The American Cough Conference was held June 11-12. Coverage from the meeting, which brought together health care professionals involved in the research and management of patients with cough, is now available.

Coverage of the American Cough Conference

The SLEEP Meeting was held June 10-13. Coverage includes session summaries and interviews with key opinion leaders in sleep and circadian science.

Coverage of the SLEEP Meeting

Coverage from the EHA2021 Virtual Congress, including session summaries, poster write-ups, and interviews with key opinion leaders is now available

Coverage of EHA 2021

If 2020 was dominated by the news of how COVID-19 spread across the globe, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

A Timeline of COVID-19 Vaccine Developments in 2021

We interview experts on investigational treatments such as liso-cel, and ask how to bring them to community practice.

Spotlight on CAR T-Cell Therapy

The American Journal of Accountable Care® features research and commentary on new payment models.

New Members for AJAC Board

We do not yet know the exact mechanism of action of sodium glucose co-transporter 2 (SGLT2) inhibitors in 

 (HF), so we must explore the possibility that a novel mechanism is at work, stated Clyde W. Yancy, MD, MSc, professor of medicine, chief of cardiology, and vice dean for diversity and inclusion at Northwestern University’s Feinberg School of Medicine.

Are we learning more about why SGLT2 inhibitors are so effective at reducing heart failure related hospitalizations?

We’d love to say that we've sorted out the mechanism of action of the [SGLT2] inhibitors. We can think only about what we know is not happening. For example, every other heart failure therapy that's been shown to be beneficial has been associated with reverse remodeling, restoring the original geometry and function of the heart muscle—except with the SGLT2 inhibitors. We have seen insufficient data to say that that's the mechanism. Other therapies that are beneficial in heart failure retard or reduce neurohormonal activation. We don't see a real strong signal of that either.

What that means, then, is that we must consider that there is a novel mechanism not previously explored. Some of us think that might be in mitochondrial respiration. Some of us think that might be with mitochondrial energetics. But here is something that we do know: Small numbers, they’re very compelling. When we administer a loop diuretic to decongest the patient with symptomatic heart failure, there is a concomitant exaggeration of a neurohormonal activation cascade, almost attenuating any potential benefit we might get from volume contraction. With the SGLT2 inhibitors, there is an increase in the fractional excretion of sodium, so it does function as a diuretic, when in addition, there is not an elaboration of these same neural hormones.

Does that mean that the SGLT2 inhibitors are a better diuretic and the diuretic is more in line with homeostasis of the cardiovascular profile, particularly the neuronal activation cascade? It's just theoretical. But the point that I make here is that in the context of everything else that we're exploring, what happens to hemoglobin, for example, when we give the SGLT2 inhibitor? What happens to collagen turnover?

There's so many exciting considerations. None yet have come forward as the mechanism, and it may be multiple mechanisms. But it's very clear that we're in new territory, and we're eager to find these new questions and then solve these new answers, because I don't think that what we've known previously is going to apply to this drug.

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We do not yet know the exact mechanism of action of sodium glucose co-transporter-2 (SGLT2) inhibitors in heart failure (HF), but there are many exciting pssibilities, stated Clyde W. Yancy, MD, MSc, of Northwestern University’s Feinberg School of Medicine.

Dr Clyde Yancy: We Must Continue to Explore Why SGLT2 Inhibitors Are Effective in HF

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

Neurology, Neuroimmunology & Neuroinflammation

details the associations between body mass index (BMI), including overweight and obesity, and pediatric-onset 

Around 3% to 10% of individuals with MS are affected by POMSl; the condition can occur before age 10 years in 1% of those with MS. In addition, “a higher relapse rate is observed in children despite better recoveries after relapses, and a slower evolution toward a secondarily progressive disease has been described” in this population, authors explained.

Low-grade inflammation mediated by obesity may lead to neuroinflammation through disruption of the blood-brain barrier (BBB) or the primary activation of microglia in the central nervous system in response to adipokines released into the peripheral circulation by fatty tissues, they added.

To analyze the link between high BMI in children and the occurrence of POMS in the French pediatric population and to compare the characteristics of those with POMS who had normal weight or who had a high BMI, researchers carried out a case-control study.

