Stopping Nucleos(t)ide Analogues in Chronic Hepatitis B Using HBsAg Thresholds: A Meta-Analysis and Meta-Regression.

BACKGROUND AND AIMS: Recommendations for stopping nucleoside analogue (NA) therapy in hepatitis B e antigen-negative chronic hepatitis B (CHB) are unclear. End-of-treatment quantitative hepatitis B serum antigen (EOTqHBsAg) thresholds <100 IU/mL or <1000 IU/mL have been proposed as stopping criteria, which we assessed by meta-analysis and meta-regression. METHODS: We searched PubMed, EMBASE, and conference abstracts for studies of hepatitis B e antigen-negative CHB NA discontinuation. Extracted studies were analyzed for risk of bias, pooled risk of hepatitis B serum antigen (HBsAg) loss, virological relapse (VR), and biochemical relapse (BR). Significant heterogeneity (I2) was addressed by subgroup analysis and random-effects meta-regression with known important covariates, including EOTqHBsAg thresholds, ethnicity, duration of therapy, and follow-up. RESULTS: We found 24 articles (3732 subjects); 16 had low and 8 had moderate risk of bias. The pooled risks of HBsAg loss, VR, and BR for stopping therapy at EOTqHBsAg <100 IU/mL were 41.8%, 33.4%, and 17.3%, respectively, vs 4.6%, 72.1%, and 34.6%, respectively, for EOTqHBsAg ≥100 IU/mL. The pooled risks of HBsAg loss, VR, and BR for stopping therapy at EOTqHBsAg <1000 IU/mL were 22.0%, 52.7%, and 15.9%, respectively, vs 3.4%, 63.8%, and 26.4%, respectively, for EOTqHBsAg ≥1000 IU/mL. Multivariable analysis for HBsAg loss showed that ethnicity, follow-up duration, and EOTqHBsAg <100 IU/mL and ≥100 IU/mL explained 85% of the variance in heterogeneity; Asians with EOTqHBsAg <100 IU/mL had 28.2%, while non-Asians with EOTqHBsAg <1000 IU/mL had 38.4% HBsAg loss. Multivariable analysis showed EOTqHBsAg <100 IU/mL and ≥100 IU/mL and other covariates only explained 43% and 63% of the variance in heterogeneity for VR and BR, respectively, suggesting that other factors are also important for relapse. CONCLUSIONS: While EOTqHBsAg thresholds, ethnicity, and follow-up duration strongly predict HBsAg loss, this is not true for VR and BR, hence stopping NA therapy should be considered cautiously.

Cholestasis after Kasai operation predicts portal hypertension in native liver survivors of biliary atresia: a multicenter study.

PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.

Studying the high-rate deformation of soft materials via laser-induced membrane expansion.

Cavitation is a phenomenon that occurs when the internal pressure of a material exceeds the resistance to deformation provided by the surrounding medium. Several measurements, such as the blister test, bubble inflation, and cavitation rheology, take advantage of this phenomenon to measure the local mechanical properties of soft materials at relatively low deformation rates. Here, we introduce a new measurement called laser-induced membrane expansion (LIME) that measures the shear modulus of a thin membrane at high strain rates (≈106 s-1 to 108 s-1) by using laser ablation to rapidly expand a thin (tens of microns) elastomeric membrane. To demonstrate the capabilities of this measurement, we use LIME to study the mechanical properties of poly(dimethylsiloxane) (PDMS) membranes at several thicknesses (from 10 µm to 60 µm) and crosslink densities. We find that the shear modulus of the PDMS measured by LIME was weakly dependent on the crosslink density, but was strongly strain rate dependent with values ranging from 106 Pa to 108 Pa. This measurement platform presents a new approach to studying the mechanical properties of soft but thin materials over a range of deformation rates.

Pattern of Dental Emergencies at a Pediatric Tertiary Care Hospital during the COVID-19 Pandemic: A Retrospective Study.

