Journal of Clinical Outcomes Management

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Both patients in contact with primary care physicians and patient contact with these physicians in any form – including in office or over the phone – declined over 2-year periods occurring from 2002 to 2017.

The reasons for this less frequent contact and the ramifications for patients and doctors practicing primary care are unclear, according to various experts. But some offered possible explanations for the changes, with patients’ increased participation in high deductible plans and shortages in primary care physicians (PCPs) being among the most often cited.

The findings, which were published online Jan. 11 in Annals of Family Medicine, were derived from researchers using a repeated cross-sectional study of the 2002-2017 Medical Expenditure Panel Survey to characterize trends in primary care use. This survey, which collected information about medical care utilization from individuals and families, included 243,919 participants who were interviewed five times over 2 years. The authors defined primary care physician contact as “in-person visit or contact with a primary care physician (primarily telephone calls) with a reported specialty of family medicine, general internal medicine, geriatrics, general pediatrics, or general practice physician.” According to the paper, “the proportion of individuals with any primary care physician contact was determined for both the population and by age group using logistic regression models,” and negative binomial regression models were used to determine the number of contacts among people with visits during 2-year periods.

The study authors, Michael E. Johansen, MD, MS, and Joshua D. Niforatos, MD, MTS, said their study suggests that previously reported decreases in primary care contact was caused by fewer contacts per patient “as opposed to an absolute decrease in the number of patients in contact with primary care.”

Harold B. Betton, MD, PhD, who practices family medicine in Little Rock, Ark., questioned this claim.

"The paper draws observational conclusions and I fail to see the merit in the observation without knowing what the respondents were asked and not asked," he added. 

Other primary care physicians suggested patients’ participation in alternative pay models and high-deductible plans have played a factor in the declines.

Courtesy of Ada Stewart, MD

“Most of us have gone from fee-for-service, volume-based care to more value-based care,” Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. The data reflect that trend, “whereas we were rewarded more for the number of people we were seeing, now we are trying to get towards more of the value that we provide,” suggested Dr. Stewart, who also practices family medicine with Cooperative Health in Columbia, S.C.

“Given the rise of high-deductible plans and copays, it is not surprising that younger patients, a generally healthier population, might well decrease their visits to a primary care physician. I would suspect that data for patients over 50 might well be different,” William E. Golden, MD, who is medical director at the Arkansas Department of Health & Human Services, noted in an interview.

Eileen Barrett, MD, MPH, also cited greater participation in high-deductible plans as a possible factor that could be leading some patients to forgo visits, as well as increased financial insecurity, rendering it expensive to have the visit and also to take time from work for the visit.

“I would wonder if some of this is also due to how overloaded most primary care offices are so that instead of stopping accepting new patients or shedding patients, it is just harder for existing patients to be seen,” said Dr. Barrett, who is a general internist and associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque. “Some of this could be from administrative burden – 2 hours per hour of clinic – and consequently reducing clinical time,” continued Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, which is affiliated with Family Practice News.

Other experts pointed to data showing an insufficient supply of PCPs as a potential explanation for the new study’s findings. The Health Resources and Services Organization, for example, reported that 83 million Americans live in primary care “health professional shortage areas,” as of Jan. 24, 2021, on their website.
 

New data

“The rate of any contact with a [PCP] for patients in the population over multiple 2-year periods decreased by 2.5% over the study period (adjusted odds ratio, 0.99 per panel; 95% [confidence interval], 0.98-0.99; P < .001),” wrote Dr. Johansen and Dr. Niforatos. The rate of contact for patients aged 18-39 years (aOR, 0.99 per panel; 95% CI, 0.98-0.99; P < .001) and patients aged 40-64 years (aOR, 0.99 per panel; 95% CI, 0.99-1.00; P = .002), specifically, also fell. These decreased contact rates correspond “to a predicted cumulative 5% absolute decrease for the younger group and a 2% absolute decrease for the older group,” the authors added.

“The number of contacts with a [PCP] decreased among individuals with any contact by 0.5 contacts over 2 years (P < .001). A decrease in the number of [PCP] contacts was observed across all age groups (P < .001 for all), with the largest absolute decrease among individuals with higher contact rates (aged less than 4 years and aged greater than 64 years),” according to the paper.

Outlook for PCPs

Physicians questioned about how concerning these data are for the future of PCPs and their ability to keep their practices running were hesitant to speculate, because of uncertainty about the causes of the study findings.

“A quote from the paper indicates that the respondents were interviewed five times over 2 years; however, without a copy of the questionnaire it is impossible to know what they were asked and not asked,” said Dr. Betton, who also serves on the editorial advisory board of Family Practice News and runs his own private practice. “In addition, it is impossible for the reader to know whether they understood what a primary care physician was to do.

“To draw a conclusion that PCP visits are falling off per patient per provider is only helpful if patients are opting out of the primary care model of practice and opting in for point-of-care [urgent] care,” Dr. Betton added.

Internist Alan Nelson, MD, said he was also undecided about whether the findings of the study are good or bad news for the physician specialty of primary care.

“Similar findings have been reported by the Medicare Payment Advisory Commission. They certainly merit further investigation,” noted Dr. Nelson, who is a member of the editorial advisory board of Internal Medicine News. “Is it because primary care physicians are too busy to see additional patients? Is it because nonphysician practitioners seem to be more caring? Should residency training be modified, and if so, how? In the meantime, I would not be surprised if the trend continues, at least in the short term.”

Ann Greiner, president and CEO of the Primary Care Collaborative, a nonprofit organization that advocates to strengthen primary care and make it more responsive to patient needs and preferences, on the other hand, reacted with a concerned outlook for primary care.

This study and others show that “the U.S. health care system is moving away from a primary care orientation, and that is concerning,” Ms. Greiner said in an interview. “Health systems that are more oriented toward primary care have better population health outcomes, do better on measures of equity across different population groups, and are less costly.”
 

Authors’ take

“Future research is needed to determine whether fewer contacts per patient resulted in clinically meaningful differences in outcomes across disease processes,” wrote Dr. Johansen, who is a family medicine doctor affiliated with OhioHealth Family Medicine Grant in Columbus and with the Heritage College of Osteopathic Medicine at Ohio University, Dublin, and Dr. Niforatos, who is affiliated with the department of emergency medicine at Johns Hopkins University, Baltimore.

The study’s limitations included reliance on self-reported categorization of PCP versus specialty care physician contact, insufficient accounting for nurse practitioner and physician assistant contact, and improved contact reporting having started in 2013, they said.
 

How to grow patient contact

For those PCPs looking to grow their visits and patient contact, Dr. Golden suggested they strengthen their medical home model in their practice.

“Medical home models help and transform practice operations. The Arkansas model is a multipayer model – private, Medicaid and CPC+ (Medicare),” said Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News. It includes community-based doctors, not Federally Qualified Health Centers, and “requires 24/7 live voice access that promotes regular contact with patients and can reduce dependency on ER and urgent care center visits.”

“Greater use of patient portals and email communications facilitate access and patient engagement with their PCP,” Dr. Golden explained.

 “Over the last 6 years, the Arkansas [patient-centered medical home] initiatives have altered culture and made our practice sites stronger to withstand COVID and other challenges. As our sites became more patient centered and incorporated behavioral health options, patients perceived greater value in the functionality of primary care” he said.

Dr. Barrett proposed PCPs participate in team-based care “for professional sustainability and also for patients to continue to experience high-quality, person-centered care.” She added that “telemedicine can also help practices maintain and increase patients, as it can lessen burden on patients and clinicians – if it is done right.”

“More flexible clinic hours is also key – after usual business hours and on weekends – but I would recommend in lieu of usual weekday hours and for those who can make it work with their family and other duties,” Dr. Barrett said. “Evening or Saturday morning clinic isn’t an option for everyone, but it is an option for many some of the time, and it would be great for access to care if it were available in more locations.”
 

Pandemic effect

The data examined by Dr. Johansen and Dr. Niforatos predates the pandemic, but PCPs interviewed by this news organization have seen declining patient contact occur in 2020 as well.

In fact, a survey of 1,485 mostly physician primary care practitioners that began after the pandemic onset found that 43% of participants have fewer in-person visits, motivated largely by patient preferences (66%) and safety concerns (74%). This ongoing survey, which was conducted by the Larry Green Center in partnership with the Primary Care Collaborative, also indicated that, while 25% of participants saw a total increase in patient volume, more than half of primary care practitioners reported that chronic and wellness visits are down, 53% and 55%, respectively.

“Sometimes we have to go looking for our patients when we have not seen them in a while,” Dr. Stewart noted. “We saw that with COVID because people were fearful of coming into our offices, and we had to have some outreach.”

The study authors had no conflicts of interest. Dr. Barrett, Dr. Betton, Dr. Golden, Dr. Nelson, and Dr. Stewart had no relevant disclosures.

Jake Remaly contributed to this article.

[email protected]

Both patients in contact with primary care physicians and patient contact with these physicians in any form – including in office or over the phone – declined over 2-year periods occurring from 2002 to 2017.

The reasons for this less frequent contact and the ramifications for patients and doctors practicing primary care are unclear, according to various experts. But some offered possible explanations for the changes, with patients’ increased participation in high deductible plans and shortages in primary care physicians (PCPs) being among the most often cited.

The findings, which were published online Jan. 11 in Annals of Family Medicine, were derived from researchers using a repeated cross-sectional study of the 2002-2017 Medical Expenditure Panel Survey to characterize trends in primary care use. This survey, which collected information about medical care utilization from individuals and families, included 243,919 participants who were interviewed five times over 2 years. The authors defined primary care physician contact as “in-person visit or contact with a primary care physician (primarily telephone calls) with a reported specialty of family medicine, general internal medicine, geriatrics, general pediatrics, or general practice physician.” According to the paper, “the proportion of individuals with any primary care physician contact was determined for both the population and by age group using logistic regression models,” and negative binomial regression models were used to determine the number of contacts among people with visits during 2-year periods.

The study authors, Michael E. Johansen, MD, MS, and Joshua D. Niforatos, MD, MTS, said their study suggests that previously reported decreases in primary care contact was caused by fewer contacts per patient “as opposed to an absolute decrease in the number of patients in contact with primary care.”

Harold B. Betton, MD, PhD, who practices family medicine in Little Rock, Ark., questioned this claim.

"The paper draws observational conclusions and I fail to see the merit in the observation without knowing what the respondents were asked and not asked," he added. 

Other primary care physicians suggested patients’ participation in alternative pay models and high-deductible plans have played a factor in the declines.

Courtesy of Ada Stewart, MD

“Most of us have gone from fee-for-service, volume-based care to more value-based care,” Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. The data reflect that trend, “whereas we were rewarded more for the number of people we were seeing, now we are trying to get towards more of the value that we provide,” suggested Dr. Stewart, who also practices family medicine with Cooperative Health in Columbia, S.C.

“Given the rise of high-deductible plans and copays, it is not surprising that younger patients, a generally healthier population, might well decrease their visits to a primary care physician. I would suspect that data for patients over 50 might well be different,” William E. Golden, MD, who is medical director at the Arkansas Department of Health & Human Services, noted in an interview.

Eileen Barrett, MD, MPH, also cited greater participation in high-deductible plans as a possible factor that could be leading some patients to forgo visits, as well as increased financial insecurity, rendering it expensive to have the visit and also to take time from work for the visit.

“I would wonder if some of this is also due to how overloaded most primary care offices are so that instead of stopping accepting new patients or shedding patients, it is just harder for existing patients to be seen,” said Dr. Barrett, who is a general internist and associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque. “Some of this could be from administrative burden – 2 hours per hour of clinic – and consequently reducing clinical time,” continued Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, which is affiliated with Family Practice News.

