Hemospray® (hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multicenter prospective study.

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB. Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05). Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved. Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy.

Two AIS Cases, 2 Surgeons, 1 Operating Room, 1 Day: Faster and Safer Than 1 Case in a Day.

BACKGROUND: To lessen surgical times for patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal instrumentation and fusion (PSIF), our department developed a quality improvement initiative where 2 AIS cases were completed in 1 day by the same 2 surgeons operating together in 1 operating room (OR). We describe the results of this initiative, comparing operative times and outcomes to cases of these surgeons operating individually. METHODS: From 2017 to 2023, patients aged 10 to 18 years with AIS undergoing PSIF were prospectively enrolled for "Two Spine Tuesday." Patients were matched by age, sex, curve severity, and number of levels fused to historical AIS controls. Outcomes included surgery time, total OR time, estimated blood loss (EBL), volume of cell saver transfused, allogenic blood transfusion, length of stay, 90-day readmissions, Clavien-Dindo-Sink Complication Classification System complication rates, and percentage who achieved the minimal clinically important difference (MCID) for SRS-22. RESULTS: Fifty-five patients composing the 2-spine group (group 2) were compared with 55 historical sex-matched and age-matched controls (group 1). Major coronal curve and average number of levels fused were similar between groups. Overall surgery time (203 vs. 296 min, P<0.001), total OR time (P<0.001), and EBL (400 vs. 550 mL, P<0.001) were lower for group 2. Group 2 had fewer complications [n=17 (31%) vs. n=28 (51%), P=0.03]. CONCLUSIONS: Performing 2 AIS cases in 1 OR by 2 surgeons the same day resulted in shorter surgery times, less total time in the operating room, lower complication rates, and less blood loss compared with single-surgeon matched controls. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Transiliac-Shortening Osteotomy to Treat Ischial Pressure Injury due to Fixed Pelvic Obliquity: A Case Report.

CASE: A 17-year-old adolescent boy with Gross Motor Function Classification System 5 cerebral palsy and neuromuscular scoliosis underwent posterior spinal fusion and segmental spinal instrumentation from T3 to the pelvis. He developed a right ischial pressure injury a few months postoperatively, which persisted despite nonoperative measures. He subsequently underwent an ipsilateral transiliac-shortening osteotomy 16 months after spinal surgery to treat his residual pelvic obliquity and the ischial pressure injury, which healed completely. At the 1-year follow-up visit, there were no further signs of pressure injury. CONCLUSION: This case report describes transiliac-shortening osteotomy as a viable treatment option for non-healing ischial pressure injuries secondary to fixed pelvic obliquity.

Surgeon and SterEOS agreement of spinal sagittal plane parameters in patients with adolescent idiopathic scoliosis.

PURPOSE: To compare agreement between surgeons and sterEOS sagittal plane measurements. METHODS: EOS radiographs of 74 patients with adolescent idiopathic scoliosis were reviewed. The measurements were generated by two surgeons and compared to sterEOS. Intraclass correlations (ICC) were calculated. Agreement was also analyzed for the following subgroups: Cobb angle < 70° vs ≥ 70°, lumbar modifier A vs B/C, and BMI of < 24.5 kg/m2 vs ≥ 24.5 kg/m2. Agreement was poor if the ICC was < 0.5, moderate if 0.5-0.75, good if 0.75-0.9, and excellent if > 0.9. Paired t tests were performed to compare the surgeon's and sterEOS means. RESULTS: For the surgeons, agreement was good (0.75-0.89) except for pelvic tilt (PT) and sacral slope (SS), which were excellent (0.91-0.92). Agreement between the surgeons and sterEOS were good (0.78-0.9) except PT and SS, which were excellent (0.91-0.93). Agreement was negatively affected for T4-T12 kyphosis, PI, and SS in the ≥ 70°group, LL when BMI was ≥ 24.5 kg/m2, and LL, PI, and SS in the lumbar modifier B/C group. The ICCs overlapped with the 95% confidence intervals (95% CI). Paired t-test showed a significant difference for T4-T12 kyphosis (p < 0.001). This was also true in the < 70° group (p < 0.001), the ≥ 70° group (p = 0.04), and the BMI < 24.5 kg/m2 group. PT was significantly different for the ≥ 70° group. CONCLUSIONS: There was good to excellent agreement between the surgeons and surgeons and sterEOS. Some variables may affect agreement. The surgeons overestimated T4-T12 kyphosis.

Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes.

PURPOSE: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program. METHODS: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes. RESULTS: Diagnostic rates ranged from 11% in patients with prior negative genetic testing to 34.5% in naive patients. Incorporating SVs from genome sequencing added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs compared with srGS. Variants and genes of unknown significance remain the most common finding (58% of nondiagnostic cases). CONCLUSION: Computational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated using HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation and by providing HiFi variant (SNV/SV) resources from >1000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses.

Health-related quality of life in primary immunodeficiencies: Impact of delayed diagnosis and treatment burden.

Accurate and timely diagnosis of primary immunodeficiencies (PID) is an ongoing effort. Individuals with PID can be severely impacted by their disease and many experience chronic complications, treatment burden, and reduced quality of life (QoL). This review focuses on the impact of delayed diagnosis and treatment burden on patient QoL and outcomes. Adults tend to experience longer delays in diagnosis than pediatric populations. The median diagnostic delay has reduced over recent decades, but remains high for some antibody deficiency variants, such as common variable immunodeficiency. The largest burden impacting QoL tends to be poorly controlled disease and persistent chronic conditions rather than treatment burden. Hospitalization, physician/emergency room visits, and bronchiectasis were the most expensive PID complications prior to diagnosis and cost analyses estimate cost reductions once appropriate treatment is initiated. A combination of poor awareness, lack of infrastructure, and resources supporting national registries play a major role in delayed diagnosis.

Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, potentially life-threatening attacks, resulting in significant physical and emotional burdens for patients and families. To optimize care for patients with HAE, an individualized management plan should be considered in partnership with the physician, requiring comprehensive assessment of the patient's frequency and severity of attacks, disease burden, and therapeutic control. Although several guidelines and consensus papers have been published concerning the diagnosis and treatment of HAE, there has been limited specific clinical guidance on the assessment of disease burden and quality of life (QoL) in this patient population. Practical guidance is critical in supporting effective long-term clinical management of HAE and improving patient outcomes. The objective of this review is to provide evidence-based guidelines for an individualized assessment of disease burden and QoL in patients with HAE. METHODS: A consensus meeting was held on February 29, 2020, consisting of 9 HAE experts from the United States and Europe with extensive clinical experience in the treatment of HAE. Consensus statements were developed based on a preliminary literature review and discussions from the consensus meeting. RESULTS: Final statements reflect the consensus of the expert panel and include the assessment of attack severity, evaluation of disease burden, and long-term clinical management of HAE caused by C1-esterase inhibitor deficiency. Patient-reported outcome measures for assessing HAE attack severity and frequency are available and valuable tools; however, attack frequency and severity are insufficient markers of disease severity unless they are evaluated in the broader context of the effect on an individual patient's QoL. QoL assessments should be individualized for each patient and minimally, they should address the interference of HAE with work, school, social, family, and physical activity, along with access to and burden of HAE treatment. Advances in HAE therapies offer the opportunity for comprehensive, individualized treatment plans, allowing patients to achieve minimal attack burden with reduced disease and treatment burden. CONCLUSION: This consensus report builds on existing guidelines by expanding the assessment of disease burden and QoL measures for patients with HAE.

An intraoperative laterally placed distractor for gradual load sharing correction of severe spastic neuromuscular spinal deformity.

