Overall Certainty Of Evidence Research Articles

Effects of high-fat, low-carbohydrate enteral nutrition in critically ill patients: A systematic review with meta-analysis

Background & aimsHigh-fat, low-carbohydrate enteral nutrition has gained attention, with expectations of an improved respiratory condition, fewer complications, and lower mortality. The present study performed a systematic review and meta-analysis of randomized controlled trials to examine the effects of high-fat, low-carbohydrate enteral nutrition in critically ill adult patients. MethodsWe searched MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and ICHUSHI for randomized controlled trials comparing high-fat, low-carbohydrate enteral nutrition to standard enteral nutrition in critically ill adult patients who received enteral nutrition. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) mortality, length of ICU stay, length of mechanical ventilation, and adverse events of diarrhea and gastric residual volume. We examined the risk of bias using the Cochrane risk-of-bias tool for randomized trials version 2. We assessed the overall certainty of evidence based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Synthesis results were calculated with risk ratios and 95% confidence intervals using a Mantel-Haenszel random-effects model. ResultsEight trials with 607 patients were included. The effects of high-fat, low-carbohydrate enteral nutrition on mortality did not significantly differ from those of standard enteral nutrition (62/280 [22.1%] vs. 39/207 [18.8%], risk ratios=1.14, 95% confidence intervals 0.80 to 1.62, P=0.47). No significant differences were observed in ICU mortality, ICU length of stay, diarrhea, or gastric residual volume between the two groups. However, high-fat, low-carbohydrate enteral nutrition was associated with a significantly shorter duration of mechanical ventilation (mean difference -1.72 days, 95% confidence intervals -2.93 to -0.50, P=0.005). ConclusionHigh-fat, low-carbohydrate enteral nutrition may not affect mortality, but may decrease the duration of mechanical ventilation in critically ill adult patients. Limitations include the small number of studies and potential for bias. Further research is needed to confirm these results and investigate effects on other outcomes and in a subgroup of patients requiring mechanical ventilation.

Hearing preservation and quality of life in small to medium sized vestibular schwannomas after a wait and scan approach or stereotactic radiosurgery: a systematic review and meta-analysis.

The management of vestibular schwannomas (VS) encompasses a choice between conservative "wait-and-scan" (WAS) approach, stereotactic radiosurgery (SRS) or open microsurgical resection. Currently, there is no consensus on the optimal management approach for small to mediumsized VS. This study aims to compared outcomes related to hearing in patients with small and mediumsized VS who underwent initial treatment with WAS versus SRS. A systematic review of the available literature was conducted using PubMed/MEDLINE, Embase, and Cochrane up December 08, 2023. Meta-analysis was performed using a random-effect model to calculate mean difference (MD) and relative risk (RR). A leave-one-out analysis was conducted. The risk of bias was assessed via the Risk of Bias in Non-randomized Studies-Interventions (ROBINS-I) and Cochrane Risk of Bias assessment tool (RoB-2). Ultimately, the certainty of evidence was evaluated using the GRADE assessment. The primary outcomes were serviceable hearing, and pure-tone average (PTA). The secondary outcome was the Penn Acoustic Neuroma Quality of Life Scale (PANQOL) total score. Nine studies were eligible for inclusion, comprising a total of 1,275 patients. Among these, 674 (52.86%) underwent WAS, while 601 patients (47.14%) received SRS. Follow-up duration ranged from two to eight years. The meta-analysis indicated that WAS had a better outcome for serviceable hearing (0.47; 95% CI: 0.32 - 0.68; p < 0.001), as well as for postoperative functional measures including PTA score (MD 13.48; 95% CI 3.83 - 23.13; p < 0.01), and PANQOL total score (MD 3.83; 95% CI 0.42 - 7.25; p = 0.03). The overall certainty of evidence ranged from "very low" to "moderate". Treating small to mediumsized VS with WAS increases the likelihood of preserving serviceable hearing and optimized PANQOL overall postoperative score compared to SRS. Nevertheless, the limited availability of literature and the methodological weakness observed in existing studies outline the need for higher-quality studies.

