Prevalence of Polypharmacy and Potential Drug-Drug Interactions Associated with Risk Factors in the Era of HIV Integrase Inhibitors: A Prospective Clinical Study.

People living with human immunodeficiency virus (PLWH), with the availability of modern antiretroviral drugs, have multiple comorbidities, which increase the risk of polypharmacy and potential drug-drug interactions (PDDIs). This is a particularly important issue for the aging population of PLWH. This study aims to review the prevalence and risk factors for PDDIs and polypharmacy in the era of HIV integrase inhibitors. A cross-sectional, two-center, prospective observational study was conducted on Turkish outpatients between October 2021 and April 2022. Polypharmacy was defined as the use of ≥5 non-HIV medications, excluding over-the-counter (OTC) drugs, and PDDIs were classified using the University of Liverpool HIV Drug Interaction Database (harmful/red flagged and potentially clinically relevant/amber flagged). The median age of the 502 PLWH included in the study was 42 ± 12.4 years and 86.1% were males. Most individuals (96.4%) were given integrase-based regimens (unboosted 68.7% and boosted 27.7%). In total, 30.7% of individuals were taking at least one OTC drug. The prevalence of polypharmacy was 6.8% (9.2% when OTC drugs were included). During the study period, the prevalence of PDDIs was 1.2% for red flag PDDIs and 16% for amber flag PDDIs. CD4+ T cell count >500 cells/mm3, number of comorbidities ≥3, comedication with drugs affecting blood and blood-forming organs, cardiovascular drugs, and vitamin/mineral supplements were associated with red flag or amber flag PDDIs. Drug interaction prevention is still important in HIV care. Individuals with multiple comorbidities should be closely monitored for non-HIV medications to prevent PDDIs.

Development of a Metric to Detect and Decrease Low-Value Prescribing in Older Adults.

Importance: Metrics that detect low-value care in common forms of health care data, such as administrative claims or electronic health records, primarily focus on tests and procedures but not on medications, representing a major gap in the ability to systematically measure low-value prescribing. Objective: To develop a scalable and broadly applicable metric that contains a set of quality indicators (EVOLV-Rx) for use in health care data to detect and reduce low-value prescribing among older adults and that is informed by diverse stakeholders' perspectives. Design, Setting, and Participants: This qualitative study used an online modified-Delphi method to convene an expert panel of 15 physicians and pharmacists. This panel, comprising clinicians, health system leaders, and researchers, was tasked with rating and discussing candidate low-value prescribing practices that were derived from medication safety criteria; peer-reviewed literature; and qualitative studies of patient, caregiver, and physician perspectives. The RAND ExpertLens online platform was used to conduct the activities of the panel. The panelists were engaged for 3 rounds between January 1 and March 31, 2021. Main Outcomes and Measures: Panelists used a 9-point Likert scale to rate and then discuss the scientific validity and clinical usefulness of the criteria to detect low-value prescribing practices. Candidate low-value prescribing practices were rated as follows: 1 to 3, indicating low validity or usefulness; 3.5 to 6, uncertain validity or usefulness; and 6.5 to 9, high validity or usefulness. Agreement among panelists and the degree of scientific validity and clinical usefulness were assessed using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method. Results: Of the 527 low-value prescribing recommendations identified, 27 discrete candidate low-value prescribing practices were considered for inclusion in EVOLV-Rx. After round 1, 18 candidate practices were rated by the panel as having high scientific validity and clinical usefulness (scores of ≥6.5). After round 2 panel deliberations, the criteria to detect 19 candidate practices were revised. After round 3, 18 candidate practices met the inclusion criteria, receiving final median scores of 6.5 or higher for both scientific validity and clinical usefulness. Of those practices that were not included in the final version of EVOLV-Rx, 3 received high scientific validity (scores ≥6.5) but uncertain clinical usefulness (scores <6.5) ratings, whereas 6 received uncertain scientific validity rating (scores <6.5). Conclusions and Relevance: This study culminated in the development of EVOLV-Rx and involved a panel of experts who identified the 18 most salient low-value prescribing practices in the care of older adults. Applying EVOLV-Rx may enhance the detection of low-value prescribing practices, reduce polypharmacy, and enable older adults to receive high-value care across the full spectrum of health services.

