Long-term performance of single-connector (DF4) implantable defibrillator leads.

AIMS: Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports. METHODS AND RESULTS: We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction. CONCLUSION: DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.

Using Parallel Streams of Evidence to Inform Guideline Development: The Case of the 2021 American College of Rheumatology Management of Rheumatoid Arthritis Guideline.

OBJECTIVE: We aim to describe an evidence synthesis approach using parallel streams of evidence that informed the development of the 2021 American College of Rheumatology (ACR) guideline for the management of rheumatoid arthritis (RA). METHODS: We developed the evidence synthesis approach using parallel streams of evidence in multiple rounds of discussion, piloting, feedback, and revisions. A number of working groups involving ACR staff, content experts, and methodologists coordinated to develop and implement the approach. RESULTS: We used a major stream of evidence that identified evidence specific to the clinical questions being addressed in the guideline (ie, we were able to match relevant articles to specific questions). We also used additional streams that identified data that applied across multiple questions. We describe in this article the different steps of the major stream, ie, screening and tagging, matching articles to question clusters, matching articles to individual questions, data abstraction and analysis, and Grading of Recommendations Assessment, Development and Evaluation (GRADEing). We then describe how we packaged the parallel streams of evidence into standardized structured tables to facilitate formulating the recommendations. These tables included information for the following factors: desirable effects, undesirable effects, certainty of evidence, valuation of outcomes, cost of interventions, and cost-effectiveness of interventions. The approach allowed us to match eligible articles for 47 of 81 clinical questions. We identified no eligible articles that addressed the remaining 34 questions. CONCLUSION: We were successful in using parallel streams of evidence to inform the development of the 2021 ACR guideline for the management of RA.

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

OBJECTIVE: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

OBJECTIVE: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

Relationship between device-detected burden and duration of atrial fibrillation and risk of ischemic stroke.

BACKGROUND: Wider availability of continuous rhythm monitoring has made feasible the incorporation of metrics of atrial fibrillation (AF) burden and duration into the decision to initiate anticoagulation. However, the relationship between thresholds of burden and duration and underlying risk factors at which anticoagulation should be considered remains unclear. OBJECTIVE: The purpose of this study was to evaluate the relationships of these metrics with each other and the outcome of stroke/transient ischemic attack (TIA). METHODS: We identified patients with cardiovascular implantable electronic devices (CIEDs) with atrial leads who had at least 1 interrogation in 2016 demonstrating nonpermanent AF and were not receiving oral anticoagulation (OAC). We evaluated the relationship between burden (ie, percentage of time spent in AF), the longest single episode of AF, and risk factors (ie, CHA2DS2-VASc score) in predicting risk of stroke/TIA. RESULTS: The study included 384 patients with mean follow-up of 3.2 ± 0.8 years and incidence of stroke/TIA of 14.8% during follow-up (∼4.6% per year). The burden of AF and the duration of longest episode demonstrated a significant positive correlation to each other but not CHA2DS2-VASc score. Importantly, although the CHA2DS2-VASc score was predictive of stroke/TIA, neither burden nor duration was associated with stroke/TIA. CONCLUSION: Among patients with CIED-detected AF not receiving OAC, the amount of AF (measured by either burden or duration) does not seem to significantly impact stroke risk, whereas CHA2DS2-VASc score does. These data suggest that among patients with CIED-detected AF, once AF occurs, stroke risk seems to be predominantly driven by underlying risk factors.

Reporting of conflicts of interest by authors of primary studies on health policy and systems research: a cross-sectional survey.

