Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol.

Background: Diffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD. Methods: Role of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan. Discussion: REVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

Cost-effectiveness of Web-Based and Home-Based Postnatal Psychoeducational Interventions for First-time Mothers: Economic Evaluation Alongside Randomized Controlled Trial.

BACKGROUND: The cost-effectiveness of interventions has attracted increasing interest among researchers. Although web-based and home-based psychoeducational interventions have been developed to improve first-time mothers' postnatal health outcomes, very limited studies have reported their cost-effectiveness. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of web-based and home-based postnatal psychoeducational interventions for first-time mothers during the early postpartum period. METHODS: A randomized controlled 3-group pretest and posttest design was adopted, and cost-effectiveness analysis from the health care's perspective was conducted. A total of 204 primiparas were recruited from a public tertiary hospital in Singapore from October 2016 to August 2017 who were randomly allocated to the web-based intervention (n=68), home-based intervention (n=68), or control (n=68) groups. Outcomes of maternal parental self-efficacy, social support, postnatal depression, anxiety, and health care resource utilization were measured using valid and reliable instruments at baseline and at 1 month, 3 months, and 6 months after childbirth. The generalized linear regression models on effectiveness and cost were used to assess the incremental cost-effectiveness ratios of the web-based and home-based intervention programs compared to routine care. Projections of cumulative cost over 5 years incurred by the 3 programs at various coverage levels (ie, 10%, 50%, and 100%) were also estimated. RESULTS: The web-based intervention program dominated the other 2 programs (home-based program and routine care) with the least cost (adjusted costs of SGD 376.50, SGD 457.60, and SGD 417.90 for web-based, home-based, and control group, respectively; SGD 1=USD 0.75) and the best improvements in self-efficacy, social support, and psychological well-being. When considering the implementation of study programs over the next 5 years by multiplying the average cost per first-time mother by the estimated average number of first-time mothers in Singapore during the 5-year projection period, the web-based program was the least costly program at all 3 coverage levels. Based on the 100% coverage, the reduced total cost reached nearly SGD 7.1 million and SGD 11.3 million when compared to control and home-based programs at the end of the fifth year, respectively. CONCLUSIONS: The web-based approach was promisingly cost-effective to deliver the postnatal psychoeducational intervention to first-time mothers and could be adopted by hospitals as postnatal care support. TRIAL REGISTRATION: ISRCTN registry ISRCTN45202278; https://www.isrctn.com/ISRCTN45202278.

Radiofrequency microtenotomy for plantar fasciitis: A systematic review and meta-analysis.

BACKGROUND: Currently, there is limited evidence on outcomes for plantar fascia radiofrequency microtenotomy. An evidence-based systematic review and meta-analysis for outcomes of radiofrequency microtenotomy for the treatment of plantar fasciitis was conducted. METHODS: A comprehensive evidence-based literature review of PubMed and Cochrane Databases was conducted in March 2019, which identified 11 relevant articles assessing the efficacy of plantar fascia radiofrequency microtenotomy. The studies were then assigned to a level of evidence (I-IV). Individual studies were reviewed to provide a grade of recommendation (A-C, I) according to the Wright classification in support of or against endoscopic plantar fascia release. Meta-analysis was performed for 7 of the studies that measured AOFAS scores. RESULTS: Based on the results of this evidence-based review, there was fair (grade B) evidence to support plantar fascia radiofrequency microtenotomy. There was a statistically significant mean increase of 40.9 in AOFAS scores post procedure. CONCLUSION: There was fair (grade B) evidence to recommend radiofrequency microtenotomy for plantar fasciitis. There is a need for more high quality level I randomized controlled trials with validated outcome measures to allow for stronger recommendations to be made. LEVEL OF EVIDENCE: Level II, systematic review of level II studies.

Evaluating the effectiveness and utility of a novel culturally-adapted telemonitoring system in improving the glycaemic control of Asians with type-2 diabetes mellitus: a mixed method study protocol.

