Bisphosphonates and risk of atrial fibrillation: a meta-analysis

Abstract Introduction Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Although a recent FDA review of the results of clinical trials reported no clear link between bisphosphonates and serious or non-serious atrial fibrillation (AF), some epidemiologic studies have suggested an association between AF and bisphosphonates. Methods We conducted a meta-analysis of non-experimental studies to evaluate the risk of AF associated with bisphosphonates. Studies were identified by searching MEDLINE and EMBASE using a combination of the Medical Subject Headings and keywords. Our search was limited to English language articles. The pooled estimates of odds ratios (OR) as a measure of effect size were calculated using a random effects model. Results Seven eligible studies with 266,761 patients were identified: three cohort, three case-control, and one self-controlled case series. Bisphosphonate exposure was not associated with an increased risk of AF [pooled multivariate OR 1.04, 95% confidence interval (CI) 0.92-1.16] after adjusting for known risk factors. Moderate heterogeneity was noted (I-squared score = 62.8%). Stratified analyses by study design, cohort versus case-control studies, yielded similar results. Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively). No clear asymmetry was observed in the funnel plot analysis. Few studies compared risk between bisphosphonates or by dosing. Conclusions Our study did not find an association between bisphosphonate exposure and AF. This finding is consistent with the FDA's statement

Measuring patient perceptions about osteoporosis pharmacotherapy

Abstract Background Adherence to osteoporosis pharmacotherapy is poor, and linked with patient perceptions of the benefits of, and barriers to taking these treatments. To better understand the association between patient perceptions and osteoporosis pharmacotherapy, we generated thirteen items that may tap into patient perceptions about the benefits of, and barriers to osteoporosis treatment; and included these items as part of a standardized telephone interview of women aged 65–90 years (n = 871). The purpose of this paper is to report the psychometric evaluation of our scale. Findings Upon detailed analysis, six of the thirteen items were omitted: four redundant, one did not correlate well with any other item and one factorial complex. From the remaining seven items, two distinct unidimensional domains emerged (variance explained = 78%). Internal consistency of the 5-item osteoporosis drug treatment benefits domain was good (Cronbach's alpha = 0.88), and was supported by construct validity; women reporting a physician-diagnosis or taking osteoporosis pharmacotherapy had higher osteoporosis treatment benefit scores compared to those reporting no osteoporosis diagnosis or treatment respectively. Because only two items were identified as tapping into treatment barriers, we recommend they each be used as a separate item assessing potential barriers to adherence to osteoporosis pharmacotherapy, rather than combined into a single scale. Conclusion The 5-item osteoporosis drug treatment benefits scale may be useful to examine perceptions about the benefits of osteoporosis pharmacotherapy. Further research is needed to develop scales that adequately measure perceived barriers to osteoporosis pharmacotherapy

Disease risk score as a confounder summary method: systematic review and recommendations: DRS AS A CONFOUNDER SUMMARY METHOD

To systematically examine trends and applications of the disease risk score (DRS) as a confounder summary method

Confounder summary scores when comparing the effects of multiple drug exposures

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS) and disease risk score (DRS)

Predictors of locating women six to eight years after contact: internet resources at recruitment may help to improve response rates in longitudinal research

<p>Abstract</p> <p>Background</p> <p>The ability to locate those sampled has important implications for response rates and thus the success of survey research. The purpose of this study was to examine predictors of locating women requiring tracing using publicly available methods (primarily Internet searches), and to determine the additional benefit of vital statistics linkages.</p> <p>Methods</p> <p>Random samples of women aged 65–89 years residing in two regions of Ontario, Canada were selected from a list of those who completed a questionnaire between 1995 and 1997 (n = 1,500). A random sample of 507 of these women had been searched on the Internet as part of a feasibility pilot in 2001. All 1,500 women sampled were mailed a newsletter and information letter prior to recruitment by telephone in 2003 and 2004. Those with returned mail or incorrect telephone number(s) required tracing. Predictors of locating women were examined using logistic regression.</p> <p>Results</p> <p>Tracing was required for 372 (25%) of the women sampled, and of these, 181 (49%) were located. Predictors of locating women were: younger age, residing in less densely populated areas, having had a web-search completed in 2001, and listed name identified on the Internet prior to recruitment in 2003. Although vital statistics linkages to death records subsequently identified 41 subjects, these data were incomplete.</p> <p>Conclusion</p> <p>Prospective studies may benefit from using Internet resources at recruitment to determine the listed names for telephone numbers thereby facilitating follow-up tracing and improving response rates. Although vital statistics linkages may help to identify deceased individuals, these may be best suited for post hoc response rate adjustment.</p

A Cohort Study of Thiazolidinediones and Fractures in Older Adults with Diabetes

Context: Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-␥ and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. Objective: The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. Design: We conducted a cohort study. Participants: Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. Main Outcome: We measured the incidence of fracture within the cohort. Results: Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98 -1.77; P ϭ 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94 -1.55; P ϭ 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. Conclusions: As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin

Design choices for observational studies of the effect of exposure on disease incidence.

The purpose of this paper is to help readers choose an appropriate observational study design for measuring an association between an exposure and disease incidence. We discuss cohort studies, sub-samples from cohorts (case-cohort and nested case-control designs), and population-based or hospital-based case-control studies. Appropriate study design is the foundation of a scientifically valid observational study. Mistakes in design are often irremediable. Key steps are understanding the scientific aims of the study and what is required to achieve them. Some designs will not yield the information required to realise the aims. The choice of design also depends on the availability of source populations and resources. Choosing an appropriate design requires balancing the pros and cons of various designs in view of study aims and practical constraints. We compare various cohort and case-control designs to estimate the effect of an exposure on disease incidence and mention how certain design features can reduce threats to study validity

Placebo Adherence, Clinical Outcomes, and Mortality in the Womenʼs Health Initiative Randomized Hormone Therapy Trials

Medication adherence may be a proxy for healthy behaviors and other factors that affect outcomes. Prior studies of the association between placebo adherence and health outcomes have been limited primarily to men enrolled in clinical trials and cardiovascular disease outcomes. We examined associations between adherence to placebo and the risk of fracture, coronary heart disease, cancer, and all-cause mortality in the two Women’s Health Initiative (WHI) hormone therapy randomized trials

Temporal Trends and Factors Associated with Bisphosphonate Discontinuation and Restart

Adverse events related to long-term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long-term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as 6512\u2009months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120-day period preceding discontinuation or restart referent to the 120-day preceding control periods. Among 73,800 long-term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12\u2009months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual-energy X-ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long-term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. \ua9 2019 American Society for Bone and Mineral Research