Association Between Medications Acting on the Central Nervous System and Fall-Related Injuries in Community-Dwelling Older Adults: A New User Cohort Study.

BACKGROUND: It is well established that individual medications that affect the central nervous system (CNS) increase falls risk in older adults. However, less is known about risks associated with taking multiple CNS-active medications. METHODS: Employing a new user design, we used data from the Adult Changes in Thought study, a prospective cohort of community-dwelling people aged 65 and older without dementia. We created a time-varying composite measure of CNS-active medication exposure from electronic pharmacy fill data and categorized into mutually exclusive categories: current (within prior 30 days), recent (31-90 days), past (91-365 days), or nonuse (no exposure in prior year). We calculated standardized daily dose and identified new initiation. Cox proportional hazards models examined the associations between exposures and the outcome of fall-related injury identified from health plan electronic databases. RESULTS: Two thousand five hundred ninety-five people had 624 fall-related injuries over 15,531 person-years of follow-up. Relative to nonuse, fall-related injury risk was significantly greater for current use of CNS-active medication (hazard ratio [HR] = 1.95; 95% CI = 1.57-2.42), but not for recent or past use. Among current users, increased risk was noted with all doses. Risk was increased for new initiation compared with no current use (HR = 2.81; 95% CI = 2.09-3.78). Post hoc analyses revealed that risk was especially elevated with new initiation of opioids. CONCLUSIONS: We found that current use, especially new initiation, of CNS-active medications was associated with fall-related injury in community-dwelling older adults. Increased risk was noted with all dose categories. Risk was particularly increased with new initiation of opioids.

A Scoping Review of Medications Studied in Pediatric Polypharmacy Research.

PURPOSE: The purpose of this study is to describe medications most commonly studied in pediatric polypharmacy research by pharmacologic classes and disease using a scoping review methodology. METHODS: A search of electronic databases was conducted in July 2019 that included Ovid Medline, PubMed, Elsevier Embase, and EBSCO CINAHL. Primary observational studies were selected if they evaluated polypharmacy as an aim, outcome, predictor, or covariate in children 0-21 years of age. Studies not differentiating between adults and children or those not written in English were excluded. Study characteristics, pharmacologic categories, medication classes, and medications were extracted from the included studies. RESULTS: The search identified 8790 titles and after de-duplicating and full-text screening, 414 studies were extracted for the primary data. Regarding global pharmacologic categories, central nervous system (CNS) agents were most studied (n = 185, 44.9%). The most reported pharmacologic category was the anticonvulsants (n = 250, 60.4%), with valproic acid (n = 129), carbamazepine (n = 123), phenobarbital (n = 87), and phenytoin (n = 83) being the medications most commonly studied. In studies that reported medication classes (n = 105), serotonin reuptake inhibitors (n = 32, 30.5%), CNS stimulants (n = 30, 28.6%), and mood stabilizers (n = 27, 25.7%) were the most studied medication classes. CONCLUSION: While characterizing the literature on pediatric polypharmacy in terms of the types of medication studied, we further identified substantive gaps within this literature outside of epilepsy and psychiatric disorders. Medications frequently identified in use of polypharmacy for treatment of epilepsy and psychiatric disorders reveal opportunities for enhanced medication management in pediatric patients.

Variation of the prevalence of pediatric polypharmacy: A scoping review.

PURPOSE: To examine the range of prevalence of pediatric polypharmacy in literature through a scoping review, focusing on factors that contribute to its heterogeneity in order to improve the design and reporting of quality improvement, pharmacovigilance, and research studies. METHODS: We searched Ovid Medline, PubMed, EMBASE, CINAHL, Ovid PsycINFO, Cochrane CENTRAL, and Web of Science Core Collection databases for studies with concepts of children and polypharmacy, along with a hand search of the bibliographies of six reviews and 30 included studies. We extracted information regarding study design, disease conditions, and prevalence of polypharmacy. RESULTS: Two hundred eighty-four studies reported prevalence of polypharmacy. They were more likely to be conducted in North America (37.7%), published after 2010 (44.4%), cross-sectional (67.3%), in outpatient settings (59.5%). Prevalence ranged from 0.9% to 98.4%, median 39.7% (interquartile range [IQR] 22.0%-54.0%). Studies from Asia reported the highest median prevalence of 45.4% (IQR 27.3%-61.0%) while studies from North America reported the lowest median prevalence of 30.4% (IQR 14.7%-50.2%). Prevalence decreased over time: median 45.6% before 2001, 38.1% during 2001 to 2010, and 34% during 2011 to 2017. Studies involving children under 12 years had a higher median prevalence (46.9%) than adolescent studies (33.7%). Inpatient setting studies had a higher median prevalence (50.3%) than studies in outpatient settings (38.8%). Community level samples, higher number and duration of medications defining polypharmacy, and psychotropic medications were associated with lower prevalence. CONCLUSIONS: The prevalence of pediatric polypharmacy is high and variable. Studies reporting pediatric polypharmacy should account for context, design, polypharmacy definition, and medications evaluated.