Efficacy and safety of probiotics in IBD: An overview of systematic reviews and updated meta-analysis of randomized controlled trials.

Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random-effects model in R. The quality of systematic reviews was assessed using the AMSTAR-2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta-analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28-3.11) and 1.61 (95% CI 0.21-12.50), respectively. The subgroup analysis suggested that combining 5-ASA and probiotics may be beneficial for inducing remission in mild-to-moderate UC (OR 2.35, 95% CI 1.29-4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00-0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42-1.01). No protective effect against recurrence was identified for CD. Multi-strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. Probiotics, particularly multi-strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.

Predictive Accuracy of Infant Clinical Sign Algorithms for Mortality in Young Infants Aged 0 to 59 Days: A Systematic Review.

Clinical sign algorithms are a key strategy to identify young infants at risk of mortality. Synthesize the evidence on the accuracy of clinical sign algorithms to predict all-cause mortality in young infants 0-59 days. MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. Studies evaluating the accuracy of infant clinical sign algorithms to predict mortality. We used Cochrane methods for study screening, data extraction, and risk of bias assessment. We determined certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. We included 11 studies examining 26 algorithms. Three studies from non-hospital/community settings examined sign-based checklists (n = 13). Eight hospital-based studies validated regression models (n = 13), which were administered as weighted scores (n = 8), regression formulas (n = 4), and a nomogram (n = 1). One checklist from India had a sensitivity of 98% (95% CI: 88%-100%) and specificity of 94% (93%-95%) for predicting sepsis-related deaths. However, external validation in Bangladesh showed very low sensitivity of 3% (0%-10%) with specificity of 99% (99%-99%) for all-cause mortality (ages 0-9 days). For hospital-based prediction models, area under the curve (AUC) ranged from 0.76-0.93 (n = 13). The Score for Essential Neonatal Symptoms and Signs had an AUC of 0.89 (0.84-0.93) in the derivation cohort for mortality, and external validation showed an AUC of 0.83 (0.83-0.84). Heterogeneity of algorithms and lack of external validation limited the evidence. Clinical sign algorithms may help identify at-risk young infants, particularly in hospital settings; however, overall certainty of evidence is low with limited external validation.

Optimizing intrauterine insemination: A systematic review and meta-analysis of the effectiveness and safety of clinical treatment add-ons.

Intrauterine insemination (IUI) is one of the most widespread fertility treatments. However, IUI protocols vary significantly amongst fertility clinics. Various add-on interventions have been proposed to boost success rates. These are mostly chosen arbitrarily or empirically. The aim of this systematic review and meta-analysis is to assess the effectiveness and safety of add-on interventions to the standard IUI protocol and to provide evidence-based recommendations on techniques used to optimize the clinical outcomes of IUI treatment. Systematic review and meta-analyses were performed in accordance with PRISMA guidelines. A computerized literature search was performed from database inception to May 2023. Randomized controlled trials (RCTs) were included reporting on couples/single women undergoing IUI with any protocol for any indication using partner's or donor sperm. A meta-analysis based on random effects was performed for each outcome and add-on. Three authors independently assessed the trials for quality and risk of bias and overall certainty of evidence. Uncertainties were resolved through consensus. Primary outcomes were ongoing pregnancy rate (OPR) or live birth rate (LBR) per cycle/per woman randomized. Registration number PROSPERO: CRD42022300857. Sixty-six RCTs were included in the analysis (16 305 participants across 20 countries). Vaginal progesterone as luteal phase support in stimulated cycles was found to significantly increase LBR/OPR (RR 1.37, 95% CI 1.09-1.72, I2 = 4.9%) (moderate/low certainty of the evidence). Endometrial scratch prior/during stimulated IUI cycles may increase LBR/OPR (RR 1.44, 95% CI 1.03-2.01, I2 = 1.8%), but evidence is very uncertain. Results from two studies suggest that follicular phase ovarian stimulation increases LBR/OPR (RR 1.39, 95% CI 1.00-1.94, I2 = 0%) (low certainty of evidence). No significant difference was seen for the primary outcome for the other studied interventions. The findings of this systematic review and meta-analysis suggest that vaginal luteal phase progesterone support probably improves LBR/OPR in stimulated IUI treatments. In view of moderate/low certainty of the evidence more research is needed for solid conclusions. Further research is also recommended for the use of endometrial scratch and ovarian stimulation. Future studies should report on results according to subfertility background as it is possible that different add-ons could benefit specific patient groups.