BACKGROUND: The onset of the COVID-19 pandemic and government restrictions affecting dental health care professionals had an impact on pediatric dental emergency trends. The purpose of this study was to describe the effect of the COVID-19 pandemic on the characteristics, outcomes and management of pediatric dental emergencies in a single tertiary care hospital. METHODS: A retrospective review of children presenting to Montreal Children's Hospital for dental emergencies before and during the pandemic was conducted. Data collected included children's demographic characteristics, type of emergency visit, clinical signs and symptoms, as well as emergency management. For the pandemic period, data regarding patient symptoms of COVID-19 infection were also noted. RESULTS: Of the 2745 pediatric dental emergencies included, 1336 (48.7%) occurred in 2019 and 1409 (51.3%) in 2020. During the first wave of COVID-19, the number of pediatric dental emergencies increased by 21% over pre-pandemic levels. A significant increase in the number of emergencies associated with dental infection was noted during the pandemic period (p = 0.04). A significant increase in the number of visits not receiving effective immediate treatment (p < 0.01) occurred during the early pandemic period. CONCLUSION: Our study shows a significant increase in the rates of dental emergencies and acuity of dental conditions during the first wave of the pandemic. Increased public health measures and adaptation to this ongoing public health crisis are important to ensure continued high-quality dental care for pediatric patients.

Modified vertical lid split orbitotomy: a case series and literature review.

PURPOSE: To describe the modified vertical lid split (VLS) technique for anterior orbitotomy and report surgical outcomes in patients with intraconal lesion removal using this surgical technique. METHOD: Retrospective review of medical records and orbital images. RESULTS: A total of four (female = 3) patients with intraconal orbital lesions underwent modified VLS orbitotomy from January 1, 2019 to June 30, 2021 in Hong Kong East Cluster. The average age was 49.3 years old (range: 35-65). Complete excision of intraconal orbital lesion was performed in all four cases. All cases were cavernous haemangioma histologically. All patients were satisfied with their cosmesis postoperatively and most had satisfactory postoperative extraocular movement. CONCLUSION: Modified VLS approach is simple and provides good intraoperative surgical exposure for intraconal lesions, giving the additional advantage of better scar camouflage.

Single or double? A comparison of evisceration techniques.

PURPOSE: We compared the rates of implant exposure and extrusion after evisceration with single and double scleral closure techniques. METHODS: This retrospective cohort study included all patients who underwent evisceration with an implant insertion over the past 18 years at Tung Wah Eastern Hospital and Pamela Youde Nethersole Eastern Hospital. Clinical documents and operation records were reviewed. RESULTS: A total of 81 ethnic Chinese patients (44 male) who underwent evisceration with primary implant insertion were reviewed. 39 (48%) patients underwent the double scleral closure technique with an implant placed posterior to the posterior sclera, and 42 (52%) patients underwent the single scleral closure technique with an implant inserted in the intra-scleral cavity. The follow-up interval was 70 months. The surgical indications were endophthalmitis (35%), painful blind eye (23%), traumatic disfigured globe (22%) and phthisis bulbi (20%). Silicone was the most used implant material (69%). The patients who underwent double scleral closure had a larger size of the implant (19.7 vs 17.9 mm, p < 0.05). Both implant exposure (26% vs 3%, p < 0.05) and implant extrusion (26% vs 0%, p < 0.05) were more common in patients who underwent single scleral. CONCLUSIONS: Double scleral closure technique allows a larger implant, and it is associated with a lower rate of implant exposure and extrusion. The double scleral closure technique is a superior technique of choice in these patients with primary implant placement.

Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT.

BACKGROUND & AIMS: The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA. METHODS: We conducted a randomized controlled trial of CHB patients on NA >12 months with HBV DNA(-) randomized to switch or add-on peginterferon-alpha2b (1.5 µg/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg) >1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg <200 IU/mL, qHBsAg <100 IU/mL, HBV DNA(-), viral relapse, and safety. Analysis was by intention-to-treat (ITT). RESULTS: A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P < .0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P < .001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P < .0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy). CONCLUSIONS: ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy. ClincialTrials.gov number: NCT01928511.