Risk interval analysis of emergency room visits following colonoscopy in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Prior studies suggest that colonoscopy may exacerbate inflammatory bowel disease (IBD) symptoms. Thus, our study aimed to determine risk of emergency room (ER) visits associated with colonoscopy among IBD patients and evaluate potential modifiers of this risk. METHODS: The study population included IBD patients in the Multi-Payer Claims Database who were >20 years old and had a colonoscopy from 2007-2010. We used a self-controlled risk interval design and mixed-effects Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI) comparing the incidence of ER visits in the 1-4 weeks following colonoscopy (risk interval) to the incidence of ER visits in the 7-10 weeks after colonoscopy (control interval). We also conducted stratified analyses by patient characteristics, bowel preparation type, and medication. RESULTS: There were 212,205 IBD patients with at least 1 colonoscopy from 2007-2010, and 3,699 had an ER visit during the risk and/or control interval. The risk of an ER visit was higher in the 4-week risk interval following colonoscopy compared to the control interval (RR = 1.24; 95% CI: 1.17-1.32). The effect was strongest in those <41 years old (RR = 1.60; 95% CI: 1.21-2.11), in women (RR = 1.32; 95% CI: 1.21-1.44), and in those with sodium phosphate bowel preparation (RR = 2.09; 95% CI: 1.02-4.29). Patients using immunomodulators had no increased risk of ER visits (RR = 0.75; 95% CI: 0.35-1.59). CONCLUSIONS: Our results suggest that there is an increased risk of ER visits following colonoscopy among IBD patients, but that immunomodulators and mild bowel preparation agents may mitigate this risk.

Outcome measures in pediatric polypharmacy research: a scoping review.

INTRODUCTION: Various methods have been used to interpret the reports of pediatric polypharmacy across the literature. This is the first scoping review that explores outcome measures in pediatric polypharmacy research. OBJECTIVES: The aim of our study was to describe outcome measures assessed in pediatric polypharmacy research. METHODS: A search of electronic databases was conducted in July 2017, including Ovid Medline, PubMed, Elsevier Embase, Wiley Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO CINAHL, Ovid PsyclNFO, Web of Science Core Collection, ProQuest Dissertations and Thesis A&I. Data were extracted about study characteristics and outcome measures, and also synthesized by harms or benefits mentioned. RESULTS: The search strategy initially identified 8169 titles and screened 4398 using the inclusion criteria after de-duplicating. After the primary screening, a total of 363 studies were extracted for the data analysis. Polypharmacy (prevalence) was identified as an outcome in 31.4% of the studies, prognosis-related outcomes in 25.6%, and adverse drug reactions in 16.5%. A total of 265 articles (73.0%) mentioned harms, including adverse drug reactions (26.4%), side effects (24.2%), and drug-drug interactions (20.9%). A total of 83 studies (22.9%) mentioned any benefit, 48.2% of which identified combination for efficacy, 24.1% combination for treatment of complex diseases, and 19.3% combination for treatment augmentation. Thirty-eight studies reported adverse drug reaction as an outcome, where polypharmacy was a predictor, with various designs. CONCLUSIONS: Most studies of pediatric polypharmacy evaluate prevalence, prognosis, or adverse drug reaction-related out-comes, and underscore harms related to polypharmacy. Clinicians should carefully weigh benefits and harms when introducing medications to treatment regimens.

Defining pediatric polypharmacy: A scoping review.

