METHODS: We will acquire eligible studies through a systematic search of MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, CINAHL plus, IPA and clinicaltrials.gov website. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are the incidence of CRC, the incidence/recurrence of any adenoma or change in polyp burden (number or size). Quantitative synthesis or meta-analysis will be considered. We will also construct a network meta-analysis (NMA) to improve precision of the comparisons among chemo-preventive interventions by combining direct and indirect evidence. The probability of each treatment being the best and/or safest, the number-needed-to-treat [NNT; 95% credible interval (CrIs)], and the number-needed-to-harm (NNH; 95% CrIs) will be calculated to provide measures of treatment efficacy. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA.

RESULTS: This protocol has been registered (registration number: CRD42015025849) with the PROSPERO (International Prospective Register of Systematic Reviews). The procedures of this systematic review and NMA will be conducted in accordance with the PRISMA-compliant guideline. The results of this systematic review and NMA will be submitted to a peer-reviewed journal for publication.

METHODS: We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131).

FINDINGS: A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors).

INTERPRETATION: Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged.

Methods: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.

Results: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.

METHODS: Four attributes (ie, the scientific proof of effectiveness, the scientific proof of safety, the source of recommendation, and cost) were identified from a systematic review and focus group interviews. They were used to develop a DCE questionnaire. Consumers at community pharmacies in Malaysia were asked to respond to 8 DCE choice sets. A conditional logit model was employed to obtain the relative importance of each attribute and to estimate respondents' WTP for nutraceuticals.

RESULTS: A total of 111 valid responses were analyzed. A negative constant term in the developed model indicated that generally the respondents preferred not to use nutraceuticals before they considered the study attributes. The respondents preferred nutraceuticals with no side effect, clear evidence of effectiveness, and recommendation of a healthcare professional. The respondents were willing to pay $252/month more for nutraceuticals proven with no side effect than for those without proof of safety, and $102/month more for nutraceuticals proven with clear effectiveness than for those without proof of effectiveness.

METHODS: We conducted a systematic review and meta-analysis of prospective observational studies that have investigated the relationship of door-to-balloon delay and clinical outcomes. The main outcomes include mortality and heart failure.

RESULTS: 32 studies involving 299 320 patients contained adequate data for quantitative reporting. Patients with ST-elevation MI who experienced longer (>90 min) door-to-balloon delay had a higher risk of short-term mortality (pooled OR 1.52, 95% CI 1.40 to 1.65) and medium-term to long-term mortality (pooled OR 1.53, 95% CI 1.13 to 2.06). A non-linear time-risk relation was observed (P=0.004 for non-linearity). The association between longer door-to-balloon delay and short-term mortality differed between those presented early and late after symptom onset (Cochran's Q 3.88, P value 0.049) with a stronger relationship among those with shorter prehospital delays.

CONCLUSION: Longer door-to-balloon delay in primary percutaneous coronary intervention for ST-elevation MI is related to higher risk of adverse outcomes. Prehospital delays modified this effect. The non-linearity of the time-risk relation might explain the lack of population effect despite an improved door-to-balloon time in the USA.

OBJECTIVE: This systematic review aims to provide a critical summary of EEs of PCVs and identify key drivers of EE findings in LMICs.

METHODS: We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from their inception to 30 September 2015 and limited the search to LMICs. The search was undertaken using the search strings 'pneumococc* AND conjugat* AND (vaccin* OR immun*)' AND 'economic OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-effectiveness OR cost-benefit OR cost-utility' in the abstract, title or keyword fields. To be included, each study had to be a full EE of a PCV and conducted for an LMIC. Studies were extracted and reviewed by two authors. The review involved standard extraction of the study overview or the characteristics of the study, key drivers or parameters of the EE, assumptions behind the analyses and major areas of uncertainty.

RESULTS: Out of 134 records identified, 22 articles were included. Seven studies used a Markov model for analysis, while 15 studies used a decision-tree analytic model. Eighteen studies performed a cost-utility analysis (CUA), with disability-adjusted life-years, quality-adjusted life-years or life-years gained as a measure of health outcome, while four studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA findings were provided by eight studies. Herd effects and serotype replacement were considered in 10 and 13 studies, respectively. The current evidence shows that both the 10-valent and 13-valent PCVs are probably cost effective in comparison with the 7-valent PCV or no vaccination. The most influential parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22 studies). The findings were found to be supportive of the products owned by the manufacturers.