Polypharmacy occurrence and the related risk of premature death among older adults in Denmark: A nationwide register-based cohort study.

BACKGROUND: Polypharmacy, defined as the concurrent use of ≥5 medications, increases the risk of drug-drug and drug-disease interactions as well as non-adherence to drug therapy. This may have negative health consequences particularly among older adults due to age-related pharmacokinetic and pharmacodynamic changes. This study aims to uncover the occurrence of polypharmacy among older adults in Denmark and investigate how polypharmacy relates to mortality. METHOD: This nationwide register-based study included 1,338,058 adults aged 65+ years between January 2013 and December 2017 in Denmark. Polypharmacy prevalence was measured at time of inclusion while incidence and the association between polypharmacy and mortality were measured over the five-year follow-up using Cox regression. In an attempt to adjust for confounding by indication, propensity scores with overlap weighting were introduced to the regression model. RESULTS: At time of inclusion, polypharmacy prevalence was 29% and over the five years follow-up, 47% of the remaining adults transitioned into polypharmacy. Identified risk factors included multimorbidity (2+ morbidities: HR = 3.51; 95% CI = 3.48-3.53), age (95+ years: HR = 2.85; 95% CI = 2.74-2.96), socioeconomic factors (Highest income quartile: HR = 0.81; 95% CI = 0.80-0.81), region of birth region (Non-western migrants: HR = 0.77; 95% CI = 0.75-0.79), marital status (Divorced: HR = 1.10; 95% CI = 1.10-1.12) and year of inclusion (2017: HR = 1.19; 95% CI = 1.19-1.22). Further analyses showed that polypharmacy involves many different drug cocktails with medication for the cardiovascular system (95%), blood and blood-forming organs (69%), alimentary tract and metabolism (61%) and nervous system (54%) contributing the most. After adjustment for propensity scores with OW, both polypharmacy (HR = 3.48, CI95% = 3.41-3.54) and excessive polypharmacy (HR = 3.48, CI95% = 3.43-3.53) increased the risk of death substantially. CONCLUSION: A considerable proportion of older adults in Denmark were exposed to polypharmacy dependent on health status, socio-economic status, and societal factors. The associated three- to four-fold mortality risk indicate a need for further exploration of the appropriateness of polypharmacy among older adults.

GP-delivered medication review of polypharmacy, deprescribing, and patient priorities in older people with multimorbidity in Irish primary care (SPPiRE Study): A cluster randomised controlled trial.

BACKGROUND: There is a rising prevalence of multimorbidity, particularly in older patients, and a need for evidence-based medicines management interventions for this population. The Supporting Prescribing in Older Adults with Multimorbidity in Irish Primary Care (SPPiRE) trial aimed to investigate the effect of a general practitioner (GP)-delivered, individualised medication review in reducing polypharmacy and potentially inappropriate prescriptions (PIPs) in community-dwelling older patients with multimorbidity in primary care. METHODS AND FINDINGS: We conducted a cluster randomised controlled trial (RCT) set in 51 GP practices throughout the Republic of Ireland. A total of 404 patients, aged ≥65 years with complex multimorbidity, defined as being prescribed ≥15 regular medicines, were recruited from April 2017 and followed up until October 2020. Furthermore, 26 intervention GP practices received access to the SPPiRE website where they completed an educational module and used a template for an individualised patient medication review that identified PIP, opportunities for deprescribing, and patient priorities for care. A total of 25 control GP practices delivered usual care. An independent blinded pharmacist assessed primary outcome measures that were the number of medicines and the proportion of patients with any PIP (from a predefined list of 34 indicators based predominantly on the STOPP/START version 2 criteria). We performed an intention-to-treat analysis using multilevel modelling. Recruited participants had substantial disease and treatment burden at baseline with a mean of 17.37 (standard deviation [SD] 3.50) medicines. At 6-month follow-up, both intervention and control groups had reductions in the numbers of medicines with a small but significantly greater reduction in the intervention group (incidence rate ratio [IRR] 0.95, 95% confidence interval [CI]: 0.899 to 0.999, p = 0.045). There was no significant effect on the odds of having at least 1 PIP in the intervention versus control group (odds ratio [OR] 0.39, 95% CI: 0.140 to 1.064, p = 0.066). Adverse events recorded included mortality, emergency department (ED) presentations, and adverse drug withdrawal events (ADWEs), and there was no evidence of harm. Less than 2% of drug withdrawals in the intervention group led to a reported ADWE. Due to the inability to electronically extract data, primary outcomes were measured at just 2 time points, and this is the main limitation of this work. CONCLUSIONS: The SPPiRE intervention resulted in a small but significant reduction in the number of medicines but no evidence of a clear effect on PIP. This reduction in significant polypharmacy may have more of an impact at a population rather than individual patient level. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12752680.

