Clinician Reviews

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

Treatment with tapinarof 1%, a nonsteroidal topical cream in clinical development, was associated with durable control of plaque psoriasis in a 52-week phase 3 trial presented as a late-breaker at the virtual annual congress of the European Academy of Dermatology and Venereology.

The drug has several unique features with meaningful clinical differences from other topical psoriasis therapies, according to Linda Stein Gold, MD, director of dermatology clinical research, Henry Ford Health System, Detroit.

“The currently available nonsteroidal topical therapies are typically associated with significant irritation. We did not see that with tapinarof,” said Dr. Stein Gold. This is one of several reasons she believes this drug will be a valuable addition if it receives regulatory approval.

Tapinarof is a small-molecule aryl hydrocarbon receptor (AhR) modulating agent. AhR is widely expressed in immune cells, including macrophages, mast cells, and antigen-presenting cells. It is believed that modulation of AhR signaling by tapinarof reverses immune dysregulation that is involved in the formation of psoriatic lesions.

The newly presented PSOARING 3 data with tapinarof 1% build on the data from the 12-week PSOARING 1 and PSOARING 2 trials, which were released in August 2020 but have yet to be published.

The primary endpoint in both of the 12-week trials, each of which enrolled about 500 patients with plaque psoriasis, was a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear). Relative to a placebo response rate of about 6% in both trials, the proportion of patients who achieved scores of 0/1 with tapinarof 1% was 35.4% and 40.2% in the PSOARING 1 and PSOARING 2 trials, respectively (P < .0001 vs. placebo in both studies).

For the key secondary endpoint of at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75), the relative advantage for tapinarof over placebo was similar. The results were highly statistically significant (P < .0001) in both of the 12-week trials.

More than 90% of the patients who participated in PSOARING 1 and PSOARING 2 and were eligible for the open-label PSOARING 3 extension trial, according to Dr. Stein Gold.

For the 79 patients with a score of 0 at the time of enrollment, tapinarof 1% was reapplied only if the PGA score reached at least 2 during the course of the study. For the 680 patients who entered with a PGA score of at least 1, once-daily applications of tapinarof 1% cream were maintained until a PGA score of 0 was achieved.

In the outcome analysis, response was defined as the proportion of patients with an initial PGA score of at least2 who achieved PGA 0. A remittive effect was defined as duration of a PGA score of 0 or 1 while off therapy after achieving a PGA score of 0. Durability of response was defined as the proportion of patients who achieved a PGA sore of 0 or 1 at least once during the study while on therapy. This last outcome provided a test of tachyphylaxis.

“Overall, 40.9% of patients achieved complete disease clearance at least once during the trial, and 58.2% who entered the study with a PGA score of 2 or higher achieved a PGA score of 0 or 1,” Dr. Stein Gold reported.

For the 79 patients who entered PSOARING 3 with a PGA score of 0 and were off treatment, the median duration of a remittive effect was 115 days. For the patients who entered the trial with a higher PGA score but who achieved a score of 0 during the study (312 patients), the mean remittive effect after discontinuing therapy was 130 days.

There was no evidence of tachyphylaxis. Rather, “there was no loss of effect despite intermittent therapy observed over the course of the trial,” Dr. Stein Gold reported.

The most common treatment-emergent adverse events in PSOARING 3, as in the previous PSOARING studies, were folliculitis, which was observed in 24.0% of patients; contact dermatitis, which occurred in 5.9% of patients; and headache, which was reported in 2%. Rates of study drug discontinuations for folliculitis and contact dermatitis were 1.2% and 1.4%, respectively. Headache did not lead to any study discontinuations.

Calling tapinarof a “first-in-class nonsteroidal,” Dr. Stein Gold suggested that this is likely to be a useful adjunctive therapy for psoriasis control. It avoids the adverse events associated with long-term topical steroid use, and its tolerability might be particularly attractive for use in sensitive areas.

“This is likely to be very useful in patients who are looking for a topical therapy for skin folds or the face, where there is a need for well-tolerated topical treatments,” Dr. Stein Gold said.

