuptake inhibitor with a simultaneous effect on both transporters. It has been effective in improving wakefulness and reducing sleepiness in patients with residual OSA. In the landmark trial TONES 3, dose-dependent (37.5, 75, 150, and 300 mg/day) effects were observed, with improvements in ESS scores of –1.9 to –4.7 points and sleep latency in MWT by 4.5 to 12.8 minutes (Schweitzer PK, et al. Am J Respir Crit Care Med. 2019;199[11]:1421). The current recommended dosing for REDS in OSA is to start with the lowest dose of 37.5 mg/day and increase to the maximum dose of 150 mg/day by titrating up every 3 days if needed. A recent meta-analysis showed an indirect treatment comparison between efficacy and safety among the medications solriamfetol, modafinil, and armodafinil (Ronnebaum S, et al. J Clin Sleep Med. 2021;17[12]:2543). Six parallel-arm, placebo-controlled, randomized, controlled trials were looked at. The ESS score, MWT20 sleep latency, and CGI-C (Clinical Global Impression of Change) all got better in comparison to the placebo. Relative to the comparators and placebo at 12 weeks, solriamfetol at 150 mg and 300 mg had the highest degree of improvement in all the outcomes studied. Common adverse effects of solriamfetol include headache, nausea, decreased appetite, insomnia, dry mouth, anxiety, and minimal increase in blood pressure and heart rate. The adverse effects in terms of blood pressure and heart rate change have a dose-dependent relationship, and serial vitals monitoring is recommended for patients every 6 months to a year. This medication is contraindicated in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of an MAOI because of the risk of hypertensive reactions. Solriamfetol is renally excreted, so dose adjustment is needed in patients with moderate to severe renal impairment. It is not recommended for use in end-stage renal disease (eGFR <15 mL/min/1.73 m²) (SUNOSI. Full prescribing information. Axsome; revised 06/2023. https://www.sunosihcp.com/assets/files/sunosi.en.uspi.pdf. Accessed: Sept 24, 2023). Solriamfetol demonstrates a comparatively shorter half-life when compared with traditional pharmaceuticals like modafinil and armodafinil, implying the possibility of a decreased duration of its effects. The effect in question may exhibit interpersonal diversity in its impact on quality of life when applied in a therapeutic setting.

Pitolisant is another potential medication to treat REDS in patients with OSA. While only approved for treating EDS and cataplexy in adult US patients with narcolepsy, it is currently approved for REDS in OSA in Europe (Ozawade. European Medicines Agency. Last updated 12/05/2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ozawade#product-information-­section. Accessed: Oct 2, 2023). It is a selective histamine H3 receptor antagonist and an inverse agonist of the presynaptic H3 receptor. The fact that this medication is not scheduled and has a negligible or nonexistent risk of abuse is one of its advantages. It is dosed once daily, and the most frequent adverse effects include headaches and insomnia. A prolonged QT interval was observed in a few patients; caution is needed with concomitant use of other medications with known similar effects. Dosage modification is recommended in patients with moderate hepatic impairment and moderate to severe renal impairment. Drug interactions are also observed with the concomitant use of CYP2D6 inhibitors and CYP3A4 inducers. Pitolisant may reduce the efficacy of hormonal contraception, including up to 21 days after its discontinuation (WAKIX. Full prescribing information. Harmony biosciences; revised 12/2022.https://wakixhcp.com/pdf/wakix-­tablets-pi.pdf. Accessed: Sept 24, 2023).
 

Dr. Mechineni is Sleep Attending Physician, Ascension Illinois, Alexian Brothers Medical Center, Chicago. Dr. Sahni is Assistant Professor of Clinical Medicine, Associate Program Director, Sleep Medicine Fellowship; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago.

Patients admitted to ICUs require modifications to their medication regimen due to their critical illness and rapidly changing clinical status. Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.

While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)

The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).

The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.

Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.

In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
 

Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.

Patients admitted to ICUs require modifications to their medication regimen due to their critical illness and rapidly changing clinical status. Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.

While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)

The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).

The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.

Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.

In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
 

Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.

Patients admitted to ICUs require modifications to their medication regimen due to their critical illness and rapidly changing clinical status. Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.

While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)

The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).

The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.

Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.

In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
 

Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.

TOPLINE:

Most patients with psoriasis are not participating in highly shared decision-making (SDM) with clinicians about their care.

METHODOLOGY:

• Researchers drew from the 2014-2017 and 2019 Medical Expenditure Panel Survey (MEPS) to identify 3,715,027 patients with psoriasis, to evaluate the association between SDM (a patient-centered approach to selecting treatment on the basis of a discussion between the clinician and patient) and satisfaction with care.
• SDM was determined by patient responses on a 4-point Likert scale to seven MEPS variables, including the question, “How often did doctors or other health providers listen carefully to you?”
• Patient satisfaction with care was measured with a MEPS variable that asked respondents to rate their health care providers on a scale of 1-10.
• Researchers used multiple logistic regression to assess the association between SDM and demographic and clinical characteristics in patients with psoriasis, and multiple linear regression analysis to assess the association between SDM and patient satisfaction with care.

TAKEAWAY:

• The average SDM score was 3.6 out of 4, and the average satisfaction with care score was 8.6 out of 10.
• However, only about 42% of the cohort reported a high SDM, defined as a score of 3.9 or greater.
• After adjusting for covariates, the researchers found that patients who had high SDM had, on average, 85% higher satisfaction with care (P < .001).
• Compared with men, women had about 27% higher satisfaction with care (P = .023), whereas non-Hispanic patients had lower satisfaction with care compared with Hispanic patients (P = .037).

IN PRACTICE:

“It is important to construct a framework for carrying out SDM with patients with psoriasis to enhance clinician-patient communication and improve patient outcomes,” the authors concluded.

SOURCE:

April W. Armstrong, MD, MPH, chief of dermatology at the University of California, Los Angeles, led the research. The study was published online  in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The ability to measure SDM in patients with psoriasis was limited by the seven items from MEPS. The diagnosis of psoriasis was based on self-report.

DISCLOSURES:

The study was funded by the National Psoriasis Foundation. Dr. Armstrong disclosed that she has served as a research investigator and/or scientific adviser to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

A version of this article first appeared on Medscape.com.

TOPLINE:

Most patients with psoriasis are not participating in highly shared decision-making (SDM) with clinicians about their care.

METHODOLOGY:

• Researchers drew from the 2014-2017 and 2019 Medical Expenditure Panel Survey (MEPS) to identify 3,715,027 patients with psoriasis, to evaluate the association between SDM (a patient-centered approach to selecting treatment on the basis of a discussion between the clinician and patient) and satisfaction with care.
• SDM was determined by patient responses on a 4-point Likert scale to seven MEPS variables, including the question, “How often did doctors or other health providers listen carefully to you?”
• Patient satisfaction with care was measured with a MEPS variable that asked respondents to rate their health care providers on a scale of 1-10.
• Researchers used multiple logistic regression to assess the association between SDM and demographic and clinical characteristics in patients with psoriasis, and multiple linear regression analysis to assess the association between SDM and patient satisfaction with care.

