Medication Use Quality and Safety in Older Adults: 2019 Update.

Improving the quality of medication use and medication safety are important priorities for prescribers who care for older adults. The objective of this article was to identify four exemplary articles with this focus in 2019. We selected high-quality studies that moved the field of research forward and were not merely replication studies. The chosen articles cover domains related to aspects of suboptimal prescribing and medication safety. The first study used a nationally representative sample of Medicare beneficiaries to examine the continuation of medications with limited benefit in patients admitted for cancer and non-cancer diagnoses in hospice (domain: potentially inappropriate medications). The second study, a retrospective cohort study of older adults in Ontario, Canada, assessed the association between prescribing oral anticoagulants in an emergency department relative to not prescribing anticoagulants in the emergency department and their persistence at 6 months (domain: underuse of medications). The third study, a cluster randomized trial in Quebec, Canada, evaluated the effect of conducting electronic medication reconciliation on several outcomes including adverse drug events and medication discrepancies (domain: medication safety). Lastly, the fourth study, a retrospective study using national inpatient and outpatient Veteran Health Administration combined with clinical and Medicare Claims data, examined the effects of intensification of antihypertensive medications on older adults' likelihood for hospital re-admission and other important clinical outcomes (domain: medication safety). Collectively, this review succinctly highlights pertinent topics related to promoting safe use of medications and promotes awareness of optimizing older adults' medication regimens.

The British Pharmacological Society's WDM Paton Memorial Lecture 2019: How doctors were informed about pharmaceutical products through advertising in the British Medical Journal from 1955/6 to 1985/6.

We have reviewed pharmaceutical advertisements in every available issue of the British Medical Journal (BMJ) in 12-month periods during 1955/6, 1965/6, 1975/6, and 1985/6. We have determined the amount of advertising, the therapeutic areas covered, and whether adverts reflected the large number of New Chemical Entities (NCEs) launched during that time. For each product we recorded the therapeutic indications, the marketing company, and the number of adverts appearing. The total number of products advertised fell from 340 in 1955/6 to 260 in 1965/6, 70 in 1975/6, and 16 in 1985/6. Advertisement numbers and companies advertising also fell. Antimicrobial drugs and cardiovascular drugs were the top products advertised over the 30 years, with respiratory, analgesic, and gastrointestinal drugs also in the top five. The number of different drugs advertised by individual companies fell from around eight per company in 1955/6 to one or two in 1985/6. There was good concordance between the most advertised therapeutic areas and NCEs entering the market. From the 1950s to the 1980s prescribers were extensively informed about pharmacological advances in therapeutics through BMJ advertisements. Many novel drugs that were advertised proved to be of lasting value. The Medicines Act 1968 introduced product licensing, regulations requiring demonstration of quality, efficacy, and safety, and restrictions on advertising. Subsequently many companies reduced their advertising or stopped altogether. Since advertising influences prescribing, and since antimicrobial drugs were the most commonly advertised products during 1955-86, we speculate that advertising, resulting in excess use, may have, at least partly, driven bacterial drug resistance.

Prevalence of potentially serious drug-drug interactions among South African elderly private health sector patients using the Mimica Matanovic/Vlahovic-Palcevski protocol.

OBJECTIVES: To determine the prevalence of potentially serious drug-drug interactions (DDIs) and their relationship with gender and age, among elderly in South Africa. METHODS: A cross-sectional study was conducted using pharmaceutical claims data for 2013, for a total of 103 420 medical scheme beneficiaries' ≥65 years. All medications dispensed within one calendar month where the days' supply of medication dispensed overlapped, were grouped as one prescription. DDIs per prescription were then identified using the Mimica Matanovic/Vlahovic-Palcevski DDI protocol. Results were interpreted using effect sizes, that is Cramér's V, Cohen's d and Cohen's ƒ2 . KEY FINDINGS: A total of 331 659 DDIs were identified on 235 870 (25.8%, N = 912 713) prescriptions (mean 0.36 (SD 0.7) (95% CI, 0.36 to 0.37)). Women encountered 63.5% of all DDIs. Effect sizes for the association between DDIs and age group (Cramér's V = 0.06), and gender (Cramér's V = 0.05) was negligible. There was no difference between men and women regarding the mean number of DDIs identified per prescription (Cohen's d = 0.10). The number of medicine per prescription (ƒ2 = 0.51) was the biggest predictor of the DDIs. The most frequent interacting drug combinations were between central nervous system medicines (30.6%). CONCLUSION: Our study is the first to report the prevalence of potentially serious DDIs among an elderly population in the South African private health sector utilising the Mimica Matanovic/Vlahovic-Palcevski DDI protocol. Overall, we identified DDIs in approximately 26% of the prescriptions in our study. Age and gender were not found to be predictors of potentially serious DDIs.

Brand Medications and Medicare Part D: How Eye Care Providers' Prescribing Patterns Influence Costs.

