Efficacy and safety of metformin for melasma treatment: a systematic review and meta-analysis

Objective: Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking. The objective of this study was to assess the efficacy and safety of metformin in the treatment of melasma.Methods: MEDLINE, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, CINAHL, and grey literature databases were searched to 4 October 2022 and updated on 26 February 2023. Randomized controlled trials (RCTs), quasi-RCTs, observational studies, case series, and case reports investigating the efficacy and safety of metformin for melasma were included. The Melasma Area Severity Index (MASI) scores that changed from baseline were pooled using fixed-effects model and expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs).Results: Three RCTs including 140 patients with melasma were included. The results demonstrated that after 8 weeks, 15% topical metformin significantly reduced the Melasma Area Severity Index (MASI) score compared to placebo (1 trial; n = 60; MD, −0.56; 95% CI, −1.07 to −0.04; p = 0.034). Furthermore, when compared to triple combination cream (TCC), 30% topical metformin demonstrated similar efficacy in reducing the MASI score after 8 weeks (2 trials; n = 80; MD, 0.19, 95% CI, −0.25 to 0.63; p = 0.390). Patients using 30% topical metformin had fewer adverse events compared to TCC users, although no statistical difference was found.Conclusion: Topical metformin was as effective as triple combination cream (TCC) in decreasing changes in the MASI score in patients with melasma, with minimum adverse events. Further studies with larger sample sizes, longer follow-up times, and well-designed trials are required.Systematic Review Registration: Identifier PROSPERO (CRD42022351966)

Effectiveness of home-based records on maternal, newborn and child health outcomes: A systematic review and metaanalysis

Abstract : Home-based records (HBRs) may improve the health of pregnant women, new mothers and their children, and support health care systems. We assessed the effectiveness of HBRs on maternal, newborn and child health reporting, care seeking and self-care practice, mortality, morbidity and women’s empowerment in low-, middle- and high-income countries. We con- ducted a systematic search in MEDLINE, EMBASE, CENTRAL, Health Systems Evidence, CINAHL, HTA database, NHS EED, and DARE from 1950 to 2017. We also searched the WHO, CDC, ECDC, JICA and UNAIDS. We included randomised controlled trials, prospec- tive controlled trials, and cost-effectiveness studies. We used the Cochrane Risk of Bias tool to appraise studies. We extracted and analyzed data for outcomes including maternal, new- born and child health, and women’s empowerment. We synthesized and presented data using GRADE Evidence Profiles. We included 14 studies out of 16,419 identified articles. HBRs improved antenatal care and reduced likelihood of pregnancy complications; improved patient–provider communication and enhanced women’s feelings of control and empower- ment; and improved rates of vaccination among children (OR: 2�39, 95% CI: 1.45–3�92) and mothers (OR 1�98 95% CI:1�29–3�04). A three-year follow-up shows that HBRs reduced risk of cognitive delay in children (p = 0.007). HBRs used during the life cycle of women and chil- dren in Indonesia showed benefits for continuity of care. There were no significant effects on healthy pregnancy behaviors such as smoking and consumption of alcohol during preg- nancy. There were no statistically significant effects on newborn health outcomes. We did not identify any formal studies on cost or economic evaluation. HBRs show modest but important health effects for women and children. These effects with minimal-to-no harms, multiplied across a population, could play an important role in reducing health inequities in maternal, newborn, and child health. PLO

Distributive Laws for Monotone Specifications

Turi and Plotkin introduced an elegant approach to structural operational semantics based on universal coalgebra, parametric in the type of syntax and the type of behaviour. Their framework includes abstract GSOS, a categorical generalisation of the classical GSOS rule format, as well as its categorical dual, coGSOS. Both formats are well behaved, in the sense that each specification has a unique model on which behavioural equivalence is a congruence. Unfortunately, the combination of the two formats does not feature these desirable properties. We show that monotone specifications - that disallow negative premises - do induce a canonical distributive law of a monad over a comonad, and therefore a unique, compositional interpretation.Comment: In Proceedings EXPRESS/SOS 2017, arXiv:1709.0004

Examining usage behavior of a goal-supporting mHealth app in primary care among patients with multiple chronic conditions:A qualitative study