TAKEAWAY:

• The average SDM score was 3.6 out of 4, and the average satisfaction with care score was 8.6 out of 10.
• However, only about 42% of the cohort reported a high SDM, defined as a score of 3.9 or greater.
• After adjusting for covariates, the researchers found that patients who had high SDM had, on average, 85% higher satisfaction with care (P < .001).
• Compared with men, women had about 27% higher satisfaction with care (P = .023), whereas non-Hispanic patients had lower satisfaction with care compared with Hispanic patients (P = .037).

IN PRACTICE:

“It is important to construct a framework for carrying out SDM with patients with psoriasis to enhance clinician-patient communication and improve patient outcomes,” the authors concluded.

SOURCE:

April W. Armstrong, MD, MPH, chief of dermatology at the University of California, Los Angeles, led the research. The study was published online  in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The ability to measure SDM in patients with psoriasis was limited by the seven items from MEPS. The diagnosis of psoriasis was based on self-report.

DISCLOSURES:

The study was funded by the National Psoriasis Foundation. Dr. Armstrong disclosed that she has served as a research investigator and/or scientific adviser to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

A version of this article first appeared on Medscape.com.

TOPLINE:

Most patients with psoriasis are not participating in highly shared decision-making (SDM) with clinicians about their care.

METHODOLOGY:

• Researchers drew from the 2014-2017 and 2019 Medical Expenditure Panel Survey (MEPS) to identify 3,715,027 patients with psoriasis, to evaluate the association between SDM (a patient-centered approach to selecting treatment on the basis of a discussion between the clinician and patient) and satisfaction with care.
• SDM was determined by patient responses on a 4-point Likert scale to seven MEPS variables, including the question, “How often did doctors or other health providers listen carefully to you?”
• Patient satisfaction with care was measured with a MEPS variable that asked respondents to rate their health care providers on a scale of 1-10.
• Researchers used multiple logistic regression to assess the association between SDM and demographic and clinical characteristics in patients with psoriasis, and multiple linear regression analysis to assess the association between SDM and patient satisfaction with care.

TAKEAWAY:

• The average SDM score was 3.6 out of 4, and the average satisfaction with care score was 8.6 out of 10.
• However, only about 42% of the cohort reported a high SDM, defined as a score of 3.9 or greater.
• After adjusting for covariates, the researchers found that patients who had high SDM had, on average, 85% higher satisfaction with care (P < .001).
• Compared with men, women had about 27% higher satisfaction with care (P = .023), whereas non-Hispanic patients had lower satisfaction with care compared with Hispanic patients (P = .037).

IN PRACTICE:

“It is important to construct a framework for carrying out SDM with patients with psoriasis to enhance clinician-patient communication and improve patient outcomes,” the authors concluded.

SOURCE:

April W. Armstrong, MD, MPH, chief of dermatology at the University of California, Los Angeles, led the research. The study was published online  in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The ability to measure SDM in patients with psoriasis was limited by the seven items from MEPS. The diagnosis of psoriasis was based on self-report.

DISCLOSURES:

The study was funded by the National Psoriasis Foundation. Dr. Armstrong disclosed that she has served as a research investigator and/or scientific adviser to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

A version of this article first appeared on Medscape.com.

For some patients with atopic dermatitis (AD), dupilumab treatment can cause a benign reversible lymphoid reaction (LR) that mimics mycosis fungoides (MF) but differs histologically, according to a study published in JAMA Dermatology

The potential for such reactions requires diagnosing AD carefully, monitoring patients on dupilumab for new and unusual symptoms, and thoroughly working up suspicious LRs, according to an accompanying editorial and experts interviewed for this article.

“Dupilumab has become such an important first-line systemic medication for our patients with moderate to severe atopic dermatitis. It’s important for us to understand everything we can about its use in the real world – both good and bad,”Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Northwestern University, Chicago, said in an interview. He was uninvolved with either publication.

Robert Sidbury, MD, MPH, added that, although the affected patient group was small, studying lymphoid reactions associated with dupilumab is important because of the risk for diagnostic misadventure that these reactions carry. He is a professor of pediatrics and division head of dermatology at Seattle Children’s Hospital and the University of Washington, Seattle.

“AD and MF are easily confused for one another at baseline,” explained Dr. Sidbury, who was not involved with the study or editorial. “Dupilumab is known to make AD better and theoretically could help MF via its effect on interleukin (IL)–13, yet case reports of exacerbation and/or unmasking of MF are out there.”

For the study, researchers retrospectively examined records of 530 patients with AD treated with dupilumab at the University Medical Center Utrecht (the Netherlands). Reviewing pretreatment biopsies revealed that among 14 (2.6%) patients who developed clinical suspicion of cutaneous T-cell lymphoma (CTCL) while on treatment, three actually had preexisting MF.

All 14 patients with LR initially responded to dupilumab then developed worsening symptoms at a median of 4 months. Patients reported that the worsening lesions looked and felt different than did previous lesions, with symptoms including burning/pain and an appearance of generalized erythematous maculopapular plaques, sometimes with severe lichenification, on the lower trunk and upper thighs.

The 14 patients’ posttreatment biopsies showed an atypical lymphoid infiltrate with lichenoid or perivascular distribution and intraepithelial T-cell lymphocytes. Whereas patients with MF had hyperconvoluted cerebriform lymphocytes aligned in the epidermal basal layer at the dermoepidermal junction, the 11 with LR had similar-looking lesions dispersed throughout the upper epidermis.

Immunohistochemically, both groups had a dysregulated (mostly increased) CD4:CD8 ratio. CD30 overexpression, usually absent in early-stage MF, affected only patients with LR and one patient with advanced MF. In addition, patients with LR maintained pan–T-cell antigens (CD2, CD3, and CD5), whereas those with MF did not. The 11 patients with LR experienced biopsy-confirmed resolution once they discontinued dupilumab.

It is reassuring that the LRs resolved after dupilumab discontinuation, writes the author of the accompanying editorial, Joan Guitart, MD, chief of dermatopathology at Northwestern University. Nevertheless, he added, such patients deserve “a comprehensive workup including skin biopsy with T-cell receptor clonality assay, blood cell counts with flow cytometry analysis, serum lactate dehydrogenase, and documentation of possible adenopathy, followed with imaging studies and/or local biopsies in cases with abnormal results.”

The possibility that these LRs may represent a first step toward lymphoma requires dermatologists to remain vigilant in ruling out MF, Dr. Guitart wrote, particularly in atypical presentations such as adult-onset AD, cases lacking a history of AD, and cases involving erythrodermic and other uncharacteristic presentations such as plaques, nodules, or spared flexural sites.

For dermatopathologists, Dr. Guitart recommended a cautious approach that resists overdiagnosing MF and acknowledging that insufficient evidence exists to report such reactions as benign. The fact that one study patient had both MF and LR raises concerns that the LR may not always be reversible, Dr. Guitart added.

Clinicians and patients must consider the possibility of dupilumab-induced LR as part of the shared decision-making process and risk-benefit calculus, Dr. Sidbury said. In cases involving unexpected responses or atypical presentations, he added, clinicians must have a low threshold for stopping dupilumab.

For patients who must discontinue dupilumab because of LR, the list of treatment options is growing. “While more investigation is required to understand the role of newer IL-13–blocking biologics and JAK inhibitors among patients experiencing lymphoid reactions,” said Dr. Chovatiya, “traditional atopic dermatitis therapies like narrowband UVB phototherapy and the oral immunosuppressant methotrexate may be reassuring in this population.” Conversely, cyclosporine has been associated with progression of MF.