PURPOSE: To quantify costs of eye care providers' Medicare Part D prescribing patterns for ophthalmic medications and to estimate the potential savings of generic or therapeutic drug substitutions and price negotiation. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Eye care providers prescribing medications through Medicare Part D in 2013. METHODS: Medicare Part D 2013 prescriber public use file and summary file were used to calculate medication costs by physician specialty and drug. Savings from generic or therapeutic drug substitutions were estimated for brand drugs. The potential savings from price negotiation was estimated using drug prices negotiated by the United States Veterans Administration (USVA). MAIN OUTCOME MEASURES: Total cost of brand and generic medications prescribed by eye care providers. RESULTS: Eye care providers accounted for $2.4 billion in total Medicare part D prescription drug costs and generated the highest percentage of brand name medication claims compared with all other providers. Brand medications accounted for a significantly higher proportion of monthly supplies by volume, and therefore, also by total cost for eye care providers compared with all other providers (38% vs. 23% by volume, P < 0.001; 79% vs. 56% by total cost, P < 0.001). The total cost attributable to eye care providers is driven by glaucoma medications, accounting for $1.2 billion (54% of total cost; 72% of total volume). The second costliest category, dry eye medications, was attributable mostly to a single medication, cyclosporine ophthalmic emulsion (Restasis, Allergan, Irvine, CA), which has no generic alternative, accounting for $371 million (17% of total cost; 4% of total volume). If generic medications were substituted for brand medications when available, $148 million would be saved (7% savings); if generic and therapeutic substitutions were made, $882 million would be saved (42% savings). If Medicare negotiated the prices for ophthalmic medications at USVA rates, $1.09 billion would be saved (53% savings). CONCLUSIONS: Eye care providers prescribe more brand medications by volume than any other provider group. Efforts to reduce prescription expenditures by eye care providers should focus on increasing the use of generic medications, primarily through therapeutic substitutions. Policy changes enabling Medicare to negotiate prescription drug prices could decrease costs to Medicare.

Association Between Opioid Prescribing Patterns and Abuse in Ophthalmology.

Importance: Drug overdoses have become the number 1 cause of mortality in American adults 50 years and younger. Prescription opioid abuse is a growing concern that has garnered widespread attention among policymakers and the general public. Objective: To determine the opioid prescribing patterns among ophthalmologists and elucidate their role in the prescription opioid abuse epidemic. Design, Setting, and Participants: In this observational cohort study, beneficiaries and their physicians were analyzed using 2013 to 2015 Medicare Part D Prescriber Data. The Centers for Medicare and Medicaid Services Medicare Part D Prescriber Public Use Files for 2013, 2014, and 2015 were accessed. Analysis began in June 2017. Data were collected and analyzed regarding the prescribing patterns for opioid drugs (eg, number of prescriptions written including refills, number of days' supply, and prescriber rates) for all participating ophthalmologists. Main Outcomes and Measures: The mean number of opioid prescriptions written annually by ophthalmologists; prescriber rates compared with all prescriptions written; and geographic distribution of opioid prescriptions written per ophthalmologist. Results: In 2013, 4167 of 19 615 ophthalmologists were women (21.2%). Consistently, most ophthalmologists (88%-89%) wrote 10 opioid prescriptions or fewer annually. Approximately 1% (0.94%-1.03%) of ophthalmologists wrote more than 100 prescriptions per year. On average, ophthalmologists wrote 7 opioid prescriptions per year (134 290 written annually by 19 638 physicians, on average) with a mean supply of 5 days. The 6 states with the highest volume of opioid prescriptions written annually per ophthalmologist were located in the southern United States. Conclusions and Relevance: In general, ophthalmologists show discretion in their opioid prescribing patterns. The present opioid abuse epidemic should prompt physicians to consider revisiting their prescribing protocols given the high risk for dependency.

Review of outcomes associated with restricted access to atypical antipsychotics.

OBJECTIVES: Cost containment policies, such as prior authorization (PA), have increasingly been used by formulary decision makers to manage drug spending of the atypical antipsychotic (AAP) drug class. However, these drug cost containment policies may result in cost shifting rather than cost savings. Given the interest in coordination of care, the objective of this study was to evaluate the impact of restricted access to AAPs on healthcare costs and health outcomes in individuals with schizophrenia or bipolar disorder. STUDY DESIGN: Narrative literature review. METHODS: A literature search was conducted using MEDLINE (via PubMed) for studies published between January 1993 and December 2013. RESULTS: A total of 15 published studies were identified that evaluated restricted access to AAPs in regard to healthcare costs or health outcomes: 11 studies assessed PAs, 2 studies assessed carve-outs, 1 study assessed a payment limit (cap), and 1 study assessed Medicare Part D cost sharing. Among 8 studies evaluating changes in pharmacy costs and clinical outcomes, 5 studies reported that formulary restrictions were associated with pharmacy cost savings and increases in healthcare utilization or treatment discontinuation. Of the 4 studies that measured overall cost changes, 3 studies reported increases in overall cost burden and 1 study showed modest cost savings associated with formulary restrictions. CONCLUSIONS: Study findings revealed there exists a gap in the literature as to whether restricted access to AAPs results in overall cost savings or, rather, shifts the cost burden from pharmacy spending to other parts of the healthcare system, such as service utilization.

