Incidence Of Adverse Effects Research Articles

The efficacy and safety of GLP-1 agonists to modify cardiovascular morbidity in patients with obesity without diabetes mellitus: a meta-analysis involving 32,884 patients

Abstract Background While the cardioprotective effects of glucagon-like peptide -1 (GLP-10) agonists are well-documented in diabetic patients, their impact on cardiovascular outcomes in patients with obesity without diabetes mellitus remains debated. Purpose This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of GLP-1 on cardiovascular outcomes in patients with obesity without diabetes mellitus. Methods A systematic review and meta-analysis synthesizing RCTs were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 26th, 2023. Dichotomous data were pooled using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Results We included 19 RCTs with a total of 32,884 patients. There was no difference between GLP-1 agonists and placebo regarding cardiovascular mortality (RR: 0.85, 95% CI [0.71- 1.01], P= 0.07). However, GLP-1 agonists significantly decreased the incidence of all-cause mortality (RR 0.83, 95% CI 0.72 to 0.94, p < 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63 to 0.96, p = 0.02), and myocardial infarction (RR 0.73, 95% CI 0.62 to 0.87, p < 0.0001). Also, GLP-1 agonists significantly increased the incidence of any adverse events (RR 1.11, 95% CI 1.05 to 1.16, p < 0.0001), with no difference regarding the incidence of serious adverse events. Conclusion GLP-1 agonists not only demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, but also effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.

Effect of baseline anemia on the efficacy of docetaxel and ramucirumab for advanced non-small cell lung cancer treatment

BackgroundDocetaxel (DOC) and ramucirumab (RAM) is one of the most effective regimens for advanced non-small cell lung cancer (NSCLC) treatment. In our previous study, baseline anemia was identified as a preventive factor against the development of severe adverse effects during the first treatment cycle. It was hypothesized that anemia directly promotes tumor angiogenesis, leading to the elevation of RAM efficacy with increased DOC delivery to tumors, while reducing DOC delivery to other organs, potentially mitigating severe adverse effects. If this hypothesis is correct, patients with baseline anemia may have better clinical outcomes than those with normal hemoglobin levels. In this study, we aimed to investigate the effect of baseline anemia on the efficacy of DOC + RAM in treating advanced NSCLC in a real-word setting.MethodsPatients with advanced NSCLC receiving DOC + RAM (n = 72) were retrospectively assessed. They were categorized into a control group with normal baseline hemoglobin levels and an anemia group with baseline anemia. The primary endpoint was progression-free survival (PFS) evaluation.ResultsPatients in the anemia group had a significantly shorter PFS than that of patients in the control group (median PFS: 3.2 and 6.2 months; 95% confidence interval [CI]: 2.2–4.8 and 4.3–9.9 months, respectively;P = 0.008). In addition, the disease control rate in the anemia group was 65.8%, which was significantly lower than that in the control group (93.6%; P = 0.007). Overall survival tended to be shorter in patients with anemia than in controls, although the difference was not statistically significant (P = 0.07). Multivariate Cox hazard analysis suggested that baseline anemia was a singular risk factor for poor PFS (adjusted hazard ratio 1.84, 95% CI 1.08–3.13; P = 0.02). The incidence of severe adverse effects did not differ between the two groups.ConclusionsThis study suggests that the PFS of patients with anemia treated with DOC + RAM for advanced NSCLC is shorter than that of those without the symptoms.

Exploring the therapeutic mechanisms of millet in obesity through molecular docking, pharmacokinetics, and dynamic simulation

Obesity, a prevalent global health concern, is characterized by excessive fat accumulation, which confers significant nutritional and health risks, including a shortened lifespan and diminished wellbeing. Central to the regulation of energy balance and food intake is the fat mass and obesity-associated (FTO) protein, which modulates the interplay between caloric consumption and energy expenditure. Given its pivotal role in obesity regulation, the identification of effective inhibitors targeting the FTO protein is imperative for developing therapeutic interventions. Currently available anti-obesity drugs are often plagued by undesirable side effects. In contrast, natural plant-derived bioactive compounds are gaining prominence in the pharmaceutical industry due to their efficacy and lower incidence of adverse effects. Little Millet, a traditional cereal known for its rich nutritional profile and high satiety index, was investigated in this study using molecular docking and dynamics simulation approach for its potential as an anti-obesity agent. Our research demonstrates that four bioactive compounds from Little Millet exhibit superior binding energies ranging from 7.22 to 8.83 kcal/mol, compared to the standard anti-obesity drug, orlistat, which has a binding energy of 5.96 kcal/mol. These compounds fulfilled all drug-like criteria, including the Lipinski, Ghose, Veber, Egan, and Muegge rules, and exhibited favorable profiles in terms of distribution, metabolism, and prolonged half-life without toxicity. Conversely, orlistat was associated with hepatotoxicity, a reduced half-life, and multiple violations of drug-likeness parameters, undermining its efficacy. Molecular dynamics simulations and Gibbs free energy assessments revealed that the four identified compounds maintain stable interactions with key residues in the FTO protein’s active site. We propose further validation through extensive In vitro, In vivo, and clinical studies to ascertain the therapeutic potential of these compounds in combating obesity.