There are a lot of reasons to be positive about a new, well-tolerated topical agent for psoriasis, particularly as an alternative to topical steroids, agreed Adam Friedman, MD, director of translational research and professor and chair of the department of dermatology at George Washington University, Washington. He considers the data with tapinarof promising in general, but he also likes any new, effective topical psoriasis therapy.

“Patients and physicians are always hungry for new options, especially psoriasis patients, given many have ‘been there and done that’ with topical steroids,” Dr. Friedman said.

“Topical steroids are not irritating, but long-term use beyond recommended dosing can lead to skin thinning, lightening, tachyphylaxis, and, if really abused, HPA [hypothalamic-pituitary-adrenal] axis suppression and adrenal insufficiency,” he observed.

A topical therapy with a durable effect is particularly intriguing.

“The other issue with topical steroids is that psoriatic plaques return rather easily after stopping. The data I have seen with tapinarof show more sustainability after cessation, owing to its mechanism of action,” Dr. Friedman said. Rather than its potential for application to sensitive areas, such as the face, the durability “to me is more interesting.”

He suspects that, owing to “the incurable steroid phobia that haunts many of our patients,” an effective nonsteroidal topical option is also likely to lead to better compliance with topical treatment over time.

“A well-tolerated nonsteroidal topical drug will probably find an important place in the future management of chronic inflammatory diseases,” Marius-Anton Ionescu, MD, PhD, a dermatologist at the Hôpital Saint Louis, Paris, said in an interview. He referred to the positive effects of treatment with tapinarof in clinical trials in adults with atopic dermatitis, in addition to psoriasis.

Tapinarof 1% is also being investigated in a phase 3 study involving patients with moderate to severe atopic dermatitis. In that study, patients are as young as age 2 years. The drug is under review at the Food and Drug Administration for the plaque psoriasis indication in adults.

Dr. Stein Gold has financial relationships with Arcutis, Amgen, Bristol-Myers Squibb, Eli Lilly, Leo Pharma Ortho Dermatologic, UCB, and Dermavant Sciences, which is developing tapinarof and is provided funding for the PSOARING 3 trial. Dr. Friedman reported financial relationships with Amgen, Biogen, Encore, Galderma, GlaxoSmithKline, IntraDerm, Johnson & Johnson, Nerium, Novartis, Oculus, Onset, Pfizer, Sanova, and Valeant Pharmaceuticals. Dr. Ionescu has been a speaker or investigator (honoraria) for Celgene, Novartis, Lilly, and Uriage Cosmetics.

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

Treatment with tapinarof 1%, a nonsteroidal topical cream in clinical development, was associated with durable control of plaque psoriasis in a 52-week phase 3 trial presented as a late-breaker at the virtual annual congress of the European Academy of Dermatology and Venereology.

The drug has several unique features with meaningful clinical differences from other topical psoriasis therapies, according to Linda Stein Gold, MD, director of dermatology clinical research, Henry Ford Health System, Detroit.

“The currently available nonsteroidal topical therapies are typically associated with significant irritation. We did not see that with tapinarof,” said Dr. Stein Gold. This is one of several reasons she believes this drug will be a valuable addition if it receives regulatory approval.

Tapinarof is a small-molecule aryl hydrocarbon receptor (AhR) modulating agent. AhR is widely expressed in immune cells, including macrophages, mast cells, and antigen-presenting cells. It is believed that modulation of AhR signaling by tapinarof reverses immune dysregulation that is involved in the formation of psoriatic lesions.

The newly presented PSOARING 3 data with tapinarof 1% build on the data from the 12-week PSOARING 1 and PSOARING 2 trials, which were released in August 2020 but have yet to be published.

The primary endpoint in both of the 12-week trials, each of which enrolled about 500 patients with plaque psoriasis, was a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear). Relative to a placebo response rate of about 6% in both trials, the proportion of patients who achieved scores of 0/1 with tapinarof 1% was 35.4% and 40.2% in the PSOARING 1 and PSOARING 2 trials, respectively (P < .0001 vs. placebo in both studies).

For the key secondary endpoint of at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75), the relative advantage for tapinarof over placebo was similar. The results were highly statistically significant (P < .0001) in both of the 12-week trials.

More than 90% of the patients who participated in PSOARING 1 and PSOARING 2 and were eligible for the open-label PSOARING 3 extension trial, according to Dr. Stein Gold.

