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Aim: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea. Methods: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method. Results: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% (n = 43/77) achieved a clinical response and 18.2% (n = 14/77) achieved clinical remission. At week 14, 73.2% (n = 52/71) achieved a clinical response and 39.4% (n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% (n = 43/105) and 49.5% (n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785). Conclusions: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

ObjectiveThis study aims to determine the relationship between door-to-balloon delay in primary percutaneous coronary intervention and ST-elevation myocardial infarction (MI) outcomes and examine for potential effect modifiers.MethodsWe 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.Results32 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.ConclusionLonger 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 registrationPROSPERO (CRD42015026069).

Background: Influenza is a contagious respiratory illness responsible for seasonal epidemics and with potential to cause pandemics. The decline in influenza-related studies published since 2018 resulted in data gaps, particularly in emerging markets. Methods: This systematic review searched for studies in six databases and gray literature sources to define the clinical burden of influenza and influenza-like illness (ILIs) and their associated sequelae among humans across emerging markets. Eligible studies were published in English, Spanish, or Chinese between January 2018 and September 2023 and conducted in Asia, the Middle East, Africa, and Latin America. Results: In total, 256 articles were included, mostly on lab-confirmed influenza infections (n = 218). Incidences of lab-confirmed influenza cases in Asia (range 540–1279 cases/100,000 persons) and Sub-Saharan Africa (range 34,100–47,800 cases/100,000 persons) were higher compared to Latin America (range 0.7–112 cases/100,000 persons) and the Middle East and North Africa (range 0.1–10 cases/100,000 persons). Proportions of lab-confirmed influenza cases and influenza-associated outcomes (i.e., hospitalization, ICU admission and death) varied widely across regions. Temporal variation in influenza trend was observed before and during the COVID-19 pandemic. Conclusions: In conclusion, influenza causes significant disease burden in emerging markets. Robust large real-world studies using a similar methodology are needed to have more accurate estimates and compare studies within age groups and regions. Continuous monitoring of influenza epidemiology is important to inform vaccine programs in emerging markets with heavy influenza disease burden.

Alterations in the three chemosensory modalities—smell, taste, and chemesthesis—have been implicated in Coronavirus Disease 2019 (COVID-19), yet emerging data suggest a wide geographic and ethnic variation in the prevalence of these symptoms. Studies on chemosensory disorders in COVID-19 have predominantly focused on Caucasian populations whereas Asians remain understudied. We conducted a nationwide, multicentre cross-sectional study using an online questionnaire on a cohort of RT-PCR-confirmed adult COVID-19 patients in Malaysia between 6 June and 30 November 2020. The aim of our study was to investigate their presenting symptoms and assess their chemosensory function using self-ratings of perceived smell, taste, chemesthesis, and nasal blockage. In this cohort of 498 patients, 41.4% reported smell and/or taste loss when diagnosed with COVID-19, which was the commonest symptom. Blocked nose, loss of appetite, and gastrointestinal disturbances were independent predictors of smell and/or taste loss on multivariate analysis. Self-ratings of chemosensory function revealed a reduction in smell, taste, and chemesthesis across the entire cohort of patients that was more profound among those reporting smell and/or taste loss as their presenting symptom. Perceived nasal obstruction accounted for only a small proportion of changes in smell and taste, but not for chemesthesis, supporting viral disruption of sensorineural mechanisms as the dominant aetiology of chemosensory dysfunction. Our study suggests that chemosensory dysfunction in COVID-19 is more widespread than previously reported among Asians and may be related to the infectivity of viral strains. Study Registration: NMRR-20-934-54803 and NCT04390165.

Background The value of pulsed electromagnetic field (PEMF) in postoperative pain management, due to the inconsistent findings so far, remains unclear. We extended the evaluation of PEMF on postoperative pain and intravenous (IV) analgesic use to a group of post-appendicectomy Asian patients. Methods This is a double-blinded, randomized trial. Adults with a clinical diagnosis of acute appendicitis were enrolled. Patients were allocated randomly to receive an active-PEMF device or an inactive device after the surgery in addition to the standard postoperative pain management. The primary outcome measure was the 12-h cumulative postoperative pain intensity measured at four different time points using the visual analogue scale. The secondary outcome measure was the total amount of IV fentanyl used (in mg) via PCA over the first 12 postoperative hours. The primary analysis in this trial compared the two study groups for the reported cumulative pain score (both at rest and on movement) and the cumulative amount of IV fentanyl uses over the first 12 postoperative hours using the Wilcoxon rank sum test. Analyses were performed based on the intention-to-treat principal. Multiple imputation was used to handle the missing data assuming that the data were missing at random. Findings One hundred eighteen subjects were randomized; 58 were allocated to the active-PEMF group and 60 to the inactive control group. Pooled mean pain score of both intervention groups by time point declined in a similar fashion over the course of 12 postoperative hours. The 12-h cumulative postoperative pain score at rest and on movement did not differ significantly after the procedure. ( W  = 1832.5 ~ 1933.0, p -value 0.6192 ~ 0.2985 for resting pain score comparison; W  = 1737.0 ~ 1804.5, p -value 0.9892 ~ 0.7296 for movement pain score comparison). For the secondary outcome measure of 12-h total fentanyl use, a comparison between the PEMF vs. placebo arm also revealed no statistically significant difference across all the 20 imputed datasets ( W  = 1676.5 ~ 1859.0, p -value 0.7344 ~ 0.5234). Discussion PEMF was not superior to placebo as an adjunct pain management for up to 12 h post-appendicectomy. Previously reported effect of PEMF on postoperative pain intensity and analgesia uses in similar surgical settings cannot be verified. Trial registration National Medical Research Register Malaysia (NMRR-15–670-25,805) and Thai Clinical Trials Registry (retrospectively registered on November 01, 2019, Study ID—TCTR20191102002).