The Ambivalence of Post COVID-19 Vaccination Responses in Humans.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has prompted a massive global vaccination campaign, leading to the rapid development and deployment of several vaccines. Various COVID-19 vaccines are under different phases of clinical trials and include the whole virus or its parts like DNA, mRNA, or protein subunits administered directly or through vectors. Beginning in 2020, a few mRNA (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and adenovirus-based (AstraZeneca ChAdOx1-S and the Janssen Ad26.COV2.S) vaccines were recommended by WHO for emergency use before the completion of the phase 3 and 4 trials. These vaccines were mostly administered in two or three doses at a defined frequency between the two doses. While these vaccines, mainly based on viral nucleic acids or protein conferred protection against the progression of SARS-CoV-2 infection into severe COVID-19, and prevented death due to the disease, their use has also been accompanied by a plethora of side effects. Common side effects include localized reactions such as pain at the injection site, as well as systemic reactions like fever, fatigue, and headache. These symptoms are generally mild to moderate and resolve within a few days. However, rare but more serious side effects have been reported, including allergic reactions such as anaphylaxis and, in some cases, myocarditis or pericarditis, particularly in younger males. Ongoing surveillance and research efforts continue to refine the understanding of these adverse effects, providing critical insights into the risk-benefit profile of COVID-19 vaccines. Nonetheless, the overall safety profile supports the continued use of these vaccines in combating the pandemic, with regulatory agencies and health organizations emphasizing the importance of vaccination in preventing COVID-19's severe outcomes. In this review, we describe different types of COVID-19 vaccines and summarize various adverse effects due to autoimmune and inflammatory response(s) manifesting predominantly as cardiac, hematological, neurological, and psychological dysfunctions. The incidence, clinical presentation, risk factors, diagnosis, and management of different adverse effects and possible mechanisms contributing to these effects are discussed. The review highlights the potential ambivalence of human response post-COVID-19 vaccination and necessitates the need to mitigate the adverse side effects.

Ultrasound-guided Genicular Nerve Block in Patients Undergoing Knee Arthroscopy: A Randomized Controlled Trial

This study was to investigate the efficacy of ultrasound-guided genicular nerve block for patients who underwent knee arthroscopy. Patients were randomized into two groups: 1. nerve block group: ultrasound-guided genicular nerve block (superomedial, superolateral and inferomedial genicular nerve, 2-ml 0.5% ropivacaine each nerve.) prior to the general anesthesia, 2. control group: no intervention prior to the general anesthesia. The measurements were pain severity at 3,6, 12, 24, 48, and 72 hours after surgery at rest and at activity(Pain severity was primary outcome at 3 hours after surgery at rest); the time for first ambulation; straight leg raise; mechanical pain threshold of the block areas; time of the surgery, anesthesia and extubation; the use of analgesics in the perioperative period and 72 hours after the surgery; the number of patients awakening from pain on the first two nights after the surgery; the length of hospital stay; postoperative adverse effects. The pain severity was performed by VAS (A 10-point visual analogue scale, 0 points painless, 10 points severe pain) and median (interquartile range; IQR). A total of 70 patients (median age: 53 y, 32 men; 35 per group) were included. Compared to the control group, the nerve block group had a lower pain VAS score at rest (2[2-2] vs. 3[2-4], P<0.01) at 3 hours, and lower pain VAS score at rest persisted for 24 hours and activity persisted for 12 hours after the surgery, also had lower intraoperative dosage of sufentanil (20±4.8 vs. 28.5±5.1 mg; P<0.001), lower requirement for analgesics for pain and lower PONV (postoperative nausea and vomiting) throughout the 72-hour observation period. There were no significant difference for the incidence of postoperative adverse effects and straight leg raise. In conclusion, ultrasound-guided genicular nerve block could reduce the pain severity after knee arthroscopy and decrease the use of intraoperative sufentanil without affecting motor function.

Effect of sacubitril and valsartan combined with conventional therapy on patients with heart failure

Purpose: To investigate the clinical effectiveness of the combination of sacubitril and valsartan with conventional therapy in the treatment of patients with heart failure. Methods: This was a retrospective study comprising 100 heart failure patients randomized into study (n = 57) and control groups (n = 43). The study group received sacubitril/valsartan along with conventional drug therapy while control group received only conventional drugs, viz, irbesartan, metoprolol slow release, and furosemide tablets. Echocardiogram showing left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left anterior descending artery (LAD), Nterminal pro-b-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), glomerular filtration rate (eGFR), and homocysteine (HCY) of the two groups were compared before and after treatment. Multiple regression was used to analyze the correlation between re-hospitalization and sacubitril/valsartan intervention. Results: The study group showed significantly lower LVEF, LVESD, LVEDD, LAD, NT-proBNP, and homocysteine levels after treatment compared to control group (p < 0.05). Re-hospitalization for abnormal cardiovascular events between the two groups was significantly different in the adjusted Cox proportional hazards regression model. Furthermore, multiple regression analysis showed that sacubitril/valsartan treatment was the independent variable (p < 0.001). Conclusion: Sacubitril/valsartan improves heart function, with reduced incidence of adverse effects without affecting renal function. Further studies are required to validate these findings by expanding sample size, strictly controlling data quality and strengthening follow-up.

Sublingual Administration of Tacrolimus is Safe and Provides Similar Drug Exposure to Per-oral Route in Liver Transplant Recipients During Early Postoperative Period–A Large, Retrospective, Observational Study

BackgroundPer-oral(PO) administration of Tacrolimus(TAC) results in inadequate trough levels in early post-operative period in liver-transplant(LT) recipients who undergo Roux-en-Y hepaticojejunostomy for biliary reconstruction. Sublingual administration(SL) of tacrolimus provides an alternative route in such patients. ObjectiveTo assess feasibility and safety of SL tacrolimus in adult LT-recipients in early post-operative period and to compare therapeutic efficacy of SL administration of tacrolimus vs.PO route. Patients and MethodSingle-centre, retrospective, observational study carried out in adult living donor liver transplant(LDLT) recipients between January 2022 till December 2022. Recipients who underwent Roux-en-Y hepaticojejunostomy for biliary reconstruction, received tacrolimus through SL route till post-operative day(POD)5 as they were kept nil per oral constituted the study group while recipients who underwent duct-to-duct(D-D) anastomosis for biliary reconstruction were allowed orally from POD1 and received PO-tacrolimus were chosen as controls. Feasibility and safety of SL-Tacrolimus was assessed in terms of patient acceptance, need to discontinue SL-Tacrolimus, incidence of local adverse effects and systemic adverse events like neurotoxicity and nephrotoxicity. Therapeutic efficacy was evaluated by comparing median trough levels(TAC level) achieved and incidence of graft rejection between two groups. Results212 patients underwent LT during the study period of which 125 were included(58 in SL-group and 67 in PO-group). Both groups had comparable baseline characteristics. In SL-group, all patients tolerated SL-Tacrolimus well and no local adverse events were observed. Patients with SL-Tacrolimus administration achieved higher median TAC level(ng/ml) vs.PO route(5.85 vs 5(p=0.06)) despite similar median cumulative tacrolimus dose before assessing TAC-level. 50% patients achieved TAC level ≥6ng/ml in SL-group vs. 35.8% in PO-group(p=0.14). Incidence of neurotoxicity, nephrotoxicity and graft rejection during hospital stay were similar in both the groups(p=0.56,0.82 and 0.28 respectively). ConclusionSL-tacrolimus is safe and provides similar trough levels to PO-tacrolimus and may be considered as viable alternative whenever inadequate TAC-levels are anticipated through per-oral route.

Herbs for the Therapy of Diabetes Mellitus: A Thorough Analysis with Particular Emphasis on Preclinical, Clinical Trials, and their Hypothesised Mechanisms

Background: In recent times, herbal medicines have experienced an expansion in both developing and developed countries due to their natural origin and low incidence of adverse effects. A systematic review was performed to gather information regarding herbal plants used to treat diabetes mellitus. Objective: The aim of this article was to review evidence from preclinical and clinical trials and the proposed mechanism of herbal drugs in diabetes mellitus. Methods: A literature survey was carried out mainly focused on scientific papers published in recent years. The search strategy involved interrelated keywords, like “Diabetes mellitus,” “Herbs,” “Hyperglycaemia,” and other uniterms. Electronic databases used were Scopus, Web of Science, PubMed, and Elsevier. Results: Twenty studies, including preclinical and clinical trials, were selected for evaluating the mechanism of the anti-hyperglycaemic effect of herbal drugs in diabetes mellitus. Conclusion: Through clinical and preclinical research as well as an analysis of the mechanism of action of herbs, the current review provides preliminary evidence for possible anti-diabetic benefits of herbal medicines.

Efficacy of Rectal Versus Oral Chloral Hydrate in Pediatric Auditory Brainstem Response: Randomized Controlled Trial.

To compare sedation success rates between rectal (RCH) and oral chloral hydrate (OCH) administration in children undergoing auditory brainstem response (ABR) testing and assess the incidence of adverse effects. Randomized controlled trial, performed between May 2023 and August 2023. Ear, Nose, and Throat Outpatient Department at tertiary care hospital. Pediatric patients aged 1 to 5 years, who were indicated for ABR testing were enrolled and randomly divided into 2 groups. The control group received 10% wt/vol chloral hydrate orally at a dose of 50 mg/kg, while the other group received the same dose through rectal administration. Onset of sedation, duration of sedation, recovery time, vital signs, and adverse effects were recorded and analyzed to assess sedative effectiveness and safety. Eighty-eight children were randomly assigned to RCH or OCH administration groups, the sedation success rates of RCH and OCH groups were 84.09% and 90.91%, respectively (P = .33). Adverse effects were detected in 11 children (12.5%), with a vomiting rate of 20.45% in the oral group versus 0% in the rectal group (P = .002). The diarrhea rate was 4.55% in the rectal group versus 0% in the oral group (P = .16). In either group, no serious adverse effects were documented. RCH and OCH are both safe and effective for short-term sedation in pediatric patients during ABR testing. Interestingly, RCH administration offers a high success rate without vomiting or major adverse effects. This study established the effectiveness of RCH for sedation in children under specialized supervision.

Pilot Clinical Safety and Efficacy Evaluation of a Topical 3% Tranexamic Acid Cream and Serum Protocol for Managing Facial Hyperpigmentation in Caucasian Patients

Facial hyperpigmentation is a highly prevalent dermatological condition, characterized by dark spots on the skin resulting from excess melanin production. Hyperpigmentation significantly impacts patients’ quality of life and self-esteem. Current treatments often present disadvantages linked to poor product tolerability. A topical cosmetic approach combining three lightening active ingredients (tranexamic acid, niacinamide, vitamin C) offers a new option for treating dark spots on the skin. The present in-use test under dermatological control evaluated the clinical safety and efficacy of a cream and serum containing these three ingredients, formulated with hyaluronic acid for enhanced delivery, stability, and efficacy. A total of 22 Caucasian patients with facial hyperpigmentation, both male and female, aged between 45 and 67 years, applied the cream and serum for 8 weeks. Clinical assessments, colorimetric evaluations, standardized photography, and self-assessment questionnaires were used to measure outcomes. No serious adverse effects were recorded, and the incidence of local adverse effects was low, highlighting good tolerability of the investigated test items. In most participants, significant improvements in hyperpigmented areas were recorded. Clinical scoring by the dermatologist investigator indicated a statistically significant 13% reduction in color intensity and a 6% reduction in the size of dark spots after 8 weeks of treatment. Colorimetric evaluation showed a statistically significant 1% increase in luminosity (L* parameter) and an 8% improvement in the Individual Typological Angle (ITA°) in endpoint, indicating lighter skin spots. Subjective assessments reflected high user satisfaction, with 95% of participants noting improvements in skin hydration and luminosity, and 77% reporting a reduced appearance of dark spots. Overall, the present work supports the use of tranexamic acid, niacinamide, and vitamin C as an effective and well-tolerated combined topical management option for hyperpigmentation. This combination offers a viable alternative to classical whiteners for individuals seeking to reduce facial skin coloration imbalance and improve skin tone.

