Anticholinergic medication use and falls in postmenopausal women: Findings from the women's health initiative cohort study

Background: Results from studies assessing the association between anticholinergic use and falls are mixed, and prior studies are limited in their ability to control for important potential confounders. Thus, we sought to examine the association between anticholinergic medication use, including over-the-counter medications, and recurrent falls in community-dwelling older women. Methods: We analyzed data from a prospective cohort study of women aged 65 to 79 years from the Women's Health Initiative Observational Study and Clinical Trials. Women were recruited between 1993 and 1998, and analyses included 61,451 women with complete information. Medications with moderate or strong anticholinergic effects were ascertained directly from drug containers during face-to-face interviews. The main outcome measure was recurrent falls (≥2 falls in previous year), which was determined from self-report within 1.5 years subsequent to the medication assessment. Results: At baseline, 11.3 % were using an anticholinergic medication, of which antihistamines (commonly available over-the-counter) were the most common medication class (received by 45.2 % of individuals on anticholinergic medication). Using multivariable GEE models and controlling for potential confounders, the adjusted odds ratio for anticholinergic medication use was 1.51 (95 % CI, 1.43-1.60) for recurrent falls. Participants using multiple anticholinergic medications had a 100 % increase in likelihood of recurrent falls (adjusted odds ratio 2.00, 95 % CI 1.73-2.32). Results were robust to sensitivity analysis. Conclusions: Anticholinergic medication use was associated with increased risk for recurrent falls. Our findings reinforce judicious use of anticholinergic medications in older women. Public health efforts should emphasize educating older women regarding the risk of using over-the-counter anticholinergics, such as first-generation antihistamines

Urinary antihypertensive drug metabolite screening using molecular networking coupled to high-resolution mass spectrometry fragmentation

Introduction Mass spectrometry is the current technique of choice in studying drug metabolism. High-resolution mass spectrometry in combination with MS/MS gas-phase experiments has the potential to contribute to rapid advances in this field. However, the data emerging from such fragmentation spectral files pose challenges to downstream analysis, given their complexity and size. Objectives This study aims to detect and visualize antihypertensive drug metabolites in untargeted metabolomics experiments based on the spectral similarity of their fragmentation spectra. Furthermore, spectral clusters of endogenous metabolites were also examined. Methods Here we apply a molecular networking approach to seek drugs and their metabolites, in fragmentation spectra from urine derived from a cohort of 26 patients on antihypertensive therapy. The mass spectrometry data was collected on a Thermo Q-Exactive coupled to pHILIC chromatography using data dependent analysis (DDA) MS/MS gas-phase experiments. Results In total, 165 separate drug metabolites were found and structurally annotated (17 by spectral matching and 122 by classification based on a clustered fragmentation pattern). The clusters could be traced to 13 drugs including the known antihypertensives verapamil, losartan and amlodipine. The molecular networking approach also generated clusters of endogenous metabolites, including carnitine derivatives, and conjugates containing glutamine, glutamate and trigonelline. Conclusions The approach offers unprecedented capability in the untargeted identification of drugs and their metabolites at the population level and has great potential to contribute to understanding stratified responses to drugs where differences in drug metabolism may determine treatment outcome

Can a Multifaceted Intervention Including Motivational Interviewing Improve Medication Adherence, Quality of Life, and Mortality Rates in Older Patients Undergoing Coronary Artery Bypass Surgery? A Multicenter, Randomized Controlled Trial with 18-Month Follow-Up.

BACKGROUND: Patients undergoing coronary artery bypass graft (CABG) surgery are required to take a complex regimen of medications for extended periods, and they may have negative outcomes because they struggle to adhere to this regimen. Designing effective interventions to promote medication adherence in this patient group is therefore important. OBJECTIVE: The present study aimed to evaluate the long-term effects of a multifaceted intervention (psycho-education, motivational interviewing, and short message services) on medication adherence, quality of life (QoL), and mortality rates in older patients undergoing CABG surgery. METHODS: Patients aged over 65 years from 12 centers were assigned to the intervention (EXP; n = 144) or treatment-as-usual (TAU; n = 144) groups using cluster randomization at center level. Medication adherence was evaluated using the Medication Adherence Rating Scale (MARS), pharmacy refill rate, and lipid profile; QoL was evaluated using Short Form-36. Data were collected at baseline; 3, 6, and 18 months after intervention. Survival status was followed up at 18 months. Multi-level regressions and survival analyses for hazard ratio (HR) were used for analyses. RESULTS: Compared with patients who received TAU, the MARS, pharmacy refill rate, and lipid profile of patients in the EXP group improved 6 months after surgery (p < 0.01) and remained so 18 months after surgery (p < 0.01). QoL also increased among patients in the EXP group as compared with those who received TAU at 18 months post-surgery (physical component summary score p = 0.02; mental component summary score p = 0.04). HR in the EXP group compared with the TAU group was 0.38 (p = 0.04). CONCLUSION: The findings suggest that a multifaceted intervention can improve medication adherence in older patients undergoing CABG surgery, with these improvements being maintained after 18 months. QoL and survival rates increased as a function of better medication adherence. ClinicalTrials.gov NCT02109523

