Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol

Introduction Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysis This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work

Thermal based remediation technologies for soil and groundwater: a review

Thermal remediation technologies are fast and effective tools for the remediation of contaminated soils and sediments. Nevertheless, the high energy consumption and the effect of high temperature on the soil properties may hinder the wide applications of thermal remediation methods. This review highlights the recent studies focused on thermal remediation. Eight types of thermal remediation processes are discussed, including incineration, thermal desorption, stream enhanced extraction, electrical resistance heating, microwave heating, smoldering, vitrification, and pyrol-ysis. In addition, the combination of thermal remediation with other remediation technologies is presented. Finally, thermal remediation sustainability is evaluated in terms of energy efficiency and their impact on soil properties. The developments of the past decade show that thermal-based technologies are quite effective in terms of contaminant removal but that these technologies are associated with high energy use and costs and can has an adverse impact on soil properties. Nonetheless, it is anticipated that continued research on thermally based technologies can increase their sustainability and expand their applications. Low temperature thermal desorption is a prom-ising remediation technology in terms of land use and energy cost as it has no adverse effect on soil function after treatment and low temperature is required. Overall, selecting the sustainable remediation technology depends on the contaminant properties, soil properties and predicted risk level. © 2022 Desalination Publications. All rights reserved

Hughes Abdominal Repair Trial (HART)—abdominal wall closure techniques to reduce the incidence of incisional hernias: feasibility trial for a multicentre, pragmatic, randomised controlled trial

Objectives Incisional hernias are common complications of midline abdominal closure. The ‘Hughes Repair’ combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. There is evidence to suggest this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared Hughes repair with standard mass closure for the prevention of incisional hernia formation. This paper aims to test the feasibility of running a randomised controlled trial of a comparison of abdominal wall closure methods following midline incisional surgery for colorectal cancer, in preparation to a definitive randomised controlled trial. Design and setting A feasibility trial (with 1:1 randomisation) conducted perioperatively during colorectal cancer surgery. Participants Patients undergoing midline incisional surgery for resection of colorectal cancer. Interventions Comparison of two suture techniques (Hughes repair or standard mass closure) for the closure of the midline abdominal wound following surgery for colorectal cancer. Primary and secondary outcomes A 30-patient feasibility trial assessed recruitment, randomisation, deliverability and early safety of the surgical techniques used. Results A total of 30 patients were randomised from 43 patients recruited and consented, over a 5-month period. 14 and 16 patients were randomised to arms A and B, respectively. There was one superficial surgical site infection (SSI) and two organ space SSIs reported in arm A, and two superficial SSIs and one complete wound dehiscence in arm B. There were no suspected unexpected serious adverse reactions reported in either arm. Independent data monitoring committee found no early safety concerns. Conclusions The feasibility trial found no early safety concerns and demonstrated that the trial was acceptable to patients. Progression to the pilot and main phases of the trial has now commenced following approval by the independent data monitoring committee

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Left-sided gall bladder: Report of two cases

Left-sided gall bladder without situs inversus viscerum is a rare albeit recognized clinical entity. We report our experience of two cases of left-sided gall bladder in two women aged 36 and 48 who underwent laparoscopic cholecystectomy for chronic calculous cholecystitis. Left-sided gall bladder may provide an unusual surprise to the surgeons during laparoscopy as routine pre-operative studies may not always detect the anomaly. Awareness of the unpredictable confluence of the cystic duct into the common bile duct (CBD) and selective use of intraoperative cholangiography aid in the safe laparoscopic management of this unusual entity

Hughes Abdominal Repair Trial (HART)-abdominal wall closure techniques to reduce the incidence of incisional hernias: feasibility trial for a multicentre, pragmatic, randomised controlled trial.