Other experts pointed to data showing an insufficient supply of PCPs as a potential explanation for the new study’s findings. The Health Resources and Services Organization, for example, reported that 83 million Americans live in primary care “health professional shortage areas,” as of Jan. 24, 2021, on their website.
 

New data

“The rate of any contact with a [PCP] for patients in the population over multiple 2-year periods decreased by 2.5% over the study period (adjusted odds ratio, 0.99 per panel; 95% [confidence interval], 0.98-0.99; P < .001),” wrote Dr. Johansen and Dr. Niforatos. The rate of contact for patients aged 18-39 years (aOR, 0.99 per panel; 95% CI, 0.98-0.99; P < .001) and patients aged 40-64 years (aOR, 0.99 per panel; 95% CI, 0.99-1.00; P = .002), specifically, also fell. These decreased contact rates correspond “to a predicted cumulative 5% absolute decrease for the younger group and a 2% absolute decrease for the older group,” the authors added.

“The number of contacts with a [PCP] decreased among individuals with any contact by 0.5 contacts over 2 years (P < .001). A decrease in the number of [PCP] contacts was observed across all age groups (P < .001 for all), with the largest absolute decrease among individuals with higher contact rates (aged less than 4 years and aged greater than 64 years),” according to the paper.

Outlook for PCPs

Physicians questioned about how concerning these data are for the future of PCPs and their ability to keep their practices running were hesitant to speculate, because of uncertainty about the causes of the study findings.

“A quote from the paper indicates that the respondents were interviewed five times over 2 years; however, without a copy of the questionnaire it is impossible to know what they were asked and not asked,” said Dr. Betton, who also serves on the editorial advisory board of Family Practice News and runs his own private practice. “In addition, it is impossible for the reader to know whether they understood what a primary care physician was to do.

“To draw a conclusion that PCP visits are falling off per patient per provider is only helpful if patients are opting out of the primary care model of practice and opting in for point-of-care [urgent] care,” Dr. Betton added.

Internist Alan Nelson, MD, said he was also undecided about whether the findings of the study are good or bad news for the physician specialty of primary care.

“Similar findings have been reported by the Medicare Payment Advisory Commission. They certainly merit further investigation,” noted Dr. Nelson, who is a member of the editorial advisory board of Internal Medicine News. “Is it because primary care physicians are too busy to see additional patients? Is it because nonphysician practitioners seem to be more caring? Should residency training be modified, and if so, how? In the meantime, I would not be surprised if the trend continues, at least in the short term.”

Ann Greiner, president and CEO of the Primary Care Collaborative, a nonprofit organization that advocates to strengthen primary care and make it more responsive to patient needs and preferences, on the other hand, reacted with a concerned outlook for primary care.

This study and others show that “the U.S. health care system is moving away from a primary care orientation, and that is concerning,” Ms. Greiner said in an interview. “Health systems that are more oriented toward primary care have better population health outcomes, do better on measures of equity across different population groups, and are less costly.”
 

Authors’ take

“Future research is needed to determine whether fewer contacts per patient resulted in clinically meaningful differences in outcomes across disease processes,” wrote Dr. Johansen, who is a family medicine doctor affiliated with OhioHealth Family Medicine Grant in Columbus and with the Heritage College of Osteopathic Medicine at Ohio University, Dublin, and Dr. Niforatos, who is affiliated with the department of emergency medicine at Johns Hopkins University, Baltimore.

The study’s limitations included reliance on self-reported categorization of PCP versus specialty care physician contact, insufficient accounting for nurse practitioner and physician assistant contact, and improved contact reporting having started in 2013, they said.
 

How to grow patient contact

For those PCPs looking to grow their visits and patient contact, Dr. Golden suggested they strengthen their medical home model in their practice.

“Medical home models help and transform practice operations. The Arkansas model is a multipayer model – private, Medicaid and CPC+ (Medicare),” said Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News. It includes community-based doctors, not Federally Qualified Health Centers, and “requires 24/7 live voice access that promotes regular contact with patients and can reduce dependency on ER and urgent care center visits.”

“Greater use of patient portals and email communications facilitate access and patient engagement with their PCP,” Dr. Golden explained.

 “Over the last 6 years, the Arkansas [patient-centered medical home] initiatives have altered culture and made our practice sites stronger to withstand COVID and other challenges. As our sites became more patient centered and incorporated behavioral health options, patients perceived greater value in the functionality of primary care” he said.

Dr. Barrett proposed PCPs participate in team-based care “for professional sustainability and also for patients to continue to experience high-quality, person-centered care.” She added that “telemedicine can also help practices maintain and increase patients, as it can lessen burden on patients and clinicians – if it is done right.”

“More flexible clinic hours is also key – after usual business hours and on weekends – but I would recommend in lieu of usual weekday hours and for those who can make it work with their family and other duties,” Dr. Barrett said. “Evening or Saturday morning clinic isn’t an option for everyone, but it is an option for many some of the time, and it would be great for access to care if it were available in more locations.”
 

Pandemic effect

The data examined by Dr. Johansen and Dr. Niforatos predates the pandemic, but PCPs interviewed by this news organization have seen declining patient contact occur in 2020 as well.

In fact, a survey of 1,485 mostly physician primary care practitioners that began after the pandemic onset found that 43% of participants have fewer in-person visits, motivated largely by patient preferences (66%) and safety concerns (74%). This ongoing survey, which was conducted by the Larry Green Center in partnership with the Primary Care Collaborative, also indicated that, while 25% of participants saw a total increase in patient volume, more than half of primary care practitioners reported that chronic and wellness visits are down, 53% and 55%, respectively.

“Sometimes we have to go looking for our patients when we have not seen them in a while,” Dr. Stewart noted. “We saw that with COVID because people were fearful of coming into our offices, and we had to have some outreach.”

The study authors had no conflicts of interest. Dr. Barrett, Dr. Betton, Dr. Golden, Dr. Nelson, and Dr. Stewart had no relevant disclosures.

Jake Remaly contributed to this article.

[email protected]

Both patients in contact with primary care physicians and patient contact with these physicians in any form – including in office or over the phone – declined over 2-year periods occurring from 2002 to 2017.

The reasons for this less frequent contact and the ramifications for patients and doctors practicing primary care are unclear, according to various experts. But some offered possible explanations for the changes, with patients’ increased participation in high deductible plans and shortages in primary care physicians (PCPs) being among the most often cited.

The findings, which were published online Jan. 11 in Annals of Family Medicine, were derived from researchers using a repeated cross-sectional study of the 2002-2017 Medical Expenditure Panel Survey to characterize trends in primary care use. This survey, which collected information about medical care utilization from individuals and families, included 243,919 participants who were interviewed five times over 2 years. The authors defined primary care physician contact as “in-person visit or contact with a primary care physician (primarily telephone calls) with a reported specialty of family medicine, general internal medicine, geriatrics, general pediatrics, or general practice physician.” According to the paper, “the proportion of individuals with any primary care physician contact was determined for both the population and by age group using logistic regression models,” and negative binomial regression models were used to determine the number of contacts among people with visits during 2-year periods.

The study authors, Michael E. Johansen, MD, MS, and Joshua D. Niforatos, MD, MTS, said their study suggests that previously reported decreases in primary care contact was caused by fewer contacts per patient “as opposed to an absolute decrease in the number of patients in contact with primary care.”

Harold B. Betton, MD, PhD, who practices family medicine in Little Rock, Ark., questioned this claim.

"The paper draws observational conclusions and I fail to see the merit in the observation without knowing what the respondents were asked and not asked," he added. 

Other primary care physicians suggested patients’ participation in alternative pay models and high-deductible plans have played a factor in the declines.

Courtesy of Ada Stewart, MD

“Most of us have gone from fee-for-service, volume-based care to more value-based care,” Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. The data reflect that trend, “whereas we were rewarded more for the number of people we were seeing, now we are trying to get towards more of the value that we provide,” suggested Dr. Stewart, who also practices family medicine with Cooperative Health in Columbia, S.C.

“Given the rise of high-deductible plans and copays, it is not surprising that younger patients, a generally healthier population, might well decrease their visits to a primary care physician. I would suspect that data for patients over 50 might well be different,” William E. Golden, MD, who is medical director at the Arkansas Department of Health & Human Services, noted in an interview.

Eileen Barrett, MD, MPH, also cited greater participation in high-deductible plans as a possible factor that could be leading some patients to forgo visits, as well as increased financial insecurity, rendering it expensive to have the visit and also to take time from work for the visit.

“I would wonder if some of this is also due to how overloaded most primary care offices are so that instead of stopping accepting new patients or shedding patients, it is just harder for existing patients to be seen,” said Dr. Barrett, who is a general internist and associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque. “Some of this could be from administrative burden – 2 hours per hour of clinic – and consequently reducing clinical time,” continued Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, which is affiliated with Family Practice News.

Other experts pointed to data showing an insufficient supply of PCPs as a potential explanation for the new study’s findings. The Health Resources and Services Organization, for example, reported that 83 million Americans live in primary care “health professional shortage areas,” as of Jan. 24, 2021, on their website.
 

New data

“The rate of any contact with a [PCP] for patients in the population over multiple 2-year periods decreased by 2.5% over the study period (adjusted odds ratio, 0.99 per panel; 95% [confidence interval], 0.98-0.99; P < .001),” wrote Dr. Johansen and Dr. Niforatos. The rate of contact for patients aged 18-39 years (aOR, 0.99 per panel; 95% CI, 0.98-0.99; P < .001) and patients aged 40-64 years (aOR, 0.99 per panel; 95% CI, 0.99-1.00; P = .002), specifically, also fell. These decreased contact rates correspond “to a predicted cumulative 5% absolute decrease for the younger group and a 2% absolute decrease for the older group,” the authors added.

“The number of contacts with a [PCP] decreased among individuals with any contact by 0.5 contacts over 2 years (P < .001). A decrease in the number of [PCP] contacts was observed across all age groups (P < .001 for all), with the largest absolute decrease among individuals with higher contact rates (aged less than 4 years and aged greater than 64 years),” according to the paper.

Outlook for PCPs

Physicians questioned about how concerning these data are for the future of PCPs and their ability to keep their practices running were hesitant to speculate, because of uncertainty about the causes of the study findings.

“A quote from the paper indicates that the respondents were interviewed five times over 2 years; however, without a copy of the questionnaire it is impossible to know what they were asked and not asked,” said Dr. Betton, who also serves on the editorial advisory board of Family Practice News and runs his own private practice. “In addition, it is impossible for the reader to know whether they understood what a primary care physician was to do.

“To draw a conclusion that PCP visits are falling off per patient per provider is only helpful if patients are opting out of the primary care model of practice and opting in for point-of-care [urgent] care,” Dr. Betton added.

Internist Alan Nelson, MD, said he was also undecided about whether the findings of the study are good or bad news for the physician specialty of primary care.

“Similar findings have been reported by the Medicare Payment Advisory Commission. They certainly merit further investigation,” noted Dr. Nelson, who is a member of the editorial advisory board of Internal Medicine News. “Is it because primary care physicians are too busy to see additional patients? Is it because nonphysician practitioners seem to be more caring? Should residency training be modified, and if so, how? In the meantime, I would not be surprised if the trend continues, at least in the short term.”

Ann Greiner, president and CEO of the Primary Care Collaborative, a nonprofit organization that advocates to strengthen primary care and make it more responsive to patient needs and preferences, on the other hand, reacted with a concerned outlook for primary care.

This study and others show that “the U.S. health care system is moving away from a primary care orientation, and that is concerning,” Ms. Greiner said in an interview. “Health systems that are more oriented toward primary care have better population health outcomes, do better on measures of equity across different population groups, and are less costly.”
 

