Implementing an enhanced recovery after surgery (ERAS) program for cesarean delivery led to decreased opioid use, shorter length of stay, and decreased costs, according to recent research published in Obstetrics & Gynecology.

©Cameron Whitman/Thinkstock

Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
 

The ERAS program

ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.

For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.

Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.

Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
 

Improved outcomes after ERAS

The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).

There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.

The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
 

ERAS implementation lagging in obstetrics

In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”

Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”

Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.

“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”

Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.

“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”

Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.

SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.

Implementing an enhanced recovery after surgery (ERAS) program for cesarean delivery led to decreased opioid use, shorter length of stay, and decreased costs, according to recent research published in Obstetrics & Gynecology.

©Cameron Whitman/Thinkstock

Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
 

The ERAS program

ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.

For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.

Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.

Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
 

Improved outcomes after ERAS

The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).

There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.

The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
 

ERAS implementation lagging in obstetrics

In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”

Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”

Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.

“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”

Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.

“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”

Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.

SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.

Implementing an enhanced recovery after surgery (ERAS) program for cesarean delivery led to decreased opioid use, shorter length of stay, and decreased costs, according to recent research published in Obstetrics & Gynecology.

©Cameron Whitman/Thinkstock

Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
 

The ERAS program

ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.

For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.

Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.

Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
 

Improved outcomes after ERAS

The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).

There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.

The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
 

ERAS implementation lagging in obstetrics

In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”

Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”

Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.

“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”

Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.

“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”

Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.

SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.

Inhaled corticosteroids (ICS) do not protect patients with chronic respiratory conditions against COVID-19-related death, a study of almost 1 million individuals in the United Kingdom has shown.

Patients with chronic obstructive pulmonary disease or asthma who used ICS on a regular basis were more likely to die from COVID-19 than COPD or asthma patients who were prescribed non-ICS therapies, reported co-lead author Anna Schultze, PhD, of London School of Hygiene & Tropical Medicine and colleagues.

Of note, the increased risk of death among ICS users likely stemmed from greater severity of preexisting chronic respiratory conditions, instead of directly from ICS usage, which has little apparent impact on COVID-19 mortality, the investigators wrote in Lancet Respiratory Medicine.

These findings conflict with a hypothesis proposed early in the pandemic: that ICS may protect individuals from SARS-CoV-2 infection and poor outcomes with COVID-19.

According to Megan Conroy, MD, of the department of internal medicine at the Ohio State University Wexner Medical Center, Columbus, this hypothesis was based on some unexpected epidemiological findings.

“In general, we tend to think people with underlying lung disease – like COPD or asthma – to be at higher risk for severe forms of lower respiratory tract infections,” Dr. Conroy said. “Somewhat surprisingly, early data in the pandemic showed patients with COPD and asthma [were] underrepresented [among patients with COVID] when compared to the prevalence of these diseases in the population.”

This raised the possibility of an incidental protective effect from regular ICS therapy, which “had some strong theoretic pathophysiologic basis,” Dr. Conroy said, referring to research that demonstrated ICS-mediated downregulation of SARS-CoV-2 entry receptors ACE2 and TMPRSS2.

Dr. Schultze and colleagues noted that investigators for two ongoing randomized controlled trials (NCT04331054, NCT04330586) are studying ICS as an intervention for COVID-19; but neither trial includes individuals already taking ICS for chronic respiratory disease.

The present observational study therefore aimed to assess mortality risk within this population. Data were drawn from electronic health records and a U.K. national mortality database, with follow-up ranging from March 1 to May 6, 2020. Eligibility required a relevant prescription within 4 months of first follow-up. In the COPD group, patients were prescribed a long-acting beta agonist plus a long-acting muscarinic antagonist (LABA–LAMA), LABA alone, LABA plus ICS, LABA–LAMA plus ICS, or ICS alone (if prescribed LABA within 4 months).

In the asthma group, patients received low/medium-dose ICS, high-dose ICS, or a short-acting beta agonist (SABA) alone. Patients with COPD were at least 35 years of age, while those with asthma were 18 years or older. Hazard ratios were adjusted for a variety of covariates, including respiratory disease–exacerbation history, age, sex, body mass index, hypertension, diabetes, and others.

These eligibility criteria returned 148,557 patients with COPD and 818,490 with asthma.

Patients with COPD who were prescribed ICS plus LABA-LAMA or ICS plus LABA had an increased risk of COVID-19-related death, compared with those who did not receive ICS (adjusted hazard ratio, 1.39; 95% confidence interval, 1.10-1.76). Separate analyses of patients who received a triple combination (LABA–LAMA plus ICS) versus those who took a dual combination (LABA plus ICS) showed that triple-combination therapy was significantly associated with increased COVID-19-related mortality (aHR, 1.43; 95% CI, 1.12-1.83), while dual-combination therapy was less so (aHR, 1.29; 95% CI, 0.96-1.74). Non–COVID-19–related mortality was significantly increased for all COPD patients who were prescribed ICS, with or without adjustment for covariates.

Asthma patients prescribed high-dose ICS instead of SABA alone had a slightly greater risk of COVID-19–related death, based on an adjusted hazard ratio of 1.55 (95% CI, 1.10-2.18). Those with asthma who received low/medium–dose ICS demonstrated a slight trend toward increased mortality risk, but this was not significant (aHR, 1.14; 95% CI, 0.85-1.54). ICS usage in the asthma group was not linked with a significant increase in non–COVID-19–related death.

“In summary, we found no evidence of a beneficial effect of regular ICS use among people with COPD and asthma on COVID-19–related mortality,” the investigators concluded.

In agreement with the investigators, Dr. Conroy said that the increased mortality rate among ICS users should not be misconstrued as a medication-related risk.

“While the study found that those with COPD or asthma taking ICS and high-dose ICS were at an increased risk of death, this could easily be explained by the likelihood that those are the patients who are more likely to have more severe underlying lung disease,” Dr. Conroy said. “While this observational study did attempt to control for exacerbation history, the ability to do so by electronic health records data is certainly imperfect.”

With this in mind, patients with chronic respiratory disease should be encouraged to adhere to their usual treatment regimen, Dr. Conroy added.

“There isn’t evidence to increase or decrease medications just because of the pandemic,” she said. “A patient with asthma or COPD should continue to take the medications that are needed to achieve good control of their lung disease.”

The study was funded by the U.K. Medical Research Council. The investigators reported additional relationships with the Wellcome Trust, the Good Thinking Foundation, the Laura and John Arnold Foundation, and others. Dr. Conroy reported no conflicts of interest.

SOURCE: Schultze A et al. Lancet Respir Med. 2020 Sep 24. doi: 10.1016/ S2213-2600(20)30415-X.

Inhaled corticosteroids (ICS) do not protect patients with chronic respiratory conditions against COVID-19-related death, a study of almost 1 million individuals in the United Kingdom has shown.

Patients with chronic obstructive pulmonary disease or asthma who used ICS on a regular basis were more likely to die from COVID-19 than COPD or asthma patients who were prescribed non-ICS therapies, reported co-lead author Anna Schultze, PhD, of London School of Hygiene & Tropical Medicine and colleagues.

Of note, the increased risk of death among ICS users likely stemmed from greater severity of preexisting chronic respiratory conditions, instead of directly from ICS usage, which has little apparent impact on COVID-19 mortality, the investigators wrote in Lancet Respiratory Medicine.

These findings conflict with a hypothesis proposed early in the pandemic: that ICS may protect individuals from SARS-CoV-2 infection and poor outcomes with COVID-19.

According to Megan Conroy, MD, of the department of internal medicine at the Ohio State University Wexner Medical Center, Columbus, this hypothesis was based on some unexpected epidemiological findings.

“In general, we tend to think people with underlying lung disease – like COPD or asthma – to be at higher risk for severe forms of lower respiratory tract infections,” Dr. Conroy said. “Somewhat surprisingly, early data in the pandemic showed patients with COPD and asthma [were] underrepresented [among patients with COVID] when compared to the prevalence of these diseases in the population.”

This raised the possibility of an incidental protective effect from regular ICS therapy, which “had some strong theoretic pathophysiologic basis,” Dr. Conroy said, referring to research that demonstrated ICS-mediated downregulation of SARS-CoV-2 entry receptors ACE2 and TMPRSS2.

Dr. Schultze and colleagues noted that investigators for two ongoing randomized controlled trials (NCT04331054, NCT04330586) are studying ICS as an intervention for COVID-19; but neither trial includes individuals already taking ICS for chronic respiratory disease.

The present observational study therefore aimed to assess mortality risk within this population. Data were drawn from electronic health records and a U.K. national mortality database, with follow-up ranging from March 1 to May 6, 2020. Eligibility required a relevant prescription within 4 months of first follow-up. In the COPD group, patients were prescribed a long-acting beta agonist plus a long-acting muscarinic antagonist (LABA–LAMA), LABA alone, LABA plus ICS, LABA–LAMA plus ICS, or ICS alone (if prescribed LABA within 4 months).

In the asthma group, patients received low/medium-dose ICS, high-dose ICS, or a short-acting beta agonist (SABA) alone. Patients with COPD were at least 35 years of age, while those with asthma were 18 years or older. Hazard ratios were adjusted for a variety of covariates, including respiratory disease–exacerbation history, age, sex, body mass index, hypertension, diabetes, and others.

These eligibility criteria returned 148,557 patients with COPD and 818,490 with asthma.

Patients with COPD who were prescribed ICS plus LABA-LAMA or ICS plus LABA had an increased risk of COVID-19-related death, compared with those who did not receive ICS (adjusted hazard ratio, 1.39; 95% confidence interval, 1.10-1.76). Separate analyses of patients who received a triple combination (LABA–LAMA plus ICS) versus those who took a dual combination (LABA plus ICS) showed that triple-combination therapy was significantly associated with increased COVID-19-related mortality (aHR, 1.43; 95% CI, 1.12-1.83), while dual-combination therapy was less so (aHR, 1.29; 95% CI, 0.96-1.74). Non–COVID-19–related mortality was significantly increased for all COPD patients who were prescribed ICS, with or without adjustment for covariates.

Asthma patients prescribed high-dose ICS instead of SABA alone had a slightly greater risk of COVID-19–related death, based on an adjusted hazard ratio of 1.55 (95% CI, 1.10-2.18). Those with asthma who received low/medium–dose ICS demonstrated a slight trend toward increased mortality risk, but this was not significant (aHR, 1.14; 95% CI, 0.85-1.54). ICS usage in the asthma group was not linked with a significant increase in non–COVID-19–related death.

“In summary, we found no evidence of a beneficial effect of regular ICS use among people with COPD and asthma on COVID-19–related mortality,” the investigators concluded.

In agreement with the investigators, Dr. Conroy said that the increased mortality rate among ICS users should not be misconstrued as a medication-related risk.

“While the study found that those with COPD or asthma taking ICS and high-dose ICS were at an increased risk of death, this could easily be explained by the likelihood that those are the patients who are more likely to have more severe underlying lung disease,” Dr. Conroy said. “While this observational study did attempt to control for exacerbation history, the ability to do so by electronic health records data is certainly imperfect.”

With this in mind, patients with chronic respiratory disease should be encouraged to adhere to their usual treatment regimen, Dr. Conroy added.

“There isn’t evidence to increase or decrease medications just because of the pandemic,” she said. “A patient with asthma or COPD should continue to take the medications that are needed to achieve good control of their lung disease.”

The study was funded by the U.K. Medical Research Council. The investigators reported additional relationships with the Wellcome Trust, the Good Thinking Foundation, the Laura and John Arnold Foundation, and others. Dr. Conroy reported no conflicts of interest.

SOURCE: Schultze A et al. Lancet Respir Med. 2020 Sep 24. doi: 10.1016/ S2213-2600(20)30415-X.

Inhaled corticosteroids (ICS) do not protect patients with chronic respiratory conditions against COVID-19-related death, a study of almost 1 million individuals in the United Kingdom has shown.

Patients with chronic obstructive pulmonary disease or asthma who used ICS on a regular basis were more likely to die from COVID-19 than COPD or asthma patients who were prescribed non-ICS therapies, reported co-lead author Anna Schultze, PhD, of London School of Hygiene & Tropical Medicine and colleagues.

Of note, the increased risk of death among ICS users likely stemmed from greater severity of preexisting chronic respiratory conditions, instead of directly from ICS usage, which has little apparent impact on COVID-19 mortality, the investigators wrote in Lancet Respiratory Medicine.

These findings conflict with a hypothesis proposed early in the pandemic: that ICS may protect individuals from SARS-CoV-2 infection and poor outcomes with COVID-19.

According to Megan Conroy, MD, of the department of internal medicine at the Ohio State University Wexner Medical Center, Columbus, this hypothesis was based on some unexpected epidemiological findings.

“In general, we tend to think people with underlying lung disease – like COPD or asthma – to be at higher risk for severe forms of lower respiratory tract infections,” Dr. Conroy said. “Somewhat surprisingly, early data in the pandemic showed patients with COPD and asthma [were] underrepresented [among patients with COVID] when compared to the prevalence of these diseases in the population.”

This raised the possibility of an incidental protective effect from regular ICS therapy, which “had some strong theoretic pathophysiologic basis,” Dr. Conroy said, referring to research that demonstrated ICS-mediated downregulation of SARS-CoV-2 entry receptors ACE2 and TMPRSS2.

Dr. Schultze and colleagues noted that investigators for two ongoing randomized controlled trials (NCT04331054, NCT04330586) are studying ICS as an intervention for COVID-19; but neither trial includes individuals already taking ICS for chronic respiratory disease.

The present observational study therefore aimed to assess mortality risk within this population. Data were drawn from electronic health records and a U.K. national mortality database, with follow-up ranging from March 1 to May 6, 2020. Eligibility required a relevant prescription within 4 months of first follow-up. In the COPD group, patients were prescribed a long-acting beta agonist plus a long-acting muscarinic antagonist (LABA–LAMA), LABA alone, LABA plus ICS, LABA–LAMA plus ICS, or ICS alone (if prescribed LABA within 4 months).

