CONTEXT:Concerns about potential prostate-related complications associated with testosterone replacement therapy (TRT) often lead hypogonadal men to remain untreated. METHODS:This large-scale retrospective cohort study aimed to address these concerns by analyzing Medicare enrollment and claims data (Parts A/B/C/D) from 2007 to 2020 for men aged ≥65 with diagnosed primary or secondary hypogonadism. Cox regression analysis and 1:1 propensity score matching, both stratified by age group, were employed to evaluate the association between prostate outcomes and TRT use. TRT use was further categorized by treatment duration, administration route, and aromatase inhibitor (AI) coadministration. RESULTS:Following propensity score matching, the prostate cancer (PCa) and benign prostatic hyperplasia (BPH) risk analyses included 546 964 and 412 782 hypogonadal men, respectively, with comparable baseline characteristics at the time of hypogonadism diagnosis. TRT use was linked to a significant 16% reduction in the hazard of PCa (HR = 0.84; 95% CI: 0.82-0.86), including reductions observed across long-term (15%), short-term (16%), parenteral (12%), and topical (13%) use. Sensitivity analyses excluding individuals with elevated prostate-specific antigen and family history of PCa similarly demonstrated a 18% reduction in the hazard of PCa among TRT users. Conversely, TRT use exhibited a 13% increase in the hazard of BPH (HR = 1.13; 95% CI: 1.11-1.14), with a larger increase for parenteral (19%) vs topical TRT (12%). Notably, long-term topical use was linked to a modest 9% increase. CONCLUSION:TRT use was associated with reduction in PCa hazard and modest increase in BPH hazard. These associations varied by treatment duration, route, and AI coadministration. These findings may inform clinical decision-making regarding TRT use in hypogonadal men and support a more individualized approach to care.

Introduction Apixaban and rivaroxaban are the most prescribed direct oral anticoagulants, and the safety of different doses in patients at high risk for bleeding is not fully defined. The objective of this study was to compare the rate of hospitalizations due to bleeding in patients prescribed apixaban versus rivaroxaban at specific doses. Methods We conducted a retrospective cohort study of more than 1.9 million Medicare beneficiaries who filled prescriptions for apixaban or rivaroxaban from 2014 to 2020 using the Medicare Parts A, B, C and D encounter and prescription claims database. The primary outcomes measured were hospitalizations due to bleeding categorized by location (intracranial, gastrointestinal [GI], and other) and all-cause mortality. Results Among the population studied, 1,022,170 (53 %) filled a prescription for apixaban 5 mg during the study period, followed by rivaroxaban 20 mg (27 %) and rivaroxaban 10 mg (11 %). Compared to the reference group of apixaban 5 mg, combination prescriptions for rivaroxaban 15–20 mg were associated with more than twice the risk of hospitalization due to GI bleeding (hazard ratio [HR] = 2.41, 95 % confidence interval [CI]: 2.15–2.70) and other bleeding (HR = 2.42, 95 % CI: 1.92–3.05) and were associated with a 51 % higher risk of hospitalization due to intracranial bleeding (HR = 1.51, 95 % CI: 1.15–1.98). There were 88,740 (4.6 %) deaths during the study period, with a 27 % increased risk of death associated with prescriptions for apixaban 2.5 mg (HR = 1.27, 95 % CI: 1.24–1.30) and a 19 % decreased risk of death associated with prescriptions for rivaroxaban 10 mg (HR = 0.81, 95 % CI: 0.78–0.85). Conclusion Rivaroxaban doses of 15 mg and greater were associated with higher bleeding risk. This data may aid clinicians in making an informed decision when prescribing specific doses of apixaban and rivaroxaban, particularly for patients with a high risk of bleeding.