OBJECTIVES: The objective of this study was to assess the frequency and types of conflict of interest (COI) disclosed by authors of primary studies of health policy and systems research (HPSR). DESIGN: We conducted a cross-sectional survey using standard systematic review methodology for study selection and data extraction. We conducted descriptive analyses. SETTING: We collected data from papers published in 2016 in 'health policy and service journals' category in Web of Science database. PARTICIPANTS: We included primary studies (eg, randomised controlled trials, cohort studies, qualitative studies) of HPSR published in English in 2016 peer-reviewed health policy and services journals. OUTCOME MEASURES: Reported COI disclosures including whether authors reported COI or not, form in which COI disclosures were provided, number of authors per paper who report any type of COI, number of authors per paper who report specific types and subtypes of COI. RESULTS: We included 200 eligible primary studies of which 132 (66%) included COI disclosure statements of authors. Of the 132 studies, 19 (14%) had at least one author reporting at least one type of COI and the most frequently reported type was individual financial COI (n=15, 11%). None of the authors reported individual intellectual COIs or personal COIs. Financial and individual COIs were reported more frequently compared with non-financial and institutional COIs. CONCLUSION: A low percentage of HPSR primary studies included authors reporting COI. Non-financial or institutional COIs were the least reported types of COI.

Reporting of Financial and Non-financial Conflicts of Interest in Systematic Reviews on Health Policy and Systems Research: A Cross Sectional Survey.

BACKGROUND: Systematic reviews are increasingly used to inform health policy-making. The conflicts of interest (COI) of the authors of systematic reviews may bias their results and influence their conclusions. This may in turn lead to misguided public policies and systems level decisions. In order to mitigate the adverse impact of COI, scientific journals require authors to disclose their COIs. The objective of this study was to assess the frequency and different types of COI that authors of systematic reviews on health policy and systems research (HSPR) report. METHODS: We conducted a cross sectional survey. We searched the Health Systems Evidence (HSE) database of McMaster Health Forum for systematic reviews published in 2015. We extracted information regarding the characteristics of the systematic reviews and the associated COI disclosures. We conducted descriptive analyses. RESULTS: Eighty percent of systematic reviews included authors' COI disclosures. Of the 160 systematic reviews that included COI disclosures, 15% had at least one author reporting at least one type of COI. The two most frequently reported types of COI were individual financial COI and individual scholarly COI (11% and 4% respectively). Institutional COIs were less commonly reported than individual COIs (3% and 15% respectively) and non-financial COIs were less commonly reported than financial COIs (6% and 14% respectively). Only one systematic review reported the COI disclosure by editors, and none reported disclosure by peer reviewers. All COI disclosures were in the form of a narrative statement in the main document and none in an online document. CONCLUSION: A fifth of systematic reviews in HPSR do not include a COI disclosure statement, highlighting the need for journals to strengthen and/or better implement their COI disclosure policies. While only 15% of identified disclosure statements report any COI, it is not clear whether this indicates a low frequency of COI versus an underreporting of COI, or both.

The reporting of funding in health policy and systems research: a cross-sectional study.

BACKGROUND: Major research-reporting statements, such as PRISMA and CONSORT, require authors to provide information about funding. The objectives of this study were (1) to assess the reporting of funding in health policy and systems research (HPSR) papers and (2) to assess the funding reporting policies of journals publishing on HPSR. METHODS: We conducted two cross-sectional surveys for papers published in 2016 addressing HPSR (both primary studies and systematic reviews) and for journals publishing on HPSR (both journals under the 'Health Policy and Services' (HPS) category in the Web of Science, and non-HPS journals that published on HPSR). Teams of two reviewers selected studies and abstracted data in duplicate and independently. We conducted descriptive analyses and a regression analysis to investigate the association between reporting of funding by papers and the journal's characteristics. RESULTS: We included 400 studies (200 systematic reviews and 200 primary studies) that were published in 198 journals. Approximately one-third (31%) of HPSR papers did not report on funding. Of those that did, only 11% reported on the role of funders (15% of systematic reviews and 7% of primary studies). Of the 198 journals publishing on HPSR, 89% required reporting of the source of funding. Of those that did, about one-third (34%) required reporting of the role of funders. Journals classified under the HPS category (n = 72) were less likely than non-HPS journals that published HPSR studies (n = 142) to require information on the role of funders (15% vs. 32%). We did not find any of the journals' characteristics to be associated with the reporting of funding by papers. CONCLUSIONS: Despite the majority of journals publishing on HPSR requiring the reporting of funding, approximately one-third of HPSR papers did not report on the funding source. Moreover, few journals publishing on HPSR required the reporting of the role of funders, and few HPSR papers reported on that role.