In the asthma group, patients received low/medium-dose ICS, high-dose ICS, or a short-acting beta agonist (SABA) alone. Patients with COPD were at least 35 years of age, while those with asthma were 18 years or older. Hazard ratios were adjusted for a variety of covariates, including respiratory disease–exacerbation history, age, sex, body mass index, hypertension, diabetes, and others.

These eligibility criteria returned 148,557 patients with COPD and 818,490 with asthma.

Patients with COPD who were prescribed ICS plus LABA-LAMA or ICS plus LABA had an increased risk of COVID-19-related death, compared with those who did not receive ICS (adjusted hazard ratio, 1.39; 95% confidence interval, 1.10-1.76). Separate analyses of patients who received a triple combination (LABA–LAMA plus ICS) versus those who took a dual combination (LABA plus ICS) showed that triple-combination therapy was significantly associated with increased COVID-19-related mortality (aHR, 1.43; 95% CI, 1.12-1.83), while dual-combination therapy was less so (aHR, 1.29; 95% CI, 0.96-1.74). Non–COVID-19–related mortality was significantly increased for all COPD patients who were prescribed ICS, with or without adjustment for covariates.

Asthma patients prescribed high-dose ICS instead of SABA alone had a slightly greater risk of COVID-19–related death, based on an adjusted hazard ratio of 1.55 (95% CI, 1.10-2.18). Those with asthma who received low/medium–dose ICS demonstrated a slight trend toward increased mortality risk, but this was not significant (aHR, 1.14; 95% CI, 0.85-1.54). ICS usage in the asthma group was not linked with a significant increase in non–COVID-19–related death.

“In summary, we found no evidence of a beneficial effect of regular ICS use among people with COPD and asthma on COVID-19–related mortality,” the investigators concluded.

In agreement with the investigators, Dr. Conroy said that the increased mortality rate among ICS users should not be misconstrued as a medication-related risk.

“While the study found that those with COPD or asthma taking ICS and high-dose ICS were at an increased risk of death, this could easily be explained by the likelihood that those are the patients who are more likely to have more severe underlying lung disease,” Dr. Conroy said. “While this observational study did attempt to control for exacerbation history, the ability to do so by electronic health records data is certainly imperfect.”

With this in mind, patients with chronic respiratory disease should be encouraged to adhere to their usual treatment regimen, Dr. Conroy added.

“There isn’t evidence to increase or decrease medications just because of the pandemic,” she said. “A patient with asthma or COPD should continue to take the medications that are needed to achieve good control of their lung disease.”

The study was funded by the U.K. Medical Research Council. The investigators reported additional relationships with the Wellcome Trust, the Good Thinking Foundation, the Laura and John Arnold Foundation, and others. Dr. Conroy reported no conflicts of interest.

SOURCE: Schultze A et al. Lancet Respir Med. 2020 Sep 24. doi: 10.1016/ S2213-2600(20)30415-X.

The wholesale shuffling of employees triggered by the COVID-19 pandemic has raised many questions about the differences between full-time, part-time, and full-time equivalent employees, and how employment laws apply to them. While rules vary from state to state, some generalizations can be made.

Even the definitions of full-time and part-time vary. For instance, under the Affordable Care Act (ACA), full time means working at least 30 hours per week. Under the Families First Coronavirus Response Act (FFCRA), it is 40 hours.

Full-time equivalent (FTE) is a concept designed to document a part-time workforce in terms of full-time employment, by taking the total hours worked by all part-time employees and dividing by the full-time schedule. Of course, the ACA and the Paycheck Protection Program (PPP) calculate that number differently: The ACA requires you to total all the hours worked by part-time employees per month, and divide by 120. For the PPP, you divide the total part-time hours per week by 40, and round to the nearest tenth. (You can also use a simplified method that assigns a 1.0 for employees who work 40 hours or more per week and 0.5 for those who work fewer; whichever method you choose, you must apply it consistently on all PPP forms.)

FTEs are important for the purposes of the ACA because employers with 50 or more full-timers plus FTEs must offer health coverage to their full-timers and dependents. But most private practitioners need an accurate FTE total to deal with the PPP: If staffing levels weren’t maintained after you received a PPP loan, your loan forgiveness amount may be reduced. Staffing levels are determined by comparing the average number of full-timers plus FTEs during the “covered period” to either the period from Feb. 15 through June 30, 2019, or Jan. 1 through Feb. 28, 2020.

The PPP aside, FTEs have created confusion over when an employee is entitled to overtime pay. Under federal law, overtime is due whenever an employee works more than 40 hours per week; up to 40 hours, the regular wage is paid. (There are exemptions, and a few states use a daily number.) For example, if a part-timer receiving $900 per week for a 30-hour workweek works more than 30 hours, the hours from 30 to 40 would be compensated at their normal wage of $30 per hour ($900 ÷ 30). If the employee worked more than 40 hours, you would pay overtime (in this case $45 per hour, $30 x 1.5) for the hours in excess of 40.

To address a few other employment questions that I am frequently asked:

Under the FFCRA, you must provide both full- and part-time employees with emergency paid sick leave (EPSL) if they’re unable to work from your office or their home because of illness attributable to COVID-19, quarantine, or caring for a sick family member or child whose school is closed. Full-time employees are entitled to up to 80 hours of EPSL, and part-timers an average of what they work every 2 weeks. Some states have their own laws independent from the FFCRA. Check your state or local laws.

• Some states require you to provide meal and rest breaks to both full- and part-time employees. In California, for example, employers must provide a 30-minute meal break after no more than 5 hours of work, unless the total workday is less than 6 hours and both employers and employees consent to waive breaks. California also requires rest breaks after every 4 hours worked. Check the laws in your state.
• You must include part-time employees in a 401(k) retirement plan if they work at least 1,000 hours in a year, which is about 20 hours per week. That rule is changing in 2021 to 500 hours for employees older than 21. There are state-run retirement programs in California, Connecticut, New Jersey, Washington, and Oregon, among other states. Check your state law for details.
• If you offer paid vacations to full-time employees, you do not have to do the same for part-timers. (In fact, there is no requirement in most states to offer vacation time at all.) My office does offer it to part-time employees on a pro rata basis, as do many others in my area. Again, check your state law.

As always, consult with your attorney if it’s not clear which rules apply in your specific situation.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. He has no relevant disclosures related to the topic of this column. Write to him at [email protected].

The wholesale shuffling of employees triggered by the COVID-19 pandemic has raised many questions about the differences between full-time, part-time, and full-time equivalent employees, and how employment laws apply to them. While rules vary from state to state, some generalizations can be made.

Even the definitions of full-time and part-time vary. For instance, under the Affordable Care Act (ACA), full time means working at least 30 hours per week. Under the Families First Coronavirus Response Act (FFCRA), it is 40 hours.

Full-time equivalent (FTE) is a concept designed to document a part-time workforce in terms of full-time employment, by taking the total hours worked by all part-time employees and dividing by the full-time schedule. Of course, the ACA and the Paycheck Protection Program (PPP) calculate that number differently: The ACA requires you to total all the hours worked by part-time employees per month, and divide by 120. For the PPP, you divide the total part-time hours per week by 40, and round to the nearest tenth. (You can also use a simplified method that assigns a 1.0 for employees who work 40 hours or more per week and 0.5 for those who work fewer; whichever method you choose, you must apply it consistently on all PPP forms.)

FTEs are important for the purposes of the ACA because employers with 50 or more full-timers plus FTEs must offer health coverage to their full-timers and dependents. But most private practitioners need an accurate FTE total to deal with the PPP: If staffing levels weren’t maintained after you received a PPP loan, your loan forgiveness amount may be reduced. Staffing levels are determined by comparing the average number of full-timers plus FTEs during the “covered period” to either the period from Feb. 15 through June 30, 2019, or Jan. 1 through Feb. 28, 2020.

The PPP aside, FTEs have created confusion over when an employee is entitled to overtime pay. Under federal law, overtime is due whenever an employee works more than 40 hours per week; up to 40 hours, the regular wage is paid. (There are exemptions, and a few states use a daily number.) For example, if a part-timer receiving $900 per week for a 30-hour workweek works more than 30 hours, the hours from 30 to 40 would be compensated at their normal wage of $30 per hour ($900 ÷ 30). If the employee worked more than 40 hours, you would pay overtime (in this case $45 per hour, $30 x 1.5) for the hours in excess of 40.

To address a few other employment questions that I am frequently asked:

Under the FFCRA, you must provide both full- and part-time employees with emergency paid sick leave (EPSL) if they’re unable to work from your office or their home because of illness attributable to COVID-19, quarantine, or caring for a sick family member or child whose school is closed. Full-time employees are entitled to up to 80 hours of EPSL, and part-timers an average of what they work every 2 weeks. Some states have their own laws independent from the FFCRA. Check your state or local laws.

• Some states require you to provide meal and rest breaks to both full- and part-time employees. In California, for example, employers must provide a 30-minute meal break after no more than 5 hours of work, unless the total workday is less than 6 hours and both employers and employees consent to waive breaks. California also requires rest breaks after every 4 hours worked. Check the laws in your state.
• You must include part-time employees in a 401(k) retirement plan if they work at least 1,000 hours in a year, which is about 20 hours per week. That rule is changing in 2021 to 500 hours for employees older than 21. There are state-run retirement programs in California, Connecticut, New Jersey, Washington, and Oregon, among other states. Check your state law for details.
• If you offer paid vacations to full-time employees, you do not have to do the same for part-timers. (In fact, there is no requirement in most states to offer vacation time at all.) My office does offer it to part-time employees on a pro rata basis, as do many others in my area. Again, check your state law.

As always, consult with your attorney if it’s not clear which rules apply in your specific situation.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. He has no relevant disclosures related to the topic of this column. Write to him at [email protected].

The wholesale shuffling of employees triggered by the COVID-19 pandemic has raised many questions about the differences between full-time, part-time, and full-time equivalent employees, and how employment laws apply to them. While rules vary from state to state, some generalizations can be made.

Even the definitions of full-time and part-time vary. For instance, under the Affordable Care Act (ACA), full time means working at least 30 hours per week. Under the Families First Coronavirus Response Act (FFCRA), it is 40 hours.

Full-time equivalent (FTE) is a concept designed to document a part-time workforce in terms of full-time employment, by taking the total hours worked by all part-time employees and dividing by the full-time schedule. Of course, the ACA and the Paycheck Protection Program (PPP) calculate that number differently: The ACA requires you to total all the hours worked by part-time employees per month, and divide by 120. For the PPP, you divide the total part-time hours per week by 40, and round to the nearest tenth. (You can also use a simplified method that assigns a 1.0 for employees who work 40 hours or more per week and 0.5 for those who work fewer; whichever method you choose, you must apply it consistently on all PPP forms.)

FTEs are important for the purposes of the ACA because employers with 50 or more full-timers plus FTEs must offer health coverage to their full-timers and dependents. But most private practitioners need an accurate FTE total to deal with the PPP: If staffing levels weren’t maintained after you received a PPP loan, your loan forgiveness amount may be reduced. Staffing levels are determined by comparing the average number of full-timers plus FTEs during the “covered period” to either the period from Feb. 15 through June 30, 2019, or Jan. 1 through Feb. 28, 2020.

The PPP aside, FTEs have created confusion over when an employee is entitled to overtime pay. Under federal law, overtime is due whenever an employee works more than 40 hours per week; up to 40 hours, the regular wage is paid. (There are exemptions, and a few states use a daily number.) For example, if a part-timer receiving $900 per week for a 30-hour workweek works more than 30 hours, the hours from 30 to 40 would be compensated at their normal wage of $30 per hour ($900 ÷ 30). If the employee worked more than 40 hours, you would pay overtime (in this case $45 per hour, $30 x 1.5) for the hours in excess of 40.

To address a few other employment questions that I am frequently asked:

Under the FFCRA, you must provide both full- and part-time employees with emergency paid sick leave (EPSL) if they’re unable to work from your office or their home because of illness attributable to COVID-19, quarantine, or caring for a sick family member or child whose school is closed. Full-time employees are entitled to up to 80 hours of EPSL, and part-timers an average of what they work every 2 weeks. Some states have their own laws independent from the FFCRA. Check your state or local laws.

• Some states require you to provide meal and rest breaks to both full- and part-time employees. In California, for example, employers must provide a 30-minute meal break after no more than 5 hours of work, unless the total workday is less than 6 hours and both employers and employees consent to waive breaks. California also requires rest breaks after every 4 hours worked. Check the laws in your state.
• You must include part-time employees in a 401(k) retirement plan if they work at least 1,000 hours in a year, which is about 20 hours per week. That rule is changing in 2021 to 500 hours for employees older than 21. There are state-run retirement programs in California, Connecticut, New Jersey, Washington, and Oregon, among other states. Check your state law for details.
• If you offer paid vacations to full-time employees, you do not have to do the same for part-timers. (In fact, there is no requirement in most states to offer vacation time at all.) My office does offer it to part-time employees on a pro rata basis, as do many others in my area. Again, check your state law.

As always, consult with your attorney if it’s not clear which rules apply in your specific situation.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. He has no relevant disclosures related to the topic of this column. Write to him at [email protected].

Adolescent alcohol use among boys was prospectively associated with use of legal performance-enhancing substances in young adulthood, based on prospective cohort data from more than 12,000 individuals, wrote Kyle T. Ganson, PhD, MSW, of the University of Toronto, and colleagues.

Nikada/iStockphoto

In addition, legal use of performance-enhancing substances (PES) among young men was associated with increased risk of alcohol use problems.

Although previous studies have shown a range of adverse effects associated with the use of anabolic-androgenic steroid derivatives (defined as illegal PES), the possible adverse effects of legal PES (defined in this report as protein powders, creatine monohydrate, dehydroepiandrostenedione, and amino acids) have not been well studied, the researchers wrote.

In a study published in Pediatrics, the researchers reviewed data from 12,133 young adults aged 18-26 years who were part of the National Longitudinal Study of Adolescent to Adult Health from 1994 to 2008.

Overall, 16% of young men and 1% of young women reported using legal PES in the past year. Among men, legal PES use was prospectively associated with increased risk of a range of alcohol-related problem behaviors including binge drinking (adjusted odds ratio, 1.35), injurious and risky behaviors (aOR, 1.78), legal problems (aOR, 1.52), reduced activities and socializing (aOR, 1.91), and problems with emotional or physical health (aOR, 1.44).