Authors’ take

“Future research is needed to determine whether fewer contacts per patient resulted in clinically meaningful differences in outcomes across disease processes,” wrote Dr. Johansen, who is a family medicine doctor affiliated with OhioHealth Family Medicine Grant in Columbus and with the Heritage College of Osteopathic Medicine at Ohio University, Dublin, and Dr. Niforatos, who is affiliated with the department of emergency medicine at Johns Hopkins University, Baltimore.

The study’s limitations included reliance on self-reported categorization of PCP versus specialty care physician contact, insufficient accounting for nurse practitioner and physician assistant contact, and improved contact reporting having started in 2013, they said.
 

How to grow patient contact

For those PCPs looking to grow their visits and patient contact, Dr. Golden suggested they strengthen their medical home model in their practice.

“Medical home models help and transform practice operations. The Arkansas model is a multipayer model – private, Medicaid and CPC+ (Medicare),” said Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News. It includes community-based doctors, not Federally Qualified Health Centers, and “requires 24/7 live voice access that promotes regular contact with patients and can reduce dependency on ER and urgent care center visits.”

“Greater use of patient portals and email communications facilitate access and patient engagement with their PCP,” Dr. Golden explained.

 “Over the last 6 years, the Arkansas [patient-centered medical home] initiatives have altered culture and made our practice sites stronger to withstand COVID and other challenges. As our sites became more patient centered and incorporated behavioral health options, patients perceived greater value in the functionality of primary care” he said.

Dr. Barrett proposed PCPs participate in team-based care “for professional sustainability and also for patients to continue to experience high-quality, person-centered care.” She added that “telemedicine can also help practices maintain and increase patients, as it can lessen burden on patients and clinicians – if it is done right.”

“More flexible clinic hours is also key – after usual business hours and on weekends – but I would recommend in lieu of usual weekday hours and for those who can make it work with their family and other duties,” Dr. Barrett said. “Evening or Saturday morning clinic isn’t an option for everyone, but it is an option for many some of the time, and it would be great for access to care if it were available in more locations.”
 

Pandemic effect

The data examined by Dr. Johansen and Dr. Niforatos predates the pandemic, but PCPs interviewed by this news organization have seen declining patient contact occur in 2020 as well.

In fact, a survey of 1,485 mostly physician primary care practitioners that began after the pandemic onset found that 43% of participants have fewer in-person visits, motivated largely by patient preferences (66%) and safety concerns (74%). This ongoing survey, which was conducted by the Larry Green Center in partnership with the Primary Care Collaborative, also indicated that, while 25% of participants saw a total increase in patient volume, more than half of primary care practitioners reported that chronic and wellness visits are down, 53% and 55%, respectively.

“Sometimes we have to go looking for our patients when we have not seen them in a while,” Dr. Stewart noted. “We saw that with COVID because people were fearful of coming into our offices, and we had to have some outreach.”

The study authors had no conflicts of interest. Dr. Barrett, Dr. Betton, Dr. Golden, Dr. Nelson, and Dr. Stewart had no relevant disclosures.

Jake Remaly contributed to this article.

[email protected]

Many patients are receiving inadequate eradication therapy for Helicobacter pylori infection, according to analysis of a European registry.

In their analysis, published in the Journal of Clinical Gastroenterology, Olga P. Nyssen, BSc, PhD, of the Autonomous University of Madrid and colleagues discussed seven errors, which included prescribing a triple instead of quadruple regimen, prescribing therapy for too short of a duration, and prescribing a low dose of proton pump inhibitors (PPIs).

“[E]ven after more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined,” the investigators wrote. The European Registry on Helicobacter pylori management “represents a good mapping overview of the current situation regarding H. pylori management, allowing not only continuous assessment of the integration of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement.”

Patient data were drawn from registry-participating countries that each had more than 1,000 cases of H. pylori available; most came from Spain, followed by Russia, Italy, Slovenia, and Lithuania. Of these patients, data for 26,340 patients were analyzed, which ultimately represented 80% of the total registry from 2013 to 2019.

The first mistake discussed in the paper regarded use of less-effective triple therapies (typically PPI plus two antibiotics); one review showed that these regimens fail in 20%-40% of cases. Increasing antibiotic resistances have only worsened the success rate. According to this study, a triple regimen was given as first-line treatment in 46% of cases. Overall, frequency of triple-therapy prescriptions decreased from more than 50% in 2013 to about 40% in 2019. More significant improvements in this area were achieved in Spain, where use of triple therapies decreased from 24% in 2014 to 0% in 2019. According to the investigators, this finding serves as a “paradigmatic example of improvement with time.”

The authors pointed out that “overwhelming evidence” supports 14-day treatment; however, 69% of triple-therapy durations and 58% of quadruple therapy cases were for 7 or 10 days. Triple therapy at this duration showed only 81% cure rate, while it was 88% with 14 days, and quadruple therapy was only 80% effective at 7-10 days but 90% effective at 14 days.

“Fortunately,” the investigators wrote, “this mistake was progressively found less frequently and, at present, the prescription of 7-day standard triple therapy regimens has almost disappeared.”

The authors noted acid suppression via PPIs improves cure rates: In one meta-analysis, the cure rate of triple therapy regimens increased by 6%-10% with high doses of PPIs. However, the current study found that 48% of triple therapies included low-dose PPIs. This number decreased over time, the authors noted: from 67% in 2013 to 20% in 2019.

“From another perspective, the daily PPI dose has increased from a dose equivalent to 54 mg of omeprazole in 2013 to 104 mg in 2019,” they wrote.

The other four errors they discussed were failing to adequately consider penicillin allergies in prescription choices, failing to consider the importance of treatment compliance, repeating certain antibiotics after failures, and not checking eradication success after treatment.

Based on these findings, Dr. Nyssen and colleagues suggested that “penetration of recommendations in the participating European countries is still poor and delayed, even though some improvements from guidelines have been partially incorporated.”

According to Grigorios I. Leontiadis, MD, PhD, of McMaster University, Hamilton, Ont., who coauthored the 2017 American College of Gastroenterology H. pylori management guidelines and the Canadian Association of Gastroenterology “Toronto Consensus” in 2016, “This study is important and timely given the steadily increasing antibiotic resistance of H. pylori worldwide.”

Although Dr. Leontiadias described the results as “suboptimal,” he was partially reassured by the improvements over time, “especially following publication of the 2016 European clinical practice guidelines.” He also noted that some older clinical practice guidelines issued conditional recommendations, which could “justify the lower adherence seen in the early period of this study.”

“The unanswered question,” Dr. Leontiadias went on, “is whether the practice of gastroenterologists who volunteered to participate in this prospective registry is truly representative of how H. pylori is managed in Europe. Most likely it isn’t. Nonparticipating gastroenterologists and nongastroenterologist health care practitioners are probably less aware of and less adherent to clinical practice guidelines. This means that the actual situation in the real world is probably grimmer than what this study shows.”

William D. Chey, MD, Nostrant Collegiate Professor of Gastroenterology at the University of Michigan, Ann Arbor, considered the results “not entirely surprising, but nonetheless, noteworthy.”

Dr. Chey noted that the United States lacks a similar registry to compare real-world H. pylori management; even so, he suggested several findings that “bear reiteration” for clinicians in the United States.

“U.S. providers should consider regimens other than clarithromycin triple therapy when treating H. pylori infection,” Dr. Chey said. “Since U.S. providers do not have reliable data on H. pylori antimicrobial resistance, it is useful to ask about prior macrolide antibiotic exposure, and if a patient has received a macrolide for any reason, clarithromycin triple therapy should be avoided. Bismuth quadruple therapy remains a reliable first-line treatment option in the U.S. Another recently approved first-line treatment option is the combination of a proton pump inhibitor, rifabutin, and amoxicillin. Treatment regimens in the U.S. should be given for a minimum of 10 days and, preferably, for 14 days. Another point made by the article is that providers should be maximizing gastric acid suppression by using higher doses of proton pump inhibitors when treating H. pylori.”

Dr. Chey also noted an emerging treatment option that could soon be available. “Results from phase 3 trials in North America and Europe with the potassium-competitive acid blocker vonoprazan combined with amoxicillin, with and without clarithromycin, are expected in 2021 and may provide another novel first-line treatment option.”

Dr. Nyssen and colleagues disclosed relationships with Allergan, Mayoly, Janssen, and others. Dr. Chey is a consultant for Redhill, Phathom, and Takeda, which is developing vonoprazan. Dr. Leontiadias disclosed no conflicts of interest.

This article was updated 2/16/21.

Many patients are receiving inadequate eradication therapy for Helicobacter pylori infection, according to analysis of a European registry.

In their analysis, published in the Journal of Clinical Gastroenterology, Olga P. Nyssen, BSc, PhD, of the Autonomous University of Madrid and colleagues discussed seven errors, which included prescribing a triple instead of quadruple regimen, prescribing therapy for too short of a duration, and prescribing a low dose of proton pump inhibitors (PPIs).

“[E]ven after more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined,” the investigators wrote. The European Registry on Helicobacter pylori management “represents a good mapping overview of the current situation regarding H. pylori management, allowing not only continuous assessment of the integration of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement.”

Patient data were drawn from registry-participating countries that each had more than 1,000 cases of H. pylori available; most came from Spain, followed by Russia, Italy, Slovenia, and Lithuania. Of these patients, data for 26,340 patients were analyzed, which ultimately represented 80% of the total registry from 2013 to 2019.

The first mistake discussed in the paper regarded use of less-effective triple therapies (typically PPI plus two antibiotics); one review showed that these regimens fail in 20%-40% of cases. Increasing antibiotic resistances have only worsened the success rate. According to this study, a triple regimen was given as first-line treatment in 46% of cases. Overall, frequency of triple-therapy prescriptions decreased from more than 50% in 2013 to about 40% in 2019. More significant improvements in this area were achieved in Spain, where use of triple therapies decreased from 24% in 2014 to 0% in 2019. According to the investigators, this finding serves as a “paradigmatic example of improvement with time.”

The authors pointed out that “overwhelming evidence” supports 14-day treatment; however, 69% of triple-therapy durations and 58% of quadruple therapy cases were for 7 or 10 days. Triple therapy at this duration showed only 81% cure rate, while it was 88% with 14 days, and quadruple therapy was only 80% effective at 7-10 days but 90% effective at 14 days.

“Fortunately,” the investigators wrote, “this mistake was progressively found less frequently and, at present, the prescription of 7-day standard triple therapy regimens has almost disappeared.”

The authors noted acid suppression via PPIs improves cure rates: In one meta-analysis, the cure rate of triple therapy regimens increased by 6%-10% with high doses of PPIs. However, the current study found that 48% of triple therapies included low-dose PPIs. This number decreased over time, the authors noted: from 67% in 2013 to 20% in 2019.

“From another perspective, the daily PPI dose has increased from a dose equivalent to 54 mg of omeprazole in 2013 to 104 mg in 2019,” they wrote.

The other four errors they discussed were failing to adequately consider penicillin allergies in prescription choices, failing to consider the importance of treatment compliance, repeating certain antibiotics after failures, and not checking eradication success after treatment.

Based on these findings, Dr. Nyssen and colleagues suggested that “penetration of recommendations in the participating European countries is still poor and delayed, even though some improvements from guidelines have been partially incorporated.”

According to Grigorios I. Leontiadis, MD, PhD, of McMaster University, Hamilton, Ont., who coauthored the 2017 American College of Gastroenterology H. pylori management guidelines and the Canadian Association of Gastroenterology “Toronto Consensus” in 2016, “This study is important and timely given the steadily increasing antibiotic resistance of H. pylori worldwide.”

