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The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all-cause mortality vs other commonly used antibiotics. We conducted a self-controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014-FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole-trimethoprim), adjusted for time-varying covariates. Using a 30-day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all-cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.

BackgroundThe objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).MethodsA retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.ResultsThere were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first-line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.ConclusionOur analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real-world setting than in clinical trials, and dose reductions and ADEs are more common.

Over the past decade, the Department of Veterans Affairs (VA) Pharmacy Benefits Management Services (PBM) has enhanced its formulary management activities and added programs to ensure that the national drug plan continues to meet the pharmacy needs of veterans and to promote safe and appropriate drug therapy in the face of rising medication expenditures. This article describes the broad range of services provided by the VA PBM that work in partnership to deliver a high-quality and sustainable pharmacy benefit for veterans. In support of formulary management, VA PBM pharmacists prepare extensive clinical guidance documents (e.g., drug monographs and criteria for use) that are used by physicians and pharmacists with operational and clinical oversight of the VA national formulary. The VA PBM has utilized various contracting techniques and continually evaluates drug utilization data to identify opportunities for potential savings. Remarkably, since before 2004, the average acquisition cost for a 1-month supply of medication has remained fairly stable at approximately $13-$15. Two new VA PBM programs are the VA Center for Medication Safety (VA MedSAFE) and the Clinical Pharmacy Practice Office (CPPO). VA MedSAFE is a comprehensive pharmacovigilance program focused on the detection, assessment, and prevention of adverse drug events, and CPPO is dedicated to improving safe and appropriate medication use by supporting and expanding clinical pharmacy practice. Moving forward, the VA PBM will consider new initiatives to stay at the forefront of providing quality care while maintaining economic viability.DisclosuresNo outside funding supported this research. This work was supported by VA Pharmacy Benefits Management Services (VA PBM), Hines, Illinois, and VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Glassman is co-director of the VA Center for Medication Safety, which is part of the VA PBM. He is also part of the Medical Advisory Panel for the VA PMB. All other authors are employed by the VA PBM. The views expressed in this article are those of the authors, and no official endorsement by the U.S. Department of Veteran Affairs or the U.S. government is intended or should be inferred. Study concept and design were contributed by Valentino, Cunningham, Good, Aspinall, and Sales. Calabrese and Ourth took the lead in data collection, along with Good, Cunningham, Aspinall, Sales, Burk, Moore, Neuhauser, and Golterman. Data interpretation was performed by Burk, Newhauser, and Golterman, along with Glassman, Calabrese, Moore, and Ourth. The manuscript was written by Aspinall and Sales, along with Burk, Newhauser, Golterman, Ourth, and Cunningham. Good, Glassman, and Moore revised the manuscript, along with Calabrese, Valentino, and Aspinall.

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy may result from inappropriate prescribing of medications to treat adverse drug reactions (ADRs), i.e., "prescribing cascade." A potentially harmful prescribing cascade affecting those with severe dementia can result when anticholinergics are prescribed to manage side effects of cholinesterase inhibitors (ChEIs). We investigated 1) factors associated with co‐prescribing of anticholinergics and ChEIs and 2) whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics—a potentially beneficial reversal or "deprescribing cascade." Methods: We conducted a retrospective analysis of linked Medicare Part A/B/D claims, Master Beneficiary Summary File, Minimum Data Set, Area Health Resource File, and Nursing Home Compare from 2015 to 2016. Subjects were Medicare beneficiaries residing in nursing homes, ≥65 years old with severe dementia admitted for non‐skilled stays, who were prescribed ChEIs. Cross‐sectional analysis evaluated factors associated with co‐prescribing of anticholinergics with ChEIs. Longitudinal Cox proportional hazards regression examined whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics over a 1‐year period. Results: We found 15% of our sample experienced co‐prescribing of anticholinergics and ChEIs. Several resident and facility‐level factors were associated with co‐prescribing anticholinergics. Advancing age, minority race or ethnicity, end‐stage renal disease, heart failure, and poor appetite were associated with a decreased likelihood of co‐prescribing. Female sex, polypharmacy, and non‐geriatric prescriber‐type were associated with a higher likelihood of co‐prescribing. In longitudinal analyses, we observed that discontinuation of ChEIs was associated with a reduced likelihood (HR 0.58 [95% CI, 0.47–0.71]) of discontinuing any medications with anticholinergic properties, except for bladder antimuscarinics (HR 1.32 [95% CI, 0.83–2.09]). Conclusions: Younger, healthier older adults with dementia were more likely to experience co‐prescribing anticholinergics and ChEIs. Discontinuation of anticholinergics was infrequent. Further research is needed to understand prescribers' ability to recognize and reverse potential prescribing cascades through deprescribing. [ABSTRACT FROM AUTHOR]

Objective: Guidelines advocate against tight glycemic control in older nursing home (NH) residents with advanced dementia (AD) or limited life expectancy (LLE). We evaluated the effect of deintensifying diabetes medications with regard to all-cause emergency department (ED) visits, hospitalizations, and death in NH residents with LLE/AD and tight glycemic control.Research Design and Methods: We conducted a national retrospective cohort study of 2,082 newly admitted nonhospice veteran NH residents with LLE/AD potentially overtreated for diabetes (HbA1c ≤7.5% and one or more diabetes medications) in fiscal years 2009-2015. Diabetes treatment deintensification (dose decrease or discontinuation of a noninsulin agent or stopping insulin sustained ≥7 days) was identified within 30 days after HbA1c measurement. To adjust for confounding, we used entropy weights to balance covariates between NH residents who deintensified versus continued medications. We used the Aalen-Johansen estimator to calculate the 60-day cumulative incidence and risk ratios (RRs) for ED or hospital visits and deaths.Results: Diabetes medications were deintensified for 27% of residents. In the subsequent 60 days, 28.5% of all residents were transferred to the ED or acute hospital setting for any cause and 3.9% died. After entropy weighting, deintensifying was not associated with 60-day all-cause ED visits or hospitalizations (RR 0.99 [95% CI 0.84, 1.18]) or 60-day mortality (1.52 [0.89, 2.81]).Conclusions: Among NH residents with LLE/AD who may be inappropriately overtreated with tight glycemic control, deintensification of diabetes medications was not associated with increased risk of 60-day all-cause ED visits, hospitalization, or death. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the impact of deprescribing acetylcholinesterase inhibitors (AChEIs) on aggressive behaviors and incident antipsychotic use in nursing home (NH) residents with severe dementia. Methods: We conducted a retrospective study of Medicare claims, Part D, Minimum Data Set for NH residents aged 65+ with severe dementia receiving AChEIs in 2016. Aggressive behaviors were measured using the aggressive behavior scale (ABS; n = 30,788). Incident antipsychotic prescriptions were evaluated among antipsychotic non‐users (n = 25,188). Marginal structural models and inverse probability of treatment weights were used to evaluate associations of AChEI deprescribing and outcomes. Results: The severity of aggressive behaviors was low at baseline (mean ABS = 0.5) and was not associated with deprescribing AChEIs (0.002 increase in ABS, P =.90). Incident antipsychotic prescribing occurred in 5.1% of residents and was less likely with AChEI deprescribing (adjusted odds ratio = 0.52 [0.40–0.68], P <.001]). Discussion: Deprescribing AChEIs was not associated with a worsening of aggressive behaviors or incident antipsychotic prescriptions. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Many older adults with limited life expectancy and/or advanced dementia (LLE/AD) are potentially overtreated for diabetes and may benefit from deintensification. Our aim was to examine the incidence and predictors of diabetes medication deintensification in older Veterans with LLE/AD who were potentially overtreated at admission to Veterans Affairs (VA) nursing homes (community living centers [CLCs]). DESIGN: Retrospective cohort study using linked VA and Medicare clinical/administrative data and Minimum Data Set assessments. SETTING: VA CLCs. PARTICIPANTS: A total of 6960 Veterans with diabetes and LLE/AD admitted to VA CLCs in fiscal years 2009 to 2015 with hemoglobin (Hb)A1c measured within 90 days of admission. MEASUREMENTS: We evaluated treatment deintensification (discontinuation or dose reduction for a consecutive 7‐day period) among residents who were potentially overtreated (HbA1c ≤7.5% and receiving