Controlling toughness of polymer-grafted nanoparticle composites for impact mitigation.

Toughness in an entangled polymer network is typically controlled by the number of load-bearing topological constraints per unit volume. In this work, we demonstrate a new paradigm for controlling toughness at high deformation rates in a polymer-grafted nanoparticle composite system where the entanglement density increases with the molecular mass of the graft. An unexpected peak in the toughness is observed right before the system reaches full entanglement that cannot be described through the entanglement concept alone. Quasi-elastic neutron scattering reveals enhanced segmental fluctuations of the grafts on the picosecond time scale, which propagate out to nanoparticle fluctuations on the time scale 100s of seconds as evidenced by X-ray photon correlation spectroscopy. This surprising multi-scale dissipation process suggests a nanoparticle jamming-unjamming transition. The realization that segmental dynamics can be coupled with the entanglement concept for enhanced toughness at high rates of deformation is a novel insight with relevance to the design of composite materials.

Tuning the mechanical impedance of disordered networks for impact mitigation.

Disordered-Network Mechanical Materials (DNMM), comprised of random arrangements of bonds and nodes, have emerged as mechanical metamaterials with the potential for achieving fine control over their mechanical properties. Recent computational studies have demonstrated this control whereby an extremely high degree of mechanical tunability can be achieved in disordered networks via a selective bond removal process called pruning. In this study, we experimentally demonstrate how pruning of a disordered network alters its macroscopic dynamic mechanical response and its capacity to mitigate impact. Impact studies with velocities ranging from 0.1 m s-1 to 1.5 m s-1 were performed, using a mechanical impactor and a drop tower, on 3D printed pruned and unpruned networks comprised of materials spanning a range of stiffness. High-speed videography was used to quantify the changes in Poisson's ratio for each of the network samples. Our results demonstrate that pruning is an efficient way to reduce the transmitted force and impulse from impact in the medium strain rate regime (101 s-1 to 102 s-1). This approach provides an interesting alternative route for designing materials with tailored impact mitigating properties compared to random material removal based on open cell foams.

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Patient cost consciousness in the emergency department.

BACKGROUND: 'Surprise billing', or the phenomenon of unexpected coverage gaps in which patients receiving out-of-network medical bills after what they thought was in-network care, has been a major focus of policymakers and advocacy groups recently, particularly in the Emergency Department (ED) setting, where patients' ability to choose a provider is exceedingly limited. The No Surprises Act is the legislative culmination to address "surprise bills," with the aim of promoting price transparency as a solution for billing irregularities. However, the knowledge and perceptions of patients regarding emergency care price transparency, particularly the degree to which ED patients are cost conscious is unknown. Accordingly, we sought to quantify that perception by measuring patients' direct predictions for the cost of their care. METHODS: We conducted an in-person survey of patients in Emergency Departments (EDs) over an 10-month period at two campuses within a large academic hospital system in southern Connecticut. We surveyed a convenience sample of patients at the bedside regarding demographics, care seeking perceptions and their estimates of the total and out-of-pocket costs for their ED care. Survey data was linked to institutional hospital finance datasets including actual charges and payments. We then later obtained the actual costs and billed amounts and compared these to the patients' estimates using a paired t-test. We also analyzed results according to certain patient demographics. RESULTS: A total of 600 patients were approached for survey, and data from 455 were available for the final analysis. On average, patients overestimated the cost of their care by $2484 and overestimated out-of-pocket cost by $144; both of these results met statistical significance (p < .005). Patients were better able to predict both total and out-of-pocket costs if they were: college educated or above; unemployed or retired; aged 65 or older; or had private insurance. Uninsured patients could better predict total cost but not out-of-pocket costs. One in 4 patients reported considering the cost of care prior to visiting the ED. Only 12 patients reported trying to look up that price before coming. CONCLUSIONS: This study is the first to our knowledge that sought to quantify how patients perceive the cost of acute, unscheduled care in the ED. We found that ED patients generally do not consider the price before going to the ED, and subsequently overestimate the negotiated total costs of acute, unscheduled emergency care as well as their out-of-pocket responsibility for care. Certain demographics are less predictive of this association. Notably, patients with Medicare/Medicaid and those with high school education or below were of the furthest off in predicting the actual cost of care. This lends credence to the established trend of patients' limited knowledge of the total cost of healthcare; moreover, that they overestimate the cost of their care could serve as a barrier to accessing that care particularly in more vulnerable groups. We hope that this finding adds useful information to policymakers in sculpting future legislation around surprise billing.