Association of healthy lifestyle and all-cause mortality according to medication burden.

BACKGROUND: Healthy lifestyle is associated with reduced all-cause mortality, but it is not known whether this association persists for individuals with high medication burden. We examined the association between healthy lifestyle behaviors and all-cause mortality across different degrees of polypharmacy. METHODS: This was a secondary analysis of 20,417 adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study. The primary exposure was healthy lifestyle (adherence to Mediterranean diet, physical activity, smoking abstinence, sedentary behavior avoidance, and composite healthy behavior score [HBS]). The primary outcome was all-cause mortality. Strata of medication burden were based on the number of medications taken (no polypharmacy: 0-4, polypharmacy: 5-9, hyperpolypharmacy: ≥10). We used Cox proportional hazards regression models to examine the association between healthy lifestyle behaviors and mortality within each medication burden stratum and examined for interactions with age. RESULTS: The healthiest category of each lifestyle behavior, except sedentary behavior avoidance among the hyperpolypharmacy group, was associated with lower all-cause mortality (hazard ratio [HR]) regardless of medication burden: Mediterranean diet (no polypharmacy: HR 0.77, polypharmacy: HR 0.78, hyperpolypharmacy: HR 0.85), physical activity (no polypharmacy: HR 0.87, polypharmacy: HR 0.82, hyperpolypharmacy: HR 0.79), smoking abstinence (no polypharmacy: HR 0.40, polypharmacy: HR 0.45, hyperpolypharmacy: HR 0.52), and sedentary behavior avoidance (no polypharmacy: HR 0.88, polypharmacy: HR 0.86, hyperpolypharmacy: HR 0.95). Higher HBS was inversely associated with all-cause mortality within each medication burden stratum (no polypharmacy: HR 0.52, polypharmacy: HR 0.55, hyperpolypharmacy: HR 0.69). Although there was an interaction with age among those with no polypharmacy and those with polypharmacy, point estimates for HBS followed a graded pattern whereby higher HBS was incrementally associated with improved mortality across all age strata. CONCLUSION: Greater adherence to a healthy lifestyle was associated with lower all-cause mortality irrespective of medication burden and age.

Automated multi-dose dispensing in persons with and without Alzheimer's disease-impacts on pharmacotherapy.

PURPOSE: We investigated the drug use before and after transition to automated multi-dose dispensing (MDD) service among persons with Alzheimer's disease (AD) and compared whether the changes were similar in persons without AD. METHODS: The register-based Finnish nationwide MEDALZ cohort includes 70,718 community-dwelling persons diagnosed with AD during 2005-2011. Each person who initiated MDD was matched in both groups with a comparison person without MDD by age, gender and for persons with AD, also time since AD diagnosis at the start of MDD. The study cohort included 15,604 persons with AD in MDD and 15,604 no-MDD, and 5224 persons without AD in MDD and 5224 no-MDD. Point prevalence of drug use was assessed every 3 months, from 1 year before to 2 years after the start of MDD and compared between persons in MDD to those who did not have MDD. RESULTS: MDD was started on average 2.9 (SD 2.1) years after AD diagnosis. At the start of MDD, the prevalence of drug use increased especially for antipsychotics, antidepressants, opioids, paracetamol and use of ≥ 10 drugs among persons with and without AD. Prevalence of benzodiazepine use (from 12% 12 months before to 17% at start of MDD), memantine (from 29 to 46%) and ≥ 3 psychotropics (from 3.2 to 6.0%) increased among persons with AD. Decreasing trend was observed for benzodiazepine-related drugs, urinary antispasmodics and non-steroidal anti-inflammatory drugs. CONCLUSION: MDD seems to be initiated when use of psychotropics is initiated and the number of drugs increases.

