Overall survival associated with CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer in the United States: A SEER-Medicare population-based study.

BACKGROUND: Evidence on overall survival (OS) with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors is generally limited to data from clinical trials or a few observational studies with limited generalizability to Medicare population. The aim of this study was to determine OS benefits associated with CDK4/6 inhibitors in older Medicare patients with hormone receptor (HR)-positive and human epidermal growth factor receptor-2 overexpressing (HER2-) metastatic breast cancer (MBC). METHODS: In a retrospective cohort design, female patients aged ≥65 years with diagnosis of HR+/HER2- MBC from 2015 to 2017 who initiated first-line systemic therapy within 12 months of MBC diagnosis were selected from the Survey Epidemiology and End Results-Medicare database. The effect of treatment type (endocrine therapy [ET]+CDK4/6 inhibitor vs. ET alone) on OS was analyzed using Kaplan-Meier methods and multivariable Cox regression models. Adjusted hazard ratio (aHR) and 95% CIs were estimated. RESULTS: A total of 630 eligible patients were identified (169 patients treated with ET+CDK4/6 inhibitor and 461 patients treated with ET alone). In the Kaplan-Meier analysis, OS rate at 3 years after first-line treatment initiation was 73.0% for ET+CDK4/6 inhibitor versus 49.1% for ET alone (log-rank p < .0001). In Cox regression analysis, first-line ET+CDK4/6 inhibitor therapy was associated with 41% lower rate of mortality versus ET alone (aHR, 0.590; 95% CI, 0.423-0.823). CONCLUSIONS: The findings of this real-world study demonstrate significant OS benefit associated with ET+CDK4/6 inhibitor therapy over ET alone in an older Medicare population of patients with HR+/HER2- MBC, largely consistent with the evidence from clinical trials.

Impact of CDK4/6 inhibitors on chemotherapy utilization in earlier therapy lines for HR+/HER2- metastatic breast cancer in the United States.

PURPOSE: Delaying chemotherapy remains a vital goal in therapeutic management of HR+/HER2- metastatic breast cancer (MBC). However, recent reports continue to highlight substantially high chemotherapy utilization in earlier therapy lines. In this study, we explored the impact of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy class, introduced in 2015, on early chemotherapy utilization in an older population of patients with HR+/HER2- MBC in the United States (US). METHODS: Using an interrupted time series design, patients with a confirmed diagnosis of MBC aged ≥ 65 years initiating systemic therapy during 2010-2019 were selected from the SEER-Medicare database. The proportion of chemotherapy use was summarized quarterly based on the date of treatment initiation separately in the first, second, and third lines. Segmented regression models adjusted for autocorrelation over time were fitted to estimate trends before and after the availability of CDK4/6 inhibitors in the first quarter of 2015. RESULTS: Of the 3244 eligible women (median age at diagnosis: 74 years), all initiated first-line therapy; 47.9% (n = 1581) initiated second-line therapy, and 50.1% (n = 792) initiated third-line therapy. Overall utilization of chemotherapy (alone or in combination) during the study period was 15.7% for the first line, 19.6% for the second line, and 24.8% for the third line. Chemotherapy utilization in the period immediately after introduction of CDK4/6 inhibitor therapy decline by estimated 2.5% in the first line (P = 0.408), 15.5% in the second line (P = 0.005), and 16.3% in the third line (P = 0.003). CONCLUSIONS: This population-based study illustrates that chemotherapy utilization in earlier therapy lines for HR+/HER2- MBC declined steadily between 2010 and 2019. These declines were significantly accelerated by the introduction of CDK4/6 therapy class in 2015, notably in the second- and third-line settings.

Dose-dependent relation between metformin and the risk of hormone receptor-positive, her2-negative breast cancer among postmenopausal women with type-2 diabetes.

PURPOSE: Metformin has demonstrated a chemoprotective effect in breast cancer but there is limited evidence on the effect of cumulative exposure to metformin and the risk of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR + /HER2-) breast cancer. This study assessed this risk with dose and intensity of metformin in postmenopausal women with type-2 diabetes mellitus (T2DM). METHODS: This nested case-control study used the Surveillance, Epidemiology, and End Results-Medicare data (2008-2015). Cohort entry was the date of incident T2DM diagnosis. Cases were those diagnosed with HR + /HER2- breast cancer (event date) as their first/only cancer. Non-cancer T2DM controls were matched using variable-ratio-matching. Cumulative dose and average intensity of metformin were measured during the 1-year lookback period. Dose(mg) was categorized as: (1)0, (2)0-30,000, (3)30,001-136,000, (4)136,001-293,000, and (5) > 293,000, and intensity(mg/day) as: 0, 1-500, and > 500. Covariates were conceptualized using the Andersen Behavioral Model. Conditional logistic regression was used to assess the risk of HR + /HER2- breast cancer with metformin-use. RESULTS: There were 690 cases and 2747 controls. The median duration of T2DM was 1178 days in controls and 1180 days in cases. Higher cumulative dose categories: 4 (adjusted odds ratio(aOR) = 0.72, 95% CI 0.55-0.95,p = 0.02), and 5 (OR = 0.60, 95% CI 0.42-0.85,p < 0.01) had significantly lower odds of HR + /HER2- breast cancer compared to category 0. The highest intensity category of metformin had 39% lower odds of HR + /HER2- breast cancer (OR = 0.61, 95% CI 0.46-0.82,p < 0.01) compared to the 0 mg/day group. CONCLUSIONS: Higher metformin exposure was associated with reduced risk of HR + /HER2- breast cancer, adding to the evidence supporting metformin's chemoprotective effect.

Adherence to concomitant diabetes, hypertension, and hyperlipidemia treatments among older patients.

BACKGROUND: Diabetes, hypertension, and hyperlipidemia have been identified as common modifiable risk factors of cardiovascular disease, frequently occurring together, especially among older people. Medication adherence to concomitant triple therapy is of vital importance among this population. OBJECTIVES: The objective of the current study was to examine adherence to concurrent oral antidiabetics, renin-angiotensin system antagonists, and statins (triple therapy) among older patients and further evaluate the predictors associated with adherence to concurrent triple therapy among older patients. METHODS: Patients on concurrent triple therapy were identified using a Texas Medicare Advantage dataset. Patients had to have an overlap of 30 days of triple therapy and a second prescription of each component of triple therapy within the identification period. Medication adherence was measured using Proportion of Days Covered during the 1-year follow-up period to determine different adherence groups. A multinomial logistic regression was further conducted to determine various demographic and clinical factors associated with each adherence group. RESULTS: The final patient cohort comprised 7847 patients. Of these, 68.05% were adherent to triple therapy, 21.43% were adherent to double therapy, and 10.51% were adherent to monotherapy or none. Compared with the triple therapy adherent group, females had a higher likelihood of being in the triple therapy nonadherent groups, while a refill of 90 days or more and prevalent use of triple therapy was associated with a lower likelihood of being in the triple therapy nonadherent groups. Finally, predictors associated with the adherent to monotherapy or none group included older age and a higher number of total other medications. CONCLUSION: Adherence to triple therapy among older patients was 68.05%, and several demographic and clinical factors were associated with the different adherence groups.

Comparative risk of adverse outcomes associated with nonselective and selective antimuscarinic medications in older adults with dementia and overactive bladder.

OBJECTIVE: The differential muscarinic receptor selectivity could cause selective antimuscarinics to offer advantages over nonselective agents with respect to adverse effects. The objective was to examine the comparative risk of falls/fractures and all-cause hospitalizations among older adults with dementia and overactive bladder (OAB) using nonselective and selective antimuscarinics METHODS/DESIGN: A retrospective cohort study design was conducted among older patients with dementia and OAB using incident antimuscarinics. The primary exposure was classified as nonselective (oxybutynin, tolterodine, trospium, and fesoterodine) and selective (solifenacin and darifenacin). Cox proportional-hazards regression using inverse probability of treatment weighting (IPTW) evaluated the risk of falls/fractures and all-cause hospitalizations within 6 months of nonselective and selective antimuscarinic use. RESULTS: The study cohort consisted of 13,896 (76.9%) nonselective and 4,179 (23.1%) selective antimuscarinic incident users. The unadjusted falls/fractures rate was 27.14% (3,772) for nonselective and 24.55% (1,026) for selective users (p-value< 0.01). The unadjusted all-cause hospitalizations rate was 24.14% (3,354) for nonselective and 21.58% (902) for selective users (p-value <0.01). The IPTW models did not find a significant difference in the risk of falls/fractures (Hazard Ratio [HR] 1.03; 95% Confidence Interval [CI] 0.99-1.07) and risk of all-cause hospitalizations (HR 1.04; 95% CI 0.99-1.08) between nonselective and selective antimuscarinics. Several sensitivity analyses corroborated the main findings. CONCLUSIONS: The study did not find a differential risk of falls/fractures and all-cause hospitalizations in older adults with dementia and OAB using nonselective and selective antimuscarinics. More research is needed to understand the role of pharmacodynamics and pharmacokinetics in the safety profile of antimuscarinics in dementia.