For the 79 patients with a score of 0 at the time of enrollment, tapinarof 1% was reapplied only if the PGA score reached at least 2 during the course of the study. For the 680 patients who entered with a PGA score of at least 1, once-daily applications of tapinarof 1% cream were maintained until a PGA score of 0 was achieved.

In the outcome analysis, response was defined as the proportion of patients with an initial PGA score of at least2 who achieved PGA 0. A remittive effect was defined as duration of a PGA score of 0 or 1 while off therapy after achieving a PGA score of 0. Durability of response was defined as the proportion of patients who achieved a PGA sore of 0 or 1 at least once during the study while on therapy. This last outcome provided a test of tachyphylaxis.

“Overall, 40.9% of patients achieved complete disease clearance at least once during the trial, and 58.2% who entered the study with a PGA score of 2 or higher achieved a PGA score of 0 or 1,” Dr. Stein Gold reported.

For the 79 patients who entered PSOARING 3 with a PGA score of 0 and were off treatment, the median duration of a remittive effect was 115 days. For the patients who entered the trial with a higher PGA score but who achieved a score of 0 during the study (312 patients), the mean remittive effect after discontinuing therapy was 130 days.

There was no evidence of tachyphylaxis. Rather, “there was no loss of effect despite intermittent therapy observed over the course of the trial,” Dr. Stein Gold reported.

The most common treatment-emergent adverse events in PSOARING 3, as in the previous PSOARING studies, were folliculitis, which was observed in 24.0% of patients; contact dermatitis, which occurred in 5.9% of patients; and headache, which was reported in 2%. Rates of study drug discontinuations for folliculitis and contact dermatitis were 1.2% and 1.4%, respectively. Headache did not lead to any study discontinuations.

Calling tapinarof a “first-in-class nonsteroidal,” Dr. Stein Gold suggested that this is likely to be a useful adjunctive therapy for psoriasis control. It avoids the adverse events associated with long-term topical steroid use, and its tolerability might be particularly attractive for use in sensitive areas.

“This is likely to be very useful in patients who are looking for a topical therapy for skin folds or the face, where there is a need for well-tolerated topical treatments,” Dr. Stein Gold said.

There are a lot of reasons to be positive about a new, well-tolerated topical agent for psoriasis, particularly as an alternative to topical steroids, agreed Adam Friedman, MD, director of translational research and professor and chair of the department of dermatology at George Washington University, Washington. He considers the data with tapinarof promising in general, but he also likes any new, effective topical psoriasis therapy.

“Patients and physicians are always hungry for new options, especially psoriasis patients, given many have ‘been there and done that’ with topical steroids,” Dr. Friedman said.

“Topical steroids are not irritating, but long-term use beyond recommended dosing can lead to skin thinning, lightening, tachyphylaxis, and, if really abused, HPA [hypothalamic-pituitary-adrenal] axis suppression and adrenal insufficiency,” he observed.

A topical therapy with a durable effect is particularly intriguing.

“The other issue with topical steroids is that psoriatic plaques return rather easily after stopping. The data I have seen with tapinarof show more sustainability after cessation, owing to its mechanism of action,” Dr. Friedman said. Rather than its potential for application to sensitive areas, such as the face, the durability “to me is more interesting.”

He suspects that, owing to “the incurable steroid phobia that haunts many of our patients,” an effective nonsteroidal topical option is also likely to lead to better compliance with topical treatment over time.

“A well-tolerated nonsteroidal topical drug will probably find an important place in the future management of chronic inflammatory diseases,” Marius-Anton Ionescu, MD, PhD, a dermatologist at the Hôpital Saint Louis, Paris, said in an interview. He referred to the positive effects of treatment with tapinarof in clinical trials in adults with atopic dermatitis, in addition to psoriasis.

Tapinarof 1% is also being investigated in a phase 3 study involving patients with moderate to severe atopic dermatitis. In that study, patients are as young as age 2 years. The drug is under review at the Food and Drug Administration for the plaque psoriasis indication in adults.