All study participants were under the age of 18 at MS diagnosis and were diagnosed between 2010 and 2018. Any patient who took treatments likely to influence BMI or who had other conditions likely to impact BMI were excluded.

Data from 60 patients (39 girls, 21 boys) with POMS, 113 nonneurologic controls (NNCs; serving as a local control population) (68 girls, 45 boys), and 18,614 healthy controls (HCs) (9271 girls, 9343 boys) were included in the final analysis.

Researchers used HC data “to model the mean corpulence (BMI) trajectories of healthy French boys and girls (data not shown), and these trajectories served as a reference against which to compare our patients with POMS and NNCs,” they explained.

International Obesity Task Force (IOTF) categories were used to define normal weight (BMI < 25), overweight (BMI between 25 and 30), and obesity (BMI > 30).

In boys, crude BMI (cBMI) and residual BMI (rBMI) were significantly higher in patients with POMS compared with NNCs (cBMI: +2.9; rBMI: +2.95; 

In girls, cBMI or rBMI did not differ between POMS and NNCs patients (cBMI 

Cerebral spinal fluid (CSF) inflammatory markers increased with BMI in prepubertal patients (

 < .01), whereas vitamin D level at diagnosis was lower in boys with higher BMI (

Increased BMI was not associated with clinical and radiologic disease characteristics.

“We observed a higher prevalence of overweight and obesity in our sample of French patients with POMS at diagnosis, and one of our findings is the possible sexual dimorphism, attributing a higher risk to male sex,” authors wrote. They continued, “We have also noticed that overweight and obesity were associated with a higher probability to observe CSF inflammatory markers in younger patients.”

Researchers hypothesized testosterone may account for the stronger association between POMS and obesity seen in boys in the current study, as the hormone is known for its anti-inflammatory actions at the cerebral level and is depleted during puberty. Furthermore, “In adult men with MS, testosterone depletion is associated with increased disease severity and neuroinflammation progression,” they explained. Future studies are needed to better explore this hypothesis.

Given the study’s sample size, results should be interpreted with caution and larger-scale studies are warranted to better clarify the role of sex hormones in POMS.

Overall, “overweight and obesity are observed more frequently in boys with POMS at the time of diagnosis compared with a local control population (NNC) and the healthy French pediatric population (HC),” authors concluded. “Excess body fat appears to influence initial inflammation in the CSF in prepubertal patients, but would not influence the annual relapse rate, the age of diagnosis of the pathology, or the initial clinical and radiologic parameters.”

Milles P, De Filippo G, Maurey H, Tully T, Deiva K. Obesity in pediatric-onset multiple sclerosis: a French cohort study. 

Published online July 20, 2021. doi:10.1212/NXI.0000000000001044

Articles

Investigators explored the associations between body weight and pediatric-onset multiple sclerosis.

Assessing the Relationship Between Obesity and Pediatric-Onset MS

Oncologists from the Alliance for Patient Access wrote a 

 from the physician’s perspective regarding the benefits of using oncology 

, reasons behind physician hesitancy to switch patients away from reference products, and best practices to ensure physician and patient confidence in these products.

 can be deadly, decisions about treatment must be made with the utmost precision. Whether in determining the initial course of treatment or navigating changes along the way, the best care stems from shared decision-making between a patient and a trusted clinician,” wrote coauthors Arturo Loaiza-Bonilla, MD, and Jeffrey B. VanDeusen, MD, PhD.

One of the benefits beyond cost-effectiveness that the authors mentioned about biosimilars was that the subtle, clinically meaningless differences between biosimilars and their reference products allow doctors to prescribe the same therapeutic pathway while potentially avoiding adverse side effects.

“These differences, while not clinically meaningful, can be an asset if a patient experiences an adverse reaction to the reference product,” wrote the authors.

This phenomenon is unique to biologic drugs because generic drugs are identical to brand drugs and if a patient experiences adverse events serious enough to discontinue treatment, they would need to switch drugs completely.

Additionally, biosimilars offer a way around potential drug shortages and supply chain disruptions, such as those observed during the COVID-19 pandemic, ensuring that patients could continue therapy.

