A pair of recent randomized clinical trials examined escalating doses of allopurinol for the progression of 

and reported no benefits. However, these studies did report a potential for increased risk of death.

Investigators, led by Jie Wei, PhD, Health Management Center, Xiangya Hospital, Central South University, conducted a cohort study to determine whether the risk could present in patients with gout and concurrent chronic kidney disease.

Investigators found no associations, in their population-based data, relating allopurinol initiation, achieving target serum urate level with allopurinol, nor allopurinol dose escalation to an increased mortality in patients with gout and concurrent chronic kidney disease.

In the past few decades, the prevalence of gout, the most common form of inflammatory arthritis, has increased. Urate-lowering therapy is the cornerstone to long-term management of this disease, according to investigators.

Rheumatology guidelines for the treatment of gout recommend lowering serum urate (SU) level to below 0.36 mmol/L, a treat-to-target approach, for patients with recurrent gout flares, tophi or radiographic joint damage due to gout.

Typically, the urate-lowering medication allopurinol is used, beginning with a low dose that’s increased over weeks to months. Inconclusive research has examined the medication’s relation to the risk of death in patients with gout.

In at least 20% of patients with gout, chronic kidney disease is a comorbidity. Previous studies have found that hyperuricemia is associated with an increased risk for incident chronic kidney disease and halting the progression could be targeted by serum urate therapy.

Recently, 2 randomized controlled trials revealed data indicating allopurinol has no renal function-preserving benefits in patients with renal disease, but without gout. Both trials indicated an association between allopurinol and a 2-fold increased risk for death in patients with renal disease.

Investigators aimed to determine if allopurinol use could increase mortality in patients with both gout and chronic kidney disease in this population-based cohort study.

“In addition, we conducted 2 cohort studies emulating randomized controlled trials to examine the effects of achieving target SU level with allopurinol and allopurinol dose escalation on mortality,” investigators wrote.

The association between allopurinol initiation and all-cause mortality was examined over a 5-year follow-up in propensity score-matched cohorts.

Patients were included if they had gout and concurrent moderate-to-severe chronic kidney disease and were between 40-89 years old from January 2000-January 2018 with at least 1 year of continuous enrollment with a general practitioner.

“The diagnosis of gout was based on the presence of at least 1 Read code for gout,” investigators wrote. “Moderate-to-severe CKD (≥stage 3) was identified by either estimated glomerular filtration rate (eGFR) less than 60 mL/min/ 1.73 m2 on at least 2 occasions more than 90 days apart within 1 year, with no intervening eGFR of 75 mL/min/ 1.73 m2 or greater, or at least 1 Read code for CKD stage 3 to 5, hemodialysis, or peritoneal dialysis.”

A propensity score-matched cohort study compared mortality in patients who were initiated on allopurinol and those who were not. Next, a cloning, censoring, and weighting approach assessed the effect of either achieving target serum urate levels or allopurinol dose escalation on mortality in initiated patients using observational data.

Patients who were initiated on allopurinol showed a higher serum urate level, a lower estimated glomerular filtration rate, a higher prevalence of prescriptions of diuretics, systemic corticosteroids, nonsteroidal anti-inflammatory drugs, and colchicine, as well as more general practitioner visits, compared with patients who were not initiated on allopurinol.

However, after propensity score matching, the characteristics between the 2 cohorts were balanced with all standardized differences appearing less than 0.10.

“In this large database of GP electronic health records from the United Kingdom, allopurinol initiation was associated with a modestly lower mortality compared with nonallopurinol use in participants with both gout and moderate-to-severe CKD. In addition, emulating a target randomized control trial in allopurinol initiators, we showed that a treat-to-target approach of lowering serum urate level with allopurinol does not seem to increase mortality in participants with both gout and CKD,” investigators concluded.

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease

Articles

Contrary to recent research that indicated a higher risk of death associated with escalating doses of allopurinol for chronic kidney disease, investigators announce no association between allopurinol initiation and increased mortality among patients with gout and CKD.

New Data Examines Mortality Risk and Allopurinol Use in Patients with Gout and CKD

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the New Drug Application for gefapixant, an investigative receptor antagonist therapy from Merck seeking approval for the treatment of refractory or unexplained chronic cough.