Deprescribing interventions and their impact on medication adherence in community-dwelling older adults with polypharmacy: a systematic review

Background: Polypharmacy, and the associated adverse drug events such as non-adherence to prescriptions, is a common problem for elderly people living with multiple comorbidities. Deprescribing, i.e. the gradual withdrawal from medications with supervision by a healthcare professional, is regarded as a means of reducing adverse effects of multiple medications including non-adherence. This systematic review examines the evidence of deprescribing as an effective strategy for improving medication adherence amongst older, community dwelling adults. Methods: A mixed methods review was undertaken. Eight bibliographic database and two clinical trials registers were searched between May and December 2017. Results were double screened in accordance with pre-defined inclusion/exclusion criteria related to polypharmacy, deprescribing and adherence in older, community dwelling populations. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal and an a priori data collection instrument was used. For the quantitative studies, a narrative synthesis approach was taken. The qualitative data was analysed using framework analysis. Findings were integrated using a mixed methods technique. The review was performed in accordance with the PRISMA reporting statement. Results: A total of 22 original studies were included, of which 12 were RCTs. Deprescribing with adherence as an outcome measure was identified in randomised controlled trials (RCTs), observational and cohort studies from 13 countries between 1996 and 2017. There were 17 pharmacy-led interventions; others were led by General Practitioners (GP) and nurses. Four studies demonstrated an overall reduction in medications of which all studies corresponded with improved adherence. A total of thirteen studies reported improved adherence of which 5 were RCTs. Adherence was reported as a secondary outcome in all but one study. Conclusions: There is insufficient evidence to show that deprescribing improves medication adherence. Only 13 studies (of 22) reported adherence of which only 5 were randomised controlled trials. Older people are particularly susceptible to non-adherence due to multi-morbidity associated with polypharmacy. Bio-psycho-social factors including health literacy and multi-disciplinary team interventions influence adherence. The authors recommend further study into the efficacy and outcomes of medicines management interventions. A consensus on priority outcome measurements for prescribed medications is indicated

Underuse of medication for circulatory disorders among unmarried women and men in Norway?

BACKGROUND: It is well established that unmarried people have higher mortality from circulatory diseases and higher all-cause mortality than the married, and these marital status differences seem to be increasing. However, much remains to be known about the underlying mechanisms. Our objective was to examine marital status differences in the purchase of medication for circulatory diseases, and risk factors for them, which may indicate underuse of such medication by some marital status groups. METHODS: Using data from registers covering the entire Norwegian population, we analysed marital status differences in the purchase of medicine for eight circulatory disorders by people aged 50-79 in 2004-2008. These differences were compared with those in circulatory disease mortality during 2004-2007, considered as indicating probable differences in disease burden. RESULTS: The unmarried had 1.4-2.8 times higher mortality from the four types of circulatory diseases considered. However, the never-married in particular purchased less medicine for these diseases, or precursor risk factors of these diseases, primarily because of a low chance of making a first purchase. The picture was more mixed for the divorced and widowed. Both groups purchased less of some of these medicines than the married, but, especially in the case of the widowed, relatively more of other types of medicine. In contrast to the never-married, divorced and widowed people were as least as likely as the married to make a first purchase, but adherence rates thereafter, indicated by continuing purchases, were lower. CONCLUSION: The most plausible interpretation of the findings is that compared with married people, especially the never-married more often have circulatory disorders that are undiagnosed or for which they for other reasons underuse medication. Inadequate use of these potentially very efficient medicines in such a large population group is a serious public health challenge which needs further investigation. It is possible that marital status differences in use of medicines for circulatory disorders combined with an increasing importance of these medicines have contributed to the widening marital status gap in mortality observed in several countries. This also requires further investigation

Identification of modifiable factors associated with owner-reported equine laminitis in Britain using a web-based cohort study approach

Equine laminitis is a complex disease that manifests as pain and lameness in the feet, often with debilitating consequences. There is a paucity of data that accounts for the multifactorial nature of laminitis and considers time-varying covariates that may be associated with disease development; particularly those that are modifiable and present potential interventions. A previous case-control study identified a number of novel, modifiable factors associated with laminitis which warranted further investigation and corroboration. The aim of this study was to identify factors associated with equine laminitis in horses/ponies in Great Britain (GB) using a prospective, web-based cohort study design, with particular interest in evaluating modifiable factors previously identified in the case-control study