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      The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta‐analysis

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          Abstract

          Deprescribing is a suggested intervention to reverse the potential iatrogenic harms of inappropriate polypharmacy. The review aimed to determine whether or not deprescribing is a safe, effective and feasible intervention to modify mortality and health outcomes in older adults.

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          Most cited references 146

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          Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.

          The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years. Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT). One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003). The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens. Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years. clinicaltrials.gov Identifier: NCT 00398931.
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            The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010

            Background The escalating use of prescribed drugs has increasingly raised concerns about polypharmacy. This study aims to examine changes in rates of polypharmacy and potentially serious drug-drug interactions in a stable geographical population between 1995 and 2010. Methods This is a repeated cross-sectional analysis of community-dispensed prescribing data for all 310,000 adults resident in the Tayside region of Scotland in 1995 and 2010. The number of drug classes dispensed and the number of potentially serious drug-drug interactions (DDIs) in the previous 84 days were calculated, and age-sex standardised rates in 1995 and 2010 compared. Patient characteristics associated with receipt of ≥10 drugs and with the presence of one or more DDIs were examined using multilevel logistic regression to account for clustering of patients within primary care practices. Results Between 1995 and 2010, the proportion of adults dispensed ≥5 drugs doubled to 20.8%, and the proportion dispensed ≥10 tripled to 5.8%. Receipt of ≥10 drugs was strongly associated with increasing age (20–29 years, 0.3%; ≥80 years, 24.0%; adjusted OR, 118.3; 95% CI, 99.5–140.7) but was also independently more common in people living in more deprived areas (adjusted OR most vs. least deprived quintile, 2.36; 95% CI, 2.22–2.51), and in people resident in a care home (adjusted OR, 2.88; 95% CI, 2.65–3.13). The proportion with potentially serious drug-drug interactions more than doubled to 13% of adults in 2010, and the number of drugs dispensed was the characteristic most strongly associated with this (10.9% if dispensed 2–4 drugs vs. 80.8% if dispensed ≥15 drugs; adjusted OR, 26.8; 95% CI 24.5–29.3). Conclusions Drug regimens are increasingly complex and potentially harmful, and people with polypharmacy need regular review and prescribing optimisation. Research is needed to better understand the impact of multiple interacting drugs as used in real-world practice and to evaluate the effect of medicine optimisation interventions on quality of life and mortality. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0322-7) contains supplementary material, which is available to authorized users.
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              Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis

              Objective To synthesise qualitative studies that explore prescribers’ perceived barriers and enablers to minimising potentially inappropriate medications (PIMs) chronically prescribed in adults. Design A qualitative systematic review was undertaken by searching PubMed, EMBASE, Scopus, PsycINFO, CINAHL and INFORMIT from inception to March 2014, combined with an extensive manual search of reference lists and related citations. A quality checklist was used to assess the transparency of the reporting of included studies and the potential for bias. Thematic synthesis identified common subthemes and descriptive themes across studies from which an analytical construct was developed. Study characteristics were examined to explain differences in findings. Setting All healthcare settings. Participants Medical and non-medical prescribers of medicines to adults. Outcomes Prescribers’ perspectives on factors which shape their behaviour towards continuing or discontinuing PIMs in adults. Results 21 studies were included; most explored primary care physicians’ perspectives on managing older, community-based adults. Barriers and enablers to minimising PIMs emerged within four analytical themes: problem awareness; inertia secondary to lower perceived value proposition for ceasing versus continuing PIMs; self-efficacy in regard to personal ability to alter prescribing; and feasibility of altering prescribing in routine care environments given external constraints. The first three themes are intrinsic to the prescriber (eg, beliefs, attitudes, knowledge, skills, behaviour) and the fourth is extrinsic (eg, patient, work setting, health system and cultural factors). The PIMs examined and practice setting influenced the themes reported. Conclusions A multitude of highly interdependent factors shape prescribers’ behaviour towards continuing or discontinuing PIMs. A full understanding of prescriber barriers and enablers to changing prescribing behaviour is critical to the development of targeted interventions aimed at deprescribing PIMs and reducing the risk of iatrogenic harm.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                British Journal of Clinical Pharmacology
                Br J Clin Pharmacol
                Wiley
                0306-5251
                1365-2125
                June 17 2016
                September 2016
                June 13 2016
                September 2016
                : 82
                : 3
                : 583-623
                Affiliations
                [1 ]School of Medicine and PharmacologyUniversity of Western Australia 35 Stirling Highway Crawley 6009 Western Australia Australia
                [2 ]Graylands Hospital Mt Claremont Western Australia Australia
                [3 ]Royal Perth Hospital Perth Western Australia Australia
                Article
                10.1111/bcp.12975
                5338123
                27077231
                © 2016

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