Also reassuring, said Dr. Sidbury and Dr. Chovatiya, is the rarity of LR overall. Dr. Sidbury said, “The numbers of patients in whom LR or onset/exacerbation of MF occurs is extraordinarily low when compared to those helped immeasurably by dupilumab.”

Dr. Sidbury added that the study and accompanying editorial also will alert clinicians to the potential for newer AD biologics that target solely IL-13 and not IL-4/13, as dupilumab does. “If the deregulated response leading to LR and potentially MF in the affected few is driven by IL-4 inhibition,” he said, “drugs such as tralokinumab (Adbry), lebrikizumab (once approved), and perhaps other newer options might calm AD without causing LRs.”

(Lebrikizumab is not yet approved. In an Oct. 2 press release, Eli Lilly and Company, developer of lebrikizumab, said that it would address issues the U.S. Food and Drug Administration had raised about a third-party manufacturing facility that arose during evaluation of the lebrikizumab biologic license application.)

Study limitations include the fact that most patients who experienced LR had already undergone skin biopsies before dupilumab treatment, which suggests that they had a more atypical AD presentation from the start. The authors add that their having treated all study patients in a tertiary referral hospital indicates a hard-to-treat AD subpopulation.

Study authors reported relationships with several biologic drug manufacturers including Sanofi and Regeneron (dupilumab), LEO Pharma (tralokinumab), and Eli Lilly (lebrikizumab). However, none of these companies provided support for the study.

Dr. Sidbury has been an investigator for Regeneron, Pfizer, and Galderma and a consultant for LEO Pharma and Eli Lilly. Dr. Chovatiya has served as an advisor, consultant, speaker, and investigator for Sanofi and Regeneron. Dr. Guitart reported no conflicts of interest.

A version of this article appeared on Medscape.com.

For some patients with atopic dermatitis (AD), dupilumab treatment can cause a benign reversible lymphoid reaction (LR) that mimics mycosis fungoides (MF) but differs histologically, according to a study published in JAMA Dermatology

The potential for such reactions requires diagnosing AD carefully, monitoring patients on dupilumab for new and unusual symptoms, and thoroughly working up suspicious LRs, according to an accompanying editorial and experts interviewed for this article.

“Dupilumab has become such an important first-line systemic medication for our patients with moderate to severe atopic dermatitis. It’s important for us to understand everything we can about its use in the real world – both good and bad,”Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Northwestern University, Chicago, said in an interview. He was uninvolved with either publication.

Robert Sidbury, MD, MPH, added that, although the affected patient group was small, studying lymphoid reactions associated with dupilumab is important because of the risk for diagnostic misadventure that these reactions carry. He is a professor of pediatrics and division head of dermatology at Seattle Children’s Hospital and the University of Washington, Seattle.

“AD and MF are easily confused for one another at baseline,” explained Dr. Sidbury, who was not involved with the study or editorial. “Dupilumab is known to make AD better and theoretically could help MF via its effect on interleukin (IL)–13, yet case reports of exacerbation and/or unmasking of MF are out there.”

For the study, researchers retrospectively examined records of 530 patients with AD treated with dupilumab at the University Medical Center Utrecht (the Netherlands). Reviewing pretreatment biopsies revealed that among 14 (2.6%) patients who developed clinical suspicion of cutaneous T-cell lymphoma (CTCL) while on treatment, three actually had preexisting MF.

All 14 patients with LR initially responded to dupilumab then developed worsening symptoms at a median of 4 months. Patients reported that the worsening lesions looked and felt different than did previous lesions, with symptoms including burning/pain and an appearance of generalized erythematous maculopapular plaques, sometimes with severe lichenification, on the lower trunk and upper thighs.

The 14 patients’ posttreatment biopsies showed an atypical lymphoid infiltrate with lichenoid or perivascular distribution and intraepithelial T-cell lymphocytes. Whereas patients with MF had hyperconvoluted cerebriform lymphocytes aligned in the epidermal basal layer at the dermoepidermal junction, the 11 with LR had similar-looking lesions dispersed throughout the upper epidermis.

Immunohistochemically, both groups had a dysregulated (mostly increased) CD4:CD8 ratio. CD30 overexpression, usually absent in early-stage MF, affected only patients with LR and one patient with advanced MF. In addition, patients with LR maintained pan–T-cell antigens (CD2, CD3, and CD5), whereas those with MF did not. The 11 patients with LR experienced biopsy-confirmed resolution once they discontinued dupilumab.

It is reassuring that the LRs resolved after dupilumab discontinuation, writes the author of the accompanying editorial, Joan Guitart, MD, chief of dermatopathology at Northwestern University. Nevertheless, he added, such patients deserve “a comprehensive workup including skin biopsy with T-cell receptor clonality assay, blood cell counts with flow cytometry analysis, serum lactate dehydrogenase, and documentation of possible adenopathy, followed with imaging studies and/or local biopsies in cases with abnormal results.”

The possibility that these LRs may represent a first step toward lymphoma requires dermatologists to remain vigilant in ruling out MF, Dr. Guitart wrote, particularly in atypical presentations such as adult-onset AD, cases lacking a history of AD, and cases involving erythrodermic and other uncharacteristic presentations such as plaques, nodules, or spared flexural sites.

For dermatopathologists, Dr. Guitart recommended a cautious approach that resists overdiagnosing MF and acknowledging that insufficient evidence exists to report such reactions as benign. The fact that one study patient had both MF and LR raises concerns that the LR may not always be reversible, Dr. Guitart added.

Clinicians and patients must consider the possibility of dupilumab-induced LR as part of the shared decision-making process and risk-benefit calculus, Dr. Sidbury said. In cases involving unexpected responses or atypical presentations, he added, clinicians must have a low threshold for stopping dupilumab.

For patients who must discontinue dupilumab because of LR, the list of treatment options is growing. “While more investigation is required to understand the role of newer IL-13–blocking biologics and JAK inhibitors among patients experiencing lymphoid reactions,” said Dr. Chovatiya, “traditional atopic dermatitis therapies like narrowband UVB phototherapy and the oral immunosuppressant methotrexate may be reassuring in this population.” Conversely, cyclosporine has been associated with progression of MF.

Also reassuring, said Dr. Sidbury and Dr. Chovatiya, is the rarity of LR overall. Dr. Sidbury said, “The numbers of patients in whom LR or onset/exacerbation of MF occurs is extraordinarily low when compared to those helped immeasurably by dupilumab.”

Dr. Sidbury added that the study and accompanying editorial also will alert clinicians to the potential for newer AD biologics that target solely IL-13 and not IL-4/13, as dupilumab does. “If the deregulated response leading to LR and potentially MF in the affected few is driven by IL-4 inhibition,” he said, “drugs such as tralokinumab (Adbry), lebrikizumab (once approved), and perhaps other newer options might calm AD without causing LRs.”

(Lebrikizumab is not yet approved. In an Oct. 2 press release, Eli Lilly and Company, developer of lebrikizumab, said that it would address issues the U.S. Food and Drug Administration had raised about a third-party manufacturing facility that arose during evaluation of the lebrikizumab biologic license application.)

Study limitations include the fact that most patients who experienced LR had already undergone skin biopsies before dupilumab treatment, which suggests that they had a more atypical AD presentation from the start. The authors add that their having treated all study patients in a tertiary referral hospital indicates a hard-to-treat AD subpopulation.

