Reports of Injection Site Necrosis After 23-Valent Pneumococcal Vaccine Use.

This case series uses postmarketing data to evaluate the incidence of injection site necrosis after 23-valent pneumococcal vaccine use in the global market.

Reporting rates for VAERS death reports following COVID-19 vaccination, December 14, 2020-November 17, 2021.

PURPOSE: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). We aimed to provide information and context about reports of death to VAERS following COVID-19 vaccination. METHODS: This is a descriptive study evaluating reporting rates for VAERS death reports for COVID-19 vaccine recipients in the United States between December 14, 2020, and November 17, 2021. Reporting rates were calculated as death events per million persons vaccinated and compared to expected all-cause (background) death rates. RESULTS: 9201 death events were reported for COVID-19 vaccine recipients aged 5 years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within 7 days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Limitations of VAERS data include potential reporting bias, missing or inaccurate information, lack of a control group, and reported diagnoses, including deaths, are not causally verified diagnoses. CONCLUSIONS: Reporting rates for death events were lower than the all-cause death rates expected in the general population. Trends in reporting rates reflected known trends in background death rates. These findings do not suggest an association between vaccination and overall increased mortality.

Thromboembolic events after Ad.26.COV2.S COVID-19 vaccine: Reports to the Vaccine Adverse Event Reporting System.

PURPOSE: The Food and Drug Administration (FDA) has identified a potential safety concern for thromboembolic events (TEEs) after Ad.26.COV2.S COVID-19 Vaccine. We sought to characterize the frequency, severity, type, and anatomic location of TEEs reported to the Vaccine Adverse Event Reporting System (VAERS) following Ad.26.COV2.S. METHODS: Reports of TEEs after Ad.26.COV2.S were identified in VAERS, and demographics, clinical characteristics, and relevant medical history were summarized. For a subset of reports, physicians reviewed available medical records and evaluated clinical presentation, diagnostic evaluation, risk factors, and treatment. The crude reporting rate of TEEs was estimated based on case counts in VAERS and vaccine administration data. RESULTS: Through February 28, 2022, FDA identified 3790 reports of TEEs after Ad.26.COV2.S. Median age was 56 years, and 1938 individuals (51.1%) were female. Most reports, 2892 (76.3%), were serious, including 421 deaths. Median time to onset was 12 days post-vaccination. Obesity and ischemia were among the most commonly documented risk factors. Thrombocytopenia (platelet count less than 150 000/µl) was documented in 63 records (11.5%) and anti-platelet 4 antibodies in 25 (4.6%). Medical review identified cases of severe clot burden (e.g., bilateral, saddle, or other massive pulmonary embolism with or without cor pulmonale; lower extremity thrombus involving the external iliac, common femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins). The crude reporting rate was ~20.7 cases of TEE per 100 000 doses of Ad.26.COV2.S administered. CONCLUSIONS: Life-threatening or fatal TEEs have been reported after Ad.26.COV2.S, including bilateral massive pulmonary embolism or other severe clot burden.

Impact evaluation of a brief online training module on physician use of the Maryland, USA, Prescription Drug Monitoring Program.

BACKGROUND: Prescription Drug Monitoring Programs (PDMPs) are electronic databases that track controlled substance prescriptions in a state. They are underused tools in preventing opioid abuse. Most PDMP education research measures changes in knowledge or confidence rather than behavior. OBJECTIVE: To evaluate the impact of online case-based training on healthcare provider use of the Maryland (USA) PDMP. METHODS: We used e-mail distribution lists to recruit providers to complete a brief educational module. Using a pre-training and post-training survey in the module, we measured self-reported PDMP use patterns and perceived PDMP value in specific clinical situations and compared pre- and post-training responses. Within the module, we presented three fictional pain cases and asked participants how they would manage each, both before, and then after presenting prescription drug history simulating a PDMP report. We measured changes in the fictional case treatment plans before and after seeing prescription history. Finally, we measured and compared how often each participant accessed the Maryland PDMP database before and after completing the educational module. We used multivariate logistic regression to measure the effect of the intervention on actual PDMP use frequency. RESULTS: One hundred and fifty participants enrolled and completed the training module, and we successfully retrieved real-world PDMP use data of 137 of them. Participants' decisions to prescribe opioids changed significantly after reviewing PDMP data in each of the fictional cases provided in the module. In the months following the training, the rate of PDMP use increased by a median of four use-cases per month among providers in practice for less than 20 years (p = 0.039) and two use-cases per month among infrequent opioid prescribers (p = 0.014). CONCLUSION: A brief online case-based educational intervention was associated with a significant increase in the rate of PDMP use among infrequent opioid prescribers and those in practice less than 20 years.

