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Objectives To perform a systematic review and meta-analysis to pool the incremental net benefit (INB) of each herpes zoster vaccine (i.e., Zoster Vaccine Live (ZVL) and Recombinant Zoster Vaccine (RZV)). Methods We initially identified individual studies by hand-searching reference lists of the relevant systematic review articles. An updated comprehensive search was performed in Medline, Scopus, and Embase until June 2020 for additional studies. Studies were eligible if they assessed the cost-effectiveness/utility of any pair among ZVL and RZV, and no vaccine and reported economic outcomes. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. INB was calculated with monetary units adjusting for purchasing power parity for 2019 US dollars and pooled by meta-analysis. Results A total of 37 studies were pooled for meta-analysis stratified by perspectives (i.e., societal (SP) and third-party payer (TPP)) and vaccine types. In SP, ZVL was cost-effective compared to no vaccine when vaccinated at ages of 50-59 and 70-79 years with INBs (95% CI) of $0.61 (0.37, 0.85) and $9.67 (5.20, 14.14), respectively. RZV was cost-effective for those aged 60-69 and 70-79 years with INBs of $75.61 (17.98, 133.23) and $85.01 (30.02, 140.01), respectively. In TPP, ZVL was cost-effective compared to no vaccine when vaccinated at age 70-79 years with INB of $7.57 (0.27, 14.86) and RZV was cost effective at 60-69 years with INB $220.87 (47.80, 393.93). The cost-effectiveness of RZV was robust across series of sensitivity analyses, but ZVL differs on different vaccination ages. Conclusions RZV may be cost-effective for vaccination in ages of 60-79 years for both SP and TPP perspectives, while ZVL might be cost-effective in some age groups, but results are not robust.

Backgound: The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted. Methods: A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al. Two reviewers independently extracted the following data: the author’s name, year of publication, ethnicity, drugs, diseases, genetic polymorphisms, onset, type of myelosuppression and results of Hardy-Weinberg equilibrium. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of NUDT15 and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by NUDT15 genetic polymorphisms was performed. Results: A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia in Asian populations were 11.43 (95% CI 7.11–18.35) and 16.35 (95% CI 10.20–26.22). Among NUDT15 polymorphisms, NUDT15*3 showed a significantly increased risk of early leukopenia (OR 15.31; 95% CI 9.65–24.27) and early neutropenia (OR 15.85; 95% CI 8.80–28.53). A significantly higher thiopurine-induced early neutropenic risk was also found for NUDT15*2 (OR 37.51; 95% CI 1.99–708.69). Whereas, NUDT15*5 and NUDT15*6 variants showed a lower risk of leukopenia. Conclusion: This study suggests that NUDT15*3 and NUDT15*2 are important genetic markers of thiopurine-induced early onset of myelotoxicity in Asians, therefore, early detection of these variants before initiating thiopurine therapy is necessary.

New oral anticoagulants (NOACs; ie, direct thrombin inhibitor [DTI] and factor Xa [FXa] inhibitors) were used as alternatives to warfarin. Specific antidotes (idarucizumab for dabigatran and andexanet alfa for FXa inhibitors) and hemostatic reversal agents were used for lowering bleeding, but their efficacies were still uncertain. The objectives of this study were to estimate and compare the efficacy of NOAC antidotes on bleeding reversal and death. Studies were identified from MEDLINE and Scopus databases until May 2018. Case reports/series and cohorts were selected if they assessed reversal or death rates. Data were independently extracted by 2 reviewers. Individual patient data and aggregated data of outcomes were extracted from case reports/series and cohorts. Binary regression was used to estimate outcome rates, risk ratio (RR) along with 95% confidence interval (CI). Interventions were NOACs and reversal agents (ie, DTI-specific, DTI-standard, FXa-specific, and FXa-standard). Among 220 patients of 93 case reports/series, reversal rates were 95.9%, 77.6%, and 71.5% for DTI-specific, FXa-standard, and DTI-standard. Pooled RRs for DTI-specific and FXa-standard versus DTI-standard, respectively, were 1.34 (CI: 1.13-1.60) and 1.09 (CI: 0.84-1.40). Death rate was 0.18 (CI: 0.06-0.57) times lower in DTI-specific versus DTI-standard. For pooling 10 subcohorts, pooled RRs were 1.08 (CI: 1.00-1.16), 1.29 (CI: 1.20-1.39), and 1.13 (CI: 1.01-1.25) for DTI-specific, FXa-specific, and FXa-standard versus DTI-standard. In conclusion, specific reversal agents might be useful for reversal of bleeding and lowering the risk of death than standard reversal agents. Our findings were based on case reports/series and selected cohorts, further comparative studies are thus needed.