Objectives Incisional hernias are common complications of midline abdominal closure. The ‘Hughes Repair’ combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. There is evidence to suggest this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared Hughes repair with standard mass closure for the prevention of incisional hernia formation. This paper aims to test the feasibility of running a randomised controlled trial of a comparison of abdominal wall closure methods following midline incisional surgery for colorectal cancer, in preparation to a definitive randomised controlled trial. Design and setting A feasibility trial (with 1:1 randomisation) conducted perioperatively during colorectal cancer surgery. Participants Patients undergoing midline incisional surgery for resection of colorectal cancer. Interventions Comparison of two suture techniques (Hughes repair or standard mass closure) for the closure of the midline abdominal wound following surgery for colorectal cancer. Primary and secondary outcomes A 30-patient feasibility trial assessed recruitment, randomisation, deliverability and early safety of the surgical techniques used. Results A total of 30 patients were randomised from 43 patients recruited and consented, over a 5-month period. 14 and 16 patients were randomised to arms A and B, respectively. There was one superficial surgical site infection (SSI) and two organ space SSIs reported in arm A, and two superficial SSIs and one complete wound dehiscence in arm B. There were no suspected unexpected serious adverse reactions reported in either arm. Independent data monitoring committee found no early safety concerns. Conclusions The feasibility trial found no early safety concerns and demonstrated that the trial was acceptable to patients. Progression to the pilot and main phases of the trial has now commenced following approval by the independent data monitoring committee

Recent Advances of Nanoremediation Technologies for Soil and Groundwater Remediation: A Review

Nanotechnology has been widely used in many fields including in soil and groundwater remediation. Nanoremediation has emerged as an effective, rapid, and efficient technology for soil and groundwater contaminated with petroleum pollutants and heavy metals. This review provides an overview of the application of nanomaterials for environmental cleanup, such as soil and groundwater remediation. Four types of nanomaterials, namely nanoscale zero-valent iron (nZVI), carbon nanotubes (CNTs), and metallic and magnetic nanoparticles (MNPs), are presented and discussed. In addition, the potential environmental risks of the nanomaterial application in soil remediation are highlighted. Moreover, this review provides insight into the combination of nanoremediation with other remediation technologies. The study demonstrates that nZVI had been widely studied for high-efficiency environmental remediation due to its high reactivity and excellent contaminant immobilization capability. CNTs have received more attention for remediation of organic and inorganic contaminants because of their unique adsorption characteristics. Environmental remediations using metal and MNPs are also favorable due to their facile magnetic separation and unique metal-ion adsorption. The modified nZVI showed less toxicity towards soil bacteria than bare nZVI; thus, modifying or coating nZVI could reduce its ecotoxicity. The combination of nanoremediation with other remediation technology is shown to be a valuable soil remediation technique as the synergetic effects may increase the sustainability of the applied process towards green technology for soil remediation

Nanoscale zero-valent iron application for the treatment of soil, wastewater and groundwater contaminated with heavy metals: a review

Nanoscale zero-valent iron (nZVI) has been extensively investigated for the remediation of soil, wastewater, and groundwater contaminated with heavy metals. This paper presents a collective review of nZVI synthesis, nZVI interaction mechanisms with heavy metals, factors affecting nZVI reactivity, recent applications of nZVI for heavy metals removal, and the environmental concerns of nZVI application for soil microorganisms and plants. Modified nZVI, spatially biochar supported nZVI (BC@nZVI) and sulfidation nanoscale zero-valent iron (S-nZVI) showed high heavy metals removal efficiency and more stable performance compared to nZVI alone. The removal of heavy metals by nZVI is as a synergistic process where adsorption, oxidation/reduction and precipitation occur simultaneously or in series. pH and organic matter are the main factors that significantly affect nZVI reactivity. Toxic effects of nZVI are observed for the soil microorganisms as the direct contact may cause a decrease in cell viability and membrane damage. A low concentration of nZVI promotes the growth of plant whereas high concentration decreases root length. It is observed that, further research is needed to enhance nZVI recovery techniques, evaluate the effectiveness of novel modified nZVI and their effects on the environment, and the full-scale application of nZVI

Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D):Trial protocol

INTRODUCTION: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications. Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis. METHODS AND ANALYSIS: This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D. Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible. Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1. MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work. ETHICS AND DISSEMINATION: This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018. The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN14274380