The selective P2X3 receptor antagonist was supported by findings from the phase 3 COUGH-1 and COUGH-2 trials, a pair of multinational randomized studies showing 45 mg gefapixant reduced 24-hour cough frequency in patients by 18.45% (95% CI, -32.92 to -0.86; 

 = .041) and 14.64% (95% CI, -26.07 to -1.43; 

 = .031), respectively, by 24 weeks versus placebo.

The FDA’s letter to Merck regarding the application included a request for additional information “related to measurement of efficacy,” the company stated in a 

“The CRL was not related to the safety of gefapixant,” the statement read. “Merck is reviewing the letter and will meet with the agency to discuss next steps.”

Merck leadership expressed their commitment to advancing the regulatory status of gefapixant, which would be the first newly approved drug for chronic cough in 6 decades.

Stuart Green, MD, Vice President of Late Stage Development at Merck, previously 

 the difficulty within the market to identify and progress a new viable drug for chronic cough has been in actually understanding the mediating pathways associated with the condition.

“What we find is that there’s many different pathways, but some of these appear to more important in disease states than others,” he explained. “It’s because of advances in developing not only the understanding of the science, but drugs than can selectively target those pathways, that we’ve now been able to do the kind of studies that allow us to hopefully demonstrate benefit for people with this condition.”

The selective inhibitor therapy is being investigated for the treatment of 2 forms of chronic cough—an indication that's been unmet in 60 years.

Merck Receives FDA Complete Response Letter for Chronic Cough Drug Candidate Gefapixant

A new molecular test could accurately diagnose 

 infections (CDI), which could be especially impactful in developing countries.

A team, led by Adriane C. Maestri, Laboratório de Bacteriologia, Complexo Hospital de Clínicas da Universidade Federal do Paraná - Rua Padre Camargom, developed and validated a new in-house quantitative polymerase chain reaction (qPCR) targeting the C difficile toxin B gene (tcdB) using 2 distinct methodologies—SYBR Green and hydrolysis probes—for the diagnosis of C difficile infections.

While the burden of C difficile infections can cause nosocomial diarrhea in adult patients, commercial molecular tests can be expensive and restrictive in developing countries. The disease has also been linked to an imbalance of intestinal microbiota largely due to antimicrobial use but remains a neglected disease in developing countries.

There are also issues with CDI laboratory tests due to inadequate performance of available conventional tests that have low sensitivity.

However, molecular tests can be faster, with better performance. The issue with this family of tests is they can present false-positive results in asymptomatic patients.

In the study, the investigators used glutamate dehydrogenase (GDH) with toxigenic culture as the standard reference diagnostic method and examined 392 samples using the SYBR Green method and hydrolysis probes simultaneously to assess the diagnostic value of the real-time PCR assays in detecting CDI from the clinical samples.

The qPCR test is a sensitive and accurate technique able to detect human pathogens in clinical samples, even fecal samples commonly used for C difficile diagnosis.

SYBR Green is a deoxyribonucleic acid intercalating dye able to detect all double-stranded DNA present in the reaction and hydrolysis probes have fluorophores attached to oligonucleotides activated during the reaction to allow for the detection of a specific product of interest.

Specifically for CDI diagnosis, the target region used more in the gene that codes for toxin B because it is a determining factor for virulence.

The analytical detection limited was based on the curves of 10 CFU/mL.

Overall, the SYBR Green assays showed 97.9% sensitive and 99.1% specificity, while the hydrolysis probe assay showed 87.5% sensitivity and 100% specificity. The SYBR Green also showed 94% positive predictive value, 99.7% negative predictive value, and 99% accuracy.

The hydrolysis probe assay showed 100% positive predictive value, 98.3% negative predictive value, and 98.5% accuracy.

“The two qPCR methodologies evaluated could offer an adequate tool as part of an algorithm in the laboratory diagnosis of CDI,” the authors wrote.

Last year, investigators found a new PCR assay features enhanced specificity and sensitivity in detecting both CDI and norovirus.

The sensitivity for testing C difficile infections for the new PCR test was 100%, with a specificity of 100% on fecal samples. While these numbers dropped on the rectal swab, the PCR test still had a sensitivity of 90.9% and a specificity of 99.1%.