OBJECTIVES:The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. METHODS:Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. RESULTS:Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). CONCLUSIONS:Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Purpose To study the effects of benign prostatic hyperplasia treatments, namely: alpha-adrenergic receptor blockers, 5-alpha-reductase inhibitors and phosphodiesterase-5 inhibitors on the risk of Parkinson's disease, Alzheimer's disease and mortality.Materials and methods All male Medicare enrollees aged 65 or above who were diagnosed with benign prostatic hyperplasia and received one of the study drugs between 2007-2020 were followed-up for the three outcomes. We used Cox regression analysis to assess the relative risk of each of the outcomes for each study drug compared to the most prescribed drug, tamsulosin, while controlling for demographic, socioeconomic and comorbidity factors.Results and conclusions The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68-0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91-0.97). For Parkinson's disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66-0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72-0.88). For Alzheimer's disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65-0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76-0.92). Tadalafil was associated with risk reduction (27-40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases.

Objectives: To examine the variation in patient’s health outcomes across different type, route, and strength of menopausal hormone therapy (HT). Design: Retrospective case-control study Setting: United States 2007-2020 Population: 10 million women aged 65 or more in US Medicare. Methods: Cox regression models with time-varying type, route, and strength of HT as well as patient characteristics. Main Outcome(s): all-cause mortality; 5 cancers- breast, lung, endometrial, colorectal, ovarian cancers; 6 CV conditions- ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction; and dementia. Results Estrogen monotherapy (ET) exhibited a significant, 19% (HR=0.81; 95% CI 0.79-0.82), relative risk reduction on mortality. The reduction was greater with estradiol and vaginal/transdermal than conjugated estrogen and oral preparations. ET also exhibited significant risk reductions for all study cancers; breast (15%), lung (13%), endometrial (29%), colorectal (13%) and ovarian (14%). All ET preparations except low-dose slightly increased risk of ischemic heart diseases (1-4%). Both combination therapy and progestogen monotherapy exhibited significantly increased risk of breast cancer (7-14%). Oral ET exhibited moderately increased risk of stroke (6%) and dementia (2%). Conclusions: Among senior Medicare women, the effect of menopausal HT varies by type, route, and strength. The use of estradiol, vaginal/transdermal, and low/medium for menopausal care is safer than its counterparts.

Background: Incidence of long COVID in the elderly is difficult to estimate and can be under-reported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call "long Flu". In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients. Methods and Findings: This is a cohort study of Medicare (the U.S. federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza and residual symptoms. Long COVID was identified by a) the designated long COVID-19 code B94.8 (code-based definition), or b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from one to 3 months post infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in four outcome measures: a) hospitalization (any cause), b) hospitalization (for long COVID symptom), c) emergency department (ED) visit (for long COVID symptom), and d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) vs. 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05-1.08, p<0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) vs. 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08-1.10, p<0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified. Conclusions: Relying on specific long COVID diagnostic codes results in significant under-reporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.

BACKGROUND:Incidence of long COVID in the elderly is difficult to estimate and can be underreported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call "long Flu." In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients. METHODS AND FINDINGS:This is a cohort study of Medicare (the US federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza, and residual symptoms. Long COVID was identified by (a) the designated long COVID code B94.8 (code-based definition), or (b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from 1 to 3 months post-infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in 4 outcome measures: (a) hospitalization (any cause); (b) hospitalization (for long COVID symptom); (c) emergency department (ED) visit (for long COVID symptom); and (d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients, respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell, and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) versus 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05 to 1.08, p < 0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) versus 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08 to 1.10, p < 0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified. CONCLUSIONS:Relying on specific long COVID diagnostic codes results in significant underreporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.

Despite the universal healthcare coverages, racial disparities in healthcare expenditures among senior Medicare beneficiaries exist. A few studies explored how racial disparities in healthcare expenditures changed over past decades and how it affected differently across 4 minoritized races, by type of Medicare and poverty levels. We conducted a longitudinal study of 21 healthcare expenditures from senior Medicare fee-for-service enrollees to determine overall and secular trends in racial disparities in healthcare expenditures between 2007 and 2020, during which the Affordable Care Act (ACA) came into full force and the COVID-19 pandemic had begun. We found important disparities in healthcare expenditures across 4 minoritized races compared to Whites, even after adjusting for possible confounders for such disparities. Disparities between Hispanics/Asians and Whites were much greater than disparities between Blacks and Whites, in all Parts A, B, and D expenditures. This reality has not been sufficiently emphasized in the literature. Importantly, Black-White disparities in total Part B expenditure gradually worsened between 2007 and 2020, and Hispanic-White and Asian-White disparities worsened greatly during that time window. Health planners need to focus on these large disparities and develop methods to shrink them.