Study authors reported relationships with several biologic drug manufacturers including Sanofi and Regeneron (dupilumab), LEO Pharma (tralokinumab), and Eli Lilly (lebrikizumab). However, none of these companies provided support for the study.

Dr. Sidbury has been an investigator for Regeneron, Pfizer, and Galderma and a consultant for LEO Pharma and Eli Lilly. Dr. Chovatiya has served as an advisor, consultant, speaker, and investigator for Sanofi and Regeneron. Dr. Guitart reported no conflicts of interest.

A version of this article appeared on Medscape.com.

For some patients with atopic dermatitis (AD), dupilumab treatment can cause a benign reversible lymphoid reaction (LR) that mimics mycosis fungoides (MF) but differs histologically, according to a study published in JAMA Dermatology

The potential for such reactions requires diagnosing AD carefully, monitoring patients on dupilumab for new and unusual symptoms, and thoroughly working up suspicious LRs, according to an accompanying editorial and experts interviewed for this article.

“Dupilumab has become such an important first-line systemic medication for our patients with moderate to severe atopic dermatitis. It’s important for us to understand everything we can about its use in the real world – both good and bad,”Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Northwestern University, Chicago, said in an interview. He was uninvolved with either publication.

Robert Sidbury, MD, MPH, added that, although the affected patient group was small, studying lymphoid reactions associated with dupilumab is important because of the risk for diagnostic misadventure that these reactions carry. He is a professor of pediatrics and division head of dermatology at Seattle Children’s Hospital and the University of Washington, Seattle.

“AD and MF are easily confused for one another at baseline,” explained Dr. Sidbury, who was not involved with the study or editorial. “Dupilumab is known to make AD better and theoretically could help MF via its effect on interleukin (IL)–13, yet case reports of exacerbation and/or unmasking of MF are out there.”

For the study, researchers retrospectively examined records of 530 patients with AD treated with dupilumab at the University Medical Center Utrecht (the Netherlands). Reviewing pretreatment biopsies revealed that among 14 (2.6%) patients who developed clinical suspicion of cutaneous T-cell lymphoma (CTCL) while on treatment, three actually had preexisting MF.

All 14 patients with LR initially responded to dupilumab then developed worsening symptoms at a median of 4 months. Patients reported that the worsening lesions looked and felt different than did previous lesions, with symptoms including burning/pain and an appearance of generalized erythematous maculopapular plaques, sometimes with severe lichenification, on the lower trunk and upper thighs.

The 14 patients’ posttreatment biopsies showed an atypical lymphoid infiltrate with lichenoid or perivascular distribution and intraepithelial T-cell lymphocytes. Whereas patients with MF had hyperconvoluted cerebriform lymphocytes aligned in the epidermal basal layer at the dermoepidermal junction, the 11 with LR had similar-looking lesions dispersed throughout the upper epidermis.

Immunohistochemically, both groups had a dysregulated (mostly increased) CD4:CD8 ratio. CD30 overexpression, usually absent in early-stage MF, affected only patients with LR and one patient with advanced MF. In addition, patients with LR maintained pan–T-cell antigens (CD2, CD3, and CD5), whereas those with MF did not. The 11 patients with LR experienced biopsy-confirmed resolution once they discontinued dupilumab.

It is reassuring that the LRs resolved after dupilumab discontinuation, writes the author of the accompanying editorial, Joan Guitart, MD, chief of dermatopathology at Northwestern University. Nevertheless, he added, such patients deserve “a comprehensive workup including skin biopsy with T-cell receptor clonality assay, blood cell counts with flow cytometry analysis, serum lactate dehydrogenase, and documentation of possible adenopathy, followed with imaging studies and/or local biopsies in cases with abnormal results.”

The possibility that these LRs may represent a first step toward lymphoma requires dermatologists to remain vigilant in ruling out MF, Dr. Guitart wrote, particularly in atypical presentations such as adult-onset AD, cases lacking a history of AD, and cases involving erythrodermic and other uncharacteristic presentations such as plaques, nodules, or spared flexural sites.

For dermatopathologists, Dr. Guitart recommended a cautious approach that resists overdiagnosing MF and acknowledging that insufficient evidence exists to report such reactions as benign. The fact that one study patient had both MF and LR raises concerns that the LR may not always be reversible, Dr. Guitart added.

Clinicians and patients must consider the possibility of dupilumab-induced LR as part of the shared decision-making process and risk-benefit calculus, Dr. Sidbury said. In cases involving unexpected responses or atypical presentations, he added, clinicians must have a low threshold for stopping dupilumab.

For patients who must discontinue dupilumab because of LR, the list of treatment options is growing. “While more investigation is required to understand the role of newer IL-13–blocking biologics and JAK inhibitors among patients experiencing lymphoid reactions,” said Dr. Chovatiya, “traditional atopic dermatitis therapies like narrowband UVB phototherapy and the oral immunosuppressant methotrexate may be reassuring in this population.” Conversely, cyclosporine has been associated with progression of MF.

Also reassuring, said Dr. Sidbury and Dr. Chovatiya, is the rarity of LR overall. Dr. Sidbury said, “The numbers of patients in whom LR or onset/exacerbation of MF occurs is extraordinarily low when compared to those helped immeasurably by dupilumab.”

Dr. Sidbury added that the study and accompanying editorial also will alert clinicians to the potential for newer AD biologics that target solely IL-13 and not IL-4/13, as dupilumab does. “If the deregulated response leading to LR and potentially MF in the affected few is driven by IL-4 inhibition,” he said, “drugs such as tralokinumab (Adbry), lebrikizumab (once approved), and perhaps other newer options might calm AD without causing LRs.”

(Lebrikizumab is not yet approved. In an Oct. 2 press release, Eli Lilly and Company, developer of lebrikizumab, said that it would address issues the U.S. Food and Drug Administration had raised about a third-party manufacturing facility that arose during evaluation of the lebrikizumab biologic license application.)

Study limitations include the fact that most patients who experienced LR had already undergone skin biopsies before dupilumab treatment, which suggests that they had a more atypical AD presentation from the start. The authors add that their having treated all study patients in a tertiary referral hospital indicates a hard-to-treat AD subpopulation.

Study authors reported relationships with several biologic drug manufacturers including Sanofi and Regeneron (dupilumab), LEO Pharma (tralokinumab), and Eli Lilly (lebrikizumab). However, none of these companies provided support for the study.

Dr. Sidbury has been an investigator for Regeneron, Pfizer, and Galderma and a consultant for LEO Pharma and Eli Lilly. Dr. Chovatiya has served as an advisor, consultant, speaker, and investigator for Sanofi and Regeneron. Dr. Guitart reported no conflicts of interest.

A version of this article appeared on Medscape.com.

Human insulin can be left unrefrigerated for much longer than previously thought, findings from a new Cochrane review suggest.

The review included 17 studies in 22 published articles and additional unpublished information from major insulin manufacturers. The data suggest it is possible to store unopened short- and intermediate-acting human insulin vials, pens/cartridges or prefilled plastic syringes at temperatures up to 25 °C (77 °F) for a maximum of 6 months and up to 37 °C (98.6 °F) for a maximum of 2 months without a clinically relevant loss of insulin potency.

Two studies found small decrements in potency at higher temperatures and/or longer durations unrefrigerated, but the rest did not.

