Pain Management in Older Adults before and during the First Year of Covid-19 Pandemic: Prevalence, Trends, and Correlates.

BACKGROUND: There is limited knowledge on whether and how healthcare access restrictions imposed by the Covid-19 pandemic have affected utilization of both opioid and non-pharmacological treatments among US older adults living with chronic pain. METHODS: We compared prevalence of chronic pain and high impact chronic pain (HICP; i.e., chronic pain limiting life or work activities on most days or every day in the past 6 months) between 2019 (pre-pandemic) and 2020 (first year of pandemic) and utilization of opioids and non-pharmacological pain treatments among adults aged ≥65 years enrolled in the National Health Interview Survey (NHIS), a nationally representative sample of non-institutionalized civilian US adults. RESULTS: Of 12,027 survey participants aged ≥65 (representing 32.6 million non-institutionalized older adults nationally), the prevalence of chronic pain was not significantly different from 2019 (30.8%; 95% confidence interval [CI], 29.7-32.0%) to 2020 (32.1%; 95% CI, 31.0-33.3%; p=0.06). Among older adults with chronic pain, the prevalence of HICP was also unchanged (38.3%; 95% CI, 36.1-40.6% in 2019 versus 37.8%; 95% CI, 34.9-40.8% in 2020; p=0.79). Use of any non-pharmacological interventions for pain management decreased significantly from 61.2% (95 CI, 58.8-63.5%) in 2019 to 42.1% (95% CI, 40.5-43.8%) in 2020 (p<0.001) among those with chronic pain, as did opioid use in the past 12 months from 20.2% (95% CI, 18.9-21.6%) in 2019 to 17.9% (95% CI, 16.7-19.1%) in 2020 (p=0.006). Predictors of treatment utilization were similar in both chronic pain and HICP. CONCLUSION: Use of pain treatments among older adults with chronic pain declined in the first year of Covid-19 pandemic. Future research is needed to assess long-term effects of Covid-19 pandemic on pain management in older adults.

Population-Level Strategies for Nirmatrelvir/Ritonavir Prescribing-A Cost-effectiveness Analysis.

Background: New coronavirus disease 2019 (COVID-19) medications force decision-makers to weigh limited evidence of efficacy and cost in determining which patient populations to target for treatment. A case in point is nirmatrelvir/ritonavir, a drug that has been recommended for elderly, high-risk individuals, regardless of vaccination status, even though clinical trials have only evaluated it in unvaccinated patients. A simple optimization framework might inform a more reasoned approach to the trade-offs implicit in the treatment allocation decision. Methods: We conducted a cost-effectiveness analysis using a decision-analytic model comparing 5 nirmatrelvir/ritonavir prescription policy strategies, stratified by vaccination status and risk for severe disease. We considered treatment effectiveness at preventing hospitalization ranging from 21% to 89%. Sensitivity analyses were performed on major parameters of interest. A web-based tool was developed to permit decision-makers to tailor the analysis to their settings and priorities. Results: Providing nirmatrelvir/ritonavir to unvaccinated patients at high risk for severe disease was cost-saving when effectiveness against hospitalization exceeded 33% and cost-effective under all other data scenarios we considered. The cost-effectiveness of other allocation strategies, including those for vaccinated adults and those at lower risk for severe disease, depended on willingness-to-pay thresholds, treatment cost and effectiveness, and the likelihood of severe disease. Conclusions: Priority for nirmatrelvir/ritonavir treatment should be given to unvaccinated persons at high risk of severe disease from COVID-19. Further priority may be assigned by weighing treatment effectiveness, disease severity, drug cost, and willingness to pay for deaths averted.

Comparison of Clinical Study Results Reported in medRxiv Preprints vs Peer-reviewed Journal Articles.