Standardization and validation of an in-house quantitative real-time polymerase chain reaction (qPCR) assay for the diagnosis of Clostridioides difficile infection

Due to costs, it is difficult to screen for and diagnose patients with C difficile infections.

Molecular Test Adds to Accuracy for C Difficile Infection Diagnosis

New research from a tertiary care center for children in San Diego observed the incidence of new-onset 

 in 2020 and 2021 increased compared to previous years.

Led by Jane J. Kim, MD, Department of Pediatrics, University of California, San Diego, a 6-year retrospective review evaluated the significance of the increased incidence and whether or not more children had diabetic ketoacidosis (DKA) or required pediatric intensive care unit admission.

Ultimately, Kim and colleagues noted the number of inpatient admissions decreased by 19% from 2019 - 2020, while the number of children seen at the pediatric endocrine clinic and residing in the surrounding region did not change substantially.

“Therefore, the observed increase in diabetes diagnoses during the COVID-19 pandemic is unlikely to reflect changes in referral number or pattern,” they wrote.

The cross-sectional study used a self-service reporting tool from the electronic medical record at Rady Children’s Hospital San Diego. Inclusion criteria included admission to the hospital, patients aged ≤19 years, and ≤1 positive T1D antibody tier.

Additionally, age, sex, hemoglobin A1c, body mass index z score, COVID-19 infection results, DKA evidenced by use of insulin infusion, and PICU admission extracted from each patient’s medical record.

Patients were tested for acute COVID-19 infection on admission, defined as the year after California’s stay-at-home orders from March 2020 - March 2021. Then, prior data from March 2015 - March 2020 were analyzed to ensure that the increase in new-onset T1D diagnosis was not due to previous annual rate of increase.

Investigators performed an autoregressive integrated moving average to forecast the predicted trend of new-onset T1D cases during the COVID-19 year.

The results showed from March 2020 - March 2021, 187 children (mean age, 9.6 years; 106 girls, 56.7%) were admitted for new-onset T1D, compared to 119 children admitted the previous year (57% increase).

From July 2020 - February 2021, the number of new diagnoses of T1D exceeded the number of patients anticipated within the 95% confidence interval based on the quarterly moving average of the preceding 5 years (July 2020, 15 diagnoses; 10 forecasted diagnoses; 95% CI, 6.79 - 13.89 versus February 2021, 21 diagnoses; 10 forecasted diagnoses; 95% CI, 6.88 - 13.54).

At the time of presentation, 4 of 187 (2.1%) had a COVID-19 infection at the time of presentation. An increase in the percentage of patients who presented with DKA was observed, with no difference in mean age at presentation (9.6 versus 9.7 years), body mass index z score (-0.39 versus -0.43), hemoglobin A1c (11.6% versus 11.7%), or percentage of children requiring PICU admission (16 of 187, 8.6% versus 41 of 641, 6.4%).

Further, Kim and colleagues observed a significant increase in the frequency of DKA at the time of T1D diagnosis. Data show 93 of 187 patients (49.7%) required an insulin infusion during the COVID-19 pandemic, which increased from 261 of 641 patients (40.7%) in the 5 years before the pandemic.

Incidence of New-Onset Type 1 Diabetes Among US Children During the COVID-19 Global Pandemic

An increase of 57% in new-onset type 1 diabetes admissions was observed from March 2020 - 2021. 

Increase in T1D Diagnosis During COVID-19 Pandemic Unlikely To Reflect New Pattern 

A new study on gene therapy was published in 

 metachromatic leukodystrophy (MLD) have not had an effective treatment; investigators examined the safety and efficacy of atidarsagene autotemcel (arsa-cel) as a treatment for this population.

Atidarsagene autotemcel is a gene therapy that contains an autologous haematopoietic stem and progenitor cell (HSPC) population transduced ex vivo with a lentiviral vector encoding human arylsulfatase A (ARSA) cDNA.

The results showed clinically relevant benefits in children with early-onset metachromatic leukodystrophy. The treatment slowed demyelination and brain atrophy, preserved cognitive function and motor development in most patients.

Francesca Fumagalli, MD, San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, led an integrated analysis of results from a prospective, non-randomized, phase 1/2 clinical study and expanded-access frameworks.

Investigators treated 29 pediatric patients who had pre-symptomatic or early symptomatic early-onset MLD with biochemical and molecular confirmation of diagnosis with atidarsagene autotemscel and compared the group to an untreated natural history cohort of 31 patients with early onset metachromatic leukodystrophy, matched by age and disease subtype.

An improvement of more than 10% in total gross motor function measure score at 2 years after treatment in patients who received treatment compared with controls was required to meet one of the co-primary efficacy endpoints.

A change from baseline of total peripheral blood mononuclear cell arylsulfatase A activity at 2 years after treatment compared with values before treatment was required to meet the second co-primary endpoint of the study.

When analyzed, 26 of the patients who were treated with atidarsagene autotemcel were alive with a median follow up of 3.16 years. Due to disease progression, 2 patients died, and one passed due to a sudden event that investigators deemed unlikely to be related to treatment.

The co-primary endpoints were met for both cohorts of patients including those with late-infantile MLD, as well as those with early-juvenile MLD.

Arylsulfatase A activity in peripheral blood mononuclear cells displayed a significant increase above baseline 2 years after treatment in patients with the late-infantile variant, and 5.7-fold in patients with the early-juvenile variant.

Investigators reported significant mean differences in total scores for gross motor function between treated patients and the control group for both cohorts of patients with late-infantile MLD and early-juvenile MLD when examined 2 years after treatment.

“Most treated patients progressively acquired motor skills within the predicted range of healthy children or had stabilized motor performance (maintaining the ability to walk),” investigators wrote.

The infusion was well tolerated with no evidence of abnormal clonal proliferation or replication-competent lentivirus.

“Further, most displayed normal cognitive development and prevention or delay of central and peripheral demyelination and brain atrophy throughout follow-up,” investigators stated. “Treatment benefits were particularly apparent in patients treated before symptom onset.”

At least one grade 3 adverse event, or higher, was experienced by all patients. According to investigators, most were related to conditioning or background disease. 4 patients experienced an adverse event related to atidarsagene autotemcel treatment where they developed anti-arylsulfatase A antibodies, but it didn’t affect clinical outcomes.

“Treatment with arsa-cel resulted in sustained, clinically relevant benefits in children with early-onset MLD by preserving cognitive function and motor development in most patients, and slowing demyelination and brain atrophy,” investigators concluded.

Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label phase 1/2 trial and expanded access

Since an effective treatment for the rare disease metachromatic leukodystrophy had not previously been distinguished, investigators analyzed data on the safety and efficacy of arsa-cel, a gene therapy.

New Data Reveals a Stem-Cell Gene Therapy for Metachromatic Leukodystrophy

A new investigation into pre-conception paternal smoking found no associations with birth weight or adverse neonatal outcomes at delivery.

Previous studies maintained a focus on paternal smoking during pregnancy as an indicator of passive maternal exposure as opposed to prior to conception. However, there is limited data on the potential effect of pre-conception paternal smoking.

In the current study, investigators led by Shi Wu Wen, PhD, School of Epidemiology and Public Health at the University of Ottawa, evaluated the association of paternal smoking with neonatal outcomes.

For the prospective preconception observational cohort study, investigators recruited newly married couples intending to conceive a child in Liuyang, China.

Between February 1, 2009, and November 4, 2015, all participating couples underwent baseline (pre-gravid) assessments and were monitored throughout the pregnancy.

Association of paternal smoking with birth weight and categorical neonatal outcomes were assessed by multiple linear regression and logistic regression analyses, respectively. For the study, a P < .05 was considered significant.

Wen and colleagues used t tests to evaluate the P values for the multiple linear regression analyses and χ2 tests to calculate P values for multiple logistic regression analyses. All tests that were performed were 2-sided, and all analyses were performed using the Statistical Analysis System version 9.4 (SAS Institute).

Statistical analyses were then performed between January 2021 and August 2021.

A total of 1174 couples who underwent baseline assessment were enrolled in the study, at a median of 23.3 (IQR, 5.6-65.6) weeks before a singleton pregnancy. The mean age of the sample was 24 (3) years for women and 26 (3.5) years for men.

Throughout the pre-conception assessment, 538 male partners (45.8%) had reported currently smoking, which was in contrast to only 5 women (0.4%) smoking.