This contrasts with current guidance and labeling that advises storing unopened human insulin at temperatures between 2 °C (35.6 °F) and 8°C (46.4 °F), necessitating refrigeration. Once the vial or pen cartridge is opened, the guidance is to store at “room temperature” and use within about 4-6 weeks.

The recommendations vary, however, and there is no clear consensus on how human insulin should be stored in settings where reliable refrigeration can’t be guaranteed, such as low-income countries, those affected by extreme heat, or areas of conflict or natural disasters. Such areas are home to growing numbers of people with diabetes, according to the Cochrane Database of Systematic Reviews report, published online.

The review also found that oscillating temperatures between 25 °C (77 °F) and 37 °C (98.6 °F), typical of daytime and nighttime fluctuations in tropical countries, for up to 3 months do not result in clinically relevant loss of insulin activity for short-acting, intermediate-acting, or mixed human insulin.   

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being,” the study’s lead author, Bernd Richter, MD, of the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany, said in a statement.

In addition, one small pilot clinical study showed that human insulin stored for 6 weeks in an unglazed clay pot with temperatures ranging between 25 °C (77 °F) and 27°C (80.6 °F) did not result in differences in plasma glucose–lowering in eight healthy volunteers, compared with refrigerator-stored insulin. “With the help of simple cooling devices for insulin storage such as clay pots, it is possible to effectively reduce high outside temperatures in many high-temperature regions of the world,” wrote Dr. Richter and colleagues Brenda Bongaerts, PhD, and Maria-Inti Metzendorf, also from Heinrich-Heine-University.

Asked to comment, Leonardo Scapozza, PhD, of the School of Pharmaceutical Sciences at the University of Geneva, Switzerland, said that these findings align with a study he published in 2021.   

“Indeed ... we have done a small-scale study by analyzing the insulin coming back from the field and showing that insulin potency and stability was conserved. An extended clinical study where the insulin is submitted to varying controlled condition is not possible and ethically debatable. But an extended study where patients are given a log tag to monitor their real storage condition and the remaining samples are collected back and sent back for analysis in a specialized lab would be very good to further confirm the [conclusions],” said Dr. Scapozza, who was not part of Dr. Richter’s team on this review. 

While the issue of insulin refrigeration is less urgent in higher-income countries, it does arise, as in situations where people accidentally leave their unopened insulin out of the refrigerator or when they carry backup insulin while traveling.

The Cochrane Review excluded studies of insulin analogs, used in most developed countries, but Dr. Scapozza’s study had included them. “We observed the same stability as the ones used in low-income countries.” He added that his data combined with those in the new report provide evidence that would make it “possible to better and optimally use the available insulin that is becoming more and more costly.”

Dr. Scapozza also told this news organization that after he presented his data to Médecins Sans Frontières (Doctors Without Borders), he heard from a collaborator with that group who has diabetes. “He always used his insulin for his own treatment when he was in the field working and his insulin pen was in his backpack or pocket and his treatment was working. After hearing the data, he was very happy because he got a scientific explanation why his treatment was working, whether he was in Switzerland or during his mission in the camps submitted to the same condition of storage as any other patient in low income countries.”

Dr. Richter and Dr. Scapozza report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Human insulin can be left unrefrigerated for much longer than previously thought, findings from a new Cochrane review suggest.

The review included 17 studies in 22 published articles and additional unpublished information from major insulin manufacturers. The data suggest it is possible to store unopened short- and intermediate-acting human insulin vials, pens/cartridges or prefilled plastic syringes at temperatures up to 25 °C (77 °F) for a maximum of 6 months and up to 37 °C (98.6 °F) for a maximum of 2 months without a clinically relevant loss of insulin potency.

Two studies found small decrements in potency at higher temperatures and/or longer durations unrefrigerated, but the rest did not.

This contrasts with current guidance and labeling that advises storing unopened human insulin at temperatures between 2 °C (35.6 °F) and 8°C (46.4 °F), necessitating refrigeration. Once the vial or pen cartridge is opened, the guidance is to store at “room temperature” and use within about 4-6 weeks.

The recommendations vary, however, and there is no clear consensus on how human insulin should be stored in settings where reliable refrigeration can’t be guaranteed, such as low-income countries, those affected by extreme heat, or areas of conflict or natural disasters. Such areas are home to growing numbers of people with diabetes, according to the Cochrane Database of Systematic Reviews report, published online.

The review also found that oscillating temperatures between 25 °C (77 °F) and 37 °C (98.6 °F), typical of daytime and nighttime fluctuations in tropical countries, for up to 3 months do not result in clinically relevant loss of insulin activity for short-acting, intermediate-acting, or mixed human insulin.   

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being,” the study’s lead author, Bernd Richter, MD, of the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany, said in a statement.

In addition, one small pilot clinical study showed that human insulin stored for 6 weeks in an unglazed clay pot with temperatures ranging between 25 °C (77 °F) and 27°C (80.6 °F) did not result in differences in plasma glucose–lowering in eight healthy volunteers, compared with refrigerator-stored insulin. “With the help of simple cooling devices for insulin storage such as clay pots, it is possible to effectively reduce high outside temperatures in many high-temperature regions of the world,” wrote Dr. Richter and colleagues Brenda Bongaerts, PhD, and Maria-Inti Metzendorf, also from Heinrich-Heine-University.

Asked to comment, Leonardo Scapozza, PhD, of the School of Pharmaceutical Sciences at the University of Geneva, Switzerland, said that these findings align with a study he published in 2021.   

“Indeed ... we have done a small-scale study by analyzing the insulin coming back from the field and showing that insulin potency and stability was conserved. An extended clinical study where the insulin is submitted to varying controlled condition is not possible and ethically debatable. But an extended study where patients are given a log tag to monitor their real storage condition and the remaining samples are collected back and sent back for analysis in a specialized lab would be very good to further confirm the [conclusions],” said Dr. Scapozza, who was not part of Dr. Richter’s team on this review. 

While the issue of insulin refrigeration is less urgent in higher-income countries, it does arise, as in situations where people accidentally leave their unopened insulin out of the refrigerator or when they carry backup insulin while traveling.

The Cochrane Review excluded studies of insulin analogs, used in most developed countries, but Dr. Scapozza’s study had included them. “We observed the same stability as the ones used in low-income countries.” He added that his data combined with those in the new report provide evidence that would make it “possible to better and optimally use the available insulin that is becoming more and more costly.”

Dr. Scapozza also told this news organization that after he presented his data to Médecins Sans Frontières (Doctors Without Borders), he heard from a collaborator with that group who has diabetes. “He always used his insulin for his own treatment when he was in the field working and his insulin pen was in his backpack or pocket and his treatment was working. After hearing the data, he was very happy because he got a scientific explanation why his treatment was working, whether he was in Switzerland or during his mission in the camps submitted to the same condition of storage as any other patient in low income countries.”

Dr. Richter and Dr. Scapozza report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Human insulin can be left unrefrigerated for much longer than previously thought, findings from a new Cochrane review suggest.

The review included 17 studies in 22 published articles and additional unpublished information from major insulin manufacturers. The data suggest it is possible to store unopened short- and intermediate-acting human insulin vials, pens/cartridges or prefilled plastic syringes at temperatures up to 25 °C (77 °F) for a maximum of 6 months and up to 37 °C (98.6 °F) for a maximum of 2 months without a clinically relevant loss of insulin potency.