Swiss University Students' Attitudes toward Pharmacological Cognitive Enhancement.

Pharmacological cognitive enhancement (PCE) refers to the nonmedical use of prescription or recreational drugs to enhance cognitive performance. Several concerns about PCE have been raised in the public. The aim of the present study was to investigate students' attitudes toward PCE. Students at three Swiss universities were invited by e-mail to participate in a web-based survey. Of the 29,282 students who were contacted, 3,056 participated. Of these students, 22% indicated that they had used prescription drugs (12%) or recreational substances including alcohol (14%) at least once for PCE. The use of prescription drugs or recreational substances including alcohol prior to the last exam was reported by 16%. Users of pharmacological cognitive enhancers were more likely to consider PCE fair (24%) compared with nonusers (11%). Only a minority of the participants agreed with the nonmedical use of prescription drugs by fellow students when assuming weak (7%) or hypothetically strong efficacy and availability to everyone (14%). Two-thirds (68%) considered performance that is obtained with PCE less worthy of recognition. Additionally, 80% disagreed that PCE is acceptable in a competitive environment. More than half (64%) agreed that PCE in academia is similar to doping in sports. Nearly half (48%) claimed that unregulated access to pharmacological cognitive enhancers increases the pressure to engage in PCE and educational inequality (55%). In conclusion, Swiss students' main concerns regarding PCE were related to coercion and fairness. As expected, these concerns were more prevalent among nonusers than among users of pharmacological cognitive enhancers. More balanced information on PCE should be shared with students, and future monitoring of PCE is recommended.

Contribution of metabolites to P450 inhibition-based drug-drug interactions: scholarship from the drug metabolism leadership group of the innovation and quality consortium metabolite group.

Recent European Medicines Agency (final) and US Food and Drug Administration (draft) drug interaction guidances proposed that human circulating metabolites should be investigated in vitro for their drug-drug interaction (DDI) potential if present at ≥ 25% of the parent area under the time-concentration curve (AUC) (US Food and Drug Administration) or ≥ 25% of the parent and ≥ 10% of the total drug-related AUC (European Medicines Agency). To examine the application of these regulatory recommendations, a group of scientists, representing 18 pharmaceutical companies of the Drug Metabolism Leadership Group of the Innovation and Quality Consortium, conducted a scholarship to assess the risk of contributions by metabolites to cytochrome P450 (P450) inhibition-based DDIs. The group assessed the risk of having a metabolite as the sole contributor to DDI based on literature data and analysis of the 137 most frequently prescribed drugs, defined structural alerts associated with P450 inhibition/inactivation by metabolites, and analyzed current approaches to trigger in vitro DDI studies for metabolites. The group concluded that the risk of P450 inhibition caused by a metabolite alone is low. Only metabolites from 5 of 137 drugs were likely the sole contributor to the in vivo P450 inhibition-based DDIs. Two recommendations were provided when assessing the need to conduct in vitro P450 inhibition studies for metabolites: 1) consider structural alerts that suggest P450 inhibition potential, and 2) use multiple approaches (e.g., a metabolite cut-off value of 100% of the parent AUC and the R(met) strategy) to predict P450 inhibition-based DDIs caused by metabolites in the clinic.

Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists.

PURPOSE: We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study. METHODS: We used a self-controlled case series to estimate the incidence rate ratio (IRR) comparing the rate of INR measurements of ≥4.0 in concomitant tramadol and VKA-exposed periods to VKA-only-exposed periods. Secondary analyses considered specific subgroups, alternative exposure criteria, alternative outcome definitions, and other drugs. RESULTS: We identified 513 VKA users with at least 1 INR measurement ≥4.0 and concomitant tramadol and VKA exposure during the observation period. The overall IRR was 1.80 (95% confidence interval [CI], 1.53-2.10), with a stronger association among users of phenprocoumon compared to warfarin (IRR, 3.37; 95%CI, 2.50-4.53 and IRR, 1.46; 95%CI, 1.20-1.76, respectively). We observed larger IRRs with stricter outcome definitions. Concomitant tramadol and VKA exposure was also associated with an increased rate of low INR measurements (i.e., <1.5; IRR, 1.70; 95%CI, 1.37-2.13). Morphine and, to some extent, oxycodone, penicillin, beta-blockers, and inhaled beta-agonists were associated with high INR. CONCLUSIONS: The approach successfully identified an interaction between tramadol and VKA. However, associations observed for other drugs with no known VKA interaction suggest that the current approach may have too low specificity to be useful as a screening tool, at least for drugs for which time-varying confounding may be present.

Windmills and pill mills: can PDMPs tilt the prescription drug epidemic?

Prescription drug monitoring programs (PDMPs) are state-based registries of prescriptions for specific controlled substances. This overview will describe the history and funding of these databases, address those characteristics thought to be of greatest utility for PDMPs and review current literature regarding PDMP effectiveness and their potential limitations. Although more extensive research on PDMP outcomes is needed, these databases are an essential component in ongoing efforts to establish safe and compassionate prescription opioid stewardship.