Dr. Stein Gold has financial relationships with Arcutis, Amgen, Bristol-Myers Squibb, Eli Lilly, Leo Pharma Ortho Dermatologic, UCB, and Dermavant Sciences, which is developing tapinarof and is provided funding for the PSOARING 3 trial. Dr. Friedman reported financial relationships with Amgen, Biogen, Encore, Galderma, GlaxoSmithKline, IntraDerm, Johnson & Johnson, Nerium, Novartis, Oculus, Onset, Pfizer, Sanova, and Valeant Pharmaceuticals. Dr. Ionescu has been a speaker or investigator (honoraria) for Celgene, Novartis, Lilly, and Uriage Cosmetics.

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

Treatment with tapinarof 1%, a nonsteroidal topical cream in clinical development, was associated with durable control of plaque psoriasis in a 52-week phase 3 trial presented as a late-breaker at the virtual annual congress of the European Academy of Dermatology and Venereology.

The drug has several unique features with meaningful clinical differences from other topical psoriasis therapies, according to Linda Stein Gold, MD, director of dermatology clinical research, Henry Ford Health System, Detroit.

“The currently available nonsteroidal topical therapies are typically associated with significant irritation. We did not see that with tapinarof,” said Dr. Stein Gold. This is one of several reasons she believes this drug will be a valuable addition if it receives regulatory approval.

Tapinarof is a small-molecule aryl hydrocarbon receptor (AhR) modulating agent. AhR is widely expressed in immune cells, including macrophages, mast cells, and antigen-presenting cells. It is believed that modulation of AhR signaling by tapinarof reverses immune dysregulation that is involved in the formation of psoriatic lesions.

The newly presented PSOARING 3 data with tapinarof 1% build on the data from the 12-week PSOARING 1 and PSOARING 2 trials, which were released in August 2020 but have yet to be published.

The primary endpoint in both of the 12-week trials, each of which enrolled about 500 patients with plaque psoriasis, was a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear). Relative to a placebo response rate of about 6% in both trials, the proportion of patients who achieved scores of 0/1 with tapinarof 1% was 35.4% and 40.2% in the PSOARING 1 and PSOARING 2 trials, respectively (P < .0001 vs. placebo in both studies).

For the key secondary endpoint of at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75), the relative advantage for tapinarof over placebo was similar. The results were highly statistically significant (P < .0001) in both of the 12-week trials.

More than 90% of the patients who participated in PSOARING 1 and PSOARING 2 and were eligible for the open-label PSOARING 3 extension trial, according to Dr. Stein Gold.

For the 79 patients with a score of 0 at the time of enrollment, tapinarof 1% was reapplied only if the PGA score reached at least 2 during the course of the study. For the 680 patients who entered with a PGA score of at least 1, once-daily applications of tapinarof 1% cream were maintained until a PGA score of 0 was achieved.

In the outcome analysis, response was defined as the proportion of patients with an initial PGA score of at least2 who achieved PGA 0. A remittive effect was defined as duration of a PGA score of 0 or 1 while off therapy after achieving a PGA score of 0. Durability of response was defined as the proportion of patients who achieved a PGA sore of 0 or 1 at least once during the study while on therapy. This last outcome provided a test of tachyphylaxis.

“Overall, 40.9% of patients achieved complete disease clearance at least once during the trial, and 58.2% who entered the study with a PGA score of 2 or higher achieved a PGA score of 0 or 1,” Dr. Stein Gold reported.

For the 79 patients who entered PSOARING 3 with a PGA score of 0 and were off treatment, the median duration of a remittive effect was 115 days. For the patients who entered the trial with a higher PGA score but who achieved a score of 0 during the study (312 patients), the mean remittive effect after discontinuing therapy was 130 days.

There was no evidence of tachyphylaxis. Rather, “there was no loss of effect despite intermittent therapy observed over the course of the trial,” Dr. Stein Gold reported.

The most common treatment-emergent adverse events in PSOARING 3, as in the previous PSOARING studies, were folliculitis, which was observed in 24.0% of patients; contact dermatitis, which occurred in 5.9% of patients; and headache, which was reported in 2%. Rates of study drug discontinuations for folliculitis and contact dermatitis were 1.2% and 1.4%, respectively. Headache did not lead to any study discontinuations.