Propensity score matching-based analysis of the effect of corticosteroids in treating severe drug-induced liver injury

Background and aimThere is no conventional treatment for patients with severe drug-induced liver injury (DILI) except for discontinuation of liver injury drugs and symptomatic supportive therapy. Opinions on whether corticosteroids can be used to treat severe DILI are conflicting, and most of the relevant clinical studies are case reports or retrospective studies, which still need to be supported by high-level evidence-based medical studies. This study aimed to evaluate the effect and tolerance of corticosteroids in patients with severe DILI. Risk factors associated with patient failure to cure were also explored. MethodsPropensity score matching based on nearest-neighbor 1:1 matching was used to screen severe DILI patients in the corticosteroids and control groups. Severe DILI was defined as elevated serum ALT and/or ALP with TBIL≥5 ULN (5 mg/dL or 85.5 μmol/L) with or without INR ≥1.5. Patients were treated with conventional therapy combined with corticosteroids in the corticosteroids group and only conventional therapy in the control group. ResultsA total of 146 patients, 73 each in the corticosteroids and control groups, were included in this study. By analyzing the entire cohort, we found no significant difference in cure rates between patients in the corticosteroid group and control group (34.2% vs. 20.5 %, p = 0.095), and there was no significant difference in the incidence of adverse effects between the two groups (20.5% vs. 20.5 %, p = 1.000). However, TBIL decreased more in the corticosteroids group on day 7 (89.2 ± 107.6 μmol/L vs. 58.8 ± 70.7 μmol/L, p = 0.046). In subgroup analyses, patients whose TBIL remained elevated despite conventional treatment had a higher TBIL decline on day 7,14 after use of corticosteroid (99.2 ± 98.5μmol/L vs. -23.3 ± 50.4μmol/L, p < 0.001; 120 ± 119.1μmol/L vs. 61.2 ± 98.5μmol/L, p = 0.047). The cure rate of patients in the corticosteroid group was significantly higher than that of the control group (36.1 % versus 4.5 %, p = 0.016). The proportion of patients with TBIL <85.5 μmol/L was also significantly higher in the corticosteroid group than in the control group at day 7 (p = 0.016) and day 14 (p = 0.004) after treatment. In the subgroup analysis of patients with different clinical phenotypes, the causative agent was herbal, autoimmune antibody-positive and 40 % < PTA ≤ 50 % of patients, corticosteroid use did not increase the cure rate of the patients. Univariate and multifactorial analyses found corticosteroid use to be a protective factor for failure to cure in patients with severe DILI (p < 0.001, OR:0.191,95 % CI:0.072–0.470), and peak TBIL to be a risk factor (p = 0.003, OR:1.016,95 % CI:1.007–1.028). ConclusionsThe addition of corticosteroids could not increase the cure rate in patients with severe DILI, but it could rapidly reduce the patient's TBIL at an earlier stage. Corticosteroids could also promote curing in patients with elevated TBIL after conventional treatment. Corticosteroid use was a protective factor for failure to cure in patients with severe DILI and peak TBIL was a risk factor.

Repetitive transcranial magnetic stimulation (rTMS) in the treatment and diagnosis of eating disorders in athletes and patients: a systematic review

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive technique used to treat and diagnose eating disorders (EDs) by targeting brain regions like the dorsolateral prefrontal cortex, which is involved in impulse control and emotion regulation. Particularly beneficial for athletes, rTMS can reduce symptoms of EDs. Therefore, this study aimed to carry out a systematic review of the scientific literature on the therapeutic or diagnostic use of rTMS in athletes and patients with EDs, with an emphasis on binge eating disorder (BED), anorexia nervosa (AN), and bulimia nervosa (BN). A literature survey was carried out in the Directory of Open Access Journals (DOAJ), Medline, Directory of Open Access Scholarly Resources (ROAD), Academic Search Premier, Wiley-Blackwell Full Collection, Nature Open Access, BioMed Central Open Access, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). A total of 26 original papers published until November 21, 2021, were included. The selected studies were grouped for each respective protocol: total number of patients or athletes, sociodemographic aspects of the participants, parameters performed in rTMS: type of coil, intensity, frequency, number of pulses, stimulation site, preliminary results, and incidence of adverse effects. Recent evidence suggests a low rate of side effects with the technique and a substantial high frequency rTMS response in both the dorsolateral prefrontal cortex and the ventromedial region, especially in studies where internal comparison was performed. The great tolerance and safety of neuromodulatory treatment with rTMS encourage the application of the technique, especially in patients with refractory eating disorders. In addition to the therapeutic potential, rTMS is an essential diagnostic tool in elucidating the complex neurobiology of eating disorders. A more significant increase in publications on the subject is expected in a controlled, blind, and randomized manner, leading to a homogenization of results and generalization of its potential use. Keywords: Eating disorders, Neurology, Neuromodulation, Psychology, Psychiatry, Noninvasive brain stimulation.

Impact of Lumbar Fusion Internal Fixation on Lumbar Disc Herniation in Young Patients: A Retrospective Study.