Background Widespread use of prescription opioids is associated with adverse outcomes. Objective To identify factors associated with adverse health outcomes and health care use using a statewide health information exchange. Methods This is a retrospective cohort study using the Indiana Network for Patient Care. Adult opioid-naive patients who received an opioid prescription between January 2012 and December 2017 were included. The outcomes included (1) a composite outcome of any combination of opioid abuse, dependence, or overdose, (2) all-cause mortality, and (3) health care use. Independent variables included opioid dosage, dispensed amount, days supply, concurrent use of short-acting (SA) and long-acting (LA) opioids, and concurrent use with benzodiazepine or gabapentinoids. Additional variables included patients’ age, sex, race, modified Charlson Comorbidity Index score, mental health conditions, and medications for opioid use disorders. Factors associated with composite outcome and mortality were identified using Cox proportional hazards and reported as adjusted hazard ratio (aHR) and 95% CI. Factors associated with health care use were identified using Poisson regression and reported as adjusted incidence rate ratio (aIRR) and 95% CI. Results 1,328,287 opioid prescriptions were identified for 341,722 patients. Opioid-related factors associated with the composite outcome, mortality, and hospitalizations, respectively, included opioid dosage (aHR 1.003 [95% CI 1.001–1.006]; aHR not applicable; aIRR 1.07 [1.06–1.08]), opioid days supply (aHR 1.03 [1.02–1.03]; aHR 1.009 [1.005–1.014]; aIRR 0.94 [0.92–0.96]), concurrent SA/LA opioids (aHR 2.12 [1.78–2.54]; aHR 1.40 [1.14–1.70]; aIRR 1.40 [1.37–1.42]), and use of benzodiazepines/gabapentinoids (aHR 1.68 [1.38–2.04]; aHR 1.23 [1.01–1.51]; aIRR 1.25 [1.23–1.27]). Conclusion Many factors are associated with poor health outcomes, especially concurrent use of SA and LA opioids and overlapping prescriptions of opioids with benzodiazepines or gabapentinoids. Identification of factors associated with adverse outcomes may help identify patients at risk for poor outcomes and could inform possible interventions.

Widespread use of prescription opioids has been a major public health concern since 1999. Many consequences are associated with the problem, such as opioid misuse, abuse, and drug overdose deaths. Opioids are not the only medications involved with drug overdose deaths. Due to stricter control of prescription opioids, those who misused opioids are associated with initiation of another illicit drug abuse. This results in increased drug overdose death involving heroin and semisynthetic/synthetic opioids. Another risk factor for increased overdose death is concurrent use of opioids with other central nervous system (CNS) depressants and some anticonvulsants. Concurrent use of opioids and benzodiazepine, z-drugs (zolpidem and zaleplon), gabapentin, and/or pregabalin is associated with increased risk of respiratory depression and drug overdose death. To combat problematic opioid use, many mitigation strategies were introduced. However, opioid-related problems remain.

Supplemental Material, Appendix_revise_11-06-2018 for The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis by Sariya Udayachalerm, Sasivimol Rattanasiri, Teeranan Angkananard, John Attia, Nakarin Sansanayudh, and Ammarin Thakkinstian in Clinical and Applied Thrombosis/Hemostasis