PURPOSE: To analyze the overall deformity correction for severe neuromuscular scoliosis using laterally placed intra-operative distraction and compare to those receiving standard surgical technique. METHODS: This was a retrospective, IRB-approved, cohort study of patients with GMFCS 4 or 5 spastic cerebral palsy with neuromuscular scoliosis, age greater than 10 years, who underwent posterior spinal fusion from 2007 to 2019. All patients had vectored cervical traction with Gardner-Wells tongs, with hips flexed in a relative sitting position. The study cohort underwent intraoperative, laterally placed correction using a distractor placed between two upper ribs and the ipsilateral greater trochanter while the control cohort did not. The 24 study patients were compared to 22 control patients. RESULTS: Preoperative comparisons identified significant differences in Cobb angle, preoperative flexibility, and pelvic obliquity with the study group having larger, stiffer deformities with greater obliquity. There were no differences in pre-operative sagittal plane deformity. Mean post-operative upright Cobb angle correction was 67.3° ± 14.8° in the study and 55.3° ± 9.9° in the control group, representing a 66% and 60% correction, respectively. No neurological or other complications were noted from the use of this technique. CONCLUSION: The use of a laterally placed distraction device from upper ribs to ipsilateral greater trochanter allowed gradual lateral un-bending of large stiff neuromuscular spine deformities with greater correction than that of standard technique. In this small series, the technique allowed load-sharing during correction, with hips remaining in a functional sitting position, and without neurological complications. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Iliac screw instrumentation to the pelvis in children with neuromuscular and syndromic scoliosis. No lateral connectors and respect sagittal balance.

STUDY DESIGN: One-center retrospective cohort study. BACKGROUND: Compared to the traditional iliac screw technique, the modified iliac screw technique has a lower rate of distal implant failure in the treatment of neuromuscular scoliosis patients with pelvic obliquity. However, the reasons for decreased failure with the modified iliac screw technique are controversial. QUESTIONS/PURPOSES: (1) Is distal implant failure, as evident by implant breakage or disconnection, more likely to occur in patients receiving the traditional iliac screw technique (PSIS) compared to the modified S2AI (MODS2) technique? (2) After controlling for relevant confounding variables, are there other identifiable risk factors for distal implant failure? METHODS: We identified patients who underwent pelvic screw fixation by three pediatric spine surgeons from January 2007 to July 2017. Based on the starting point of the iliac screws, patients were divided into two groups. Group 1 consisted of PSIS fixation with an offset connector. Group 2 consisted of modified S2AI fixation without an offset connector. Demographic, operative, and radiographic data were obtained. RESULTS: Cobb angle, lumbar lordosis, and pelvic obliquity were not significantly different between the two groups. Overall distal implant failure was 40/100 (40%) and significant between Group 1 PSIS 29/53 (55%) and Group 2 MODS2 11/47 (23%) (p = 0.002). No other complications were significant. Three risk factors were identified with implant failure: high pelvic incidence (17-fold increase, 95% confidence interval [CI] = 5.5 to 53.1, p < 0.001), high angle rod contour (3.8-fold increase, 95% CI = 1.2 to 11.9, p = 0.023), and use of an offset connector (3.2-fold increase, 95% CI = 1.0 to 10.3, p = 0.049). Failure did not correlate with the use of a cross-link, iliac screw diameter, or screw density. Revision surgery related to distal implant failure did not significantly differ between the two groups. CONCLUSIONS: Compared to the use of an offset connector with PSIS fixation, MODS2 fixation had a lower rate of implant failure. Sagittal balance parameters, namely pelvic incidence and angle of rod bend, were the major risk factors for implant failure. LEVEL OF EVIDENCE: III.

Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study.

PURPOSE: To evaluate the safety and tolerability of subcutaneous IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) administered at high infusion parameters (> 25 mL and > 25 mL/h per injection site) in patients with primary immunodeficiency. METHODS: The Hizentra® Label Optimization (HILO) study was an open-label, parallel-arm, non-randomized study (NCT03033745) of IgPro20 using a forced upward titration design for infusion parameters. Patients experienced with pump-assisted IgPro20 infusions received weekly IgPro20 infusions at a stable dose in the Pump-Assisted Volume Cohort (N = 15; 25-50 mL per injection site) and in the Pump-Assisted Flow Rate Cohort (N = 18; 25-100 mL/h per injection site). Responder rates (percentage of patients who successfully completed ≥ 75% of planned infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. RESULTS: Responder rates were 86.7% (13/15, 25 mL) and 73.3% (11/15, 40 and 50 mL) in the Volume Cohort, and 77.8% (14/18, 25 and 50 mL/h), 66.7% (12/18, 75 mL/h), and 61.1% (11/18, 100 mL/h) in the Flow Rate Cohort. Infusion compliance was ≥ 90% in all patients in the Volume Cohort and in 83.3% of patients in the Flow Rate Cohort. The number of injection sites (Volume Cohort) and the infusion duration (Flow Rate Cohort) decreased with increasing infusion parameters. The rate of treatment-emergent adverse events per infusion was low (0.138 [Volume Cohort] and 0.216 [Flow Rate Cohort]). Serum IgG levels remained stable during the study. CONCLUSION: Pump-assisted IgPro20 infusions are feasible at 50 mL and 100 mL/h per injection site in treatment-experienced patients, which may result in fewer injection sites and shorter infusion times. TRIAL REGISTRATION: NCT03033745 ; registered January 27, 2017.