BACKGROUND Lumbar fusion and internal fixation techniques have shown promise in treating lumbar disc herniation (LDH), yet the impact on lumbar function in young patients remains unclear. This study aimed to investigate the impact of lumbar fusion on lumbar function in young patients. MATERIAL AND METHODS A retrospective analysis was conducted on 330 patients diagnosed with LDH admitted to our hospital. Patients were divided into 2 groups: a control group (n=264) that underwent a minimally invasive procedure with a keyhole lens, and a research group (n=66) that underwent lumbar fusion internal fixation. Clinical features and therapeutic outcomes were assessed using Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) Lumbar Scores before surgery and 12 months postoperatively. Additionally, intervertebral space height, degree of vertebral spondylolisthesis (grades I, II, and III), incidence of adverse effects, and treatment efficacy were measured pre-and post-surgically. RESULTS No significant difference in ODI and JOA scores was found between the groups before surgery (P>0.05). Postoperatively, the research group had lower ODI scores, higher JOA scores, and lower intervertebral space heights compared to the control group (P=0.001). While grade 1 and 2 spondylolisthesis showed slight improvement (P>0.05), a significant difference was observed in grade III spondylolisthesis between the 2 groups (P=0.001). Additionally, the research group had a lower incidence of adverse effects (P=0.049) and higher treatment efficacy, although the difference was not statistically significant (P>0.05). CONCLUSIONS Lumbar fusion with internal fixation produced better postoperative outcomes and fewer adverse effects than minimally invasive procedures in young patients with lumbar disc herniation.

The effect of transcutaneous electrical acupoint stimulation on postoperative awakening after general anaesthesia: a systematic review and meta-analysis.

The existing body of research concerning the impact of transcutaneous electrical acupoint stimulation (TEAS) on early postoperative recovery is marked by a lack of consensus. This meta-analysis, encompassing a systematic review of randomised controlled trials, seeks to critically assess the efficacy of TEAS in relation to awakening from general anaesthesia in the postoperative period. The inclusion criteria for this study were peer-reviewed randomised controlled trials that evaluated the influence of TEAS on the process of regaining consciousness following general anaesthesia. A comprehensive search was conducted across several reputable databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the VIP Database, the SinoMed Database, and the WANFANG Medical Database. The search was not limited by date, extending from the inception of each database up to December 2023. The methodological quality and risk of bias within the included studies were appraised in accordance with the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1, and its associated tool for assessing risk of bias. The analysis encompassed 29 studies involving a total of 2,125 patients. Participants in the TEAS group demonstrated a significantly shorter duration to achieve eye-opening [mean difference (MD), -3.16 min; 95% confidence interval (CI), -3.93 to -2.39], endotracheal extubation (MD, -4.28 min; 95% CI, -4.79 to -3.76), and discharge from the post-anaesthesia care unit (MD, -8.04 min; 95% CI, -9.48 to -6.61) when compared to the control group receiving no or sham stimulation. Additionally, the TEAS group exhibited markedly reduced mean arterial blood pressure (MD, -9.00 mmHg; 95% CI, -10.69 to -7.32), heart rate (MD, -7.62 beats/min; 95% CI, -9.02 to -6.22), and plasma concentrations of epinephrine (standardised MD, -0.81; 95% CI, -1.04 to -0.58), norepinephrine (MD, -47.67 pg/ml; 95% CI, -62.88 to -32.46), and cortisol (MD, -110.92 nmol/L; 95% CI, -131.28 to -90.56) at the time of extubation. Furthermore, the incidence of adverse effects, including agitation and coughing, was considerably lower in the TEAS group relative to the control group (odds ratio, 0.30; 95% CI, 0.22-0.40). The findings of this study indicate that TEAS may hold promise in facilitating the return of consciousness, reducing the interval to awakening post-general anaesthesia, and enhancing the awakening process to be more tranquil and secure with a diminished likelihood of adverse events. However, caution must be exercised in interpreting these results due to the notable publication and geographical biases present among the studies under review. There is an imperative for further high-quality, low-bias research to substantiate these observations. The review protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42022382017).

