Disparities in ABO blood type determination across diverse ancestries: a systematic review and validation in the All of Us Research Program.

OBJECTIVES: ABO blood types have widespread clinical use and robust associations with disease. The purpose of this study is to evaluate the portability and suitability of tag single-nucleotide polymorphisms (tSNPs) used to determine ABO alleles and blood types across diverse populations in published literature. MATERIALS AND METHODS: Bibliographic databases were searched for studies using tSNPs to determine ABO alleles. We calculated linkage between tSNPs and functional variants across inferred continental ancestry groups from 1000 Genomes. We compared r2 across ancestry and assessed real-world consequences by comparing tSNP-derived blood types to serology in a diverse population from the All of Us Research Program. RESULTS: Linkage between functional variants and O allele tSNPs was significantly lower in African (median r2 = 0.443) compared to East Asian (r2 = 0.946, P = 1.1 × 10-5) and European (r2 = 0.869, P = .023) populations. In All of Us, discordance between tSNP-derived blood types and serology was high across all SNPs in African ancestry individuals and linkage was strongly correlated with discordance across all ancestries (ρ = -0.90, P = 3.08 × 10-23). DISCUSSION: Many studies determine ABO blood types using tSNPs. However, tSNPs with low linkage disequilibrium promote misinference of ABO blood types, particularly in diverse populations. We observe common use of inappropriate tSNPs to determine ABO blood type, particularly for O alleles and with some tSNPs mistyping up to 58% of individuals. CONCLUSION: Our results highlight the lack of transferability of tSNPs across ancestries and potential exacerbation of disparities in genomic research for underrepresented populations. This is especially relevant as more diverse cohorts are made publicly available.

Comparative efficacy of later-line therapies for metastatic colorectal cancer: a network meta-analysis of survival curves.

INTRODUCTION: We evaluated the comparative efficacy of 6 later-line (≥3) therapies for metastatic colorectal cancer (mCRC) over placebo. We applied a novel statistical method of reconstructing pseudo patient-level data (pseudo-IPD) to inform a network meta-analysis of survival curves that considers shape in addition to scale parameters. METHODS: A literature search yielded 10 phase II/III trials. We digitized all survival curves and applied a novel method incorporating curve coordinates, patients-at-risk, and events reported to generate pseudo-IPD. Using fitted random effects lognormal distributions, we estimated the survival proportions and HRs(95CrI) of progression-free (PFS) and overall survival(OS) over 12 months of follow-up. RESULTS: Compared to placebo, in ascending order, 12-month OS HRs were 0.50(95%CrI = 0.35, 0.69; PFS = 0.11(95%CrI = 0.06, 0.14)) for TAS+bevacizumab; 0.71(95%CrI = 0.51, 0.97; PFS = 0.26(95%CrI = 0.16, 0.41)) for regorafenib; 0.75(95%CrI = 0.61, 0.91; (PFS = 0.24(95%CrI = 0.17, 0.31)) for TAS-102; 0.80(95%CrI = 0.79, 0.90; PFS = 0.18(95%CrI = 0.13, 0.24)) for fruquintinib; 0.83(95%CrI = 0.50, 0.99; PFS = 0.42(95%CrI = 0.20, 0.75)) for atezolizumab+cobimetinib; and 1.03(95%CrI = 0.55, 1.65; PFS = 0.67(95%CrI = 0.29, 1.01)) for atezolizumab. CONCLUSION: In this independent NMA of survival data all later-line mCRC therapies but atezolizumab monotherapy exhibited superiority in 12-month PFS and OS over placebo. TAS+bevacizumab emerged as the most dominant option and may be the preferred choice; with fruquintinib, regorafenib and TAS-102 monotherapy showing statistically significant but lower PFS and OS benefits. REGISTRATION: PROSPERO: CRD42022371953.

Adverse effects of nonsteroidal anti-inflammatory drugs in critically ill patients: A scoping review.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often recommended as opioid-sparing agents. The objective of this scoping review was to conduct a thorough search of the current literature to determine whether in adult critically ill patients there is an association between exposure to NSAIDs vs no NSAIDs and the subsequent development of serious adverse events, particularly gastrointestinal bleeding and acute kidney injury (AKI). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews was utilized as a guideline for reporting. Searches were performed in PubMed (National Library of Medicine), Cochrane Library (Wiley), EMBASE (Elsevier), Stat!Ref (Teton), and Access Pharmacy (McGraw Hill) for articles published from January 2016 to August 2022. RESULTS: Of the 3,062 citations and titles identified in the search, 2,737 titles remained after removal of duplicates, 2,588 were excluded at title and abstract screening, and 149 articles remained for full-text review. None of the studies involved heterogeneous groups of critically ill patients in nonspecialty intensive care unit settings. Most studies evaluated were conducted in the perioperative setting and had limited adverse events reporting, particularly with respect to serious NSAID-related adverse effects of concern in critically ill patients. CONCLUSION: In published studies primarily involving perioperative patients, there is insufficient detail concerning the definitions and reporting of NSAID-related serious adverse events such as bleeding and AKI. These events are of particular concern in heterogeneous critically ill patient populations predisposed to such complications. In most (if not all) critically ill patients, sustained dosing of NSAIDs should be avoided regardless of COX-1 selectivity due to the paucity of safety data.