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Overall survival after mastectomy versus breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer: meta-analysis.

Breast-conserving surgery with adjuvant radiotherapy and mastectomy are currently offered as equivalent surgical options for early-stage breast cancer based on RCTs from the 1970s and 1980s. However, the treatment of breast cancer has evolved and recent observational studies suggest a survival advantage for breast-conserving surgery with adjuvant radiotherapy. A systematic review and meta-analysis was undertaken to summarize the contemporary evidence regarding survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for women with early-stage breast cancer. A systematic search of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase that identified studies published between 1 January 2000 and 18 December 2023 comparing overall survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for patients with unilateral stage 1-3 breast cancer was undertaken. The main exclusion criteria were studies evaluating neoadjuvant chemotherapy, rare breast cancer subtypes, and specific breast cancer populations. The ROBINS-I tool was used to assess risk of bias, with the overall certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Studies without critical risk of bias were included in a quantitative meta-analysis. From 11 750 abstracts, 108 eligible articles were identified, with one article including two studies; 29 studies were excluded from the meta-analysis due to an overall critical risk of bias, 42 studies were excluded due to overlapping study populations, and three studies were excluded due to reporting incompatible results. A total of 35 observational studies reported survival outcomes for 909 077 patients (362 390 patients undergoing mastectomy and 546 687 patients undergoing breast-conserving surgery with adjuvant radiotherapy). The pooled HR was 0.72 (95% c.i. 0.68 to 0.75, P < 0.001), demonstrating improved overall survival for patients undergoing breast-conserving surgery with adjuvant radiotherapy. The overall certainty of the evidence was very low. This meta-analysis provides evidence suggesting a survival advantage for women undergoing breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer compared with mastectomy. Although these results should be interpreted with caution, they should be shared with patients to support informed surgical decision-making.

Comparison of the Clinical Efficacy of Anabolic Agents and Bisphosphonates in the Patients With Osteoporotic Vertebral Fracture: Systematic Review and Meta-analysis of Randomized Controlled Trials.

We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs). Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) ver. 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively. Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs. alendronate and risedronate [RR, 0.57; 95% confidence interval, 0.45-0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs. risedronate [RR, 0.50; 95% confidence interval, 0.37-0.68; p < 0.0001; high-certainty of evidence]). However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR, 1.23; 95% confidence interval, 0.95-1.60; p = 0.12; low-certainty of evidence). In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.

GRADE pearls and pitfalls-Part 2: Clinical practice guidelines.

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is the de facto standard framework for summarising evidence in systematic reviews and developing recommendations in clinical practice guidelines. We describe how the GRADE approach is used in clinical practice guidelines, including key points and examples. The intended audience of this overview of GRADE is clinicians and researchers who are, or plan to be, involved in the development or assessment of clinical practice guidelines. We cover guideline endorsement and adaptation; guideline panels and sponsors; conflicts of interest; guideline questions and outcome prioritisation; systematic review creation, updating and re-use; rating the overall certainty of evidence; development of recommendations and implications; and peer review, publication, implementation and updating of guidelines. This overview aims to help developers, assessors and users of clinical practice guidelines understand how trustworthy, high-quality guidelines are developed using the GRADE approach.

