Recent Randomized Controlled Trials Research Articles

Chronic Rhinosinusitis with Nasal Polyps and Biologics: A Call for Better Data Standardisation and Presentation in Clinical Studies.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often severe, debilitating and difficult to treat. Recent randomised control trials (RCTs) of biologics that target key inflammatory pathways have demonstrated clinical efficacy in treating CRSwNP. Such RCTs must facilitate meta-analysis. Here we report the need for urgent improvement in double-blind randomised controlled trials of biologics in CRSwNP, having previously undertaken a systematic review and meta-analysis of such studies. The RCTs included in that systematic review did not conform to a standard study design. Patient selection criteria was not consistent in studies with several heterogeneous disease subgroups of CRSwNP patients present in each study. Different durations of treatment and variable outcome measures also made the comparative assessment of efficacy between different biologics difficult. Data presentation to allow extraction for meta-analysis was not always clear, such that on occasion selected data sets or even an entire RCT had to be excluded from further evaluation. As such, the high heterogeneity between studies made the overall interpretation of the findings difficult. We make an urgent call to design and conduct future RCTS of biologics in CRSwNP in a more standardised manner, and to present data in a clear way that is easily extractable. This will facilitate more inclusive and thus robust evaluation and interpretation via meta-analysis, which will in turn enable clearer insight into which CRSwNP patient subgroups might benefit from specific biologics and thus achieve better clinical outcomes.

Noninvasive respiratory support following extubation in critically ill adults with obesity: a systematic review and network meta-analysis

Patients with obesity are at high-risk of extubation failure. Discrepancies were found in the results of recent randomized controlled trials (RCTs) regarding the roles of noninvasive ventilation (NIV), high flow nasal cannula (HFNC) and conventional oxygen therapy (COT) to prevent extubation failure in critically ill patients with obesity. In this systematic review and network meta-analysis, we searched MEDLINE, Cochrane Center Register of Controlled Trials and Web of Science from 1 January 1998 to 1 July 2024 for RCTs evaluating noninvasive respiratory support therapies (NIV, HFNC, COT, NIV+HFNC) after extubation in critically ill adults with obesity. Primary outcome was reintubation at day 7. Secondary outcome was 28-day mortality. We generated pooled risk ratios (RR) and numbers needed to treat (NNT). We rated risk of bias using the Cochrane risk-of-bias 2.0 tool. The study was registered with PROSPERO (CRD 42022308995). In seven RCTs including 1933 patients, NIV+HFNC (RR 0.36 [95% confidence interval (CI) 0.16-0.82], NNT=10 [95% CI 7-33]) and NIV (RR 0.45 [95% CI 0.23-0.88], NNT=11 [95% CI 8-50]) but not HFNC (RR 0.79 [95% CI 0.40-1.59]) reduced reintubation at day 7, compared to COT. Compared to HFNC, NIV+HFNC (RR 0.46 [95% CI 0.23-0.90], NNT=14 [95% CI 10-77]) but not NIV (RR 0.57 [95% CI 0.32-1.02]) reduced reintubation at day 7. Compared to HFNC, both NIV (RR 0.31 [95% CI 0.13-0.74], NNT=15 [95% CI 12-40]) and NIV+HFNC (RR 0.30 [95% CI 0.10-0.89], NNT=15 [95% CI 11-90]) reduced 28-day mortality. The results suggest that compared to COT and HFNC, NIV alone or with HFNC reduces reintubation in critically ill patients with obesity after extubation. Compared to HFNC, NIV alone or with HFNC reduces mortality. The number needed to treat with NIV or NIV+HFNC to avoid one death was 15. These findings support the application of NIV to mitigate extubation failure in critically ill adults with obesity. None.

The role of macrolides in severe community-acquired pneumonia and the potential impact of macrolide-resistant Mycoplamsa pneumoniae.