Importance: Preprints have been widely adopted to enhance the timely dissemination of research across many scientific fields. Concerns remain that early, public access to preliminary medical research has the potential to propagate misleading or faulty research that has been conducted or interpreted in error. Objective: To evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies posted to medRxiv that are subsequently published in peer-reviewed journals (preprint-journal article pairs). Design, Setting, and Participants: This cross-sectional study assessed all preprints describing clinical studies that were initially posted to medRxiv in September 2020 and subsequently published in a peer-reviewed journal as of September 15, 2022. Main Outcomes and Measures: For preprint-journal article pairs describing clinical trials, observational studies, and meta-analyses that measured health-related outcomes, the sample size, primary end points, corresponding results, and overarching conclusions were abstracted and compared. Sample size and results from primary end points were considered concordant if they had exact numerical equivalence. Results: Among 1399 preprints first posted on medRxiv in September 2020, a total of 1077 (77.0%) had been published as of September 15, 2022, a median of 6 months (IQR, 3-8 months) after preprint posting. Of the 547 preprint-journal article pairs describing clinical trials, observational studies, or meta-analyses, 293 (53.6%) were related to COVID-19. Of the 535 pairs reporting sample sizes in both sources, 462 (86.4%) were concordant; 43 (58.9%) of the 73 pairs with discordant sample sizes had larger samples in the journal publication. There were 534 pairs (97.6%) with concordant and 13 pairs (2.4%) with discordant primary end points. Of the 535 pairs with numerical results for the primary end points, 434 (81.1%) had concordant primary end point results; 66 of the 101 discordant pairs (65.3%) had effect estimates that were in the same direction and were statistically consistent. Overall, 526 pairs (96.2%) had concordant study interpretations, including 82 of the 101 pairs (81.2%) with discordant primary end point results. Conclusions and Relevance: Most clinical studies posted as preprints on medRxiv and subsequently published in peer-reviewed journals had concordant study characteristics, results, and final interpretations. With more than three-fourths of preprints published in journals within 24 months, these results may suggest that many preprints report findings that are consistent with the final peer-reviewed publications.

Characteristics of Retracted Research Articles About COVID-19 vs Other Topics.

This cross-sectional study compares the author and journal characteristics of retracted articles on COVID-19 with retracted articles from other topics.

Clinical trial transparency and data sharing among biopharmaceutical companies and the role of company size, location and product type: a cross-sectional descriptive analysis

ObjectivesTo examine company characteristics associated with better transparency and to apply a tool used to measure and improve clinical trial transparency among large companies and drugs, to smaller companies and biologics.DesignCross-sectional descriptive analysis.Setting and participantsNovel drugs and biologics Food and Drug Administration (FDA) approved in 2016 and 2017 and their company sponsors.Main outcome measuresUsing established Good Pharma Scorecard (GPS) measures, companies and products were evaluated on their clinical trial registration, results dissemination and FDA Amendments Act (FDAAA) implementation;companies were ranked using these measures and a multicomponent data sharing measure. Associations between company transparency scores with company size (large vs non-large), location (US vs non-US) and sponsored product type (drug vs biologic) were also examined.Results26% of products (16/62) had publicly available results for all clinical trials supporting their FDA approval and 67% (39/58) had public results for trials in patients by 6 months after their FDA approval;58% (32/55) were FDAAA compliant. Large companies were significantly more transparent than non-large companies (overall median transparency score of 95% (IQR 91–100) vs 59% (IQR 41–70), p<0.001), attributable to higher FDAAA compliance (median of 100% (IQR 88–100) vs 57% (0–100), p=0.01) and better data sharing (median of 100% (IQR 80–100) vs 20% (IQR 20–40), p<0.01). No significant differences were observed by company location or product type.ConclusionsIt was feasible to apply the GPS transparency measures and ranking tool to non-large companies and biologics. Large companies are significantly more transparent than non-large companies, driven by better data sharing procedures and implementation of FDAAA trial reporting requirements. Greater research transparency is needed, particularly among non-large companies, to maximise the benefits of research for patient care and scientific innovation.

Agreement of treatment effects from observational studies and randomized controlled trials evaluating hydroxychloroquine, lopinavir-ritonavir, or dexamethasone for covid-19: meta-epidemiological study.