The Impact of Variability in Patient Exposure During Premarket Clinical Development on Postmarket Safety Outcomes.

We characterized the size of the premarket safety population for 278 small-molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by the US Food and Drug Administration (FDA) between October 1, 2002, and December 31, 2014, evaluating the relationship of premarket safety population size to regulatory characteristics and postmarket safety outcomes. The median size of the safety population was 1,044, and was lower for NTBs than NMEs (median: 920 vs. 1,138, P = 0.04), orphan products than nonorphan products (393 vs. 1,606, P < 0.001), and for products with fast-track designation (617 vs. 1,455, P < 0.001), priority review (630 vs. 1,735, P < 0.001), and accelerated approval (475 vs. 1,164, P < 0.001), than products without that designation. The median number of postmarket safety label updates and issues added to the label were higher with larger premarket exposure among nonorphan products, but not among orphan products. Products with accelerated approval using a surrogate end point had a higher median number of safety issues added to the label than those with full approval, but this did not vary with the size of the safety population; fast-track and priority review were not associated with the number of safety issues added to the label. A smaller safety population size was associated with a longer time to first safety outcome for nonorphan products but not orphan products. For orphan and nonorphan products combined, smaller premarket safety population size is not associated with the number or timing of postmarket safety outcomes, regardless of expedited program participation.

Postmarketing Safety-Related Regulatory Actions for New Therapeutic Biologics Approved in the United States 2002-2014: Similarities and Differences With New Molecular Entities.

We examined the relationship of regulatory and review characteristics to postmarketing safety-related regulatory actions for 61 new therapeutic biologics (NTBs) approved between October 1, 2002 and December 31, 2014. We also compared NTBs with small-molecule new molecular entities (NMEs) on these measures. Postmarketing safety-related regulatory actions were defined as a safety-related withdrawal or a safety-related update to a safety section of the label through June 30, 2018. Four NTBs were withdrawn, two for safety reasons. At least one safety-related update was added to the labels of 54 (88.5%) NTBs. Label updates occurred throughout the follow-up period. Time to the first safety-related regulatory action was shorter for NTBs approved under accelerated approval. The occurrence of safety events was more likely to occur with NTBs than with NMEs. This may be explained in part by the higher proportion of NTBs in the anatomical therapeutic chemical classification categories with higher frequency of safety-related updates. NTBs also had shorter time to safety events than NMEs. These findings underscore the importance of continued development of the life cycle safety surveillance system for both drugs and biologics with consideration for product type and its characteristics, including pharmacologic action.

Evaluating for Differences by Race/Ethnicity in the Association Between Income and Gambling Disorder.

Multiple studies show an increased prevalence of gambling disorder among African Americans compared to whites. However, few studies take an analytic approach to understanding differences in risk factors by race/ethnicity. Income is inversely associated with gambling disorder; we hypothesized that this association would vary by race/ethnicity. The main objective was to evaluate whether the association between income and gambling disorder varies by race/ethnicity. With data from the baseline visit of a prospective cohort study, Prevention and Etiology of Gambling Addiction Study in the United States, we used multivariable logistic regression analysis to determine whether the association between income and gambling disorder varies by race/ethnicity. 1164 participants were included in the final analyses. Measures included: demographics (age, sex, race/ethnicity, education, employment, annual household income), veteran status, marital status, homelessness, smoking, substance abuse, alcohol abuse, marijuana use, and lifetime gambling disorder diagnosis as derived from Alcohol Use Disorder and Associated Disabilities Interview Schedule. There was no evidence of effect modification by race/ethnicity in the association between income and gambling disorder (global p value = 0.17). Income was associated with increased odds of gambling disorder, but only for those with low income (< $15,000; OR 2.27, 95% CI 1.46, 3.53). There was no evidence that the effect of income on gambling disorder varies by race/ethnicity. For all race/ethnicities combined, low income was associated with significantly increased odds of gambling disorder (OR 2.27, 95% CI 1.46, 3.53). Further research is needed to better understand racial/ethnic differences in gambling disorder.

Differences in prevalence and associated factors of underweight and overweight/obesity according to rural-urban residence strata among women of reproductive age in Bangladesh: evidence from a cross-sectional national survey.