Characteristics of funding of clinical trials: cross-sectional survey and proposed guidance.

OBJECTIVES: To provide a detailed and current characterisation of funding of a representative sample clinical trials. We also aimed to develop guidance for standardised reporting of funding information. METHODS: We addressed the extent to which clinical trials published in 2015 in any of the 119 Core Clinical Journals included a statement on the funding source (eg, whether a not-for-profit organisation was supported by a private-for-profit organisation), type of funding, amount and role of funder. We used a stepwise approach to develop a guidance and an instrument for standardised reporting of funding information. RESULTS: Of 200 trials, 178 (89%) included a funding statement, of which 171 (96%) reported being funded. Funding statements in the 171 funded trials indicated the source in 100%, amount in 1% and roles of funders in 50%. The most frequent sources were governmental (58%) and private-for-profit (40%). Of 54 funding statements in which the source was a not-for-profit organisation, we found evidence of undisclosed support of those from private-for-profit organisation(s) in 26 (48%). The most frequently reported roles of funders in the 171 funded trials related to study design (42%) and data analysis, interpretation or management (41%). Of 139 randomised controlled trials (RCTs) addressing pharmacological or surgical interventions, 29 (21%) reported information on the supplier of the medication or device. The proposed guidance addresses both the funding information that RCTs should report and the reporting process. Attached to the guidance is a fillable PDF document for use as an instrument for standardised reporting of funding information. CONCLUSION: Although the majority of RCTs report funding, there is considerable variability in the reporting of funding source, amount and roles of funders. A standardised approach to reporting of funding information would address these limitations. Future research should explore the implications of funding by not-for-profit organisations that are supported by for-profit organisations.

Authors of clinical trials reported individual and financial conflicts of interest more frequently than institutional and nonfinancial ones: a methodological survey.

BACKGROUND AND OBJECTIVE: Conflicts of interest (COIs) are increasingly recognized as important to disclose and manage in health research. The objective of this study was to assess the reporting of both financial and nonfinancial COI by authors of randomized controlled trials published in a representative sample of clinical journals. METHODS: We searched Ovid Medline and included a random sample of 200 randomized controlled trials published in 2015 in one of the 119 Core Clinical Journals. We classified COI using a comprehensive framework that includes the following: individual COIs (financial, professional, scholarly, advocatory, personal) and institutional COIs (financial, professional, scholarly, and advocatory). We conducted descriptive and regression analyses. RESULTS: Of the 200 randomized controlled trials, 188 (94%) reported authors' COI disclosures that were available in the main document (92%) and as International Committee of Medical Journal Editors forms accessible online (12%). Of the 188 trials, 57% had at least one author reporting at least one COI; in all these trials, at least one author reported financial COI. Institutional COIs (11%) and nonfinancial COIs (4%) were less commonly reported. References to COI disclosure statements for editors (1%) and medical writers (0%) were seldom present. Regression analyses showed positive associations between reporting individual financial COI and higher journal impact factor (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.02-1.10), larger number of authors (OR = 1.10, 95% CI 1.02-1.20), affiliation with an institution from a high-income country (OR = 16.75, 95% CI 3.38-82.87), and trials reporting on pharmacological interventions (OR = 2.28, 95% CI 1.13-4.62). CONCLUSION: More than half of published randomized controlled trials report that at least one author has a COI. Trial authors report financial COIs more often than nonfinancial COIs and individual COIs more frequently than institutional COIs.

Pharmacists' views and reported practices in relation to a new generic drug substitution policy in Lebanon: a mixed methods study.