OBJECTIVES: Lack of consensus regarding the semantics and definitions of pediatric polypharmacy challenges researchers and clinicians alike. We conducted a scoping review to describe definitions and terminology of pediatric polypharmacy. METHODS: Medline, PubMed, EMBASE, CINAHL, PsycINFO, Cochrane CENTRAL, and the Web of Science Core Collection databases were searched for English language articles with the concepts of "polypharmacy" and "children". Data were extracted about study characteristics, polypharmacy terms and definitions from qualifying studies, and were synthesized by disease conditions. RESULTS: Out of 4,398 titles, we included 363 studies: 324 (89%) provided numeric definitions, 131 (36%) specified duration of polypharmacy, and 162 (45%) explicitly defined it. Over 81% (n = 295) of the studies defined polypharmacy as two or more medications or therapeutic classes. The most common comprehensive definitions of pediatric polypharmacy included: two or more concurrent medications for ≥1 day (n = 41), two or more concurrent medications for ≥31 days (n = 15), and two or more sequential medications over one year (n = 12). Commonly used terms included polypharmacy, polytherapy, combination pharmacotherapy, average number, and concomitant medications. The term polypharmacy was more common in psychiatry literature while epilepsy literature favored the term polytherapy. CONCLUSIONS: Two or more concurrent medications, without duration, for ≥1 day, ≥31 days, or sequentially for one year were the most common definitions of pediatric polypharmacy. We recommend that pediatric polypharmacy studies specify the number of medications or therapeutic classes, if they are concurrent or sequential, and the duration of medications. We propose defining pediatric polypharmacy as "the prescription or consumption of two or more distinct medications for at least one day". The term "polypharmacy" should be included among key words and definitions in manuscripts.

A transdisciplinary team approach to scoping reviews: the case of pediatric polypharmacy.

BACKGROUND: Polypharmacy can be either beneficial or harmful to children. We conducted a scoping review to examine the concept of pediatric polypharmacy: its definition, prevalence, extent and gaps in research. In this manuscript, we report our transdisciplinary scoping review methodology. METHODS: After establishing a transdisciplinary team, we iteratively developed standard operating procedures for the study's search strategy, inclusion/exclusion criteria, screening, and data extraction. We searched eight bibliographic databases, screened abstracts and full text articles, and extracted data from included studies using standardized forms. We held regular team meetings and performed ongoing internal validity measurements to maintain consistent and quality outputs. RESULTS: With the aid of EPPI Reviewer collaborative software, our transdisciplinary team of nine members performed dual reviews of 363 included studies after dual screening of 4398 abstracts and 1082 full text articles. We achieved overall agreement of 85% and a kappa coefficient of 0.71 (95% CI 0.68-0.74) while screening full text articles. The screening and review processes required about seven hours per extracted study. The two pharmacists, an epidemiologist, a neurologist, and a librarian on the review team provided internal consultation in these key disciplines. A stakeholder group of 10 members with expertise in evidence synthesis, research implementation, pediatrics, mental health, epilepsy, pharmacoepidemiology, and pharmaceutical outcomes were periodically consulted to further characterize pediatric polypharmacy. CONCLUSIONS: A transdisciplinary approach to scoping reviews, including internal and external consultation, should be considered when addressing complex cross-disciplinary questions.

Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative.

Nitrate medications may increase bone mineral density (BMD), although information on fracture outcomes is sparse. We examined the association of nitrate medications with fractures (hip, wrist/arm, and total fractures) and changes in BMD (hip, spine, and whole body) in the Women's Health Initiative (WHI) Clinical Trials and Observational Study. A total of 139,211 postmenopausal women 50 to 79 years old without history of hip fracture were included in this prospective study. Medication use was ascertained directly from drug containers at baseline during in-person interviews in 1993 to 1998. Exposure measures included any use (use/non-use), type of nitrate (as-needed, maintenance) and duration of use (≤5 years, >5 years). We used separate multivariable Cox proportional hazard models to analyze associations between each exposure and fracture outcome, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariable linear regression models were used to examine 3-year and 6-year changes in BMD. At baseline, 1.2% (n = 1647) women were using a nitrate. During the mean ± SD follow-up of 7.7 ± 1.5 years through 2005, women experienced 1582 hip fractures, 5156 wrist or arm fractures, and 22, 589 total fractures. After adjustment for confounders, nitrate use was not statistically associated with risk for hip (HR, 0.81; 95% CI, 0.56 to 1.18), wrist/arm (HR, 0.95; 95% CI, 0.74 to 1.23), or total fractures (HR, 0.96; 95% CI, 0.85 to 1.08). As-needed nitrate use, but not maintenance therapy, was associated with a lower risk of total fractures (HR, 0.77; 95% CI, 0.62 to 0.95) and wrist/arm fractures (HR, 0.57; 95% CI, 0.34 to 0.98). Nitrate use was not associated with 3-year or 6-year changes in BMD at any site. We conclude that any nitrate use was not significantly associated with lower risk of fractures or higher BMD; however, as-needed nitrate use was associated with lower risks of total and wrist/arm fractures. © 2016 American Society for Bone and Mineral Research.