The authors cited the natural skepticism the oncologists have regarding biosimilar products as a reason that physicians are hesitant to use biosimilars, saying that failed innovations in the past combined with the high stakes patients with cancer face make oncologists “intrinsically risk averse” when it comes to using new medicines.

Physicians also experience confusion surrounding the evidence supporting biosimilar approvals, which makes data difficult to keep up with and could lead to more hesitancy among doctors and patients. The authors suggested that data and other information needs to be collected and shared regularly and real-world data needs to be consistently relayed to physicians to reassure them of the efficacy and safety of biosimilars.

“The potential benefits of biosimilars are meaningless if the medications are not utilized,” the authors said.

Another polarizing issue for biosimilars is the concept of nonmedical switching, which involves health care policies requiring patients to be switched from 1 product to another without a medical reason. Health plans typically base their formulary preferences on which agents best meet their financial interests.

However, insurers overriding treatment decisions based on their preference lists can make patients feel uncertain, powerless, or resentful. Agents may be switched if an insurer changes their formulary lists or a patient changes their insurance provider, which could result in patients being forced to switch to a product that could produce adverse events and potentially pay more out-of-pocket costs.

“It should not be discounted, particularly in the case of a lengthy battle with cancer, that patients also may have an emotional attachment to medication that’s working for them and not want to change,” wrote the authors.

Nonmedical switching can also create a lot of administrative work for clinics, which may not have the manpower needed to handle it. Insurer-directed switches may require filling out new paperwork, sending letters, making phone calls, and obtaining new patient consent forms, which could undermine confidence in the switched medication and create a sense of increased risks among patients.

“Physicians and patients both benefit when policies support access to multiple treatment options and allow shared decision-making about which treatments work best for each individual patient,” the authors noted.

Loaiza-Bonilla A, VanDeusen JB. Biosimilars: Expanding options for cancer care. IfPA website. 

https://admin.allianceforpatientaccess.org/wp-content/uploads/2021/06/AfPA_Biosimilars_Oncology_Paper_June2021.pdf

. Published June 24, 2021. Accessed July 26, 2021.

Two oncologists dive into the reasons behind physician hesitancy and unwillingness to prescribe biosimilars to patients with cancer and make suggestions on how to increase confidence in these agents.

Alliance for Patient Access Releases Paper on Biosimilar Best Practices in Oncology

 is significantly associated with irritable bowel syndrome (IBS) and peptic ulcers among middle-aged and older patients, according to results of a UK Biobank study. Findings were published in 

Findings of previous studies have indicated a potential link between migraine and disruptions in the gut-brain-axis, “which entails that there are bidirectional relationships between neurological and gastrointestinal (GI) symptoms,” authors explained.

Several mechanisms have been proposed to explain this link, including disruptions to the serotonergic system and increased gut permeability and inflammatory processes.

In an effort to map the associations between migraine and IBS, peptic ulcers, 

(HP) infection, celiac disease, Crohn disease, and ulcerative colitis in middle-aged and older individuals, researchers obtained data from the UK Biobank resource. The large prospective cohort study includes health-related information from over 500,000 participants aged between 37 and 69 years at the time of recruitment.

Baseline assessments, including physical measurements, questionnaires, and verbal interviews, were carried out between 2006 and 2010.

Due to missing information, data from 489,753 individuals were included in the final analysis. Results were adjusted for potentially confounding conditions—such as cardiovascular diseases (CVD) and neurological or GI conditions other than those studied—and for use of nonsteroidal anti-inflammatory drugs (NSAIDs). Adjustments were also made for gender, age, and other factors.

Among the individuals included, total prevalence of migraine was 2.9%, and prevalence was higher among women (4.2%) than men (1.4%). Migraineurs were also more likely to be younger, have a lower body mass index, and have a college or university degree.

Migraine was significantly associated with IBS (odds ratio [OR], 2.24; 95% CI, 2.08-2.40; 

 < .001) and peptic ulcers (OR, 1.55; 95% CI, 1.35-1.77; 

Migraine was not associated with HP infection (OR, 1.34; 95% CI, 1.04-1.73; 

 = .024), celiac disease (OR, 1.29; 95% CI, 1.04-1.60; 

 = .023), Crohn disease (OR, 1.08; 95% CI, 0.80-1.45; 

 = .617), or ulcerative colitis (OR, 1.00; 95% CI, 0.79-1.27; 

 = .979) after adjusting for multiple testing.