OBJECTIVES: Our study used data from the most recent network meta-analysis (NMA) and local parameters to assess the cost effectiveness of non-statin agents in statin-treated patients with a history of CVD.

METHODS: A published Markov model was adopted to investigate lifetime outcomes: (1) number of recurrent CVD events prevented, (2) quality-adjusted life-years (QALYs) gained, (3) costs and (4) incremental cost-effectiveness ratios (ICERs) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe added to statin therapy. Event rates and effectiveness inputs were obtained from the NMA. Cost and utility data were gathered from published studies conducted in Thailand. A series of sensitivity analyses were performed.

RESULTS: Patients receiving PCSK9i and ezetimibe experienced fewer recurrent CVD events (number needed to treat [NNT] 17 and 30) and more QALYs (0.168 and 0.096 QALYs gained per person). However, under the societal perspective and at current acquisition costs in 2018, ICERs of both agents were $US1,223,995 and 27,361 per QALY gained, respectively. Based on threshold analyses, the costs need to be reduced by 97 and 85%, respectively, for PCSK9i and ezetimibe to be cost-effective.

METHODS: The review protocol was registered on PROSPERO (CRD42022270039), and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Relevant studies were identified through searches in six generic and specialized bibliographic databases, i.e. PubMed, Embase, NHS Economic Evaluation Database, PsycINFO, Health Economic Evaluations Database, tufts CEA registry and EconLit, from their inception to 23 October 2022. The cost-effectiveness of adherence interventions is represented by the incremental cost-effectiveness ratio (ICER). The quality of studies was assessed using the quality of the health economics studies (QHES) instrument. Data were narratively synthesized in the form of tables and texts. Due to the heterogeneity of the data, a permutation matrix was used for quantitative data synthesis rather than a meta-analysis.

RESULTS: Fifteen studies, mostly conducted in North America (8/15 studies), were included in the review. The time horizon ranged from a year to a lifetime. Ten out of 15 studies used a micro-simulation, 4/15 studies employed Markov and 1/15 employed a dynamic model. The most commonly used interventions reported include technology based (5/15), nurse involved (2/15), directly observed therapy (2/15), case manager involved (1/15) and others that involved multi-component interventions (5/15). In 1/15 studies, interventions gained higher quality-adjusted life years (QALYs) with cost savings. The interventions in 14/15 studies were more effective but at a higher cost, and the overall ICER was well below the acceptable threshold mentioned in each study, indicating the interventions could potentially be implemented after careful interpretation. The studies were graded as high quality (13/15) or fair quality (2/15), with some methodological inconsistencies reported.

METHODS: A state-transition microsimulation model was developed to compare the clinical and economic outcomes of 4 treatments: standard care, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists. Cost-effectiveness was assessed from a healthcare provider's perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of people with T2D. Data input were informed from literature and local data when available. Outcome measures include costs, quality-adjusted life-years, incremental cost-effectiveness ratios, and net monetary benefits. Univariate and probabilistic sensitivity analyses were performed to assess uncertainties.

RESULTS: Over a lifetime horizon, the costs to treat a person with T2D ranged from RM 12 494 to RM 41 250, whereas the QALYs gains ranged from 6.155 to 6.731, depending on the treatment. Based upon a willingness-to-pay threshold of RM 29 080 per QALY, we identified SGLT2i as the most cost-effective glucose-lowering treatment, as add-on to standard care over patient's lifetime, with the net monetary benefit of RM 176 173 and incremental cost-effectiveness ratios of RM 12 279 per QALY gained. The intervention also added 0.577 QALYs and 0.809 LYs compared with standard care. Cost-effectiveness acceptability curve showed that SGLT2i had the highest probability of being cost-effective in Malaysia across varying willingness-to-pay threshold. The results were robust to various sensitivity analyses.