BACKGROUND: Regular supervision of patients with type-2 diabetes mellitus (T2DM) by healthcare providers is essential to optimise their glycaemic control but is challenging to achieve in current care models. Telemonitoring is postulated to bridge this gap by leveraging on internet-of-things and mobile-health technology. This study aims to determine the effectiveness of a novel telemonitoring system (OPTIMUM) in improving the glycaemic control of patients with T2DM compared with standard of care alone. METHODS: This mixed-method study comprises an initial randomised controlled trial involving 330 Asian adults with T2DM, aged 26-65 years old with an HbA1c of 7.5-10%, with 115 in the intervention and control arms each. Those in the intervention arm will use standardised Bluetooth-enabled devices to transmit their capillary glucose, blood pressure and weight measurements to the OPTIMUM system. Primary care physicians and nurses will remotely supervise them according to an embedded management algorithm for 6 months, including tele-education via weekly videos over 8 weeks and asynchronous tele-consultation if abnormal or absent parameters are detected. Patients in both arms will be assessed at baseline, 6, 12 and 24 months post-recruitment. The primary outcome will be their HbA1c difference between both arms at baseline and 6 months. Blood pressure and weight control; quality of life, medication adherence, confidence in self-management, diabetic literacy and related distress and healthcare utilisation using validated questionnaires; and incident retinal, renal, cardiac and cerebrovascular complications will be compared between the two arms as secondary outcomes at stipulated time-points. Intervention arm patients will be interviewed using qualitative research methods to understand their experience, acceptance and perceived usefulness of the OPTIMUM system. DISCUSSION: Overall, this study seeks to evaluate the effectiveness of cultural-adapted telemonitoring system in improving glycaemic control of Asians with type-2 diabetes mellitus compared to standard of care. The results of this trial will better inform policy makers in adopting telemedicine for population health management. TRIAL REGISTRATION: ClinicalTrials.gov NCT04306770 . Registered on March 13, 2020.

Non-steroidal anti-inflammatory drugs (NSAIDs) for trigger finger.

BACKGROUND: Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration, inflammation, and swelling. This causes pain and restricted movement of the affected finger. Non-surgical treatment options include activity modification, oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), splinting, and local injections with anti-inflammatory drugs. OBJECTIVES: To review the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, and the WHO trials portal until 30 September 2020. We applied no language or publication status restrictions. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and quasi-randomised trials of adult participants with trigger finger that compared NSAIDs administered topically, orally, or by injection versus placebo, glucocorticoid, or different NSAIDs administered by the same route. DATA COLLECTION AND ANALYSIS: Two or more review authors independently screened the reports, extracted data, and assessed risk of bias and GRADE certainty of evidence. The seven major outcomes were resolution of trigger finger symptoms, persistent moderate or severe symptoms, recurrence of symptoms, total active range of finger motion, residual pain, patient satisfaction, and adverse events. Treatment effects were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: Two RCTs conducted in an outpatient hospital setting were included (231 adult participants, mean age 58.6 years, 60% female, 95% to 100% moderate to severe disease). Both studies compared a single injection of a non-selective NSAID (12.5 mg diclofenac or 15.0 mg ketorolac) given at lower than normal doses with a single injection of a glucocorticoid (triamcinolone 20 mg or 5 mg), with maximum follow-up duration of 12 weeks or 24 weeks. In both studies, we detected risk of attrition and performance bias. One study also had risk of selection bias. The effects of treatment were sensitive to assumptions about missing outcomes. All seven outcomes were reported in one study, and five in the other. NSAID injection may offer little to no benefit over glucocorticoid injection, based on low- to very low-certainty evidence from two trials. Evidence was downgraded for bias and imprecision. There may be little to no difference between groups in resolution of symptoms at 12 to 24 weeks (34% with NSAIDs, 41% with glucocorticoids; absolute effect 7% lower, 95% confidence interval (CI) 16% lower to 5% higher; 2 studies, 231 participants; RR 0.83, 95% CI 0.62 to 1.11; low-certainty evidence). The rate of persistent moderate to severe symptoms may be higher at 12 to 24 weeks in the NSAIDs group (28%) compared to the glucocorticoid group (14%) (absolute effect 14% higher, 95% CI 2% to 33% higher; 2 studies, 231 participants; RR 2.03, 95% CI 1.19 to 3.46; low-certainty evidence). We are uncertain whether NSAIDs result in fewer recurrences at 12 to 24 weeks (1%) compared to glucocorticoid (21%) (absolute effect 20% lower, 95% CI 21% to 13% lower; 2 studies, 231 participants; RR 0.07, 95% CI 0.01 to 0.38; very low-certainty evidence). There may be little to no difference between groups in mean total active motion at 24 weeks (235 degrees with NSAIDs, 240 degrees with glucocorticoid) (absolute effect 5% lower, 95% CI 34.54% lower to 24.54% higher; 1 study, 99 participants; MD -5.00, 95% CI -34.54 to 24.54; low-certainty evidence). There may be little to no difference between groups in residual pain at 12 to 24 weeks (20% with NSAIDs, 24% with glucocorticoid) (absolute effect 4% lower, 95% CI 11% lower to 7% higher; 2 studies, 231 participants; RR 0.84, 95% CI 0.54 to 1.31; low-certainty evidence). There may be little to no difference between groups in participant-reported treatment success at 24 weeks (64% with NSAIDs, 68% with glucocorticoid) (absolute effect 4% lower, 95% CI 18% lower to 15% higher; 1 study, 121 participants; RR 0.95, 95% CI 0.74 to 1.23; low-certainty evidence). We are uncertain whether NSAID injection has an effect on adverse events at 12 to 24 weeks (1% with NSAIDs, 1% with glucocorticoid) (absolute effect 0% difference, 95% CI 2% lower to 3% higher; 2 studies, 231 participants; RR 2.00, 95% CI 0.19 to 21.42; very low-certainty evidence). AUTHORS' CONCLUSIONS: For adults with trigger finger, by 24 weeks' follow-up, results from two trials show that compared to glucocorticoid injection, NSAID injection offered little to no benefit in the treatment of trigger finger. Specifically, there was no difference in resolution, symptoms, recurrence, total active motion, residual pain, participant-reported treatment success, or adverse events.