The percentage of participants with CVD was lower in the migraine group.

The use of NSAIDs indicated for the treatment of migraine was twice as common in the migraine group as in the control group.

Among the GI disorders studied, IBS was the most common diagnosis (2.3%) in the full sample, followed by peptic ulcers (1.2%), ulcerative colitis (0.5%), celiac disease (0.4%), Crohn disease (0.3%), and HP infection (0.3%).

The research indicates that lifestyle factors appear to play a role in IBS and peptic ulcers. Because of this, “future studies may wish to evaluate whether the same lifestyle interventions could affect both GI and migraine symptoms in patients with comorbidity,” authors explained.

As there were limited participants with Crohn disease and ulcerative colitis in the current sample, researchers suggested the low prevalence of these conditions may have limited their power to detect potential associations and noted future ad hoc studies may be warranted.

Low prevalence rates for all conditions studied and the age range of those included also mark limitations to the generalizability of findings.

Overall, results indicate “the link between migraine and autoimmune GI conditions is weaker than that of migraine and IBS and peptic ulcers,” authors concluded.

Welander NZ, Olivo G, Pisanu C, Rukh G, Schiöth HB, and Mwinyi J. Migraine and gastrointestinal disorders in middle and old age: a UK biobank study. 

 Published online July 21, 2021. doi:10.1002/brb3.2291

Results of a UK Biobank study outline the association between migraine and several gastrointestinal disorders.

UK Biobank Study Reveals IBS, Peptic Ulcers Linked With Migraine 

Calling it the “logical fulfillment of the ethical commitment of all health care workers” to put patients first, 57 medical groups Monday called for mandatory COVID-19 vaccination for all staff working in health care and long-term care.

“Vaccination is the primary way to put the pandemic behind us and avoid the return of stringent public health measures,” the American Medical Association, the American Public Health Association, the American Pharmaceutical Association, the American Nurses Association and other groups wrote in 

Later in the day, the Department of Veterans Affairs announced that 115,000 of its health care workers would be required to get vaccinated, 

. And New York City, which last week mandated vaccines for staff in its public health system, expanded it to all municipal workers, including police officers and teachers, while California also announced a vaccine requirement for state workers as well as health care staff.

The increasing alarm comes as the delta variant is causing cases in the United States 

 this month, and even more in Southern states where vaccination rates are particularly lagging, such as Missisippi and Arkansas.

The statement noted that vaccination is already required by many organizations for 

, and that vaccination protects children who can't get shots and those with compromised immune systems.

The problem is particularly concerning in long-term care facilities; nationally, about 80% of nursing home residents are vaccinated, 

 but just about 59% of nursing home staff are. While some in the industry are fearful that a mandate could exacerbate already-existing staffing shortages, one of the groups who signed Monday’s statement indicated in its own release that the concern is manageable.

“Providers that have required staff vaccinations have reported high vaccine acceptance by previously hesitant care professionals, and many providers report that when staff vaccination rates are high, they become providers of choice in their communities” the organization Leading Age said in a statement.

The Biden administration is reluctant to call for a vaccine mandate for nursing homes, the AP reported.

Citing interviews with virologists and epidemiologists, 

Monday that signs are increasing that the more contagious delta variant is able to infect fully vaccinated individuals at a greater rate than past versions, and concerns have been raised that the vaccinated may even spread the virus.

In Singapore and Israel, the vaccinated represent a majority of those falling ill, although in the United States, the majority of those filling up ICU beds remain unvaccinated.

Thus far, vaccine mandates have been upheld by the courts. Houston Methodist Hospital in Texas dismissed 117 workers for refusing COVID-19 vaccinations; they sued, but a federal court ruled in favor of the hospital.

 dismissed 6 supervisors for refusing to get vaccinated and said it would expand the mandate to all staff. RWJBarnabasHealth, which has 35,000 employees, gave supervisory staff until June 30 to get vaccinated or obtain an exemption or deferral. Other large health care systems in the state, Hackensack Meridian Health and Virtua Health, have also implemented mandates. 