Define the utility of adjunctive macrolide therapy in patients with more severe forms of community-acquired pneumonia (CAP). Guidelines recommend adjunctive macrolide therapy as an option for patients with CAP, admitted to the hospital. A large data set collected both retrospectively and prospectively, including several recent randomized controlled trials (RCTs) have shown that adjunctive macrolide therapy can reduce mortality and improve outcomes in patients with severe CAP, more effectively than other alternative therapies. This effect appears to be most evident in those with severe illness and appears to be independent of direct antimicrobial effects and may be a result of the immunomodulatory properties of macrolides. A recent RCT, the ACCESS study, showed a clinical benefit of macrolides in severe CAP patients, but this may have been the result of a reversal of infection-related immunoparalysis. Macrolides appear to be valuable for patients with more severe CAP, but their therapeutic value is being challenged by the recent emergence of macrolide-resistant Mycoplasma pneumoniae; however, the optimal therapy for this pathogen still needs to be defined. New evidence has further advanced the role of macrolides as preferred adjunctive therapy for patients with severe CAP.

Psychological Treatments for Alexithymia: A Systematic Review.

Alexithymia, a psychological condition characterized by emotional suppression, is positively correlated with depression and anxiety and can develop into various mental disorders. Although alexithymia affects 10% of the symptomatic population and 25% of psychiatric patients, there has been a paucity of intervention studies. Even though several effective psychological treatments, including cognitive behavioral therapy (CBT), have been tested in recent years, there is a lack of comprehensive reviews on their efficacy. The objectives of this systematic review were to explore and synthesize findings from recent randomized controlled trials (RCTs) about psychological treatments, with the following inclusion criteria: (1) published from 2010 to 2024; (2) full text being available in English; (3) peer-reviewed journals; and (4) baselines and outcomes measured by TAS-20 and raw data were provided. We excluded non-psychological studies and studies involving mindfulness and DBT. We searched electronic databases (PubMed, PsycInfo, and Google Scholar) and found 18 RCTs and 21 arms for alexithymia, with a combined total of 1251 participants. Fourteen arms (67%) investigated the effect of CBT on alexithymia, including acceptance and commitment therapy (seven arms), behavioral activation therapy (two arms), schema therapy, and compassion-focused therapy. The results indicated that most psychological interventions significantly decreased TAS-20, illustrating a showcase of treatments from each trial with different effect sizes (within-intervention group, ranging from 0.41 to 13.25). However, due to the heterogeneity between the studies, this review study may not be conclusive enough to make each intervention standardized. Further high-quality RCTs with larger sample sizes and more consistent methodologies are needed, and corrective findings from such studies should be applied to produce more robust evidence-based psychological interventions for treating alexithymia.

Non-Invasive Ventilation in Acute Asthma Exacerbations: A Systematic Review.

Multiple clinical practice guidelines lack recommendations pertaining to non-invasive ventilation (NIV) in acute asthma exacerbations due to a paucity of evidence. However, the evidence syntheses for these guidelines were performed years ago and more recent randomized controlled trials (RCTs) and observational studies have been published. Update the evidence syntheses from previous guidelines to further clarify the effects of NIV in acute asthma exacerbations. A systematic search of Medline, Embase and the Cochrane Library was conducted, studies comparing NIV plus standard medical therapy to standard medical therapy alone in adults with acute asthma exacerbation were selected using a priori selection criteria, and relevant data were extracted. Weighted aggregation (meta-analysis) was performed to summarize effects, which were appraised using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Eight RCTs and five observational studies were selected. NIV was associated with a reduced intubation rate (RCTs RR 0.46, CI 0.16-1.29 and observational studies RR 0.55, CI 0.45-0.68), admission rate (RR 0.57, CI 0.34-0.98), and time to improvement in accessory muscle use (Mean difference -1.13 hours, CI -1.28 - -0.99). Additional outcomes favored NIV plus standard medical therapy but didn't reach statistical significance including dyspnea measures and spirometry measures. There were too few deaths to reliably assess mortality. The quality of evidence ranged from low to very low for all outcomes. All statistically significant outcomes favored NIV plus standard medical therapy over standard medical therapy alone in adults with acute asthma exacerbation. Our aggregate data suggests that intubation rate may be reduced with NIV plus SMT, though the overall quality of the evidence is low. If this is a true effect, it may be clinically important because intubation has been shown to correlate with mortality in multiple observational trials. Given these findings, patients with acute asthma exacerbations may benefit from a trial of NIV in addition to standard medical therapy.

