Improving inpatient paediatric de-labelling of allergies to beta-lactams: a quality improvement study.

OBJECTIVE: To evaluate the implementation of an antimicrobial stewardship programme-led inpatient beta-lactam allergy de-labelling programme using a direct oral provocation test (OPT). DESIGN: One-year quality improvement study using a before-after design. SETTING: Free-standing tertiary care paediatric hospital. PATIENTS: Patients with a reported beta-lactam allergy admitted to the paediatric medicine inpatient unit. INTERVENTIONS: Following standardised assessment and risk stratification of reported symptoms, patients with a low-risk history were offered an OPT. Beta-lactam allergy labels were removed if a reported history was considered non-allergic or after successful OPT. MAIN OUTCOME MEASURES: Removal of inappropriate beta-lactam allergy labels. RESULTS: 80 patients with 85 reported beta-lactam allergies were assessed. Median age was 8.1 years (IQR 4.8-12.9) and 34 (42%) were female. The majority (n=55, 69%) had an underlying medical condition. Amoxicillin was the most reported allergy (n=25, 29%). Reported reactions were primarily dermatological (n=65, 77%). Half of participants (n=40) were ineligible for OPT, with equal proportions due to clinical reasons or the nature of the reported reaction. Of the 40 eligible patients, 28 patients (70%) were de-labelled either by history alone (n=10) or OPT (n=18). All OPTs were successful. De-labelling allowed five additional patients (11% of those receiving antibiotics) to receive the preferred beta-lactam. Including patients who were subsequently assessed in the allergy clinic, almost half of all evaluated patients were de-labelled (n=37, 46%). CONCLUSIONS: An antimicrobial stewardship programme-led programme using a direct OPT was feasible and safe for expanding beta-lactam allergy de-labelling to paediatric patients admitted to the paediatric medicine inpatient unit.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

The Effect of Transversus Abdominis Plane Block Timing on Milliequivalents of Opioid Use and Immediate Postoperative Pain Scores in Patients Undergoing Minimally Invasive Hysterectomy: A Retrospective Cohort Study.

STUDY OBJECTIVE: To examine the effect of transversus abdominis plane (TAP) block timing (preoperative or postoperative) on postoperative opioid use (quantified via morphine milligram equivalents; MME) and pain scores in patients undergoing minimally invasive hysterectomy for benign indications. DESIGN: Retrospective, single-institution cohort study SETTING: Academic-affiliated community hospital PATIENTS: A total of 2982 patients were included who underwent a minimally invasive total hysterectomy between January 2018 and December 2022, excluding patients with a malignancy diagnosis, concurrent urogynecological procedure, vaginal hysterectomy, supracervical hysterectomy, or those with baseline narcotic use (opioid use within the 3 months before surgery). Patients were separated into 3 groups: no TAP blocks (n = 1966, 65.9%), preoperative TAP blocks (854, 28.6%), and postoperative TAP blocks (162, 5.4%). INTERVENTIONS: Summary statistics and mixed-effects regression methods were used for data analysis. MEASUREMENTS AND MAIN RESULTS: There was a statistically significant lower mean use of opioids (MME 43.2 vs 53.9, p = .002) among patients who received a TAP block (either pre or postoperatively) than those who did not receive a block. However, when comparing preoperative vs postoperative patients with TAP block, there was no statistically significant difference in mean opioid use (MME 43.4 vs 42.1, p = .752). There were no differences in postoperative pain scores between patients with and without a TAP block, however, more opioids were required in patients who did not receive a TAP block to achieve the same pain scores as those who did receive a TAP block. There was a statistically significant shorter time to discharge for TAP versus patients without TAP block(median 5.5 vs 6.3 hours, p ≤ .001) as well as preoperative versus postoperative patients with TAP block (median 5.3 vs 6.2 hours, p = .001). CONCLUSION: While TAP block use at the time of minimally invasive hysterectomy reduced use of postoperative opioids, the timing of TAP block, either preoperatively or postoperatively, did not significantly affect opioid use. Preoperative compared with postoperative TAP block administration significantly shortened the time to discharge.