hypoglycemic medications). Competing risk models assessed 90‐day cumulative incidence of deintensification. RESULTS: More than 40% (n = 3056) of Veteran CLC residents with diabetes were potentially overtreated. The cumulative incidence of deintensification at 90 days was 45.5%. Higher baseline HbA1c values were associated with a lower likelihood of deintensification (e.g., HbA1c 7.0‐7.5% vs <6.0%; adjusted risk ratio [aRR] =.57; 95% confidence interval [CI] =.50‐.66). Compared with non‐sulfonylurea oral agents (e.g., metformin), other treatment regimens were more likely to be deintensified (aRR = 1.31‐1.88), except for basal insulin (aRR =.59; 95% CI =.52‐.66). The only resident factor associated with increased likelihood of deintensification was documented end‐of‐life status (aRR = 1.12; 95% CI = 1.01‐1.25). Admission from home/assisted living (aRR =.85; 95% CI =.75‐.96), obesity (aRR =.88; 95% CI =.78‐.99), and peripheral vascular disease (aRR =.90; 95% CI =.81‐.99) were associated with decreased likelihood of deintensification. CONCLUSION: Deintensification of treatment regimens occurred in less than one‐half of potentially overtreated Veterans and was more strongly associated with low HbA1c values and use of medications with high risk for hypoglycemia, rather than other resident characteristics. J Am Geriatr Soc 68:736–745, 2020 See related editorial by Joseph G. Ouslander in this issue. [ABSTRACT FROM AUTHOR]

OBJECTIVES Continuation of aspirin for secondary prevention in persons with limited life expectancy (LLE) is controversial. We sought to determine the incidence and predictors of aspirin discontinuation in veterans with LLE and/or advanced dementia (LLE/AD) who were taking aspirin for secondary prevention at nursing home admission, stratified by whether their limited prognosis (LP) was explicitly documented at admission. DESIGN Retrospective cohort study using linked Veterans Affairs (VA) and Medicare clinical/administrative data and Minimum Data Set resident assessments. SETTING All VA nursing homes (referred to as community living centers [CLCs]) in the United States. PARTICIPANTS Older (≥65 y) CLC residents with LLE/AD, admitted for 7 days or longer in fiscal years 2009 to 2015, who had a history of coronary artery disease and/or stroke/transient ischemic attack, and used aspirin within the first week of CLC admission (n = 13 844). MEASUREMENTS The primary dependent variable was aspirin discontinuation within the first 90 days after CLC admission, defined as 14 consecutive days of no aspirin receipt. Independent variables included an indicator for explicit documentation of LP, sociodemographics, environment of care characteristics, cardiovascular risk factors, bleeding risk factors, individual markers of poor prognosis (eg, cancer, weight loss), and facility characteristics. Fine and Gray subdistribution hazard models with death as a competing risk were used to assess predictors of discontinuation. RESULTS: Cumulative incidence of aspirin discontinuation was 27% (95% confidence interval [CI] = 26%‐28%) in the full sample, 34% (95% CI = 33%‐36%) in residents with explicit documentation of LP, and 24% (95% CI = 23%‐25%) in residents with no such documentation. The associations of independent variables with aspirin discontinuation differed in residents with vs without explicit LP documentation at admission. CONCLUSION: Just over one‐quarter of patients discontinued aspirin, possibly reflecting the unclear role of aspirin in end of life among prescribers. Future research should compare outcomes of aspirin deprescribing in this population. J Am Geriatr Soc 68:725–735, 2020 See related editorial by Joseph G. Ouslander in this issue. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVE: Reevaluation of the appropriateness of acetylcholinesterase inhibitors (AChEIs) is recommended in older adults with severe dementia, given the lack of strong evidence to support their continued effectiveness and risk for medication‐induced adverse events. We sought to evaluate the impact of deprescribing AChEIs on risk of all‐cause events (hospitalizations, emergency department visits, and mortality) and serious falls or fractures in older nursing home (NH) residents with severe dementia. DESIGN: Analysis of 2015 to 2016 data from Medicare claims, Part D prescriptions, Minimum Data Set (MDS) version 3.0, Area Health Resource File, and Nursing Home Compare. Marginal structural models with inverse probability of treatment weights were used to evaluate the association of deprescribing AChEIs and all‐cause negative events as well as serious falls or fractures. SETTING: US Medicare‐certified NHs. PARTICIPANTS: Nonskilled NH residents, aged 65 years and older, with severe dementia receiving AChEIs within the first 14 days of an MDS assessment in 2016 (n = 37 106). RESULTS: The sample was primarily white (78.7%), female (75.5%), and aged 80 years or older (77.4%). Deprescribing AChEIs was associated with an increased likelihood of all‐cause negative events in unadjusted models (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.11‐1.23; P <.01), but not in fully adjusted models (adjusted OR [aOR] = 1.00; 95% CI = 0.94‐1.06; P =.94). By contrast, deprescribing was associated with a reduced likelihood of serious falls or fractures in unadjusted models (OR = 0.59; 95% CI = 0.52‐0.66; P <.001) and remained significant in adjusted models (aOR = 0.64; 95% CI = 0.56‐0.73; P <.001). CONCLUSION: Deprescribing AChEIs was not associated with a significant increase in the likelihood for all‐cause negative events and was associated with a reduced likelihood of falls and fractures in older NH residents with dementia. Our findings suggest that deprescribing AChEIs is a reasonable approach to reduce the risk of serious falls or fractures without increasing the risk for all‐cause events. J Am Geriatr Soc 68:699–707, 2020 See related editorial by Joseph G. Ouslander in this issue. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVE: Uncertainty regarding benefits and risks associated with acetylcholinesterase inhibitors (AChEIs) in severe dementia means providers do not know if and when to deprescribe. We sought to identify which patient‐, provider‐, and system‐level characteristics are associated with AChEI discontinuation. DESIGN: Analysis of 2015 to 2016 data from Medicare claims, Part D prescriptions, Minimum Data Set (MDS), version 3.0, Area Health Resource File, and Nursing Home Compare. Cox‐proportional hazards models with time‐varying covariates were used to identify patient‐, provider‐, and system‐level factors associated with AChEI discontinuation (30‐day or more gap in supply). SETTING: US Medicare–certified nursing homes (NHs). PARTICIPANTS: Nonskilled NH residents, aged 65 years and older, with severe dementia receiving AChEIs within the first 14 days of an MDS assessment in 2016 (n = 37 106). RESULTS: The sample was primarily white (78.7%), female (75.5%), and aged 80 years or older (77.4%). The most commonly prescribed AChEIs were donepezil (77.8%), followed by transdermal rivastigmine (14.6%). The cumulative incidence of AChEI discontinuation was 29.7% at the end of follow‐up (330 days), with mean follow‐up times of 194 days for continuous users of AChEIs and 105 days for those who discontinued. Factors associated with increased likelihood of discontinuation were new admission, older age, difficulty being understood, aggressive behavior, poor appetite, weight loss, mechanically altered diet, limited prognosis designation, hospitalization in 90 days prior, and northeastern region. Factors associated with decreased likelihood of discontinuation included memantine use, use of strong anticholinergics, polypharmacy, rurality, and primary care prescriber vs geriatric specialist. CONCLUSION: Among NH residents with severe dementia being treated with AChEIs, the cumulative incidence of AChEI discontinuation was just under 30% at 1 year of follow‐up. Our findings provide insight into potential drivers of deprescribing AChEIs, identify system‐level barriers to deprescribing, and help to inform covariates that are needed to address potential confounding in studies evaluating the potential risks and benefits associated with deprescribing. J Am Geriatr Soc 67:1871–1879, 2019 [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between central nervous system (CNS) medication dosage burden and risk of serious falls, including hip fractures, in individuals with a history of a recent fall. Design: Nested case–control study. Setting: Veterans Health Administration (VHA) Community Living Centers (CLCs). Participants: CLC residents aged 65 and older with a history of a fall or hip fracture in the year before a CLC admission between July 1, 2005, and June 30, 2009. Each case (n = 316) was matched to four controls (n = 1264) on age, sex, and length of stay. Measurements: Outcomes were serious falls identified using International Classification of Diseases, Ninth Revision (ACD‐9) or Current Procedural Terminology (CPT) E codes, diagnosis codes, or procedure codes associated with a VHA emergency department visit or hospitalization during the CLC stay. Bar code medication administration data were used to calculate CNS standardized daily doses (SDDs) for opioid and benzodiazepine receptor agonists, some antidepressants, antiepileptics, and antipsychotics received in the 6 days before the outcome date by dividing residents' actual CNS daily doses by the minimum effective geriatric daily doses and adding the results. Multivariable conditional logistic regression models were used to evaluate the association between total CNS medication dosage burden, categorized as 0, 1 to 2, and 3 or more SDDs, and the outcome of recurrent serious falls. Results: More cases (44.3%) than controls (35.8%) received 3.0 or more CNS SDDs (p = .02). Risk of serious falls was greater in residents with 3.0 or more SDDs than in those with 0 (adjusted odds ratio (aOR)=1.49, 95% confidence interval (CI)=1.03–2.14). Those with 1.0 to 2.9 SDDs had a risk similar to that of those with 0 SDDs (aOR=1.03, 95%CI=0.72–1.48). Conclusion: Nursing home residents with a history of a fall or hip fracture receiving 3.0 or more CNS SDDs were more likely to have a recurrent serious fall than those taking no CNS medications. Interventions targeting this vulnerable population may help reduce serious falls. J Am Geriatr Soc 67:74–80, 2019. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the predictive validity of an adapted version of the Minimum Data Set (MDS) Mortality Risk Index—Revised (MMRI‐R) based on MDS version 3.0 assessment items (MMRI‐v3) and to compare the predictive validity of the MMRI‐v3 with that of a single MDS item indicating limited life expectancy (LLE). Design: Retrospective, cross‐sectional study of MDS assessments. Other data sources included the Veterans Affairs (VA) Residential History File and Vital Status File. Setting: VA nursing homes (NHs). Participants: Veterans aged 65 and older newly admitted to VA NHs between July 1, 2012, and September 30, 2015. Measurements: The dependent variable was death within 6 months of admission date. Independent variables included MDS items used to calculate MMRI‐v3 scores (renal failure, chronic heart failure, sex, age, dehydration, cancer, unintentional weight loss, shortness of breath, activity of daily living scale, poor appetite, acute change in mental status) and the MDS item indicating LLE. Results: The predictive ability of the MMRI‐v3 for 6‐month mortality (c‐statistic 0.81) is as good as that of the original MMRI‐R (c‐statistic 0.76). Scores generated using the MMRI‐v3 had greater predictive ability than that of the single MDS indicator for LLE (c‐statistic 0.76); using the 2 together resulted in greater predictive ability (c‐statistic 0.86). Conclusion: The MMRI‐v3 is a useful tool in research and clinical practice that accurately predicts 6‐month mortality in veterans residing in Veterans Affairs NHs. Identification of residents with LLE has great utility for studying palliative care interventions and may be helpful in guiding allocation of these services in clinical practice. J Am Geriatr Soc 66:2353–2359, 2018. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between CNS medication burden and serious falls in those with a recent fall history. Design Nested-case control study; cases matched to four controls by age, gender, and date. Setting US nursing homes. Participants 5,556 residents age ≥65 with a recent fall history admitted to a nursing home between 1/1-9/30/2010 and followed until discharge, death, or December 31, 2010. Measurements Outcome was serious falls as per Medicare Part A and B ICD/ CPT codes. CNS burden, from Medicare Part D data, was calculated by dividing the daily dose of each CNS agent (i.e., specific antidepressants, antiepileptic, antipsychotic, benzodiazepine and opioid receptor agonists) received during the 6 days prior to the index (outcome) date by the minimum effective geriatric daily dose and summing the results across medications. Results There were 367 cases and 1,468 matched controls. Those taking 3 + CNS standardized daily doses were more likely to have a serious fall than those not taking any CNS medications (Adjusted Odds Ratio 1.83; 95% confidence interval 1.35-2.48). There was no significant difference in fall risk for residents taking >0 to <3 CNS standardized daily doses compared to residents taking no CNS medications (Adjusted Odds Ratio 0.85; 95% CI 0.63-1.15). Conclusion CNS medication burden, approximately 3 + standardized daily doses, was associated with an increased risk of serious falls in nursing home residents with recent fall. Clinicians should be vigilant for opportunities to discontinue or decrease the doses of individual CNS medications and/or consider non-pharmacological alternatives. Such interventions that reduce use of CNS medications in nursing homes could reduce fall rates but further research is needed to confirm this. [ABSTRACT FROM AUTHOR]

Aims We compared the risk of mental health episodes requiring hospitalization (primary aim) or out-patient clinic visits (secondary aim) associated with varenicline versus the nicotine patch (NP) in an era prior to psychiatric boxed warnings. Design Retrospective cohort. Setting Department of Veterans Affairs (VA), USA. Participants VA patients with or without psychiatric comorbidities and a new prescription for varenicline (15 255) were propensity score-matched (1 : 2) to new users of NP (123 054) between 1 May 2006 and 30 September 2007, resulting in 11 774 and 23 548 patients in the varenicline and NP groups, respectively. Measurements The primary outcomes were hospitalizations with a primary discharge diagnosis of a range of mental health