The Effectiveness and Application of Transcutaneous Electrical Acupoint Stimulation in the Prevention of Postoperative Nausea and Vomiting

Background: Effective management of postoperative nausea and vomiting (PONV) is crucial for enhancing postoperative recovery and improving the quality of life. Transcutaneous electrical acupoint stimulation (TEAS) is an innovative non-pharmacological intervention that has gained significant attention in PONV management, especially following thoracic surgery. Methods: This systematic review aims to evaluate the effectiveness and application potential of TEAS in alleviating PONV and promoting postoperative recovery. The review includes a detailed analysis of recent randomized controlled trials (RCTs) and observational studies that investigate the use of TEAS in various surgical procedures, with a particular focus on video-assisted thoracoscopic lobectomy (VATSL). The principles, procedures, and safety aspects of TEAS are comprehensively discussed. Results: The analysis of the included studies demonstrates that TEAS is effective in reducing the incidence of PONV and improving postoperative recovery outcomes across different types of surgeries, including VATSL and other common surgical procedures. The effectiveness of TEAS in PONV management is supported by evidence from multiple RCTs and observational studies, which report a significant reduction in nausea and vomiting rates, as well as improved recovery indicators. Conclusion: TEAS shows promising potential as a non-pharmacological intervention for managing PONV and enhancing postoperative recovery. However, the current evidence highlights several limitations and controversies that require further investigation. Future research should focus on addressing these gaps and exploring new directions for the application of TEAS. Practical recommendations are provided for the clinical application of TEAS, emphasizing its role in effective PONV management to promote better postoperative outcomes.

Network Meta-Analysis and Trial Sequential Analysis of Randomised Controlled Trials Comparing Robotic, Laparoscopic, and Open Pancreatoduodenectomy.

The use of minimally invasive (laparoscopic and robotic) pancreatoduodenectomy (PD) is being increasingly adopted despite the lack of hard evidence to support its utilisation. With recent randomised controlled trials (RCTs) comparing open pancreatoduodenectomy (OPD) with robotic or laparoscopic pancreatoduodenectomy (RPD or LPD), we undertook a network meta-analysis (NMA) comparing all 3 approaches to evaluate comparative outcomes. A systematic search of MEDLINE, EMBASE, and Cochrane CENTRAL was conducted up to May 2024 and relevant RCTs were identified. A random-effects meta-analysis and trial sequential analysis (TSA) were conducted for primary outcomes, followed by a Bayesian NMA of length of stay (LOS), duration of surgery, intraoperative blood loss, and pancreas resection-related outcomes. Seven RCTs involving 1336 patients were included, 5 investigating LPD compared with OPD and 2 RPD to OPD. Pairwise meta-analysis indicated that LPD was associated with shorter hospital stay (mean difference [MD], -1.39; 95% confidence interval [CI], -2.33 to -0.45) and lower intraoperative blood loss compared with OPD (MD, -131; 95% CI, -146 to -117). However, LPD was associated with significantly longer operative duration (MD, 39.5; 95% CI, 34-45). TSA confirmed the robustness of the positive and negative findings on pairwise meta-analysis. In comparison, there were no significant differences between RPD and OPD in pairwise meta-analysis, which could not be confirmed by TSA. Network meta-analysis tended to favour LPD in most outcome parameters including LOS, duration of surgery, and pancreas resection-related outcomes. The current RCT evidence suggests potential better outcomes in LPD in comparison with RPD and OPD. However, few studies demonstrated robust statistical significance in outcome measures, suggesting an underpowered evidence base and possible selection bias. Hence, with current equivocal data, there is a need for ongoing RCTs to validate the role of minimally invasive approaches in PD.

Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early Clostridioides difficile infection: economic evaluation alongside a randomized controlled trial

For Clostridioides difficile infection (CDI), faecal microbiota transplantation (FMT) is currently recommended for patients with three or more CDI episodes. A recent randomised controlled trial (RCT) show that FMT may be considered early, defined as intervention during the first or second CDI episode. Compared with standard care for first or second CDI, patients randomised to FMT had €1,645 lower hospital costs over 26 weeks owing to fewer admissions and hospital contacts and less medication use.

Abstract 4146376: Efficacy of Early Vs Delayed Catheter Ablation in Atrial Fibrillation: an Updated Meta-analysis

Background: Although observational studies have shown a higher rate of atrial arrhythmia recurrences in patients with atrial fibrillation (AF) undergoing delayed catheter ablation as compared with early ablation, a recent randomized controlled trial (RCT) did not show any such difference. We aimed to perform an updated meta-analysis of the available studies. Methods: Multiple online databases were searched for studies comparing early ablation (< 1 year) to delayed ablation (> 1 year) in patients diagnosed with AF. The outcome of interest was atrial arrhythmia recurrence at the longest follow up available. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Results: A total of 8 studies (1 RCT and 7 observational) with 5,171 patients (early ablation n=1,636, delayed ablation n=3,535) were included. Around 70% patients were men, mean age was 61 years and mean duration of follow up was 28 months. Patients with AF undergoing early catheter ablation had a lower rate of atrial arrhythmia recurrence when compared with the delayed ablation group (OR 0.57, 95% CI 0.44 to 0.73, p < 0.0001). Substantial level of heterogeneity was present between the studies (I2 = 67%). Conclusion: Performing catheter ablation early (within 1 year of diagnosis) in patients with AF may lead to significant reduction in atrial arrhythmia recurrence as compared with delayed ablation. The results of this meta-analysis, however, are subject to potential bias and heterogeneity.

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p<0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Does Silodosin Improve Primary Ureteroscopy Access and Outcomes: Meta-Analysis of Randomized Controlled Trials.

Background: Ureteroscopy (URS) is a widely utilized procedure for the management of urinary stones, though failed access due to ureteral orifice tightness or spasms can be a potential outcome. Silodosin, an alpha-1A adrenergic receptor antagonist, has shown promise in recent randomized controlled trials (RCTs) in improving URS outcomes by relaxing ureteral smooth muscle. Objective: This systematic review and meta-analysis aims to determine whether preoperative administration of silodosin enhances ureteroscopy outcomes, including ureteral access rates, operative time, complication rates, and stone-free rates. Methods: After PROSPERO registration, a comprehensive search of PubMed, EMBASE, and the Cochrane Library was conducted for RCTs comparing silodosin with placebo or no medication before URS. Data extraction and bias assessment were performed independently by two reviewers. Statistical analysis was undertaken by Review Manager V5.4, employing random-effects models for heterogeneous variables. Results: Eight RCTs with a total of 892 patients (416 in the silodosin group and 476 in the control group) met the inclusion criteria. Silodosin significantly reduced operative time by 15.74 minutes (p < 0.00001). The access rate was higher in the silodosin group (96.9%) compared with the control group (87.2%)(p = 0.0004). Total complication rates were lower in the silodosin group (14.39% vs 27.47%, p < 0.00001), as were moderate to significant complications (5.0% vs 11.7%, p = 0.003). Stone-free rates were also higher in the silodosin group (92.16% vs 81.5%, p < 0.0001). Conclusion: Preoperative administration of silodosin significantly improves URS outcomes by reducing operative time, increasing access rates, decreasing complication rates, and enhancing stone-free rates. These findings support the integration of silodosin into clinical practice guidelines for URS, potentially improving procedural efficiency and patient outcomes.

Surgical management of first-time patellar dislocations in paediatric patients may lower rates of redislocation compared to conservative management: A systematic review and meta-analysis.