Although Dr. Leontiadias described the results as “suboptimal,” he was partially reassured by the improvements over time, “especially following publication of the 2016 European clinical practice guidelines.” He also noted that some older clinical practice guidelines issued conditional recommendations, which could “justify the lower adherence seen in the early period of this study.”

“The unanswered question,” Dr. Leontiadias went on, “is whether the practice of gastroenterologists who volunteered to participate in this prospective registry is truly representative of how H. pylori is managed in Europe. Most likely it isn’t. Nonparticipating gastroenterologists and nongastroenterologist health care practitioners are probably less aware of and less adherent to clinical practice guidelines. This means that the actual situation in the real world is probably grimmer than what this study shows.”

William D. Chey, MD, Nostrant Collegiate Professor of Gastroenterology at the University of Michigan, Ann Arbor, considered the results “not entirely surprising, but nonetheless, noteworthy.”

Dr. Chey noted that the United States lacks a similar registry to compare real-world H. pylori management; even so, he suggested several findings that “bear reiteration” for clinicians in the United States.

“U.S. providers should consider regimens other than clarithromycin triple therapy when treating H. pylori infection,” Dr. Chey said. “Since U.S. providers do not have reliable data on H. pylori antimicrobial resistance, it is useful to ask about prior macrolide antibiotic exposure, and if a patient has received a macrolide for any reason, clarithromycin triple therapy should be avoided. Bismuth quadruple therapy remains a reliable first-line treatment option in the U.S. Another recently approved first-line treatment option is the combination of a proton pump inhibitor, rifabutin, and amoxicillin. Treatment regimens in the U.S. should be given for a minimum of 10 days and, preferably, for 14 days. Another point made by the article is that providers should be maximizing gastric acid suppression by using higher doses of proton pump inhibitors when treating H. pylori.”

Dr. Chey also noted an emerging treatment option that could soon be available. “Results from phase 3 trials in North America and Europe with the potassium-competitive acid blocker vonoprazan combined with amoxicillin, with and without clarithromycin, are expected in 2021 and may provide another novel first-line treatment option.”

Dr. Nyssen and colleagues disclosed relationships with Allergan, Mayoly, Janssen, and others. Dr. Chey is a consultant for Redhill, Phathom, and Takeda, which is developing vonoprazan. Dr. Leontiadias disclosed no conflicts of interest.

This article was updated 2/16/21.

Many patients are receiving inadequate eradication therapy for Helicobacter pylori infection, according to analysis of a European registry.

In their analysis, published in the Journal of Clinical Gastroenterology, Olga P. Nyssen, BSc, PhD, of the Autonomous University of Madrid and colleagues discussed seven errors, which included prescribing a triple instead of quadruple regimen, prescribing therapy for too short of a duration, and prescribing a low dose of proton pump inhibitors (PPIs).

“[E]ven after more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined,” the investigators wrote. The European Registry on Helicobacter pylori management “represents a good mapping overview of the current situation regarding H. pylori management, allowing not only continuous assessment of the integration of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement.”

Patient data were drawn from registry-participating countries that each had more than 1,000 cases of H. pylori available; most came from Spain, followed by Russia, Italy, Slovenia, and Lithuania. Of these patients, data for 26,340 patients were analyzed, which ultimately represented 80% of the total registry from 2013 to 2019.

The first mistake discussed in the paper regarded use of less-effective triple therapies (typically PPI plus two antibiotics); one review showed that these regimens fail in 20%-40% of cases. Increasing antibiotic resistances have only worsened the success rate. According to this study, a triple regimen was given as first-line treatment in 46% of cases. Overall, frequency of triple-therapy prescriptions decreased from more than 50% in 2013 to about 40% in 2019. More significant improvements in this area were achieved in Spain, where use of triple therapies decreased from 24% in 2014 to 0% in 2019. According to the investigators, this finding serves as a “paradigmatic example of improvement with time.”

The authors pointed out that “overwhelming evidence” supports 14-day treatment; however, 69% of triple-therapy durations and 58% of quadruple therapy cases were for 7 or 10 days. Triple therapy at this duration showed only 81% cure rate, while it was 88% with 14 days, and quadruple therapy was only 80% effective at 7-10 days but 90% effective at 14 days.

“Fortunately,” the investigators wrote, “this mistake was progressively found less frequently and, at present, the prescription of 7-day standard triple therapy regimens has almost disappeared.”

The authors noted acid suppression via PPIs improves cure rates: In one meta-analysis, the cure rate of triple therapy regimens increased by 6%-10% with high doses of PPIs. However, the current study found that 48% of triple therapies included low-dose PPIs. This number decreased over time, the authors noted: from 67% in 2013 to 20% in 2019.

“From another perspective, the daily PPI dose has increased from a dose equivalent to 54 mg of omeprazole in 2013 to 104 mg in 2019,” they wrote.

The other four errors they discussed were failing to adequately consider penicillin allergies in prescription choices, failing to consider the importance of treatment compliance, repeating certain antibiotics after failures, and not checking eradication success after treatment.

Based on these findings, Dr. Nyssen and colleagues suggested that “penetration of recommendations in the participating European countries is still poor and delayed, even though some improvements from guidelines have been partially incorporated.”

According to Grigorios I. Leontiadis, MD, PhD, of McMaster University, Hamilton, Ont., who coauthored the 2017 American College of Gastroenterology H. pylori management guidelines and the Canadian Association of Gastroenterology “Toronto Consensus” in 2016, “This study is important and timely given the steadily increasing antibiotic resistance of H. pylori worldwide.”

Although Dr. Leontiadias described the results as “suboptimal,” he was partially reassured by the improvements over time, “especially following publication of the 2016 European clinical practice guidelines.” He also noted that some older clinical practice guidelines issued conditional recommendations, which could “justify the lower adherence seen in the early period of this study.”

“The unanswered question,” Dr. Leontiadias went on, “is whether the practice of gastroenterologists who volunteered to participate in this prospective registry is truly representative of how H. pylori is managed in Europe. Most likely it isn’t. Nonparticipating gastroenterologists and nongastroenterologist health care practitioners are probably less aware of and less adherent to clinical practice guidelines. This means that the actual situation in the real world is probably grimmer than what this study shows.”

William D. Chey, MD, Nostrant Collegiate Professor of Gastroenterology at the University of Michigan, Ann Arbor, considered the results “not entirely surprising, but nonetheless, noteworthy.”

Dr. Chey noted that the United States lacks a similar registry to compare real-world H. pylori management; even so, he suggested several findings that “bear reiteration” for clinicians in the United States.

“U.S. providers should consider regimens other than clarithromycin triple therapy when treating H. pylori infection,” Dr. Chey said. “Since U.S. providers do not have reliable data on H. pylori antimicrobial resistance, it is useful to ask about prior macrolide antibiotic exposure, and if a patient has received a macrolide for any reason, clarithromycin triple therapy should be avoided. Bismuth quadruple therapy remains a reliable first-line treatment option in the U.S. Another recently approved first-line treatment option is the combination of a proton pump inhibitor, rifabutin, and amoxicillin. Treatment regimens in the U.S. should be given for a minimum of 10 days and, preferably, for 14 days. Another point made by the article is that providers should be maximizing gastric acid suppression by using higher doses of proton pump inhibitors when treating H. pylori.”

Dr. Chey also noted an emerging treatment option that could soon be available. “Results from phase 3 trials in North America and Europe with the potassium-competitive acid blocker vonoprazan combined with amoxicillin, with and without clarithromycin, are expected in 2021 and may provide another novel first-line treatment option.”

Dr. Nyssen and colleagues disclosed relationships with Allergan, Mayoly, Janssen, and others. Dr. Chey is a consultant for Redhill, Phathom, and Takeda, which is developing vonoprazan. Dr. Leontiadias disclosed no conflicts of interest.

This article was updated 2/16/21.

The combination of liothyronine (LT₃) with levothyroxine (LT₄) for the treatment of hypothyroidism shows no evidence of any increased risk of breast cancer in a large, long-term study, contrary to concerns raised in some prior trials.

“An increasing number of patients ask their physicians for a prescription of combination therapy, often causing tensions. Thus, the question of whether combination therapy does any harm to patients is crucial,” say Tereza Planck, MD, PhD, of Skane University Hospital, Malmo, Sweden, and colleagues, in their article published online Jan. 5 in Thyroid.

“Our data provide reassuring evidence regarding the risk of cancer and mortality,” they stress.

Asked to comment, Caroline T. Nguyen, MD, agrees that the study results are welcome in light of some previous evidence.

“The findings of these [prior] studies were concerning as they suggested an association between T₃ and breast cancer, breast cancer-specific mortality, and poorer prognosis with potential estrogen-like activity of T₃ on the estrogen receptor,” Dr. Nguyen of the division of endocrinology, diabetes & metabolism at Keck Medical Center of University of Southern California, Los Angeles, told this news organization.

“Therefore, the findings of this paper provide some reassurance, which is important because, as the paper states, the use of T₃ is becoming increasingly common.”
 

Many patients with hypothyroidism opt to add liothyronine

Although the standard treatment for hypothyroidism, levothyroxine, increases free thyroxine (T₄) to high-normal levels, it may potentially lower triiodothyronine (T₃) to relatively low levels. There is speculation that the imbalance in a subset of patients could explain why some fail to have an adequate reduction of symptoms with levothyroxine alone.

To offset the effect, some add liothyronine (a synthetic version of T₃) to levothyroxine treatment as so-called “combination therapy.” However, a long-term study conducted in Scotland showed a borderline significant increase in breast cancer risk with the combination, raising concern.

To further investigate, Dr. Planck and coauthors used Swedish adult population data, identifying 575,461 individuals who had made at least three purchases of thyroid hormone therapy between July 2005 and December 2017, and had no history of breast cancer at the time of their first prescription.

Among the individuals, 11,147 had made at least three purchases of LT₃, including combinations with LT₄. LT₄-only users were an average age of 54.4 years, and the average age of those who also took LT₃ was 44.7 years.

Over a median follow-up of 8.1 years, there was no significantly increased risk of breast cancer among women treated with LT₃ plus LT₄ versus LT₄ alone (hazard ratio, 0.93), after adjusting for differences in age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose.

Further evaluation of women as well as men showed those treated with LT₃ also had no increased incidence of any cancer (HR, 0.97).

In dose-adjusted models, LT₃ treatment did, surprisingly, appear to have a protective effect in terms of all-cause mortality (HR, 0.69) and any cancer mortality (HR, 0.78) for men and women.

However, the implications of these latter results remain uncertain, first author Dr. Planck said in an interview.

“We think the data on reduced mortality should be interpreted with caution, as we only observe the differences in the models adjusting for dose,” she noted.

 

LT3 treatment still considered ‘experimental’

Despite the dramatic increase in LT₃ prescribing in recent years noted by the authors, as many as five systematic reviews/meta-analyses have shown no superiority of combination therapy over LT₄ alone in terms of hypothyroid symptoms, quality of life, or patient preference.

As a result, many international guidelines still consider the combination-treatment approach to be experimental.

Other trials that have raised concerns about the combination include previous large, prospective Swedish studies that have linked higher endogenous T₃ levels to breast cancer in postmenopausal women.

As for the mechanism, some small experimental studies have suggested an estrogenlike effect whereby T₃ could enhance the proliferation of breast cancer cells.

On a broader level, thyroid hormones, in general, have been extensively studied in cancer research as possibly promoting cancer cell proliferation in a variety of cancer types.

However, the current findings should lay some of those concerns to rest, Dr. Planck reiterated: “Our data provide reassuring evidence regarding the risk of cancer and mortality.”

“We did not identify any increase in breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality between individuals using LT₃ and LT₄ treatment.”