Understanding the information-seeking behavior of pharmacy college faculty, staff, and students: implications for improving embedded librarian services.

OBJECTIVE: Research was conducted on the embedded librarian program at The University of Arizona College of Pharmacy and the Health Sciences Library to understand how this service is relevant to users and identify the potential for further improvement. This study examined users' information-seeking behaviors and considered the implications for the effectiveness of the embedded librarian service. METHODS: The authors conducted 18 semi-structured interviews of faculty, researchers, and students at the College of Pharmacy to obtain descriptive accounts of how they seek information, manage information, and use the library and library services. The authors examined the interview transcripts through qualitative descriptive analysis. RESULTS: The interview responses confirm that users seek information outside of the physical library and tend to ask their peers for information or assistance in obtaining information. They mostly feel comfortable in searching, but some of them may lack sufficient search skills and tend to use a few known databases. While those who are familiar with the librarian seek the librarian's assistance more often, others tend not to seek the librarian's assistance. The ways they manage information vary, which requires customized assistance. CONCLUSIONS: The close proximity of a physically embedded librarian is beneficial to users and positions the librarian to provide proactive assistance in the existing user information-seeking behavior environment. While some users do not seek assistance, the embedded librarian can provide proactive assistance in such areas as making users aware of other database options and helping them choose relevant databases and effectively manage information.

Impact of Telehealth Interventions on Medication Adherence for Patients With Type 2 Diabetes, Hypertension, and/or Dyslipidemia: A Systematic Review.

OBJECTIVE: To describe telehealth interventions and determine their effect on medication adherence for patients with type 2 diabetes, hypertension, and/or dyslipidemia. DATA SOURCES: PubMed/MEDLINE, EMBASE, Cochrane, CINAHL Plus, PsycINFO, Academic Search Ultimate, International Pharmaceutical Abstracts, Scopus, Web of Science, WHO Global Index Medicus, association websites, and gray literature were searched from January 1, 1998, to December 31, 2019. STUDY SELECTION AND DATA EXTRACTION: Eligible studies reported eHealth, mobile health, and telehealth interventions for adult patients prescribed medications for chronic condition management (eg, type 2 diabetes, hypertension, and/or dyslipidemia). Studies were required to evaluate medication adherence outcomes (eg, medication possession ratio [MPR], proportion of days covered (PDC)]. Randomized controlled trials, cohort studies, and controlled before-and-after studies were included. Multiple reviewers independently extracted data and evaluated risk of bias. DATA SYNTHESIS: Of 8693 studies identified, 13 reported either an MPR or PDC and were included in the systematic review. The systematic review demonstrated that electronic health (eHealth) and telehealth interventions were successful at improving medication adherence, whereas mobile health interventions did not improve medication adherence. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This systematic review highlighted the available research and findings of studies assessing interventions to improve medication nonadherence among patients with type 2 diabetes, hypertension, and/or dyslipidemia. The evaluated findings lend support to the need for targeted medication adherence interventions based on patient population and practice settings. CONCLUSIONS: Telehealth modalities include telephonic outreach and specialized tools designed to increase health literacy. eHealth and telehealth medication adherence interventions were associated with improved MPR and/or PDC rates.

Evaluation of drug information resources for interactions between therapeutic drugs and drugs of abuse.