Basal characteristics of patients who responded to Ovarian Fragmentation for Follicular Activation (OFFA) or In Vitro Activation (IVA): a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

The influence of exercise on pain, disability and quality of life in office workers with chronic neck pain: A systematic review and meta-analysis

BackgroundExercise is recommended for office workers with neck pain. However, recent reviews evaluated the effectiveness of workplace interventions only. ObjectivesTo evaluate the effect of exercise on pain, disability, and quality of life (QoL) in office workers with chronic neck pain. DesignSystematic review with meta-analysis. MethodsElectronic databases were searched from inception to April 30, 2022, to identify studies in which participants were adults aged ≥18 years undergoing any form of neck exercises (e.g., strengthening, motor control) or physical activity (e.g., aerobic exercise) performed for a minimum of two-weeks without any other additional treatment besides advice or education. Two reviewers independently screened papers and determined the certainty of the evidence. ResultsEight randomised controlled trials met the eligibility criteria. Seven studies reported a significant decrease in Visual Analogue Scale (VAS) scores for neck pain intensity and five studies reported a significant decrease in Neck Disability Index (NDI) scores following strengthening exercises. Only one study assessed the effect of strengthening exercises on QoL and reported no significant effect. All eight included studies had a high risk of bias and the overall certainty of evidence was low. Meta-analyses demonstrated a significant decrease of neck pain intensity and disability for strengthening exercises compared to a control (p < 0.01). ConclusionThere is low certainty of evidence that strengthening of the neck, shoulder and scapular musculature is effective at reducing neck pain and disability in office workers. Further research evaluating the effect of exercise on QoL is required.

Uncovering gaps in GRADE reporting of Eastern Association for the Surgery of Trauma (EAST) guidelines

ObjectivesTo formally evaluate the uptake and reporting of the Grading of Recommendation Assessments, Development and Evaluation (GRADE) approach in clinical practice guidelines (CPGs) developed by the Eastern Association for the Surgery of Trauma (EAST). Study Design and SettingBased on an a priori, written protocol, we developed a dedicated data abstraction form that included the six suggested criteria for using and applying GRADE. By searching the EAST website, we identified all EAST guidelines that referenced the use of GRADE. All steps of the data abstraction process were completed independently and in duplicate by two members of the research team. ResultsWe identified a total of 48 CPGs that used GRADE. Trauma and violence prevention (n = 11; 23.9%) was the most common topic. The median number of patient/population, intervention, comparison, and outcomes (PICO) questions addressed was 3 (interquartile range: 2; 4) with a median of 2.5 (interquartile range: 1; 4) critical outcomes. A conditional/weak recommendation was provided for n = 79 (51.4%) PICOs, whereas a strong recommendation was provided for 33 PICOs (23.9%). For 22 PICOs (15.9%), no recommendation was made. Nearly all guideline documents provided search dates (n = 44; 95.7%) and a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram (n = 44; 95.7%). Most described categories for rating down (n = 35; 76.1%). GRADE decision-making domains related to the ratio of benefits to harms, values and preferences, and resource utilization were referenced by 43.5% (n = 20), 43.5% (n = 20), and 30.4% (n = 14) of CPGs, respectively. For nearly half of PICO questions (n = 59; 44.2%) authors did not provide an evidence profile or summary of findings table. Comparing time periods from 2014–2018 to 2019–2022, the proportion of recommendations with an overall certainty of evidence increased (52.4% vs 83.9%; P < 0.001). ConclusionEAST has successfully adopted GRADE to develop many trauma-related guidelines, each addressing a finite number of focused clinical questions based on systematic reviews conducted in-house. Overall reporting improved over time. There is for improvement when it comes to consistent provision of an overall certainty of evidence, the reporting of the evidence to decision-making process, and the justification of strong recommendations based on low/very low certainty evidence.