The purpose of this study is to assess whether early surgical intervention for first-time patellar dislocations in paediatric patients is superior to conservative management. We hypothesized that surgical intervention would lead to lower redislocation rates compared to conservative treatment. Three online databases (PubMed, MEDLINE and EMBASE) were searched from inception to 14 March 2024 to identify studies investigating the management options for acute first-time patellar dislocations in paediatric patients. Data pertaining to patient demographics, patient management, redislocation rates and Kujala scores, evaluating function, were abstracted. Weighted means and meta-analyses were conducted to compare rates of redislocation, as well as Kujala scores. The quality of included studies was assessed using the methodological index for non-randomized studies criteria for non-randomized studies and the ROB2 tool for randomized controlled trials (RCTs). A total of 11 studies and 761 patients were included in this review. The weighted mean post-operative combined rates of redislocation in the surgical group was 25.1%, compared to 46.4% in the conservative group at a mean follow-up of 53.2 months (12-168). The relative risk (RR) of redislocation was 0.82 (95% confidence interval [CI]: 0.65-1.04, I2 = 0%, p = 0.11), favouring surgery compared to conservative management. A subgroup meta-analysis of two recent RCTs with 110 patients demonstrated an RR of redislocation of 0.53 (95% CI: 0.31-0.91, I2 = 0%, p = 0.02), favouring surgery. Kujala scores among three comparative studies showed a mean difference of -2.7 (95% CI: -6.1 to 0.68, I2 = 0%, p = 0.12), favouring conservative treatment. The weighted mean redislocation rate in 131 patients undergoing medial patellofemoral ligament reconstruction (MPFLR) was 3.1%, compared to 39.4% in 203 patients undergoing other surgical procedures, such as lateral release and medial imbrication, Roux-Goldwaith and MPFL repair. Furthermore, the conservative groups experienced a complication rate of 0.9% compared to 2.9% across the surgical groups. Surgical management for first-time patellar dislocations in a paediatric population, particularly MPFLR, may be more beneficial in lowering redislocation rates than conservative management. No significant differences in Kujala scores were found. Level IV.

Atrial fibrillation detection on implantable loop recorders in embolic stroke of undetermined source

Abstract Introduction Embolic stroke of undetermined source (ESUS) represents 17% of all ischaemic strokes, and has a 5% annual stroke recurrence risk. Recent large randomised control trials failed to demonstrate a benefit of empirical anticoagulation for all ESUS patients, with sub-analyses supporting the need for a tailored approach to those patients at greatest risk of atrial fibrillation (AF) development. Understanding how the increased incidence of ILR-detected AF in the ESUS cohort, compares with ILR-detected AF in other cohorts is an essential step in understanding the significance of this finding. Purpose To compare the incidence of ILR-detected AF following ESUS against patients undergoing ILR implantation for non-stroke indications for example syncope and palpitations. Methods We retrospectively studied all patients without known AF who were referred to our institution for ILR implantation following ESUS, syncope or palpitations from 2009 to 2019. The primary endpoint was any detection of AF or atrial flutter (AFL) by ILR. Kaplan-Meier and multivariable Cox-regression analyses were utilised to account for time-to-event. Results A total of 750 patients were included and followed up for a mean of 731 days (SD 443). An ILR was implanted following ESUS in 323 patients and for another reason in 427 patients (figure 1). The incidence of AF was significantly higher among patients with ESUS compared to the non-ESUS group; 48.6% versus 13.8% (for any duration of AF) and 32.2% versus 12.4% (for AF lasting &amp;gt; 30 seconds) both p &amp;lt;0.001. Kaplan-Meier analysis (figure 2), showed significantly higher incidence of AF for ESUS for any duration of AF. This was driven predominantly by AF duration &amp;lt;6 minutes and between 5.5 hours and 24 hours. Importantly, in a multivariable Cox regression analysis, ESUS independently conferred an almost 5-fold increase in the hazard for any duration of AF (Hazard Ratio 4.948, 95% confidence interval 3.587 – 6.825, p&amp;lt;0.001). Conclusion The incidence of AF is significantly higher amongst ESUS versus non-ESUS patients monitored constantly by an ILR. A high number of ESUS survivors have short duration AF episodes. Further work is needed to determine the optimal treatment strategy of these AF episodes in ESUS considering AF duration and overall burden.