The authors and Nguyen have reported no relevant financial relationships.

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

The combination of liothyronine (LT₃) with levothyroxine (LT₄) for the treatment of hypothyroidism shows no evidence of any increased risk of breast cancer in a large, long-term study, contrary to concerns raised in some prior trials.

“An increasing number of patients ask their physicians for a prescription of combination therapy, often causing tensions. Thus, the question of whether combination therapy does any harm to patients is crucial,” say Tereza Planck, MD, PhD, of Skane University Hospital, Malmo, Sweden, and colleagues, in their article published online Jan. 5 in Thyroid.

“Our data provide reassuring evidence regarding the risk of cancer and mortality,” they stress.

Asked to comment, Caroline T. Nguyen, MD, agrees that the study results are welcome in light of some previous evidence.

“The findings of these [prior] studies were concerning as they suggested an association between T₃ and breast cancer, breast cancer-specific mortality, and poorer prognosis with potential estrogen-like activity of T₃ on the estrogen receptor,” Dr. Nguyen of the division of endocrinology, diabetes & metabolism at Keck Medical Center of University of Southern California, Los Angeles, told this news organization.

“Therefore, the findings of this paper provide some reassurance, which is important because, as the paper states, the use of T₃ is becoming increasingly common.”
 

Many patients with hypothyroidism opt to add liothyronine

Although the standard treatment for hypothyroidism, levothyroxine, increases free thyroxine (T₄) to high-normal levels, it may potentially lower triiodothyronine (T₃) to relatively low levels. There is speculation that the imbalance in a subset of patients could explain why some fail to have an adequate reduction of symptoms with levothyroxine alone.

To offset the effect, some add liothyronine (a synthetic version of T₃) to levothyroxine treatment as so-called “combination therapy.” However, a long-term study conducted in Scotland showed a borderline significant increase in breast cancer risk with the combination, raising concern.

To further investigate, Dr. Planck and coauthors used Swedish adult population data, identifying 575,461 individuals who had made at least three purchases of thyroid hormone therapy between July 2005 and December 2017, and had no history of breast cancer at the time of their first prescription.

Among the individuals, 11,147 had made at least three purchases of LT₃, including combinations with LT₄. LT₄-only users were an average age of 54.4 years, and the average age of those who also took LT₃ was 44.7 years.

Over a median follow-up of 8.1 years, there was no significantly increased risk of breast cancer among women treated with LT₃ plus LT₄ versus LT₄ alone (hazard ratio, 0.93), after adjusting for differences in age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose.

Further evaluation of women as well as men showed those treated with LT₃ also had no increased incidence of any cancer (HR, 0.97).

In dose-adjusted models, LT₃ treatment did, surprisingly, appear to have a protective effect in terms of all-cause mortality (HR, 0.69) and any cancer mortality (HR, 0.78) for men and women.

However, the implications of these latter results remain uncertain, first author Dr. Planck said in an interview.

“We think the data on reduced mortality should be interpreted with caution, as we only observe the differences in the models adjusting for dose,” she noted.

 

LT3 treatment still considered ‘experimental’

Despite the dramatic increase in LT₃ prescribing in recent years noted by the authors, as many as five systematic reviews/meta-analyses have shown no superiority of combination therapy over LT₄ alone in terms of hypothyroid symptoms, quality of life, or patient preference.

As a result, many international guidelines still consider the combination-treatment approach to be experimental.

Other trials that have raised concerns about the combination include previous large, prospective Swedish studies that have linked higher endogenous T₃ levels to breast cancer in postmenopausal women.

As for the mechanism, some small experimental studies have suggested an estrogenlike effect whereby T₃ could enhance the proliferation of breast cancer cells.

On a broader level, thyroid hormones, in general, have been extensively studied in cancer research as possibly promoting cancer cell proliferation in a variety of cancer types.

However, the current findings should lay some of those concerns to rest, Dr. Planck reiterated: “Our data provide reassuring evidence regarding the risk of cancer and mortality.”

“We did not identify any increase in breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality between individuals using LT₃ and LT₄ treatment.”

The authors and Nguyen have reported no relevant financial relationships.

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

The combination of liothyronine (LT₃) with levothyroxine (LT₄) for the treatment of hypothyroidism shows no evidence of any increased risk of breast cancer in a large, long-term study, contrary to concerns raised in some prior trials.

“An increasing number of patients ask their physicians for a prescription of combination therapy, often causing tensions. Thus, the question of whether combination therapy does any harm to patients is crucial,” say Tereza Planck, MD, PhD, of Skane University Hospital, Malmo, Sweden, and colleagues, in their article published online Jan. 5 in Thyroid.

“Our data provide reassuring evidence regarding the risk of cancer and mortality,” they stress.

Asked to comment, Caroline T. Nguyen, MD, agrees that the study results are welcome in light of some previous evidence.

“The findings of these [prior] studies were concerning as they suggested an association between T₃ and breast cancer, breast cancer-specific mortality, and poorer prognosis with potential estrogen-like activity of T₃ on the estrogen receptor,” Dr. Nguyen of the division of endocrinology, diabetes & metabolism at Keck Medical Center of University of Southern California, Los Angeles, told this news organization.

“Therefore, the findings of this paper provide some reassurance, which is important because, as the paper states, the use of T₃ is becoming increasingly common.”
 

Many patients with hypothyroidism opt to add liothyronine

Although the standard treatment for hypothyroidism, levothyroxine, increases free thyroxine (T₄) to high-normal levels, it may potentially lower triiodothyronine (T₃) to relatively low levels. There is speculation that the imbalance in a subset of patients could explain why some fail to have an adequate reduction of symptoms with levothyroxine alone.

To offset the effect, some add liothyronine (a synthetic version of T₃) to levothyroxine treatment as so-called “combination therapy.” However, a long-term study conducted in Scotland showed a borderline significant increase in breast cancer risk with the combination, raising concern.

To further investigate, Dr. Planck and coauthors used Swedish adult population data, identifying 575,461 individuals who had made at least three purchases of thyroid hormone therapy between July 2005 and December 2017, and had no history of breast cancer at the time of their first prescription.

Among the individuals, 11,147 had made at least three purchases of LT₃, including combinations with LT₄. LT₄-only users were an average age of 54.4 years, and the average age of those who also took LT₃ was 44.7 years.

Over a median follow-up of 8.1 years, there was no significantly increased risk of breast cancer among women treated with LT₃ plus LT₄ versus LT₄ alone (hazard ratio, 0.93), after adjusting for differences in age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose.

Further evaluation of women as well as men showed those treated with LT₃ also had no increased incidence of any cancer (HR, 0.97).

In dose-adjusted models, LT₃ treatment did, surprisingly, appear to have a protective effect in terms of all-cause mortality (HR, 0.69) and any cancer mortality (HR, 0.78) for men and women.

However, the implications of these latter results remain uncertain, first author Dr. Planck said in an interview.

“We think the data on reduced mortality should be interpreted with caution, as we only observe the differences in the models adjusting for dose,” she noted.

 

LT3 treatment still considered ‘experimental’

Despite the dramatic increase in LT₃ prescribing in recent years noted by the authors, as many as five systematic reviews/meta-analyses have shown no superiority of combination therapy over LT₄ alone in terms of hypothyroid symptoms, quality of life, or patient preference.

As a result, many international guidelines still consider the combination-treatment approach to be experimental.

Other trials that have raised concerns about the combination include previous large, prospective Swedish studies that have linked higher endogenous T₃ levels to breast cancer in postmenopausal women.

As for the mechanism, some small experimental studies have suggested an estrogenlike effect whereby T₃ could enhance the proliferation of breast cancer cells.

On a broader level, thyroid hormones, in general, have been extensively studied in cancer research as possibly promoting cancer cell proliferation in a variety of cancer types.

However, the current findings should lay some of those concerns to rest, Dr. Planck reiterated: “Our data provide reassuring evidence regarding the risk of cancer and mortality.”

“We did not identify any increase in breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality between individuals using LT₃ and LT₄ treatment.”

The authors and Nguyen have reported no relevant financial relationships.

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

Study Overview

Objective. To determine the effect of the timing of nonculprit-lesion percutaneous coronary intervention (PCI) on outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Design. Planned substudy of an international, multicenter, randomized controlled trial blinded to outcome.

Setting and participants. Among 4041 patients with STEMI who had multivessel coronary disease, randomization to nonculprit PCI versus culprit-only PCI was stratified according to intended timing of nonculprit lesion PCI. A total of 2702 patients with intended timing of nonculprit PCI during the index hospitalization and 1339 patients with intended timing of nonculprit PCI after the index hospitalization within 45 days were included.

Main outcome measures. The first co-primary endpoint was a composite of cardiovascular (CV) death or myocardial infarction (MI).

Main results. In both groups, the composite endpoint of CV death or MI was reduced with complete revascularization compared to the culprit-only strategy (index hospitalization: hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.59-1.00; after hospital discharge: HR, 0.69, 95% CI, 0.49-0.97; interaction, P = 0.62). Landmark analyses demonstrated a HR of 0.86 (95% CI, 0.59-1.24) during the first 45 days and 0.69 (95% CI,0.54-0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit-lesion-only PCI.

Conclusion. Among patients with STEMI and multivessel disease, the benefit of complete revascularization over culprit-lesion-only PCI was consistent, irrespective of the investigator-determined timing of staged nonculprit lesion intervention.

Commentary

Patients presenting with STEMI often have multivessel disease^.1 Although the question of whether to revascularize the nonculprit vessel has been controversial, multiple contemporary studies have reported benefit of nonculprit-vessel revascularization compared to the culprit-only strategy.^2-5 Compared to these previous medium-sized randomized controlled trials that included ischemia-driven revascularization as a composite endpoint, the COMPETE trial was unique in that it enrolled a large number of patients and reported a benefit in hard outcomes of a composite of CV death or MI.⁶

As the previous studies point toward the benefit of complete revascularization in patients presenting with STEMI, another important question has been the optimal timing of nonculprit vessel revascularization. Operators have 3 possible options: during the index procedure as primary PCI, as a staged procedure during the index admission, or as a staged procedure as an outpatient following discharge. Timing of nonculprit PCI has been inconsistent in the previous studies. For example, in the PRAMI trial, nonculprit PCI was performed during the index procedure,² while in the CvPRIT and COMPARE ACUTE trials, the nonculprit PCI was performed during the index procedure or as a staged procedure during the same admission at the operator’s discretion.^3,5

In this context, the COMPLETE investigators report their findings of the prespecified substudy regarding the timing of staged nonculprit vessel PCI. In the COMPLETE trial, 4041 patients were stratified by intended timing of nonculprit lesion PCI (2702 patients during index hospitalization, 1339 after discharge), which was predetermined by the operator prior to the randomization. Among the patients with intended staged nonculprit PCI during index hospitalization, the incidence of the first co-primary outcome of CV death or MI was 2.7% per year in patients with complete revascularization, as compared to 3.5% per year in patients with culprit-lesion only PCI (HR, 0.77; 95% CI, 0.59-1.00). Similarly, in patients with intended nonculprit PCI after the index hospitalization, the incidence of the first co-primary outcome of CV death or MI was 2.7% per year in patients randomized to complete revascularization, as compared to 3.9% per year in patients with culprit-lesion-only PCI (HR, 0.69; 95% CI, 0.49-0.97). These findings were similar for the second co-primary outcome of CV death, MI, or ischemia-driven revascularization (3.0% vs 6.6% per year for intended timing of nonculprit PCI during index admission, and 3.1% vs 5.4% per year for intended timing of nonculprit PCI after discharge, both favoring complete revascularization).

