Murad, M. Hassan

Background. Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. Methods. We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. Results. We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. Conclusions. Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

Abstract Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). Results Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P < .001; I 2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. Conclusions Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

AbstractMeta‐analysis is commonly used to combine results from multiple clinical trials, but traditional meta‐analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently‐introduced causally interpretable meta‐analysis methods and apply their treatment effect estimators to two individual‐participant data sets. These estimators transport estimated treatment effects from studies in the meta‐analysis to a specified target population using the individuals' potentially effect‐modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated‐data meta‐analysis methods. In our applications, certain versions of the causally interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally interpretable approach gives meta‐analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments.

ObjectiveTo determine if the efficacy of biologics differ based on magnetic resonance imaging (MRI) and C‐reactive protein (CRP) findings.MethodsWe compared four subgroups (MRI+/CRP+, MRI+/CRP−, MRI−/CRP+, MRI−/CRP−) from randomized controlled trials (RCTs). A comprehensive database search was performed to include axial spondylarthritis (axSpA; both radiographic axSpA [r‐axSpA] and nonradiographic axSpA [nr‐axSpA]) RCTs with treatment efficacy reported by different MRI and CRP subgroups. Study‐specific disease activity scores (at 12‐16 weeks) were pooled using a random‐effects model and compared between the four subgroups.ResultsFive trials (all nr‐axSpA) were included: three with tumor necrosis factor inhibitors (TNFi, N = 729) and two with interleukin‐17 inhibitors (IL‐17i, N = 794). TNFi and IL‐17i showed efficacy based on the Assessment of Spondyloarthritis International Society 40 (ASAS40) and Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) in all MRI and CRP subgroups, except the CRP−/MRI− subgroup, which had a single study with only 39 patients. There was no statistically significant difference between the four subgroups in terms of patients achieving ASAS40 (P = 0.60, I2 = 0%) or BASDAI50 (P = 0.27, I2 = 23.9%). The number needed to treat was three for the CRP+/MRI+ and CRP+/MRI− subgroups and six for the CRP−/MRI+ and CRP−/MRI− subgroups. All trials had a low risk of bias. Between‐study heterogeneity was low to moderate. Sensitivity analyses comparing TNFi or IL‐17i versus placebo similarly showed no difference between subgroups in terms of ASAS40 (TNFi, P = 0.57; IL‐17i, P = 0.28) and BASDAI50 (TNFi, P = 0.37; IL‐17i, P = 0.18).ConclusionIn this systematic review, there was no statistically significant difference between the four subgroups in terms of efficacy based on ASAS40 or BASDAI50.

The objective of this observational study is to determine whether vaccination for SARS-CoV-2 alters the clinical presentation of post-COVID conditions (PCC). Self-reported data provided by patients requesting care for PCC at the Mayo Clinic were analyzed to assess for a relationship between vaccination status prior to COVID infection and PCC symptoms. In all, 477 subjects were included in this study. In total, 245 (51.4%) were vaccinated. Vaccinated subjects with PCC reported less abdominal pain, anosmia, parosmia, chest pain/tightness, dizziness, numbness/tingling, dyspnea, spells/tremors, and weakness. For hospitalized patients who developed PCC, vaccinated patients reported less chest pain, cough, dizziness, and dyspnea. After applying Bonferroni correction for multiple comparisons, decreased abdominal pain remained significant. We conclude that vaccination against SARS-CoV-2 may reduce the symptoms of PCC, leading to improved morbidity and function. Further studies on the impact of vaccination on PCC and recovery are needed.