OBJECTIVES: This study aimed to investigate the differences in prevalence and factors influencing underweight and overweight/obesity stratified by region of residence among women of reproductive age in Bangladesh. DESIGN: Secondary analysis of cross-sectional nationwide data. SETTING: This study used Bangladesh Demographic and Health Survey 2014 data. PARTICIPANTS: A weighted sample of 16 478 women of reproductive age (15-49 years) were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Using the Asian-specific cut-off for body mass index, the primary outcome of this study was categorised as: underweight (<18.5 kg/m2), normal weight (18.5 to <23.0) kg/m2 and overweight/obese (≥23.0 kg/m2) stratified according to rural-urban residence. RESULTS: More than half of urban women (53%, n=2493) and one-third of rural women (33%, n=3968) were found to be overweight/obese. Around one-fifth of rural women (21%, n=2490) and almost one in eight urban women (12%, n=571) were reported as underweight. In the final multivariable analyses, increasing age, higher educational status and higher order wealth quintile, each had a significant positive association with being overweight/obese and an inverse association with being underweight. Urban unmarried women had lower odds of being overweight/obese compared with their married counterparts. Rural women who used contraceptives had significantly decreased odds (adjusted OR (AOR) 0.8, 95% CI 0.7 to 0.9) of being underweight compared with contraceptive non-users; no such association was noted in urban women. Women from Sylhet division in both urban (AOR 1.7, 95% CI 1.2 to 2.5) and rural regions (AOR 1.5, 95% CI 1.2 to 1.8) had increased odds of being underweight compared with women in Barisal division. CONCLUSIONS: This study found association of multiple factors with both overweight/obesity and underweight among Bangladeshi women of reproductive age. Public health programmes in Bangladesh aiming to prevent the double burden of malnutrition should focus these factors through comprehensive public awareness and cost-effective operational health interventions.

Prevalence and factors associated with underweight, overweight and obesity among women of reproductive age in India.

INTRODUCTION: Although the prevalence of underweight is declining among Indian women, the prevalence of overweight/obesity is increasing. This study examined the prevalence and factors associated with underweight and overweight/obesity among reproductive-aged (i.e., 15-49 years) women in India. METHODS: This cross-sectional study analyzed data from the 2015-16 National Family Health Survey. The Asian and World Health Organization (WHO) recommended cutoffs for body mass index (BMI) were used to categorize body weight. The Asian and WHO BMI cutoffs for combined overweight/obesity were ≥ 23 and ≥ 25 kg/m2, respectively. Both recommendations had the same cutoff for underweight, < 18.5 kg/m2. After prevalence estimation, logistic regression was applied to investigate associated factors. RESULTS: Among 647,168 women, the median age and BMI was 30 years and 21.0 kg/m2, respectively. Based on the Asian cutoffs, the overall prevalence of underweight was 22.9%, overweight was 22.6%, and obesity was 10.7%, compared to 15.5% overweight and 5.1% obesity as per WHO cutoffs. The prevalence and odds of underweight were higher among young, nulliparous, contraceptive non-user, never-married, Hindu, backward castes, less educated, less wealthy, and rural women. According to both cutoffs, women who were older, ever-pregnant, ever-married, Muslims, castes other than backwards, highly educated, wealthy, and living in urban regions had higher prevalence and odds of overweight/obesity. CONCLUSION: The prevalence of both non-normal weight categories (i.e., underweight and overweight/obesity) was high. A large proportion of women are possibly at higher risks of cardiovascular and reproductive adverse events due to these double nutrition burdens. Implementing large-scale interventions based on these results is essential to address these issues.

Social isolation proxy variables and prescription opioid and benzodiazepine misuse among older adults in the U.S.: A cross-sectional analysis of data from the National Survey on Drug Use and Health, 2015-2017.

BACKGROUND: Prescription drug misuse in older adults is a growing public health problem. It is important to understand factors which predispose older adults to misuse prescription drugs, and social isolation may play an important role. In this study, we examined the association between social isolation proxy variables (living alone, being unmarried, and not attending religious services) and prescription opioid/benzodiazepine misuse in older adults. METHODS: With pooled cross-sectional data from the National Survey on Drug Use and Health (2015-2017), we used multinomial multiple logistic regression models to analyze the association between each social isolation proxy variable and past-year prescription opioid/benzodiazepine misuse. We controlled for potentially confounding variables including sociodemographic, physical/mental health, and substance use variables. RESULTS: Being unmarried was associated with approximately three times increased odds of combined opioid and benzodiazepine misuse (OR 2.98, 95% CI 1.75, 5.08), a finding that persisted after adjusting for multiple potential confounders. Further analysis showed this finding persisted for divorced/separated and never married individuals, but not widowed. Not attending religious services was also associated with prescription opioid/benzodiazepine misuse, but only in unadjusted analyses. There was no association between living alone and opioid/benzodiazepine misuse. CONCLUSION: Increased odds of combined opioid and benzodiazepine prescription drug misuse was observed among unmarried older adults. Given the susceptibility of older adults to the harms of these medications, further exploration of the role of marital relationships and other forms of social connectedness in prescription drug misuse in this vulnerable population is indicated.

Age-stratified prevalence, treatment status, and associated factors of hypertension among US adults following application of the 2017 ACC/AHA guideline.