Patient-reported barriers to statin adherence: Excerpts from a motivational interviewing intervention in older adults.

OBJECTIVE: Despite a known benefit in the reduction of cardiovascular risk, adherence to statins remains suboptimal. A qualitative analysis was conducted within an intervention that identified trajectories of statin adherence in patients and used motivational interviewing (MoI) to improve adherence. The objective of this qualitative study was to evaluate transcripts of an MoI telephonic intervention to identify potential, past, and current barriers to statin adherence and barriers specific to distinct adherence trajectories. METHODS: The MoI intervention was customized by past 1-year adherence trajectories (rapid discontinuation, gradual decline, and gaps in adherence). Two authors independently extracted and documented barriers from phone transcripts. Themes were derived from literature a priori and by cataloging recurring themes from the transcripts. RESULTS: The transcripts of calls made to 157 patients were reviewed of which 25.2% did not communicate a specific adherence barrier despite falling into a low-adherence trajectory when examining refill data. The most commonly reported barriers to statin adherence included adverse effects (40.1%), forgetfulness (30.0%), and lack of skills or knowledge pertaining to statins (25%). More patients in the rapid discontinuation group perceived medication as unnecessary, whereas more patients in the gaps in adherence group reported a communication barrier with their health care provider. Several barriers among patients who fell into low-adherence trajectories were reported. Some patients did not report any barriers, which may have indicated denial. MoI phone calls were useful in providing knowledge, clarifying medication regimens, and reinforcing the need to take statins. CONCLUSION: This study identified patient-reported barriers to statin adherence elicited during an MoI telephonic intervention conducted by student pharmacists. There were differences in barriers reported by patients from each trajectory, which emphasize the need for additional tailored interventions to improve patient adherence.

Risk of Mortality Associated with Non-selective Antimuscarinic medications in Older Adults with Dementia: a Retrospective Study.

BACKGROUND: Selective antimuscarinics may offer a favorable safety profile over non-selective antimuscarinics for the management of overactive bladder (OAB) in patients with dementia. OBJECTIVE: To test the hypothesis that non-selective antimuscarinics are associated with increased risk of mortality compared to selective antimuscarinics in older adults with dementia and OAB. DESIGN: Propensity score-matched retrospective new-user cohort design among Medicare beneficiaries in community settings. PATIENTS: Older adults with dementia and OAB with incident antimuscarinic use. MAIN MEASURES: The primary exposure was antimuscarinic medications classified as non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) agents. All-cause mortality within 180 days of incident antimuscarinic use formed the outcome measure. New users of non-selective and selective antimuscarinics were matched on propensity scores using the Greedy 5 → 1 matching technique. Cox proportional-hazards model stratified on matched pairs was used to evaluate the risk of mortality associated with the use of non-selective versus selective antimuscarinics in the sample. KEY RESULTS: The study identified 16,955 (77.6%) non-selective antimuscarinic users and 4893 (22.4%) selective antimuscarinic users. Propensity score matching yielded 4862 patients in each group. The unadjusted mortality rate at 180 days was 2.6% (126) for non-selective and 1.6% (78) for selective antimuscarinic users in the matched cohort (p value < 0.01). The Cox model stratified on matched pairs found 50% higher risk of 180-day mortality with non-selective antimuscarinics as compared to selective ones (hazard ratio (HR) 1.50; 95% confidence interval (CI) 1.04-2.16). The study findings remained consistent across multiple sensitivity analyses. CONCLUSIONS: Use of non-selective antimuscarinics was associated with a 50% increase in mortality risk among older adults with dementia and OAB. Given the safety concerns regarding non-selective antimuscarinic agents, there is a significant need to optimize their use in the management of OAB for older patients with dementia.

Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson's Disease.