Legal PES use among young adult women was associated with an increased risk of emotional or physical health problems (aOR, 3.00).
 

Adolescent impact

Between adolescence and young adulthood (an average of 7 years’ follow-up), alcohol use was prospectively associated with legal PES use in young men (OR, 1.39), but neither cigarette smoking nor marijuana use in adolescence was associated with later use of legal PES. Among young women, no type of adolescent substance use was prospectively associated with later use of legal PES.

“To date, legal PES have not been largely considered as part of the spectrum of substances used among adolescents, have not been subject to the same regulatory scrutiny as other substances known to be linked to subsequent substance use and are freely available over the counter to adolescents,” Dr. Ganson and associates noted.

“Clearly, the robust reciprocal temporal relationship between substance use and legal PES suggests that each may serve as a gateway for the other,” they wrote.

The study findings were limited by several factors including the inability to identify outcomes associated with variable PES components, incomplete data collection on several drinking-related risk behaviors, and inability to analyze prospective use of illegal or other substances associated with use of legal PES, the researchers wrote.

However, “these results provide further evidence in support of the gateway theory and prospective health risk behaviors associated with legal PES and substance use,” they wrote.

The data may inform policy on the additional regulation of legal PES use in minors. In the meantime, “it is important for medical providers and clinicians to assess problematic alcohol use and drinking-related risk behaviors among young adult men who have previously used legal PES,” Dr. Ganson and associates concluded.
 

Challenges to clinicians

An important point to recognize is that PES is a misleading term, Steven Cuff, MD, of the Ohio State University, Columbus, and Michele LaBotz, MD, of Tufts University, Boston, wrote in an accompanying editorial. “Most legal supplements marketed for athletic performance enhancement are ineffective at increasing muscle mass or athletic performance beyond what can be achieved through appropriate nutrition and training,” they emphasized. The current study findings suggest that “legal PES should be integrated into the gateway hypothesis regarding patterns and progression of substance use through adolescence and early adulthood,” and support discouragement of any PES use among adolescents and young adults.

Even legal PES can be dangerous because of the lack of oversight of dietary supplements by the Food and Drug Administration. “There is widespread evidence that many over-the-counter dietary supplements lack stated ingredients, contain unlabeled ingredients (including potential allergens), or are contaminated with impurities or illegal or dangerous substances, such as steroids and stimulants,” the editorialists emphasized.

In addition, the association found in the study between muscle dysphoria and both PES use and substance use disorders, notably alcohol-related morbidity, highlights the need for a proactive approach by pediatricians to minimize the risk, they noted.

“For pediatricians uncomfortable with initiating discussions on PES use with their patients, an American Academy of Pediatrics–supported role-play simulation is available,” they concluded.

The study is important because “PES use is ubiquitous among adolescents and young adults,” Dr. LaBotz said in an interview. “Although it is widely believed that PES use serves as a likely ‘gateway’ to use of anabolic steroids and other substances, this is one of the very few studies that explores this relationship. Their findings that alcohol use appears to correlate with subsequent use of PES, and that PES use appears to correlate with future alcohol-related issues, suggest that this is not a simple linear progression of problematic behavior.”

Dr. LaBotz added that she was not surprised by the study findings, and emphasized that pediatric health care providers should be aware of the association between PES and alcohol use. “PES screening should be incorporated into screening done for alcohol and other substance use. This appears to be particularly true for athletes and other subpopulations who are at higher risk for problematic alcohol use.”

She said much of PES use is driven by the desire by young men for a muscular appearance, but more research is needed on young women. “In the past, this was a goal primarily associated with males, but females have become increasingly interested in achieving muscularity as well, which suggests an increasing risk of PES use among females as compared to earlier reports. We need updated data on patterns, prevalence and consequences of PES use in females.”

In addition, “although preparticipation physical examination forms include screening questions for PES use among athletes, further information is needed on how to incorporate PES into substance use screening that is performed in a general pediatric population, such as including athletes and nonathletes,” Dr. LaBotz said.

The study was supported by the National Institutes of Health and by grants to one of the coauthors from the Pediatric Scientist Development Program funded by the American Academy of Pediatrics and the American Pediatric Society, as well as the American Heart Association Career Development Award. The researchers had no financial conflicts to disclose. Dr. Cuff and Dr. LaBotz had no financial conflicts to disclose.

SOURCE: Ganson KT et al. Pediatrics. 2020 Sep. doi: 10.1542/peds.2020-0409.

Adolescent alcohol use among boys was prospectively associated with use of legal performance-enhancing substances in young adulthood, based on prospective cohort data from more than 12,000 individuals, wrote Kyle T. Ganson, PhD, MSW, of the University of Toronto, and colleagues.

Nikada/iStockphoto

In addition, legal use of performance-enhancing substances (PES) among young men was associated with increased risk of alcohol use problems.

Although previous studies have shown a range of adverse effects associated with the use of anabolic-androgenic steroid derivatives (defined as illegal PES), the possible adverse effects of legal PES (defined in this report as protein powders, creatine monohydrate, dehydroepiandrostenedione, and amino acids) have not been well studied, the researchers wrote.

In a study published in Pediatrics, the researchers reviewed data from 12,133 young adults aged 18-26 years who were part of the National Longitudinal Study of Adolescent to Adult Health from 1994 to 2008.

Overall, 16% of young men and 1% of young women reported using legal PES in the past year. Among men, legal PES use was prospectively associated with increased risk of a range of alcohol-related problem behaviors including binge drinking (adjusted odds ratio, 1.35), injurious and risky behaviors (aOR, 1.78), legal problems (aOR, 1.52), reduced activities and socializing (aOR, 1.91), and problems with emotional or physical health (aOR, 1.44).

Legal PES use among young adult women was associated with an increased risk of emotional or physical health problems (aOR, 3.00).
 

Adolescent impact

Between adolescence and young adulthood (an average of 7 years’ follow-up), alcohol use was prospectively associated with legal PES use in young men (OR, 1.39), but neither cigarette smoking nor marijuana use in adolescence was associated with later use of legal PES. Among young women, no type of adolescent substance use was prospectively associated with later use of legal PES.

“To date, legal PES have not been largely considered as part of the spectrum of substances used among adolescents, have not been subject to the same regulatory scrutiny as other substances known to be linked to subsequent substance use and are freely available over the counter to adolescents,” Dr. Ganson and associates noted.

“Clearly, the robust reciprocal temporal relationship between substance use and legal PES suggests that each may serve as a gateway for the other,” they wrote.

The study findings were limited by several factors including the inability to identify outcomes associated with variable PES components, incomplete data collection on several drinking-related risk behaviors, and inability to analyze prospective use of illegal or other substances associated with use of legal PES, the researchers wrote.

However, “these results provide further evidence in support of the gateway theory and prospective health risk behaviors associated with legal PES and substance use,” they wrote.

The data may inform policy on the additional regulation of legal PES use in minors. In the meantime, “it is important for medical providers and clinicians to assess problematic alcohol use and drinking-related risk behaviors among young adult men who have previously used legal PES,” Dr. Ganson and associates concluded.
 

Challenges to clinicians

An important point to recognize is that PES is a misleading term, Steven Cuff, MD, of the Ohio State University, Columbus, and Michele LaBotz, MD, of Tufts University, Boston, wrote in an accompanying editorial. “Most legal supplements marketed for athletic performance enhancement are ineffective at increasing muscle mass or athletic performance beyond what can be achieved through appropriate nutrition and training,” they emphasized. The current study findings suggest that “legal PES should be integrated into the gateway hypothesis regarding patterns and progression of substance use through adolescence and early adulthood,” and support discouragement of any PES use among adolescents and young adults.

Even legal PES can be dangerous because of the lack of oversight of dietary supplements by the Food and Drug Administration. “There is widespread evidence that many over-the-counter dietary supplements lack stated ingredients, contain unlabeled ingredients (including potential allergens), or are contaminated with impurities or illegal or dangerous substances, such as steroids and stimulants,” the editorialists emphasized.

In addition, the association found in the study between muscle dysphoria and both PES use and substance use disorders, notably alcohol-related morbidity, highlights the need for a proactive approach by pediatricians to minimize the risk, they noted.

“For pediatricians uncomfortable with initiating discussions on PES use with their patients, an American Academy of Pediatrics–supported role-play simulation is available,” they concluded.

The study is important because “PES use is ubiquitous among adolescents and young adults,” Dr. LaBotz said in an interview. “Although it is widely believed that PES use serves as a likely ‘gateway’ to use of anabolic steroids and other substances, this is one of the very few studies that explores this relationship. Their findings that alcohol use appears to correlate with subsequent use of PES, and that PES use appears to correlate with future alcohol-related issues, suggest that this is not a simple linear progression of problematic behavior.”

Dr. LaBotz added that she was not surprised by the study findings, and emphasized that pediatric health care providers should be aware of the association between PES and alcohol use. “PES screening should be incorporated into screening done for alcohol and other substance use. This appears to be particularly true for athletes and other subpopulations who are at higher risk for problematic alcohol use.”

She said much of PES use is driven by the desire by young men for a muscular appearance, but more research is needed on young women. “In the past, this was a goal primarily associated with males, but females have become increasingly interested in achieving muscularity as well, which suggests an increasing risk of PES use among females as compared to earlier reports. We need updated data on patterns, prevalence and consequences of PES use in females.”

In addition, “although preparticipation physical examination forms include screening questions for PES use among athletes, further information is needed on how to incorporate PES into substance use screening that is performed in a general pediatric population, such as including athletes and nonathletes,” Dr. LaBotz said.

The study was supported by the National Institutes of Health and by grants to one of the coauthors from the Pediatric Scientist Development Program funded by the American Academy of Pediatrics and the American Pediatric Society, as well as the American Heart Association Career Development Award. The researchers had no financial conflicts to disclose. Dr. Cuff and Dr. LaBotz had no financial conflicts to disclose.

SOURCE: Ganson KT et al. Pediatrics. 2020 Sep. doi: 10.1542/peds.2020-0409.

Adolescent alcohol use among boys was prospectively associated with use of legal performance-enhancing substances in young adulthood, based on prospective cohort data from more than 12,000 individuals, wrote Kyle T. Ganson, PhD, MSW, of the University of Toronto, and colleagues.

Nikada/iStockphoto

In addition, legal use of performance-enhancing substances (PES) among young men was associated with increased risk of alcohol use problems.

Although previous studies have shown a range of adverse effects associated with the use of anabolic-androgenic steroid derivatives (defined as illegal PES), the possible adverse effects of legal PES (defined in this report as protein powders, creatine monohydrate, dehydroepiandrostenedione, and amino acids) have not been well studied, the researchers wrote.

In a study published in Pediatrics, the researchers reviewed data from 12,133 young adults aged 18-26 years who were part of the National Longitudinal Study of Adolescent to Adult Health from 1994 to 2008.

Overall, 16% of young men and 1% of young women reported using legal PES in the past year. Among men, legal PES use was prospectively associated with increased risk of a range of alcohol-related problem behaviors including binge drinking (adjusted odds ratio, 1.35), injurious and risky behaviors (aOR, 1.78), legal problems (aOR, 1.52), reduced activities and socializing (aOR, 1.91), and problems with emotional or physical health (aOR, 1.44).

Legal PES use among young adult women was associated with an increased risk of emotional or physical health problems (aOR, 3.00).
 

Adolescent impact

Between adolescence and young adulthood (an average of 7 years’ follow-up), alcohol use was prospectively associated with legal PES use in young men (OR, 1.39), but neither cigarette smoking nor marijuana use in adolescence was associated with later use of legal PES. Among young women, no type of adolescent substance use was prospectively associated with later use of legal PES.

“To date, legal PES have not been largely considered as part of the spectrum of substances used among adolescents, have not been subject to the same regulatory scrutiny as other substances known to be linked to subsequent substance use and are freely available over the counter to adolescents,” Dr. Ganson and associates noted.

“Clearly, the robust reciprocal temporal relationship between substance use and legal PES suggests that each may serve as a gateway for the other,” they wrote.

The study findings were limited by several factors including the inability to identify outcomes associated with variable PES components, incomplete data collection on several drinking-related risk behaviors, and inability to analyze prospective use of illegal or other substances associated with use of legal PES, the researchers wrote.

However, “these results provide further evidence in support of the gateway theory and prospective health risk behaviors associated with legal PES and substance use,” they wrote.

The data may inform policy on the additional regulation of legal PES use in minors. In the meantime, “it is important for medical providers and clinicians to assess problematic alcohol use and drinking-related risk behaviors among young adult men who have previously used legal PES,” Dr. Ganson and associates concluded.
 

Challenges to clinicians

An important point to recognize is that PES is a misleading term, Steven Cuff, MD, of the Ohio State University, Columbus, and Michele LaBotz, MD, of Tufts University, Boston, wrote in an accompanying editorial. “Most legal supplements marketed for athletic performance enhancement are ineffective at increasing muscle mass or athletic performance beyond what can be achieved through appropriate nutrition and training,” they emphasized. The current study findings suggest that “legal PES should be integrated into the gateway hypothesis regarding patterns and progression of substance use through adolescence and early adulthood,” and support discouragement of any PES use among adolescents and young adults.

Even legal PES can be dangerous because of the lack of oversight of dietary supplements by the Food and Drug Administration. “There is widespread evidence that many over-the-counter dietary supplements lack stated ingredients, contain unlabeled ingredients (including potential allergens), or are contaminated with impurities or illegal or dangerous substances, such as steroids and stimulants,” the editorialists emphasized.

In addition, the association found in the study between muscle dysphoria and both PES use and substance use disorders, notably alcohol-related morbidity, highlights the need for a proactive approach by pediatricians to minimize the risk, they noted.

“For pediatricians uncomfortable with initiating discussions on PES use with their patients, an American Academy of Pediatrics–supported role-play simulation is available,” they concluded.