Efficacy and safety of modified Atkins diet therapy for drug‐resistant epilepsy in children and adults: A systematic review and meta‐analysis

AbstractIntroductionDiet‐based treatments have been proposed for drug‐resistant epilepsy (DRE), and the Modified Atkins Diet (MAD) is an alternative. This study aimed to assess the efficacy and safety of MAD as an adjunctive therapy for reducing seizures in patients with drug‐resistant epilepsy.MethodsA literature search was done on six databases. Randomized controlled trial (RCT) studies were included, comparing DRE patients of all ages on standard antiseizure medications (ASD) who received MAD compared to no‐dietary or other dietary interventions. The outcomes are the seizure frequency reduction and the adverse events. Cochrane risk‐of‐bias tool and GRADE were used to assess study quality and the overall certainty of evidence. The effect size of the efficacy of MAD was computed as risk ratio (95% CI). Subgroup analysis based on each type of comparator was done.ResultsTen RCT studies (905 participants) were included, comparing MAD to no dietary intervention, ketogenic diet (KD), and low glycemic index treatment (LGIT). Overall, MAD is constantly and significantly more efficacious than no dietary intervention in reducing seizures ≥50% (RR 7.90, 95% CI 4.59–13.62), ≥90% (RR 4.61, 95% CI 2.05–10.36), and inducing complete seizure‐free (RR 7.79, 95% 2.61–23.22) with high certainty. Other dietary therapies and MAD did not differ significantly from one another in terms of efficacy. The risk of adverse events in MAD is insignificantly higher than in others (RR 1.19, 95% 0.92–1.55).ConclusionThe Modified Atkins Diet has better seizure reduction than no diet intervention but is comparable to other dietary interventions with a negligible increased risk of adverse events.

Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis.

Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C.difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic. Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-classified as either high, moderate, low, or very low. Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96-1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95%CI 1.07-1.21; low-certainty evidence). In one phase2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95%CI 1.01-2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95%CI 0.96-1.14; moderate-certainty evidence). Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics.

A systematic review of the scientific evidence of venous supercharging in autologous breast reconstruction with abdominally based flaps

BackgroundAbdominally based free flaps are commonly used in breast reconstruction. A frequent complication is venous congestion, which might contribute to around 40% of flap failures. One way to deal with it is venous supercharging. The primary aim of this study was to investigate the scientific evidence for the effects of venous supercharging.MethodsA systematic literature search was conducted in PubMed, CINAHL, Embase, and Cochrane library. The included articles were critically appraised, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.ResultsThirty-six studies were included. Most studies had serious study limitations and problems with directness. Three studies report ‘routine’ use of venous supercharging and performed it prophylactically in patients who did not have clinical signs of venous congestion. Seventeen studies report on flap complications, of which one is a randomised controlled trial demonstrating statistically significant lower complication rates in the intervention group. The overall certainty of evidence for the effect of a venous supercharging on flap complications, length of hospital stay and operative time, in patients without clinical signs of venous congestion, is very low (GRADE ⊕ ⊕ ⊝ ⊝), and low on and surgical takebacks (GRADE ⊕ ⊕ ⊝ ⊝). Twenty-one studies presented data on strategies and overall certainty of evidence for using radiological findings, preoperative measurements, and clinical risk factors to make decisions on venous supercharging is very low (GRADE ⊕ ⊝ ⊝ ⊝).ConclusionThere is little scientific evidence for how to predict in which cases, without clinical signs of venous congestion, venous supercharging should be performed. The complication rate might be lower in patients in which a prophylactic venous anastomosis has been performed.Trial registrationPROSPERO (CRD42022353591).