OBJECTIVE: To systematically identify, match, and compare treatment effects and study demographics from individual or meta-analysed observational studies and randomized controlled trials (RCTs) evaluating the same covid-19 treatments, comparators, and outcomes. DESIGN: Meta-epidemiological study. DATA SOURCES: National Institutes of Health Covid-19 Treatment Guidelines, a living review and network meta-analysis published in The BMJ, a living systematic review with meta-analysis and trial sequential analysis in PLOS Medicine (The LIVING Project), and the Epistemonikos "Living OVerview of Evidence" (L·OVE) evidence database. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: RCTs in The BMJ's living review that directly compared any of the three most frequently studied therapeutic interventions for covid-19 across all data sources (that is, hydroxychloroquine, lopinavir-ritonavir, or dexamethasone) for any safety and efficacy outcomes. Observational studies that evaluated the same interventions, comparisons, and outcomes that were reported in The BMJ's living review. DATA EXTRACTION AND SYNTHESIS: Safety and efficacy outcomes from observational studies were identified and treatment effects for dichotomous (odds ratios) or continuous (mean differences or ratios of means) outcomes were calculated and, when possible, meta-analyzed to match the treatment effects from individual RCTs or meta-analyses of RCTs reported in The BMJ's living review with the same interventions, comparisons, and outcomes (that is, matched pairs). The analysis compared the distribution of study demographics and the agreement between treatment effects from matched pairs. Matched pairs were in agreement if both observational and RCT treatment effects were significantly increasing or decreasing (P<0.05) or if both treatment effects were not significant (P≥0.05). RESULTS: 17 new, independent meta-analyses of observational studies were conducted that compared hydroxychloroquine, lopinavir-ritonavir, or dexamethasone with an active or placebo comparator for any safety or efficacy outcomes in covid-19 treatment. These studies were matched and compared with 17 meta-analyses of RCTs reported in The BMJ's living review. 10 additional matched pairs with only one observational study and/or one RCT were identified. Across all 27 matched pairs, 22 had adequate reporting of demographical and clinical data for all individual studies. All 22 matched pairs had studies with overlapping distributions of sex, age, and disease severity. Overall, 21 (78%) of the 27 matched pairs had treatment effects that were in agreement. Among the 17 matched pairs consisting of meta-analyses of observational studies and meta-analyses of RCTs, 14 (82%) were in agreement; seven (70%) of the 10 matched pairs consisting of at least one observational study or one RCT were in agreement. The 18 matched pairs with treatment effects for dichotomous outcomes had a higher proportion of agreement (n=16, 89%) than did the nine matched pairs with treatment effects for continuous outcomes (n=5, 56%). CONCLUSIONS: Meta-analyses of observational studies and RCTs evaluating treatments for covid-19 have summary treatment effects that are generally in agreement. Although our evaluation is limited to three covid-19 treatments, these findings suggest that meta-analyzed evidence from observational studies might complement, but should not replace, evidence collected from RCTs.

A multicenter evaluation of computable phenotyping approaches for SARS-CoV-2 infection and COVID-19 hospitalizations.

Diagnosis codes are used to study SARS-CoV2 infections and COVID-19 hospitalizations in administrative and electronic health record (EHR) data. Using EHR data (April 2020-March 2021) at the Yale-New Haven Health System and the three hospital systems of the Mayo Clinic, computable phenotype definitions based on ICD-10 diagnosis of COVID-19 (U07.1) were evaluated against positive SARS-CoV-2 PCR or antigen tests. We included 69,423 patients at Yale and 75,748 at Mayo Clinic with either a diagnosis code or a positive SARS-CoV-2 test. The precision and recall of a COVID-19 diagnosis for a positive test were 68.8% and 83.3%, respectively, at Yale, with higher precision (95%) and lower recall (63.5%) at Mayo Clinic, varying between 59.2% in Rochester to 97.3% in Arizona. For hospitalizations with a principal COVID-19 diagnosis, 94.8% at Yale and 80.5% at Mayo Clinic had an associated positive laboratory test, with secondary diagnosis of COVID-19 identifying additional patients. These patients had a twofold higher inhospital mortality than based on principal diagnosis. Standardization of coding practices is needed before the use of diagnosis codes in clinical research and epidemiological surveillance of COVID-19.

Heart Watch Study: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04468321.

Loneliness, sadness, and feelings of social disconnection in older adults during the COVID-19 pandemic.