Gaps in predicting water quality impacts of unbound air-cooled blast furnace slag utilized for roadway construction

Air-cooled blast furnace slag (ACBFS) is often used as road construction aggregate. Several incidences of adverse environmental effects have been reported in Indiana where unbound slag has been used. The aggregates that caused issues in the field had been previously approved for use by passing State of Indiana standard slag leaching procedures. The study goal was to test several hypotheses posed to the Indiana Department of Transportation and authors by the industry about slag leaching, and to better understand water quality impacts. Ten slags from two suppliers underwent leaching procedures adopted by two U.S. states, but additional test procedures and material and leachate chemical characterization were also conducted to better interpret results. Aggregates varied in size and age (24 h to 2 years old). Like prior literature reports, the chemical composition among the slag samples was similar. However, water quality impacts observed at the bench-scale in this study differed substantially across the slags. Results were consistent with those previously reported at Indiana field sites, but not with literature reported results from standardized leaching tests (i.e., TCLP, percolation, etc.). In the present study, no relationship was found between slag age and leachate composition. Leachate pH, conductivity, and color levels exceeded thresholds of regulatory and aquatic toxicity significance. For one slag, leachate pH reached 12.9, but the effluent was colorless. During both stagnation and rinsing tests, aqueous chloride, sulfate, and zinc concentrations sometimes exceeded regulatory water quality and aquatic toxicity levels. Repeated rinsing of the slag resulted in water conductivity and sulfate concentration differences. To better understand and predict the impacts of unbound ACBFS, additional fundamental studies and field investigations are recommended. Unbound ACBFS is not recommended for use near environmentally sensitive areas, drinking water sources, habituated areas, and where it may have water contact (i.e., waterways, wetlands, reservoirs, and groundwater).

A double-blinded randomised control study to compare the effectiveness and safety of intralesional vitamin D3 with intralesional triamcinolone and its correlation with tissue expression of vitamin D receptors in patients with keloid.

Intralesional steroids commonly used for keloid treatment have adverse effects like cutaneous atrophy and telangiectasias. Safer and more effective therapies are needed. Preliminary studies suggest intralesional vitamin D as a potential alternative treatment. The aim of this study was to compare efficacy and safety of intralesional vitamin D with triamcinolone for keloids, and correlate tissue expression of vitamin D receptors (VDRs) with treatment outcomes. Sixty patients were randomly assigned to two groups: Group A (intralesional vitamin D) and Group B (intralesional triamcinolone). Four injections were given at 4-week intervals, with an 8-week follow-up. Biopsies were taken pre- and post-treatment to examine VDR expression levels and treatment response correlation. The primary outcome of interest was the proportion of patients achieving a 50% reduction in Vancouver Scar Scale (VSS). Secondary outcomes included incidence of adverse effects, and changes in VDR expression before and after treatment. Baseline VSS scores were 9.73 ± 1.01 (vitamin D group) and 10.13 ± 1.07 (triamcinolone group). After treatment, mean VSS decreased to 5.17 ± 0.59 (vitamin D group, p < 0.001) and 4.77 ± 0.77 (triamcinolone group, p < 0.001), with significantly better response in latter (p = 0.03). More than 50% reduction in VSS score was higher in the triamcinolone group (76.7% vs. 50%, p = 0.032). No recurrences were noted during the 8-week follow-up. Hypopigmentation (80% vs. 36.7%, p < 0.001) and atrophy (73.3% vs. 40%, p = 0.009) were more common in the triamcinolone group. No significant difference in pre- and post-treatment VDR receptor expression was observed in either group. Both triamcinolone acetonide and vitamin D were effective for keloids. Triamcinolone was more efficacious, whereas vitamin D was safer, suggesting it as a viable alternative for keloid management.

Efficacy and safety of Vonoprazan-based treatment of Helicobacter pylori infection: a systematic review and network meta-analysis

ObjectiveThe aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection.DesignThrough searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly.ResultsThe RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety.ConclusionCompared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

Efficacy and safety of the S1PR modulator etrasimod in the treatment of moderately to severely active ulcerative colitis during the induction phase: a systematic review and meta-analysis of randomized controlled trials.