Interactions in cancer treatment considering cancer therapy, concomitant medications, food, herbal medicine and other supplements.

PURPOSE: The aim of our study was to analyse the frequency and severity of different types of potential interactions in oncological outpatients' therapy. Therefore, medications, food and substances in terms of complementary and alternative medicine (CAM) like dietary supplements, herbs and other processed ingredients were considered. METHODS: We obtained data from questionnaires and from analysing the patient records of 115 cancer outpatients treated at a German university hospital. Drug-drug interactions were identified using a drug interaction checking software. Potential CAM-drug interactions and food-drug interactions were identified based on literature research. RESULTS: 92.2% of all patients were at risk of one or more interaction of any kind and 61.7% of at least one major drug-drug interaction. On average, physicians prescribed 10.4 drugs to each patient and 6.9 interactions were found, 2.5 of which were classified as major. The most prevalent types of drug-drug interactions were a combination of QT prolonging drugs (32.3%) and drugs with a potential for myelotoxicity (13.4%) or hepatotoxicity (10.1%). In 37.2% of all patients using CAM supplements the likelihood of interactions with medications was rated as likely. Food-drug interactions were likely in 28.7% of all patients. CONCLUSION: The high amount of interactions could not be found in literature so far. We recommend running interaction checks when prescribing any new drug and capturing CAM supplements in medication lists too. If not advised explicitly in another way drugs should be taken separately from meals and by using nonmineralized water to minimize the risk for food-drug interactions.

Medication-related adverse events in health care-what have we learned? A narrative overview of the current knowledge.

PURPOSE: Although medication-related adverse events (MRAEs) in health care are vastly studied, high heterogeneity in study results complicates the interpretations of the current situation. The main objective of this study was to form an up-to-date overview of the current knowledge of the prevalence, risk factors, and surveillance of MRAEs in health care. METHODS: Electronic databases (PubMed, MEDLINE, Web of Science, and Scopus) were searched with applicable search terms to collect information on medication-related adverse events. In order to obtain an up-to-date view of MRAEs, only studies published after 2000 were accepted. RESULTS: The prevalence rates of different MRAEs vary greatly between individual studies and meta-analyses. Study setting, patient population, and detection methods play an important role in determining detection rates, which should be regarded while interpreting the results. Medication-related adverse events are more common in elderly patients and patients with lowered liver or kidney function, polypharmacy, and a large number of additional comorbidities. However, the risk of MRAEs is also significantly increased by the use of high-risk medicines but also in certain care situations. Preventing MRAEs is important as it will decrease patient mortality and morbidity but also reduce costs and functional challenges related to them. CONCLUSIONS: Medication-related adverse events are highly common and have both immediate and long-term effects to patients and healthcare systems worldwide. Conclusive solutions for prevention of all medication-related harm are impossible to create. In the future, however, the development of efficient real-time detection methods can provide significant improvements for event prevention and forecasting.

Medication Burden and Prescribing Patterns in Patients on Hemodialysis in the USA, 2013-2017.

INTRODUCTION: The medication burden of patients with end-stage renal disease (ESRD) on hemodialysis, a patient population with a high comorbidity burden and complex care requirements, is among the highest of any of the chronic diseases. The goal of this study was to describe the medication burden and prescribing patterns in a contemporary cohort of patients with ESRD on hemodialysis in the USA. METHODS: We used the United States Renal Data System database from January 1, 2013, and December 31, 2017, to quantify the medication burden of patients with ESRD on hemodialysis aged ≥18 years. We calculated the average number of prescription medications per patient during each respective year (January-December), number of medications within classes, including potentially harmful medications, and trends in the number of medications and classes over the 5-year study period. RESULTS: We included a total of 163,228 to 176,133 patients from 2013 to 2017. The overall medication burden decreased slightly, from a mean of 7.4 (SD 3.8) medications in 2013 to 6.8 (SD 3.6) medications in 2017. Prescribing of potentially harmful medications decreased over time (74.0% with at least one harmful medication class in 2013-68.5% in 2017). In particular, the prescribing of non-benzodiazepine hypnotics, benzodiazepines, and opioids decreased from 2013 to 2017 (12.2%-6.3%, 23.4%-19.3%, and 60.0%-53.4%, respectively). This trend was consistent across subgroups of age, sex, race, and low-income subsidy status. CONCLUSIONS: Patients with ESRD on hemodialysis continued to have a high overall medication burden, with a slight reduction over time accompanied by a decrease in prescribing of several classes of harmful medications. Continued emphasis on assessment of appropriateness of high medication burden in patients with ESRD is needed to avoid exposure to potentially harmful or futile medications in this patient population.