OBJECTIVE: The study evaluated point-of-care resources for scope, completeness, and consistency of information describing interactions between therapeutic drugs and drugs of abuse (DoA). METHODS: A cross-sectional evaluation study was conducted focusing on seven resources: Clinical Pharmacology, Facts & Comparisons eAnswers, Lexicomp Online, Micromedex, Drug Interactions Analysis and Management, Drug Interaction Facts, and Stockley's Drug Interactions. A sample of clinically relevant interactions was developed through review of tertiary literature and resources, and input was solicited from subject matter experts. Entries from each resource for each interaction were evaluated for scope (i.e., whether there was an entry for the interaction); completeness (i.e., whether there was information addressing mechanism; clinical effects, severity, course of action, and level of certainty, described as a median rating on a 5-point scale); and consistency (i.e., whether the information in the resource was similar to the majority) among resources with an entry. RESULTS: Following review by subject matter experts, the final sample contained 159 interactions. Scope scores ranged from 0.6% (Drug Interactions Analysis and Management) to 43.4% (Lexicomp Online). Completeness scores ranged from 2 (interquartile range [IQR] 0 to 3, Stockley's Drug Interactions) to 5 (IQR 5 to 5, Drug Interaction Facts, Micromedex, Facts & Comparisons eAnswers). Consistency scores ranged from 30.8% (Stockley's Drug Interactions) to 87.1% (Clinical Pharmacology) for severity and from 15.4% (Facts & Comparisons eAnswers) to 71.4% (Drug Interaction Facts) for course of action. CONCLUSIONS: Although coverage of drug-DoA interactions was low and content was often inconsistent among resources, the provided information was generally complete.

Corticosteroid Tapering Regimens in Rheumatic Disease: A Systematic Review.

BACKGROUND/OBJECTIVE: Corticosteroids have long been used to effectively treat rheumatic disorders, but adverse effects associated with extended-duration regimens generate disagreement among clinicians regarding optimal tapering strategies. The objective of this systematic review was to assess clinical outcomes of differing tapering regimens after corticosteroid monotherapy in adults with rheumatic disorders. METHODS: A systematic review of Medline/PubMed, Embase, Cochrane, International Pharmaceutical Abstracts, Web of Science, Scopus, Global Index Medicus, American College of Rheumatology, gray literature, and reference lists up to June 27, 2018, was conducted by 2 authors. Randomized controlled trials, case-control studies, and prospective observational studies comparing at least 2 tapering strategies of medium- to high-dose (>7.5 mg but ≤100 mg oral prednisone equivalent daily), extended-duration (≥10 days) corticosteroids were included if they reported at least 1 efficacy and 1 adverse effect parameter. RESULTS: Two studies met criteria for the review, which included 62 patients. One study examined a prednisolone versus a modified release prednisone taper for giant cell arteritis and suggested 80% (n = 4) and 85.7% (n = 6) remission rates, respectively, at 26 weeks. The other study examined a methylprednisolone versus a prednisone taper for polymyalgia rheumatica and reported 100% and 89% remission rates, respectively, at 26 weeks. Adverse effects reported between the 2 studies included sleep, hyperglycemia, infection, and fractures. However, the studies were not powered to detect differences in these outcomes. CONCLUSIONS: There is no high-level evidence to guide tapering until discontinuation after extended courses of medium- to high-dose treatment regimens, as current guidelines rely heavily on expert opinion and small case series with a trial-and-error approach. This review supports the need for additional research to shift tapering recommendations to a more evidence-based practice.

Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis.

Objectives: To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I2 = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I2 = 87.9%).Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.

Melatonin for the prevention of postoperative delirium in older adults: a systematic review and meta-analysis.

BACKGROUND: Older surgical patients are at high risk of developing postoperative delirium. Non-pharmacological strategies are recommended for delirium prevention, but no pharmacological agents have compelling evidence to decrease the incidence of delirium. The purpose of this study was to assess whether perioperative melatonin decreases the incidence of delirium in older adults undergoing surgical procedures. METHODS: A systematic search using PubMed/Medline, Embase, PsycINFO, CINAHL, and references of identified articles published in English between January 1990 and October 2017 was performed. Two independent reviewers screened titles and abstracts, and then extracted data following a full-text review of included articles with consensus generation and bias assessment. Studies reporting outcomes for melatonin or ramelteon use to prevent delirium in postoperative hospitalized patients (mean age ≥ 50 years) were eligible for inclusion. Data were pooled using a fixed-effects model to generate a forest plot and obtain a summary odds ratio for the outcome of interest (delirium incidence). Cochran's Q and I2 values were used to investigate heterogeneity. RESULTS: Of 335 records screened, 6 studies were selected for the qualitative analysis and 6 were included in the meta-analysis (n = 1155). The mean age of patients in included studies ranged from 59 to 84 years. Patients in intervention groups typically received melatonin or ramelteon at daily doses of two to eight milligrams around cardiothoracic, orthopedic, or hepatic surgeries for one to nine days, starting on the evening before or the day of surgery. The incidence of delirium ranged from 0 to 30% in the intervention groups versus 4-33% in the comparator groups, and was significantly reduced in the melatonin group, with a summary effect of the meta-analysis yielding an odds ratio of 0.63 (95% CI 0.46 to 0.87; 0.006; I2 = 72.1%). A one study removed analysis reduced overall odds ratio to 0.310 (95% CI 0.19 to 0.50), while reducing heterogeneity (Cochran's Q = 0.798, I2 = 0.000). CONCLUSION: Perioperative melatonin reduced the incidence of delirium in older adults in the included studies. While optimal dosing remains an unanswered question, the potential benefit of melatonin and melatonin receptor agonists may make them a reasonable option to use for delirium prevention in older adults undergoing surgical procedures.