The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder.

BACKGROUND: Symptoms of autism spectrum disorder (ASD) have been associated, in part, with the dysfunction of N-methyl-D-aspartate (NMDA) glutamate receptors at excitatory synapses and glutamate abnormalities. Medications related to glutamatergic neurotransmission, such as D-cycloserine - which is a partial agonist of the NMDA glutamate receptor - are potential treatment options for the core features of ASD. However, the potential effect of D-cycloserine on the social and communication skills deficits of individuals with ASD has not been thoroughly explored and no systematic reviews of the evidence have been conducted. OBJECTIVES: To assess the efficacy and adverse effects of D-cycloserine compared with placebo for social and communication skills in individuals with ASD. SEARCH METHODS: In November 2020, we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers. We also searched the reference lists of relevant publications and contacted the authors of the included study, Minshawi 2016, to identify any additional studies. In addition, we contacted pharmaceutical companies, searched manufacturers' websites and sources of reports of adverse events.  SELECTION CRITERIA: All randomised controlled trials (RCTs) of any duration and dose of D-cycloserine, with or without adjunct treatment, compared to placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted relevant data, assessed the risk of bias, graded the certainty of the evidence using the GRADE approach, and analysed and evaluated the data. We provide a narrative report of the findings as only one study is included in this review. MAIN RESULTS: We included a single RCT (Minshawi 2016) funded by the United States Department of Defense. It was conducted at two sites in the USA: Indiana University School of Medicine and Cincinnati Children's Hospital Medical Centre. In the included study, 67 children with ASD aged between 5 and 11 years were randomised to receive either 10 weeks (10 doses) of (50 mg) D-cycloserine plus social skills training, or placebo plus social skills training. Randomisation was carried out 1:1 between D-cycloserine and placebo arms, and outcome measures were recorded at one-week post-treatment. The 'risk of bias' assessment for the included study was low for five domains and unclear for two domains. The study (67 participants) reported low certainty evidence of little to no difference between the two groups for all outcomes measured at one week post-treatment: social interaction impairment (mean difference (MD) 3.61 (assessed with the Social Responsiveness Scale), 95% confidence interval (CI) -5.60 to 12.82); social communication impairment (MD -1.08 (measured using the inappropriate speech subscale of the Aberrant Behavior Checklist (ABC)), 95% CI -2.34 to 0.18); restricted, repetitive, stereotyped patterns of behaviour (MD 0.12 (measured by the ABC stereotypy subscale), 95% CI -1.71 to 1.95); serious adverse events (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31); non-core symptoms of ASD (RR 0.97 (measured by the Clinical Global Impression-Improvement scale), 95% CI 0.49 to 1.93); and tolerability of D-cycloserine (RR 0.32 (assessed by the number of dropouts), 95% CI 0.01 to 7.68).  AUTHORS' CONCLUSIONS: We are unable to conclude with certainty whether D-cycloserine is effective for individuals with ASD. This review included low certainty data from only one study with methodological issues and imprecision. The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings.

Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients: A Systematic Review and Meta-analysis.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. METHODS: We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. RESULT: From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). CONCLUSION: Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.

Academic school readiness in children born very preterm and associated risk factors.

BACKGROUND AND AIMS: Although the intelligence quotient (IQ) test is useful to assess general cognitive function, it may miss more specific and subtle deficits of learning, working memory, attention and executive function. This study aims to evaluate cognitive performance and academic school readiness (SR) concepts in preterm very low birth weight (PT/VLBW) children, compared to typically developing term controls and to evaluate factors affecting basic (SR) concepts in children with IQ>85. METHODS: A prospective cohort study of 123 PT/VLBW survivors with birth weights ≤1250 g and 74 term controls born between 2007 and 2009 in Singapore were assessed for school readiness using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Bracken School Readiness Assessment (BSRA-3) and Beery-Buktenica Developmental Test of Visual Motor Integration (VMI) at age 5.5 years. Social risk composite score (SRCS) was calculated based on ethnicity, parental education and family income and marital status. Uni- and multi-variable regressions were conducted to evaluate risk factors associated with poor academic SR in the entire cohort and in those with IQ >85. RESULTS: Mean gestational age and birth weight of the 123 PT/VLBW children were 27.8 (2.3) weeks and 939 (194) grams while that of the 74 term controls were 38.8 (1.2) weeks and 3165 (402) grams. PT/VLBW survivors had statistically significant lower full composite scores on WPPSI-III (97.0 vs 114), BSRA-3 (98.5 vs 112.3) and VMI (107.2 vs 112.9) compared to controls. The differences remained significant in preterm and children with higher SRCS even after adjustment. CONCLUSIONS: Prematurity and high social composite risk scores were risk factors affecting academic SR and this difference persisted in PT/VLBW children with normal cognitive scores with IQ >85.

Is chemoprophylaxis required after total knee and total hip arthroplasty in the Asian population? A systematic review and network meta-analysis.

INTRODUCTION: Although chemoprophylaxis against venous thromboembolism (VTE) after Total Joint Arthroplasty (TJA) is commonly practiced, epidemiology studies have shown Asians have a much lower incidence of VTE. The authors aim to investigate if chemoprophylaxis is really necessary in the Asian population undergoing TJA. MATERIAL AND METHODS: Literature searched was conducted for randomized controlled trials or quasi-experimental studies investigating efficacy and/or safety of chemoprophylaxis for TJA without language restrictions. Network meta-analysis, comparing the incidence of 'VTE to be treated', 'VTE not to be treated', 'Minor bleeding', and 'Major bleeding' amongst the different interventions was performed using multivariate meta-regression model. RESULTS: 38 studies (11,769 patients) were included. Total incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) were 14.2% and 0.73% respectively. For outcome on efficiency, edoxaban, low-molecular-weight-heparin (LMWH), fondaparinux, and enoxaparin showed significantly lower Risk Ratio (RR) for 'VTE to be treated' compared to Control/Placebo. Although no interventions showed increased incidence of major bleeding, LMWH and fondaparinux showed higher RR for minor bleeding. Enoxaparin displayed the best efficacy and safety profile. Total incidence of symptomatic DVT in studies involving enoxaparin was 1.98% (1.07% in patients who received enoxaparin, 2.92% in Control/Placebo). Total incidence of proximal DVT was 2.93% (2.67% in patients who received enoxaparin, 3.11% in Control/Placebo). CONCLUSION: Asian population has a much lower incidence of VTE events after TJA compared to the Western population. Although Enoxaparin is still efficacious in reducing symptomatic and proximal DVT after TJA, its benefit-to-risk ratio is much lower than described in the Western literature.

A systematic review and meta-analysis of the COVID-19 associated liver injury.

