METHOD: We will search PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, CINAHL Database, and the Cochrane Library using a predefined search strategy. Other sources of literature will include proceedings from the European Society of Cardiology, the American College of Cardiology, the American Heart Association, the EUROPCR, and the ProQuest Dissertations and Theses Database. We will include data from observational studies (case-control and cohort study design) and randomized control trials (that have investigated the relationship of D2B time and clinical outcome(s) in an adult (older than 18) STEMI population). Mortality (cardiac related and all-cause) and incidence heart failure (HF) have been prioritized as the primary outcomes. All eligible studies will be assessed for risk of bias using the Risk Of Bias in Non-randomized Studies - of Interventions tool. The Grading of Recommendations, Assessment, and Evaluation (GRADE) framework will be used to report the quality of evidence and strength of recommendations. We will proceed to analyze the data quantitatively if the pre-specified conditions are satisfied.
DISCUSSION: Recent discussion on the negative findings of improved D2B delay over time being unrelated to better STEMI outcomes at the population level has reminded us of an important knowledge gap we have on this domain. This systematic review will serve to address some of these key questions not previously examined. Answers to these questions could clarify the controversies and offer empirical support for or against the suggested hypotheses.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026069.
METHODS: We implemented a deterministic, prevalence-based mathematical model to project the annual cost of rheumatoid arthritis (RA) management within the public healthcare system in Malaysia. We also calculated the annual productivity loss due to uncontrolled RA in monetary value. Using the projection model, we compared the projected costs of the status quo scenario vs. several scenarios of improved advanced therapy (AT) access over a 5-year period.
RESULTS: We projected that between 10,765 and 11,024 RA patients in Malaysia over the period of 2020-2024 will need access to AT due to treatment failure with conventional synthetic disease modifying antirheumatic drugs (DMARDs). The projected net total medical cost under the status quo scenario were 163.5 million annually on average (approximately MYR 15,000 per patient per year). Cost related to health service utilization represented the heaviest component, amounting to 71.8% followed by drug cost (24.7%). Under the access improvement scenarios, drug cost constituted a higher proportion of the total medical, ranging from 25.6% to 30.4%. In contrast, the cost of health service utilization shown a reverse pattern (reducing to between 66.3% and 70.1%). Productivity costs were also expected to reduce as AT access improved leading to better outcomes. Treatment shifts to targeted synthetic DMARDs in anticipation of price adjustment appeared to have a cost saving advantage to the health system if all other parameters remain unchanged.
DISCUSSION: Improving AT access for RA patients towards the aspirational target appeared to be feasible given the current health budget in Malaysia. Broader socio-economic consequences of productivity and income loss should be included as an important part of the policy consideration. The financial implication of different AT utilization mixes and the anticipated price adjustment will likely result in some cost saving to the health system.
METHODS: This study involved a retrospective analysis of the Health Insurance Review and Assessment (HIRA) database. Patients (≥18 years) who had a new prescription for an overactive bladder (OAB) target medication (mirabegron/antimuscarinic) within an 8-month index period (July 1, 2015-February 29, 2016) were included. The date when the target (index) medication was dispensed was the index date. The 6-month period before the index date was used to assess patient eligibility. A 12-month post-index period was used to assess medication persistence, which was defined as the time to discontinuation. Overall data were analyzed and the results were also stratified by age group (≤65, >65 years), sex, or prior OAB medication experience. Persistence rates were calculated after the 1st, 3rd, 6th, 9th, and 12th months.
RESULTS: A data set of 52 722 cases was obtained (mirabegron: 11 424, antimuscarinics: 41 298). The mean age was 60.9 ± 16.1 years and the majority of the patients were female (30 862 [58.5%] patients). Median persistence was longer with mirabegron (51 days) versus antimuscarinics (25 days). The persistence rate with mirabegron was higher throughout the study compared with all the antimuscarinics (12-month data: 13.5% and 4.9%, respectively). Longer treatment persistence was noted in older, male, and treatment-experienced patients.
CONCLUSION: The results from the HIRA database showed that persistence was longer with mirabegron than with antimuscarinics in South Korea. This finding may help inform clinical decision-making within the South Korean healthcare system.
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.
FUNDING: None.
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.
CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42015026069).
METHODS: A decision tree model was developed based on literature and expert inputs. An epidemiological projection model was then added to the decision tree to calculate the target population size. The budget impact of adapting the different enteral nutrition (EN) formulas was calculated by multiplying the population size with the costs of the formula and ICU length of stay (LOS). A one-way sensitivity analysis (OWSA) was conducted to examine the effect each input parameter has on the calculated output.
RESULTS: Replacing SPF with SEF would lower ICU cost by MYR 1059 (USD 216) per patient. The additional cost of increased LOS due to EFI was MYR 5460 (USD 1114) per patient. If the MOH replaces SPF with SEF for ICU patients with high EFI risk (estimated 7981 patients in 2022), an annual net cost reduction of MYR 8.4 million (USD 1.7 million) could potentially be realized in the MOH system. The cost-reduction finding of replacing SPF with SEF remained unchanged despite the input uncertainties assessed via OWSA.
CONCLUSION: Early use of SEF in ICU patients with high EFI risk could potentially lower the cost of ICU care for the MOH system in Malaysia.