High-flow nasal cannulas versus standard oxygen therapy for moderate bronchiolitis: a quasi-experimental analysis.

In the last decades none of the medical therapies investigated have shown clear efficacy in the treatment of bronchiolitis, and literature agrees on a general de-implementation of pharmacological therapies, recognizing an effective role only to nutritional support and oxygen therapy. High-flow nasal cannulas (HFNC) has become increasingly popular in the last decade, despite its lack of clear efficacy. Recent randomized controlled trials (RCT) comparing standard oxygen therapy (SOT) and HFNC did not demonstrate significant benefit of HFNC. To acquire more clinical data on HFNC efficacy we performed a retrospective, quasi-experimental analysis of patients admitted for bronchiolitis in the epidemic seasons 2021-2022 and 2022-2023. To assess the efficacy of SOT and HFNC we used a pragmatic approach, a fuzzy regression discontinuity design, which is a quasi-experimental test. Unlike RCTs, this process is not a true randomization, but may be interpreted as quasi-randomization in an observational setting. HFNC did not reduce length of oxygen therapy (LOO) nor length of hospitalization (LOS) (respectively, p: 0.383 and p: 0.454). Treatment failure was not significantly different in the treatment groups (p: 0.354). It is crucial to perform additional RCTs with uniform protocols to determine the efficacy of HFNC more accurately in the treatment of bronchiolitis. HFNC does not reduce LOO, suggesting that early use of HFNC does not change the course of disease in moderate bronchiolitis. In view of the greater complexity and higher cost, HFNC should not be routinely used as first-line treatment in children with moderate respiratory distress and mild hypoxemia.

Current Trends in the Treatment of Acute Uncomplicated Diverticulitis.

Introduction: Acute diverticulitis represents a significant disease burden in the United States and developed world. This article examines current trends in the treatment of acute diverticulitis and concentrates on the utility of antibiotics in acute uncomplicated cases managed in the outpatient setting. Methods: The literature was reviewed for randomized controlled trials (RCTs) to discern the best practice and recommendations for antibiotics for diverticulitis. The time period included relevant RCTs after 2000. Results: Four recent RCTs examine the use of antibiotics in acute uncomplicated diverticulitis. The AVOD study was an RCT that managed inpatients with either antibiotics or IV fluids alone and demonstrated non-inferiority of non-antibiotic management with respect to recovery, complication rates, or recurrence. The DIABLO trial randomized first episodes of acute uncomplicated diverticulitis admitted to the hospital with antibiotics or supportive care and found no difference in morbidity or mortality between the two groups and longer hospital stay for patients treated with antibiotics. The DINAMO study examined outpatients managed with antibiotics by mouth or without and found no difference in morbidity in 90 day follow-up. The STAND study was the only of these four to use a placebo and found no difference between hospital stay or other adverse events at 30 days. In response to this, the ASCRS, AAFP and other societies now recommend against the routine use of antibiotics in acute uncomplicated diverticulitis. Conclusions: Several quality studies found similar outcomes in cases of acute uncomplicated diverticulitis treated with or without antibiotics. Based on these findings, societal guidelines do not recommend routine antibiotics for acute diverticulitis.

Employment Effects of Skills Trainings in Sub-Saharan Africa: A Systematic Review of Recent Randomized Controlled Trials

AbstractThis study provides a comprehensive systematic review of recent randomized controlled trials (RCTs) to evaluate the employment effects of skills training programs in sub-Saharan Africa. The review focuses on studies conducted between 2019 and 2024, a period marked by a significant increase in the number of RCTs of training interventions in this region, and we thus fill a gap left by earlier reviews that did not reflect this recent surge in experimental studies. We employ the standard SPIDER approach for defining search terms and the PRISMA procedure for search and selection to systematically analyze the impact of these training programs on employment outcomes. The findings reveal a shift towards a more optimistic assessment compared to previous analyses, suggesting that many recent skills training programs do contribute to improving employment-related outcomes.