Restrictive Versus Liberal Red Blood Cell Transfusion Strategies for Patients with Hematologic Malignancies Receiving Intensive Chemotherapy

Background: It is estimated that one-quarter to one-half of people diagnosed with hematologic malignancies experience anemia and red blood cell (RBC) transfusion plays an essential supportive role in their management. There are different strategies for RBC transfusions to treat anemia. A restrictive transfusion strategy seeks to maintain a lower hemoglobin level (usually between 70 g/L to 90 g/L with a trigger for transfusion when the hemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher hemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when hemoglobin drops below 100 g/L). The most effective and safest strategy is unknown in people with hematological malignancies. Objectives: To determine the efficacy and safety of a restrictive versus liberal RBC transfusion strategies for people diagnosed with hematological malignancies treated with intensive chemotherapy, radiotherapy, or both, with or without a hematopoietic stem cell transplant (HSCT). Methods: Review was completed using Cochrane standard methodological procedures. We included randomized controlled trials RCTs and prospective non-randomized studies NRS that evaluated a liberal compared with a restrictive RBC transfusion strategy in children or adults with malignant hematological disorders receiving intensive chemotherapy/radiotherapy or undergoing HSCT. We searched for RCTs and NRS in MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and eight other databases and three trial registries to 21 March 2023. For dichotomous outcomes such as mortality, results were presented as a risk ratio (RR) with 95% confidence interval (CI) to compare restrictive versus liberal transfusion strategies. For continuous outcomes using the same scale, we assessed the mean difference (MD) with 95% CI. Where outcome measures were heterogenous, a narrative synthesis was used. Review Manager Web was used to meta-analyze the data. GRADE rating methodology was used for the overall certainty of evidence from included studies. Main Results: Nine studies were included: eight RCTs and one NRS. 644 participants were included in analyses from six completed RCTs (n=560) and one completed NRS (n=84). Two ongoing RCTs consisting of 294 participants (260 adult and 34 pediatric) are pending inclusion. One completed RCT included children receiving HSCT (n=6) and five RCTs only included adults (n=239 with acute leukemia receiving chemotherapy and n=315 with a hematological malignancy receiving HSCT). The restrictive strategies varied from 70 g/L to 80 g/L and liberal strategies from 80 g/L to 120 g/L. A restrictive strategy was found to result in a reduction in the number of RBC units per participant compared to a liberal strategy (Four studies; 457 participants; MD: -2.39, 95%CI -3.38 to -1.39, P = &amp;lt;0.00001). No difference was seen in bleeding between strategies although there was high concern for bias in included trials. Effects were reported in the summary of findings tables for RCTs (Table 1) which included results from adults only to reduce indirectness as a result of limited information from the single published pediatric RCT which was terminated early. Overall, a restrictive RBC transfusion strategy may result in little to no difference in the risk of death at 31 to 100 days compared to a liberal transfusion strategy (three studies; 382 participants; RR 0.74, 95% CI 0.13 to 4.09, P= 0.73; I 2=28%; low-certainty evidence). Two outcomes (mortality at 31 to 100 days and clinically significant bleeding) were reported from the one NRS (Table 2). The evidence is very uncertain whether there is a difference in mortality and clinically significant bleeding between the transfusion strategies based on the very low-certainty evidence. Conclusions: A restrictive transfusion strategy demonstrated a reduction in RBC usage, while there may be no impact on mortality. Definite conclusions are challenging given the relatively few studies with low numbers of included participants, concern for bias, heterogeneity of intervention and outcome reporting and overall certainty of evidence. There is a need for larger and methodologically better designed and executed studies. There is insufficient evidence to answer this review's primary outcome. Further RCTs are required overall, particularly trials inclusive of pediatric participants.