OBJECTIVES:To access the accuracy of the Logical Observation Identifiers Names and Codes (LOINC) mapping to local laboratory test codes that is crucial to data integration across time and healthcare systems.MATERIALS AND METHODS:We used software tools and manual reviews to estimate the rate of LOINC mapping errors among 179 million mapped test results from 2 DataMarts in PCORnet. We separately reported unweighted and weighted mapping error rates, overall and by parts of the LOINC term.RESULTS:Of included 179 537 986 mapped results for 3029 quantitative tests, 95.4% were mapped correctly implying an 4.6% mapping error rate. Error rates were less than 5% for the more common tests with at least 100 000 mapped test results. Mapping errors varied across different LOINC classes. Error rates in chemistry and hematology classes, which together accounted for 92.0% of the mapped test results, were 0.4% and 7.5%, respectively. About 50% of mapping errors were due to errors in the property part of the LOINC name.DISCUSSIONS:Mapping errors could be detected automatically through inconsistencies in (1) qualifiers of the analyte, (2) specimen type, (3) property, and (4) method. Among quantitative test results, which are the large majority of reported tests, application of automatic error detection and correction algorithm could reduce the mapping errors further.CONCLUSIONS:Overall, the mapping error rate within the PCORnet data was 4.6%. This is nontrivial but less than other published error rates of 20%-40%. Such error rate decreased substantially to 0.1% after the application of automatic detection and correction algorithm.

This observational cohort study assesses the occurrence of post–COVID-19 condition symptoms in Medicare enrollees prescribed nirmatrelvir and molnupiravir.

BackgroundMaintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. MethodsUsing claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. ResultsUp to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB, statins, warfarin, direct factor Xa inhibitors and P2Y12 inhibitors were associated with reduced risks, compared to never users. Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. ConclusionMaintenance use of ACEI, ARB, warfarin, statins, direct factor Xa inhibitors and P2Y12 inhibitors was associated with reduction in risk of acquiring COVID-19 and dying from it.

BACKGROUND & AIMS: Observational studies have linked proton pump inhibitors (PPIs) with increased risk of mortality and other safety outcomes, in contradiction with a recent PPI randomized controlled trial (RCT). Observational studies may be prone to reverse causality, where deaths are attributed to the treatment rather than the conditions that are treated (protopathic bias). METHODS: We analyzed an incident drug user cohort of 1,930,728 elderly Medicare fee-for-service beneficiaries to evaluate the PPI-associated risk of death with a Cox regression analysis with time-varying covariates and propensity score adjustments. To correct for protopathic bias which occurs when a given drug is associated with prodromal signs of death, we implemented a lag-time approach by which any study drug taken during a 90-day look-back window before each death was disregarded. RESULTS: Among 1,930,728 study individuals, 80,972 (4.2%) died during a median 3.8 years of follow-up, yielding an overall unadjusted death rate/1000 person-years of 9.85; 14.31 for PPI users and 7.93 for non- users. With no lag-time, PPI use (vs no use) was associated with 10% increased mortality risk (adjusted HR= 1.10; 95% CI 1.08-1.12). However, with a lag-time of 90 days, mortality risk associated with PPI use was near zero (adjusted HR= 1.01; 95% CI 0.99-1.02). CONCLUSION: Given the usage patterns of PPIs in patients with conditions that may presage death, protopathic bias may explain the association of PPIs with increased risk of death reported in observational studies.