The 2017 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults reduced the systolic/diastolic blood pressure thresholds to define hypertension, including recommendations about treatment initiations and goals. We estimated the age-stratified prevalence, treatment status, and factors associated with hypertension among US adults aged ≥ 20 years based on this guideline. This cross-sectional study used the 2011-2016 National Health and Nutrition Examination Survey data. The primary outcomes were the presence and treatment status of hypertension. Among 16,103 participants, the proportions (95% confidence interval) of hypertensive, treatment-indicated, untreated individuals among treatment-indicated, and treatment goals not met among treated for hypertension by age groups were, respectively, 17.4% (15.8-19.1), 6.9% (6.1-7.8), 67.6% (61.0-73.5), and 58.6% (46.1-70.2) among 20-34 years; 39.2% (37.0-41.5), 24.4% (22.4-26.5), 41.8% (37.7-46.0), and 50.4% (44.7-56.1) among 35-49 years; 62.3% (60.1-64.6), 51.4% (49.0-53.8), 31.0% (28.2-34.0), and 51.9% (47.6-56.1) among 50-64 years; 77.7% (75.3-79.8), 77.0% (74.7-79.2), 27.0% (24.3-29.8), and 63.1% (59.4-66.5) among ≥ 65 years; and 46.8% (45.4-48.3), 36.9% (35.4-38.5), 33.2% (30.9-35.5), and 56.7% (54.1-59.3) among overall population. Despite some dissimilarities, the prevalence, treatment eligibility, and odds of hypertension were higher among non-Hispanic blacks and among people with high cholesterol, low high-density lipoprotein, chronic kidney disease, diabetes, increased body weight, and low leisure-time physical activity in all age strata. The prevalence and treatment eligibility were high among adults from all age groups; however, a significant proportion of participants, especially those who were younger, had blood pressure levels above the treatment goals or were untreated. Addressing the associated characteristics from a younger age may help prevent the complications of hypertension.

Estimated Change in Prevalence and Trends of Childhood Blood Pressure Levels in the United States After Application of the 2017 AAP Guideline.

INTRODUCTION: Childhood hypertension is associated with higher risks of cardiovascular disease during adulthood. This study estimated the prevalence of hypertension and high blood pressure among children aged 8 to 17 years in the United States per the 2017 American Academy of Pediatrics (AAP) guideline and compared that with the 2004 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) guideline's prevalence estimate during 2005-2008 and 2013-2016. METHODS: This cross-sectional study analyzed the National Health and Nutrition Examination Survey data. High blood pressure included hypertension and elevated blood pressure (per the 2017 AAP guideline)/prehypertension (per the 2004 NIH/NHLBI guideline). RESULTS: The analysis included 3,633 children in 2005-2008 and 3,471 children in 2013-2016. Per the 2004 NIH/NHLBI guideline, 3.1% (95% confidence interval [CI], 2.3%-4.3%) had hypertension in 2005-2008 and 1.9% (95% CI, 1.4%-2.6%) had hypertension in 2013-2016. Per the 2017 AAP guideline, prevalence was 5.7% (95% CI, 4.6%-7.1%) in 2005-2008 and 3.5% (95% CI, 2.7%-4.5%) in 2013-2016. About 2.5% (95% CI, 2.0%-3.1%) children in 2005-2008 and 1.5% (95% CI, 0.9%-2.0%) children in 2013-2016 were reclassified as hypertensive. We observed a similar change in prevalence for high blood pressure after application of the new guideline. The prevalence of high blood pressure also declined from 2005-2008 to 2013-2016 per both guidelines. CONCLUSION: Although the new guideline would reclassify a small proportion of children as having hypertension or high blood pressure, the prevalence declined from 2005-2008 to 2013-2016.

Effects of incentives and prenotification on response rates and costs in a national web survey of physicians.

Little is known about what strategies are cost-effective in increasing participation among physicians in surveys that are conducted exclusively via the web. To assess the effects of incentives and prenotification on response rates and costs, general internists (N = 3,550) were randomly selected from the American Medical Association (AMA) Masterfile and assigned to experimental groups that varied in the amount of a promised incentive (none, entry into a $200 lottery, $50, or $100) and prenotification (none, prenotification letter only, or prenotification letter containing a $2 preincentive). Results indicated that the response rates were highest in the groups promised $100 and $50, respectively. While the postal prenotification letter increased response rates, the inclusion of a small token $2 preincentive had no effect on participation. Further, unlike mail surveys of physicians, the $2 preincentive was not cost-effective. Among physicians, larger promised incentives of $50 or $100 are more effective than a nominal preincentive in increasing participation in a web-only survey. Consistent with prior research, there was little evidence of nonresponse bias among the experimental groups.