Supersonic Impact Response of Polymer Thin Films via Large-Scale Atomistic Simulations.

Recent nanoscale ballistic tests have shown the applicability of nanomaterials for ballistic protection but have raised questions regarding the nanoscale structure-property relationships that contribute to the ballistic response. Herein, we report on multimillion-atom reactive molecular dynamics simulations of the supersonic impact, penetration, and failure of polyethylene (PE) and polystyrene (PS) ultrathin films. The simulated specific penetration energy (Ep*) versus impact velocity predicts to within 15% the experimentally determined Ep* for PS. For impact velocities less than 1 km s-1, a crazing/petalling failure mode is observed due to chain disentanglement, transitioning to fragmentation coupled with large amounts of adiabatic heating at velocities greater than 1 km s-1. Interestingly, the high entanglement density of PE provides enhanced penetration resistance at low velocities, whereas increased adiabatic heating in PS promotes greater penetration resistance at elevated velocities. By understanding nanoscale mechanisms of energy absorption, nanomaterials can be designed to provide superior penetration resistance.

Randomized Controlled Trial Comparing Drug-coated Balloon Angioplasty versus Conventional Balloon Angioplasty for Treating Below-the-Knee Arteries in Critical Limb Ischemia: The SINGA-PACLI Trial.

Background There is a paucity of randomized trials demonstrating superior efficacy of drug-coated balloon angioplasty (DCBA) compared with conventional percutaneous transluminal angioplasty (PTA) for below-the-knee arterial disease in patients with -critical limb ischemia. Purpose To compare DCBA versus PTA for below-the-knee lesions in participants with critical limb ischemia through 12 months. Materials and Methods In this prospective, randomized, two-center, double-blind superiority study, participants with critical limb ischemia with rest pain or tissue loss with atherosclerotic disease in the native below-the-knee arteries were randomly assigned (in a one-to-one ratio) to DCBA or PTA after stratification for diabetes and renal failure between November 2013 and October 2017. The primary efficacy end point was angiographic primary patency at 6 months analyzed on an intention-to-treat basis. Secondary end points through 12 months were composed of major adverse events including death and major amputations, wound healing, limb salvage, clinically driven target-lesion revascularization, and amputation-free survival. Primary and binary secondary end points, analyzed by using generalized-linear model and time-to-event analyses, were estimated with Kaplan-Meier survival curves and hazard ratios (Cox regression). Results Seventy participants (mean age, 61 years ± 10 [standard deviation]; 43 men) in the DCBA group and 68 (mean age, 64 years ± 10; 50 men) in the PTA group were evaluated. The percentage of patients with angiographic primary patency at 6 months was 43% (30 of 70) in the DCBA group and 38% (26 of 68) in the PTA group (P = .48). Through 12 months, the percentage of deaths was similar: 21% in the DCBA group and 16% in the PTA group (P = .43). Amputation-free survival rate assessed with Kaplan-Meier curves differed through 12 months: 59% (41 of 70) in the DCBA group compared with 78% (53 of 68) in the PTA group (P = .01). Conclusion In participants with critical limb ischemia, the drug-coated balloon angioplasty group and the conventional percutaneous transluminal angioplasty group had similar primary patency rates at 6 months after treatment of below-the-knee arteries. Amputation-free survival rates through 12 months were higher in the percutaneous transluminal angioplasty group. © RSNA, 2021 Online supplemental material is available for this article.