Baseline characteristics and delivery outcomes were stratified into 3 distinct groups based on the degree of paternal smoking before conception.

A total of 635 couples (54.2%) answered that they had smoked no cigarettes before the conception of their child, while 343 (29.2%) reported smoking 1 to 10 cigarettes a day. Only 195 couples (16.6%) reported having smoked more than 10 cigarettes per day.

Despite the differences in smoking habits, the birth weight and length of gestation did not differ between the 3 groups.

Investigators observed positive independent factors associated with birth weight during the multiple linear regression analysis, including maternal baseline body mass index (BMI), (regression coefficient, 39.2; 95% CI, 27.5 to 50.9; P < .001), paternal baseline BMI (regression coefficient, 17.0; 95% CI, 7.7 to 26.3; P = .001), maternal age (regression coefficient, 14.4; 95% CI, 2.7 to 26.1; P = .02), length of gestation (regression coefficient, 128.7; 95% CI, 108.4 to 149.0; P < .001), gestational weight gain (regression coefficient, 16.5; 95% CI, 12.3 to 20.8; P < .0001), and male neonate (regression coefficient, 89.1; 95% CI, 36.2 to 142.1; P = .001).

Preeclampsia was associated with lower birth weight (regression coefficient, −214.0; 95% CI, −422.9 to −5.1; P = .04), though either maternal or paternal smoking were associated with lower birth weight.

Preconception paternal smoking was not associated with birth weight (P = 37). Likewise, investigators observed no significant interaction between paternal BMI and smoking status.

Despite this new data, investigators noted they could not determine if the influence of pre-conception paternal smoking would show at later stages in the children’s lives.

“These findings cannot rule out the possibility that paternal origins of health and disease (POHaD) programming effects of preconception paternal smoking may yet emerge later in life.”

"Analysis of Preconception Paternal Smoking and Neonatal Outcomes,"

Preconception paternal smoking was also not associated with birth weight or paternal BMI.

Pre-Conception Paternal Smoking Not Associated with Adverse Neonatal Outcomes

New research investigated the association of future cardiovascular disease with 

hypertensive disorders of pregnancy (HDP)

 and the role of natriuretic peptides in detecting subclinical cardiac dysfunction following pregnancy.

The results of the cohort study found higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations throughout early pregnancy were associated with a lower risk of HDP and hypertension 2 - 7 years postpartum.

“In this cohort study, contrary to our hypothesis, we demonstrated that higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of HDP,” said study author Alisse Hauspurg, MD, Magee-Womens Research Institute, University of Pittsburgh School of Medicine.

The study used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) Heart Health study (HHS), which enrolled women from 8 centers in the US.

Women were eligible for enrollment if they had a viable singleton gestation, no previous pregnancy that lasted more than 20 weeks of gestation, and were between 6 and less than 14 weeks of gestation at enrollment.

After delivery, interviews were performed at 6-month intervals to update health status and schedule an in-person cardiovascular assessment ≥2 years after delivery. Self-reported data on race and ethnicity were collected.

Exposures in the study were NT-proBNP concentration measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. Main outcomes were considered HDP and incident hypertension (systolic blood pressure of 130 mm HG or diastolic blood pressure of 80 mm Hg) at follow-up.

A total of 4508 women attended the nuMoM2b Heart HHS follow-up visit at an interval of 2 - 7 years after their delivery that occurred during the nuMoM2b study. For the analysis, exclusions left 4103 women eligible.

Out of the women included in the analysis, 909 of 410 (22.2%) had an adverse pregnancy outcome (APO) and were more likely to self-report race and ethnicity as non-Hispanic Black.

Data show women who had an APO had lower NT-proBNP concentration in early pregnancy compared to those that did not develop an APO (median, 56.0 pg/mL versus 63.0 pg/mL, 

Further, higher NT-proBNP concentrations were associated with a lower risk of HDP (adjusted OR per doubling, 0.81; 95% CI, 0.73 - 0.91), which investigators noted persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use.

Additionally, 817 (19.9%) met criteria for stage 1 hypertension of greater, while 49 (1.2%) self-reported the use of antihypertensive medication at the follow-up visit 2 - 7 years postpartum.