INTRODUCTION AND OBJECTIVES: The novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19. METHODS: We performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model. RESULTS: Among 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I2 = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I2 = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I2 = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I2 = 71%) were higher subjects in critical COVID-19. CONCLUSION: COVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.

Drug induced liver injury: East versus West - a systematic review and meta-analysis.

Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic profiles. To review existing literature on causative agents of DILI in the East compared to the West, a comprehensive literature search was performed on electronic databases: MEDLINE/PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure without language restrictions. Studies which involve patients having DILI and reported the frequency of causative agents were included. A random effects model was applied to synthesize the current evidence using prevalence of class-specific and agent-specific causative drugs with 95% confidence intervals. Of 6,914 articles found, 12 showed the distribution of drugs implicated in DILI in the East with a total of 33,294 patients and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications (25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest. For individual agents, the most common agents in the East were isoniazid-rifampicin-pyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillin-potassium clavulanate combination acid (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. There was significant heterogeneity due to variability in single-centre compared to multi-centre studies. Differences in DILI in the East versus the West both in drug classes and individual agents are important for clinicians to recognize.

Endoscopic plantar fasciotomy for plantar fasciitis: A systematic review and network meta-analysis of the English literature.

BACKGROUND: Currently, there is limited evidence on outcomes for endoscopic plantar fasciotomy. OBJECTIVES: An evidence-based literature review for outcomes of endoscopic plantar fasciotomy for the treatment of plantar fasciitis is provided. METHODS: A comprehensive evidence-based literature review of PubMed and Cochrane databases was conducted on 9th March 2019, which identified 12 relevant articles assessing the efficacy of endoscopic plantar fasciotomy. The studies were then assigned to a level of evidence (I-IV). Individual studies were reviewed to provide a grade of recommendation (A-C, I) according to the Wright classification in support of or against endoscopic plantar fascia release. RESULTS: Based on the results of this evidence-based review, there is poor evidence (grade C) to support endoscopic plantar fascia release. Release of the medial 2/3 of the plantar fascia in endoscopic plantar fasciotomy was associated with higher AOFAS score. CONCLUSION: Although the majority of the level of evidence was low (level IV) and grade of recommendation was poor (grade C), there seemed to be good outcomes for endoscopic plantar fasciotomy. There is a need for more high quality level I randomized controlled trials with validated outcome measures to allow for stronger recommendations to be made.

The safest and most efficacious route of tranexamic acid administration in total joint arthroplasty: A systematic review and network meta-analysis.

INTRODUCTION: Blood loss in Total Joint Arthroplasty can be significant and often under-estimated. This study aims to investigate the safety and efficacy of different routes of tranexamic acid (TXA) administration in reducing blood transfusion after Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA). The secondary aim is to find the safest and most efficacious route and dose of TXA. MATERIAL AND METHODS: PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, and OpenGrey were systemically searched for randomised controlled trials investigating the efficacy and/or safety of TXA for THA and/or TKA. Network meta-analysis, comparing the number of transfusion and deep vein thrombosis (DVT) among different interventions, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. RESULTS: 211 publications (20,639 individuals) were included. For outcome of transfusion, all interventions showed significantly lower transfusion rates compared to placebo. When compared to placebo, TXA via intra-venous and topical showed statistically significant lowest risk ratio (RR = 0.11, 95CI: 0.03, 0.41). For safety, TXA via topical showed relatively lowest risk ratio (RR = 0.75, 95CI 0.44, 1.30). TXA via topical and intra-articular had the highest but statistically insignificant RR (RR = 1.10, 95%CI: 0.51, 2.38). Therefore, current studies did not reveal any significant safety issue in using TXA. CONCLUSION: All forms of TXA administration showed significantly lower transfusion rate compared to control. There is a trend towards better efficacy with intra-venous and topical. In patients with higher risk of thrombosis, physicians may consider topical alone for its best safety profile.

Asian Liver Transplant Network Clinical Guidelines on Immunosuppression in Liver Transplantation.

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.

Topiramate and Metformin Are Effective Add-On Treatments in Controlling Antipsychotic-Induced Weight Gain: A Systematic Review and Network Meta-Analysis.