The study is important because “PES use is ubiquitous among adolescents and young adults,” Dr. LaBotz said in an interview. “Although it is widely believed that PES use serves as a likely ‘gateway’ to use of anabolic steroids and other substances, this is one of the very few studies that explores this relationship. Their findings that alcohol use appears to correlate with subsequent use of PES, and that PES use appears to correlate with future alcohol-related issues, suggest that this is not a simple linear progression of problematic behavior.”

Dr. LaBotz added that she was not surprised by the study findings, and emphasized that pediatric health care providers should be aware of the association between PES and alcohol use. “PES screening should be incorporated into screening done for alcohol and other substance use. This appears to be particularly true for athletes and other subpopulations who are at higher risk for problematic alcohol use.”

She said much of PES use is driven by the desire by young men for a muscular appearance, but more research is needed on young women. “In the past, this was a goal primarily associated with males, but females have become increasingly interested in achieving muscularity as well, which suggests an increasing risk of PES use among females as compared to earlier reports. We need updated data on patterns, prevalence and consequences of PES use in females.”

In addition, “although preparticipation physical examination forms include screening questions for PES use among athletes, further information is needed on how to incorporate PES into substance use screening that is performed in a general pediatric population, such as including athletes and nonathletes,” Dr. LaBotz said.

The study was supported by the National Institutes of Health and by grants to one of the coauthors from the Pediatric Scientist Development Program funded by the American Academy of Pediatrics and the American Pediatric Society, as well as the American Heart Association Career Development Award. The researchers had no financial conflicts to disclose. Dr. Cuff and Dr. LaBotz had no financial conflicts to disclose.

SOURCE: Ganson KT et al. Pediatrics. 2020 Sep. doi: 10.1542/peds.2020-0409.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how oe who would implement that in practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Consistent and strongly positive findings from more observationsal studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the surrent study don't warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to unmeasured confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

This story was updated on 11/24/2020.

Help your patients understand the risks and benefits of long-term PPI use by sharing the AGA Clinical Practice Update patient companion at http://ow.ly/N1 

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how oe who would implement that in practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Consistent and strongly positive findings from more observationsal studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the surrent study don't warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to unmeasured confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

This story was updated on 11/24/2020.

Help your patients understand the risks and benefits of long-term PPI use by sharing the AGA Clinical Practice Update patient companion at http://ow.ly/N1 

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how oe who would implement that in practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Consistent and strongly positive findings from more observationsal studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the surrent study don't warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to unmeasured confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

This story was updated on 11/24/2020.

Help your patients understand the risks and benefits of long-term PPI use by sharing the AGA Clinical Practice Update patient companion at http://ow.ly/N1 

Neurofilament light chain (NfL), a biomarker previously measured in blood or cerebrospinal fluid and used to indicate neurodegeneration, is detectable in the vitreous humor of the eye, opening the door to a potential new method of predicting neurodegenerative disease, new research suggests.

In a study of 77 patients undergoing eye surgery for various conditions, more than 70% had more than 20 pg/mL of NfL in their vitreous humor. Higher levels of NfL were associated with higher levels of other biomarkers known to be associated with Alzheimer’s disease, including amyloid-beta and tau proteins.

“The study had three primary findings,” said lead author Manju L. Subramanian, MD, associate professor of ophthalmology at Boston University.

First, the investigators were able to detect levels of NfL in eye fluid; and second, those levels were not in any way correlated to the patient’s clinical eye condition, Dr. Subramanian said. “The third finding was that we were able to correlate those neurofilament light levels with other markers that have been known to be associated with conditions such as Alzheimer’s disease,” she noted.

For Dr. Subramanian, these findings add to the hypothesis that the eye is an extension of the brain. “This is further evidence that the eye might potentially be a proxy for neurodegenerative diseases,” she said. “So finding neurofilament light chain in the eye demonstrates that the eye is not an isolated organ, and things that happen in the body can affect the eye and vice versa.”

The findings were published online Sept. 17 in Alzheimer’s Research & Therapy.
 

Verge of clinical applicability?

Early diagnosis of neurodegenerative diseases remains a challenge, the investigators noted. As such, there is a palpable need for reliable biomarkers that can help with early diagnosis, prognostic assessment, and measurable response to treatment for Alzheimer’s disease and other neurologic disorders

Recent research has identified NfL as a potential screening tool and some researchers believe it to be on the verge of clinical applicability. In addition, increased levels of the biomarker have been observed in both the cerebrospinal fluid (CSF) and blood of individuals with neurodegeneration and neurological diseases, including Alzheimer’s disease. In previous studies, for example, elevated levels of NfL in CSF and blood have been shown to reliably distinguish between patients with Alzheimer’s disease and healthy volunteers.

Because certain eye diseases have been associated with Alzheimer’s disease in epidemiological studies, they may share common risk factors and pathological mechanisms at the molecular level, the researchers noted. In an earlier study, the current investigators found that cognitive function among patients with eye disease was significantly associated with amyloid-beta and total tau protein levels in the vitreous humor.

Given these connections, the researchers hypothesized that NfL could be identified in the vitreous humor and may be associated with other relevant biomarkers of neuronal origin. “Neurofilament light chain is detectable in the cerebrospinal fluid, but it’s never been tested for detection in the eye,” Dr. Subramanian noted.

In total, vitreous humor samples were collected from 77 unique participants (mean age, 56.2 years; 63% men) as part of the single-center, prospective, cross-sectional cohort study. The researchers aspirated 0.5 to 1.0 ml of undiluted vitreous fluid during vitrectomy, while whole blood was drawn for APOE genotyping.

Immunoassay was used to quantitatively measure for NfL, amyloid-beta, total tau, phosphorylated tau 181 (p-tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous humor. The trial’s primary outcome measures were the detection of NfL levels in the vitreous humor, as well as its associations with other proteins.


 

Significant correlations

Results showed that 55 of the 77 participants (71.4%) had at least 20 pg/ml of NfL protein present in the vitreous humor. The median level was 68.65 pg/ml. Statistically significant associations were found between NfL levels in the vitreous humor and Abeta40, Abeta42, and total tau; higher NfL levels were associated with higher levels of all three biomarkers. On the other hand, NfL levels were not positively associated with increased vitreous levels of p-tau181.

Vitreous NfL concentration was significantly associated with inflammatory cytokines, including interleukin-15, interleukin-16, and monocyte chemoattractant protein-1, as well as vascular proteins such as vascular endothelial growth factor receptor-1, VEGF-C, vascular cell adhesion molecule-1, Tie-2, and intracellular adhesion molecular-1.

Despite these findings, NfL in the vitreous humor was not associated with patients’ clinical ophthalmic conditions or systemic diseases such as hypertension, diabetes, and hyperlipidemia. Similarly, NfL was not significantly associated with APOE genotype E2 and E4, the alleles most commonly associated with Alzheimer’s disease.

Finally, no statistically significant associations were found between NfL and Mini-Mental State Examination (MMSE) scores.
 

A “first step”

Most research currently examining the role of the eye in neurodegenerative disease is focused on retinal biomarkers imaged by optical coherence tomography, the investigators noted. Although promising, data obtained this way have yielded conflicting results.

Similarly, while the diagnostic potential of the core CSF biomarkers for AD (Abeta40, Abeta42, p-tau, and total tau) is well established, the practical utility of testing CSF for neurodegenerative diseases is limited, wrote the researchers.

As such, an additional biomarker source such as NfL–which is quantifiable and protein-based within eye fluid – has the potential to play an important role in predicting neurodegenerative disease in the clinical setting, they added.

“The holy grail of neurodegenerative-disease diagnosis is early diagnosis. Because if you can implement treatment early, you can slow down and potentially halt the progression of these diseases,” Dr. Subramanian said.

“This study is the first step toward determining if the eye could play a potential role in early diagnosis of conditions such as Alzheimer’s disease,” she added.

That said, Dr. Subramanian was quick to recognize the findings’ preliminary nature and that they do not offer reliable evidence that vitreous NfL levels definitively represent neurodegeneration. As such, the investigators called for more research to validate the association between this type of biomarker with other established biomarkers of neurodegeneration, such as those found in CSF fluid or on MRI and PET scans.

“At this point, we can’t look at eye fluid and say that people have neurodegenerative diseases,” she noted. “The other thing to consider is that vitreous humor is at the back of the eye, so it’s actually a fairly invasive procedure.

“I think the next step is to look at other types of eye fluids such as the aqueous fluid in the front of the eye, or even tear secretions, potentially,” Dr. Subramanian said.

Other study limitations include the lack of an association between NfL levels and MMSE scores and that none of the study participants were actually diagnosed with Alzheimer’s disease. Validation studies are needed to compare vitreous levels of NfL in patients with mild cognitive impairment/AD to normal controls, the investigators noted.
 

Fascinating but impractical?

Commenting on the findings, Sharon Fekrat, MD, professor of ophthalmology, Duke University, Durham, N.C., agreed that there’s potential importance of the eye in diagnosing neurodegeneration. However, she suggested that vitreous humor may not be the most expedient medium to use.

“I commend the authors for this fascinating work. But practically speaking, if we ultimately want to use intraocular fluid to diagnose Alzheimer’s and perhaps other neurodegeneration, I think aqueous humor might be more practical than the vitreous humor,” said Dr. Fekrat, who was not involved with the research. “What might be even better is to have a device that can be held against the eyeball that measures the levels of various substances inside the eyeball without having to enter the eye,” added Justin Ma, a Duke University medical student working under Dr. Fekrat’s guidance. “It could be similar technology to what’s currently used to measure blood glucose levels,” Mr. Ma added.

The study was supported in part by the National Institute of Aging. Dr. Subramanian, Dr. Fekrat, and Mr. Ma have disclosed no relevant financial relationships. Disclosures for other study authors are listed in the original article.

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

Neurofilament light chain (NfL), a biomarker previously measured in blood or cerebrospinal fluid and used to indicate neurodegeneration, is detectable in the vitreous humor of the eye, opening the door to a potential new method of predicting neurodegenerative disease, new research suggests.

In a study of 77 patients undergoing eye surgery for various conditions, more than 70% had more than 20 pg/mL of NfL in their vitreous humor. Higher levels of NfL were associated with higher levels of other biomarkers known to be associated with Alzheimer’s disease, including amyloid-beta and tau proteins.

“The study had three primary findings,” said lead author Manju L. Subramanian, MD, associate professor of ophthalmology at Boston University.

First, the investigators were able to detect levels of NfL in eye fluid; and second, those levels were not in any way correlated to the patient’s clinical eye condition, Dr. Subramanian said. “The third finding was that we were able to correlate those neurofilament light levels with other markers that have been known to be associated with conditions such as Alzheimer’s disease,” she noted.

For Dr. Subramanian, these findings add to the hypothesis that the eye is an extension of the brain. “This is further evidence that the eye might potentially be a proxy for neurodegenerative diseases,” she said. “So finding neurofilament light chain in the eye demonstrates that the eye is not an isolated organ, and things that happen in the body can affect the eye and vice versa.”

The findings were published online Sept. 17 in Alzheimer’s Research & Therapy.
 

Verge of clinical applicability?

Early diagnosis of neurodegenerative diseases remains a challenge, the investigators noted. As such, there is a palpable need for reliable biomarkers that can help with early diagnosis, prognostic assessment, and measurable response to treatment for Alzheimer’s disease and other neurologic disorders

Recent research has identified NfL as a potential screening tool and some researchers believe it to be on the verge of clinical applicability. In addition, increased levels of the biomarker have been observed in both the cerebrospinal fluid (CSF) and blood of individuals with neurodegeneration and neurological diseases, including Alzheimer’s disease. In previous studies, for example, elevated levels of NfL in CSF and blood have been shown to reliably distinguish between patients with Alzheimer’s disease and healthy volunteers.

Because certain eye diseases have been associated with Alzheimer’s disease in epidemiological studies, they may share common risk factors and pathological mechanisms at the molecular level, the researchers noted. In an earlier study, the current investigators found that cognitive function among patients with eye disease was significantly associated with amyloid-beta and total tau protein levels in the vitreous humor.

Given these connections, the researchers hypothesized that NfL could be identified in the vitreous humor and may be associated with other relevant biomarkers of neuronal origin. “Neurofilament light chain is detectable in the cerebrospinal fluid, but it’s never been tested for detection in the eye,” Dr. Subramanian noted.

In total, vitreous humor samples were collected from 77 unique participants (mean age, 56.2 years; 63% men) as part of the single-center, prospective, cross-sectional cohort study. The researchers aspirated 0.5 to 1.0 ml of undiluted vitreous fluid during vitrectomy, while whole blood was drawn for APOE genotyping.

Immunoassay was used to quantitatively measure for NfL, amyloid-beta, total tau, phosphorylated tau 181 (p-tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous humor. The trial’s primary outcome measures were the detection of NfL levels in the vitreous humor, as well as its associations with other proteins.


 

Significant correlations

Results showed that 55 of the 77 participants (71.4%) had at least 20 pg/ml of NfL protein present in the vitreous humor. The median level was 68.65 pg/ml. Statistically significant associations were found between NfL levels in the vitreous humor and Abeta40, Abeta42, and total tau; higher NfL levels were associated with higher levels of all three biomarkers. On the other hand, NfL levels were not positively associated with increased vitreous levels of p-tau181.

Vitreous NfL concentration was significantly associated with inflammatory cytokines, including interleukin-15, interleukin-16, and monocyte chemoattractant protein-1, as well as vascular proteins such as vascular endothelial growth factor receptor-1, VEGF-C, vascular cell adhesion molecule-1, Tie-2, and intracellular adhesion molecular-1.

Despite these findings, NfL in the vitreous humor was not associated with patients’ clinical ophthalmic conditions or systemic diseases such as hypertension, diabetes, and hyperlipidemia. Similarly, NfL was not significantly associated with APOE genotype E2 and E4, the alleles most commonly associated with Alzheimer’s disease.

Finally, no statistically significant associations were found between NfL and Mini-Mental State Examination (MMSE) scores.
 

A “first step”

Most research currently examining the role of the eye in neurodegenerative disease is focused on retinal biomarkers imaged by optical coherence tomography, the investigators noted. Although promising, data obtained this way have yielded conflicting results.

Similarly, while the diagnostic potential of the core CSF biomarkers for AD (Abeta40, Abeta42, p-tau, and total tau) is well established, the practical utility of testing CSF for neurodegenerative diseases is limited, wrote the researchers.

As such, an additional biomarker source such as NfL–which is quantifiable and protein-based within eye fluid – has the potential to play an important role in predicting neurodegenerative disease in the clinical setting, they added.

“The holy grail of neurodegenerative-disease diagnosis is early diagnosis. Because if you can implement treatment early, you can slow down and potentially halt the progression of these diseases,” Dr. Subramanian said.

“This study is the first step toward determining if the eye could play a potential role in early diagnosis of conditions such as Alzheimer’s disease,” she added.

That said, Dr. Subramanian was quick to recognize the findings’ preliminary nature and that they do not offer reliable evidence that vitreous NfL levels definitively represent neurodegeneration. As such, the investigators called for more research to validate the association between this type of biomarker with other established biomarkers of neurodegeneration, such as those found in CSF fluid or on MRI and PET scans.

“At this point, we can’t look at eye fluid and say that people have neurodegenerative diseases,” she noted. “The other thing to consider is that vitreous humor is at the back of the eye, so it’s actually a fairly invasive procedure.

“I think the next step is to look at other types of eye fluids such as the aqueous fluid in the front of the eye, or even tear secretions, potentially,” Dr. Subramanian said.

Other study limitations include the lack of an association between NfL levels and MMSE scores and that none of the study participants were actually diagnosed with Alzheimer’s disease. Validation studies are needed to compare vitreous levels of NfL in patients with mild cognitive impairment/AD to normal controls, the investigators noted.
 

Fascinating but impractical?

Commenting on the findings, Sharon Fekrat, MD, professor of ophthalmology, Duke University, Durham, N.C., agreed that there’s potential importance of the eye in diagnosing neurodegeneration. However, she suggested that vitreous humor may not be the most expedient medium to use.

“I commend the authors for this fascinating work. But practically speaking, if we ultimately want to use intraocular fluid to diagnose Alzheimer’s and perhaps other neurodegeneration, I think aqueous humor might be more practical than the vitreous humor,” said Dr. Fekrat, who was not involved with the research. “What might be even better is to have a device that can be held against the eyeball that measures the levels of various substances inside the eyeball without having to enter the eye,” added Justin Ma, a Duke University medical student working under Dr. Fekrat’s guidance. “It could be similar technology to what’s currently used to measure blood glucose levels,” Mr. Ma added.

The study was supported in part by the National Institute of Aging. Dr. Subramanian, Dr. Fekrat, and Mr. Ma have disclosed no relevant financial relationships. Disclosures for other study authors are listed in the original article.

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

Neurofilament light chain (NfL), a biomarker previously measured in blood or cerebrospinal fluid and used to indicate neurodegeneration, is detectable in the vitreous humor of the eye, opening the door to a potential new method of predicting neurodegenerative disease, new research suggests.

In a study of 77 patients undergoing eye surgery for various conditions, more than 70% had more than 20 pg/mL of NfL in their vitreous humor. Higher levels of NfL were associated with higher levels of other biomarkers known to be associated with Alzheimer’s disease, including amyloid-beta and tau proteins.

“The study had three primary findings,” said lead author Manju L. Subramanian, MD, associate professor of ophthalmology at Boston University.

First, the investigators were able to detect levels of NfL in eye fluid; and second, those levels were not in any way correlated to the patient’s clinical eye condition, Dr. Subramanian said. “The third finding was that we were able to correlate those neurofilament light levels with other markers that have been known to be associated with conditions such as Alzheimer’s disease,” she noted.

For Dr. Subramanian, these findings add to the hypothesis that the eye is an extension of the brain. “This is further evidence that the eye might potentially be a proxy for neurodegenerative diseases,” she said. “So finding neurofilament light chain in the eye demonstrates that the eye is not an isolated organ, and things that happen in the body can affect the eye and vice versa.”

The findings were published online Sept. 17 in Alzheimer’s Research & Therapy.
 

Verge of clinical applicability?

Early diagnosis of neurodegenerative diseases remains a challenge, the investigators noted. As such, there is a palpable need for reliable biomarkers that can help with early diagnosis, prognostic assessment, and measurable response to treatment for Alzheimer’s disease and other neurologic disorders

Recent research has identified NfL as a potential screening tool and some researchers believe it to be on the verge of clinical applicability. In addition, increased levels of the biomarker have been observed in both the cerebrospinal fluid (CSF) and blood of individuals with neurodegeneration and neurological diseases, including Alzheimer’s disease. In previous studies, for example, elevated levels of NfL in CSF and blood have been shown to reliably distinguish between patients with Alzheimer’s disease and healthy volunteers.

Because certain eye diseases have been associated with Alzheimer’s disease in epidemiological studies, they may share common risk factors and pathological mechanisms at the molecular level, the researchers noted. In an earlier study, the current investigators found that cognitive function among patients with eye disease was significantly associated with amyloid-beta and total tau protein levels in the vitreous humor.

Given these connections, the researchers hypothesized that NfL could be identified in the vitreous humor and may be associated with other relevant biomarkers of neuronal origin. “Neurofilament light chain is detectable in the cerebrospinal fluid, but it’s never been tested for detection in the eye,” Dr. Subramanian noted.

In total, vitreous humor samples were collected from 77 unique participants (mean age, 56.2 years; 63% men) as part of the single-center, prospective, cross-sectional cohort study. The researchers aspirated 0.5 to 1.0 ml of undiluted vitreous fluid during vitrectomy, while whole blood was drawn for APOE genotyping.

Immunoassay was used to quantitatively measure for NfL, amyloid-beta, total tau, phosphorylated tau 181 (p-tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous humor. The trial’s primary outcome measures were the detection of NfL levels in the vitreous humor, as well as its associations with other proteins.


 

Significant correlations

Results showed that 55 of the 77 participants (71.4%) had at least 20 pg/ml of NfL protein present in the vitreous humor. The median level was 68.65 pg/ml. Statistically significant associations were found between NfL levels in the vitreous humor and Abeta40, Abeta42, and total tau; higher NfL levels were associated with higher levels of all three biomarkers. On the other hand, NfL levels were not positively associated with increased vitreous levels of p-tau181.

Vitreous NfL concentration was significantly associated with inflammatory cytokines, including interleukin-15, interleukin-16, and monocyte chemoattractant protein-1, as well as vascular proteins such as vascular endothelial growth factor receptor-1, VEGF-C, vascular cell adhesion molecule-1, Tie-2, and intracellular adhesion molecular-1.

Despite these findings, NfL in the vitreous humor was not associated with patients’ clinical ophthalmic conditions or systemic diseases such as hypertension, diabetes, and hyperlipidemia. Similarly, NfL was not significantly associated with APOE genotype E2 and E4, the alleles most commonly associated with Alzheimer’s disease.

Finally, no statistically significant associations were found between NfL and Mini-Mental State Examination (MMSE) scores.
 

A “first step”

Most research currently examining the role of the eye in neurodegenerative disease is focused on retinal biomarkers imaged by optical coherence tomography, the investigators noted. Although promising, data obtained this way have yielded conflicting results.

Similarly, while the diagnostic potential of the core CSF biomarkers for AD (Abeta40, Abeta42, p-tau, and total tau) is well established, the practical utility of testing CSF for neurodegenerative diseases is limited, wrote the researchers.

As such, an additional biomarker source such as NfL–which is quantifiable and protein-based within eye fluid – has the potential to play an important role in predicting neurodegenerative disease in the clinical setting, they added.

“The holy grail of neurodegenerative-disease diagnosis is early diagnosis. Because if you can implement treatment early, you can slow down and potentially halt the progression of these diseases,” Dr. Subramanian said.

“This study is the first step toward determining if the eye could play a potential role in early diagnosis of conditions such as Alzheimer’s disease,” she added.

That said, Dr. Subramanian was quick to recognize the findings’ preliminary nature and that they do not offer reliable evidence that vitreous NfL levels definitively represent neurodegeneration. As such, the investigators called for more research to validate the association between this type of biomarker with other established biomarkers of neurodegeneration, such as those found in CSF fluid or on MRI and PET scans.

“At this point, we can’t look at eye fluid and say that people have neurodegenerative diseases,” she noted. “The other thing to consider is that vitreous humor is at the back of the eye, so it’s actually a fairly invasive procedure.

“I think the next step is to look at other types of eye fluids such as the aqueous fluid in the front of the eye, or even tear secretions, potentially,” Dr. Subramanian said.

Other study limitations include the lack of an association between NfL levels and MMSE scores and that none of the study participants were actually diagnosed with Alzheimer’s disease. Validation studies are needed to compare vitreous levels of NfL in patients with mild cognitive impairment/AD to normal controls, the investigators noted.
 

Fascinating but impractical?

Commenting on the findings, Sharon Fekrat, MD, professor of ophthalmology, Duke University, Durham, N.C., agreed that there’s potential importance of the eye in diagnosing neurodegeneration. However, she suggested that vitreous humor may not be the most expedient medium to use.

“I commend the authors for this fascinating work. But practically speaking, if we ultimately want to use intraocular fluid to diagnose Alzheimer’s and perhaps other neurodegeneration, I think aqueous humor might be more practical than the vitreous humor,” said Dr. Fekrat, who was not involved with the research. “What might be even better is to have a device that can be held against the eyeball that measures the levels of various substances inside the eyeball without having to enter the eye,” added Justin Ma, a Duke University medical student working under Dr. Fekrat’s guidance. “It could be similar technology to what’s currently used to measure blood glucose levels,” Mr. Ma added.

The study was supported in part by the National Institute of Aging. Dr. Subramanian, Dr. Fekrat, and Mr. Ma have disclosed no relevant financial relationships. Disclosures for other study authors are listed in the original article.

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

Whether physicians or advanced practice practitioners, we are the backbone of our nation’s network of acute care facilities, and on a daily basis, we see just about everything. We have valuable insight into how to improve our nation’s health care system, especially now, as our nation continues to battle COVID-19.

Our role, squarely on the front lines during this pandemic, has given us an important perspective that needs to be heard. We spend our days managing patients with complexity, coordinating with specialists and subspecialists, and advocating – at local, state, and national levels – so that our patients can more easily transition to their lives out of the hospital.

Our current polarized political climate makes it seem that individual voices will not make a difference. It is easy to feel frustrated and powerless. However, those in our specialty are actually in a perfect position to have an educated and influential say in how we move forward, not only about the immediate health crises, but also regarding future health care issues. That voice begins with voting.

Historically, physicians have had surprisingly low rates of voting. For example, a 2007 study found significantly lower rates of voting among physicians, compared with the general public.¹ While physician voter turnout may have improved in the past decade, given the substantial changes in health care and the increasing amount of physician engagement in the public sphere, our participation should be greater still. Elected officials listen to, and follow up with, constituents who make their voices heard. Each of us can ensure that the health care policy priorities of our fast-growing specialty are addressed by mobilizing to the voting booth.

Candidates we elect shape our health care system for the future, directly impacting us and our patients. Cost, coverage, access to health care, the Centers for Medicare & Medicaid Services inpatient fee schedules, the ongoing pandemic response, surprise billing, use of telehealth, observation status, and the three-midnight rule are just a few of the issues most important to hospital medicine.

Therefore, we, the SHM Public Policy Committee, urge all of our colleagues, regardless of political sway, to make your voice heard this and every election henceforth. The first step is to register to vote, if you have not done so already.² Next, exercise that privilege. Given the pandemic, this is not as simple a process as it has been in the past. Take the time to plan your approach to early voting, mail-in voting, or election day voting. Check your County Supervisor of Elections’ website for further information, including how to register, view candidate profiles, check your precinct, and request a mail-in ballot.

In addition to casting your vote, we encourage you to share your opinions and engage in dialogue about health care issues. Clinical fact can dispel rumor and misinformation, and daily experiences can personalize our patients’ health care stories and the impact laws and rules have on our ability to practice. We are part of a trusted profession and have a unique perspective; others need and want to hear it. They can only do that if we are part of the process. Arming yourself with information and voting are the first steps on the path of advocacy. Interpersonal advocacy can also be done on social media. For example, SHM has an active grassroots advocacy network on Twitter. Tag @SHMadvocacy in your tweets to share your thoughts with their network.

Finally, as advocates for our patients in health care, we can also help ensure their safety during this election, in particular regarding COVID-19. Some patients may not wish to engage us in politics, and we must respect their decision. Others may seek our counsel and we should provide it in an unbiased fashion. We can ask our patients if they have considered a safe voting plan, help patients review the alternatives to voting in person if desired, and inform those who wish to physically cast a vote on Election Day of how to mitigate the risk of in-person voting.

Every election is important and health care is front and center for a multitude of reasons. We who practice hospital medicine are integral to our communities and need to be more politically involved. This is our chance to share our voice through our vote, not just this year, but in future elections as well.

Ann Sheehy, MD, SFHM, is division chief of the Division of Hospital Medicine at the University of Wisconsin, Madison, and chair of the SHM Public Policy Committee. Other members of the SHM PPC include Marta Almli, MD; John Biebelhausen, MD; Robert Burke, MD, MS, FHM; George Cheely, MD; Hyung (Harry) Cho, MD, SFHM; Jennifer Cowart, MD, FHM; Suparna Dutta, MD, MS, MPH; Bradley Flansbaum, DO, MPH, MHM; Alain Folefack, MD; Rick Hilger MD SFHM; Melinda Johnson, MD; Sevan Karadolian, MD; Joshua D. Lenchus, DO, FACP, SFHM; Steve Phillipson, MD; Dahlia Rizk, DO; Kendall Rogers, MD, SFHM; Brett Stauffer, MD, MHS; Amit Vashist, MD, SFHM; Robert Zipper, MD, SFHM.

References

1. Grande D et al. Do doctors vote? J Gen Int Med. 2007 May;22(5):585-9.

2. How to register to vote, confirm or change your registration and get a voter registration card. https://www.usa.gov/voter-registration/.