Exploring the Important Determinants Shaping Treatment Preferences: Qualitative Insights into Breast Cancer Patient Experiences and Perspectives in New Zealand.

Purpose: Despite the importance of acknowledging patient preferences in treatment decision-making, little is known about the treatment preferences and the factors underlying those preferences of breast cancer patients. This study aims explore patient experience and perspective regarding treatment preferences and identify the important determinants that shape these preferences in the context of New Zealand. Patients and Methods: Semi-structured online interviews comprised of six focus group discussions and five individual interviews were performed with 26 breast cancer patients. The interviews were recorded, transcribed, and analyzed using the reflexive thematic analysis approach. Results: Four main themes were derived: (1) positive treatment outcomes; (2) the negative impact of treatment-related side effects on quality of life; (3) treatment accessibility, availability, and timeliness; (4) cost of treatment. Patients revealed a strong preference towards treatments that yield longer survival, achieve remission, and prevent cancer recurrence. Additionally, patients favored treatments with minimal side effects that had minimal impact on their quality of life. There was a notable preference for treatments that were easily accessible and available in a timely manner. However, patients faced challenging decisions in balancing the costs of treatments with their benefits, leading to a consistent preference for treatments supported by government funding or medical insurance to alleviate financial burdens. Conclusion: Our study reveals that breast cancer patients in New Zealand have different perceptions and preferences regarding cancer treatment. Patients frequently find themselves making trade-offs among various attributes of a treatment, aligning these decisions with their personal values and beliefs. By considering these preferences and trade-offs in future studies that measure patient preferences, healthcare professionals can enhance their support for patients in making informed choices that align with their values and priorities. Additionally, healthcare policymakers can develop patient-centered policies that cater to the unique needs and preferences of breast cancer patients.

Therapeutic plasma exchange in alloimmune platelet refractoriness.

Patients with alloimmune platelet refractoriness can present complex clinical conundrums. Herein we describe a case of platelet refractoriness in the setting of combined HLA and HPA alloimmunization in a patient with acute myeloid leukemia and life-threatening bleeding. We discuss causative antibodies and compare prevailing therapeutic modalities. We highlight plasma exchange as a potentially feasible, repeatable, and personalized treatment option for patients with extensive platelet alloimmunization who require transfusion.

Children hospitalized with community-acquired pneumonia complicated by effusion: a single-centre retrospective cohort study.

OBJECTIVES: To describe children hospitalized with community-acquired pneumonia complicated by effusion (cCAP). DESIGN: Retrospective cohort study. SETTING: A Canadian children's hospital. PARTICIPANTS: Children without significant medical comorbidities aged < 18 years admitted from January 2015-December 2019 to either the Paediatric Medicine or Paediatric General Surgery services with any pneumonia discharge code who were documented to have an effusion/empyaema using ultrasound. OUTCOME MEASURES: Length of stay; admission to the paediatric intensive care unit; microbiologic diagnosis; antibiotic use. RESULTS: There were 109 children without significant medical comorbidities hospitalized for confirmed cCAP during the study period. Their median length of stay was 9 days (Q1-Q3 6-11 days) and 35/109 (32%) were admitted to the paediatric intensive care unit. Most (89/109, 74%) underwent procedural drainage. Length of stay was not associated with effusion size but was associated with time to drainage (0.60 days longer stay per day delay in drainage, 95%CI 0.19-1.0 days). Microbiologic diagnosis was more often made via molecular testing of pleural fluids (43/59, 73%) than via blood culture (12/109, 11%); the main aetiologic pathogens were S. pneumoniae (40/109, 37%), S. pyogenes (15/109, 14%), and S. aureus (7/109, 6%). Discharge on a narrow spectrum antibiotic (i.e. amoxicillin) was much more common when the cCAP pathogen was identified as compared to when it was not (68% vs. 24%, p < 0.001). CONCLUSIONS: Children with cCAP were commonly hospitalized for prolonged periods. Prompt procedural drainage was associated with shorter hospital stays. Pleural fluid testing often facilitated microbiologic diagnosis, which itself was associated with more appropriate antibiotic therapy.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

A Pediatric Investigators Collaborative Network on Infections in Children (PICNIC) multi-centre Canadian descriptive analysis of Haemophilus influenzae bacteremia in children: Emerging serotypes.