Women with incident hypertension at the follow-up had lower NT-proBNP concentration in early pregnancy compared with women without hypertension (median, 54.0 pg/mL versus 64.0 pg/mL, 

A higher NT-proBNP concentration in early pregnancy was additionally associated with a lower risk of incidence hypertension 2 - 7 years after delivery (adjusted OR per doubling, 0.84; 95% CI, 0.77 - 0.93). The association continued after controlling for confounders such as HDP. 

"Taken together, these findings suggest that early-pregnancy cardiovascular physiology, as assessed with NT-proBNP concentration, may be an important determinant of both pregnancy outcome as well as future CVD,” investigators concluded.

Association of N-Terminal Pro–Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension

Early-pregnancy NT-proBNP level may be an important determinant of pregnancy outcomes and CV risk. 

Higher NT-proBNP Level in Early Pregnancy Linked to Lower Risk of HDP, Hypertension 

Caregivers continue to face increased responsibilities and stress due to the 

 pandemic and knowing where to turn for help is not easy. A recent study shows that pharmacists will have an expanded role in patient care, and caregivers will want to take note of how they can tap into pharmacists’ expertise, which is often an underutilized resource.

Together, our organizations, Express Scripts® Pharmacy and Columbia University Mailman School of Public Health, partnered on new research to more deeply understand the expanding role of pharmacists in transforming patient care in the decade ahead. Between November and December 2021, we surveyed more than 3,000 patients, 1,000 pharmacists, and 500 providers (including physicians and nurse practitioners). The resulting Prescription of Trust report is the largest and most comprehensive research study ever conducted on this topic.

Our survey found that pharmacists currently spend about 50% of their time dispensing and filling medications, but that percentage is expected to decrease over the next decade. More than 80% of pharmacists agree they will see increased patient counseling responsibilities, take on an increased role in preventive care measures, and be more integrated in care management teams. We recognize this expansion of duties cannot happen fast enough, as the COVID-19 pandemic has accelerated the shortage of physicians and nurses available to serve patients.

The best part about the findings from our research is that patients and health care providers truly trust pharmacists to play a greater role in providing care. In fact, our research found that 72% of doctors and nurse practitioners already consider pharmacists to be part of the patient care team.In addition, nearly 80% of patients said they see pharmacists as an integral part of their health care team.

So, what should caregivers know about pharmacists, and how should they engage with them to make the most of their expertise?Caregivers should keep in mind that pharmacists do much more than dispense medications. Our research found pharmacists in ambulatory clinics, health systems (hospitals), and home delivery pharmacies often serve as specialists, advising patients with specific diseases or interacting with a larger health team to help manage complex patient care.

Pharmacists can help ease a caregiver’s stress by addressing medication issues including polypharmacy and adherence, as well as condition issues. Additional Express Scripts Pharmacy 

 shows there’s a link to better health outcomes when pharmacists get involved with patient counseling and chronic disease management

For example, patients with diabetes often need continuing care to help manage their condition. Caregivers can reach out to their pharmacist for medication consults but also for information about disease management and preventive care.

Similarly, pharmacists can assist with many other conditions, including high blood pressure and high cholesterol. As part of their expanding role, pharmacists can perform blood pressure and cholesterol screenings that allow them to make recommendations for potential future treatment. The more caregivers can partner with pharmacists to prevent emergency room trips, hospitalizations, or the advancement of a chronic disease by supporting adherence, the better we can affect a patient’s health outcomes.

Caregivers may also want to consider the benefits of telepharmacy services (via phone or video.) With the COVID-19 pandemic, the use of telehealth skyrocketed, but the use of telepharmacy has not been as quickly adopted. However, our study showed that nearly half (49.7%) of patients would find it extremely or very helpful to have routine testing and medical visits done from home. Telepharmacy is an underutilized resource for people to connect with a pharmacist anytime, anywhere. At many home delivery pharmacies, such as Express Scripts Pharmacy, their members can access pharmacists by phone 24/7.

Lastly, caregivers should keep in mind that most pharmacists chose their profession because of their desire to take care of patients, and the Prescription of Trust shows they are embracing their growing responsibilities with 70.1% saying they are excited about the evolving role of the pharmacist.

