A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder.

OBJECTIVE: The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes. DATA SOURCES: We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone. METHODS: A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder. RESULTS: A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes. CONCLUSION: Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.

A systematic literature review of health disparities among rural people with epilepsy (RPWE) in the United States and Canada.

BACKGROUND: Epilepsy is a leading cause of global disease burden, with people with epilepsy (PWE) experiencing adverse health outcomes related to the psychiatric comorbidities and socioeconomic consequences of the disorder. Rural populations are more likely to be impoverished or uninsured, which could impact health outcomes for rural-dwelling PWE (RPWE). AIMS: This systematic literature review identified original research studying health disparities and outcomes among RPWE in the United States and Canada to (1) characterize the disparities faced by RPWE and (2) elucidate the effects of these disparities upon clinical outcomes. METHODS: We performed a systematic search of six electronic databases: Pubmed, Cochrane, PsychInfo, Web of Science, Scopus, and Ovid. Articles considered were original research reports conducted in Canada or the United States before August 2020. A modified Newcastle Ottawa Scale was used to assess the quality of the included studies. RESULTS: Our search returned 2093 articles that examined the health disparities of RPWE, of which six met criteria for this review. Outcome measures of health disparity included in these papers were mortality (2; 33%), use of health resources (2; 33%), and epilepsy prevalence (2; 33%). Only one paper (16%) concluded that RPWE experienced worse health outcomes relative to urban-dwelling PWE, while 5 (84%) found no difference. CONCLUSION: Our study did not find sufficient evidence that RPWE in the US and Canada experience significant health disparities compared to similar urban populations of PWE. More research using prospective studies and datasets allowing better characterization of rurality is required.

Tympanoplasty in the Setting of Complex Middle Ear Pathology: A Systematic Review.

OBJECTIVE: To assess the prognostic factors for anatomic and hearing success after tympanoplasty in the setting of complex middle ear pathology. METHODS: A systematic review was performed in January 2022. English-language articles describing outcome data for tympanoplasty repair variables including underlying pathology, perforation location, smoking status, graft technique, reconstruction material, anatomic success, and hearing success were extracted. Articles were included when tympanosclerosis, retraction pockets, adhesions, cholesteatoma, chronic suppurative otitis media, anterior perforations, and smoking were included. Underlying pathology, perforation location, smoking status, graft technique, reconstruction material, anatomic success, and hearing success were extracted. Any factors analyzed as potential indicators of success were sought out. RESULTS: Data sources included PubMed, OVID, Cochrane, Web of Science, Scopus, and manual search of bibliographies. Ninety-three articles met final criteria, which accounted for 6685 patients. Fifty articles presented data on both anatomic and hearing outcomes, 32 articles presented data on anatomic outcomes only, and 11 articles presented data on hearing outcomes only. This systematic review found that adhesions and tympanosclerosis were prognostic factors for poorer hearing. Additionally, smoking and tympanosclerosis may be predictive of anatomic failure; however, the significance of this finding was mixed in included studies. This analysis is significantly limited by both the heterogeneity within the patients and the lack of controls. CONCLUSION: Adhesions and tympanosclerosis were prognostic factors for poorer hearing. Clearly documented methods and outcomes for the included pathologies could lead to more definitive conclusions regarding prognostic factors for success. LEVEL OF EVIDENCE: 3B.

Clinician approaches to spinal manipulation for persistent spinal pain after lumbar surgery: systematic review and meta-analysis of individual patient data.

BACKGROUND: This review aimed to identify variables influencing clinicians' application of spinal manipulative therapy (SMT) for persistent spine pain after lumbar surgery (PSPS-2). We hypothesized markers of reduced clinical/surgical complexity would be associated with greater odds of applying SMT to the lumbar region, use of manual-thrust lumbar SMT, and SMT within 1-year post-surgery as primary outcomes; and chiropractors would have increased odds of using lumbar manual-thrust-SMT compared to other practitioners. METHODS: Per our published protocol, observational studies describing adults receiving SMT for PSPS-2 were included. PubMed, Web of Science, Scopus, OVID, PEDro, and Index to Chiropractic Literature were searched from inception to January 6, 2022. Individual patient data (IPD) were requested from contact authors when needed for selection criteria. Data extraction and a customized risk-of-bias rubric were completed in duplicate. Odds ratios (ORs) for primary outcomes were calculated using binary logistic regressions, with covariates including age, sex, symptom distribution, provider, motion segments, spinal implant, and surgery-to-SMT interval. RESULTS: 71 articles were included describing 103 patients (mean age 52 ± 15, 55% male). The most common surgeries were laminectomy (40%), fusion (34%), and discectomy (29%). Lumbar SMT was used in 85% of patients; and of these patients was non-manual-thrust in 59%, manual-thrust in 33%, and unclear in 8%. Clinicians were most often chiropractors (68%). SMT was used > 1-year post-surgery in 66% of cases. While no primary outcomes reached significance, non-reduced motion segments approached significance for predicting use of lumbar-manual-thrust SMT (OR 9.07 [0.97-84.64], P = 0.053). Chiropractors were significantly more likely to use lumbar-manual-thrust SMT (OR 32.26 [3.17-327.98], P = 0.003). A sensitivity analysis omitting high risk-of-bias cases (missing ≥ 25% IPD) revealed similar results. CONCLUSIONS: Clinicians using SMT for PSPS-2 most often apply non-manual-thrust SMT to the lumbar spine, while chiropractors are more likely to use lumbar-manual-thrust SMT relative to other providers. As non-manual-thrust SMT may be gentler, the proclivity towards this technique suggests providers are cautious when applying SMT after lumbar surgery. Unmeasured variables such as patient or clinician preferences, or limited sample size may have influenced our findings. Large observational studies and/or international surveys are needed for an improved understanding of SMT use for PSPS-2. Systematic review registration PROSPERO (CRD42021250039).