OBJECTIVES: This study examined the risk of all-cause-mortality in patients with Parkinson's Disease (PD) and comorbid depression using inappropriate atypical antipsychotics (AAPs), based on the 2015 American Geriatrics Society Beers criteria. METHODS: A retrospective analysis of 2007-2010 Minimum Data Set linked Medicare data was conducted using a propensity-matched approach. The cohort included PD patients aged 65 years or older without schizophrenia or bipolar disorder who started AAPs. All patients had a diagnosis of comorbid depression. Risk of 6-month all-cause-mortality was compared across appropriate AAPs (aripiprazole, clozapine, or quetiapine) and inappropriate AAPs (olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone) using robust Cox regression models involving the matched cohort. RESULTS: All-cause mortality rate was 15.65% in appropriate AAP group (n = 6,038) and 16.91% in inappropriate AAP group (n = 6,038) over 6-month follow-up in the matched cohort. The robust Cox proportional hazards models revealed increased risk of all-cause mortality (hazard ratio [HR] 1.13 [95% confidence interval {CI}: 1.01-1.28)] for patients who used inappropriate compared to appropriate AAPs. Risk of death was also higher for risperidone compared to quetiapine (HR: 1.20 [95% CI: 1.03-1.40]) in sensitivity analysis. However, there was a significant relationship between pneumonia and death in all analyses. The impact of inappropriate AAP use on mortality was not significant when pneumonia was modeled as a mediator. CONCLUSIONS: Inappropriate AAP use is associated with a higher risk of all-cause-mortality in older patients with PD which is mainly mediated by pneumonia. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.

Impact of Chlorhexidine Bathing on Antimicrobial Utilization in Surgical Intensive Care Unit.

BACKGROUND: This secondary analysis compared antimicrobial utilization among surgical intensive care unit patients randomized to every other day chlorhexidine bathing (chlorhexidine) versus daily soap and water bathing (soap-and-water) using data from the CHlorhexidine Gluconate BATHing trial. MATERIALS AND METHODS: Antimicrobial utilization was quantified using defined daily dose (DDD)/100 patient-days and agent-days/100 patient-days for systemic antimicrobials. Antivirals (except oseltamivir), antiparasitics, and prophylaxis agents were excluded. The 2018 anatomic therapeutic chemical/DDD index was used to calculate DDD. Agent-days were calculated as the sum of calendar days where antimicrobials were administered. Patient-days were defined as time patients were at risk for health care-acquired infections plus up to 14 d. Primary analyses were conducted using linear regression adjusted for baseline Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Of 325 CHlorhexidine Gluconate BATHing trial patients, 312 (157 in soap-and-water and 155 in chlorhexidine) were included. The median (interquartile range) of total antimicrobial DDD/100 patient-days was 135.4 (75.2-231.8) for soap-and-water and 129.9 (49.2-215.3) for chlorhexidine. The median (interquartile range) of total antimicrobial agent-days/100 patient-days was 155.6 (83.3-243.2) for soap-and-water and 146.7 (66.7-217.4) for chlorhexidine. After adjusting for Acute Physiology and Chronic Health Evaluation II scores, chlorhexidine bathing was associated with a nonsignificant reduction in total antimicrobial DDD/100 patient-days (-3.9; 95% confidence interval, -33.9 to 26.1; P = 0.80) and total antimicrobial agent-days/100 patient-days (-10.3; 95% confidence interval, -34.7 to 14.1; P = 0.41). CONCLUSIONS: Compared with daily soap and water bathing, every other day chlorhexidine bathing did not significantly reduce total antimicrobial utilization in surgical intensive care unit patients.

Patient-reported outcomes in light of supportive medications in treatment-naïve lung cancer patients.

