Oral semaglutide adequate glycaemia control with safe cardiovascular ‎profile

BackgroundType 2 diabetes is a chronic and progressive disease that ‎associated with series complication such as major adverse ‎cardiovascular events. Adequate glycaemic control proven ‎to reduce this risk. Orally administered semaglutide ‎promising medication in managing patient with type 2 ‎diabetes.‎AimsTo assess the cardiovascular safety and efficacy of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes.Methods Pub Med, ‎Google Scholar, and EBSCO ‎ databases were ‎systematically search for relevant articles. The terms‎ diabetes‎, Glucagon-like peptide, semaglutide‎ were used. Out of hundred twenty-two records, only ‎four fulfilled ‎the inclusion criteria.Results Four placebo-controlled studies with oral semaglutide ‎were included. Single study concern about the cardiovascular safety of oral semaglutide ‎and showed that, ‎compared with placebo, semaglutide ‎ was not associated ‎with increased in the cardiovascular events. On the other ‎hand, the remaining trials shown that, semaglutide ‎ can ‎effectively control the blood glucose as evident by ‎reduction in HA1c.ConclusionOral semaglutide can effectively and safely lower blood glucose without increase in the major adverse ‎cardiovascular events‎‎ (MACE).

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Influence of CAD/CAM Milling and 3D-Printing Fabrication Methods on the Mechanical Properties of 3-Unit Interim Fixed Dental Prosthesis after Thermo-Mechanical Aging Process

This study assessed the influence of CAD/CAM milling and 3D-printing fabrication methods on mechanical properties of 3-unit interim fixed dental prosthesis (IFDPs) after thermo-mechanical aging. Forty 3-unit IFDPs were fabricated on a mandibular right second premolar and second molar of a typodont cast. Samples were fabricated from the following materials; auto-polymerized polymethyl methacrylate (conventional resin), CAD/CAM PMMA (milled resin) and two different CAD/CAM 3D-printed composite resins; digital light processing Asiga (DLP AS) and stereolithography NextDent (SLA ND). Mechanical properties were compared between the studied materials using Kruskal–Wallis test, followed by multiple pairwise comparisons using Bonferroni adjusted significance. There was a significant difference in flexural strength and microhardness between the studied materials (p p = 0.02). In conclusion, superior flexural strength, elastic modulus, and hardness were reported for milled IFDPs. SLA ND printed IFDPs showed comparable mechanical properties to milled ones except for the elastic modulus

Effect of Different Scaling Methods on the Surface Topography of Different CAD/CAM Ceramic Compositions

This study evaluated the effect of ultrasonic and manual scaling using different scaler materials on the surface topography of computer-aided designing and computer-aided manufacturing (CAD/CAM) ceramic compositions. After scaling with manual and ultrasonic scalers, the surface properties of four classes of CAD/CAM ceramic discs: lithium disilicate (IPE), leucite-reinforced (IPS), advanced lithium disilicate (CT), and zirconia-reinforced lithium silicate (CD) of 1.5 mm thickness were evaluated. Surface roughness was measured before and after treatment, and scanning electron microscopy was used to evaluate the surface topography following the performed scaling procedures. Two-way ANOVA was conducted to assess the association of the ceramic material and scaling method with the surface roughness. There was a significant difference in the surface roughness between the ceramic materials subjected to different scaling methods (p < 0.001). Post-hoc analyses revealed significant differences between all groups except for IPE and IPS where no significant differences were detected between them. CD showed the highest surface roughness values, while CT showed the lowest surface roughness values for the control specimens and after exposure to different scaling methods. Moreover, the specimens subjected to ultrasonic scaling displayed the highest roughness values, while the least surface roughness was noted with the plastic scaling method

Comparative Evaluation of TiO₂ Nanoparticle Addition and Postcuring Time on the Flexural Properties and Hardness of Additively Fabricated Denture Base Resins

Three-dimensionally (3D)-printed fabricated denture bases have shown inferior strength to conventional and subtractively fabricated ones. Several factors could significantly improve the strength of 3D-printed denture base resin, including the addition of nanoparticles and post-curing factors. This study evaluated the effect of TiO2 nanoparticle (TNP) addition and the post-curing time (PCT) on the flexural properties and hardness of three-dimensionally (3D)-printed denture base resins. A total of 360 specimens were fabricated, with 180 specimens from each type of resin. For evaluating the flexural properties, bar-shaped specimens measuring 64 × 10 × 3.3 mm were used, while, for the hardness testing, disc-shaped specimens measuring 15 × 2 mm were employed. The two 3D-printed resins utilized in this study were Asiga (DentaBASE) and NextDent (Vertex Dental B.V). Each resin was modified by adding TNPs at 1% and 2% concentrations, forming two groups and an additional unmodified group. Each group was divided into three subgroups according to the PCT (15, 60, and 90 min). All the specimens were subjected to artificial aging (5000 cycles), followed by testing of the flexural strength and elastic modulus using a universal testing machine, and the hardness using the Vickers hardness test. A three-way ANOVA was used for the data analysis, and a post hoc Tukey’s test was used for the pairwise comparisons (α = 0.05). Scanning electron microscopy (SEM) was used for the fracture surface analysis. The addition of the TNPs increased the flexural strength in comparison to the unmodified groups (p p p p < 0.001). Both concentrations of the TNPs increased the flexural strength, while the 2% TNP concentration decreased the elastic modulus and hardness of the 3D-printed nanocomposites. The flexural strength and hardness increased as the PCT increased. The material type, TNP concentration, and PCT are important factors that affect the strength of 3D-printed nanocomposites and could improve their mechanical performance

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol

Abstract Background Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2–2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8–1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. Methods The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. Discussion The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. Trial registration ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020

Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially