Genome sequence of Microbacterium foliorum phage CandC.

We report the discovery and genome sequence of CandC, a lytic bacteriophage with siphovirus morphology. CandC was isolated from a soil sample from Plattsburgh, NY, USA (Fall 2021). It has a genome size of 62,344 bp with 106 predicted protein-encoding genes, 30 of which are assigned putative functions.

Treatment patterns and outcomes following disease progression on anti-PD-1 therapies for advanced melanoma.

Background: Anti-PD-1-based therapies prolong survival in advanced melanoma, but disease progression is common. This study evaluated treatment patterns and overall survival (OS) after anti-PD-1 progression. Methods: Retrospective data from patients with advanced melanoma and progression on anti-PD-1 treatment between 2014 and 2019 were taken from Flatiron Health, which reflects largely community practice. Treatment patterns and OS were analyzed for BRAF mutant (mt) and wild-type (wt) subgroups; OS was also examined across all patients. Results: Progression following anti-PD-1 was recorded for 679 patients. Median OS ranged from 5.0 to 11.3 months. Of 275 BRAFmt and 374 BRAFwt patients, 113 (41.1%) and 228 (61.0%) received no subsequent therapy, respectively. However, 48.4% of BRAFmt and 57.8% of BRAFwt patients continued anti-PD-1 treatment beyond progression. Conclusion: This real-world study underscores the need for effective treatments for advanced melanoma post-progression on anti-PD-1 therapy.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

Comparison of ICD-9-CM to ICD-10-CM Crosswalks Derived by Physician and Clinical Coder vs. Automated Methods.

Purpose: To evaluate whether automated methods are sufficient for deriving ICD-10-CM algorithms by comparing ICD-9-CM to ICD-10-CM crosswalks from general equivalence mappings (GEMs) with physician/clinical coder-derived crosswalks. Patients and methods: Forward mapping was used to derive ICD-10-CM crosswalks for 10 conditions. As a sensitivity analysis, forward-backward mapping (FBM) was also conducted for three clinical conditions. The physician/coder independently developed crosswalks for the same conditions. Differences between the crosswalks were summarized using the Jaccard similarity coefficient (JSC). Results: Physician/coder crosswalks were typically far more inclusive than GEMs crosswalks. Crosswalks for peripheral artery disease were most dissimilar (JSC: 0.06), while crosswalks for mild cognitive impairment (JSC: 1) and congestive heart failure (0.85) were most similar. FBM added ICD-10-CM codes for all three conditions but did not consistently increase similarity between crosswalks. Conclusion: The GEMs and physician/coder algorithms rarely aligned fully; human review is still required for ICD-9-CM to ICD-10-CM crosswalk development.

STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world.

BACKGROUND: Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. METHODS: This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). RESULTS: Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9-2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3-2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2-1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. CONCLUSIONS: This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.

Burden of asthma exacerbations and health care utilization in pediatric patients with asthma in the US and England.

BACKGROUND: Data on asthma burden in pediatric patients are limited; this real-world study investigated exacerbation frequency and health care resource utilization (HCRU) in pediatric asthma patients from the US and England. METHODS: Data from pediatric patients (aged 6-17 years) in the Optum claims database (US) or Clinical Practice Research Datalink with linkage to Hospital Episode Statistics (England) were analyzed. Patients were categorized into four hierarchical groups: treated asthma (patients with ≥1 baseline asthma medication), severe asthma (plus Global Initiative for Asthma Step 4/5), severe refractory asthma ([SRA] plus ≥2 baseline severe asthma exacerbations), and eosinophilic SRA (SRA plus blood eosinophil count ≥150 cells/µL). Exacerbation frequency and HCRU during the 12 months postindex were described. RESULTS: Of 151 549 treated asthma patients in the US, 18 086 had severe asthma, 2099 SRA, and 109 eosinophilic SRA. There were 32 893 treated asthma patients in England, of whom 2711 had severe asthma, 265 SRA, and 8 eosinophilic SRA. In the 12 months postindex, ≥1 exacerbation occurred in 12.4% and 10.8% of patients with severe asthma, and 32.6% and 42.6% with SRA in the US and England, respectively. The proportions of patients with ≥1 asthma hospitalization in the 30 days after the first asthma exacerbation were 2.7% and 4.4% (treated), 3.5% and 8.2% (severe asthma), and 6.0% and 16.8% (SRA) in the US and England, respectively. CONCLUSION: This study provides insights into current asthma management practices in the US and England and indicates that some patients with severe disease have an unmet need for effective management.

Understanding Prediabetes in a Medicare Advantage Population Using Data Adaptive Techniques.

The objective was to identify individuals with undiagnosed prediabetes from administrative data using adaptive techniques. The data source was a national Medicare Advantage Prescription Drug (MAPD) plan administrative data set. A retrospective, cross-sectional study developed and evaluated data adaptive logistic regression, decision tree, neural network, and ensemble predictive models for metabolic syndrome and prediabetes using 3 mutually exclusive cohorts (N = 279,903). The misclassification rate (MCR), average squared error (ASE), c-statistics, sensitivity (SN), and false positive (FP) rates were compared to select the final predictive models. MAPD individuals with continuous enrollment from 2013 to 2014 were included. Metabolic syndrome and prediabetes were defined using clinical guidelines, diagnosis, and laboratory data. A total of 512 variables identified through subject matter expertise in addition to utilizing all data available were evaluated for the modeling. The ensemble model demonstrated better discrimination (c-statistics, MCR, and ASE of 0.83, 0.24, and 0.16, respectively), high SN, and low FP rate in predicting metabolic syndrome than the individual data adaptive modeling techniques. Logistic regression demonstrated better discrimination (c-statistics, MCR, and ASE of 0.67, 0.13, and 0.11 respectively), high SN, and low FP rate in predicting prediabetes than the other adaptive modeling techniques or ensemble methods. The scored data predicted prediabetes in 44% of the MAPD population, which is comparable to 2005-2006 National Health and Nutrition Examination Survey prediabetes rates of 41%. The logistic regression model demonstrated good performance in predicting undiagnosed prediabetes in MAPD individuals.

Association of obesity with healthcare resource utilization and costs in a commercial population.

OBJECTIVE: To examine the association of obesity with healthcare resource utilization (HRU) and costs among commercially insured individuals. METHODS: This retrospective observational cohort study used administrative claims from 1 January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from 2008 to 2012 classified body mass index (BMI) into the World Health Organizations' BMI categories. The date of first observed BMI code was defined as the index date and continuous eligibility for one year pre- and post- index date was ensured. Post-index claims determined individuals' HRU and costs. Sampling weights developed using the entropy balance method and National Health and Nutrition Examination Survey data ensured representation of the US adult commercially insured population. Baseline characteristics were described across BMI classes and associations between BMI categories, and outcomes were examined using multivariable regression. RESULTS: The cohort included 9651 individuals with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%), overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class III (5.4%). Increasing BMI was associated with greater prevalence of cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics, analgesics and antidepressants rose with increasing BMI. Greater BMI level was associated with increased inpatient, emergency department and outpatient utilization, and higher total healthcare, medical and pharmacy costs. CONCLUSIONS: Increasing BMI was associated with higher prevalence of cardiometabolic conditions and higher HRU and costs. There is an urgent need to address the epidemic of obesity and its clinical and economic impacts.

Predictors of all-cause 30 day readmission among Medicare patients with type 2 diabetes.

OBJECTIVE: Readmission is costly among patients with type 2 diabetes (T2DM) in Medicare Advantage Prescription Drug Plans; identifying high-risk patients is necessary for targeting reduction programs. The objective of this study was to develop a claims-based algorithm to predict all-cause 30 day readmission among patients with T2DM. METHODS: This study used administrative data from 1 January 2012 through 31 January 2014. The cohort included hospitalized T2DM patients, aged 18-90 with ≥12 months' continuous enrollment before an unplanned hospital admission and ≥1 month of enrollment post-discharge, excluding patients in long-term care >30 days pre-index. Multivariate logistic regression predicted the likelihood of readmission following hospitalization in 2013. The analytic file was randomly split into training and test datasets to build and validate the model. Candidate variables included physician and patient demographics, baseline clinical conditions, and healthcare utilization metrics. Clinical conditions were classified using the Healthcare Cost and Utilization Project clinical classification system for ICD-9-CM. RESULTS: Of 63,237 individuals, 17.1% experienced a readmission. Of nearly 200 candidate variables, 14 were predictors of readmission, including total cumulative number of days for inpatient stays and the number of emergency department visits in the baseline period. Male gender, older age, and certain comorbidities were associated with higher likelihood of readmission. The final model demonstrated good discriminant ability (c-statistic = 0.82). CONCLUSIONS: This study provided evidence that certain patient characteristics and healthcare utilization are predictive of readmission. An algorithm with good discriminant ability was developed which could be used to target readmission reduction programs. Physician gender, specialty, and ownership status did not appear to influence the likelihood of readmission.

Impact of Overactive Bladder Step Therapy Policies on Medication Utilization and Expenditures Among Treated Medicare Members.

BACKGROUND: The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs. OBJECTIVE: To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients. METHODS: A retrospective cross-sectional study design was utilized. Subjects included individuals enrolled in Humana MAPD plans or PDPs, aged ≥ 65 years, with ≥ 1 prescription for an OAB medication in 2013. Patient demographic characteristics, OAB medication utilization, and pharmacy cost trends in 2013 were described. OAB medication use was calculated as the number of 30-day-supply equivalent medication claims and reported as a percentage of the total number of 30-day-supply equivalent claims across all OAB products. OAB medication expenditures were calculated as a percentage of the sum of pharmacy costs for OAB medications and reported separately for each month and drug during 2013. Temporal trends of OAB medication utilization and expenditures in 2013 were calculated using ordinary least squares regression. RESULTS: Of 194,511 patients, trends in utilization of OAB medications indicated that on average, there was a statistically significant monthly increase in utilization of mirabegron (regression coefficient [B] = 274; P < 0.001; 95% CI: 218, 330), fesoterodine (B = 167; P < 0.001; 95% CI = 129, 205), oxybutynin extended release (ER; B = 357; P = 0.011; 95% CI = 99, 614), and trospium ER (B = 33; P = 0.001; 95% CI = 17, 50) and statistically significant decreases in utilization of solifenacin (B = -202; P = 0.048; 95% CI = -402, -2), tolterodine ER (B = -287; P = 0.002; 95% CI = -437, -137), darifenacin (B = -94; P < 0.001; 95% CI = -128, -61), and trospium immediate release (IR; B = -22; P = 0.001; 95% CI = -32, -12). Total OAB medication expenditures significantly increased an average of 0.12% for each month during the course of 2013 (B = 0.12; P = 0.026; 95% CI = 0.017, -0.223). While monthly oxybutynin IR utilization did not change significantly throughout 2013 (B = 228; P = 0.169; 95% CI = -114, -570), it demonstrated the largest average monthly expenditure increase (B = 0.082; P < 0.001; 95% CI = 0.056, 0.108). When removing oxybutynin IR costs from the total OAB medication costs, the trend in total OAB medication average monthly expenditures was not significant (B = 0.038; P = 0.365; 95% CI = -0.051, -0.126). An over 4-fold per-unit-cost increase for oxybutynin IR was noted. CONCLUSIONS: Utilization of 2 branded OAB products increased in the months after ST removal with minimal cost impact. One of the possible reasons total OAB expenditures increased may have been due to the increased cost of the largest-volume generic product, oxybutynin IR. DISCLOSURES: This research was funded by Astellas Pharma Global Development and was conducted as part of the Astellas-Humana Research Collaboration. Ng, Kristy, Schermer, and Bradt are employees of Astellas. Astellas manufactures mirabegron (Myrbetriq) and solifenacin (VESIcare). Abbass, Caplan, Collins, and Suehs are employees of Comprehensive Health Insights, a subsidiary of Humana, which received funding from Astellas for this study. Suehs owns stock in Humana. Chan is an employee of Humana Pharmacy Solutions. Portions of this study were presented as a poster at Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, Florida. Study concept and design were contributed by Ng, Chan, Suehs, and Abbass, along with Collins. Abbass took the lead in data collection, along with Collins and with assistance from Caplan, Chan, and Suehs. Data interpretation was provided by Kristy and Bradt, along with Abbass, Caplan, Ng, Suehs, Collins, and Chan. The manuscript was written primarily by Caplan, along with Schermer, Suehs, and Abbass, and revised by Caplan, Schermer, and Ng, along with the other authors.