PURPOSE: The impact of supportive medications on patient-reported outcomes (PROs) has not been systematically evaluated. We describe the supportive medications used by treatment-naïve lung cancer patients and assess their association with PROs from MD Anderson Symptom Inventory (MDASI). METHODS: Treatment-naïve lung cancer patients who completed PROs from MDASI at the initial visit to MD Anderson Cancer Center were included. Medications from the initial visit were abstracted from the electronic medical records system and categorized into therapeutic classes based on U.S. Pharmacopeia v7.0. A chi-square or Mann-Whitney U test was conducted as appropriate. RESULTS: Among 459 patients, ~ 50% took any analgesics and 25% were on opioids. One-third of patients with moderate-severe pain were not on any analgesics. Patients taking opioids had significantly worse median pain scores (6 vs. 0) compared with those not taking any analgesics (p < 0.0001). Higher proportion of patients with moderate-severe pain took opioids compared with those with mild pain (52% vs. 16%, p < 0.0001). Patients on opioids also reported significantly worse scores for five other cancer-specific core symptoms and all six symptoms rating interference with daily life. Only 15% of patients with higher composite score for depression-related symptoms were on antidepressants. However, patients taking antidepressants did not significantly differ in any individual MDASI symptom scores compared with those not on antidepressants (p = 0.4858). CONCLUSIONS: Our results suggest a need for better screening for pain and depression and optimization of pain management in treatment-naïve lung cancer patients since their poor functional status may result in suboptimal cancer therapy.

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer.

BACKGROUND: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. METHODS: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. RESULTS: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. CONCLUSIONS: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

Association between industry payments and prescribing costly medications: an observational study using open payments and medicare part D data.

BACKGROUND: While many new medications may offer advantages over existing drugs, some newer drugs are reformulations of existing products that provide little innovation or incremental benefit while driving up drug costs. Despite the lack of benefit of these medications, prescribers may be motivated by payments made by the pharmaceutical industry. The objective of the study was to determine the association between payments made to physicians by the pharmaceutical industry and prescriptions for certain selected costly brand name drugs. METHODS: This was a cross-sectional, retrospective study linking the Open Payments Database and Medicare Part D Prescriber Public Use File for 2014, including 667,278 physicians who prescribed one of 6 brand-name drugs with less costly but similarly effective alternatives: lovastatin ER, almotriptan, amlodipine+olmesartan, ibuprofen+famotidine, saxagliptin+metformin and naproxen+esomeprazole. The primary outcome was the odds of a physician prescribing one of the selected drugs, and the primary predictor was the receipt of any payment from the pharmaceutical industry. RESULTS: The odds of prescribing 3 of the 6 drugs were increased among physicians who received industry payment, compared to those without payment: amlodipine+olmesartan, aOR 1.42, (95% CI 1.36-1.49); saxagliptin+metformin, aOR 1.50, (95% CI 1.42-1.59); and naproxen+esomeprazole, aOR 1.45, (95% CI 1.25-1.68). Payment from the manufacturer of the specific drug, compared to not receiving payment from the drug's manufacturer, was associated with increased odds of prescribing 4 of the 6 drugs: amlodipine+olmesartan, aOR 2.40, (95% CI 2.29-2.52), ibuprofen+famotidine, aOR 8.06, (95% CI 5.42-12.00), saxagliptin+metformin, aOR 2.21, (95% CI 2.10-2.34) and naproxen+esomeprazole, aOR 5.96, (95% CI 5.08-7.00). CONCLUSIONS: A physician-industry financial relationship was associated with increased odds of prescribing costly brand-name drugs of uncertain medical benefit. Patients, as healthcare consumers, should demand transparency from their physicians about payment from the pharmaceutical industry to increase shared decision-making. Physician and policy makers need increased awareness and reflection on how industry payment influences their prescribing practices.

Prevalence and Factors Associated with Multiple Provider Episodes in Texas: An Epidemiological Analysis of Prescription Drug Monitoring Program Data.

OBJECTIVE: Prescription drug abuse has reached epidemic levels, leading to overdose-related morbidity and mortality. Patient and regional-level factors are believed to contribute to higher rates of prescription drug abuse. The objective of this study was to determine the prevalence and factors associated with multiple provider episodes (MPEs) in Texas. METHODS: This was a retrospective cohort analysis of data from the Texas Prescription Drug Monitoring Program (PDMP) database, linked with Texas county census data. Descriptive statistics and a multilevel model regression analysis were employed to estimate the prevalence of MPEs and examine the association between individual controlled substance prescription (CSP) utilization and county factors associated with MPEs. RESULTS: Among the 10,381,532 Texas residents utilizing CSPs in 2013, prescription opioids were the most frequently dispensed CSP (38.64%). The prevalence of MPEs was 71.30 per population of 100,000. Of those with MPEs, 76.98% received CSPs for more than 150 days and 11.48% had an average daily morphine equivalent dose (MED) 100 mg/day or higher. Residing in metropolitan areas, traveling more than 100 miles to obtain and fill prescriptions, chronic use of CSPs, younger age, and high MED were all significantly associated with increased risk of MPEs. CONCLUSIONS: This study revealed that previous estimates of prescription drug abuse may be drastically underestimated. Prescription drug abuse is a major public health problem in Texas, especially in metropolitan areas. Therefore, prevention efforts need to be addressed at the individual level and through public health and policy legislation.