Evidence-Based Guidelines for Prehospital Airway Management: Methods and Resources Document

Introduction Emergency airway management is a common and critical task EMS clinicians perform in the prehospital setting. A new set of evidence-based guidelines (EBG) was developed to assist in prehospital airway management decision-making. We aim to describe the methods used to develop these EBGs. Methods The EBG development process leveraged the four key questions from a prior systematic review conducted by the Agency for Healthcare Research and Quality (AHRQ) to develop 22 different population, intervention, comparison, and outcome (PICO) questions. Evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and tabulated into the summary of findings tables. The technical expert panel then used a rigorous systematic method to generate evidence to decision tables, including leveraging the PanelVoice function of GRADEpro. This process involved a review of the summary of findings tables, asynchronous member judging, and online facilitated panel discussions to generate final consensus-based recommendations. Results The panel completed the described work product from September 2022 to April 2023. A total of 17 summary of findings tables and 16 evidence to decision tables were generated through this process. For these recommendations, the overall certainty in evidence was “very low” or “low,” data for decisions on cost-effectiveness and equity were lacking, and feasibility was rated well across all categories. Based on the evidence, 16 “conditional recommendations” were made, with six PICO questions lacking sufficient evidence to generate recommendations. Conclusion The EBGs for prehospital airway management were developed by leveraging validated techniques, including the GRADE methodology and a rigorous systematic approach to consensus building to identify treatment recommendations. This process allowed the mitigation of many virtual and electronic communication confounders while managing several PICO questions to be evaluated consistently. Recognizing the increased need for rigorous evidence evaluation and recommendation development, this approach allows for transparency in the development processes and may inform future guideline development.

Exercise Interventions Delivered Through Telehealth to Improve Physical Functioning for Older Adults with Frailty, Cognitive, or Mobility Disability: A Systematic Review and Meta-Analysis.

Introductions: This study assessed the effects of telehealth-delivered exercise interventions on physical functioning for older adults and explored implementation measures related to program delivery. Methods: We conducted a systematic review of studies investigating effects of exercise interventions delivered through telehealth in adults 60+ years of age with frailty, mobility, or cognitive disability on mobility, strength, balance, falls, and quality of life (QoL). Electronic databases (MEDLINE, CINAHL, SPORTSDiscus, and Physiotherapy Evidence Database) were searched from inception until May 2022. Evidence certainty was assessed with Grading of Recommendations, Assessment, Development, and Evaluation and meta-analysis summarized study effects. Results: A total of 11 studies were included, 5 randomized controlled trials, 2 pilot studies, and 4 feasibility studies. The overall certainty of evidence was rated as "low" or "very low." Pooled between-group differences were not statistically significant, but effect sizes suggested that telehealth produced a moderate improvement on mobility (n = 5 studies; standardized mean difference [SMD] = 0.63; 95% confidence interval [CI] = -0.25 to 1.51; p = 0.000, I2 = 86%) and strength (n = 4; SMD = 0.73; 95% CI = -0.10 to 1.56; p = 0.000, I2 = 84%), a small improvement on balance (n = 3; SMD = 0.40; 95% CI = -035 to 1.15; p = 0.012, I2 = 78%), and no effect on QoL. Analysis of implementation measures suggested telehealth to be feasible in this population, given high rates of acceptability and adherence with minimal safety concerns. Discussion: Telehealth may provide small to moderate benefits on a range of physical outcomes and appears to be well received in aged care populations.

Examining the Effects of Juvenile Drug Treatment Courts: A Systematic Review and Meta-Analysis

We meta-analytically examined program graduation rates among juvenile drug treatment court (JDTC) participants, the effects of JDTCs on recidivism and substance use outcomes, and the variability in these effects. We systematically searched for controlled evaluations examining the effects of U.S.-based JDTCs relative to traditional juvenile adjudication and used mixed-effects meta-regressions with robust variance estimates. We identified 55 eligible samples (providing data from 12,310 participants); the overall certainty of evidence was low or very low. The average graduation rate among JDTC participants was 54.74% (95% confidence interval [CI] [0.50, 0.59]). JDTCs had modest beneficial effects on general recidivism assessed during court supervision (odds ratio [OR] = 1.38, 95% CI [1.03, 1.84]) but these effects did not persist after program completion. Correlational analyses suggest JDTCs may be effective when program enrollment and service provision are better tailored to youth’s treatment needs. However, due partly to implementation failures, JDTCs may have minimal to no effects on postprogram recidivism.