Colonoscopy competence assessment tools: a systematic review of validity evidence.

BACKGROUND: Assessment tools are essential for endoscopy training, being required to support feedback provision, optimize learner capabilities, and document competence. We aimed to evaluate the strength of validity evidence that supports the available colonoscopy direct observation assessment tools using the unified framework of validity. METHODS: We systematically searched five databases for studies investigating colonoscopy direct observation assessment tools from inception until 8 April 2020. We extracted data outlining validity evidence (content, response process, internal structure, relations to other variables, and consequences) from the five sources and graded the degree of evidence, with a maximum score of 15. We assessed educational utility using an Accreditation Council for Graduate Medical Education framework and methodological quality using the Medical Education Research Quality Instrument (MERSQI). RESULTS: From 10 841 records, we identified 27 studies representing 13 assessment tools (10 adult, 2 pediatric, 1 both). All tools assessed technical skills, while 10 each assessed cognitive and integrative skills. Validity evidence scores ranged from 1-15. The Assessment of Competency in Endoscopy (ACE) tool, the Direct Observation of Procedural Skills (DOPS) tool, and the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT) had the strongest validity evidence, with scores of 13, 15, and 14, respectively. Most tools were easy to use and interpret, and required minimal resources. MERSQI scores ranged from 9.5-11.5 (maximum score 14.5). CONCLUSIONS: The ACE, DOPS, and GiECAT have strong validity evidence compared with other assessments. Future studies should identify barriers to widespread implementation and report on the use of these tools in credentialing examinations.

Development and validation of a patient-reported scale for tolerability of endoscopic procedures using conscious sedation.

BACKGROUND AND AIMS: Patient-reported experience measures (PREMs) assessing the tolerability of endoscopic procedures are scarce. In this study, we designed and validated a PREM to assess tolerability of endoscopy using conscious sedation. METHODS: The patient-reported scale for tolerability of endoscopic procedures (PRO-STEP) consists of questions within 2 domains and is administered to outpatients at discharge from the endoscopy unit. Domain 1 (intraprocedural) consists of 2 questions regarding discomfort/pain and awareness, whereas domain 2 (postprocedural) consists of 4 questions on pain, nausea, distention, and either throat or anal pain. All questions are scored on a Likert scale from 0 to 10. Cronbach's alpha was used to measure internal consistency of the questions. Multivariable logistic regression was performed to assess predictors of higher scores, reported using adjusted odds ratios and confidence intervals. RESULTS: Two hundred fifty-five patients (91 colonoscopy, 73 gastroscopy, and 91 ERCP) were included. Colonoscopy was the least tolerable procedure by recall, with mean intraprocedural awareness and discomfort scores of 5.1 ± 3.8, and 2.6 ± 2.7, respectively. Consistency between intraprocedural awareness and discomfort/pain yielded an acceptable Cronbach's alpha of .71 (95% confidence interval, .62-.78). Higher use of midazolam during colonoscopy was inversely associated with an intraprocedural awareness score of 7 or higher (per additional mg: adjusted odds ratio, .23; 95% confidence interval, .09-.54). CONCLUSIONS: PRO-STEP is a simple PREM that can be administered after multiple endoscopic procedures using conscious sedation. Future work should focus on its performance characteristics in adverse event prediction.

Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a leading cause of morbidity and is associated with a 2 % - 17 % mortality rate in the UK and USA. Bleeding peptic ulcers account for 50 % of UGIB cases. Endoscopic intervention in a timely manner can improve outcomes. Hemostatic spray is an endoscopic hemostatic powder for GI bleeding. This multicenter registry was created to collect data prospectively on the immediate endoscopic hemostasis of GI bleeding in patients with peptic ulcer disease when hemostatic spray is applied as endoscopic monotherapy, dual therapy, or rescue therapy. METHODS: Data were collected prospectively (January 2016 - March 2019) from 14 centers in the UK, France, Germany, and the USA. The application of hemostatic spray was decided upon at the endoscopist's discretion. RESULTS: 202 patients with UGIB secondary to peptic ulcers were recruited. Immediate hemostasis was achieved in 178/202 patients (88 %), 26/154 (17 %) experienced rebleeding, 21/175 (12 %) died within 7 days, and 38/175 (22 %) died within 30 days (all-cause mortality). Combination therapy of hemostatic spray with other endoscopic modalities had an associated lower 30-day mortality (16 %, P < 0.05) compared with monotherapy or rescue therapy. There were high immediate hemostasis rates across all peptic ulcer disease Forrest classifications. CONCLUSIONS: This is the largest case series of outcomes of peptic ulcer bleeding treated with hemostatic spray, with high immediate hemostasis rates for bleeding peptic ulcers.

Establishing key research questions for the implementation of artificial intelligence in colonoscopy: a modified Delphi method.

BACKGROUND : Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. METHODS : An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers, from nine countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. RESULTS : The top 10 ranked questions were categorized into five themes. Theme 1: clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterization, determining the optimal end points for evaluation of AI, and demonstrating impact on interval cancer rates. Theme 2: technological developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false-positive rates, and minimizing latency. Theme 3: clinical adoption/integration (1 question), concerning the effective combination of detection and characterization into one workflow. Theme 4: data access/annotation (1 question), concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: regulatory approval (1 question), related to making regulatory approval processes more efficient. CONCLUSIONS : This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy.

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.

Educational interventions are associated with improvements in colonoscopy quality indicators: a systematic review and meta-analysis.

Background and study aims The quality of screening-related colonoscopy depends on several physician- and patient-related factors. Adenoma detection rate (ADR) varies considerably between endoscopists. Educational interventions aim to improve endoscopists' ADRs, but their overall impact is uncertain. We aimed to assess whether there is an association between educational interventions and colonoscopy quality indicators. Methods A comprehensive search was performed through August 2019 for studies reporting any associations between educational interventions and any colonoscopy quality indicators. Our primary outcome of interest was ADR. Two authors assessed eligibility criteria and extracted data independently. Risk of bias was also assessed for included studies. Pooled rate ratios (RR) with 95 % confidence intervals (CI) were reported using DerSimonian and Laird random effects models. Results From 2,253 initial studies, eight were included in the meta-analysis for ADR, representing 86,008 colonoscopies. Educational interventions were associated with improvements in overall ADR (RR 1.29, 95 % CI 1.25 to 1.42, 95 % prediction interval 1.09 to 1.53) and proximal ADR (RR 1.39, 95 % CI 1.29 to 1.48), with borderline increases in withdrawal time, ([WT], mean difference 0.29 minutes, 95 % CI - 0.12 to 0.70 minutes). Educational interventions did not affect cecal intubation rate ([CIR], RR 1.01, 95 % CI 1.00 to 1.01). Heterogeneity was considerable across many of the analyses. Conclusions Educational interventions are associated with significant improvements in ADR, in particular, proximal ADR, and are not associated with improvements in WT or CIR. Educational interventions should be considered an important option in quality improvement programs aiming to optimize the performance of screening-related colonoscopy.

Hereditary angioedema: Comprehensive management plans and patient support.

Hereditary angioedema (HAE) is a rare disease. Regardless, patients with HAE have access to multiple state-of-the-art medications available for on-demand use and prevention that reduce the frequency and burden of HAE attacks. These treatments have greatly reduced the burden of disease and helped patients achieve improved quality of life. However, with greater numbers of therapeutic options, HAE care has become more complex. In this review, we addressed essential elements of an individualized comprehensive management plan for a patient with HAE. We focused on access to an expert physician, ongoing patient education, access to effective treatment options, coordination of care and management of treatment logistics, ongoing monitoring of attacks and treatments, and other resources for patient support. This plan will need to be communicated with the patient and other care providers, especially during emergent conditions, and accommodate the patient's lifestyle with consideration for work, school, travel, etc. Periodically, the physician and the patient will need to review information about attacks, triggers, and treatments to identify areas for improvement and update the plan.