BACKGROUND: Governments in both developed and developing countries have adopted generic drug substitution policies to decrease pharmaceutical expenditures and improve access to medicine. In August 2015, the Ministry of Public Health (MOPH) in Lebanon introduced generic drug substitution and a unified medical prescription form as policy instruments to promote generic drug use. The objective of this exploratory study was to examine the attitudes of community pharmacists and the reported practices in relation to the implementation of the new generic drug substitution policy. METHODS: We used a cross-sectional mixed methods approach composed of self-administered questionnaires and semi-structured interviews. The study population consisted of community pharmacists in Lebanon. We randomly approached one pharmacy personnel from each selected community pharmacy. We conducted descriptive analyses to assess responses to questionnaire and regression analyses to understand associations between responses and respondent demographics. We analyzed qualitative data thematically. RESULTS: Out of 204 invited community pharmacies, 153 pharmacies participated (75% response rate). The majority of respondents (64%) were in favor of generic drug substitution; however, less than half (40%) indicated they have substituted brand drugs for generic equivalents. Moreover, 57% indicated that the existing pricing system discourages them from performing generic drug substitution. Most respondents indicated that physicians are overusing the "non-substitutable" option (84%) and that there are technical problems with processing the new prescription form (78%). Less than half (47%) reported that the MOPH is performing regular audits on the forms collected by the pharmacy. While 45% of the respondents indicated that consumers have accepted most of the generic substitutions, 21% perceived the increase in generic drug dispensing to be significant. Findings suggested a potentially significant association between being informed about generic drugs and respondents' support of the policy. Suggested strategies to address implementation challenges included strengthening stewardship function of MOPH, securing full commitment of health care providers, conducting educational and awareness campaigns about generic drugs and generic drug substitution, and aligning incentive systems of the key stakeholders. CONCLUSIONS: The majority of community pharmacists were supportive of generic drug substitution in general but not of the current implementation of the policy in Lebanon. Findings revealed implementation challenges at the provider, patient, and system level which are hindering attainment of the policy objectives. The key lessons derived from this study can be used for continuous improvement of the policy and its implementation.

Reporting of financial and non-financial conflicts of interest by authors of systematic reviews: a methodological survey.

BACKGROUND: Conflicts of interest may bias the findings of systematic reviews. The objective of this methodological survey was to assess the frequency and different types of conflicts of interest that authors of Cochrane and non-Cochrane systematic reviews report. METHODS: We searched for systematic reviews using the Cochrane Database of Systematic Reviews and Ovid MEDLINE (limited to the 119 Core Clinical Journals and the year 2015). We defined a conflict of interest disclosure as the reporting of whether a conflict of interest exists or not, and used a framework to classify conflicts of interest into individual (financial, professional and intellectual) and institutional (financial and advocatory) conflicts of interest. We conducted descriptive and regression analyses. RESULTS: Of the 200 systematic reviews, 194 (97%) reported authors' conflicts of interest disclosures, typically in the main document, and in a few cases either online (2%) or on request (5%). Of the 194 Cochrane and non-Cochrane reviews, 49% and 33%, respectively, had at least one author reporting any type of conflict of interest (p=0.023). Institutional conflicts of interest were less frequently reported than individual conflicts of interest, and Cochrane reviews were more likely to report individual intellectual conflicts of interest compared with non-Cochrane reviews (19% and 5%, respectively, p=0.004). Regression analyses showed a positive association between reporting of conflicts of interest (at least one type of conflict of interest, individual financial conflict of interest, institutional financial conflict of interest) and journal impact factor and between reporting individual financial conflicts of interest and pharmacological versus non-pharmacological intervention. CONCLUSIONS: Although close to half of the published systematic reviews report that authors (typically many) have conflicts of interest, more than half report that they do not. Authors reported individual conflicts of interest more frequently than institutional and non-financial conflicts of interest.