The investigators also performed a landmark analysis before and after 45 days of randomization. Within the first 45 days, CV death or MI occurred in 2.5% of the complete revascularization group and 3.0% of the culprit-lesion-only PCI group (HR, 0.86; 95% CI, 0.59-1.24). On the other hand, during the interval from 45 days to the end of the study, CV death or MI occurred in 5.5% in the complete revascularization group and 7.8% in the culprit-lesion-only group (HR, 0.69; 95% CI, 0.54-0.89).

There were a number of strengths of the COMPLETE study, as we have previously described, such as multiple patients enrolled, contemporary therapy with high use of radial access, mandated use of fractional flow reserve for 50% to 69% stenosis lesions, and low cross-over rate.⁷ In addition, the current substudy is unique and important, as it was the first study to systematically evaluate the timing of the staged PCI. In addition to their finding of consistent benefit between staged procedure before or after discharge, the results from their landmark analysis suggest that the benefit of complete revascularization accumulates over the long term rather than the short term.

The main limitation of the COMPLETE study is that it was not adequately powered to find statistical differences in each subgroup studied. In addition, since all nonculprit PCIs were staged in this study, nonculprit PCI performed during the index procedure cannot be assessed.

Nevertheless, the finding of similar benefit of complete revascularization regardless of the timing of the staged PCI has clinical implication for practicing interventional cardiologists and patients presenting with STEMI. For example, if the patient presents with hemodynamically stable STEMI on a Friday, the patient can potentially be safely discharged over the weekend and return for a staged PCI as an outpatient instead of staying extra days for an inpatient staged PCI. Whether this approach may improve the patient satisfaction and hospital resource utilization will require further study.

Applications for Clinical Practice

In patients presenting with hemodynamically stable STEMI, staged complete revascularization can be performed during the admission or after discharge within 45 days.

—Taishi Hirai, MD

Study Overview

Objective. To determine the effect of the timing of nonculprit-lesion percutaneous coronary intervention (PCI) on outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Design. Planned substudy of an international, multicenter, randomized controlled trial blinded to outcome.

Setting and participants. Among 4041 patients with STEMI who had multivessel coronary disease, randomization to nonculprit PCI versus culprit-only PCI was stratified according to intended timing of nonculprit lesion PCI. A total of 2702 patients with intended timing of nonculprit PCI during the index hospitalization and 1339 patients with intended timing of nonculprit PCI after the index hospitalization within 45 days were included.

Main outcome measures. The first co-primary endpoint was a composite of cardiovascular (CV) death or myocardial infarction (MI).

Main results. In both groups, the composite endpoint of CV death or MI was reduced with complete revascularization compared to the culprit-only strategy (index hospitalization: hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.59-1.00; after hospital discharge: HR, 0.69, 95% CI, 0.49-0.97; interaction, P = 0.62). Landmark analyses demonstrated a HR of 0.86 (95% CI, 0.59-1.24) during the first 45 days and 0.69 (95% CI,0.54-0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit-lesion-only PCI.

Conclusion. Among patients with STEMI and multivessel disease, the benefit of complete revascularization over culprit-lesion-only PCI was consistent, irrespective of the investigator-determined timing of staged nonculprit lesion intervention.

Commentary

Patients presenting with STEMI often have multivessel disease^.1 Although the question of whether to revascularize the nonculprit vessel has been controversial, multiple contemporary studies have reported benefit of nonculprit-vessel revascularization compared to the culprit-only strategy.^2-5 Compared to these previous medium-sized randomized controlled trials that included ischemia-driven revascularization as a composite endpoint, the COMPETE trial was unique in that it enrolled a large number of patients and reported a benefit in hard outcomes of a composite of CV death or MI.⁶

As the previous studies point toward the benefit of complete revascularization in patients presenting with STEMI, another important question has been the optimal timing of nonculprit vessel revascularization. Operators have 3 possible options: during the index procedure as primary PCI, as a staged procedure during the index admission, or as a staged procedure as an outpatient following discharge. Timing of nonculprit PCI has been inconsistent in the previous studies. For example, in the PRAMI trial, nonculprit PCI was performed during the index procedure,² while in the CvPRIT and COMPARE ACUTE trials, the nonculprit PCI was performed during the index procedure or as a staged procedure during the same admission at the operator’s discretion.^3,5

In this context, the COMPLETE investigators report their findings of the prespecified substudy regarding the timing of staged nonculprit vessel PCI. In the COMPLETE trial, 4041 patients were stratified by intended timing of nonculprit lesion PCI (2702 patients during index hospitalization, 1339 after discharge), which was predetermined by the operator prior to the randomization. Among the patients with intended staged nonculprit PCI during index hospitalization, the incidence of the first co-primary outcome of CV death or MI was 2.7% per year in patients with complete revascularization, as compared to 3.5% per year in patients with culprit-lesion only PCI (HR, 0.77; 95% CI, 0.59-1.00). Similarly, in patients with intended nonculprit PCI after the index hospitalization, the incidence of the first co-primary outcome of CV death or MI was 2.7% per year in patients randomized to complete revascularization, as compared to 3.9% per year in patients with culprit-lesion-only PCI (HR, 0.69; 95% CI, 0.49-0.97). These findings were similar for the second co-primary outcome of CV death, MI, or ischemia-driven revascularization (3.0% vs 6.6% per year for intended timing of nonculprit PCI during index admission, and 3.1% vs 5.4% per year for intended timing of nonculprit PCI after discharge, both favoring complete revascularization).

The investigators also performed a landmark analysis before and after 45 days of randomization. Within the first 45 days, CV death or MI occurred in 2.5% of the complete revascularization group and 3.0% of the culprit-lesion-only PCI group (HR, 0.86; 95% CI, 0.59-1.24). On the other hand, during the interval from 45 days to the end of the study, CV death or MI occurred in 5.5% in the complete revascularization group and 7.8% in the culprit-lesion-only group (HR, 0.69; 95% CI, 0.54-0.89).

There were a number of strengths of the COMPLETE study, as we have previously described, such as multiple patients enrolled, contemporary therapy with high use of radial access, mandated use of fractional flow reserve for 50% to 69% stenosis lesions, and low cross-over rate.⁷ In addition, the current substudy is unique and important, as it was the first study to systematically evaluate the timing of the staged PCI. In addition to their finding of consistent benefit between staged procedure before or after discharge, the results from their landmark analysis suggest that the benefit of complete revascularization accumulates over the long term rather than the short term.

The main limitation of the COMPLETE study is that it was not adequately powered to find statistical differences in each subgroup studied. In addition, since all nonculprit PCIs were staged in this study, nonculprit PCI performed during the index procedure cannot be assessed.

Nevertheless, the finding of similar benefit of complete revascularization regardless of the timing of the staged PCI has clinical implication for practicing interventional cardiologists and patients presenting with STEMI. For example, if the patient presents with hemodynamically stable STEMI on a Friday, the patient can potentially be safely discharged over the weekend and return for a staged PCI as an outpatient instead of staying extra days for an inpatient staged PCI. Whether this approach may improve the patient satisfaction and hospital resource utilization will require further study.

Applications for Clinical Practice

In patients presenting with hemodynamically stable STEMI, staged complete revascularization can be performed during the admission or after discharge within 45 days.

—Taishi Hirai, MD

Study Overview

Objective. To determine the effect of the timing of nonculprit-lesion percutaneous coronary intervention (PCI) on outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Design. Planned substudy of an international, multicenter, randomized controlled trial blinded to outcome.

Setting and participants. Among 4041 patients with STEMI who had multivessel coronary disease, randomization to nonculprit PCI versus culprit-only PCI was stratified according to intended timing of nonculprit lesion PCI. A total of 2702 patients with intended timing of nonculprit PCI during the index hospitalization and 1339 patients with intended timing of nonculprit PCI after the index hospitalization within 45 days were included.

Main outcome measures. The first co-primary endpoint was a composite of cardiovascular (CV) death or myocardial infarction (MI).

Main results. In both groups, the composite endpoint of CV death or MI was reduced with complete revascularization compared to the culprit-only strategy (index hospitalization: hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.59-1.00; after hospital discharge: HR, 0.69, 95% CI, 0.49-0.97; interaction, P = 0.62). Landmark analyses demonstrated a HR of 0.86 (95% CI, 0.59-1.24) during the first 45 days and 0.69 (95% CI,0.54-0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit-lesion-only PCI.

Conclusion. Among patients with STEMI and multivessel disease, the benefit of complete revascularization over culprit-lesion-only PCI was consistent, irrespective of the investigator-determined timing of staged nonculprit lesion intervention.

Commentary

Patients presenting with STEMI often have multivessel disease^.1 Although the question of whether to revascularize the nonculprit vessel has been controversial, multiple contemporary studies have reported benefit of nonculprit-vessel revascularization compared to the culprit-only strategy.^2-5 Compared to these previous medium-sized randomized controlled trials that included ischemia-driven revascularization as a composite endpoint, the COMPETE trial was unique in that it enrolled a large number of patients and reported a benefit in hard outcomes of a composite of CV death or MI.⁶

As the previous studies point toward the benefit of complete revascularization in patients presenting with STEMI, another important question has been the optimal timing of nonculprit vessel revascularization. Operators have 3 possible options: during the index procedure as primary PCI, as a staged procedure during the index admission, or as a staged procedure as an outpatient following discharge. Timing of nonculprit PCI has been inconsistent in the previous studies. For example, in the PRAMI trial, nonculprit PCI was performed during the index procedure,² while in the CvPRIT and COMPARE ACUTE trials, the nonculprit PCI was performed during the index procedure or as a staged procedure during the same admission at the operator’s discretion.^3,5

In this context, the COMPLETE investigators report their findings of the prespecified substudy regarding the timing of staged nonculprit vessel PCI. In the COMPLETE trial, 4041 patients were stratified by intended timing of nonculprit lesion PCI (2702 patients during index hospitalization, 1339 after discharge), which was predetermined by the operator prior to the randomization. Among the patients with intended staged nonculprit PCI during index hospitalization, the incidence of the first co-primary outcome of CV death or MI was 2.7% per year in patients with complete revascularization, as compared to 3.5% per year in patients with culprit-lesion only PCI (HR, 0.77; 95% CI, 0.59-1.00). Similarly, in patients with intended nonculprit PCI after the index hospitalization, the incidence of the first co-primary outcome of CV death or MI was 2.7% per year in patients randomized to complete revascularization, as compared to 3.9% per year in patients with culprit-lesion-only PCI (HR, 0.69; 95% CI, 0.49-0.97). These findings were similar for the second co-primary outcome of CV death, MI, or ischemia-driven revascularization (3.0% vs 6.6% per year for intended timing of nonculprit PCI during index admission, and 3.1% vs 5.4% per year for intended timing of nonculprit PCI after discharge, both favoring complete revascularization).

The investigators also performed a landmark analysis before and after 45 days of randomization. Within the first 45 days, CV death or MI occurred in 2.5% of the complete revascularization group and 3.0% of the culprit-lesion-only PCI group (HR, 0.86; 95% CI, 0.59-1.24). On the other hand, during the interval from 45 days to the end of the study, CV death or MI occurred in 5.5% in the complete revascularization group and 7.8% in the culprit-lesion-only group (HR, 0.69; 95% CI, 0.54-0.89).

There were a number of strengths of the COMPLETE study, as we have previously described, such as multiple patients enrolled, contemporary therapy with high use of radial access, mandated use of fractional flow reserve for 50% to 69% stenosis lesions, and low cross-over rate.⁷ In addition, the current substudy is unique and important, as it was the first study to systematically evaluate the timing of the staged PCI. In addition to their finding of consistent benefit between staged procedure before or after discharge, the results from their landmark analysis suggest that the benefit of complete revascularization accumulates over the long term rather than the short term.