8197 A Captivating Case Report of Teprotumumab Induced Hyperglycemic Hyperosmolar State

Abstract Disclosure: K.M. Tuna: None. J.P. Perdomo Rodriguez: None. Introduction: Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, is increasingly utilized for moderate to severe thyroid eye disease. Initial trials noted mild hyperglycemia in patients with diabetes, while recent trials revealed a significant elevation in Hemoglobin A1c (HbA1c) among those with diabetes or pre-diabetes post-infusion. Here, we discuss a case of a patient with diet-controlled diabetes who developed hyperglycemic hyperosmolar state (HHS) two months after Teprotumumab infusion. Case Presentation: A 43-year-old male, with class III obesity, obstructive sleep apnea, dyslipidemia, coronary artery disease, and diet-controlled diabetes (HbA1c 6.5%) presented with worsening proptosis, decreased color vision, severe visual field depression. Laboratory evaluation revealed elevated TSH (6.3 mIU/ml), normal free T4 (0.67 ng/dl, ref: 0.60-1.2 ng/dl), and undetectable Thyroid Stimulating Immunoglobulin (&amp;lt;0.1 IU/L). Blood cell count, renal and liver function tests were normal. Due to high clinical suspicion of thyroid eye disease, he was treated with timolol, dorzolamide, brimonidine, and methylprednisolone 1g daily for 3 days. Glycemic control was achieved with 30 units of daily insulin while on pulse steroids. On outpatient ophthalmology follow-up, Teprotumumab was initiated and he received 2 doses. Eight weeks later, the patient was hospitalized with altered mental status caused by HHS (glucose 617 mg/dl, serum osmolality 316 osm). HbA1c was found to be significantly increased to 12% and the patient required 150 units total daily insulin and metformin upon discharge. Of note, the patient did not have significant weight changes during this time. GAD, IA2, and Zinc Transporter-8 antibodies were obtained prior to discharge and results are pending. Discussion: The IGF-1 receptor, a partial homologue of the insulin receptor, plays a pivotal role in glucose homeostasis. Inhibiting this receptor can lead to hyperglycemia. Initial randomized controlled trials (RCTs) reported a 10% incidence of mild hyperglycemia. A recent RCT from a cohort of 42 patients demonstrated a 50% incidence of hyperglycemia, in which two-thirds of the patients remained in a dysglycemic state with one patient with pre-existing prediabetes developing diabetic ketoacidosis (DKA). Our patient mirrored this scenario with no identifiable confounding factors. Conclusion: Teprotumumab-induced hyperglycemia, though rare, can lead to life-threatening complications. Baseline glycemic assessment, identification of high-risk patients, and comprehensive discussions on risks and benefits are crucial before initiating therapy. Close monitoring, especially in those with prediabetes, is recommended. Patient education plays a pivotal role in early symptom recognition, averting delayed diagnoses, and subsequent hospitalization. Presentation: 6/3/2024

Endovascular treatment in ischemic strokes with large infarct core: an updated systematic review and meta-analysis of randomized controlled trials.

Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an ASPECTs ≥ 6. Recent randomized controlled trials (RCTs) have become available on effect of EVT in patients with LVO-related large core infarct stroke (ASPECTS 0-5). We conducted a systematic review and meta-analysis of trials on patients with large core infarct treated with thrombectomy compared to best medical therapy (BMT). The study followed PRISMA guidelines. Primary endpoint was functional independence at 90days (modified Rankin Scale mRS < 3). Secondary endpoints were 3-month moderate disability (mRS < 4), excellent outcome (mRS < 2) and change in mRS (shift analysis). Safety outcomes were: symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Seven RCTs were included with a total of 1964 patients. Functional independence was significantly more frequent in EVT vs BMT group (19.4% vs 8%; OR = 2.72, 95%CI = 2.06-3.61, pheterogeneity = 0.08; I2: 47%). Moderate outcome was also more prevalent in EVT group (OR = 2.00; 95%CI = 1.61 - 2.48, pheterogeneity = 0.17; I2: 46%) as well as excellent outcome (OR: 1.54, 95%CI = 1.07 - 2.22, pheterogeneity = 0.13; I2: 40%). Shift analysis was also significant with OR 1.59 (CI = 1.33-1.82 and p < 0.001). Finally sICH, that occurred in 68 patients, was more frequent in EVT (OR = 1.63, 95%CI = 0.99 - 2.69, pheterogeneity = 0.68; I2: 0%) while 3m mortality was reduced in EVT (31% vs 37,1%, OR 0.76 CI = 0.62-0.92). This updated pooled data show that, in LVO-stroke patients with a large core infarct, EVT plus BMT (as compared to BMT alone) increases significantly the chances of achieving a good functional outcome at 90days and reduces the 3- month mortality despite a marginal increase in acute sICH.