Cross-sectional study on the prevalence of influenza and pneumococcal vaccination and its association with health conditions and risk factors among hospitalized multimorbid older patients.

BACKGROUND: Older adults with chronic conditions are at high risk of complications from influenza and pneumococcal infections. Evidence about factors associated with influenza and pneumococcal vaccination among older multimorbid persons in Europe is limited. The aim of this study was to investigate the prevalence and determinants of these vaccinations in this population. METHODS: Multimorbid patients aged ≥70 years with polypharmacy were enrolled in 4 European centers in Switzerland, Belgium, the Netherlands, and Ireland. Data on vaccinations, demographics, health care contacts, and comorbidities were obtained from self-report, general practitioners and medical records. The association of comorbidities or medical contacts with vaccination status was assessed using multivariable adjusted log-binomial regression models. RESULTS: Among 1956 participants with available influenza vaccination data (median age 79 years, 45% women), 1314 (67%) received an influenza vaccination within the last year. Of 1400 patients with available pneumococcal vaccination data (median age 79 years, 46% women), prevalence of pneumococcal vaccination was 21% (n = 291). The prevalence of vaccination remained low in high-risk populations with chronic respiratory disease (34%) or diabetes (24%), but increased with an increasing number of outpatient medical contacts. Chronic respiratory disease was independently associated with the receipt of both influenza and pneumococcal vaccinations (prevalence ratio [PR] 1.09, 95% confidence interval [CI] 1.03-1.16; and PR 2.03, 95%CI 1.22-3.40, respectively), as was diabetes (PR 1.06, 95%CI 1.03-1.08; PR 1.24, 95%CI 1.16-1.34, respectively). An independent association was found between number of general practitioner visits and higher prevalence of pneumococcal vaccination (p for linear trend <0.001). CONCLUSION: Uptake of influenza and particularly of pneumococcal vaccination in this population of European multimorbid older inpatients remains insufficient and is determined by comorbidities and number and type of health care contacts, especially outpatient medical visits. Hospitalization may be an opportunity to promote vaccination, particularly targeting patients with few outpatient physician contacts.

Antibacterial prescription and the associated factors among outpatients diagnosed with respiratory tract infections in Mbarara Municipality, Uganda.

BACKGROUND: Respiratory tract infections (RTI) are the second most frequent diagnosis after Malaria amongst Outpatients in Uganda. Majority are Non pneumonia cough and flu which are self-limiting and often do not require antibacterials. However, antibiotics are continuously prescribed for these conditions and are a major contributor to antimicrobial resistance and wastage of health resources. Little is known about this problem in Uganda hence the impetus for the study. OBJECTIVES: To determine the antibacterial prescribing rate and associated factors among RTI outpatients in Mbarara municipality METHODOLOGY: This was a retrospective cross-sectional study on records of RTI outpatients from 1st April 2019 to 31st March 2020 (prior to the novel corona virus disease pandemic) in four selected public health facilities within Mbarara municipality. A pretested data caption tool was used to capture prescribing patterns using WHO/INRUD prescribing indicators. We used logistic regression to determine factors associated to antibacterial prescribing. RESULTS: A total of 780 encounters were studied with adults (18-59 years) forming the largest proportion of age categories at (337, 43.15%) and more females (444, 56.85%) than men (337, 43.15%). The antibacterial prescribing rate was 77.6% (606) with Amoxicillin the most prescribed 80.4% (503). The prescribing pattern showed an average of 2.47 (sd 0.72) drugs per encounter and the percentage of encounters with injection at 1.5% (24). Drugs prescribed by generic (1557, 79%) and drugs prescribed from essential medicine list (1650, 84%) both not conforming to WHO/INRUD standard; an indicator of possible irrational prescribing. Female gender (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: (1.06-2.16); 18-59 years age group (aOR = 1.66, 95% CI: 1.09-2.33) and Individuals prescribed at least three drugs were significantly more likely to have an antibacterial prescribed (aOR= 2.72, 95% CI: 1.86-3.98). CONCLUSION: The study found a high antibacterial prescribing rate especially among patients with URTI, polypharmacy and non-conformity to both essential medicine list and generic name prescribing. This prescribing pattern does not comply with rational drug use policy and needs to be addressed through antimicrobial stewardship interventions, prescriber education on rational drug use and carrying out more research to determine the appropriateness of antibacterial prescribed.