The main limitation of the COMPLETE study is that it was not adequately powered to find statistical differences in each subgroup studied. In addition, since all nonculprit PCIs were staged in this study, nonculprit PCI performed during the index procedure cannot be assessed.

Nevertheless, the finding of similar benefit of complete revascularization regardless of the timing of the staged PCI has clinical implication for practicing interventional cardiologists and patients presenting with STEMI. For example, if the patient presents with hemodynamically stable STEMI on a Friday, the patient can potentially be safely discharged over the weekend and return for a staged PCI as an outpatient instead of staying extra days for an inpatient staged PCI. Whether this approach may improve the patient satisfaction and hospital resource utilization will require further study.

Applications for Clinical Practice

In patients presenting with hemodynamically stable STEMI, staged complete revascularization can be performed during the admission or after discharge within 45 days.

—Taishi Hirai, MD

Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.

Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.

klebercordeiro/Getty Images

Sleeping, more or less

A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.

“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.

“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.

Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.

It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
 

Self-medicating

Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.

“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.

Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.

“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.

“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
 

Causes for concern

“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.

“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.

It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.

Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.

It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.

“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.

“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
 

Compromised immunity

It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.

“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”

It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.

“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
 

What to do?

All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.

“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.

Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.

Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.

They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.

“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
 

Research avenues

If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.

“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”

Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.

Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.

klebercordeiro/Getty Images

Sleeping, more or less

A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.

“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.

“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.

Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.

It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
 

Self-medicating

Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.

“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.

Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.

“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.

“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
 

Causes for concern

“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.

“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.

It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.

Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.

It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.

“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.

“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
 

Compromised immunity

It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.

“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”

It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.

“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
 

What to do?

All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.

“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.

Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.

Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.

They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.

“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
 

Research avenues

If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.

“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”

Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.

Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.

klebercordeiro/Getty Images

Sleeping, more or less

A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.

“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.

“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.

Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.

It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
 

Self-medicating

Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.

“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.

Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.

“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.

“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
 

Causes for concern

“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.

“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.

It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.

Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.

It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.

“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.

“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
 

Compromised immunity

It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.

“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”

It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.

“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
 

What to do?

All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.

“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.

Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.

Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.

They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.

“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
 

Research avenues

If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.

“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”

The National Institutes of Health has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can’t recommend for or against its use, leaving the decision to physicians and their patients.

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released last week.

Passionate arguments have been waged for and against the drug’s use.

The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement Jan. 18. Point by point, the group of 10 physicians argued against each limitation that drove the NIH’s ruling.

The group’s members said that, although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total U.S. deaths surpassed 400,000 since last spring – and currently approach 4,000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.

“Patients do not have time to wait,” they write, “and we as health care providers in society do not have that time either.”

NIH, which in August had recommended against ivermectin’s use, invited the group to present evidence to its treatment guidance panel on Jan. 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug’s effectiveness.

Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, also spoke before a Senate panel on Dec. 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 “miracle” drug, a term he said he doesn’t use lightly.

Dr. Kory pleaded with the NIH to consider the emerging data. “Please, I’m just asking that they review our manuscript,” he told the senators.

“We have immense amounts of data to show that ivermectin must be implemented and implemented now,” he said.
 

Some draw parallels to hydroxychloroquine

Critics have said there’s not enough data to institute a protocol, and some draw parallels to another repurposed drug – hydroxychloroquine (HCQ) – which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.

Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV program and division of infectious diseases at Brigham and Women’s Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.

“But we’re not quite yet at the ‘practice changing’ level,” he writes. “Results from at least five randomized clinical trials are expected soon that might further inform the decision.”

He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the department of pharmacology, University of Liverpool (England).

Dr. Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.

The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because “they weren’t done in the right places.”

“That’s not just bias,” he says. “It’s also snobbery.”

Ivermectin has been approved by the U.S. Food and Drug Administration for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.

In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
 

Some physicians say they won’t prescribe it

Some physicians say they won’t be recommending it to their COVID-19 patients.

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore,said in an interview that the NIH update hasn’t changed his mind and he isn’t prescribing it for his patients.

He said although “there’s enough of a signal” that he would like to see more data, “we haven’t seen anything in terms of a really robust study.”

He noted that the Infectious Diseases Society of America has 15 recommendations for COVID-19 treatment “and not one of them has to do with ivermectin.”

He added, “It’s not enough to see if it works, but we need to see who it works in and when it works in them.”

He also acknowledged that “some prominent physicians” are recommending it.

Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Dr. Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.

The data surrounding ivermectin have met with hope, criticism, and warnings.

Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.

The study concluded that the drug resulted post infection in a 5,000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.

The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo,” the NIH guidance reads.

The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients’ severity of COVID was not always clearly described in the studies.

Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told this news organization she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.

That said, Dr. Safdar added, “in individual circumstances if a physician is confronted with a patient in dire straits and you’re not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn’t rise to the level of a policy.”

A downside of recommending a treatment without conclusive data, even if harm isn’t the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it’s effective depending on patient populations and the severity of COVID-19.

Dr. Adalja and Dr. Safdar have disclosed no relevant financial relationships.

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

The National Institutes of Health has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can’t recommend for or against its use, leaving the decision to physicians and their patients.

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released last week.

Passionate arguments have been waged for and against the drug’s use.

The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement Jan. 18. Point by point, the group of 10 physicians argued against each limitation that drove the NIH’s ruling.

The group’s members said that, although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total U.S. deaths surpassed 400,000 since last spring – and currently approach 4,000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.

“Patients do not have time to wait,” they write, “and we as health care providers in society do not have that time either.”

NIH, which in August had recommended against ivermectin’s use, invited the group to present evidence to its treatment guidance panel on Jan. 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug’s effectiveness.

Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, also spoke before a Senate panel on Dec. 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 “miracle” drug, a term he said he doesn’t use lightly.

Dr. Kory pleaded with the NIH to consider the emerging data. “Please, I’m just asking that they review our manuscript,” he told the senators.

“We have immense amounts of data to show that ivermectin must be implemented and implemented now,” he said.
 

Some draw parallels to hydroxychloroquine

Critics have said there’s not enough data to institute a protocol, and some draw parallels to another repurposed drug – hydroxychloroquine (HCQ) – which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.

Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV program and division of infectious diseases at Brigham and Women’s Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.

“But we’re not quite yet at the ‘practice changing’ level,” he writes. “Results from at least five randomized clinical trials are expected soon that might further inform the decision.”

He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the department of pharmacology, University of Liverpool (England).

Dr. Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.

The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because “they weren’t done in the right places.”

“That’s not just bias,” he says. “It’s also snobbery.”

Ivermectin has been approved by the U.S. Food and Drug Administration for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.

In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
 

Some physicians say they won’t prescribe it

Some physicians say they won’t be recommending it to their COVID-19 patients.

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore,said in an interview that the NIH update hasn’t changed his mind and he isn’t prescribing it for his patients.

He said although “there’s enough of a signal” that he would like to see more data, “we haven’t seen anything in terms of a really robust study.”

He noted that the Infectious Diseases Society of America has 15 recommendations for COVID-19 treatment “and not one of them has to do with ivermectin.”

He added, “It’s not enough to see if it works, but we need to see who it works in and when it works in them.”

He also acknowledged that “some prominent physicians” are recommending it.

Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Dr. Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.

The data surrounding ivermectin have met with hope, criticism, and warnings.

Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.

The study concluded that the drug resulted post infection in a 5,000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.

The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo,” the NIH guidance reads.

The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients’ severity of COVID was not always clearly described in the studies.

Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told this news organization she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.

That said, Dr. Safdar added, “in individual circumstances if a physician is confronted with a patient in dire straits and you’re not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn’t rise to the level of a policy.”

A downside of recommending a treatment without conclusive data, even if harm isn’t the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it’s effective depending on patient populations and the severity of COVID-19.

Dr. Adalja and Dr. Safdar have disclosed no relevant financial relationships.

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

The National Institutes of Health has dropped its recommendation against the inexpensive antiparasitic drug ivermectin for treatment of COVID-19, and the agency now advises it can’t recommend for or against its use, leaving the decision to physicians and their patients.

“Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released last week.

Passionate arguments have been waged for and against the drug’s use.

The NIH update disappointed members of the Front Line COVID-19 Critical Care Alliance (FLCCC), which outlined its case for endorsing ivermectin in a public statement Jan. 18. Point by point, the group of 10 physicians argued against each limitation that drove the NIH’s ruling.

The group’s members said that, although grateful the recommendation against the drug was dropped, a neutral approach is not acceptable as total U.S. deaths surpassed 400,000 since last spring – and currently approach 4,000 a day. Results from research are enough to support its use, and the drug will immediately save lives, they say.

“Patients do not have time to wait,” they write, “and we as health care providers in society do not have that time either.”

NIH, which in August had recommended against ivermectin’s use, invited the group to present evidence to its treatment guidance panel on Jan. 6 to detail the emerging science surrounding ivermectin. The group cited rapidly growing evidence of the drug’s effectiveness.

Pierre Kory, MD, president/cofounder of FLCCC and a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, also spoke before a Senate panel on Dec. 8 in a widely shared impassioned video, touting ivermectin as a COVID-19 “miracle” drug, a term he said he doesn’t use lightly.

Dr. Kory pleaded with the NIH to consider the emerging data. “Please, I’m just asking that they review our manuscript,” he told the senators.

“We have immense amounts of data to show that ivermectin must be implemented and implemented now,” he said.
 

Some draw parallels to hydroxychloroquine

Critics have said there’s not enough data to institute a protocol, and some draw parallels to another repurposed drug – hydroxychloroquine (HCQ) – which was once considered a promising treatment for COVID-19, based on flawed and incomplete evidence, and now is not recommended.

Paul Sax, MD, a professor of medicine at Harvard and clinical director of the HIV program and division of infectious diseases at Brigham and Women’s Hospital in Boston, wrote in a blog post earlier this month in the New England Journal of Medicine Journal Watch that ivermectin has more robust evidence for it than HCQ ever did.

“But we’re not quite yet at the ‘practice changing’ level,” he writes. “Results from at least five randomized clinical trials are expected soon that might further inform the decision.”

He said the best argument for the drug is seen in this explanation of a meta-analysis of studies of between 100 and 500 patients by Andrew Hill, MD, with the department of pharmacology, University of Liverpool (England).

Dr. Sax advises against two biases in considering ivermectin. One is assuming that because HCQ failed, other antiparasitic drugs will too.

The second bias to avoid, he says, is discounting studies done in low- and middle-income countries because “they weren’t done in the right places.”

“That’s not just bias,” he says. “It’s also snobbery.”

Ivermectin has been approved by the U.S. Food and Drug Administration for treatment of onchocerciasis (river blindness) and strongyloidiasis, but is not FDA-approved for the treatment of any viral infection. It also is sometimes used to treat animals.

In dropping the recommendation against ivermectin, the NIH gave it the same neutral declaration as monoclonal antibodies and convalescent plasma.
 

Some physicians say they won’t prescribe it

Some physicians say they won’t be recommending it to their COVID-19 patients.

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins University Center for Health Security in Baltimore,said in an interview that the NIH update hasn’t changed his mind and he isn’t prescribing it for his patients.

He said although “there’s enough of a signal” that he would like to see more data, “we haven’t seen anything in terms of a really robust study.”

He noted that the Infectious Diseases Society of America has 15 recommendations for COVID-19 treatment “and not one of them has to do with ivermectin.”

He added, “It’s not enough to see if it works, but we need to see who it works in and when it works in them.”

He also acknowledged that “some prominent physicians” are recommending it.