The Prevalence of and Factors Associated With Receiving Concurrent Controlled Substance Prescriptions.

BACKGROUND: Controlled substance prescription (CSP) use and abuse in the United States has become a public health epidemic. One common and dangerous indicator of abuse involves obtaining CSPs concurrently. OBJECTIVE: The objective of this study was to identify the prevalence and factors associated with individuals receiving potentially inappropriate concurrent CSPs. METHODS: This was a retrospective, cohort analysis using data from the 2013-2014 Texas prescription drug monitoring program (PDMP). Descriptive statistics and a multiple logistic regression analysis were conducted to examine the individual-level and prescription utilization factors associated with individuals obtaining concurrent CSPs. RESULTS: Among Texas residents, 1,640,015 individuals (6.10% of all Texas residents and 15.99% of all CSP utilizers) were identified with at least one concurrent CSP combination. Concurrent opioid prescriptions were found to be the most prevalent concurrent use combination (n = 1,574,572). Having prescriptions for opioids, being ≥18 years of age, utilizing CSPs for >30 days, utilizing greater than one CSP, having a multiple provider episode, and traveling >25 miles to obtain CSPs were all statistically significant predictors of utilizing concurrent CSPs. CONCLUSION: The study findings indicate a high prevalence of individuals utilizing concurrent CSPs. This practice is concerning when considering that many overdose deaths result from the concurrent use of CSPs. Prescribers should utilize PDMPs to ensure that aberrant prescription drug behaviors, such as the use of concurrent opioids and benzodiazepines do not readily occur.

Effect of Chlorhexidine Bathing Every Other Day on Prevention of Hospital-Acquired Infections in the Surgical ICU: A Single-Center, Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that compared with daily soap and water bathing, 2% chlorhexidine gluconate bathing every other day for up to 28 days decreases the risk of hospital-acquired catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection in surgical ICU patients. DESIGN: This was a single-center, pragmatic, randomized trial. Patients and clinicians were aware of treatment-group assignment; investigators who determined outcomes were blinded. SETTING: Twenty-four-bed surgical ICU at a quaternary academic medical center. PATIENTS: Adults admitted to the surgical ICU from July 2012 to May 2013 with an anticipated surgical ICU stay for 48 hours or more were included. INTERVENTIONS: Patients were randomized to bathing with 2% chlorhexidine every other day alternating with soap and water every other day (treatment arm) or to bathing with soap and water daily (control arm). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a composite outcome of catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection. Of 350 patients randomized, 24 were excluded due to prior enrollment in this trial and one withdrew consent. Therefore, 325 were analyzed (164 soap and water versus 161 chlorhexidine). Patients acquired 53 infections. Compared with soap and water bathing, chlorhexidine bathing every other day decreased the risk of acquiring infections (hazard ratio = 0.555; 95% CI, 0.309-0.997; p = 0.049). For patients bathed with soap and water versus chlorhexidine, counts of incident hospital-acquired infections were 14 versus 7 for catheter-associated urinary tract infection, 13 versus 8 for ventilator-associated pneumonia, 6 versus 3 for incisional surgical site infections, and 2 versus 0 for primary bloodstream infection; the effect was consistent across all infections. The absolute risk reduction for acquiring a hospital-acquired infection was 9.0% (95% CI, 1.5-16.4%; p = 0.019). Incidences of adverse skin occurrences were similar (18.9% soap and water vs 18.6% chlorhexidine; p = 0.95). CONCLUSIONS: Compared with soap and water, chlorhexidine bathing every other day decreased the risk of acquiring infections by 44.5% in surgical ICU patients.

Comparative Performance of Diagnosis-based and Prescription-based Comorbidity Scores to Predict Health-related Quality of Life.