With nearly all parts of the country seeing a steady increase in COVID-19 infection, health care and medical groups are calling for mandatory vaccinations of their staff, and on Monday, the Department of Veterans Affairs, New York City, and California also announced vaccine requirements for workers.



Medical Groups Call for Mandatory COVID-19 Vaccinations for Health Care Staff

Exploring COVID-19 Brain Fog and Alzheimer Disease Risk

, researchers from University of Texas Health San Antonio and other scientists worldwide are planning to present findings on the association between brain fog, a long-term cognitive symptom of COVID-19, and potentially elevated risk of developing Alzheimer disease (AD) at the Alzheimer’s Association International Conference that begins today. Notably, findings of PET scans taken before and after a person develops the virus have suggested that infection can cause changes that overlap with those seen in AD, with genetic studies also showing that some of the same genes that would increase the likelihood of developing severe COVID-19 would also increase the risk of developing AD.

UK Potentially Cigarette-Free Within 10 Years

, Jacek Olczak, the CEO of Philip Morris International, said the company plans to stop selling cigarettes from its flagship brand Marlboro in the United Kingdom within the next 10 years. According to 

, Olczak’s comments were similar to those made by previous senior executives within Philip Morris International on ceasing production of cigarettes, which have resulted in minimal change. The UK government has previously announced plans with a goal of ending smoking in England by 2030.

Adverse Effects of Pfizer’s COVID-19 Vaccine More Likely After Infection

, patients previously infected with COVID-19 were shown to be more likely than those who were not infected to have adverse effects after their first dose of the Pfizer/BioNTech COVID-19 vaccine. In the study, published in 

, about 74% of participants had at least 1 adverse effect, including 95% of patients with prior COVID-19 and 70% of those who had not been infected. Symptom intensity was not shown to be different between the 2 groups, with most common vaccine-related symptoms including fatigue, headache, and muscle pain.

Links between COVID-19 brain fog and risk of Alzheimer disease; cigarette manufacturer Philip Morris International discusses plans to stop selling cigarettes in the United Kingdom; COVID-19 vaccine adverse effects are more likely in people previously infected with the virus.

What We’re Reading: COVID-19 Brain Fog and Alzheimer Disease; Smoke-Free UK Goal; Vaccine Adverse Effects More Likely After Infection

 can be stratified into 4 distinct trajectories of renal function decline, according to a new study that aims to help physicians better predict which patients are at the highest risk of accelerated decline.

Patients with chronic kidney disease experience a progressive decrease in kidney function over time, and some patients will progress to end-stage renal disease, which has become an increasingly common affliction worldwide, according to corresponding author Josefina Santos, MD, of the University Hospital Center of Porto, Portugal, and colleagues.

Tracking changes in a patient’s estimated glomerular filtration rate (eGFR) is one way to understand how a patient’s kidney disease is progressing, but it can be hard to interpret because some patients experience nonlinear disease progression, and some patients can have long periods without progression.

In hopes of giving physicians a better idea of what course a patient’s kidney disease is likely to take, Santos and colleagues used a number of models to analyze the cases of 378 patients with chronic kidney disease who were 65 years of age or older and who started dialysis at a single healthcare organization between 2009 and 2015. The results of their analysis were 

Clinical data used in the analysis included sex, age, body mass index, comorbities, and smoking status, among others. Laboratory data, care practices, and mortality data were also included in the analysis.

Four pre-dialysis trajectories emerged: slower decline (18.3%), gradual decline (18.3%), early rapid decline (41.2%), and rapid decline (22.2%).

A number of factors were associated with a faster decline, including 

, cognitive impairment, and pre-dialysis hospitalization. Rapid-decline patients also tended to be younger and were more likely female. The finding that women were more likely to experience rapid decline contradicts some earlier research that suggested men had faster disease progression. However, Santos and colleagues said the existing literature is mixed.

“[I]t is not clear whether sex is independently associated with faster renal disease progression, or whether the association reflects confounding by imbalances between men and women of non-controlled factors associated with renal disease progression,” they wrote.

A patient’s trajectory group was also associated with mortality, though not at first—the higher risk of death for those in the rapid decline groups only appeared after they had been on dialysis for at least one year.