Among them is Paul Marik, MD, endowed professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. A cofounder of FLCCC, Dr. Marik has championed ivermectin and developed a protocol for its use to prevent and treat COVID-19.

The data surrounding ivermectin have met with hope, criticism, and warnings.

Australian researchers published a study ahead of print in Antiviral Research that found ivermectin inhibited the replication of SARS-CoV-2 in a laboratory setting.

The study concluded that the drug resulted post infection in a 5,000-fold reduction in viral RNA at 48 hours. After that study, however, the FDA in April warned consumers not to self-medicate with ivermectin products intended for animals.

The NIH acknowledged that several randomized trials and retrospective studies of ivermectin use in patients with COVID-19 have now been published in peer-reviewed journals or on preprint servers.

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo,” the NIH guidance reads.

The NIH acknowledges limitations: the studies have been small; doses of ivermectin have varied; some patients were taking other medications at the same time (including doxycycline, hydroxychloroquine, azithromycin, zinc, and corticosteroids, which may be potential confounders); and patients’ severity of COVID was not always clearly described in the studies.

Nasia Safdar, MD, medical director of infection prevention at the University of Wisconsin Hospital in Madison, told this news organization she agrees more research is needed before ivermectin is recommended by regulatory bodies for COVID-19.

That said, Dr. Safdar added, “in individual circumstances if a physician is confronted with a patient in dire straits and you’re not sure what to do, might you consider it? I think after a discussion with the patient, perhaps, but the level of evidence certainly doesn’t rise to the level of a policy.”

A downside of recommending a treatment without conclusive data, even if harm isn’t the primary concern, she said, is that supplies could dwindle for its intended use in other diseases. Also, premature approval can limit the robust research needed to see not only whether it works better for prevention or treatment, but also if it’s effective depending on patient populations and the severity of COVID-19.

Dr. Adalja and Dr. Safdar have disclosed no relevant financial relationships.

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

A distinguished international panel of acne experts has identified major gaps in current clinical practice guidelines for the management of acne.

“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.

The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.

Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.

Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.

The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.

“None of us felt the guidelines were very useful,” Dr. Layton noted.

It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.

With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.

PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.

“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.

Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.

Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.

[email protected]

A distinguished international panel of acne experts has identified major gaps in current clinical practice guidelines for the management of acne.

“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.

The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.

Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.

Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.

The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.

“None of us felt the guidelines were very useful,” Dr. Layton noted.

It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.

With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.

PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.

“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.

Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.

Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.

[email protected]

A distinguished international panel of acne experts has identified major gaps in current clinical practice guidelines for the management of acne.

“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.

The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.

Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.

Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.

The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.

“None of us felt the guidelines were very useful,” Dr. Layton noted.

It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.

With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.

PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.

“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.

Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.

Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.

[email protected]

The national rate of methamphetamine overdose deaths shot up significantly between 2011 and 2018, particularly among non-Hispanic American Indian and Alaska Native communities, new research shows.

Rates rose for both men and women but more so among men, the study found. The spike in these deaths underscores the need for culturally tailored prevention and treatment strategies, the study authors said.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam – particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” senior investigator Nora D. Volkow, MD, director of the National Institute on Drug Abuse, said in a press release.

The study was published online Jan. 20 in JAMA Psychiatry.
 

Highly toxic

Methamphetamine is highly toxic. Its use is associated with pulmonary and cardiovascular pathology and frequently co-occurs with other substance use and mental disorders.

In addition, there are currently no Food and Drug Administration–approved medications to reverse methamphetamine overdose or treat methamphetamine use disorder.

However, behavioral therapies can be effective in reducing the harm associated with methamphetamine use. In addition, a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorder.

For the study, the investigators used deidentified public health surveillance data from the Centers for Disease Control and Prevention’s National Vital Statistics System files for multiple causes of death.

The researchers used the psychostimulant category to estimate death rates from methamphetamine. The authors noted that up to 90% of psychostimulant-involved death certificates mentioned methamphetamine.

Researchers stratified age-adjusted overdose death rates during 2011-2018 by sex and race/ethnicity and limited the analysis to those aged 25-54 years. Approximately 80% of methamphetamine users are between the ages of 25 and 54 years.

During the study period, rates for methamphetamine-involved deaths increased from 1.8 to 10.1 per 100,000 among men (average annual percentage change, 29.1; 95% confidence interval, 25.5-32.8; P < .001) and from 0.8 to 4.5 per 100,000 among women (AAPC, 28.1; 95% CI, 25.1-31.2; P < .001).
 

Need for tailored interventions

For both men and women, those in non-Hispanic American Indian or Alaska Native communities had the highest rates. These increased from 5.6 to 26.4 per 100,000 among men and from 3.6 to 15.6 per 100,000 among women.

While American Indian and Alaska Native individuals experience sociostructural disadvantages, their cultural strengths “can be leveraged to improve addiction outcomes,” the investigators wrote.

Non-Hispanic Whites had the second highest rates. These rose from 2.2 to 12.6 per 100,000 among men (AAPC, 29.8; 95% CI, 24.3-35.4; P < .001) and from 1.1 to 6.2 per 100,000 among women (AAPC, 29.1; 95% CI, 25.2-33.2; P < .001).

Rates among Hispanic individuals increased from 1.4 to 6.6 per 100,000 for men and from 0.5 to 2.0 per 100,000 for women. Among non-Hispanic Asian individuals, rates increased to 3.4 per 100,000 for men and to 1.1 per 100,000 for women. Non-Hispanic Black individuals had low rates. Within each racial/ethnic group, rates were higher among men versus women.

Methamphetamine death rates may be underestimated because some overdose death certificates do not report specific drugs involved, the authors noted.

Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” study author Beth Han, MD, PhD, of NIDA, said in a press release.

“By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions,” she said.

The study was sponsored by NIDA.

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

The national rate of methamphetamine overdose deaths shot up significantly between 2011 and 2018, particularly among non-Hispanic American Indian and Alaska Native communities, new research shows.

Rates rose for both men and women but more so among men, the study found. The spike in these deaths underscores the need for culturally tailored prevention and treatment strategies, the study authors said.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam – particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” senior investigator Nora D. Volkow, MD, director of the National Institute on Drug Abuse, said in a press release.

The study was published online Jan. 20 in JAMA Psychiatry.
 

Highly toxic

Methamphetamine is highly toxic. Its use is associated with pulmonary and cardiovascular pathology and frequently co-occurs with other substance use and mental disorders.

In addition, there are currently no Food and Drug Administration–approved medications to reverse methamphetamine overdose or treat methamphetamine use disorder.

However, behavioral therapies can be effective in reducing the harm associated with methamphetamine use. In addition, a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorder.

For the study, the investigators used deidentified public health surveillance data from the Centers for Disease Control and Prevention’s National Vital Statistics System files for multiple causes of death.

The researchers used the psychostimulant category to estimate death rates from methamphetamine. The authors noted that up to 90% of psychostimulant-involved death certificates mentioned methamphetamine.

Researchers stratified age-adjusted overdose death rates during 2011-2018 by sex and race/ethnicity and limited the analysis to those aged 25-54 years. Approximately 80% of methamphetamine users are between the ages of 25 and 54 years.

During the study period, rates for methamphetamine-involved deaths increased from 1.8 to 10.1 per 100,000 among men (average annual percentage change, 29.1; 95% confidence interval, 25.5-32.8; P < .001) and from 0.8 to 4.5 per 100,000 among women (AAPC, 28.1; 95% CI, 25.1-31.2; P < .001).
 

Need for tailored interventions

For both men and women, those in non-Hispanic American Indian or Alaska Native communities had the highest rates. These increased from 5.6 to 26.4 per 100,000 among men and from 3.6 to 15.6 per 100,000 among women.

While American Indian and Alaska Native individuals experience sociostructural disadvantages, their cultural strengths “can be leveraged to improve addiction outcomes,” the investigators wrote.

Non-Hispanic Whites had the second highest rates. These rose from 2.2 to 12.6 per 100,000 among men (AAPC, 29.8; 95% CI, 24.3-35.4; P < .001) and from 1.1 to 6.2 per 100,000 among women (AAPC, 29.1; 95% CI, 25.2-33.2; P < .001).

Rates among Hispanic individuals increased from 1.4 to 6.6 per 100,000 for men and from 0.5 to 2.0 per 100,000 for women. Among non-Hispanic Asian individuals, rates increased to 3.4 per 100,000 for men and to 1.1 per 100,000 for women. Non-Hispanic Black individuals had low rates. Within each racial/ethnic group, rates were higher among men versus women.

Methamphetamine death rates may be underestimated because some overdose death certificates do not report specific drugs involved, the authors noted.

Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” study author Beth Han, MD, PhD, of NIDA, said in a press release.

“By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions,” she said.

The study was sponsored by NIDA.

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

The national rate of methamphetamine overdose deaths shot up significantly between 2011 and 2018, particularly among non-Hispanic American Indian and Alaska Native communities, new research shows.

Rates rose for both men and women but more so among men, the study found. The spike in these deaths underscores the need for culturally tailored prevention and treatment strategies, the study authors said.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam – particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” senior investigator Nora D. Volkow, MD, director of the National Institute on Drug Abuse, said in a press release.

The study was published online Jan. 20 in JAMA Psychiatry.
 

Highly toxic

Methamphetamine is highly toxic. Its use is associated with pulmonary and cardiovascular pathology and frequently co-occurs with other substance use and mental disorders.

In addition, there are currently no Food and Drug Administration–approved medications to reverse methamphetamine overdose or treat methamphetamine use disorder.

However, behavioral therapies can be effective in reducing the harm associated with methamphetamine use. In addition, a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorder.

For the study, the investigators used deidentified public health surveillance data from the Centers for Disease Control and Prevention’s National Vital Statistics System files for multiple causes of death.

The researchers used the psychostimulant category to estimate death rates from methamphetamine. The authors noted that up to 90% of psychostimulant-involved death certificates mentioned methamphetamine.

Researchers stratified age-adjusted overdose death rates during 2011-2018 by sex and race/ethnicity and limited the analysis to those aged 25-54 years. Approximately 80% of methamphetamine users are between the ages of 25 and 54 years.

During the study period, rates for methamphetamine-involved deaths increased from 1.8 to 10.1 per 100,000 among men (average annual percentage change, 29.1; 95% confidence interval, 25.5-32.8; P < .001) and from 0.8 to 4.5 per 100,000 among women (AAPC, 28.1; 95% CI, 25.1-31.2; P < .001).
 

Need for tailored interventions

For both men and women, those in non-Hispanic American Indian or Alaska Native communities had the highest rates. These increased from 5.6 to 26.4 per 100,000 among men and from 3.6 to 15.6 per 100,000 among women.

While American Indian and Alaska Native individuals experience sociostructural disadvantages, their cultural strengths “can be leveraged to improve addiction outcomes,” the investigators wrote.

Non-Hispanic Whites had the second highest rates. These rose from 2.2 to 12.6 per 100,000 among men (AAPC, 29.8; 95% CI, 24.3-35.4; P < .001) and from 1.1 to 6.2 per 100,000 among women (AAPC, 29.1; 95% CI, 25.2-33.2; P < .001).

Rates among Hispanic individuals increased from 1.4 to 6.6 per 100,000 for men and from 0.5 to 2.0 per 100,000 for women. Among non-Hispanic Asian individuals, rates increased to 3.4 per 100,000 for men and to 1.1 per 100,000 for women. Non-Hispanic Black individuals had low rates. Within each racial/ethnic group, rates were higher among men versus women.

Methamphetamine death rates may be underestimated because some overdose death certificates do not report specific drugs involved, the authors noted.

Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” study author Beth Han, MD, PhD, of NIDA, said in a press release.

“By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions,” she said.

The study was sponsored by NIDA.

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