Two studies found small decrements in potency at higher temperatures and/or longer durations unrefrigerated, but the rest did not.

This contrasts with current guidance and labeling that advises storing unopened human insulin at temperatures between 2 °C (35.6 °F) and 8°C (46.4 °F), necessitating refrigeration. Once the vial or pen cartridge is opened, the guidance is to store at “room temperature” and use within about 4-6 weeks.

The recommendations vary, however, and there is no clear consensus on how human insulin should be stored in settings where reliable refrigeration can’t be guaranteed, such as low-income countries, those affected by extreme heat, or areas of conflict or natural disasters. Such areas are home to growing numbers of people with diabetes, according to the Cochrane Database of Systematic Reviews report, published online.

The review also found that oscillating temperatures between 25 °C (77 °F) and 37 °C (98.6 °F), typical of daytime and nighttime fluctuations in tropical countries, for up to 3 months do not result in clinically relevant loss of insulin activity for short-acting, intermediate-acting, or mixed human insulin.   

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being,” the study’s lead author, Bernd Richter, MD, of the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany, said in a statement.

In addition, one small pilot clinical study showed that human insulin stored for 6 weeks in an unglazed clay pot with temperatures ranging between 25 °C (77 °F) and 27°C (80.6 °F) did not result in differences in plasma glucose–lowering in eight healthy volunteers, compared with refrigerator-stored insulin. “With the help of simple cooling devices for insulin storage such as clay pots, it is possible to effectively reduce high outside temperatures in many high-temperature regions of the world,” wrote Dr. Richter and colleagues Brenda Bongaerts, PhD, and Maria-Inti Metzendorf, also from Heinrich-Heine-University.

Asked to comment, Leonardo Scapozza, PhD, of the School of Pharmaceutical Sciences at the University of Geneva, Switzerland, said that these findings align with a study he published in 2021.   

“Indeed ... we have done a small-scale study by analyzing the insulin coming back from the field and showing that insulin potency and stability was conserved. An extended clinical study where the insulin is submitted to varying controlled condition is not possible and ethically debatable. But an extended study where patients are given a log tag to monitor their real storage condition and the remaining samples are collected back and sent back for analysis in a specialized lab would be very good to further confirm the [conclusions],” said Dr. Scapozza, who was not part of Dr. Richter’s team on this review. 

While the issue of insulin refrigeration is less urgent in higher-income countries, it does arise, as in situations where people accidentally leave their unopened insulin out of the refrigerator or when they carry backup insulin while traveling.

The Cochrane Review excluded studies of insulin analogs, used in most developed countries, but Dr. Scapozza’s study had included them. “We observed the same stability as the ones used in low-income countries.” He added that his data combined with those in the new report provide evidence that would make it “possible to better and optimally use the available insulin that is becoming more and more costly.”

Dr. Scapozza also told this news organization that after he presented his data to Médecins Sans Frontières (Doctors Without Borders), he heard from a collaborator with that group who has diabetes. “He always used his insulin for his own treatment when he was in the field working and his insulin pen was in his backpack or pocket and his treatment was working. After hearing the data, he was very happy because he got a scientific explanation why his treatment was working, whether he was in Switzerland or during his mission in the camps submitted to the same condition of storage as any other patient in low income countries.”

Dr. Richter and Dr. Scapozza report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

During a fellowship rotation in gynecology, Rebekah D. Fenton, MD, asked the attending physicians what pain management options they could offer patients for insertion of an intrauterine device (IUD). Their answer surprised her: None. 

The research on the effectiveness of pain management techniques during the procedure were not strong enough to warrant providing potential relief. 

But Dr. Fenton knew the attending physician was wrong: She’d received the drug lidocaine during a recent visit to her own ob.gyn. to get an IUD placed. The local anesthetic enabled her to avoid the experiences of many patients who often withstand debilitating cramping and pain during insertion, side effects that can last for hours after the procedure has ended.

By not teaching her how to administer pain treatment options such as lidocaine gel or injection, “they made the decision for me, whether I could give patients this option,” said Dr. Fenton, now an adolescent medicine specialist at Alivio Medical Center in Chicago.

Without clear guidelines, pain management decisions for routine gynecologic procedures are largely left up to individual clinicians. As a result, patients undergoing IUD placements, biopsies, hysteroscopies, and pelvic exams are often subject to pain that could be mitigated. 

Some research suggests simple numbing agents, including lidocaine, may induce less pain without the need for full anesthesia. But clinicians don’t always present these options.

During gynecologic procedures, the amount of pain a patient can expect is often downplayed by clinicians. Because every patient experiences the sensation differently, discussing options for pain management and the range of possible pain is paramount in building patient-clinician trust, and ultimately providing the best care for patients in the long run, according to Megan Wasson, DO, chair of the department of medical and surgical gynecology at Mayo Clinic Arizona in Phoenix. 

“It comes down to shared decision-making so the patient is aware of the pain that should be expected and what avenue they want to go down,” Dr. Wasson said. “It’s not a one-size-fits-all.”
 

Lack of uniform protocols

The American College of Obstetricians and Gynecologists (ACOG) has clear guidelines for pain management during pregnancy and delivery but not for many routine gynecologic procedures. Some experts say not offering options for pain management based on lack of efficacy evidence can undermine a patient’s experience. 

ACOG does have recommendations for reducing dilation pain during a hysteroscopy, including providing intravaginal misoprostol and estrogen. The organization also recommends performing a vaginoscopy instead if possible because the procedure is typically less painful than is a hysteroscopy. 

For an IUD placement, ACOG states that the procedure “may cause temporary discomfort” and recommends that patients take over-the-counter pain relief before a procedure. The most recent clinical bulletin on the topic, published in 2016, states routine misoprostol is not recommended for IUD placement, although it may be considered with difficult insertions for management of pain. 

A clinical inquiry published in 2020 outlined the efficacy of several pain options that practitioners can weigh with patients. The inquiry cited a 2019 meta-analysis of 38 studies that found lidocaine-prilocaine cream to be the most effective option for pain management during IUD placement, reducing insertion pain by nearly 30%. The inquiry concluded that a combination of 600 mcg of misoprostol and 4% lidocaine gel may be effective, while lower dosages of both drugs were not effective. A 2018 clinical trial cited in the analysis found that though a 20-cc 1% lidocaine paracervical block on its own did not reduce pain, the block mixed with sodium bicarbonate reduced pain during IUD insertion by 22%. 

Some doctors make the decision to not use lidocaine without offering it to patients first, according to Dr. Fenton. Instead, clinicians should discuss any potential drawbacks, such as pain from administering the numbing agent with a needle or the procedure taking extra time while the patient waits for the lidocaine to kick in. 

“That always felt unfair, to make that decision for [the patient],” Dr. Fenton said. 

Often clinicians won’t know how a patient will respond to a procedure: A 2014 secondary analysis of a clinical trial compared how patients rated their pain after an IUD procedure to the amount of pain physicians perceived the procedure to cause. They found that the average pain scores patients reported were nearly twice as high as clinician expectations were.

ACOG’s guideline states that the evidence backing paracervical blocks and lidocaine to IUD insertion pain is controversial. The American College of Physicians also cites “low-quality evidence” to support patient reports of pain and discomfort during pelvic exams. Some studies have found up to 60% of women report these negative experiences. 