A comparison of anticholinergic burden in older patients with and without cancer.

Aim: To compare anticholinergic burden (ACB) in older patients with and without cancer and evaluate the effects of ACB on geriatric syndromes. Methods: A total of 291 patients from the geriatric clinic and 301 patients from the oncology clinic were evaluated. ACB <2 was categorized as low ACB and ACB ≥2 was categorized as high ACB. A comprehensive geriatric assessment was performed on patients from the geriatric clinic. Results: ACB scores were significantly higher in patients without cancer compared with those with cancer (p < 0.005). Number of falls and Geriatric Depression Scale 15 scores were higher and Mini-Nutritional Assessment and Barthel/Lawton activities of daily living scores were lower in geriatric patients with high ACB scores compared with those with low ACB scores (p < 0.005). Conclusion: It is crucial to understand the potential effects of ACB for rational drug use and optimum cancer management in older patients with cancer.

Lay abstract The elderly population is increasing rapidly worldwide, and most cancer patients are over the age of 65. In this age group, preexisting medical conditions other than cancer lead to the use of multiple drugs, which is defined as polypharmacy. Additionally, the anticholinergic burden (ACB) of the drugs affects cancer treatment in the elderly. This study investigated the frequency of polypharmacy and ACB in elderly patients with and without cancer and their relationship with geriatric syndromes such as depression, falls, nutritional and cognitive impairments. We found that ACB was higher in older patients without cancer than those with cancer and is related to increased falls, depressive symptoms, and impaired nutritional and functional status in older patients. Given the prevalence of cancer among older adults, it is crucial to understand the potential effects of the ACB for rational drug use and optimum cancer management in older patients with cancer.

Antibiotic use and associated factors in adult outpatients from 2000 to 2019.

The aims of the study were to assess the changes in 19-years use of antibiotics (overall, by age, sex and geographical area) and of those classes deemed to be quality indicators for their consumption and to evaluate factors associated to antibiotic use. We analyzed drug prescription data collected in the administrative database of the Lombardy Region (Northern Italy) for outpatients aged 40+ years from 2000 to 2019. Logistic regression analyses were performed to evaluate the association between receiving at least one antibiotic prescription and year of observation, gender, age groups, area of residence, polypharmacy and hospitalizations in the index year. The prevalence of patients prescribed with antibiotics remained high from 2000 (33.8%) to 2019 (32.6%). Prevalence of use of second-line choice antibiotics (penicillin combinations with beta-lactamase inhibitors, third and fourth generation cephalosporins, macrolides) continued to increase, only fluoroquinolones decreased in 2019 (19%) comparing to 2018 (26%), at the time when the Italian Medicines Agency promulgated safety warnings. Females (OR 1.28, 95%CI 1.27-1.28), people living in Brescia (OR 1.24, 95%CI 1.24-1.25), those exposed to polypharmacy (OR 2.57, 95%CI 2.56-2.57) and those hospitalized 1 to 3 (OR 1.86, 95%CI 1.85-1.86) or more than 3 (OR 2.02, 95%CI 2.01-2.03) times a year had a statistically significant higher risk of receiving antibiotics. The high use of antibiotics over the study period further reinforces the need of impactful interventions, in order to improve the rational use of antibiotics and to reduce the risks of antimicrobial resistance. The differences outlined should be considered when monitoring and planning these interventions.