Background: There has been dramatic reduction in Haemophilus influenzae serotype b (Hib) since introduction of Hib vaccines, but children still experience serious invasive Haemophilus influenzae (Hi) disease caused by various serotype and non-typeable bacteria. The object of this study was to describe the serotype distribution and clinical spectrum of Hi bacteremia in children admitted to Canadian hospitals. Methods: All children with Hi bacteremia admitted 2013 through 2017 to 10 centres across Canada were included. Demographic, clinical, treatment and outcome data were collected. Results: Haemophilus influenzae bacteremia occurred in 118 children of median age 12 months (inter-quartile range: 7-48 months). Forty-three (36%) isolates were non-typeable (NTHi) and 8 were not typed. Of the 67 typeable (THi), Hia (H. influenzae serotype a) (n=36, 54%), Hif (serotype f) (n=19, 26%) and Hib (serotype b) (n=9, 13%) dominated. The THi was more likely than NTHi bacteremia to present as meningitis (p<0.001), particularly serotype a (p=0.04) and less likely to present as pneumonia (p<0.001). Complicated disease (defined as intensive care unit admission, need for surgery, long-term sequelae or death) occurred in 31 (26%) cases and were more likely to have meningitis (p<0.001) than were those with uncomplicated disease. Conclusion: In the era of efficacious conjugate Hib vaccines, NTHi, Hia and Hif have emerged as the leading causes of invasive Hi in Canadian children, with Hia being most likely to result in meningitis and complicated disease. A vaccine for all NTHi and THi would be ideal, but knowledge of the current disease burden from circulating strains will inform prioritization of vaccine targets.

Novel care pathway to optimise antimicrobial prescribing for uncomplicated community-acquired pneumonia: study protocol for a prospective before-after cohort study in the emergency department of a tertiary care Canadian children's hospital.

INTRODUCTION: Evidence-based recommendations for paediatric community-acquired pneumonia (CAP) diagnosis and management are needed. Uncomplicated CAP is often caused by respiratory viruses, especially in younger children; these episodes self-resolve without antibiotic treatment. Unfortunately, there are no clinical criteria that reliably discriminate between viral and bacterial disease, and so the majority of children diagnosed with CAP are given antibiotics-even though these will often not help and may cause harm. We have developed a novel care pathway that incorporates point-of-care biomarkers, radiographic patterns, microbiological testing and targeted follow-up. The primary study objective is to determine if the care pathway will be associated with less antimicrobial prescribing. METHODS AND ANALYSIS: A prospective, before-after, study. Previously well children aged≥6 months presenting to a paediatric emergency department (ED) that have at least one respiratory symptom/sign, receive chest radiography, and are diagnosed with CAP by the ED physician will be eligible. Those with medical comorbidities, recently diagnosed pulmonary infection, or ongoing fever after≥4 days of antimicrobial therapy will be excluded. In the control (before) phase, eligible participants will be managed as per the standard of care. In the intervention (after) phase, eligible participants will be managed as per the novel care pathway. The primary outcome will be the proportion of participants in each phase who receive antimicrobial treatment for CAP. The secondary outcomes include: clinical cure; re-presentation to the ED; hospitalisation; time to resolution of symptoms; drug adverse events; caregiver satisfaction; child absenteeism from daycare/school; and caregiver absenteeism from work. ETHICS AND DISSEMINATION: All study documentation has been approved by the Hamilton Integrated Research Ethics Board and informed consent will be obtained from all participants. Data from this study will be presented at major conferences and published in peer-reviewed publications to facilitate collaborations with networks of clinicians experienced in the dissemination of clinical guidelines. TRIAL REGISTRATION NUMBER: NCT05114161.