Polypharmacy in the elderly.

OBJECTIVE: The objective was to assess the frequency of polypharmacy and potential complications among local seniors. METHODS: A cross-sectional convenience sample of 59 adults aged above 65 years was interviewed at Cuyahoga county (U.S. state of Ohio) senior programs. Polypharmacy was defined as more than five prescribed medications. Primary outcomes were frequent missed doses, one or more duplicate drug/s, and equal or more than one contraindicated drug combinations. FINDINGS: Among seniors with the mean age of 76.9 years (25.4% male), 40.6% used multiple pharmacies and 35.6% had polypharmacy. Of all seniors with polypharmacy, about 57% had contraindicated drug combinations. Polypharmacy was associated with duplication (P = 0.02), but not frequent missed doses (P = 0.20). CONCLUSION: As shown by this study, polypharmacy was associated with duplicated therapy and contraindicated drug combinations. Improved communications among seniors, physicians, and pharmacists is necessary to minimize adverse consequences of polypharmacy.

Breast Cancer Stage and Treatment Among Ohio Medicaid Beneficiaries With and Without Mental Illness.

PURPOSE: There is a dearth of studies on cancer outcomes in individuals with mental illness. We compared breast cancer outcomes in Medicaid beneficiaries with and without mental illness. METHODS: Using records from the 1996 to 2005 Ohio Cancer Incidence Surveillance System (OCISS) and Medicaid files, we identified fee-for-service women age < 65 years diagnosed with incident invasive breast cancer who had enrolled in Medicaid ≥ 3 months before cancer diagnosis (n = 2,177). We retrieved cancer stage, patient demographics, and county of residence from the OCISS. From Medicaid claims data, we identified breast cancer treatment based on procedure codes and mental illness status based on diagnosis codes, prescription drugs dispensed, and service codes. We developed logistic regression models to examine the association between mental illness, cancer stage, and treatment for locoregional disease, adjusting for potential confounders. RESULTS: Women with mental illness represented 60.2% of the study population. Adjusting for potential confounders, women with mental illness were less likely than those without mental illness to have unstaged or unknown-stage cancer (adjusted odds ratio [OR], 0.61; 95% CI, 0.44 to 0.86; P = .005) or to be diagnosed with distant-stage cancer (adjusted OR, 0.59; 95% CI, 0.40 to 0.85; P = .005). We observed no difference by mental illness status in receipt of definitive treatment (adjusted OR, 1.04; 95% CI, 0.84 to 1.29; P = .08). CONCLUSION: Among Ohio Medicaid beneficiaries, women with mental illness did not experience disparities in breast cancer stage or treatment of locoregional disease. These findings may reflect the equalizing effects of Medicaid through vulnerable individuals' improved access to both physical and mental health care.

Mental illness and use of screening mammography among Medicaid beneficiaries.

BACKGROUND: Disparities in receipt of preventive services by people with mental illness have been documented previously. However, whether these disparities extend to screening mammography among individuals experiencing comparable barriers to accessing care has not been examined fully. PURPOSE: To determine whether disparities exist in receipt of screening mammography between women with and without mental illness enrolled in Medicaid, a program with documented potential to reduce healthcare disparities. METHODS: Receipt of screening mammography was examined among women aged 50-64 years enrolled in Ohio's Medicaid program during the years 2002-2008 (n=130,088). Receipt of annual screening mammography was examined among those with at least one screening mammography during the study period. Mental illness was identified through diagnostic, service, and pharmacotherapy codes (n=61,661). RESULTS: Compared to women without mental illness, more women with mental illness received at least one screening mammography during the study period (31.7% vs 38.1%, p<0.001). However, after adjusting for potential confounders, including the presence of comorbid conditions and length of enrollment in Medicaid, women with mental illness were 32% less likely to undergo at least one screening mammography (AOR=0.68, 95% CI=0.66, 0.70). Among those who received at least one screening mammography, fewer women with mental illness received screening mammography on an annual basis (5.9% vs 12.7%, p<0.001; AOR=0.53, 95% CI=0.49, 0.56). For all beneficiaries, each year of enrollment in Medicaid increased the likelihood of screening mammography use by at least 50%. CONCLUSIONS: Medicaid beneficiaries with mental illness constitute a particularly vulnerable population for suboptimal breast cancer screening.