Whether physicians or advanced practice practitioners, we are the backbone of our nation’s network of acute care facilities, and on a daily basis, we see just about everything. We have valuable insight into how to improve our nation’s health care system, especially now, as our nation continues to battle COVID-19.

Our role, squarely on the front lines during this pandemic, has given us an important perspective that needs to be heard. We spend our days managing patients with complexity, coordinating with specialists and subspecialists, and advocating – at local, state, and national levels – so that our patients can more easily transition to their lives out of the hospital.

Our current polarized political climate makes it seem that individual voices will not make a difference. It is easy to feel frustrated and powerless. However, those in our specialty are actually in a perfect position to have an educated and influential say in how we move forward, not only about the immediate health crises, but also regarding future health care issues. That voice begins with voting.

Historically, physicians have had surprisingly low rates of voting. For example, a 2007 study found significantly lower rates of voting among physicians, compared with the general public.¹ While physician voter turnout may have improved in the past decade, given the substantial changes in health care and the increasing amount of physician engagement in the public sphere, our participation should be greater still. Elected officials listen to, and follow up with, constituents who make their voices heard. Each of us can ensure that the health care policy priorities of our fast-growing specialty are addressed by mobilizing to the voting booth.

Candidates we elect shape our health care system for the future, directly impacting us and our patients. Cost, coverage, access to health care, the Centers for Medicare & Medicaid Services inpatient fee schedules, the ongoing pandemic response, surprise billing, use of telehealth, observation status, and the three-midnight rule are just a few of the issues most important to hospital medicine.

Therefore, we, the SHM Public Policy Committee, urge all of our colleagues, regardless of political sway, to make your voice heard this and every election henceforth. The first step is to register to vote, if you have not done so already.² Next, exercise that privilege. Given the pandemic, this is not as simple a process as it has been in the past. Take the time to plan your approach to early voting, mail-in voting, or election day voting. Check your County Supervisor of Elections’ website for further information, including how to register, view candidate profiles, check your precinct, and request a mail-in ballot.

In addition to casting your vote, we encourage you to share your opinions and engage in dialogue about health care issues. Clinical fact can dispel rumor and misinformation, and daily experiences can personalize our patients’ health care stories and the impact laws and rules have on our ability to practice. We are part of a trusted profession and have a unique perspective; others need and want to hear it. They can only do that if we are part of the process. Arming yourself with information and voting are the first steps on the path of advocacy. Interpersonal advocacy can also be done on social media. For example, SHM has an active grassroots advocacy network on Twitter. Tag @SHMadvocacy in your tweets to share your thoughts with their network.

Finally, as advocates for our patients in health care, we can also help ensure their safety during this election, in particular regarding COVID-19. Some patients may not wish to engage us in politics, and we must respect their decision. Others may seek our counsel and we should provide it in an unbiased fashion. We can ask our patients if they have considered a safe voting plan, help patients review the alternatives to voting in person if desired, and inform those who wish to physically cast a vote on Election Day of how to mitigate the risk of in-person voting.

Every election is important and health care is front and center for a multitude of reasons. We who practice hospital medicine are integral to our communities and need to be more politically involved. This is our chance to share our voice through our vote, not just this year, but in future elections as well.

Ann Sheehy, MD, SFHM, is division chief of the Division of Hospital Medicine at the University of Wisconsin, Madison, and chair of the SHM Public Policy Committee. Other members of the SHM PPC include Marta Almli, MD; John Biebelhausen, MD; Robert Burke, MD, MS, FHM; George Cheely, MD; Hyung (Harry) Cho, MD, SFHM; Jennifer Cowart, MD, FHM; Suparna Dutta, MD, MS, MPH; Bradley Flansbaum, DO, MPH, MHM; Alain Folefack, MD; Rick Hilger MD SFHM; Melinda Johnson, MD; Sevan Karadolian, MD; Joshua D. Lenchus, DO, FACP, SFHM; Steve Phillipson, MD; Dahlia Rizk, DO; Kendall Rogers, MD, SFHM; Brett Stauffer, MD, MHS; Amit Vashist, MD, SFHM; Robert Zipper, MD, SFHM.

References

1. Grande D et al. Do doctors vote? J Gen Int Med. 2007 May;22(5):585-9.

2. How to register to vote, confirm or change your registration and get a voter registration card. https://www.usa.gov/voter-registration/.

Whether physicians or advanced practice practitioners, we are the backbone of our nation’s network of acute care facilities, and on a daily basis, we see just about everything. We have valuable insight into how to improve our nation’s health care system, especially now, as our nation continues to battle COVID-19.

Our role, squarely on the front lines during this pandemic, has given us an important perspective that needs to be heard. We spend our days managing patients with complexity, coordinating with specialists and subspecialists, and advocating – at local, state, and national levels – so that our patients can more easily transition to their lives out of the hospital.

Our current polarized political climate makes it seem that individual voices will not make a difference. It is easy to feel frustrated and powerless. However, those in our specialty are actually in a perfect position to have an educated and influential say in how we move forward, not only about the immediate health crises, but also regarding future health care issues. That voice begins with voting.

Historically, physicians have had surprisingly low rates of voting. For example, a 2007 study found significantly lower rates of voting among physicians, compared with the general public.¹ While physician voter turnout may have improved in the past decade, given the substantial changes in health care and the increasing amount of physician engagement in the public sphere, our participation should be greater still. Elected officials listen to, and follow up with, constituents who make their voices heard. Each of us can ensure that the health care policy priorities of our fast-growing specialty are addressed by mobilizing to the voting booth.

Candidates we elect shape our health care system for the future, directly impacting us and our patients. Cost, coverage, access to health care, the Centers for Medicare & Medicaid Services inpatient fee schedules, the ongoing pandemic response, surprise billing, use of telehealth, observation status, and the three-midnight rule are just a few of the issues most important to hospital medicine.

Therefore, we, the SHM Public Policy Committee, urge all of our colleagues, regardless of political sway, to make your voice heard this and every election henceforth. The first step is to register to vote, if you have not done so already.² Next, exercise that privilege. Given the pandemic, this is not as simple a process as it has been in the past. Take the time to plan your approach to early voting, mail-in voting, or election day voting. Check your County Supervisor of Elections’ website for further information, including how to register, view candidate profiles, check your precinct, and request a mail-in ballot.

In addition to casting your vote, we encourage you to share your opinions and engage in dialogue about health care issues. Clinical fact can dispel rumor and misinformation, and daily experiences can personalize our patients’ health care stories and the impact laws and rules have on our ability to practice. We are part of a trusted profession and have a unique perspective; others need and want to hear it. They can only do that if we are part of the process. Arming yourself with information and voting are the first steps on the path of advocacy. Interpersonal advocacy can also be done on social media. For example, SHM has an active grassroots advocacy network on Twitter. Tag @SHMadvocacy in your tweets to share your thoughts with their network.

Finally, as advocates for our patients in health care, we can also help ensure their safety during this election, in particular regarding COVID-19. Some patients may not wish to engage us in politics, and we must respect their decision. Others may seek our counsel and we should provide it in an unbiased fashion. We can ask our patients if they have considered a safe voting plan, help patients review the alternatives to voting in person if desired, and inform those who wish to physically cast a vote on Election Day of how to mitigate the risk of in-person voting.

Every election is important and health care is front and center for a multitude of reasons. We who practice hospital medicine are integral to our communities and need to be more politically involved. This is our chance to share our voice through our vote, not just this year, but in future elections as well.

Ann Sheehy, MD, SFHM, is division chief of the Division of Hospital Medicine at the University of Wisconsin, Madison, and chair of the SHM Public Policy Committee. Other members of the SHM PPC include Marta Almli, MD; John Biebelhausen, MD; Robert Burke, MD, MS, FHM; George Cheely, MD; Hyung (Harry) Cho, MD, SFHM; Jennifer Cowart, MD, FHM; Suparna Dutta, MD, MS, MPH; Bradley Flansbaum, DO, MPH, MHM; Alain Folefack, MD; Rick Hilger MD SFHM; Melinda Johnson, MD; Sevan Karadolian, MD; Joshua D. Lenchus, DO, FACP, SFHM; Steve Phillipson, MD; Dahlia Rizk, DO; Kendall Rogers, MD, SFHM; Brett Stauffer, MD, MHS; Amit Vashist, MD, SFHM; Robert Zipper, MD, SFHM.

References

1. Grande D et al. Do doctors vote? J Gen Int Med. 2007 May;22(5):585-9.

2. How to register to vote, confirm or change your registration and get a voter registration card. https://www.usa.gov/voter-registration/.

Microdosing with lysergic acid diethylamide (LSD) is associated with improved mood and increased attention, early research suggests. However, at least one expert believes it’s far too soon to tell and warns against endorsing patient microdosing.

In a dose-finding exploratory study, three low doses of LSD were compared with placebo in healthy volunteers who were all recreational drug users. Adjusted results showed that the highest dose boosted attention and mood, although participants were aware of psychedelic effects, prompting researchers to conclude the results demonstrated “selective, beneficial effects.”

“The majority of participants have improved attention,” study investigator Nadia Hutten, PhD, Department of Neuropsychology and Psychopharmacology, Maastricht University, the Netherlands, told Medscape Medical News.

“So we think that patients with attention deficits might have more beneficial effects,” she added, noting her team plans to study LSD microdosing in patients with attention deficit hyperactivity disorder.

The study was presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Growing interest

Over the past 10 years there has been growing interest in psychedelic microdosing, which is defined as a dose that aims to enhance mood and/or performance but does not affect perception.

However, there has been considerable debate over what constitutes a “microdose.” One tenth of a “full” psychedelic dose is typically suggested, but users report a much wider dose range in practice, suggesting potential “individual variation in response to low doses,” the researchers note.

In the current dose-finding study, the researchers explored whether the effects of LSD on cognition and subjective measures differed between individuals.

The study included 24 healthy recreational drug users and compared the acute effects of 5 mcg, 20 mcg, and 20 mcg LSD with placebo on a computer-based psychomotor vigilance task (PVT) that measured attention and on a Digit Symbol Substitution Test (DSST).

Participants also completed the 72-item Profile of Mood States (POMS) questionnaire, a visual analog scale (VAS) on mood, and the 94-item 5-Dimensional Altered States of Consciousness Rating scales (5D-ASC).

Unadjusted results showed that the 20-mcg LSD dose significantly reduced correct substitutions on the DSST vs placebo (P < .05), but had no effect on attentional lapses on the PCT or on positive mood on the POMS.

Correcting the DSST score for the number of total responses revealed no dose effect of LSD. This suggested that participants were no less accurate when under the influence of LSD, even though they encoded fewer digits, the researchers note.

Participants also reported that both the 10-mcg and 20-mcg dose of LSD increased subjective experiences on the VAS and alternated states of consciousness on the 5D-ASC compared with placebo.

After stratifying the results by dose and participant, the effect of LSD differed between individuals. For example, both the 5-mcg and 20-mcg doses were associated with improvement in attention on the PVT (P < .05), but not the 10-mcg dose.

These results also indicated that the 20-mcg dose was associated with a significant increase in the correct number of substitutions on the DSST and with a significant increase in positive mood on the POMS (P < .05 for both outcomes).

The findings suggest that future studies in patient populations with impaired attention are needed, “including biological parameters involved in LSD receptor-binding and metabolism, in order to understand the inter-individual variation in response to LSD,” the investigators note.

In an educational session at the meeting, the study’s lead researcher, Kim Kuypers, PhD, associate professor at Maastricht University, said research shows individuals are already self-medicating with psychedelic microdosing to treat a wide range of mental health problems, and rated it as significantly more effective than conventional therapy at alleviating symptoms and improving quality of life.

Nevertheless, Kuypers noted there have been fewer than 20 published placebo-controlled studies examining psychedelic microdosing in humans – and much of the current evidence is anecdotal.

However, there is some clinical research suggesting that low-dose LSD is associated with improved mood and cognitive performance and that it also has an effect on resting-state amygdala functional connectivity and acutely increases brain-derived neurotrophic factor plasma levels.

Furthermore, said Kuypers, the evidence in healthy volunteers thus far suggests microdosing is “safe.”
 

Jumping ahead of the science?

Commenting on the study for Medscape Medical News, Jeffrey A. Lieberman, MD, professor and chair of psychiatry at Columbia University, New York City, said he “gives the investigators credit for doing such a study” but does not believe anything can be gleaned from the findings.

He said he is also concerned that the resurgence of psychedelic research is not congruent with “the methodologic rigor and scientific thinking that accompanies treatment development in other disease areas.”

Lieberman, who is also psychiatrist-in-chief at the NewYork–Presbyterian Hospital Columbia Medical Center and was not involved with the study, added that some of the research is also being conducted in individuals who are “true believers and not sufficiently dispassionate and objective.”

“If this was just a treatment . . . for some type of skin fungus, no one would pay any attention to it. But because these are such notorious and interesting compounds, they have attracted a lot of peripheral interest to promote and to disseminate; and the risk is that it will be done in the wrong way and there may be consequences,” he said.

Moreover, Lieberman noted that the psychedelic drugs may be used in practice ahead of strong evidence of safety and efficacy. As an example, he pointed to ketamine, a drug that was identified as a treatment for people with depression who had not responded to standard treatments, he noted.

“But before you knew it, there were clinics being opened up all over the place by anesthesiologists or other people that were trying to make a quick buck,” he said.

“That was alarming because they were stretching the criteria for whom the treatment was appropriate; there were no protocols for dosing, for frequency of administration, and there was inadequate psychiatric follow-up,” Lieberman added.
 

Preliminary but promising

He agreed with Kuypers that cases of microdosing with psychedelics are largely anecdotal.

“So in that context, when these investigators tried to put it to a test, which is commendable, the results in no way tell you whether it’s good, bad, or indifferent,” Lieberman said. In fact, the results are “disappointing in terms of suggesting any beneficial effect.”

Lieberman said more and larger studies are needed in order to determine whether LSD microdosing is beneficial. 

In response to Lieberman’s comments, Kuypers told Medscape Medical News that the investigators tried to base their placebo-controlled research on previous anecdotal research.