Calling tapinarof a “first-in-class nonsteroidal,” Dr. Stein Gold suggested that this is likely to be a useful adjunctive therapy for psoriasis control. It avoids the adverse events associated with long-term topical steroid use, and its tolerability might be particularly attractive for use in sensitive areas.

“This is likely to be very useful in patients who are looking for a topical therapy for skin folds or the face, where there is a need for well-tolerated topical treatments,” Dr. Stein Gold said.

There are a lot of reasons to be positive about a new, well-tolerated topical agent for psoriasis, particularly as an alternative to topical steroids, agreed Adam Friedman, MD, director of translational research and professor and chair of the department of dermatology at George Washington University, Washington. He considers the data with tapinarof promising in general, but he also likes any new, effective topical psoriasis therapy.

“Patients and physicians are always hungry for new options, especially psoriasis patients, given many have ‘been there and done that’ with topical steroids,” Dr. Friedman said.

“Topical steroids are not irritating, but long-term use beyond recommended dosing can lead to skin thinning, lightening, tachyphylaxis, and, if really abused, HPA [hypothalamic-pituitary-adrenal] axis suppression and adrenal insufficiency,” he observed.

A topical therapy with a durable effect is particularly intriguing.

“The other issue with topical steroids is that psoriatic plaques return rather easily after stopping. The data I have seen with tapinarof show more sustainability after cessation, owing to its mechanism of action,” Dr. Friedman said. Rather than its potential for application to sensitive areas, such as the face, the durability “to me is more interesting.”

He suspects that, owing to “the incurable steroid phobia that haunts many of our patients,” an effective nonsteroidal topical option is also likely to lead to better compliance with topical treatment over time.

“A well-tolerated nonsteroidal topical drug will probably find an important place in the future management of chronic inflammatory diseases,” Marius-Anton Ionescu, MD, PhD, a dermatologist at the Hôpital Saint Louis, Paris, said in an interview. He referred to the positive effects of treatment with tapinarof in clinical trials in adults with atopic dermatitis, in addition to psoriasis.

Tapinarof 1% is also being investigated in a phase 3 study involving patients with moderate to severe atopic dermatitis. In that study, patients are as young as age 2 years. The drug is under review at the Food and Drug Administration for the plaque psoriasis indication in adults.

Dr. Stein Gold has financial relationships with Arcutis, Amgen, Bristol-Myers Squibb, Eli Lilly, Leo Pharma Ortho Dermatologic, UCB, and Dermavant Sciences, which is developing tapinarof and is provided funding for the PSOARING 3 trial. Dr. Friedman reported financial relationships with Amgen, Biogen, Encore, Galderma, GlaxoSmithKline, IntraDerm, Johnson & Johnson, Nerium, Novartis, Oculus, Onset, Pfizer, Sanova, and Valeant Pharmaceuticals. Dr. Ionescu has been a speaker or investigator (honoraria) for Celgene, Novartis, Lilly, and Uriage Cosmetics.

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

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

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

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

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

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

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

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

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

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

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

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.

Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.

Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.

“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.

Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.

Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.

The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.

He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”

The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.

“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
 

Controversies in non-COVID diseases

Controversies and new treatments are plentiful in other diseases as well.

• At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
• In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
• Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
• Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
• The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
• This year’s program offers a symposium on private-public partnerships to help jump-start development.
• One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.

Around-the-world COVID view

Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.

Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.

For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.

Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.

An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.

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

Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.

Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.

Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.

“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.

Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.

Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.

The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.

He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”

The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.

“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
 

Controversies in non-COVID diseases

Controversies and new treatments are plentiful in other diseases as well.

• At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
• In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
• Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
• Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
• The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
• This year’s program offers a symposium on private-public partnerships to help jump-start development.
• One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.

Around-the-world COVID view

Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.

Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.

For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.

Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.

An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.

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

Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.

Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.

Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.

“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.

Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.

Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.

The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.

He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”

The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.

“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
 

Controversies in non-COVID diseases

Controversies and new treatments are plentiful in other diseases as well.

• At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
• In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
• Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
• Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
• The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
• This year’s program offers a symposium on private-public partnerships to help jump-start development.
• One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.

Around-the-world COVID view

Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.

Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.

For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.

Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.

An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.

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

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.