Ergonomic Assessment of Surgeon Characteristics and Laparoscopic Device Strain in Gynecologic Surgery.

STUDY OBJECTIVE: To evaluate whether surgeon characteristics, including sex and hand size, were associated with grip strength decline with laparoscopic advanced energy devices. DESIGN: Prospective cohort study. SETTING: Ergonomic simulation at an academic tertiary care site and the Society of Gynecologic Surgeons 47th Annual Meeting. PATIENTS: Thirty-eight participants (19 women and 19 men) were recruited. INTERVENTIONS: Surgeon anthropometric measurements were collected. Each participant completed a 120-second trial of maximum voluntary effort with 3 laparoscopic advanced energy devices (LigaSure, HALO PKS, and ENSEAL). Grip strength was measured using a handheld dynamometer. Subjects completed the NASA Raw Task Load Index scale after each device trial. Grip strengths and ergonomic workload scores were compared using Student t tests and Wilcoxon rank sum tests where appropriate. Univariate and multivariate models analyzed hand size and ergonomic workload. MEASUREMENTS AND MAIN RESULTS: Women had lower baseline grip strength (288 vs 451 N) than men, as did participants with glove size <7 compared with ≥7 (231 vs 397 N). Normalized grip strength was not associated with surgeon sex (p = .08), whereas it was significantly associated with surgeon glove size (p <.01). Grip strength decline was significantly greater for smaller compared to larger handed surgeons for LigaSure (p = .02) and HALO PKS devices (p <.01). The ergonomic workload of device use was significantly greater for smaller compared to larger handed surgeons (p <.01). Surgeon handspan significantly predicted grip strength decline with device use, even after accounting for potential confounders (R2 = .23, ß = .8, p <.01). CONCLUSION: Surgeons with smaller hand size experienced a greater grip strength decline and greater ergonomic workload during repetitive laparoscopic device use. No relationship was found between surgeon sex and grip strength decline or ergonomic workload. Laparoscopic device type was also identified as a significant main effect contributing to grip strength decline. These findings point toward ergonomic strain stemming from an improper fit between the laparoscopic device and the surgeon's hand during device use.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Immunotherapy in synchronous MSI-H rectal adenocarcinoma and upper tract urothelial carcinoma: a case report.

Background: A growing body of evidence suggests that conventional chemotherapy may not be effective in mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC). Alternative strategies, such as immunotherapy, are currently being investigated both in the neoadjuvant and adjuvant setting. Furthermore, immunotherapy is an attractive alternative to the use of combination chemotherapy regimens when treating synchronous primary cancers such as in the setting of inherited cancer syndromes. Case Description: Here we present a case of a middle-aged woman diagnosed with dMMR/MSI-H locally advanced rectal cancer with synchronous upper tract urothelial cancer secondary to Lynch syndrome. The patient was first treated using neoadjuvant chemotherapy followed by chemoradiation, resulting in only a partial pathologic response. Following surgery, the patient was treated with adjuvant combination immunotherapy with nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, resulting in a durable disease-free interval of nearly 21 months. Conclusions: This case report illustrates the importance of determining dMMR/MSI-H status in LARC and the consideration of immunotherapy (particularly with synchronous primaries as seen in inherited cancer syndromes), reviews the current literature, and calls for further investigation into the use of neoadjuvant and adjuvant immunotherapy in locally advanced rectal cancer along with upper tract urothelial carcinoma (UTUC).

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE).

OBJECTIVES: Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist. DESIGN: Repeated cross sectional study. SETTING: Swiss, German and Canadian research ethics committees (RECs). PARTICIPANTS: RCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reported RESULTS: The median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%-79%) in 2012 to 77% (IQR, 68%-82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%-72%) in 2012 to 76% (IQR, 64%-83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%-80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship. CONCLUSIONS: In 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of industry-sponsored protocols, which did not improve.

Investigation of the Association between Surgeon Sex and Laparoscopic Device Ergonomic Strain in Gynecologic Surgery.