Introduction: To ensure the sustainability of the AT access improvement, it is important that health system stakeholders have timely, analyzed information accessible for reference and decision-making support. In this study, we projected the direct costs required as well as the expected direct medical cost-offset and productivity benefits resulting from improving the disease control. 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.

Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are scarce. Comprehensive evidence comparing different agents is still unavailable. In this study, we examined the effects of various fibrinolytic drugs on clinical outcomes. 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). 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). 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. None.

Literature studying the door-to-balloon time-outcome relation in coronary intervention is limited by the potential of residual biases from unobserved confounders. This study re-examines the time-outcome relation with further consideration of the unobserved factors and reports the population average effect. Adults with ST-elevation myocardial infarction admitted to one of the six registry participating hospitals in Australia were included in this study. The exposure variable was patient-level door-to-balloon time. Primary outcomes assessed included in-hospital and 30 days mortality. 4343 patients fulfilled the study criteria. 38.0% (1651) experienced a door-to-balloon delay of >90 minutes. The absolute risk differences for in-hospital and 30-day deaths between the two exposure subgroups with balanced covariates were 2.81 (95% CI 1.04, 4.58) and 3.37 (95% CI 1.49, 5.26) per 100 population. When unmeasured factors were taken into consideration, the risk difference were 20.7 (95% CI −2.6, 44.0) and 22.6 (95% CI −1.7, 47.0) per 100 population. Despite further adjustment of the observed and unobserved factors, this study suggests a directionally consistent linkage between longer door-to-balloon delay and higher risk of adverse outcomes at the population level. Greater uncertainties were observed when unmeasured factors were taken into consideration.

Background Rising demand of ophthalmology care is increasingly straining Malaysia’s public healthcare sector due to its limited human and financial resources. Improving the effectiveness of ophthalmology service delivery can promote national policy goals of population health improvement and system sustainability. This study examined the performance variation of public ophthalmology service in Malaysia, estimated the potential output gain and investigated several factors that might explain the differential performance. Methods Data for 2011 and 2012 on 36 ophthalmology centres operating in the Ministry of Health hospitals were used in this analysis. We first consulted a panel of ophthalmology service managers to understand the production of ophthalmology services and to verify the production model. We then assessed the relative performance of these centres using Data Envelopment Analysis (DEA). Efficiency scores (ES) were decomposed into technical, scale, and congestion component. Potential increase in service output was estimated. Sensitivity analysis of model changes was performed and stability of the result was assessed using bootstrap approach. Second stage Tobit regression was conducted to determine if hospital type, availability of day services and population characteristics were related to the DEA scores. Results In 2011, 33 % of the ophthalmology centres were found to have ES > 1 (mean ES = 1.10). Potential output gains were 10 % (SE ± 2.92), 7.4 % (SE ± 2.06), 6.9 % (SE ± 1.97) if the centres could overcome their technical, scale and congestion inefficiencies. More centres moved to the performance frontier in 2012 (mean ES = 1.07), with lower potential output gain. The model used has good stability. Robustness checks show that the DEA correctly identified low performing centres. Being in state hospital was significantly associated with better performance. Conclusions Using DEA to benchmarking service performance of ophthalmology care could provide insights for policy makers and service managers to intuitively visualise the overall performance of resource use in an otherwise difficult to assess scenario. The considerable potential output gain estimated indicates that effort should be invested to understand what drove the performance variation and optimise them. Similar performance assessment should be undertaken for other healthcare services in the country in order to work towards a sustainable health system.

Background Acute myocardial infarction (AMI) is a medical emergency in which sudden occlusion of coronary artery(ies) results in ischemia and necrosis of the cardiac tissues. Reperfusion therapies that aim at reopening the occluded artery remain the mainstay of treatment for AMI. Primary percutaneous coronary intervention (PCI), which enables the restoration of blood flow by reopening the occluded artery(ies) via a catheter with an inflatable balloon, is currently the preferred treatment for AMI with ST segment elevation (STEMI). The door-to-balloon (D2B) delay refers to the time interval counting from the arrival of a patient with STEMI at a hospital to the time of the balloon inflation (or stent deployment) that reopens the occluded artery(ies). Reducing this delay in primary PCI is thought to be an important strategy toward achieving better patient outcomes. Unfortunately, significant reduction of D2B delay in the USA over the last decade has not been shown to be associated with improved STEMI mortality. It has been suggested that the lack of impact could be due to the expanding use of primary PCI in STEMI as well as the survival cohort effect, leading to a shift toward a higher risk population receiving the procedure. Others have suggested that reduction in D2B delay may not be as impactful as expected, given that it only represents a small fraction of the total ischemic time. Although most existing evidence have pointed to the presence of a beneficial effect of shorter D2B delay, some inconsistencies however exist. This study aims to synthesize available evidence in order to answer the following questions: (1) what is the overall effect of D2B delay on clinical outcomes in patients with STEMI treated with primary PCI? (2) What factors explain the differences of the effect estimates among the studies? (3) What are the important strength and limitation of the existing body of evidence? 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