BACKGROUND: Public health measures to control the COVID-19 pandemic have led to feelings of loneliness among older adults, which, prior to COVID, has been associated with subsequent morbidity and mortality. We sought to identify differences in feelings of loneliness, sadness, and social disconnection early in the pandemic across racial groups, and possible mitigating factors. METHODS: We performed a cross-sectional analysis using the weighted nationally-representative Medicare Current Beneficiaries Survey COVID-19 supplement, collected summer 2020. We included all Medicare beneficiaries aged 65 years and older who did not respond by proxy. We examined changes in loneliness, sadness, or feelings of social disconnection. Multivariable logistic regression models accounted for sociodemographic variables, access to primary care and the internet, and history of depression or dementia. RESULTS: Among 8125 beneficiaries, representative of 43.7 million Medicare beneficiaries, 22.6% reported loneliness or sadness, and 37.1% feeling socially disconnected. In fully-adjusted models, Hispanic/Latinx beneficiaries were most likely to report loneliness or sadness (OR = 1.3, CI: 1.02-1.65; p = 0.02) and Black beneficiaries were least likely to report feeling socially disconnected (OR = 0.55; CI: 0.42-0.73; p < 0.001). Internet access was associated with increased odds of both (OR = 1.29, 95 CI: 1.07-1.56; p = 0.009; and OR = 1.42, 95 CI: 1.24-1.63; p < 0.001, respectively). Access to primary care was associated with lower odds of both (OR = 0.77, 95 CI: 0.61-0.96; p = 0.02; and OR = 0.72, 95 CI: 0.61-0.87; p < 0.001). CONCLUSIONS: Loneliness, sadness, and feelings of social disconnection were common among older Medicare beneficiaries early in the COVID-19 pandemic. Differences by race/ethnicity may be driven by different living structures and social networks, and warrant further study. Policy makers and clinicians should consider facilitating connection by phone or in person, as internet access did not diminish feelings of loneliness, particularly for those living alone. Access to primary care, and tools for clinicians to address loneliness should be prioritized.

The Association Between History of Depression and Access to Care Among Medicare Beneficiaries During the COVID-19 Pandemic.

BACKGROUND: Depression is associated with a higher risk for experiencing barriers to care, unmet social needs, and poorer economic and mental health outcomes. OBJECTIVE: To determine the impact of COVID-19 on ability to access care, social and economic needs, and mental health among Medicare beneficiaries with and without depression. DESIGN AND PARTICIPANTS: Cross-sectional study using data from the 2020 Medicare Current Beneficiary Survey COVID-19 Summer Supplement Public Use File. MAIN MEASURES: Access to medical care, inability to access food, medications, household supplies, pay rent or mortgage, feelings of economic security, and mental health effects since COVID-19, risk-adjusted for sociodemographic and clinical characteristics. KEY RESULTS: Participants were 11,080 Medicare beneficiaries (nationally representative of 55,960,783 beneficiaries), 27.0% with and 73.0% without a self-reported history of depression. As compared to those without a history of depression, Medicare beneficiaries with a self-reported history of depression were more likely to report inability to get care because of COVID-19 (aOR = 1.28, 95% CI, 1.09, 1.51; P = 0.003), to get household supplies such as toilet paper (aOR = 1.32, 95% CI, 1.10, 1.58; P = 0.003), and to pay rent or mortgage (aOR = 1.64, 95% CI, 1.07, 2.52; P = 0.02). Medicare beneficiaries with a self-reported history of depression were more likely to report feeling less financially secure (aOR = 1.43, 95% CI, 1.22, 1.68; P < 0.001), more stressed or anxious (aOR = 1.68, 95% CI, 1.49, 1.90; P < 0.001), more lonely or sad (aOR = 1.97, 95% CI, 1.68, 2.31; P < 0.001), and less socially connected (aOR = 1.27, 95% CI, 1.10, 1.47; P = 0.001). CONCLUSION: A self-reported history of depression was associated with greater inability to access care, more unmet social needs, and poorer economic and mental health outcomes, suggesting greater risk for adverse health outcomes during COVID-19.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.