The role of senolytics in osteoporosis and other skeletal pathologies.

The skeletal system undergoes irreversible structural deterioration with aging, leading to increased fracture risk and detrimental changes in mobility, posture, and gait. This state of low bone mass and microarchitectural changes, diagnosed as osteoporosis, affects millions of individuals worldwide and has high clinical and economic burdens. Recently, pre-clinical studies have linked the onset of age-related bone loss with an accumulation of senescent cells in the bone microenvironment. These senescent cells appear to be causal to age-related bone loss, as targeted clearance of these cells leads to improved bone mass and microarchitecture in old mice. Additionally, other pathologies leading to bone loss that result from DNA damage, such as cancer treatments, have shown improvements after clearance of senescent cells. The development of new therapies that clear senescent cells, termed "senolytics", is currently underway and may allow for the modulation of bone loss that results from states of high senescent cell burden, such as aging.

Association Between Receipt of Overlapping Opioid and Benzodiazepine Prescriptions From Multiple Prescribers and Overdose Risk.

Importance: The receipt of overlapping opioid and benzodiazepine prescriptions is associated with increased overdose risk. It is unknown whether this increase in risk varies when overlapping prescriptions are written by multiple prescribers vs 1 prescriber. Objective: To evaluate the association between receipt of overlapping opioid and benzodiazepine prescriptions from multiple prescribers and overdose risk. Design, Setting, and Participants: This cohort study was conducted using 2017 to 2018 claims from the Optum deidentified Clinformatics Data Mart. Participants were patients with private insurance or Medicare Advantage aged 12 years or older with overlapping opioid and benzodiazepine prescriptions. Data were analyzed from March through November 2020. Exposures: For each patient, person-days on which opioid and benzodiazepine prescriptions overlapped were identified. The exposure was whether these prescriptions were written by multiple prescribers vs 1 prescriber. Main Outcomes and Measures: The outcome was a treated overdose, defined as the occurrence of 1 or more claims containing a diagnosis code for opioid or benzodiazepine poisoning on a person-day of opioid-benzodiazepine overlap. The association between exposure and outcome at the person-day level was estimated using logistic regression, controlling for opioid and benzodiazepine prescribing patterns, demographics, and comorbidities. The average marginal effect (AME) of the exposure, defined as the absolute difference in the probability of a treated overdose if all person-days of overlap involved prescriptions from multiple prescribers vs 1 prescriber, was calculated. Results: Among 529 053 patients, the mean (SD) age was 61.2 (15.6) years and 350 857 (66.3%) were female patients. Mean (SD) follow-up was 198.7 (249.8) days. During follow-up, overdose occurred on 1 or more person-days of opioid-benzodiazepine overlap for 2288 patients (0.4%, or 1 in 231 patients). There were 52 989 316 person-days of opioid-benzodiazepine overlap. Among 19 895 457 person-days (37.5%) involving prescriptions from multiple prescribers, there were 1390 overdoses (7.0 per 100 000 person-days), and among 33 093 859 person-days (62.5%) involving prescriptions from 1 prescriber, there were 1302 overdoses (3.9 per 100 000 person-days). Overdose risk was increased 1.8-fold (95% CI, 1.6-1.9) on person-days of overlap involving prescriptions from multiple prescribers vs 1 prescriber. The association between multiple prescribers and increased risk of overdose persisted in adjusted analyses (adjusted odds ratio, 1.20; 95% CI, 1.10-1.31; AME, 0.91 per 100 000 person-days of overlap; 95% CI, 0.46-1.37). Conclusions and Relevance: This study found that among patients already at increased risk of overdose owing to concurrent treatment with opioids and benzodiazepines, overdose risk was increased further when multiple prescribers were responsible for this treatment regimen compared with 1 prescriber. This increased risk was not fully accounted for by differences in prescribing patterns, demographics, or comorbidities. This finding suggests that other factors, such as poor care coordination, may be associated with the increase in risk.

Antipsychotic Polypharmacy Among Patients With Schizophrenia in Africa: A Systematic Review and Meta-Analysis.