One factor that did not make a difference in groupings was acute kidney injury, despite the fact that such injuries have been linked with quicker progression to ESRD. Neither inpatient diagnosis of acute kidney injury nor the presence of such an injury at the start of dialysis correlated with trajectory. Santos and colleagues said the lack of an association in their study might simply be due to the fact that a high number of patients in their cohort had acute kidney injuries.

The investigators said their study could be used to develop or strengthen electronic health record-based clinical decision tools.

“The identification and risk stratification of patients at the highest risk for worse outcomes, based on trajectory analysis of eGFR, may help to guide decision support systems and inform the patient in a shared decision-making process,” they wrote.

Santos J, Oliveira P, Severo M, Lobato L, Cabrita A, Fonseca I. Different kidney function trajectory patterns before dialysis in elderly patients: clinical implications and outcomes. 

. 2021;43(1):1049-1059. doi:10.1080/0886022X.2021.1945464

About 4 in 10 patients with chronic kidney disease will have “early rapid decline,” a trajectory more likely if the patient also has diabetes.



Kidney Function Declines Along 4 Distinct Trajectories, Study Finds

A recent systematic review supports the idea that acid suppression medications (ASMs) can increase a patient’s risk of developing recurrent 

About 1 in 6 of the half-million Americans who develop CDI each year will experience at least one recurrence of the infection. Writing in the 

, corresponding author Luigi Brunetti, PharmD, MPH, of Rutgers University, and colleagues, explained that the use of medications like antibiotics and ASMs have been linked with an increased risk of recurrent CDI, but many of the studies supporting the link between ASMs and CDI have had small sample sizes and used different definitions of exposures and outcomes.

A meta-analysis of the studies is one way to solve that problem, but Brunetti and colleagues wrote that previous meta-analyses on the ASM question were less definitive because they used both inpatient and outpatient cases.

“This distinction is important because it is commonly seen that studies that contain an outpatient population often display less integrity or accuracy in terms of data, since compliance cannot be monitored,” they wrote.

The new meta-analysis focused exclusively on inpatients. A total of 9 studies were found that looked at CDI and included medication information. Together, the studies had a patient population of 5668 people. Of those, 17.7% of patients (1003) experienced recurrent CDI, a number in line with national averages.

The data showed those patients who were taking ASMs were 64% more likely to be among those patients experiencing CDI recurrence (OR, 1.64; 95% CI, 1.13–2.38; 

2 = 79.54%). Those taking proton-pump inhibitors had an even higher risk, at 84% (OR, 1.84; 95% CI, 1.18–2.85; 

One reason these findings are important, Brunetti and colleagues noted, is that ASM use is a modifiable factor, whereas other risk factors for CDI recurrence, such as older age and recent hospitalization, are not modifiable. ASMs are also chronically over-prescribed, Brunetti said, suggesting many patients could safely be taken off their ASM because they never needed it in the first place.

“In fact, 1 study reported that 65% of ASMs prescribed in inpatients were without indication,” the authors wrote. “ASM carries many risks, especially with long-term use, that are often ill-considered.”

Those risks include pneumonia, bone fractures, and, as the current meta-analysis showed, CDI.

The reason for the link between ASMs and CDI may have to do with the impact of altered pH on gut microbial diversity, Brunetti and colleagues said, rather than on acid suppression itself. Altered pH in the upper gastrointestinal tract causes the patient’s colonic microbiome to become more susceptible to CDI. It therefore follows that proton-pump inhibitors cause the greatest increase in CDI risk, the authors wrote, since proton-pump inhibitors have a stronger effect on gastric pH than the average acid suppressor.

Brunetti and colleagues noted a few limitations, including varying in the included studies’ definitions of CDI recurrence, and a lack of information about certain patient characteristics, such as age, which limited the types of subgroup analyses the authors were able to perform. Still, the investigators said the new analysis adds strength to the case that ASMs are problematic for patients with CDI.

“Clinicians should consider discontinuation of ASMs during the treatment of CDI whenever possible,” the authors concluded.

Mehta P, Nahass RG, Brunetti L. acid suppression medications during hospitalization as a risk factor for recurrence of Clostridioides difficile infection: Systematic review and meta-analysis. 