To learn more about The Prescription of Trust report, as well as how caregivers can make the most of patient care provided by pharmacists, please follow this link: 

Susan Peppers, RPh, Chief Pharmacist, Express Scripts® Pharmacy, is dedicated to quality and patient safety with responsibility for Pharmacy Practice, Patient Consultation, and Clinical Programs.

John McHugh, MBA, PhD is an Assistant Professor in the Department of Health Policy and Management at Columbia University’s Mailman School of Public Health. His research focuses on health care organizations and how they operate and respond to changing incentives.

The views expressed in this piece are those of the author, not necessarily those of the publication.

Clinicians and health care experts interested in contributing to HCPLive can 

Caregivers Can Lean on Pharmacists Who Are Taking on Expanding Role in Patient Care

Americans with depressive symptoms are more likely to endorse COVID-19 vaccine misinformation, according to results of a national survey that highlight the need to address susceptibility to false information among persons with depression.

The new findings from the study conducted by a team of US-based investigators also showed correlates between a person more likely being unvaccinated for COVID-19 and resistant to the practice when in endorsement to any 1 of the 4 COVID-19 vaccine misinformation statements presented to them.

Led by Roy H. Perlis, MD, MSc, of the Massachusetts General Hospital, investigators sought to determine the link between depressive symptoms and likelihood of believing COVID-19 vaccine-related misinformation—a public health behavior recognized even prior to the pandemic. During the pandemic, about one-fourth of US adults have consistently reported moderate or more severe depressive symptoms.

“While misinformation is increasingly well studied, most of this work has concentrated on how and why such misinformation spreads,” Perlis and colleagues wrote. “A general bias toward negativity in information selection, processing, and recall may exacerbate misinformation exposure. In the context of political misinformation, both anger and anxiety are associated with promoting beliefs in certain types of false stories.”

The team analyzed responses compiled from 2 waves of a national nonprobability internet survey conducted from May to July 2021. The survey, provided to more than 15,000 adults aged ≥18 years old, characterized association between depressive symptoms and endorsement of misinformation, as well as potential mediators or moderators of such associations.

Investigators measured depressive symptoms from surveyed adults via the Patient Health Questionnaire 9-item (PHQ-9), and conducted population-reweighted multiple logistic regression analysis to examine the link between moderate to severe depressive symptoms and endorsement of ≥1 item of vaccine information. They further adjusted for sociodemographic features in determining associations.

Of the 15,464 survey respondents, 63.6% were women and mean respondent age was 47.9 years. Respondents were predominately White (76.7%), followed by Black (9.7%), Hispanic (6.6%), then Asian (4.7%).

Similar to previous national assessments during COVID-19, one-quarter (26.9%) of respondents identified moderate or greater depressive symptoms on the PHQ-9. About one-fifth (19.2%) endorsed at least 1 vaccine-related statement of misinformation on the survey; such statements included:

“The COVID-19 vaccines will alter people’s DNA”

“The COVID-19 vaccines contain microchips that could track people”

“The COVID-19 vaccines contain the lung tissue of aborted fetuses”

“The COVID-19 vaccines can cause infertility, making it more difficult to get pregnant”

Respondents with presence of depressive symptoms were more than twice likely to endorse COVID-19 vaccine misinformation (odds ratio [OR], 2.33; 95% CI, 2.09 – 2.61). Respondents endorsing ≥1 misinformation item were significantly less likely to be vaccinated (OR, 0.40; 95% CI, 0.36 – 0.45) and significantly more likely to report resistance to vaccination (OR, 2.54; 95% CI, 2.21 – 2.91).

Among the 2800-plus respondents to answer a subsequent survey in July, the presence of depression in the first survey from May was linked to a greater likelihood of endorsing even more information in July compared with the prior survey (OR, 1.98; 95% CI, 1.42 – 2.75).

Each of these correlates remained statistically significant when investigators adjusted for respondent sociodemographic features, as well as self-reported ideology and political party information. Though the findings do not provide conclusion on causation, the assessment of second-wave survey respondents suggested to investigators that misinformation was unlikely to cause depression.

“In general, negative biases are apparent in information processing even in the absence of depression,” they wrote. “Individuals with major depressive symptoms often exhibit a more pronounced negativity bias, a form of attentional bias in which thoughts with negative valence receive greater focus.”