OBJECTIVES: To compare the performance of the health-related quality of life-comorbidity index (HRQoL-CI) with the diagnosis-based Charlson, Elixhauser, and combined comorbidity scores and the prescription-based chronic disease score (CDS) in predicting HRQoL in Agency of Healthcare Research and Quality priority conditions (asthma, breast cancer, diabetes, and heart failure). METHODS: The Medical Expenditure Panel Survey (2005 and 2007-2011) data was used for this retrospective study. Four disease-specific cohorts were developed that included adult patients (age 18 y and above) with the particular disease condition. The outcome HRQoL [physical component score (PCS) and mental component score (MCS)] was measured using the Short Form Health Survey, Version 2 (SF-12v2). Multiple linear regression analyses were conducted with the PCS and MCS as dependent variables. Comorbidity scores were compared using adjusted R. RESULTS: Of 140,046 adult participants, the study cohort included 7436 asthma (5.3%), 1054 breast cancer (0.8%), 13,829 diabetes (9.9%), and 937 heart failure (0.7%) patients. Among individual scores, HRQoL-CI was best at predicting PCS and MCS. Adding prescription-based comorbidity scores to HRQoL-CI in the same model improved prediction of PCS and MCS. HRQoL-CI+CDS performed the best in predicting PCS (adjusted R): asthma (43.7%), breast cancer (31.7%), diabetes (32.7%), and heart failure (20.0%). HRQoL-CI+CDS and Elixhauser+CDS had superior and comparable performance in predicting MCS (adjusted R): asthma (HRQoL-CI+CDS=20.1%; Elixhauser+CDS=19.6%), breast cancer (HRQoL-CI+CDS=12.9%; Elixhauser+CDS=14.1%), diabetes (HRQoL-CI+CDS=17.7%; Elixhauser+CDS=17.7%), and heart failure (HRQoL-CI+CDS=18.1%; Elixhauser+CDS=17.7%). CONCLUSIONS: HRQoL-CI performed best in predicting HRQoL. Combining prescription-based scores to diagnosis-based scores improved the prediction of HRQoL.

Anticholinergic Medication Use and Risk of Dementia Among Elderly Nursing Home Residents with Depression.

OBJECTIVE: To examine the risk of dementia with anticholinergic use among elderly nursing home residents with depression. DESIGN: Population-based nested case-control study. SETTING: Population-based study involving 2007-2010 Minimum Data Set-linked Medicare data from all 50 states. PARTICIPANTS: Medicare beneficiaries aged 65 years and older, diagnosed with depression, and no history of dementia as of 2007 (baseline period). Cases were identified as patients with incident dementia following the baseline period. For each case, four age- and sex-matched control subjects were selected using incidence density sampling. MEASUREMENTS: Anticholinergic exposure was defined using Anticholinergic Drug Scale. Prescription of clinically significant anticholinergic medications (levels 2 and 3) 30 days preceding the event date formed the primary exposure. The primary outcome was dementia diagnosis, between January 1, 2008, and December 31, 2010. A conditional logistic regression model stratified on matched case-control sets was performed to assess dementia risk, after controlling for other risk factors. RESULTS: The study sample included 28,388 cases diagnosed with dementia and 113,352 matched control subjects. After adjusting for other risk factors, clinically significant anticholinergic use was associated with significant risk of dementia (OR: 1.26; 95% CI: 1.22-1.29) compared with non-use. The findings remained consistent across levels of anticholinergic potency (level 2, OR: 1.37, 95% CI: 1.31-1.44; level 3, OR: 1.15, 95% CI: 1.10-1.19). CONCLUSION: Use of clinically significant anticholinergic medications was associated with a 26% increase in risk of dementia among elderly nursing home residents with depression. With increasing safety concerns, there is a significant need to optimize anticholinergic use, especially for those who are at risk for dementia.

Comparative Cognitive Profile of Second-Generation Antidepressants in Elderly Nursing Home Residents With Depression.