Impact of anemia on acute ischemic stroke outcomes: A systematic review of the literature.

INTRODUCTION: Anemia has been reported in nearly 40% of acute ischemic stroke (AIS) patients and is linked to significant morbidity and disability. The presence of anemia is associated with worse outcomes in AIS, specifically in the presence of large vessel occlusion (LVO). An optimal hemoglobin (Hb) target specific to this pathology has not yet been established. The goal of this review is to systematically review literature that observes the association that exists between AIS outcomes and hemoglobin (Hb) levels. METHODS: A systematic review was performed in accordance with guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to identify studies from 2008-2022. The following inclusion and exclusion criteria were used: studies of adult patients with AIS; must describe outcomes with regard to Hb levels in AIS (not limited to LVO); must be written in English. The clinical variables extracted included Length of Stay (LOS), modified rankin score (mRS), Hb levels, and mortality. RESULTS: A total of 1,154 studies were gathered, with 116 undergoing full text review. 31 studies were included in this review. The age of patients ranged from 61.4 to 77.8. The presence of anemia in AIS increased LOS by 1.7 days on average and these patients also have a 15.2% higher rate of mortality at one year, on average. DISCUSSION: This data suggests that the contemporary thresholds for treating anemia in AIS patients may be inadequate because anemia is strongly associated with poor outcomes (e.g., mRS>2 or mortality) and increased LOS in AIS patients. The current generalized Hb threshold for transfusion (7 g/dL) is also used in AIS patients, however, a more aggressive transfusion parameter should be further explored based on these findings. Further studies are required to confirm these findings and to determine if a more liberal RBCT threshold will result in clinical benefits.

Failure of Conservatively Managed Traumatic Vertebral Compression Fractures: A Systematic Review.

BACKGROUND: Most vertebral compression fractures (VCFs) are successfully managed conservatively; however, some patients fail conservative management and require further surgical treatment. We sought to identify significant variables that contribute to progressive vertebral collapse in nonoperative treatment of traumatic VCFs. METHODS: A systematic review identified original research articles of conservatively managed VCFs secondary to trauma from inception to September 2021. Articles with patients treated with initial nonoperative therapy, AO type A0, A1, and A2 fractures, risk factor analysis, >10 patients, and vertebral fracture secondary to trauma were included. Articles with pediatric patients, burst fractures or AO type A3 and A4 fractures, vertebral fractures secondary to neoplasm or infectious disease, and operative versus nonoperative treatment comparations were excluded. Failure of nonoperative treatment was defined as salvage surgery/vertebral augmentation, progressive kyphosis, chronic pain, or functional disability. RESULTS: Of 3877 articles identified, 6 articles were included with 582 patients with conservatively managed thoracolumbar VCFs. Treatment failure was reported in 102 (17.5%) patients. Of 102 treatment failures, 37 (36.3%) were due to subsequent VCF, 33 (32.4%) were due to back pain or functional disability at follow-up, and 32 (31.4%) were due to increased compression rate or kyphotic deformity at follow-up. Prior VCF was a significant variable in 2 (33.3%) of 6 studies. Age, lumbar bone mineral density, segmental Cobb angle, and vertebral height loss were each described as a significant factor in 1 (16.7%) of the 6 studies. CONCLUSIONS: Identifying patients who are at risk for treatment failure may help select patients who would benefit from close clinical follow-up or early surgical/procedural intervention.

Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound during traditional invasive coronary angiography. Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography, an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all 4 imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with invasive coronary angiography without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.

Clinical decision-making for spinal manipulation for persistent spinal pain following lumbar surgery: a protocol for a systematic review and meta-analysis of individual participant data.