. 2021;73(1):e62-e68. doi:10.1093/cid/ciaa545

Clinicians should avoid prescribing acid-suppression medications in general, and especially proton-pump inhibitors, to patients with Clostridioides difficile infection, according to the study.

Meta-analysis Confirms Acid Suppressors Raise Recurrent CDI Risk

Providers need to put themselves in their patients' shoes and think about how they would like to receive services, while remembering that people with HIV need more than antiretroviral therapy (ART), emphasized Helen Bygrave, MD, chronic diseases advisor for the Médecins Sans Frontières (Doctors Without Borders) 

Bygrave co-introduced, "Don't Wait - Integrate! How COVID-19 Has Highlighted the Need for HIV Services to Be Person-Centered,” along with Nomthandazo Lukhele, MD, MCBC, of the World Health Organization on day 1 of IAS 2021, this year's virtual annual meeting of the International AIDS Society, which took place July 18-21.

Can you tell us about yourself and your work?

My name is Helen Bygrave. I'm a physician based in London and the UK. I have been working in supporting HIV programs, many across Sub-Saharan Africa for about 15 years now, and more recently, I've been working as a consultant with the International AIDS Society, really supporting the differentiated service delivery initiative.

What is differentiated service delivery, and how can it improve outcomes for those living with HIV?

So, the real kind of key principles of differentiated service delivery is that this is a client-centered approach. We're designing services around the needs of the client. So, it's simplifying and adapting services across the cascade of care. So we do think about differentiated testing, differentiated prevention now. These concepts are also being used in PrEP [pre-exposure prophylaxis] rollout as well. It's about serving the needs of people living with HIV, whilst at the same time reducing the burden on the health system—and we hope kind of being cost-efficient.

But the primary goal is that we're thinking about, “How would I, if I was attending these services, like to receive my care?” I think with this session, we were also thinking, people with HIV just don't just need ART; they have other health needs. Women, mainly of childbearing age, might need contraception. As our cohorts get older, many people will need care for diabetes and cardiovascular disease. So, thinking about putting the person at the center and how do we design our service delivery models to really address those needs.

In COVID, what we've really seen is a number of the principles that we've been talking about in this differentiated service delivery community for a number of years now, really accelerated. One of the key things we've pushed over the years is to try and extend ART refills, extend the duration of time, so people don't have to come so often. And COVID has really accelerated that. We've seen scale up. PEPFAR [US President's Emergency Plan for AIDS Relief] has nice data on this really kind of scale up of providing 6 months of refills. In PEPFAR programs, that's gone from 9% to 21% over the year, in terms of the portion of people that that can now get 6 months of drugs.

We also saw during COVID that eligibility was broadened. We see longer refills being given more readily to children, which was guidelines before but often countries were not implementing that. And that, again, has been scaled up during COVID.

And also thinking about eligibility. So, pregnant women were often excluded, [but] that's now changed in the new guidelines that 

, and also allowing people to have longer refills earlier. So not waiting for 1 year, but really kind of thinking about how we can simplify care for people earlier on in their treatment story.

There's been some really nice examples presented at this conference.Some great work from Ethiopia, demonstrating, in particular, this increase in eligibility to other populations.

Providers need to put themselves in their patients' shoes and think about how they would like to receive services, emphasized Helen Bygrave, MD, chronic diseases advisor for the Médecins Sans Frontières’ (Doctors Without Borders) Access Campaign.

Dr Helen Bygrave: Differentiated HIV Service Delivery Is a Client-Centered Approach

Polypharmacy is a global problem among aging adults, and a recent study conducted in Switzerland examined the risk of 30-day hospital readmission of older adults taking many medications a day.

Specifically, the researchers sought to determine the impact of sociodemographic characteristics, medical and surgical diagnoses, clinical data such as gait, fall risk, or hearing issues, and drug regimen data with the risk of readmission among patients taking 5 or more daily prescriptions at the time the hospital sent them home.

, the authors noted that multimorbidity, polypharmacy, and inadequate drug management of prescriptions in older adults are significant risk factors for adverse drug events, which they said are the most common postdischarge complications, along with procedural complications and hospital-acquired infections.

Adverse drug events may result from “inappropriate drug prescribing, discrepancies between prescribed and current regimens, poor adherence, and the inadequate surveillance of adverse effects,” possibly leading to increased frailty and early death, they said.