OBJECTIVES: In Africa, antipsychotic polypharmacy (APP) is increasing due to a high antipsychotic dose prescribing, repeated psychiatric hospitalization, uncontrolled psychotic symptoms, and greater side effect burden. Therefore, the aim of this review and meta-analysis is to assess the prevalence and correlates of APP among patients with schizophrenia in Africa. METHODS: A systematic search was performed from August 1 to 31, 2020, on PubMed, MEDLINE, Google Scholar, and Science Direct databases to select articles based on the inclusion criteria. Meta-Analysis of Observational studies in Epidemiology guidelines were employed. Cross-sectional observational studies that reported APP and/or its correlates in schizophrenia patients in English language published in peer-reviewed journals without time limits were included in the review. The quality of included articles was assessed using Newcastle-Ottawa quality assessment tool. Prevalence and correlates of APP were the outcome measures of this review and meta-analysis. Open Meta Analyst and RevMan version 5.3 software were used for meta-analysis. A random effect model was used to synthesize data based on the heterogeneity test. RESULTS: Six studies that involved 2154 schizophrenia patients met the inclusion criteria in this review and meta-analysis. The quality of included studies ranges from 6.5 to 10 based on the Newcastle-Ottawa quality assessment tool. The pooled prevalence of APP among patients with schizophrenia was 40.6% with 95% confidence interval: 27.6% to 53.7%. Depot first-generation antipsychotics and oral first-generation antipsychotics were the most commonly prescribed APP combinations. Socio-demographic, clinical, and antipsychotic treatment characteristics were significantly associated with APP. There was a wide variation in the correlates of APP assessed by studies and the way that association/correlations was determined and reported. CONCLUSIONS: APP is common and highly prevalent. Advanced age, male gender, longer duration of schizophrenia, hospital admission, and longer antipsychotic treatment were correlates of APP in Africa.

Impact of polypharmacy on all-cause mortality and hospitalization in incident hemodialysis patients: a cohort study.

BACKGROUND: Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. METHODS: Study design: cohort study. SETTING: participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. PREDICTOR: patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. OUTCOMES: all-cause mortality and hospitalization during the mean 2.8-year follow-up. MEASUREMENTS: hazard ratios (HRs) were estimated using Cox's model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. RESULTS: The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. CONCLUSIONS: PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.

Cardiovascular Outcomes and Mortality Associated With Discontinuing Statins in Older Patients Receiving Polypharmacy.

Importance: Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain. Objective: To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy. Design, Setting, and Participants: This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and antiplatelet agents from October 1, 2013, until January 31, 2015, with follow-up through June 30, 2018. Data were collected using the health care utilization database of Lombardy region in Italy. Data analysis was conducted from March to November 2020. Exposures: Cohort members were followed up to identify those who discontinued statins. Among this group, those who maintained other therapies during the first 6 months after statin discontinuation were 1:1 propensity score matched with patients who discontinued neither statins nor other drugs. Main Outcome and Measures: The pairs of patients discontinuing and maintaining statins were followed up from the initial discontinuation until June 30, 2018, to estimate the hazard ratios (HRs) and 95% CIs for fatal and nonfatal outcomes associated with statin discontinuation. Results: The full cohort inclued 29 047 patients exposed to polypharmacy (mean [SD] age, 76.5 [6.5] years; 18 257 [62.9%] men). Of them, 5819 (20.0%) discontinued statins while maintaining other medications, and 4010 (68.9%) of them were matched with a comparator. In the discontinuing group, the mean (SD) age was 76.5 (6.4) years, 2405 (60.0%) were men, and 506 (12.6%) had Multisource Comorbidity Scores of 4 or 5. In the maintaining group, the mean (SD) age was 76.1 (6.3) years, 2474 (61.7%) were men, and 482 (12.0%) had multisource comorbidity scores of 4 or 5. Compared with the maintaining group, patients in the discontinuing group had increased risk of hospital admissions for heart failure (HR, 1.24; 95% CI, 1.07-1.43) and any cardiovascular outcome (HR, 1.14; 95% CI, 1.03-1.26), deaths from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.05-1.19). Conclusions and Relevance: In this study of patients receiving polypharmacy, discontinuing statins while maintaining other drug therapies was associated with an increase in the long-term risk of fatal and nonfatal cardiovascular outcomes.