Background: Antipsychotic drugs may lead to side effects such as obesity, diabetes, dyslipidemia, and cardiovascular disease. The current systematic review and network meta-analysis analyzes and provides an update on the clinical performance of these add-ons in comparison to placebo on body weight and body mass index (BMI) reductions. Methods: A comprehensive literature search was performed on electronic databases: PubMed (1946-), Embase (1974-), Cochrane library (1992-), and OpenGrey (2000-) until 31 July 2018. Network meta-analyses, comparing the body weight change, BMI change and withdrawn due to adverse events of different pharmacological add-ons, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. To rank the prognosis for all add-ons, we used surface under the cumulative ranking (SUCRA) values. Outcomes: From 614 potential studies identified, 27 eligible studies (n = 1,349 subjects) were included. All the studies demonstrated low to moderate risk of bias. For the analysis of body weight change, all add-ons except Ranitidine showed significant weight reductions comparing to placebo. The effectiveness rank based on SUCRA results from highest to lowest was Sibutramine, Topiramate, Metformin, Reboxetine, Ranitidine, and placebo. A similar pattern was seen for BMI change. The analysis of safety outcome did not detect significantly increased withdrawn number from the add-ons. Current evidence showed relatively good tolerance and safety of using the pharmacological add-ons. Interpretation: Topiramate and Metformin are effective add-on treatments in controlling antipsychotic-induced weight gain, comparing to placebo. They are well tolerated in short-term period. Although Sibutramine has the highest rank of the effectiveness, its license has been withdrawn in many countries due to its adverse effects. Hence, Sibutramine should not be adopted to treat antipsychotic-induced weight gain.

Diagnostic yield of ambulatory oesophageal studies on versus off proton pump inhibitors: a systematic review and meta-analysis.

BACKGROUND: Patients with persistent gastroesophageal reflux disease symptoms despite proton pump inhibitors are increasingly encountered. It remains controversial if proton pump inhibitors should be stopped before functional oesophageal tests. AIM: This meta-analysis compares the positive yield of oesophageal studies performed off versus on proton pump inhibitors. METHODS: Pubmed, Embase and the Cochrane Library were searched for eligible studies. Outcomes assessed were the number of subjects with: elevated oesophageal acid exposure time when studied off versus on proton pump inhibitors; positive symptom index (≥50%) and/or positive symptom association probability (≥95%) for acid reflux; and/or non-acid reflux events off versus on proton pump inhibitors. The random effects model was applied. RESULTS: Fifteen studies (n = 5033 individuals; 33% on proton pump inhibitors; 32% men; mean age 52.1 years) were analysed. Pooled risk ratio for the comparison of high oesophageal acid exposure time off versus on proton pump inhibitors was 2.16 (95% confidence interval (CI) 1.42-3.28). The risk ratio of a positive symptom index (acid reflux) was 2.64 (95% CI 1.52-4.57) and the risk ratio of a positive symptom association probability (acid reflux) was 2.94 (95% CI 2.31-3.74). Conversely, the risk ratio of a positive symptom index (non-acid reflux) was 0.96 (95% CI 0.49-1.88) and risk ratio of a positive symptom association probability (non-acid reflux) was 0.54 (95% CI 0.30-0.99). CONCLUSIONS: Oesophageal studies after proton pump inhibitor cessation improve the positive yield for acid reflux-related events but reduce the detection of symptomatic non-acid reflux events.

Factors affecting neurodevelopmental outcome at 2 years in very preterm infants below 1250 grams: a prospective study.