She emphasized that the “whole field is still in its infancy,” including research on the use of “full” doses of psychedelics.

“I sometimes think that the message is too positive. We should never forget to communicate that not a lot of research has been done.” In addition, she agreed that researchers should “keep a balanced message.”

“All the data to date is preliminary, in my view, but promising,” she stressed, “and the evidence is growing.”

The study received financial support from the Beckley Foundation. The study authors and Lieberman have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Microdosing with lysergic acid diethylamide (LSD) is associated with improved mood and increased attention, early research suggests. However, at least one expert believes it’s far too soon to tell and warns against endorsing patient microdosing.

In a dose-finding exploratory study, three low doses of LSD were compared with placebo in healthy volunteers who were all recreational drug users. Adjusted results showed that the highest dose boosted attention and mood, although participants were aware of psychedelic effects, prompting researchers to conclude the results demonstrated “selective, beneficial effects.”

“The majority of participants have improved attention,” study investigator Nadia Hutten, PhD, Department of Neuropsychology and Psychopharmacology, Maastricht University, the Netherlands, told Medscape Medical News.

“So we think that patients with attention deficits might have more beneficial effects,” she added, noting her team plans to study LSD microdosing in patients with attention deficit hyperactivity disorder.

The study was presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Growing interest

Over the past 10 years there has been growing interest in psychedelic microdosing, which is defined as a dose that aims to enhance mood and/or performance but does not affect perception.

However, there has been considerable debate over what constitutes a “microdose.” One tenth of a “full” psychedelic dose is typically suggested, but users report a much wider dose range in practice, suggesting potential “individual variation in response to low doses,” the researchers note.

In the current dose-finding study, the researchers explored whether the effects of LSD on cognition and subjective measures differed between individuals.

The study included 24 healthy recreational drug users and compared the acute effects of 5 mcg, 20 mcg, and 20 mcg LSD with placebo on a computer-based psychomotor vigilance task (PVT) that measured attention and on a Digit Symbol Substitution Test (DSST).

Participants also completed the 72-item Profile of Mood States (POMS) questionnaire, a visual analog scale (VAS) on mood, and the 94-item 5-Dimensional Altered States of Consciousness Rating scales (5D-ASC).

Unadjusted results showed that the 20-mcg LSD dose significantly reduced correct substitutions on the DSST vs placebo (P < .05), but had no effect on attentional lapses on the PCT or on positive mood on the POMS.

Correcting the DSST score for the number of total responses revealed no dose effect of LSD. This suggested that participants were no less accurate when under the influence of LSD, even though they encoded fewer digits, the researchers note.

Participants also reported that both the 10-mcg and 20-mcg dose of LSD increased subjective experiences on the VAS and alternated states of consciousness on the 5D-ASC compared with placebo.

After stratifying the results by dose and participant, the effect of LSD differed between individuals. For example, both the 5-mcg and 20-mcg doses were associated with improvement in attention on the PVT (P < .05), but not the 10-mcg dose.

These results also indicated that the 20-mcg dose was associated with a significant increase in the correct number of substitutions on the DSST and with a significant increase in positive mood on the POMS (P < .05 for both outcomes).

The findings suggest that future studies in patient populations with impaired attention are needed, “including biological parameters involved in LSD receptor-binding and metabolism, in order to understand the inter-individual variation in response to LSD,” the investigators note.

In an educational session at the meeting, the study’s lead researcher, Kim Kuypers, PhD, associate professor at Maastricht University, said research shows individuals are already self-medicating with psychedelic microdosing to treat a wide range of mental health problems, and rated it as significantly more effective than conventional therapy at alleviating symptoms and improving quality of life.

Nevertheless, Kuypers noted there have been fewer than 20 published placebo-controlled studies examining psychedelic microdosing in humans – and much of the current evidence is anecdotal.

However, there is some clinical research suggesting that low-dose LSD is associated with improved mood and cognitive performance and that it also has an effect on resting-state amygdala functional connectivity and acutely increases brain-derived neurotrophic factor plasma levels.

Furthermore, said Kuypers, the evidence in healthy volunteers thus far suggests microdosing is “safe.”
 

Jumping ahead of the science?

Commenting on the study for Medscape Medical News, Jeffrey A. Lieberman, MD, professor and chair of psychiatry at Columbia University, New York City, said he “gives the investigators credit for doing such a study” but does not believe anything can be gleaned from the findings.

He said he is also concerned that the resurgence of psychedelic research is not congruent with “the methodologic rigor and scientific thinking that accompanies treatment development in other disease areas.”

Lieberman, who is also psychiatrist-in-chief at the NewYork–Presbyterian Hospital Columbia Medical Center and was not involved with the study, added that some of the research is also being conducted in individuals who are “true believers and not sufficiently dispassionate and objective.”

“If this was just a treatment . . . for some type of skin fungus, no one would pay any attention to it. But because these are such notorious and interesting compounds, they have attracted a lot of peripheral interest to promote and to disseminate; and the risk is that it will be done in the wrong way and there may be consequences,” he said.

Moreover, Lieberman noted that the psychedelic drugs may be used in practice ahead of strong evidence of safety and efficacy. As an example, he pointed to ketamine, a drug that was identified as a treatment for people with depression who had not responded to standard treatments, he noted.

“But before you knew it, there were clinics being opened up all over the place by anesthesiologists or other people that were trying to make a quick buck,” he said.

“That was alarming because they were stretching the criteria for whom the treatment was appropriate; there were no protocols for dosing, for frequency of administration, and there was inadequate psychiatric follow-up,” Lieberman added.
 

Preliminary but promising

He agreed with Kuypers that cases of microdosing with psychedelics are largely anecdotal.

“So in that context, when these investigators tried to put it to a test, which is commendable, the results in no way tell you whether it’s good, bad, or indifferent,” Lieberman said. In fact, the results are “disappointing in terms of suggesting any beneficial effect.”

Lieberman said more and larger studies are needed in order to determine whether LSD microdosing is beneficial. 

In response to Lieberman’s comments, Kuypers told Medscape Medical News that the investigators tried to base their placebo-controlled research on previous anecdotal research.

She emphasized that the “whole field is still in its infancy,” including research on the use of “full” doses of psychedelics.

“I sometimes think that the message is too positive. We should never forget to communicate that not a lot of research has been done.” In addition, she agreed that researchers should “keep a balanced message.”

“All the data to date is preliminary, in my view, but promising,” she stressed, “and the evidence is growing.”

The study received financial support from the Beckley Foundation. The study authors and Lieberman have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Microdosing with lysergic acid diethylamide (LSD) is associated with improved mood and increased attention, early research suggests. However, at least one expert believes it’s far too soon to tell and warns against endorsing patient microdosing.

In a dose-finding exploratory study, three low doses of LSD were compared with placebo in healthy volunteers who were all recreational drug users. Adjusted results showed that the highest dose boosted attention and mood, although participants were aware of psychedelic effects, prompting researchers to conclude the results demonstrated “selective, beneficial effects.”

“The majority of participants have improved attention,” study investigator Nadia Hutten, PhD, Department of Neuropsychology and Psychopharmacology, Maastricht University, the Netherlands, told Medscape Medical News.

“So we think that patients with attention deficits might have more beneficial effects,” she added, noting her team plans to study LSD microdosing in patients with attention deficit hyperactivity disorder.

The study was presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Growing interest

Over the past 10 years there has been growing interest in psychedelic microdosing, which is defined as a dose that aims to enhance mood and/or performance but does not affect perception.

However, there has been considerable debate over what constitutes a “microdose.” One tenth of a “full” psychedelic dose is typically suggested, but users report a much wider dose range in practice, suggesting potential “individual variation in response to low doses,” the researchers note.

In the current dose-finding study, the researchers explored whether the effects of LSD on cognition and subjective measures differed between individuals.

The study included 24 healthy recreational drug users and compared the acute effects of 5 mcg, 20 mcg, and 20 mcg LSD with placebo on a computer-based psychomotor vigilance task (PVT) that measured attention and on a Digit Symbol Substitution Test (DSST).

Participants also completed the 72-item Profile of Mood States (POMS) questionnaire, a visual analog scale (VAS) on mood, and the 94-item 5-Dimensional Altered States of Consciousness Rating scales (5D-ASC).

Unadjusted results showed that the 20-mcg LSD dose significantly reduced correct substitutions on the DSST vs placebo (P < .05), but had no effect on attentional lapses on the PCT or on positive mood on the POMS.

Correcting the DSST score for the number of total responses revealed no dose effect of LSD. This suggested that participants were no less accurate when under the influence of LSD, even though they encoded fewer digits, the researchers note.

Participants also reported that both the 10-mcg and 20-mcg dose of LSD increased subjective experiences on the VAS and alternated states of consciousness on the 5D-ASC compared with placebo.

After stratifying the results by dose and participant, the effect of LSD differed between individuals. For example, both the 5-mcg and 20-mcg doses were associated with improvement in attention on the PVT (P < .05), but not the 10-mcg dose.

These results also indicated that the 20-mcg dose was associated with a significant increase in the correct number of substitutions on the DSST and with a significant increase in positive mood on the POMS (P < .05 for both outcomes).

The findings suggest that future studies in patient populations with impaired attention are needed, “including biological parameters involved in LSD receptor-binding and metabolism, in order to understand the inter-individual variation in response to LSD,” the investigators note.

In an educational session at the meeting, the study’s lead researcher, Kim Kuypers, PhD, associate professor at Maastricht University, said research shows individuals are already self-medicating with psychedelic microdosing to treat a wide range of mental health problems, and rated it as significantly more effective than conventional therapy at alleviating symptoms and improving quality of life.

Nevertheless, Kuypers noted there have been fewer than 20 published placebo-controlled studies examining psychedelic microdosing in humans – and much of the current evidence is anecdotal.

However, there is some clinical research suggesting that low-dose LSD is associated with improved mood and cognitive performance and that it also has an effect on resting-state amygdala functional connectivity and acutely increases brain-derived neurotrophic factor plasma levels.

Furthermore, said Kuypers, the evidence in healthy volunteers thus far suggests microdosing is “safe.”
 

Jumping ahead of the science?

Commenting on the study for Medscape Medical News, Jeffrey A. Lieberman, MD, professor and chair of psychiatry at Columbia University, New York City, said he “gives the investigators credit for doing such a study” but does not believe anything can be gleaned from the findings.

He said he is also concerned that the resurgence of psychedelic research is not congruent with “the methodologic rigor and scientific thinking that accompanies treatment development in other disease areas.”

Lieberman, who is also psychiatrist-in-chief at the NewYork–Presbyterian Hospital Columbia Medical Center and was not involved with the study, added that some of the research is also being conducted in individuals who are “true believers and not sufficiently dispassionate and objective.”

“If this was just a treatment . . . for some type of skin fungus, no one would pay any attention to it. But because these are such notorious and interesting compounds, they have attracted a lot of peripheral interest to promote and to disseminate; and the risk is that it will be done in the wrong way and there may be consequences,” he said.

Moreover, Lieberman noted that the psychedelic drugs may be used in practice ahead of strong evidence of safety and efficacy. As an example, he pointed to ketamine, a drug that was identified as a treatment for people with depression who had not responded to standard treatments, he noted.

“But before you knew it, there were clinics being opened up all over the place by anesthesiologists or other people that were trying to make a quick buck,” he said.

“That was alarming because they were stretching the criteria for whom the treatment was appropriate; there were no protocols for dosing, for frequency of administration, and there was inadequate psychiatric follow-up,” Lieberman added.
 

Preliminary but promising

He agreed with Kuypers that cases of microdosing with psychedelics are largely anecdotal.

“So in that context, when these investigators tried to put it to a test, which is commendable, the results in no way tell you whether it’s good, bad, or indifferent,” Lieberman said. In fact, the results are “disappointing in terms of suggesting any beneficial effect.”

Lieberman said more and larger studies are needed in order to determine whether LSD microdosing is beneficial. 

In response to Lieberman’s comments, Kuypers told Medscape Medical News that the investigators tried to base their placebo-controlled research on previous anecdotal research.

She emphasized that the “whole field is still in its infancy,” including research on the use of “full” doses of psychedelics.

“I sometimes think that the message is too positive. We should never forget to communicate that not a lot of research has been done.” In addition, she agreed that researchers should “keep a balanced message.”

“All the data to date is preliminary, in my view, but promising,” she stressed, “and the evidence is growing.”

The study received financial support from the Beckley Foundation. The study authors and Lieberman have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

• Reduce mental illness stigma
• Ready for school? Not many preschoolers with ADHD are
• Suicide screening is key
• Alcohol, opioid misuse tied to risky behaviors
• Identify runaway risk

• Reduce mental illness stigma
• Ready for school? Not many preschoolers with ADHD are
• Suicide screening is key
• Alcohol, opioid misuse tied to risky behaviors
• Identify runaway risk

• Reduce mental illness stigma
• Ready for school? Not many preschoolers with ADHD are
• Suicide screening is key
• Alcohol, opioid misuse tied to risky behaviors
• Identify runaway risk

Remote telemedicine visits were feasible, reasonably reliable, and acceptable to individuals with Parkinson’s disease, a 1-year, phase 3 clinical trial has shown. The trial was an add-on study involving a subset of subjects from the STEADY-PD III trial of isradipine in early Parkinson’s disease.

Although the trial was conducted before SARS-CoV-2 arrived on the scene, the findings have particular relevance for being able to conduct a variety of clinical trials in the face of COVID-19 and the need to limit in-person interactions.

The 40 participants used tablets to complete three remote, video-based assessments during 1 year, with each remote visit planned to be completed within 4 weeks of an in-person visit. It was easy to enroll patients, and they completed about 95% of planned visits, said neurologist Christopher Tarolli, MD, of the University of Rochester (N.Y.).

He presented the study findings at the Movement Disorder Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.

“The visits were clearly feasible, and we were able to do them [84%] within that 4-week time frame around the in-person visit,” he said. “The visits were also reasonably reliable, particularly so for what we call the nonmotor outcomes and the patient-reported outcomes.”
 