BACKGROUND: Although mobile health (mHealth) apps are increasingly being used to support patients with multiple chronic conditions (multimorbidity), most mHealth apps experience low interaction and eventual abandonment. To tackle this engagement issue, when developing an mHealth program, it is important to understand the social-behavioral factors that affect patients’ use behavior. OBJECTIVE: The aim of this study was to explore the social and behavioral factors contributing to patients’ use behavior of an mHealth app called the electronic Patient-Reported Outcome (ePRO). The ePRO app supports goal-oriented care delivery in interdisciplinary primary care models. METHODS: A descriptive qualitative study was used to analyze interview data collected for a larger mixed methods pragmatic trial. The original 15-month trial was conducted in 6 primary care teams across Ontario, Canada, between 2018 and 2019. The eligibility criteria for patients were being aged ≥60 years with ≥10 visits within the previous 12 months of study enrollment. For this analysis, patients were classified as long-term or short-term users based on their length of use of the ePRO app during the trial. The Social Cognitive Theory by Bandura was used to categorize social-behavioral factors that contributed to patients’ decision to continue or discontinue using the app. RESULTS: The patient-provider relationship emerged as a key factor that shaped patients’ experiences with the app and subsequent decision to continue using the app. Other factors that contributed to patients’ decision to continue using the app were personal and social circumstances, perceived usefulness, patients’ previous experience with goal-related behaviors, and confidence in one’s capability. There was an overlap of experience between long- and short-term app users but, in general, long-term users perceived the app to be more useful and their goals to be more meaningful than short-term app users. This observation was complicated by the fact that patient health-related goals were dynamic and changed over time. CONCLUSIONS: Complex patients’ use behavior of a goal-supporting mHealth app is shaped by an array of sociobehavioral factors that can evolve. To tackle this dynamism, there should be an emphasis on creating adaptable health technologies that are easily customizable by patients and able to respond to their changing contexts and needs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02917954; https://clinicaltrials.gov/ct2/show/NCT0291795

Protocol for a modelling study to assess the clinical and cost-effectiveness of indefinite anticoagulant therapy for first unprovoked venous thromboembolism.

INTRODUCTION Deciding whether to stop or extend anticoagulant therapy indefinitely after completing at least 3 months of initial treatment for a first unprovoked venous thromboembolism (VTE) remains a challenge for clinicians, patients and policy makers. Guidelines suggest an indefinite duration of anticoagulant therapy in these patients, yet its benefits, harms and costs have not been formally assessed. The aim of this proposed modelling study is to assess the differences in clinical benefits, harms and costs of stopping versus continuing anticoagulant therapy indefinitely for a first unprovoked VTE. METHODS AND ANALYSIS We will develop a probabilistic Markov model, adopting a 1-month cycle length and a lifetime horizon, to estimate life-years, quality-adjusted life-years, costs and the incremental cost-effectiveness ratios for a simulated population of patients with a first unprovoked VTE who will receive indefinite duration of anticoagulant therapy versus a population who will not receive extended treatment after completing 3 months of initial anticoagulant therapy. The economic evaluation will adopt a third-party payer perspective relating to a Canadian publicly funded healthcare system. Estimates for the probability of relevant clinical events will be informed by systematic reviews and meta-analyses, while costs and utility values will be obtained from published Canadian sources. Stratified analyses based on sex, age and site of initial VTE will also be performed to identify subgroups of patients with a first unprovoked VTE in whom continuing anticoagulant therapy indefinitely might prove to be clinically beneficial and cost-effective over stopping treatment. We will also conduct sensitivity and scenario analyses to assess robustness of study findings to changes in individual or groups of key parameters. ETHICS AND DISSEMINATION Ethical approval is not applicable for this study. The results will be disseminated through presentations at relevant conferences and in a manuscript that will be submitted to a peer-reviewed journal

Advantages of the net benefit regression framework for trial-based economic evaluations of cancer treatments: an example from the Canadian Cancer Trials Group CO.17 trial.