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.

Walking for hypertension.

BACKGROUND: Increased physical activity has been recommended as an important lifestyle modification for the prevention and control of hypertension. Walking is a low-cost form of physical activity and one which most people can do. Studies testing the effect of walking on blood pressure have revealed inconsistent findings. OBJECTIVES: To determine the effect of walking as a physical activity intervention on blood pressure and heart rate. SEARCH METHODS: We searched the following databases up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 2), Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO, SPORTDiscus, PEDro, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the following Chinese databases up to May 2020: Index to Taiwan Periodical Literature System; National Digital Library of Theses and Dissertation in Taiwan; China National Knowledge Infrastructure (CNKI) Journals, Theses & Dissertations; and Wanfang Medical Online. We contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants, aged 16 years and over, which evaluated the effects of a walking intervention compared to non-intervention control on blood pressure and heart rate were included. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Where data were not available in the published reports, we contacted authors. Pooled results for blood pressure and heart rate were presented as mean differences (MDs) between groups with 95% confidence intervals (CIs). We undertook subgroup analyses for age and sex. We undertook sensitivity analyses to assess the effect of sample size on our findings. MAIN RESULTS: A total of 73 trials met our inclusion criteria. These 73 trials included 5763 participants and were undertaken in 22 countries. Participants were aged from 16 to 84 years and there were approximately 1.5 times as many females as males. The characteristics of walking interventions in the included studies were as follows: the majority of walking interventions was at home/community (n = 50) but supervised (n = 36 out of 47 reported the information of supervision); the average intervention length was 15 weeks, average walking time per week was 153 minutes and the majority of walking intensity was moderate. Many studies were at risk of selection bias and performance bias. Primary outcome We found moderate-certainty evidence suggesting that walking reduces systolic blood pressure (SBP) (MD -4.11 mmHg, 95% CI -5.22 to -3.01; 73 studies, n = 5060). We found moderate-certainty evidence suggesting that walking reduces SBP in participants aged 40 years and under (MD -4.41 mmHg, 95% CI -6.17 to -2.65; 14 studies, n = 491), and low-certainty evidence that walking reduces SBP in participants aged 41 to 60 years (MD -3.79 mmHg, 95% CI -5.64 to -1.94, P < 0.001; 35 studies, n = 1959), and those aged 60 years of over (MD -4.30 mmHg, 95% CI -6.17 to -2.44, 24 studies, n = 2610). We also found low certainty-evidence suggesting that walking reduces SBP in both females (MD -5.65 mmHg, 95% CI -7.89 to -3.41; 22 studies, n = 1149) and males (MD -4.64 mmHg, 95% CI -8.69 to -0.59; 6 studies, n = 203). Secondary outcomes We found low-certainty evidence suggesting that walking reduces diastolic blood pressure (DBP) (MD -1.79 mmHg, 95% CI -2.51 to -1.07; 69 studies, n = 4711) and heart rate (MD -2.76 beats per minute (bpm), 95% CI -4.57 to -0.95; 26 studies, n = 1747). We found moderate-certainty evidence suggesting that walking reduces DBP for participants aged 40 years and under (MD -3.01 mmHg, 95% CI -4.44 to -1.58; 14 studies, n = 491) and low-certainty evidence suggesting that walking reduces DBP for participants aged 41 to 60 years (MD -1.74 mmHg, 95% CI -2.95 to -0.52; 32 studies, n = 1730) and those aged 60 years and over (MD -1.33 mmHg, 95% CI -2.40 to -0.26; 23 studies, n = 2490). We found moderate-certainty evidence that suggests walking reduces DBP for males (MD -2.54 mmHg, 95% CI -4.84 to -0.24; 6 studies, n = 203) and low-certainty evidence that walking reduces DBP for females (MD -2.69 mmHg, 95% CI -4.16 to -1.23; 20 studies, n = 1000). Only 21 included studies reported adverse events. Of these 21 studies, 16 reported no adverse events, the remaining five studies reported eight adverse events, with knee injury being reported five times. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that walking probably reduces SBP. Moderate- or low-certainty evidence suggests that walking may reduce SBP for all ages and both sexes. Low-certainty evidence suggests that walking may reduce DBP and heart rate. Moderate- and low-certainty evidence suggests walking may reduce DBP and heart rate for all ages and both sexes.