disorders: depression, schizophrenia, bipolar disorder, suicide attempt, post-traumatic stress disorder, other psychosis and drug-induced mental disorders. Secondary outcomes were out-patient clinic visits with a primary diagnosis of the above list of mental health disorders. Findings Background characteristics of the treatment groups were similar after matching. There was no statistically significant difference in risk of hospitalization for any of the studied mental health disorders with varenicline compared with NP. Among secondary outcomes there was an increased risk of out-patient clinic visits for schizophrenia among patients who received varenicline [hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.07, 1.51], this increase being evident only in those with a pre-existing mental health disorder. Conclusion In US VA patients studied prior to the boxed warning being implemented, use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. There was an increased rate of out-patient attendances with a primary diagnosis of schizophrenia amounting to five per 100 person years of treatment. This increase was found only in patients with a pre-existing mental health disorder. [ABSTRACT FROM AUTHOR]

Background: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). Methods: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. Results: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. Conclusion: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The objectives of this study were to describe changes in glyburide prescribing in cohorts that were and were not targeted by a risk reduction project, assess factors associated with glyburide discontinuation, and evaluate changes in glycated hemoglobin (ie, HbA1c) levels and rates of serious hypoglycemia. Methods: This historical cohort study included a targeted cohort of 4368 outpatient veterans aged ≥65 years with active prescriptions for glyburide between April 1, 2007 and June 30, 2007 and serum creatinine (SCr) ≥2 mg/dL and a nontargeted cohort of 1886 outpatients meeting these same criteria between July 1, 2007 and September 3, 2007. The intervention in the risk reduction project took place on September 4, 2007 and entailed giving regional pharmacy leaders information about the increased risk of hypoglycemia with glyburide and the list of targeted patients for follow up with providers. For each patient, the study period was the time between the date they first met the eligibility criteria and March 31, 2008. All data were obtained from Veterans Affairs (VA) administrative databases. The primary outcome was the discontinuation of glyburide. Secondary outcomes were the change in HbA1c after stopping glyburide and the rate of serious hypoglycemia after intervention. Results: Incidence rate ratios (IRRs) for glyburide discontinuation in targeted versus nontargeted cohorts were statistically significantly elevated in September (IRR 2.1; 95% CI 1.7–2.5), October (IRR 1.3; 95% CI 1.1–1.6), and November 2007 (IRR 1.4; 95% CI 1.1–1.7). The intervention, black race, SCr, Charlson comorbidity score, new glyburide use, and VA region were independently associated with discontinuation. Among patients in the targeted cohort who discontinued glyburide, mean (SD) HbA1c at baseline and after discontinuation were 7.17% (1.35%), and 7.22% (1.34%), respectively (P = 0.36). The hypoglycemia rates/1000 person-days were 0.093 before the intervention and 0.070 afterwards (P = 0.10). Conclusion: A one-time intervention in a risk reduction project decreased glyburide use over a 3-month period in elderly outpatients with renal insufficiency without compromising glucose control. [Copyright &y& Elsevier]

Background: Choice of antibiotic therapy for acute exacerbations of chronic bronchitis (AECB) is important because of cost and concerns about development of resistance. Methods: A retrospective cohort study was conducted in outpatients with chronic obstructive pulmonary disease and documented AECB treated with antibiotics. Results: We compared outcomes and costs of AECB treated with first-line antibiotics having partial coverage against organisms associated with AECB (eg, amoxicillin), first-line antibiotics with full coverage against organisms associated with AECB (eg, sulfamethoxazole-trimethoprim), and newer broad-spectrum antibiotics (eg, azithromycin). There were no significant differences among the three antibiotic groups in failure rate, hospitalization rate, or time until subsequent AECB. Pharmacy costs were signiflcantly less with first-line antibiotics ($3.18 ± 0.64, 53.00 ± 0.48, and $36.70 ± 16.29, respectively; P < 0.0001), but there was no significant difference among all three groups with regard to total costs. Conclusion: We found no difference in outcome between older traditional antibiotics with adequate coverage against organisms associated with AECR and newer broad-spectrum antibiotics. [ABSTRACT FROM AUTHOR]