The varying evidence highlights the need for a personalized approach – one that includes patients – to pain management for routine gynecological procedures.

“Usually patients are pretty good predictors,” said Lisa Bayer, MD, MPH, associate professor of obstetrics and gynecology at Oregon Health & Science University in Portland. “They can anticipate what different things are going to feel like based on previous experiences.”
 

Making patients part of the discussion

Clinicians should have open discussions with patients about their past experiences and current anxieties about a gynecologic procedure, according to Dr. Bayer.

“Part of it is just creating a really safe environment of trust as a medical provider,” she said. 

A study published in 2016 of more than 800 patients undergoing oocyte retrieval, which has clear protocols for pain management, found that previous negative gynecologic experiences were significantly correlated to greater amounts of pain reported during the procedure. 

If pain isn’t properly managed, patients may avoid care in the future, putting them at risk for unplanned pregnancies, skipped cancer screenings, and complications from undiagnosed conditions and infections, Dr. Bayer added. Clinician offices will not always have access to all pain management options, so making referrals to another physician who has access to the appropriate technique may be the best thing for the patient, Dr. Bayer said. 


 

Downplaying the experience

Informing a patient that she will feel only a little discomfort during a procedure – when a clinician doesn’t know how exactly the patient will react – can also result in distrust. 

When a clinician says, “ ’It’s only going to be a little cramp, it’s only going to be a little pinch,’ we know extreme pain is a possibility, we’ve seen it,” Dr. Fenton said. “But if we choose to disregard that [possibility], it feels invalidating for patients.”

Failing to fully explain the possible pain scale can also directly interfere with the procedure at hand. 

“My first concern is if they aren’t anticipating the amount of pain they are going to experience, they may move; For biopsies and IUD insertions, we need them to be still,” Dr. Wasson said. “If they are unable to tolerate the procedure, we’ve put them through pain and not been able to accomplish the primary goal.”

Managing both pain and what patients can expect is even more crucial for adolescent and teenage patients who are often having their first gynecologic experience. 

“We’re framing what these experiences look like,” Dr. Fenton said. “That means there are opportunities for creating a space that builds trust and security for the patients moving forward.”
 

A version of this article first appeared on Medscape.com.

During a fellowship rotation in gynecology, Rebekah D. Fenton, MD, asked the attending physicians what pain management options they could offer patients for insertion of an intrauterine device (IUD). Their answer surprised her: None. 

The research on the effectiveness of pain management techniques during the procedure were not strong enough to warrant providing potential relief. 

But Dr. Fenton knew the attending physician was wrong: She’d received the drug lidocaine during a recent visit to her own ob.gyn. to get an IUD placed. The local anesthetic enabled her to avoid the experiences of many patients who often withstand debilitating cramping and pain during insertion, side effects that can last for hours after the procedure has ended.

By not teaching her how to administer pain treatment options such as lidocaine gel or injection, “they made the decision for me, whether I could give patients this option,” said Dr. Fenton, now an adolescent medicine specialist at Alivio Medical Center in Chicago.

Without clear guidelines, pain management decisions for routine gynecologic procedures are largely left up to individual clinicians. As a result, patients undergoing IUD placements, biopsies, hysteroscopies, and pelvic exams are often subject to pain that could be mitigated. 

Some research suggests simple numbing agents, including lidocaine, may induce less pain without the need for full anesthesia. But clinicians don’t always present these options.

During gynecologic procedures, the amount of pain a patient can expect is often downplayed by clinicians. Because every patient experiences the sensation differently, discussing options for pain management and the range of possible pain is paramount in building patient-clinician trust, and ultimately providing the best care for patients in the long run, according to Megan Wasson, DO, chair of the department of medical and surgical gynecology at Mayo Clinic Arizona in Phoenix. 

“It comes down to shared decision-making so the patient is aware of the pain that should be expected and what avenue they want to go down,” Dr. Wasson said. “It’s not a one-size-fits-all.”
 

Lack of uniform protocols

The American College of Obstetricians and Gynecologists (ACOG) has clear guidelines for pain management during pregnancy and delivery but not for many routine gynecologic procedures. Some experts say not offering options for pain management based on lack of efficacy evidence can undermine a patient’s experience. 

ACOG does have recommendations for reducing dilation pain during a hysteroscopy, including providing intravaginal misoprostol and estrogen. The organization also recommends performing a vaginoscopy instead if possible because the procedure is typically less painful than is a hysteroscopy. 

For an IUD placement, ACOG states that the procedure “may cause temporary discomfort” and recommends that patients take over-the-counter pain relief before a procedure. The most recent clinical bulletin on the topic, published in 2016, states routine misoprostol is not recommended for IUD placement, although it may be considered with difficult insertions for management of pain. 

A clinical inquiry published in 2020 outlined the efficacy of several pain options that practitioners can weigh with patients. The inquiry cited a 2019 meta-analysis of 38 studies that found lidocaine-prilocaine cream to be the most effective option for pain management during IUD placement, reducing insertion pain by nearly 30%. The inquiry concluded that a combination of 600 mcg of misoprostol and 4% lidocaine gel may be effective, while lower dosages of both drugs were not effective. A 2018 clinical trial cited in the analysis found that though a 20-cc 1% lidocaine paracervical block on its own did not reduce pain, the block mixed with sodium bicarbonate reduced pain during IUD insertion by 22%. 

Some doctors make the decision to not use lidocaine without offering it to patients first, according to Dr. Fenton. Instead, clinicians should discuss any potential drawbacks, such as pain from administering the numbing agent with a needle or the procedure taking extra time while the patient waits for the lidocaine to kick in. 

“That always felt unfair, to make that decision for [the patient],” Dr. Fenton said. 

Often clinicians won’t know how a patient will respond to a procedure: A 2014 secondary analysis of a clinical trial compared how patients rated their pain after an IUD procedure to the amount of pain physicians perceived the procedure to cause. They found that the average pain scores patients reported were nearly twice as high as clinician expectations were.

ACOG’s guideline states that the evidence backing paracervical blocks and lidocaine to IUD insertion pain is controversial. The American College of Physicians also cites “low-quality evidence” to support patient reports of pain and discomfort during pelvic exams. Some studies have found up to 60% of women report these negative experiences. 

The varying evidence highlights the need for a personalized approach – one that includes patients – to pain management for routine gynecological procedures.

“Usually patients are pretty good predictors,” said Lisa Bayer, MD, MPH, associate professor of obstetrics and gynecology at Oregon Health & Science University in Portland. “They can anticipate what different things are going to feel like based on previous experiences.”
 

Making patients part of the discussion

Clinicians should have open discussions with patients about their past experiences and current anxieties about a gynecologic procedure, according to Dr. Bayer.

“Part of it is just creating a really safe environment of trust as a medical provider,” she said. 

A study published in 2016 of more than 800 patients undergoing oocyte retrieval, which has clear protocols for pain management, found that previous negative gynecologic experiences were significantly correlated to greater amounts of pain reported during the procedure. 

If pain isn’t properly managed, patients may avoid care in the future, putting them at risk for unplanned pregnancies, skipped cancer screenings, and complications from undiagnosed conditions and infections, Dr. Bayer added. Clinician offices will not always have access to all pain management options, so making referrals to another physician who has access to the appropriate technique may be the best thing for the patient, Dr. Bayer said. 