This retrospective study analyzed the patient registry of a public hospital from 2015 to 2018. The electronic health records of 20,422 inpatient stays by older adults living at home included the 13,802 hospital readmissions of 8878 patients, an average of 1.55 inpatient hospital readmissions.

The mean [SD] age was 77.7 [7.48]; 57% were male. The average hospital length of stay was 8.44 days [7.58]. At the time they were sent home, 25% of the patients had impaired mobility, 4% were impaired in their activities of daily living, and 4% showed mental impairment. On average, 8.95 medications [3.24] were prescribed per patient at discharge.

The overall 30-day hospital readmission rate was 7.8%, in line with other published hospital readmission rates among community-dwelling older adults.

Results of an adjusted multivariate analyses showed that the following factors were associated with an increased risk of hospital readmission:

A longer length of stay: odds ratio (OR) = 1.014 per additional day; 95% CI, 1.006-1.021

Impaired mobility: OR = 1.218; 95% CI, 1.039-1.427

Multimorbidity: OR = 1.419 per additional disease; 95% CI, 1.282-1.572

Tumorous disease: OR = 2.538; 95% CI; 2.089-3.082

In addition, while polypharmacy carried an OR of 1.043 for each additional drug prescribed (95% CI, 1.028-1.058), certain drugs had higher risks than others:

Antiemetics and antinauseants: OR = 3.216 per additional drug unit taken; 95% CI, 1.842-5.617

Antihypertensives: OR = 1.771; 95% CI, 1.287-2.438

Gastrointestinal medications: OR = 1.424; 95% CI, 1.166-1.739

Systemic hormonal preparations: OR = 1.207; 95% CI, 1.052-1.385

Vitamins: OR = 1.201; 95% CI, 1.049-1.374

Concurrent use of beta-blocking agents and drugs for acid-related disorders: OR = 1.367; 95% CI, 1.046-1.788

At first, men with multiple illnesses were at a higher risk of readmission than women with multiple morbidities, the significance was not significant in an adjusted multivariate analysis. However, the authors noted that other studies have found that men were more likely to forget to take their medication or to implement a new dosage, leading to a high risk for readmission.

The study had several strengths, including 4-year data from a comprehensive hospital register; a range of characteristics to predict the probability of hospital readmission; and correlational analyses. However, clinically diagnosed drug–drug interactions were not included, and the researchers were unable to account for hospitalizations and readmissions lost to follow-up or to identify unnecessary hospitalizations, for instance.

The issue of what drives hospital readmissions “is an underinvestigated topic deserving of additional, well-conducted, predictive research exploiting accurate longitudinal data from large samples,” the authors concluded.

Pereira F, Verloo H, Zhivko T, et al. Risk of 30- day hospital readmission associated with medical conditions and drug regimens of polymedicated, older inpatients discharged home: a registry-based cohort study. 

 2021;11:e052755. doi:10.1136/ bmjopen-2021-052755

While polypharmacy, along with hospital length of stay and other factors, was linked to a higher risk of 30-day hospital readmission, the type of medication mattered as well.



Polypharmacy Linked to Higher Risk of Hospital Readmission

Patients may find a placebo effect beneficial, but it causes issues in a clinical trial and makes it difficult to understand the efficacy of a pharmacological agent, said Ron Eccles, BSc, PhD, DSc, emeritus professor at Cardiff University.

Is there any benefit to the placebo effect in chronic cough?

. If you are giving a medicine that has a lot of sensory impact, for example, most of the medicines you can pick up at your Walmart or your pharmacy, they made as viscous sweet setups. They have warming agents in, cooling agents in, menthol in, and they taste very medicinal, and that increases the magnitude of the placebo response. So, those medicines are really very good medicines, even without any pharmacological efficacy. They don't need the pharmacological efficacy; the patient believes the medicine is active, the anticipation is that they will have relief, and relief is what they get.

So, when you actually come to market these medicines and give them out, having a big placebo effect is greatly beneficial to the patient. However, in a clinical trial situation, where you're trying to measure the pharmacological efficacy, it confounds the clinical trial and makes it impossible to measure the pharmacological efficacy.