A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system.

Dabigatran is approved for stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data from diverse clinical practice settings will help establish whether the risk:benefit ratio seen in clinical trials is comparable with routine clinical care. This study aimed to compare the safety and effectiveness of dabigatran and warfarin in clinical practice. We undertook a propensity score-matched (PSM) cohort study (N=12,793 per group; mean age 74) comparing treatment with dabigatran or warfarin in the US Department of Defense claims database, October 2009 to July 2013. Treatment-naïve patients with first prescription claim for dabigatran (either FDA-approved dose) or warfarin between October 2010 and July 2012 (index) and a diagnosis of NVAF during the 12 months before index date were included. Primary outcomes were stroke and major bleeding. Secondary outcomes included ischaemic and haemorrhagic stroke, major gastrointestinal (GI), urogenital or other bleeding, myocardial infarction (MI) and death. Time-to-event was investigated using Kaplan-Meier survival analyses. Outcomes comparisons were made utilising Cox-proportional hazards models of PSM groups. Dabigatran users experienced fewer strokes (adjusted hazard ratio [95 % confidence intervals] 0.73 [0.55-0.97]), major intracranial (0.49 [0.30-0.79]), urogenital (0.36 [0.18-0.74]) and other (0.38 [0.22-0.66]) bleeding, MI (0.65 [0.45-0.95]) and deaths (0.64 [0.55-0.74]) than the warfarin group. Major bleeding (0.87 [0.74-1.03]) and major GI bleeding (1.13 [0.94-1.37]) was similar between groups and major lower GI bleeding events were more frequent (1.30 [1.04-1.62]) with dabigatran. In conclusion, compared with warfarin, dabigatran treatment was associated with a lower risk of stroke and most outcomes measured, but increased incidence of major lower GI bleeding.

An evaluation of variation in published estimates of schizophrenia prevalence from 1990─2013: a systematic literature review.

BACKGROUND: There is a lack of consistency in findings across studies on the prevalence of schizophrenia, and no recent systematic review of the literature exists. The purpose of this study is to provide an updated systematic review of population-based prevalence estimates and to understand the factors that could account for this variation in prevalence estimates. METHODS: MEDLINE, Embase, and PsycInfo databases were searched for observational studies describing schizophrenia prevalence in general populations from 2003-2013 and supplemented by studies from a prior review covering 1990-2002. Studies reporting prevalence estimates from specialized populations such as institutionalized, homeless, or incarcerated persons were excluded. Prevalence estimates were compared both across and within studies by factors that might contribute to variability using descriptive statistics. RESULTS: Sixty-five primary studies were included; thirty-one (48 %) were from Europe and 35 (54 %) were conducted in samples of ≥50,000 persons. Among 21 studies reporting 12-month prevalence, the median estimate was 0.33 % with an interquartile range (IQR) of 0.26 %-0.51 %. The median estimate of lifetime prevalence among 29 studies was 0.48 % (IQR: 0.34 %-0.85 %). Prevalence across studies appeared to vary by study design, geographic region, time of assessment, and study quality scores; associations between study sample size and prevalence were not observed. Within studies, age-adjusted estimates were higher than crude estimates by 17 %-138 %, the use of a broader definition of schizophrenia spectrum disorders compared to schizophrenia increased case identification by 18 %-90 %, identification of cases from inpatient-only settings versus any setting decreased prevalence by 60 %, and no consistent trends were noted by differing diagnostic criteria. CONCLUSIONS: This review provides updated information on the epidemiology of schizophrenia in general populations, which is vital information for many stakeholders. Study characteristics appear to play an important role in the variation between estimates. Overall, the evidence is still sparse; for many countries no new studies were identified.

Incidence of cardiovascular outcomes and diabetes mellitus among users of second-generation antipsychotics.

OBJECTIVE: To examine the risk of cardiovascular outcomes and diabetes mellitus in patients prescribed second-generation antipsychotics. METHOD: From the MarketScan claims database, nondiabetic adults prescribed aripiprazole between July 2003 and March 2010 were propensity score-matched with patients prescribed olanzapine, quetiapine, risperidone, and ziprasidone. Patients were followed through the claims for International Classification of Diseases, Ninth Revision codes indicating myocardial infarction, stroke, heart failure, coronary bypass/angioplasty procedures, and incident diabetes. Incidence rates of each outcome were calculated and compared between aripiprazole and the other second-generation antipsychotics using Cox models. RESULTS: Aripiprazole initiators were matched 1:1 to 9,917 olanzapine, 14,935 quetiapine, 10,192 risperidone, and 5,696 ziprasidone initiators. Increased risk was found with olanzapine for stroke (hazard ratio = 1.43; 95% confidence interval, 1.05-1.95) and any cardiovascular event (1.28; 1.05-1.55); with quetiapine for stroke (1.58; 1.19-2.09), heart failure (1.55; 1.15-2.11), and any cardiovascular event (1.50; 1.25-1.79); and with risperidone for stroke (1.54; 1.12-2.12), heart failure (1.43; 1.02-1.99), and any cardiovascular event (1.49; 1.21-1.83). Ziprasidone showed no significant difference in risk from aripiprazole for any outcome. Incidence of diabetes ranged from 18 to 21 events per 1,000 person-years in each cohort and did not differ significantly between second-generation drugs. CONCLUSIONS: This analysis of real-world data found lower risk of some cardiovascular events with aripiprazole than with olanzapine, quetiapine, or risperidone, but no differences were found with ziprasidone. There were no significant differences in risk of diabetes. Limitations include use of claims data and inability to adequately control for differential prescribing of second-generation antipsychotics to patients at higher risk of diabetes.

Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer's disease (AD) by geographic region and country. METHODS: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. RESULTS: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5-51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4-10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9-66.7), e4/4 prevalence: 14.1% (95% CI: 12.2-16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. CONCLUSIONS: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.

Over-the-counter ibuprofen and risk of gastrointestinal bleeding complications: a systematic literature review.

BACKGROUND: Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen. OBJECTIVE: To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use. METHODS: Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized. RESULTS: Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose-response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users. CONCLUSIONS: Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful.

Apolipoprotein E ε4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta-analysis.

BACKGROUND: The ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer's disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity. METHODS: A literature review and meta-analysis were conducted to estimate the prevalence of APOE4 by geographic area among AD patients. RESULTS: Although estimates varied significantly by study design and case definition, AD patients recruited in Asian and southern European/Mediterranean communities seemed to have significantly lower E4 carrier status estimates (37 and 43%) than those recruited in North America (58%) or northern Europe (64%; all: p < 0.05). CONCLUSIONS: APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population. Study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.