Why Irrigate for the Same Contamination Rate: Wound Contamination in Pediatric Spinal Surgery Using Betadine Versus Saline.

BACKGROUND: The risk of surgical site infection in pediatric posterior spine fusion (PSF) is up to 4.3% in idiopathic populations and 24% in patients with neuromuscular disease. Twenty-three percent of pediatric PSF tissue cultures are positive before closure, with a higher rate in neuromuscular patients. Our primary aim was to evaluate the feasibility of a complete randomized controlled trial to study the efficacy of surgical site irrigation with povidone-iodine (PVP-I) compared with sterile saline (SS) to reduce the bacterial contamination rate before closure in children undergoing PSF. METHODS: One hundred seventy-five subjects undergoing PSF were enrolled in a multicenter, single-blind, pilot randomized controlled trial. We recruited patients at low-risk (LR) and high-risk (HR) for infection 3:1, respectively. Before closure, a wound culture was collected. Nonviable tissues were debrided and the wound was soaked with 0.35% PVP-I or SS for 3 minutes. The wound was then irrigated with 2 L of saline and a second sample was collected. RESULTS: One hundred fifty-three subjects completed the protocol. Seventy-seven subjects were allocated to PVP-I (18 HR, 59 LR) and 76 to SS (19 HR, 57 LR). Cultures were positive in 18% (14/77) of PVP-I samples (2 HR, 12 LR) and in 17% (13/76) of SS samples (3 HR, 10 LR) preirrigation and in 16% (12/77) of PVP-I samples (5 HR, 7 LR) and in 18% (14/76) of SS samples (4 HR, 10 LR) postirrigation. Eight percent (3/37) HR subjects (1 PVP-I, 2 SS) experienced infection at 30 days postoperative. No LR subjects experienced infection. CONCLUSIONS: Positive cultures were similar across treatment and risk groups. The bacterial contamination of wounds before closure remains high regardless of irrigation type. A complete randomized controlled trial would be challenging to adequately power given the similarity of tissue positivity across groups. LEVEL OF EVIDENCE: Level II-pilot randomized controlled trial.

Treatment of femoral fractures in children aged two to six.

AIMS: Current American Academy of Orthopaedic Surgeons (AAOS) guidelines for treating femoral fractures in children aged two to six years recommend early spica casting although some individuals have recommended intramedullary stabilization in this age group. The purpose of this study was to compare the treatment and family burden of care of spica casting and flexible intramedullary nailing in this age group. METHODS: Patients aged two to six years old with acute, non-pathological femur fractures were prospectively enrolled at one of three tertiary children's hospitals. Either early closed reduction with spica cast application or flexible intramedullary nailing was accomplished under general anaesthesia. The treatment method was selected after discussion of the options by the surgeon with the family. Data were prospectively collected on patient demographics, fracture characteristics, complications, pain medication, and union. The Impact on Family Scale was obtained at the six-week follow-up visit. In all, 75 patients were included in the study: 39 in the spica group and 36 in the nailing group. The mean age of the spica group was 2.71 (2.0 to 6.9) years and the mean age of the nailing group was 3.16 (2.0 to 6.9) years. RESULTS: All fractures healed without evidence of malunion or more than 2.0 cm of shortening. The mean Impact on Family score was 70.2 for the spica group and 63.2 (55 to 99) for the nailing group, a statistically significant difference (p = 0.024) in a univariate analysis suggesting less impairment of the family in the intramedullary nailing group. There was no significant difference between pain medication requirements in the first 24 hours postoperatively. Two patients in the spica group and one patient in the intramedullary nailing group required additional treatment under anaesthesia. CONCLUSION: Both early spica casting and intramedullary nailing were effective methods for treating femoral fractures in children two to six years of age. Intramedullary stabilization provides an option in this age group that may be advantageous in some social situations that depend on the child's mobility. Fracture treatment should be individualized based on factors that extend beyond anatomical and biological factors. Cite this article: Bone Joint J 2020;102-B(8):1056-1061.