BackgroundEconomic evaluations commonly accompany trials of new treatments or interventions; however, regression methods and their corresponding advantages for the analysis of cost-effectiveness data are not widely appreciated.MethodsTo illustrate regression-based economic evaluation, we review a cost-effectiveness analysis conducted by the Canadian Cancer Trials Group's Committee on Economic Analysis and implement net benefit regression.ResultsNet benefit regression offers a simple option for cost-effectiveness analyses of person-level data. By placing economic evaluation in a regression framework, regression-based techniques can facilitate the analysis and provide simple solutions to commonly encountered challenges (e.g., the need to adjust for potential confounders, identify key patient subgroups, and/or summarize "challenging" findings, like when a more effective regimen has the potential to be cost-saving).ConclusionsEconomic evaluations of patient-level data (e.g., from a clinical trial) can use net benefit regression to facilitate analysis and enhance results

Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review

BACKGROUND: A rapid review, guided by a protocol, was conducted to inform development of the World Health Organization’s guideline on personal protective equipment in the context of the ongoing (2013-present) Western African filovirus disease outbreak, with a focus on health care workers directly caring for patients with Ebola or Marburg virus diseases. METHODS: Electronic databases and grey literature sources were searched. Eligibility criteria initially included comparative studies on Ebola and Marburg virus diseases reported in English or French, but criteria were expanded to studies on other viral hemorrhagic fevers and non-comparative designs due to the paucity of studies. After title and abstract screening (two people to exclude), full-text reports of potentially relevant articles were assessed in duplicate. Fifty-seven percent of extraction information was verified. The Grading of Recommendations Assessment, Development and Evaluation framework was used to inform the quality of evidence assessments. RESULTS: Thirty non-comparative studies (8 related to Ebola virus disease) were located, and 27 provided data on viral transmission. Reporting of personal protective equipment components and infection prevention and control protocols was generally poor. CONCLUSIONS: Insufficient evidence exists to draw conclusions regarding the comparative effectiveness of various types of personal protective equipment. Additional research is urgently needed to determine optimal PPE for health care workers caring for patients with filovirus

Exploring the perspectives of primary care providers on use of the electronic Patient Reported Outcomes tool to support goal-oriented care:a qualitative study

BACKGROUND: Digital health technologies can support primary care delivery, but clinical uptake in primary care is limited. This study explores enablers and barriers experienced by primary care providers when adopting new digital health technologies, using the example of the electronic Patient Reported Outcome (ePRO) tool; a mobile application and web portal designed to support goal-oriented care. To better understand implementation drivers and barriers primary care providers’ usage behaviours are compared to their perspectives on ePRO utility and fit to support care for patients with complex care needs. METHODS: This qualitative sub-analysis was part of a larger trial evaluating the use of the ePRO tool in primary care. Qualitative interviews were conducted with providers at the midpoint (i.e. 4.5–6 months after ePRO implementation) and end-point (i.e. 9–12 months after ePRO implementation) of the trial. Interviews explored providers’ experiences and perceptions of integrating the tool within their clinical practice. Interview data were analyzed using a hybrid thematic analysis and guided by the Technology Acceptance Model. Data from thirteen providers from three distinct primary care sites were included in the presented study. RESULTS: Three core themes were identified: (1) Perceived usefulness: perceptions of the tool’s alignment with providers’ typical approach to care, impact and value and fit with existing workflows influenced providers’ intention to use the tool and usage behaviour; (2) Behavioural intention: providers had a high or low behavioural intention, and for some, it changed over time; and (3) Improving usage behaviour: enabling external factors and enhancing the tool’s perceived ease of use may improve usage behaviour. CONCLUSIONS: Multiple refinements/iterations of the ePRO tool (e.g. enhancing the tool’s alignment with provider workflows and functions) may be needed to enhance providers’ usage behaviour, perceived usefulness and behavioural intention. Enabling external factors, such as organizational and IT support, are also necessary to increase providers’ usage behaviour. Lessons from this study advance knowledge of technology implementation in primary care. TRIAL REGISTRATION: Clinicaltrials.gov Identified NCT02917954. Registered September 2016, https://www.clinicaltrials.gov/ct2/show/study/NCT02917954 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12911-021-01734-0

Estimates and predictors of health care costs of esophageal adenocarcinoma : A population-based cohort study