OBJECTIVE: To evaluate the neurodevelopmental outcomes of preterm very-low birth weight (PT/VLBW) infants at 2 years and identify risk factors associated with significant developmental delay or neurodevelopmental impairment (NDI). STUDY DESIGN: We evaluated 165 PT/VLBW infants born between January 2010 and December 2011, using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III). NDI was defined as the presence of neurosensory impairment or significant delay with Bayley-III score < 70 in any domain and risk factors for delay/NDI were assessed using logistic regressions. RESULTS: Median Bayley-III composite scores in the cognitive, language and motor domains were 95, 89 and 94, respectively. NDI was present in 20% of the children, with 5-18% having significant delay in either cognitive, language or motor domain, seven (4%) children had cerebral palsy, three (2%) were deaf and none were blind. Regression models identified significant positive associations of delayed cognitive skills with male gender (Odds ratio (OR) 22.4, 95% confidence interval (CI) 1.5-341.1; P = 0.025), lack of anntenatal steroids (ANS) (OR 41.5, 95% CI 3.5-485.7; P = 0.003), and hypotension needing inotropes (OR 36.0, 95% CI 2.6-506.0; P = 0.008); delayed language skills with lower maternal education (OR 3.8, 95% CI 1.4-10.3; P = 0.10), lack of ANS (OR 2.8, 95% CI 1.1-7.4; P = 0.04), and 5 minute Apgar Score ≤ 5 (OR 7.4, 95% CI 1.4-38.4; P = 0.017) and delayed motor skills with chronic lung disease at 36 weeks (OR 38.3, 95% CI 2.4-603.4; P = 0.010). NDI was associated with lack of ANS (OR 2.91, 95% CI 1.21-7.00; P = 0.02) and use of postnatal steroids (OR 3.36, 95% CI 1.07-10.54; P = 0.0374). CONCLUSION: Risk factors for both NDI and individual domain delay were identified and will be helpful in planning of specific and targeted early intervention services.

Nutritional intake and growth velocity in preterm extremely low-birthweight infants in Asia: Are we doing enough?

AIM: To describe nutritional practices among preterm extremely low-birthweight (ELBW) infants and their impact on growth and to compare differences in nutritional intervention and comorbidities between those with limited growth velocity (GV < 25th percentile) and those with GV > 25th percentile. METHODS: A prospective cohort study was conducted to assess total protein and energy intake for week 1, days 14, 21 and 28 of life. Post-natal growth was calculated by measuring GV using an exponential model. Univariable analysis was applied to identify the potential risk factors associated with poor GV at day 28 and at discharge from hospital. RESULTS: The median GV from birth to day 28 was 9.84 g/kg/day and 11.87 g/kg/day for GV from birth to discharge. Increased protein and energy intake was associated with higher GV at discharge. Hypotension needing inotropes, necrotising enterocolitis (NEC), patent ductus arteriosus and chronic lung disease were significantly associated with reduced GV at discharge. Infants with NEC, hypotension needing inotropes and sepsis took a significantly longer time to achieve full enteral nutrition. A longer time to attain full enteral feeds was associated with slower GV at discharge. Small-for-gestational-age babies increased from 22% at birth to 66.6% at discharge. CONCLUSIONS: GV at discharge was positively correlated with increasing protein and energy intake in the first 28 days and adversely affected by the presence of neonatal morbidities. There was strong evidence of extra-uterine growth restriction, with the majority of preterm ELBW infants having lower z scores at discharge compared to at birth.

Effects of Aortic Valve Replacement on Severe Aortic Stenosis and Preserved Systolic Function: Systematic Review and Network Meta-analysis.

The survival benefits of aortic valve replacement (AVR) in the different flow-gradient states of severe aortic stenosis (AS) is not known. A comprehensive search in PubMed/MEDLINE, Embase, Cochrane Library, CNKI and OpenGrey were conducted to identify studies that investigated the prognosis of severe AS (effective orifice area ≤1.0 cm2) and left ventricular ejection fraction ≥50%. Severe AS was stratified by mean pressure gradient [threshold of 40 mmHg; high-gradient (HG) and low-gradient (LG)] and stroke volume index [threshold of 35 ml/m2; normal-flow (NL) and low-flow (LF)]. Network meta-analysis was conducted to assess all-cause mortality among each AS sub-type with rate ratio (RR) reported. The effects of AVR on prognosis were examined using network meta-regression. In the pooled analysis (15 studies and 9,737 patients), LF states (both HG and LG) were associated with increased mortality rate (LFLG: RR 1.88; 95% CI: 1.43-2.46; LFHG: RR: 1.77; 95% CI: 1.16-2.70) compared to moderate AS; and NF states in both HG and LG had similar prognosis as moderate AS (NFLG: RR 1.11; 95% CI: 0.81-1.53; NFHG: RR 1.16; 95% CI: 0.82-1.64). AVR conferred different survival benefits: it was most effective in NFHG (RR with AVR /RR without AVR : 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR with AVR /RR without AVR : 1.19; 95% CI: 0.74-1.94).