A Clinicians Guide to Recommending Common Cholesterol-Lowering Dietary Supplements.

The US dietary supplement (DS) market has expanded exponentially since 1994, with an estimated 50,000-80,000 individual products currently available. Many DS claim cholesterol or cardiovascular benefits. Overall, well-designed randomized controlled trials (RCTs) with DS are lacking, while studies with favorable results are commonly performed outside of the USA, resulting in inconsistent findings. The expansion of the DS market has limited the ability of the Food and Drug Administration to regulate and prevent substandard products. Eicosapentaenoic acid and docosahexaenoic acid are components of DS fish oil. Recent RCTs utilizing prescription fish oil have provided mixed findings and small but significant safety concerns. Hence, the role of DS fish oil is limited and no longer recommended by major cardiovascular guidelines. Concerns have also been observed from RCTs utilizing prescription niacin, resulting in a negligible role for DS niacin in lipid management. Red yeast rice has demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions in studies performed worldwide, including the USA. However, quality concerns and inconsistent study results have been reported on multiple occasions. Other common DS have produced modest reductions in LDL-C and may provide other cardiometabolic benefits, including garlic, phytosterols, psyllium, and berberine. Yet inconsistent study results and quality concerns continue to be reported for most. Nonetheless, there is a need for alternative therapies that can safely and effectively reduce cardiovascular risk. However, until DS routinely match label claims and are free of contaminants, the agents have a limited role in clinical practice.

Meta-analysis on Effectiveness of Palliative Care versus Conventional Care amongst Advanced Gynaecological Patients with Cancer and Caregivers.

In cancer patients, physical and psychological issues are very common. There is a need for family support and high utilisation of healthcare resources commonly. Palliative care (PC) has grown in popularity to better fulfil of needs of patients and their families and potentially lowering hospital costs. Given that the majority of patients still die in hospitals, there is a need for an effective model of PC for advanced gynaecological cancer, as well as the wise allocation of scarce resources. The main aim of this study was to compare the efficacy of PC to conventional treatment for adults with cancer, including gynaecological cancers, and their caregivers. Four randomised controlled trials (RCTs) were identified by searching PubMed, PubMed Central, Clinical Key, Embase and other grey literature from a duration of 2011-2021. Cochrane criteria were used to calculate the risk of bias, and the Grade Profiler Guideline Development Tool was used to check the quality of the included studies. Standardised mean differences (SMDs), I2 value and forest plot were prepared by using Review Manager 4.0. A total of four RCTs were extracted by following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and found to have a high risk for bias and low to poor quality of evidence. Included study sample sizes ranged from 22 to 104 participants, including 670 people in total, including 289 patients with advanced cancer patients, including gynaecological cancer and 381 unpaid caregivers. Results also showed that PC enhances patients' quality of life (SMD = 0.26; 95% confidence interval [CI] = -0.29-0.80; I2 = 76%), lowered symptom burden amongst patients (SMD = -0.75, 95% CI = -1.75-0.25; I2 = 89%), reduces patient depression (SMD = 0.08, 95% CI = -0.19-0.34; I2 = 0%) and decreases depression in unpaid caregivers (SMD = -0.16, 95% CI = -0.56-0.24; I2 = 59%). PC treatment increases patients' quality of life and lowers their symptom burden. In comparison to conventional care, it also reduces depression among patients and caregivers. We believe that the findings should be viewed with care until more recent exclusive RCTs are available.