The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta-analysis.

BACKGROUND: A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. RESULTS: A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. CONCLUSIONS: There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.

Use of multidomain management strategies by community dwelling adults with chronic pain: evidence from a systematic review.

Background and aims Multidomain strategies (i.e. two or more strategies) for managing chronic pain are recommended to avoid excessive use of opioids while producing the best outcomes possible. The aims of this systematic review were to: 1) determine if patient-reported pain management is consistent with the use of multidomain strategies; and 2) identify the role of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) in patient-reported pain management. Methods Bibliographic databases, websites, and reference lists of included studies were searched to identify published articles reporting community-based surveys of pain self-management from January 1989 to June 2017 using controlled vocabulary (and synonyms): pain; self-care; self-management; self-treatment; and adult. Two independent reviewers screened studies and extracted data on subject demographics, pain characteristics, pain self-management strategies, and pain outcomes. Pain self-management strategies were organized according to our conceptual model. Included studies were assessed for risk of bias. Differences between the researchers were resolved by consensus. Results From the 3,235 unique records identified, 18 studies published between 2002 and 2017 from 10 countries were included. Twenty-two types of pharmacological strategies were identified (16 prescription, six non-prescription). NSAIDs (15 studies, range of use 10-72%) and opioids (12 studies, range of use 5-72%) were the most commonly reported prescription pharmacological strategies. Other prescription pharmacological strategies included analgesics, acetaminophen, anticonvulsants, antidepressants, anxiolytics, salicylates, ß-blockers and calcium channel blockers, disease-modifying anti-rheumatic drugs and steroids, muscle relaxants, topical products, triptans, and others. Twenty-two types of non-pharmacological strategies were identified: four medical strategies (10 studies), 10 physical strategies (15 studies), four psychological strategies (12 studies), and four self-initiated strategies (15 studies). Medical strategies included consulting a medical practitioner, chiropractic, and surgery. Physical strategies included exercise, massage, hot and cold modalities, acupuncture, physical therapy, transcutaneous electrical nerve stimulation, activity modification or restriction, assistive devices, and altering body position/posture. Psychological strategies included relaxation, prayer or meditation, therapy, and rest/sleep. Self-initiated strategies included dietary or herbal supplements, dietary modifications, and complementary and alternative medicine. Overall, the number of strategies reported among the studies ranged from five to 28 (out of 44 identified strategies). Limited data on pain outcomes was reported in 15 studies, and included satisfaction with pain management strategies, pain interference on daily activities, adverse events, lost work or restricted activity days, emergency department visits, and disabilities. Conclusions A wide variety and large number of pharmacological and non-pharmacological strategies to manage chronic pain were reported, consistent with the use of multidomain strategies. High levels of use of both NSAIDs and opioids also were reported. Implications Comprehensive review and consultation with patients about their pain management strategies is likely needed for optimal outcomes. Additional research is needed to determine: how many, when, and why multidomain strategies are used; the relationship between opioid use, multidomain management strategies, and level of pain; how multidomain strategies relate to outcomes; and if adding strategies to a pain management plan increases the risk of adverse events or interactions, and increases an individuals pain management burden.

BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis.

Background: Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. Methods: We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Results: Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. Conclusion: The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.

Systematic review and meta-analysis of community pharmacy error rates in the USA: 1993-2015.

