METHODS: We performed systematic searches using electronic databases including PubMed and EMBASE until December 2012. Key words included "metformin" AND ("ovarian cancer" OR "ovary tumor"). All human studies assessing the effects of metformin on ovarian cancer were eligible for inclusion. All articles were reviewed independently by 2 authors with a standardized approach for the purpose of study, study design, patient characteristics, exposure, and outcomes. The data were pooled using a random-effects model.
RESULTS: Of 190 studies retrieved, only 3 observational studies and 1 report of 2 randomized controlled trials were included. Among those studies, 2 reported the effects of metformin on survival outcomes of ovarian cancer, whereas the other 2 reported the effects of metformin on ovarian cancer prevention. The findings of studies reporting the effects on survival outcomes indicated that metformin may prolong overall, disease-specific, and progression-free survival in ovarian cancer patients. The results of studies reporting the effects of metformin on ovarian cancer prevention were meta-analyzed. It indicated that metformin tended to decrease occurrence of ovarian cancer among diabetic patients with the pooled odds ratio of 0.57 (95% confidence interval, 0.16-1.99).
CONCLUSIONS: Our findings showed the potential therapeutic effects of metformin on survival outcomes of ovarian cancer and ovarian cancer prevention. However, most of the evidence was observational studies. There is a call for further well-conducted controlled clinical trials to confirm the effects of metformin on ovarian cancer survival and ovarian cancer prevention.
OBJECTIVES: This study aimed to collect real-world cost and HRQOL data, and investigate their associations with multiple disease-severity indicators among AD patients in Thailand.
METHODS: We recruited AD patients aged ≥60 years accompanied by their caregivers at a university-affiliated tertiary hospital. A one-time structured interview was conducted to collect disease-severity indicators, HRQOL, and caregiving information using standardized tools. The hospital's database was used to retrieve healthcare resource utilization occurred over 6 months preceding the interview date. Costs were annualized and stratified based on cognitive status. Generalized linear models were employed to evaluate determinants of costs and HRQOL.
RESULTS: Among 148 community-dwelling patients, average annual total societal costs of AD care were $8014 (95% confidence interval [CI]: $7295-$8844) per patient. Total costs of patients with severe stage ($9860; 95% CI: $8785-$11 328) were almost twice as high as those of mild stage ($5524; 95% CI: $4649-$6593). The major cost driver was direct medical costs, particularly those incurred by AD prescriptions. Functional status was the strongest determinant for both total costs and patient's HRQOL (P value
OBJECTIVES: This study aimed to quantify the potential lifetime productivity loss due to pneumococcal diseases among the pediatric population in Thailand using productivity-adjusted life years (PALYs).
METHODS: A decision analytic model was used to estimate the burden of pneumococcal diseases among the current Thai population aged 0-5 years and followed up until aged 99 years or death. Base-case analysis compared years of life and PALYs lost to pneumococcal diseases. Scenario analyses investigated the benefits of prevention with pneumococcal conjugated vaccine 13 (PCV 13). All health outcomes were discounted at 3% per annum.
RESULTS: The base-case analysis estimated that 453,401 years of life and 457,598 PALYs would be lost to pneumococcal diseases, equating to a loss of US$5586 (95% CI 3338-10,302) million. Vaccination with PCV13 at birth was estimated to save 82,609 years of life and 93,759 PALYs, which equated to US$1144 (95% CI 367-2591) million in economic benefits. The incidence of pneumonia in those aged 0-4 years, vaccine efficacy, and the assumed period of protection were key determinants of the health economic outputs.
CONCLUSIONS: The disease and financial burden of pneumococcal diseases in Thailand is significant, but a large proportion of this is potentially preventable with vaccination.
Methods: A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality.
Results: Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL).
Conclusions: A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.
OBJECTIVE: This study aimed to determine the effects of telemedicine on asthma control and the quality of life in adults.
METHODS: An electronic search was performed from the inception to March 2018 on the following databases: Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, EMBASE, PubMed, and Scopus. Randomized controlled trials that assessed the effects of telemedicine in adults with asthma were included in this analysis, and the outcomes of interest were levels of asthma control and quality of life. Random-effects model meta-analyses were performed.
RESULTS: A total of 22 studies (10,281 participants) were included. Each of 11 studies investigated the effects of single-telemedicine and combined-telemedicine (combinations of telemedicine approaches), and the meta-analyses showed that combined tele-case management could significantly improve asthma control compared with usual care (standardized mean difference [SMD] = 0.78; 95% confidence interval [CI]: 0.56, 1.01). Combined tele-case management and tele-consultation (SMD = 0.52 [95% CI: 0.13, 0.91]) and combined tele-consultation (SMD = 0.28 [95% CI: 0.13, 0.44]) also significantly improved asthma outcomes, but to a lesser degree. In addition, combined tele-case management (SMD = 0.59 [95% CI: 0.31, 0.88]) was the most effective telemedicine for improving quality of life, followed by combined tele-case management and tele-consultation (SMD = 0.31 [95% CI: 0.03, 0.59]), tele-case management (SMD = 0.30 [95% CI: 0.05, 0.55]), and combined tele-consultation (SMD = 0.27 [95% CI: 0.11, 0.43]), respectively.
CONCLUSIONS: Combined-telemedicine involving tele-case management or tele-consultation appear to be effective telemedicine interventions to improve asthma control and quality of life in adults. Our findings are expected to provide health care professionals with current evidence of the effects of telemedicine on asthma control and patients' quality of life.
MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines.
RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores.
CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.
OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety.
SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment.
DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading.
MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia.
AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.
METHODS: A systematic search with Embase, Cochrane CENTRAL, Google scholar, and PubMed was conducted. Studies conducted in patients with STEMI presented to non PCI-capable settings and compared fibrinolytic injection with no injection before referring patients to PCI-capable settings were included. The primary outcome was the composite outcomes of major adverse cardiac events (MACEs) at 30 days. Meta-analyses were performed using random-effect model.
RESULTS: Of 912 articles, three RCTs and three non-RCTs were included. Based on RCTs, fibrinolytic injection before the referral has failed to decrease MACEs compared to non-fibrinolytic injection [relative risk (RR) 1.18; 95% confidence interval (CI), 0.89-1.57, p = 0.237]. Fibrinolytic injection has also failed to decrease mortality, re-infarction, and ischemic stroke. On the other hand, fibrinolytic injection was associated with a higher risk of major bleeding.
CONCLUSIONS: In non PCI-capable settings, fibrinolytic injection before referring patients with STEMI to PCI-capable settings has no clinical benefit but could increase risk of major bleeding. Clinicians might more carefully consider whether fibrinolytic injection should be used in patients with STEMI before the referral.