STUDY OBJECTIVE: To assess whether female compared with male sex is associated with greater ergonomic strain with the use of 4 advanced energy laparoscopic devices (LigaSure, HALO PKS, ENSEAL, and Harmonic scalpel). DESIGN: Online survey distributed by e-mail using the REDCap platform (Vanderbilt University). All responses were anonymous. SETTING: Nationwide survey in the United States. PARTICIPANTS: Gynecologic surgeons were surveyed through the Society of Gynecologic Surgeons listserv and 4 obstetrics and gynecology departmental listservs. INTERVENTIONS: The survey was distributed between May 1, 2020, and November 1, 2020. The primary outcome was the presence of physical complaints owing to laparoscopic devices. Descriptive statistics compared surgeon characteristics and ergonomic symptoms. Logistic regression was performed, adjusted for surgeon characteristics. MEASUREMENTS AND MAIN RESULTS: The response rate was 39%, comprising 149 women (78%) and 41 men (22%). Women compared with men had a significantly younger age (mean, 34 vs 44 years; p <.01), had smaller glove size (mean, 6.5 vs 7.5; p <.01), had shorter height (median, 66 vs 71 inches; p <.01), and were less frequently in practice for >10 years (19% vs 49%; p <.01). Women significantly more often reported physical complaints related to the use of laparoscopic devices (79% vs 41%; p <.01). Women reported that all devices had too large a fit for appropriate use (p <.01). Women were found to have 5.37 times the odds of physical complaints attributed to the use of laparoscopic instruments (crude oods ratio, 5.37; 95% confidence interval, 2.56-11.25); with adjustment for glove size, age, and laparoscopic case volume and duration, this was no longer significant (adjusted odds ratio, 2.02; 95% confidence interval, 0.59-6.93). CONCLUSION: Women significantly more often report physical complaints and inappropriate fit of the LigaSure, HALO PKS, ENSEAL, and Harmonic scalpel. Female sex is associated with 5-fold greater odds of physical complaints with laparoscopic device use. Further investigation of the surgeon factors underlying device-related strain is a critical next step to understanding and reducing surgeon ergonomic injury.

Sex-Related Outcomes Following Drug Balloon Angioplasty in Patients from the BIOLUX P-III Registry: A Subgroup Analysis.

PURPOSE: To evaluate the use of drug-coated balloons in a real-world patient population with peripheral arterial disease and analyse the impact of sex on mid-term outcomes following their utilisation. METHODS: The BIOLUX P-III is a prospective, international, multi-centre, registry of patients with infra-inguinal lesions treated using the Passeo-18 Lux, a drug-coated balloon. Our study is a 24-month subgroup analysis of these patients; primary endpoints were freedom from major adverse events and clinically driven target lesion re-vascularisation within 12 months post-intervention. RESULTS: Of the 877 patients in the registry, 561 (64.0%) were male and 316 (36.0%) were female. Chronic limb threatening ischaemia (Rutherford class ≥ 4) occurred in 35.7% of males and 40.6% of females. Rates of freedom from major adverse events and clinically driven target lesion re-vascularisation at 12 months were 87.3% (95% confidence interval [CI] 84.2-89.9) and 90.4% (95% CI 86.5-93.3), and 92.3% (95% CI 89.9-94.1) and 92.9% (95% CI 89.7-95.1) in males and females, respectively. All-cause mortality at 24 months was 12.0% (95% CI 9.4-15.3) in males and 11.9% (95% CI 8.6-16.5) in females. The major target limb amputation rate at 24 months was 9.1% (95% CI 6.9-11.9) in males and 4.0% (95% CI 2.3-7.0) in females. CONCLUSION: Treatment with the Passeo-18 Lux DCB demonstrated high efficacy and low complication rates. Despite the greater proportion of chronic limb threatening ischaemia observed in females, males were at a greater risk of ipsilateral major limb amputation and major adverse events following drug-coated balloon utilisation. CLINICAL TRIAL REGISTRATION: NCT02276313. LEVEL OF EVIDENCE: Level 4.

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.