INTRODUCTION: There are limited available research and guidance regarding the use of spinal manipulative therapy (SMT) in patients with low back-related symptoms following lumbar spine surgery, a condition called persistent spinal pain syndrome type 2 (PSPS-2). This publication outlines a review protocol to identify and synthesise individual participant data (IPD) to examine associations between patient, clinical and surgical variables and SMT application in adults with PSPS-2. METHODS AND ANALYSIS: PubMed, OVID, Web of Science, Scopus, PEDro, Index to Chiropractic Literature and KoreaMed will be searched from inception to 1 January 2022 without language restrictions. Case reports, series, observational studies and cases from grey literature of adults receiving SMT for PSPS-2 will be included. Two investigators will independently screen citations, abstracts and full-text articles. A risk-of-bias assessment will be performed in duplicate to rate cases according to exposure and outcome ascertainment and data completeness. Data extraction will be performed in duplicate and missing IPD will be requested from corresponding authors. Multiple binary logistic regression will be used to identify independent predictors of the use of lumbar-SMT, lumbar-manual-thrust SMT and SMT within 1-year postsurgery. Patient, clinical and surgical variables will be summarised using descriptive statistics, while SMT-related outcomes (lumbar-SMT, lumbar-manual-thrust SMT and 1-year surgery-to-SMT interval) will be described using adjusted ORs with 95% CIs. ETHICS AND DISSEMINATION: This study was deemed not human subjects research by the University Hospitals' institutional review board. The results of this review will be disseminated at conferences and/or published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021250039.

Evaluation of Risk of Gastrostomy and Ventriculoperitoneal Shunt Placement in Pediatric Patients: A Systematic Review of the Literature.

A subset of patients with neurologic deficits require ventriculoperitoneal shunt (VPS) placement in addition to gastrostomy tubes (GTs). At present, the literature is inconsistent with respect to the sequence and time period between procedures that yields the lowest risk profile for GT and VPS placement. The purpose of this systematic literature review was to determine if time elapsed between VPS and GT placement was associated with infection (peritoneal and/or CSF). A systematic literature review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. PubMEd/MEDLINE, Scopus, Ovid, Cochrane, and EMBASE databases were queried. Precise search terminology is available in the body of the manuscript. The initial database query yielded 88 unique articles. After abstract screening, 28 articles were identified and 6 met criteria for inclusion in the final analysis. The included studies were all retrospective analyses and reported data for 217 patients between the years of 1988 and 2016. Across all included studies, the infection rate after VPS and GT placement during the studies' surveillance period was 15.2% (n = 33/217). The cumulative rate of all reported complications in patients with both VPS and GT was 24.0% (n = 52/217). These studies suggest that placement of GT in patients with preexisting VPS does not significantly contribute to increased shunt or intraperitoneal infection. Future studies should determine the optimal time interval between VPS and GT placement and to identify the most appropriate prophylactic antibiotic regimen.

Assessment of burnout prevention and wellness programs for US-based neurosurgical faculty and residents: a systematic review of the literature.

OBJECTIVE: Neurosurgeon burnout is a serious and prevalent issue that has been shown to impact professionalism, physician health, and patient outcomes. Interventions targeting physician burnout primarily focus on improving physician wellness. Many academic neurosurgery programs have established wellness curricula to combat burnout and improve wellness. No official recommendations exist for establishing a wellness program that effectively targets sources of burnout. The aim of this review was to examine measures of burnout and report objective results of wellness interventions for neurosurgical faculty and residents. METHODS: Two systematic literature reviews were performed in parallel, in accordance with PRISMA 2009 guidelines. Following removal of duplicates, a query of PubMed/MEDLINE, Scopus, Ovid, Cochrane, and EMBASE databases yielded 134 resident-related articles and 208 faculty-related articles for abstract screening. After abstract screening, 17 articles with a primary focus of resident wellness and 10 with a focus on faculty wellness met criteria for full-text screening. Of the total 27 screened articles, 9 (6 resident, 2 faculty, 1 both resident and faculty) met criteria and were included in the final analysis. Article quality was assessed using the Joanna Briggs Institute critical appraisal tools for cohort studies. RESULTS: Included studies reported burnout rates for neurosurgery residents of 30%-67%. Work-life imbalance, imbalance of duties, inadequate operative exposure, and hostile faculty were contributors to burnout. The 2 included studies reported burnout rates for neurosurgery faculty members of 27% and 56.7%. Psychosocial stressors, relational stressors, and financial uncertainty were generally associated with increased feelings of burnout. Of the 4 studies reporting on outcomes of wellness initiatives included in this review, 3 reported a positive impact of the wellness interventions and 1 study reported no significant improvement after implementing a wellness initiative. CONCLUSIONS: Burnout among neurosurgical faculty and residents is prevalent and permeates the daily lives of neurosurgeons, negatively affecting patient outcomes, career satisfaction, and quality of life. Many neurosurgery programs have instituted wellness programs to combat burnout, but few have published evidence of improvement after implementation. While studies have shown that residents and faculty recognize the importance of wellness and look favorably on such initiatives, very few studies have reported objective outcomes.