BACKGROUND: Past literature suggests that the use of second-generation antidepressants improves cognition in depressed elderly patients. OBJECTIVE: This study assessed the comparative cognitive profile of commonly used second-generation antidepressant classes in elderly residents with depression. METHODS: A multiple propensity score adjusted retrospective cohort study was conducted using 2007-2010 Medicare Part D claims and Minimum Data Set (MDS). Elderly nursing home residents (65 years or older) with depression using a new prescription of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tetracyclics constituted the study cohort. The outcome of interest was cognition, measured using the MDS Cognition Scale. Cognition was measured at each quarterly assessment after antidepressant initiation for a maximum of 1 year. The propensity score-adjusted repeated-measures mixed model was used to evaluate the comparative profile of SSRIs, SNRIs, and tetracyclics with respect to cognition. RESULTS: The study cohort comprised 1518 elderly nursing home residents. Of these, 1081 received SSRIs (71.21%), 320 received tetracyclics (21.08%), and 117 received SNRIs (7.71%). The propensity score-adjusted repeated-measures mixed model did not show any statistically significant difference in cognition with the use of SSRIs (ß = -0.14; 95% CI = -0.53, 0.25) or tetracyclics (ß = -0.36; 95% CI = -0.80, 0.08) when compared with SNRIs, after controlling for other factors. CONCLUSIONS: The cognitive effect of SSRIs, SNRIs, and tetracyclics was similar in elderly nursing home residents with depression. Further studies are needed to evaluate the long-term cognitive effects of second-generation antidepressants in this vulnerable population.

Comparative Effectiveness of Smoking Cessation Medications to Attenuate Weight Gain Following Cessation.

OBJECTIVE: To compare the postcessation weight gain following the use of different FDA-approved smoking cessation medications among obese smokers. METHODS: A retrospective cohort study was conducted using the General Electric (GE) electronic medical record database (2006-2011). The cohort consisted of obese adult smokers newly initiating use of an FDA-approved smoking cessation medication (i.e., bupropion vs. varenicline). The outcome variable was weight change at 3, 6, or 12 months following the first prescription. Descriptive analyses and t-tests were conducted to assess the frequency distribution of sample characteristics and their association with the postcessation weight change. Multivariate linear regression models were carried out to compare the weight change among the FDA-approved smoking cessation medications and to identify predictors of weight change at 3, 6, and 12 months after assessing the model assumptions. RESULTS: The mean weight gain was 1.14 pounds (±17.26), 2.06 pounds (±18.46), and 3.06 pounds (±20.78) at 3-, 6-, and 12-month, respectively. Obese smokers who were prescribed varenicline had a mean weight gain of 1.18 pounds (±16.75), 2.14 pounds (±18.14), and 3.12 pounds (±20.89) for each follow up, while those who were prescribed bupropion had a mean weight gain of 0.23 pounds (±25.90), 0.22 pounds (±25.32), and 1.47 pounds (±17.50), respectively. Descriptive analysis showed that obese smokers taking bupropion had less weight gain than those taking varenicline at each follow up; however, this association was not statistically significant after accounting for all covariates. CONCLUSIONS: While patients using bupropion gained slightly less weight compared to those using varenicline, type of smoking cessation medication was not a significant predictor of weight change in the multivariate linear regression model.

Comparison of Diabetes Risk Following Smoking Cessation Treatment Using Varenicline Versus Bupropion Among Obese Smokers.

BACKGROUND: Recent literature suggests an initial increased risk of diabetes following smoking cessation. OBJECTIVES: To compare the risk of developing diabetes among obese smokers who tried to quit smoking using bupropion versus varenicline. METHODS: A population-based retrospective cohort study was conducted using the General Electric (GE) electronic medical record database (2006-2011). The cohort consisted of obese adult smokers without a diabetes diagnosis at baseline and newly initiating use of either bupropion or varenicline. This cohort was then followed for 1 year to observe the risk of developing diabetes. The relative risk of bupropion versus varenicline on developing diabetes was assessed using Cox Proportional Hazards regression model after controlling for covariates. RESULTS: The sample comprised of 78,002 obese smokers of which 1,937 (2.36%) developed diabetes during 1 year follow-up. Diabetes incidence rate was relatively comparable who used varenicline and bupropion (23.50 versus 25.80 per 1,000 person-years). Obese smokers who were prescribed bupropion had a statistically significant higher risk of developing diabetes during 1 year following cessation treatment than those who were prescribed varenicline. ([HR]: 1.58, 95% CI: 1.09-2.27) in the multivariate model. CONCLUSIONS/IMPORTANCE: Obese smokers who were prescribed bupropion might have a higher risk of developing diabetes during 1 year follow up compared to those who were prescribed varenicline. The clinical significance of the finding that bupropion had a higher risk of developing diabetes may need further investigation.