Background: Esophageal adenocarcinoma (EAC) incidence is increasing rapidly. Esophageal cancer has the second lowest 5-year survival rate of people diagnosed with cancer in Canada. Given the poor survival and the potential for further increases in incidence, phase-specific cost estimates constitute an important input for economic evaluation of prevention, screening, and treatment interventions. The study aims to estimate phase-specific net direct medical costs of care attributable to EAC, costs stratified by cancer stage and treatment, and predictors of total net costs of care for EAC. Methods: A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data from 2003 to 2011. The mean net costs of EAC care per 30 patient-days (2016 CAD) were estimated from the payer perspective using phase of care approach and generalized estimating equations. Predictors of net cost by phase of care were based on a generalized estimating equations model with a logarithmic link and gamma distribution adjusting for sociodemographic and clinical factors. Results: The mean net costs of EAC care per 30 patient-days were $1016 (95$955-$1078) in the initial phase,$669 (95% CI, $594-$743) in the continuing care phase, and $8678 (95$8217-$9139) in the terminal phase. Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the highest cost, particularly in the terminal phase. Strong predictors of higher net costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy, radiotherapy alone, surgery alone, and chemotherapy alone in the initial and continuing care phases, stage III-IV disease and patients diagnosed with EAC later in a calendar year (2007-2011) in the initial and terminal phases, comorbidity in the continuing care phase, and older age at diagnosis (70-74 years), and geographic region in the terminal phase. Conclusions: Costs of care vary by phase of care, stage at diagnosis, and type of treatment for EAC. These cost estimates provide information to guide future resource allocation decisions, and clinical and policy interventions to reduce the burden of EAC

Periacetabular osteotomy with or without arthroscopic management in patients with hip dysplasia: Study protocol for a multicenter randomized controlled trial

BACKGROUND: Hip dysplasia is one of the most common causes of hip arthritis. Its incidence is estimated to be between 3.6 and 12.8% (Canadian Institute for Health Information, Hip and knee replacements in Canada, 2017-2018: Canadian joint replacement registry annual report, 2019; Jacobsen and Sonne-Holm, Rheumatology 44:211-8, 2004). The Periacetabular Osteotomy (PAO) has been used successfully for over 30 years (Gosvig et al., J Bone Joint Surg Am 92:1162-9, 2010), but some patients continue to exhibit symptoms post-surgery (Wyles et al., Clin Orthop Relat Res 475:336-50, 2017). A hip arthroscopy, performed using a small camera, allows surgeons to address torn cartilage inside the hip joint. Although both procedures are considered standard of care treatment options, it is unknown whether the addition of hip arthroscopy improves patient outcomes compared to a PAO alone. To delay or prevent future joint replacement surgeries, joint preservation surgery is recommended for eligible patients. While previous studies found an added cost to perform hip arthroscopies, the cost-effectiveness to Canadian Health care system is not known. METHODS: Patients randomized to the experimental group will undergo central compartment hip arthroscopy prior to completion of the PAO. Patients randomized to the control group will undergo isolated PAO. Patient-reported quality of life will be the primary outcome used for comparison between the two treatment groups as measured by The International Hip Outcome Tool (iHOT-33) (Saberi Hosnijeh et al., Arthritis Rheum 69:86-93, 2017). Secondary outcomes will include the four-square step test and sit-to-stand (validated in patients with pre-arthritic hip pain) and hip-specific symptoms and impairment using the HOOS; global health assessment will be compared using the PROMIS Global 10 Score; health status will be assessed using the EQ-5D-5L and EQ VAS questionnaires (Ganz et al., Clin Orthop Relat Res 466:264-72, 2008) pre- and post-operatively. In addition, operative time, hospital length of stay, adverse events, and health services utilization will be collected. A sub-group of patients (26 in each group) will receive a T1rho MRI before and after surgery to study changes in cartilage quality over time. A cost-utility analysis will be performed to compare costs and quality-adjusted life years (QALYs) associated with the intervention. DISCUSSION: We hypothesize that (1) concomitant hip arthroscopy at the time of PAO to address central compartment pathology will result in clinically important improvements in patient-reported outcome measures (PROMs) versus PAO alone, that (2) additional costs associated with hip arthroscopy will be offset by greater clinical improvements in this group, and that (3) combined hip arthroscopy and PAO will prove to be a cost-effective procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT03481010 . Registered on 6 March 2020. Protocol version: version 3