Abstract Background Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial-breast irradiation (PBI) compared with whole-breast irradiation (WBI). Methods A systematic review was completed to identify relevant randomized clinical trials and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs). Results Fourteen randomized clinical trials and 6 comparative observational studies with 17 234 patients evaluated the comparative effectiveness of PBI. PBI was not statistically significantly different from WBI for IBR at 5 years (RR = 1.34, 95% CI = 0.83 to 2.18; high strength of evidence [SOE]) and 10 years (RR = 1.29, 95% CI = 0.87 to 1.91; high SOE). Evidence for cosmetic outcomes was insufficient. Statistically significantly fewer acute AEs were reported with PBI compared with WBI, with no statistically significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and over than 10 years (high SOE) compared with WBI. Conclusions Ipsilateral breast recurrence was not statistically significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectiveness of PBI among selected patients with early-stage, favorable-risk breast cancer who are similar to those represented in the included studies.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Introduction Acute stroke patients presenting with large vessel occlusion secondary to intracranial atherosclerosis (ICAS‐LVO) may require rescue therapy (RT) in addition to mechanical thrombectomy (MT) to achieve and maintain successful recanalization. We performed a systematic review and meta‐analysis of comparative studies that reported outcomes of RT in ICAS‐LVO patients to evaluate its safety and efficacy. Methods Databases searched include PubMed, CINAHL Complete, and Scopus from database date of inception through August 17, 2021. We included comparative studies that reported the outcomes of ICAS‐LVO RT compared to outcomes of ICAS‐LVO patients who did not undergo RT or to those presenting with embolic LVO patients (non‐ICAS LVO). Meta‐analysis using the random effects model was used to combine estimates reporting odds ratios (OR) and 95% confidence intervals (CI). Results Total of 9 nonrandomized studies were included: 5 studies in ICAS‐LVO RT vs. ICAS‐LVO non‐RT analysis and 5 ICAS‐LVO RT vs. non‐ICAS LVO analysis. Rescue treatments included intra‐arterial antiplatelets, angioplasty, stenting or combination of treatments. Compared to non‐RT ICAS LVO, RT was associated with increased favorable 90‐day outcome (OR 3.19, 95% CI 1.91‐5.32, I2 14%) and decreased 90‐day mortality (OR 0.35, 95% CI 0.16‐0.76, I2 21%) (Figure 1). In the analysis of ICAS LVO vs embolic LVO, the incidence of favorable 90‐day outcome and 90‐day mortality did not differ between the ICAS‐LVO RT and non‐ICAS LVO (OR 0.97, 95% CI 0.58‐1.64, I2 50%) and (OR 1.22, 95% CI 0.90‐1.66, I2 0%), respectively. Conclusions Rescue treatment is associated with better outcomes in ICAS‐LVO patients. The outcomes of ICAS‐LVO patients who receive RT may be comparable to embolic LVO patients (non‐ICAS LVO).

Abstract Background Optimizing therapy and monitoring response are integral aspects of inflammatory bowel disease treatment. We conducted a systematic review and meta-analysis to determine whether serum ustekinumab trough concentrations during maintenance therapy were associated with ustekinumab treatment response in patients with inflammatory bowel disease. Methods A systematic review was performed to March 21, 2022, to identify studies using MEDLINE, EMBASE, and the Cochrane library. We included studies that reported the association between serum ustekinumab trough concentrations with clinical or endoscopic remission. Outcome measures were combined across studies using the random-effects model with an odds ratio (OR) for binary outcomes of endoscopic and clinical remission. Results We identified 14 observational studies that were included in the analysis for clinical remission (919 patients, 63% with Crohn’s disease) or endoscopic remission (290 patients, all with Crohn’s disease). Median ustekinumab trough concentrations were higher amongst individuals achieving clinical remission compared with those not achieving remission (mean difference, 1.6 ug/mL; 95% confidence interval [CI], 0.21-3.01 ug/mL). Furthermore, individuals with median serum trough concentration in the fourth quartile were significantly more likely to achieve clinical (OR, 3.61; 95% CI, 2.11-6.20) but not endoscopic remission (OR, 4.67; 95% CI, 0.86-25.19) compared with those with first quartile median trough concentrations. Conclusion Based on the results of this meta-analysis primarily relating to patients with Crohn’s disease on maintenance ustekinumab treatment, it appears that there is an association between higher ustekinumab trough concentration and clinical outcomes. Prospective studies are required to determine whether proactive dose adjustments of ustekinumab therapy provides additional clinical benefit.