The team did note that individuals with depression may exhibit less willingness to trust institutions tasked with combating misinformation, such as the Centers for Disease Control and Prevention (CDC). “However, we found that incorporating terms for trust in these institutions in regression models did not change the main association with depression, which does not support a mediating association of trust in institutions,” they wrote.

Perlis and colleagues concluded that while their findings were “associative by necessity,” the results showing a link between depression and COVID-19 misinformation endorsement broadly suggest the significance of directly testing causation in future assessments—if only to derive strategies that could reduce the consequences of depression in individual’s perception of information.

“To date, efforts to combat the impact of misinformation on public health predominantly emphasize reduction in supply,” they wrote. “In parallel, it may be possible to develop interventions targeting negativity bias that reduce demand, or at least modulate the capacity of misinformation to impact health decision-making.”

Association of Major Depressive Symptoms With Endorsement of COVID-19 Vaccine Misinformation Among US Adults

Analysis of 2 national surveys suggest a more than two-fold greater likelihood of depressed Americans endorsing a false fact about COVID-19 vaccines than others. 

Depressed Individuals Are More Susceptible to COVID-19 Vaccine Misinformation

The IL-23 inhibitor is now indicated for treatment of adults with PsA, as well as plaque psoriasis.

The US Food and Drug Administration (FDA) has approved risankizumab-rzaa (SKYRIZI) for the treatment of adults with active psoriatic arthritis (PsA).

The inflammatory pathway interleukin 23 (IL-23) inhibitor from AbbVie and Boehringer Ingelheim was 

 for the treatment of adults with moderate to severe plaque psoriasis, and is currently being assessed for further inflammatory-driven disease care indications; phase 3 assessment of risankizumab for psoriasis, Crohn’s disease, ulcerative colitis and PsA are ongoing.

This newest indication for risankizumab-rzaa was supported by findings from the pivotal KEEPsAKE-1 and KEEPsAKE-2 trials, a pair of phase 3 studies assessing the efficacy and safety of the therapy in adults with PsA as well as those who had responded inadequately or with intolerance to biologic therapy and/or disease-modifying antirheumatic drugs (DMARDs).

The primary endpoint sought by KEEPsAKE investigators was ACR20 response at week 24.

In both the KEEPsAKE-1 and KEEPsAKE-2 trials, 57% and 51% of patients, respectively, who had received risankizumab achieved ACR20 response—compared with 34% and 27% of patients, respectively, who received placebo.

In key secondary endpoints, more patients on risankizumab demonstrated significant improvements in skin clearance, physical function, and minimal disease activity. The safety profile of the inhibitor was noted to be generally consistent with safety findings in previous studies of psoriasis. As such, serious adverse events occurred in 2.5% of risankizumab patients in KEEPsAKE-1 and 4.0% in KEEPsAKE-2—versus 3.7% and 5.5% on placebo, respectively.

Further, the rates of adverse events leading to discontinuation for those on risankizumab was 0.8% and 0.9% in both trials, respectively. For those on placebo, the discontinuation rates were 0.8% and 2.3%, respectively.

 accompanying the approval announcement, KEEPsAKE trial investigator Alan J. Kivitz, MD, CPI, founder and medical director of the Altoona Center for Clinical Research and Altoona Arthritis and Osteoporosis Center, highlighted the observed improvements in patients’ multifactorial PsA symptoms: joint pain, enthesitis and dactylitis, among others.

"This approval provides both dermatologists and rheumatologists with an option that helps improve skin and joint symptoms in patients with active psoriatic arthritis, alongside a quarterly dosing schedule that may fit their patients' lifestyle,” Kivitz wrote.

Thomas Hudson, MD, senior vice president of Research and Development and chief scientific officer of AbbVie, emphasized the benefit of a cross-indicated biologic approved for patients with potentially both plaque psoriasis and PsA.

"Patients often do not suspect a connection between their psoriasis skin symptoms and the joint pain, swelling and stiffness they may be experiencing, potentially leading to a delay in diagnosis and treatment of psoriatic arthritis," Hudson said in a statement. "We're proud to expand the use of SKYRIZI to patients with psoriatic arthritis who are living with the debilitating combination of skin and joint symptoms."

FDA Approves Risankizumab for Active Psoriatic Arthritis

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