 

Downplaying the experience

Informing a patient that she will feel only a little discomfort during a procedure – when a clinician doesn’t know how exactly the patient will react – can also result in distrust. 

When a clinician says, “ ’It’s only going to be a little cramp, it’s only going to be a little pinch,’ we know extreme pain is a possibility, we’ve seen it,” Dr. Fenton said. “But if we choose to disregard that [possibility], it feels invalidating for patients.”

Failing to fully explain the possible pain scale can also directly interfere with the procedure at hand. 

“My first concern is if they aren’t anticipating the amount of pain they are going to experience, they may move; For biopsies and IUD insertions, we need them to be still,” Dr. Wasson said. “If they are unable to tolerate the procedure, we’ve put them through pain and not been able to accomplish the primary goal.”

Managing both pain and what patients can expect is even more crucial for adolescent and teenage patients who are often having their first gynecologic experience. 

“We’re framing what these experiences look like,” Dr. Fenton said. “That means there are opportunities for creating a space that builds trust and security for the patients moving forward.”
 

A version of this article first appeared on Medscape.com.

During a fellowship rotation in gynecology, Rebekah D. Fenton, MD, asked the attending physicians what pain management options they could offer patients for insertion of an intrauterine device (IUD). Their answer surprised her: None. 

The research on the effectiveness of pain management techniques during the procedure were not strong enough to warrant providing potential relief. 

But Dr. Fenton knew the attending physician was wrong: She’d received the drug lidocaine during a recent visit to her own ob.gyn. to get an IUD placed. The local anesthetic enabled her to avoid the experiences of many patients who often withstand debilitating cramping and pain during insertion, side effects that can last for hours after the procedure has ended.

By not teaching her how to administer pain treatment options such as lidocaine gel or injection, “they made the decision for me, whether I could give patients this option,” said Dr. Fenton, now an adolescent medicine specialist at Alivio Medical Center in Chicago.

Without clear guidelines, pain management decisions for routine gynecologic procedures are largely left up to individual clinicians. As a result, patients undergoing IUD placements, biopsies, hysteroscopies, and pelvic exams are often subject to pain that could be mitigated. 

Some research suggests simple numbing agents, including lidocaine, may induce less pain without the need for full anesthesia. But clinicians don’t always present these options.

During gynecologic procedures, the amount of pain a patient can expect is often downplayed by clinicians. Because every patient experiences the sensation differently, discussing options for pain management and the range of possible pain is paramount in building patient-clinician trust, and ultimately providing the best care for patients in the long run, according to Megan Wasson, DO, chair of the department of medical and surgical gynecology at Mayo Clinic Arizona in Phoenix. 

“It comes down to shared decision-making so the patient is aware of the pain that should be expected and what avenue they want to go down,” Dr. Wasson said. “It’s not a one-size-fits-all.”
 

Lack of uniform protocols

The American College of Obstetricians and Gynecologists (ACOG) has clear guidelines for pain management during pregnancy and delivery but not for many routine gynecologic procedures. Some experts say not offering options for pain management based on lack of efficacy evidence can undermine a patient’s experience. 

ACOG does have recommendations for reducing dilation pain during a hysteroscopy, including providing intravaginal misoprostol and estrogen. The organization also recommends performing a vaginoscopy instead if possible because the procedure is typically less painful than is a hysteroscopy. 

For an IUD placement, ACOG states that the procedure “may cause temporary discomfort” and recommends that patients take over-the-counter pain relief before a procedure. The most recent clinical bulletin on the topic, published in 2016, states routine misoprostol is not recommended for IUD placement, although it may be considered with difficult insertions for management of pain. 

A clinical inquiry published in 2020 outlined the efficacy of several pain options that practitioners can weigh with patients. The inquiry cited a 2019 meta-analysis of 38 studies that found lidocaine-prilocaine cream to be the most effective option for pain management during IUD placement, reducing insertion pain by nearly 30%. The inquiry concluded that a combination of 600 mcg of misoprostol and 4% lidocaine gel may be effective, while lower dosages of both drugs were not effective. A 2018 clinical trial cited in the analysis found that though a 20-cc 1% lidocaine paracervical block on its own did not reduce pain, the block mixed with sodium bicarbonate reduced pain during IUD insertion by 22%. 

Some doctors make the decision to not use lidocaine without offering it to patients first, according to Dr. Fenton. Instead, clinicians should discuss any potential drawbacks, such as pain from administering the numbing agent with a needle or the procedure taking extra time while the patient waits for the lidocaine to kick in. 

“That always felt unfair, to make that decision for [the patient],” Dr. Fenton said. 

Often clinicians won’t know how a patient will respond to a procedure: A 2014 secondary analysis of a clinical trial compared how patients rated their pain after an IUD procedure to the amount of pain physicians perceived the procedure to cause. They found that the average pain scores patients reported were nearly twice as high as clinician expectations were.

ACOG’s guideline states that the evidence backing paracervical blocks and lidocaine to IUD insertion pain is controversial. The American College of Physicians also cites “low-quality evidence” to support patient reports of pain and discomfort during pelvic exams. Some studies have found up to 60% of women report these negative experiences. 

The varying evidence highlights the need for a personalized approach – one that includes patients – to pain management for routine gynecological procedures.

“Usually patients are pretty good predictors,” said Lisa Bayer, MD, MPH, associate professor of obstetrics and gynecology at Oregon Health & Science University in Portland. “They can anticipate what different things are going to feel like based on previous experiences.”
 

Making patients part of the discussion

Clinicians should have open discussions with patients about their past experiences and current anxieties about a gynecologic procedure, according to Dr. Bayer.

“Part of it is just creating a really safe environment of trust as a medical provider,” she said. 

A study published in 2016 of more than 800 patients undergoing oocyte retrieval, which has clear protocols for pain management, found that previous negative gynecologic experiences were significantly correlated to greater amounts of pain reported during the procedure. 

If pain isn’t properly managed, patients may avoid care in the future, putting them at risk for unplanned pregnancies, skipped cancer screenings, and complications from undiagnosed conditions and infections, Dr. Bayer added. Clinician offices will not always have access to all pain management options, so making referrals to another physician who has access to the appropriate technique may be the best thing for the patient, Dr. Bayer said. 


 

Downplaying the experience

Informing a patient that she will feel only a little discomfort during a procedure – when a clinician doesn’t know how exactly the patient will react – can also result in distrust. 

When a clinician says, “ ’It’s only going to be a little cramp, it’s only going to be a little pinch,’ we know extreme pain is a possibility, we’ve seen it,” Dr. Fenton said. “But if we choose to disregard that [possibility], it feels invalidating for patients.”

Failing to fully explain the possible pain scale can also directly interfere with the procedure at hand. 

“My first concern is if they aren’t anticipating the amount of pain they are going to experience, they may move; For biopsies and IUD insertions, we need them to be still,” Dr. Wasson said. “If they are unable to tolerate the procedure, we’ve put them through pain and not been able to accomplish the primary goal.”

Managing both pain and what patients can expect is even more crucial for adolescent and teenage patients who are often having their first gynecologic experience. 

“We’re framing what these experiences look like,” Dr. Fenton said. “That means there are opportunities for creating a space that builds trust and security for the patients moving forward.”
 

A version of this article first appeared on Medscape.com.