Background The long-term influence of menopausal hormone therapy remains unanswered due to the termination of randomized clinical trials and discordant findings from observational studies.Methods From 2007-2019 enrollment records of 100% Medicare beneficiaries, we identified 7 million female enrollees aged 65 or more. We identified type, route and strength of estrogen based on their prescription drug utilization records. Using vital status record and encounter records, we defined the first onset of thirteen patient outcomes; all-cause mortality; 5 cancers (breast, lung, endometrial, colorectal, ovarian cancers); 6 CV conditions (ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction); and dementia. Then, we implemented an extended Cox regression analysis to examine the effects of type, route, and strength of estrogens on each of 13 study outcomes.Findings Estrogen monotherapy (ET) exhibited a significant, 20% (aHR=0.80; 95% CI 0.78-0.82), relative risk reduction of mortality. The reduction was greater with estradiol (aHR=0.78; 95% CI 0.75-0.80) than conjugated estrogen (aHR=0.86; 95% CI 0.85-0.88), and with vaginal (aHR=0.69; 95% CI 0.65-0.74) than oral (aHR=0.89; 95% CI 0.87-0.90) and transdermal (aHR=0.78; 95% CI 0.75-0.81) preparations. ET also exhibited significant risk reductions for all study cancers, breast (aHR=0.82; 95% CI 0.80-0.84), lung (aHR=0.87; 95% CI 0.84-0.90), endometrial (aHR=0.65; 95% CI 0.62-0.69), colorectal (aHR=0.86; 95% CI 0.82-0.90) and ovarian (aHR=0.83; 95% CI 0.79-0.88). ET slightly increased risks of ischemic heart diseases (aHR=1.03; 95% CI 1.01-1.04). However, such risk was not observed with low dose ET (aHR=0.98; 95% CI 0.97-0.99). Both combination therapy (aHR=1.11; 95% CI 1.08-1.14) and progestogen monotherapy (aHR=1.09; 95% CI 1.05-1.13) exhibited a significantly increased risk of breast cancer. Oral HT exhibited a moderately increased risk of dementia.Conclusions Among female Medicare beneficiaries aged ≥65, the effect of menopausal hormone therapy varies by type, route, and strength but overall estrogen seemed beneficial.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis research was supported by the intramural Research Program of the National Library of Medicine, National Institutes of Health.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was declared not human subject research by the Office of Human Research Protection at the National Institutes of Health and by the Centers for Medicare & Medicaid Services' Privacy Board.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present work are contained in the manuscript

When Donald A.B. Lindberg M.D. became Director in 1984, the U.S. National Library of Medicine (NLM) was a leader in the development and use of information standards for published literature but had no involvement with standards for clinical data. When Dr. Lindberg retired in 2015, NLM was the Central Coordinating Body for Clinical Terminology Standards within the U.S. Department of Health and Human Services, a major funder of ongoing maintenance and free dissemination of clinical terminology standards required for use in U.S. electronic health records (EHRs), and the provider of many services and tools to support the use of terminology standards in health care, public health, and research. This chapter describes key factors in the transformation of NLM into a significant player in the establishment of U.S. terminology standards for electronic health records.

INTRODUCTION:Serious cardiac arrhythmias caused by QT-prolonging drugs are difficult to predict based on physiological measurement and pre-approval clinical trials. Post-marketing surveillance and monitoring are important to generate safety data.OBJECTIVES:To assess whether an observational study using Medicare claims data can detect the arrhythmogenic risk of QT-prolonging drugs.METHODS:We identified 17 QT-prolonging drugs with known risk of torsades des pointes (TdP) that were not used to treat cardiac arrhythmias. Amoxicillin and four serotonin-norepinephrine reuptake inhibitors (SNRIs) were used as controls. De-identified claims data of 1.2 million Medicare beneficiaries were accessed. Two separate Cox regressions were done for short-term and chronic-use drugs. The primary outcome was a composite of ventricular arrhythmias and/or sudden death, identified by ICD diagnostic codes. We explored the independent effect of each study drug on the outcomes. Other covariates included patient demographics, comorbidities, and known risk factors for drug-induced cardiac arrhythmia.RESULTS:We were able to detect increased risk in 14 of 17 study drugs (82.3%), and none of the control drugs. Among the fluoroquinolones, ciprofloxacin was the safest. Azithromycin and clarithromycin were relatively safe compared to erythromycin. Compared to SNRIs, both citalopram and escitalopram had increased risk, more so with escitalopram than citalopram. Comorbidities associated with increased risk included ischemic heart disease, electrolyte imbalance, bradycardia, acute myocardial infarction, heart failure, and chronic kidney and liver disease.CONCLUSION:Medicare data can be utilized for post-marketing surveillance and monitoring of the proarrhythmic risk of QT-prolonging drugs in older adults.