The study aims to assess the efficacy and safety of the recently approved S1PR modulator etrasimod in adults with ulcerative colitis during the induction phase through meta-analysis. A systemic search was performed for randomized controlled trials evaluating the efficacy and safety of the S1PR modulator etrasimod using electronic databases PubMed, Embase, the Cochrane Library, Clinical Trials, and the International Clinical Trials Registry Platform. Three studies with 943 patients met the inclusion criteria and were included in this analysis. The study's primary endpoint was the proportion of patients who achieved clinical remission at week 12. Key secondary endpoints included the proportion of patients with clinical response, endoscopic improvement, and histologic remission. The incidence of adverse effects (AEs), serious AEs (SAEs), and AE-related treatment discontinuation were statistically analyzed to determine the safety of etrasimod. This study revealed that etrasimod is superior to placebo at the primary endpoint clinical remission (OR = 3.09, 95% CI: 2.04-4.69), as well as at the secondary endpoints clinical response (OR = 2.56, 95% CI: 1.91-3.43), endoscopic improvement (OR = 2.15, 95% CI: 1.51-3.05), and histologic remission (OR = 3.39, 95% CI: 2.03-5.68). The proportion of patients with TEAE (OR = 1.34, 95% CI: 1.01-1.78) and SAE (OR = 0.77, 95% CI: 0.41-1.43) was similar between the etrasimod and placebo groups. Patients receiving etrasimod had slightly higher odds of experiencing headache (OR = 2.07, 95% CI: 1.01-4.23), and nausea (OR = 1.84, 95% CI: 0.72-4.72). The incidences of upper respiratory tract infection (OR = 0.79, 95% CI: 0.27-2.32), nasopharyngitis (OR = 0.40, 95% CI: 0.15-1.07), and urinary tract infection (OR = 1.82, 95% CI: 0.59-5.60) were generally lower in the etrasimod groups and no treatment-related serious infections were reported. This study demonstrates that etrasimod is effective in treating moderately to severely active ulcerative colitis with a favorable benefit-risk profile at week 12. Etrasimod shows promise as a potential first-line oral therapy for individuals suffering from this disease. Additional RCTs with larger sample sizes and longer observation periods are needed to confirm the sustained efficacy of etrasimod beyond the initial phase.

The duration of antibiotic therapy for fracture related infection does not affect recurrence but leads to increased adverse effects: a comparison among 6, 12 and 24weeks of treatment.

The optimal duration of antibiotic therapy for fracture-related infection (FRI) has not been well defined. Our aim was to assess the recurrence rate of infection in patients who underwent six, 12, or 24weeks of antibiotic therapy following surgical treatment for FRI one year after antibiotic discontinuation. Additionally, complications were monitored. Patients with FRI underwent surgical treatment, and antibiotic therapy was initiated. The patients were divided into groups at the 6th and 12th weeks of antibiotic therapy. The primary endpoint was the recurrence of deep or superficial infection at 90days and one year after the end of antimicrobial therapy. There was no difference in the recurrence of infection 90days or one year after stopping antibiotic therapy among patients treated for six, 12, or 24weeks (p = 0.98 and p = 0.19, respectively). The overall recurrence rate of infection 90days after stopping antibiotic therapy was 4.9% (8/163), and one year after discontinuation of antibiotic therapy was 9.8% (16/163). There was a statistically significant difference in the incidence of adverse effects among the three groups (chi-square; p = 0.01). Adverse effects were more common in the group treated for 24weeks than in the groups treated for 6weeks (z score, p = 0.017) or 12weeks (z score, p = 0.005). Antibiotic therapy longer than 6weeks did not reduce the recurrence of FRI after one year of follow-up. Additionally, antibiotic treatment for 24weeks increases adverse events such as skin reactions and acute renal failure.

Adverse Effects Associated With Multimodal Analgesic Regimens in Critically Ill, Nonintubated Patients: A Systematic Review and Meta-Analysis

Objective: To evaluate the safety of utilizing multimodal analgesic regimens in critically ill, nonintubated patients. Data Sources: A systematic review was conducted using Embase, MEDLINE, Cochrane, SciELO, Web of Science, and the Korean Journal Index. Clinical trials of critically ill, nonintubated patients that contained complete safety outcomes date, including the incidence of specific adverse drug effects (ADE) associated with a multimodal analgesic medication or regimen, were included. Study Selection and Data Extraction: The primary outcome was the incidence of adverse drug effects associated with multimodal analgesics in comparison to standard-of-care analgesic strategies in our patient population. The secondary outcome was a subgroup analysis of adverse drug effect by type and by medication. Data Synthesis: 10 trials were included in this systematic review, of which 6 were randomized control trials that were evaluated in the meta-analysis. There was no statistically significant difference with respect to the primary outcome (mean difference = −0.11, P = 0.31, 95% CI = [−0.35, 0.13]). The subgroup analysis, which was conducted on randomized clinical control trials that documented a single adjunctive analgesic rather than a multimodal regimen, was stratified by the type of adverse effect encountered and the medication in question. There were no statistically significant findings regarding the incidence of specific ADE. Nonrandomized data included in this study support these findings. Conclusions: While concerns of the additive deleterious adverse effects commonly encountered in polypharmacy are valid, our findings support the use of multimodal analgesic regimens in the provision of analgesic in critically ill, nonintubated patients.