IMPORTANCE: While much is known about hospital pharmacy error rates in the USA, comparatively little is known about community pharmacy dispensing error rates. OBJECTIVE: The aim of this study was to determine the rate of community pharmacy dispensing errors in the USA. METHODS: English language, peer-reviewed observational and interventional studies that reported community pharmacy dispensing error rates in the USA from January 1993 to December 2015 were identified in 10 bibliographic databases and topic-relevant grey literature. Studies with a denominator reflecting the total number of prescriptions in the sample were necessary for inclusion in the meta-analysis. A random effects meta-analysis was conducted to estimate an aggregate community pharmacy dispensing error rate. Heterogeneity was assessed using the I2 statistic prior to analysis. RESULTS: The search yielded a total of 8490 records, of which 11 articles were included in the systematic review. Two articles did not have adequate data components to be included in the meta-analysis. Dispensing error rates ranged from 0.00003% (43/1 420 091) to 55% (55/100). The meta-analysis included 1 461 128 prescriptions. The overall community pharmacy dispensing error rate was estimated to be 0.015 (95% CI 0.014 to 0.018); however, significant heterogeneity was observed across studies (I2=99.6). Stratification by study error identification methodology was found to have a significant impact on dispensing error rate (p<0.001). CONCLUSION AND RELEVANCE: There are few published articles that describe community pharmacy dispensing error rates in the USA. Thus, there is limited information about the current rate of community pharmacy dispensing errors. A robust investigation is needed to assess dispensing error rates in the USA to assess the nature and magnitude of the problem and establish prevention strategies.

Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses.

PURPOSE: The findings from the observational studies comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban). METHODS: The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance-weighted random effects models. FINDINGS: A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57-1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83-1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67-0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59-1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66-0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77-1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40-1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59-1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding. IMPLICATIONS: Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

Impact of Diabetes Care by Pharmacists as Part of Health Care Team in Ambulatory Settings: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a comprehensive systematic review and meta-analyses examining the impact of pharmacist interventions as part of health care teams on diabetes therapeutic outcomes in ambulatory care settings. DATA SOURCES: PubMed/MEDLINE, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, Web of Science, Scopus, WHO's Global Health Library, ClinicalTrials.gov , and Google Scholar were searched (1995 to February 2017). Search terms included pharmacist, team, and diabetes. STUDY SELECTION: Full-text articles published in English with comparative designs, including randomized controlled trials, nonrandomized controlled trials, and pretest-posttest studies evaluating hemoglobin A1C (A1C), were assessed. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened for study inclusion and extracted data. Quality of the studies was assessed using tools developed based on the framework of the Cochrane Collaboration's recommendations. DATA SYNTHESIS: A total of 1908 studies were identified from the literature and reference searches; 42 studies were included in the systematic review (n = 10 860) and 35 in the meta-analyses (n = 7417). Mean age ranged from 42 to 73 years, and 8% to 100% were male. The overall standardized mean difference (SMD) for A1C for pharmacist care versus comparison was 0.57 ( P < 0.01), a moderate effect representing a mean difference of 1.1% (95% CI = 0.88-1.27). The effects for systolic blood pressure and low-density lipoprotein cholesterol were between small and moderate (SMD = 0.31 and 0.32; P < 0.01). The heterogeneity was high for all outcomes (>83%), indicating functional differences among the studies. No publication bias was detected. CONCLUSION: Pharmacists' interventions as part of the patient's health care team improved diabetes therapeutic outcomes, substantiating the important role of pharmacists in team-based diabetes management.

Ketamine for Analgosedation in the Intensive Care Unit: A Systematic Review.

OBJECTIVE: To evaluate the evidence for the use of intravenous ketamine for analgosedation in the intensive care unit. METHODS: MEDLINE and EMBASE were queried from inception until July 2015. Search terms used included ketamine, intensive care, and critical care. The search retrieved 584 articles to be screened for inclusion. The intent was to include randomized controlled studies using sustained intravenous infusions (>24 hours) of ketamine in the critically ill patients. RESULTS: One trial evaluated opioid consumption as an outcome in postoperative critically ill patients who were randomized to ketamine or saline infusions. The mean cumulative morphine consumption at 48 hours was significantly lower in the ketamine group (58 ± 35 mg) compared to the morphine-only group (80 ± 37 mg; P < .05). Other trials showed the potential safety of ketamine in terms of cerebral hemodynamics in patients with traumatic brain injury, improved gastrointestinal motility, and decreased vasopressor requirements. The observational study and case reports suggest that ketamine is safe and effective and may have a role in patients who are refractory to other therapies. CONCLUSION: Ketamine use may decrease analgesic consumption in the intensive care unit. Additional trials are needed to further delineate the role of ketamine for analgosedation.

An Embedded Librarian Program: Eight Years On.

This article examines an embedded librarian program eight years after implementation in a large academic health center. Librarians were physically moved into the colleges of pharmacy, public health, and nursing. Statistics are reported as well as comments from the participating librarians and faculty members. Strong relationships have been built between librarians, faculty members, and students. Locating the librarians among faculty and students led to a better understanding of client needs and an increased awareness of librarian competencies and services resulting in partnerships and greater utilization of library services.