A Review of Tolerance and Safety Profiles of Long-Term Botulinum Neurotoxin Type A in Asian Patients with Hemifacial Spasm and Benign Essential Blepharospasm.

This article reports the tolerance and long-term safety profiles of botulinum neurotoxin type A among Asian patients with benign essential blepharospasm (BEB) and hemifacial spasm (HFS). We performed a retrospective review of clinical documents and procedure records of consecutive BEB and HFS patients receiving onabotulinum toxin A (Botox) treatment in our clinic over the past 20 years. We reviewed the information of 105 patients diagnosed with BEB (n = 31) and HFS (n = 74). All of the patients were Asian. The mean age of disease onset was 59 (range 37-80) years old for BEB and 61 (range 31-83) for HFS. The mean follow up was 84 (range 12-240) months and the mean number of sessions per patient was 19 (range 1-61). The botulinum toxin dose per session increased significantly in both BEB (16.5 versus 21.6 units, p < .05) and HFS (22.6 versus 26.9 units, p < .05) patients after a mean of 18 sessions; however, the onset time, effective duration and subjective treatment outcome were similar over time in both BEB and HFS patients. At least one local complication was reported among 26% and 41% of patients with BEB and HFS respectively, with ptosis (32%) being most frequent.

Delayed peroneal muscle reaction time in male amateur footballers during a simulated prolonged football protocol.

Peroneal muscle fatigue could result in ankle inversion sprain injuries. This study investigated the peroneal muscle reaction time during a simulated prolonged football protocol. Nine male footballers completed a 105-minute simulated prolonged football protocol. The peroneal muscle reaction time to an ankle inversion perturbation was measured every 15 minutes by a surface electromyography system sampling at 1000 Hz. One-way repeated ANOVA with post-hoc paired t-test showed a steady upward trend starting from 48.9 ms at baseline to 57.1 ms at the end of the first half, followed by a recovery back to 50.9 ms at the start of the second half and a further delay in the last 30 minutes to 60.2 ms at the end of the protocol. Delayed peroneal muscle reaction was found after 30 minutes of the first half and 15 minutes of the second half of a football match. The risk of ankle sprain could increase in the latter minutes in each half protocol. Thus, prevention injury training strategies should focus on these specific durations in football matches.

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta-analysis.

Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end-of-study (EOS), end-of-treatment (EOT) or end-of-follow-up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random-effects model. Forty-five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI-1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs <48 weeks, and loss of efficacy >2 years of follow-up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time.

Cutting to measure the elasticity and fracture of soft gels.

The fracture properties of very soft and/or brittle materials are challenging to measure directly due to the limitations of existing fracture testing methods. To address this issue, we introduce a razorblade-initiated fracture test (RIFT) to measure the mechanical properties related to fracture for soft polymeric gels. We use RIFT to quantify the elasticity, crack initiation energy, and the fracture energy of gellan hydrogels as a function of gellan concentration. Additionally, we use RIFT to study the role of friction in quantifying the fracture properties for poly(styrene-b-ethylene butadiene-b-styrene) gels as a function of test velocity. This new method provides a simple and efficient means to quantify the fracture properties of soft materials.