By enabling more efficient and effective medical decision making, computer-based clinical decision support (CDS) could unlock widespread benefits from the significant investment in electronic health record (EHR) systems in the United States. Evidence from high-quality CDS studies is needed to enable and support this vision of CDS-facilitated care optimization, but limited guidance is available in the literature for designing and reporting CDS studies. To address this research gap, this article provides recommendations for designing, conducting, and reporting CDS studies to: 1) ensure that EHR data to inform the CDS are available; 2) choose decision rules that are consistent with local care processes; 3) target the right users and workflows; 4) make the CDS easy to access and use; 5) minimize the burden placed on users; 6) incorporate CDS success factors identified in the literature, in particular the automatic provision of CDS as a part of clinician workflow; 7) ensure that the CDS rules are adequately tested; 8) select meaningful evaluation measures; 9) use as rigorous a study design as is feasible; 10) think about how to deploy the CDS beyond the original host organization; 11) report the study in context; 12) help the audience understand why the intervention succeeded or failed; and 13) consider the financial implications. If adopted, these recommendations should help advance the vision of more efficient, effective care facilitated by useful and widely available CDS.

Objectives To assess the association of fluoroquinolone use with tendon ruptures compared with no fluoroquinolone and that of the four most commonly prescribed non-fluoroquinolone antibiotics in the USA. Design Retrospective observational study. Setting US seniors enrolled in the federal old-age, survivor’s insurance programme. Participants 1 009 925 Medicare fee-for-service beneficiaries and their inpatient, outpatient, prescription drug records were used. Interventions Seven oral antibiotics, fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and amoxicillin, amoxicillin-clavulanate, azithromycin and cephalexin. Primary and secondary outcome measures All tendon ruptures combined, and three types of tendon ruptures by anatomic site, Achilles tendon rupture, rupture of rotator cuff and other tendon ruptures occurred in 2007–2016. Results Of three fluoroquinolones, only levofloxacin exhibited a significant increased risk of tendon ruptures—16% (HR=1.16; 95% CI 1.06 to 1.28), and 120% (HR=2.20; 95% CI 1.50 to 3.24) for rotator cuff and Achilles tendon rupture, respectively, in the ≤30 days window. Ciprofloxacin (HR=0.96; 95% CI 0.89 to 1.03) and moxifloxacin (HR=0.59; 95% CI 0.37 to 0.93) exhibited no increased risk of tendon ruptures combined. Among the non-fluoroquinolone antibiotics, cephalexin exhibited increased risk of combined tendon ruptures (HR=1.31; 95% CI 1.22 to 1.41) and modest to large risks across all anatomic rupture sites (HRs 1.19–1.93) at ≤30 days window. Notably, the risk of levofloxacin never exceeded the risk of the non-fluoroquinolone, cephalexin in any comparison. Conclusions In our study, fluoroquinolones as a class were not associated with the increased risk of tendon ruptures. Neither ciprofloxacin nor moxifloxacin exhibited any risk for tendon ruptures. Levofloxacin did exhibit significant increased risk. Cephalexin with no reported effect on metalloprotease activity had an equal or greater risk than levofloxacin; so we question whether metalloprotease activity has any relevance to observed associations with tendon rupture. Confounding by indication bias may be more relevant and should be given more consideration as explanation for significant associations in observational studies of tendon rupture.