In-person versus remote assessment

For the remote visits, participants completed primarily the same battery of tests as the in-person visits. Responses on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) subscales demonstrated “that there was excellent correlation between patient-reported and nonmotor outcome measures and moderate correlation between in-person and remote-performed motor assessments,” Dr. Tarolli said.  

He explained that the study used modified motor assessments (MDS-UPDRS Part III) that excluded testing of rigidity and postural instability, which require hands-on testing by a trained examiner and thus are impossible to do remotely.

Additionally, the somewhat lower correlation on this subscale was probably the result of different investigators conducting in-person versus remote assessments, with a subset of in-person investigators who tended to rate participants more severely driving down the correlation. “I think if these methods were applied in future trials, the in-person and remote investigators would optimally be the same person,” Dr. Tarolli suggested.
 

Room for error?

Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that “the reliability of UPDRS [part] III is where I would want to have, for sure, a little bit more of a deep dive. … possibly the same patient be rated by the same person.”

She also noted that doing remote and in-person assessments within 4 weeks of each other leaves a lot of room for variability. “You could see the same patient in the morning and then do UPDRS in the afternoon, and it can be totally different depending on when you meet the person,” she said.

Only so much testing can be done remotely. Nonetheless, she questioned whether it is really a valid UPDRS if rigidity and postural stability measures are eliminated. “[Is] this now a new modified UPDRS that we’re going to use that is as good as the old UPDRS moving forward, a home version of UPDRS or whatever we’re going to call it?”

Dr. Subramanian mentioned that patients have told her that UPDRS part III does not really measure what is most important to them, such as making pastries for their grandchildren rather than rapidly tapping their fingers.

“That speaks a little bit to the fact that we should have more patient-centered outcomes and things that patients can report. … things that are not going to require necessarily an in-person exam as maybe measures that really can be used moving forward in studies,” she suggested.
 

Patient satisfaction with remote visits

Greater than 90% of the patients were satisfied or very satisfied overall with the remote visits, including the convenience, comfort, and connection (using the devices and Internet connection), with “patients describing enjoying being able to do these visits from the comfort of their own home, not having to travel,” Dr. Tarolli said. Not having to drive in an ‘off’ state “was actually something that some participants identified as a safety benefit from this as well.”

There was also a time benefit to the patients and investigators. The average length of the remote visits was 54.3 minutes each versus 74 minutes of interaction for in-person visits, mainly a result of more efficient hand-offs between the neurologist and the study coordinator during the remote visits, plus being able to pause the remote visit to give a medication dose time to take effect.

For the patient, there was a large amount of time saved when travel time was considered – a total of 190.2 minutes on average for travel and testing for the in-person visits.

About three-quarters (76%) of the study patients said that remote visits would increase their likelihood of participating in future trials. However, that result may be skewed by the fact that these were already people willing to participate in a remote trial, so the generalizability of the result may be affected. Nonetheless, Dr. Tarolli said he thinks that, as technology gets better and older people become more comfortable with it, remote visits within Parkinson’s research studies may become more common.

One caveat he mentioned is that, with remote visits, the neurologist misses a chance to observe a patient’s whole body and construct a global impression of how he or she is moving. On the other hand, remote video gives the investigator the chance to see the living environment of the patient and suggest changes for safety, such as to reduce the risk of falling for a person with unsteadiness of gait living in a crowded house.

“It really allows us to make a more holistic assessment of how our patient is functioning outside the clinic, which I think we’ve traditionally had really no way of doing,” Dr. Tarolli said.

His final suggestion for anyone contemplating conducting studies with remote visits is to develop a team that is comfortable troubleshooting the technological aspects of those visits.

UCLA’s Dr. Subramanian lauded the University of Rochester team for their efforts in moving remote visits forward. “They’re at the cutting edge of these sorts of things,” she said. “So I’m assuming that they’ll come out with more things [for visits] to become better that are going to move this forward, which is exciting.”

Dr. Tarolli has disclosed no relevant financial relationships. Dr. Subramanian has given talks for Acorda Pharmaceuticals and Acadia Pharmaceuticals in the past. The study had only university, government, foundation, and other nonprofit support.

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

Remote telemedicine visits were feasible, reasonably reliable, and acceptable to individuals with Parkinson’s disease, a 1-year, phase 3 clinical trial has shown. The trial was an add-on study involving a subset of subjects from the STEADY-PD III trial of isradipine in early Parkinson’s disease.

Although the trial was conducted before SARS-CoV-2 arrived on the scene, the findings have particular relevance for being able to conduct a variety of clinical trials in the face of COVID-19 and the need to limit in-person interactions.

The 40 participants used tablets to complete three remote, video-based assessments during 1 year, with each remote visit planned to be completed within 4 weeks of an in-person visit. It was easy to enroll patients, and they completed about 95% of planned visits, said neurologist Christopher Tarolli, MD, of the University of Rochester (N.Y.).

He presented the study findings at the Movement Disorder Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.

“The visits were clearly feasible, and we were able to do them [84%] within that 4-week time frame around the in-person visit,” he said. “The visits were also reasonably reliable, particularly so for what we call the nonmotor outcomes and the patient-reported outcomes.”
 

In-person versus remote assessment

For the remote visits, participants completed primarily the same battery of tests as the in-person visits. Responses on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) subscales demonstrated “that there was excellent correlation between patient-reported and nonmotor outcome measures and moderate correlation between in-person and remote-performed motor assessments,” Dr. Tarolli said.  

He explained that the study used modified motor assessments (MDS-UPDRS Part III) that excluded testing of rigidity and postural instability, which require hands-on testing by a trained examiner and thus are impossible to do remotely.

Additionally, the somewhat lower correlation on this subscale was probably the result of different investigators conducting in-person versus remote assessments, with a subset of in-person investigators who tended to rate participants more severely driving down the correlation. “I think if these methods were applied in future trials, the in-person and remote investigators would optimally be the same person,” Dr. Tarolli suggested.
 

Room for error?

Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that “the reliability of UPDRS [part] III is where I would want to have, for sure, a little bit more of a deep dive. … possibly the same patient be rated by the same person.”

She also noted that doing remote and in-person assessments within 4 weeks of each other leaves a lot of room for variability. “You could see the same patient in the morning and then do UPDRS in the afternoon, and it can be totally different depending on when you meet the person,” she said.

Only so much testing can be done remotely. Nonetheless, she questioned whether it is really a valid UPDRS if rigidity and postural stability measures are eliminated. “[Is] this now a new modified UPDRS that we’re going to use that is as good as the old UPDRS moving forward, a home version of UPDRS or whatever we’re going to call it?”

Dr. Subramanian mentioned that patients have told her that UPDRS part III does not really measure what is most important to them, such as making pastries for their grandchildren rather than rapidly tapping their fingers.

“That speaks a little bit to the fact that we should have more patient-centered outcomes and things that patients can report. … things that are not going to require necessarily an in-person exam as maybe measures that really can be used moving forward in studies,” she suggested.
 

Patient satisfaction with remote visits

Greater than 90% of the patients were satisfied or very satisfied overall with the remote visits, including the convenience, comfort, and connection (using the devices and Internet connection), with “patients describing enjoying being able to do these visits from the comfort of their own home, not having to travel,” Dr. Tarolli said. Not having to drive in an ‘off’ state “was actually something that some participants identified as a safety benefit from this as well.”

There was also a time benefit to the patients and investigators. The average length of the remote visits was 54.3 minutes each versus 74 minutes of interaction for in-person visits, mainly a result of more efficient hand-offs between the neurologist and the study coordinator during the remote visits, plus being able to pause the remote visit to give a medication dose time to take effect.

For the patient, there was a large amount of time saved when travel time was considered – a total of 190.2 minutes on average for travel and testing for the in-person visits.

About three-quarters (76%) of the study patients said that remote visits would increase their likelihood of participating in future trials. However, that result may be skewed by the fact that these were already people willing to participate in a remote trial, so the generalizability of the result may be affected. Nonetheless, Dr. Tarolli said he thinks that, as technology gets better and older people become more comfortable with it, remote visits within Parkinson’s research studies may become more common.

One caveat he mentioned is that, with remote visits, the neurologist misses a chance to observe a patient’s whole body and construct a global impression of how he or she is moving. On the other hand, remote video gives the investigator the chance to see the living environment of the patient and suggest changes for safety, such as to reduce the risk of falling for a person with unsteadiness of gait living in a crowded house.

“It really allows us to make a more holistic assessment of how our patient is functioning outside the clinic, which I think we’ve traditionally had really no way of doing,” Dr. Tarolli said.

His final suggestion for anyone contemplating conducting studies with remote visits is to develop a team that is comfortable troubleshooting the technological aspects of those visits.

UCLA’s Dr. Subramanian lauded the University of Rochester team for their efforts in moving remote visits forward. “They’re at the cutting edge of these sorts of things,” she said. “So I’m assuming that they’ll come out with more things [for visits] to become better that are going to move this forward, which is exciting.”

Dr. Tarolli has disclosed no relevant financial relationships. Dr. Subramanian has given talks for Acorda Pharmaceuticals and Acadia Pharmaceuticals in the past. The study had only university, government, foundation, and other nonprofit support.

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

Remote telemedicine visits were feasible, reasonably reliable, and acceptable to individuals with Parkinson’s disease, a 1-year, phase 3 clinical trial has shown. The trial was an add-on study involving a subset of subjects from the STEADY-PD III trial of isradipine in early Parkinson’s disease.

Although the trial was conducted before SARS-CoV-2 arrived on the scene, the findings have particular relevance for being able to conduct a variety of clinical trials in the face of COVID-19 and the need to limit in-person interactions.

The 40 participants used tablets to complete three remote, video-based assessments during 1 year, with each remote visit planned to be completed within 4 weeks of an in-person visit. It was easy to enroll patients, and they completed about 95% of planned visits, said neurologist Christopher Tarolli, MD, of the University of Rochester (N.Y.).

He presented the study findings at the Movement Disorder Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.

“The visits were clearly feasible, and we were able to do them [84%] within that 4-week time frame around the in-person visit,” he said. “The visits were also reasonably reliable, particularly so for what we call the nonmotor outcomes and the patient-reported outcomes.”
 

In-person versus remote assessment

For the remote visits, participants completed primarily the same battery of tests as the in-person visits. Responses on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) subscales demonstrated “that there was excellent correlation between patient-reported and nonmotor outcome measures and moderate correlation between in-person and remote-performed motor assessments,” Dr. Tarolli said.  

He explained that the study used modified motor assessments (MDS-UPDRS Part III) that excluded testing of rigidity and postural instability, which require hands-on testing by a trained examiner and thus are impossible to do remotely.

Additionally, the somewhat lower correlation on this subscale was probably the result of different investigators conducting in-person versus remote assessments, with a subset of in-person investigators who tended to rate participants more severely driving down the correlation. “I think if these methods were applied in future trials, the in-person and remote investigators would optimally be the same person,” Dr. Tarolli suggested.
 

Room for error?

Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that “the reliability of UPDRS [part] III is where I would want to have, for sure, a little bit more of a deep dive. … possibly the same patient be rated by the same person.”

She also noted that doing remote and in-person assessments within 4 weeks of each other leaves a lot of room for variability. “You could see the same patient in the morning and then do UPDRS in the afternoon, and it can be totally different depending on when you meet the person,” she said.

Only so much testing can be done remotely. Nonetheless, she questioned whether it is really a valid UPDRS if rigidity and postural stability measures are eliminated. “[Is] this now a new modified UPDRS that we’re going to use that is as good as the old UPDRS moving forward, a home version of UPDRS or whatever we’re going to call it?”

Dr. Subramanian mentioned that patients have told her that UPDRS part III does not really measure what is most important to them, such as making pastries for their grandchildren rather than rapidly tapping their fingers.

“That speaks a little bit to the fact that we should have more patient-centered outcomes and things that patients can report. … things that are not going to require necessarily an in-person exam as maybe measures that really can be used moving forward in studies,” she suggested.
 

Patient satisfaction with remote visits

Greater than 90% of the patients were satisfied or very satisfied overall with the remote visits, including the convenience, comfort, and connection (using the devices and Internet connection), with “patients describing enjoying being able to do these visits from the comfort of their own home, not having to travel,” Dr. Tarolli said. Not having to drive in an ‘off’ state “was actually something that some participants identified as a safety benefit from this as well.”

There was also a time benefit to the patients and investigators. The average length of the remote visits was 54.3 minutes each versus 74 minutes of interaction for in-person visits, mainly a result of more efficient hand-offs between the neurologist and the study coordinator during the remote visits, plus being able to pause the remote visit to give a medication dose time to take effect.

For the patient, there was a large amount of time saved when travel time was considered – a total of 190.2 minutes on average for travel and testing for the in-person visits.

About three-quarters (76%) of the study patients said that remote visits would increase their likelihood of participating in future trials. However, that result may be skewed by the fact that these were already people willing to participate in a remote trial, so the generalizability of the result may be affected. Nonetheless, Dr. Tarolli said he thinks that, as technology gets better and older people become more comfortable with it, remote visits within Parkinson’s research studies may become more common.

One caveat he mentioned is that, with remote visits, the neurologist misses a chance to observe a patient’s whole body and construct a global impression of how he or she is moving. On the other hand, remote video gives the investigator the chance to see the living environment of the patient and suggest changes for safety, such as to reduce the risk of falling for a person with unsteadiness of gait living in a crowded house.

“It really allows us to make a more holistic assessment of how our patient is functioning outside the clinic, which I think we’ve traditionally had really no way of doing,” Dr. Tarolli said.

His final suggestion for anyone contemplating conducting studies with remote visits is to develop a team that is comfortable troubleshooting the technological aspects of those visits.

UCLA’s Dr. Subramanian lauded the University of Rochester team for their efforts in moving remote visits forward. “They’re at the cutting edge of these sorts of things,” she said. “So I’m assuming that they’ll come out with more things [for visits] to become better that are going to move this forward, which is exciting.”

Dr. Tarolli has disclosed no relevant financial relationships. Dr. Subramanian has given talks for Acorda Pharmaceuticals and Acadia Pharmaceuticals in the past. The study had only university, government, foundation, and other nonprofit support.

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