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The benefits of a comprehensive enhanced recovery after surgery (ERAS) program for patients with congenital heart disease are largely unknown. This study evaluated adherence and to outcomes of a recently implemented enhanced recovery program (ERP) in congenital cardiac surgery.Patients undergoing elective procedures for simple and moderately complex congenital cardiac surgery have followed institutional ERP guidelines since October 2018. Adherence to guidelines over a 12-month period (P2) was compared with implementation data (P1, 5 months). The association of outcomes with continuous time was estimated using linear regression.Among 559 patients (representing 40% of the cardiac surgical volume) following the ERP over a period of 17 months, no differences in patient characteristics were observed between periods, except a higher incidence of previous operations in P2. Adherence to many aspects of guidelines improved from P1 to P2. The following improvements were notable: operating room extubation, 27% in P2 vs16% in P1 (P = .006); and a decrease in median ventilation time, 6.0 hours (interquartile range [IQR], 0-9.2 hours) in P2 vs 7.6 hours (IQR, 3.8-12.3 hours) in P1 (P = .002). In addition, there was a reduction in opioids, reported as oral morphine equivalents, that was most significant for intraoperative oral morphine equivalents: 5.00 mg/kg (IQR, 3.11-7.60 mg/kg) in P2 vs 6.05 mg/kg (IQR, 3.77-9.78 mg/kg) in P1 (P = .001). There was no difference in overall intensive care unit and postoperative lengths of stay, except in lower-risk surgical procedures. Surgical outcomes were similar in the 2 periods.An enhanced recovery program reduced the use of opioids, led to more extubation in the operating room, and reduced mechanical ventilation duration in patients undergoing congenital cardiac surgery.

Military deployment is a risk factor for alcohol problems, and postdeployment alcohol problems are more prevalent among part-time reservists than full-time active duty service members. However, emerging research suggests that reservists who never experience deployment are also at risk. We examined if never-deployed/activated reserve veterans differed from active duty/deployed veterans in alcohol screening and misuse. Using pooled cross-sectional data from the National Survey on Drug Use and Health (NSDUH; 2015-2019), we estimated the prevalence of past-year self-reported alcohol screening by a health care provider and measured DSM-IV alcohol abuse and alcohol dependence among U.S. veterans aged 18-49 years with at least one health care visit in the past year (N = 4,148). We used regression models to examine for differences in these outcomes between never-deployed/activated reserve veterans and active duty/deployed veterans. Overall, 15% of veterans reported not being screened for alcohol use, despite 1 in 11 meeting DSM-IV criteria for alcohol abuse/dependence. Active duty/deployed veterans were more likely to have been screened for alcohol use than never-deployed/activated reserve veterans (p .05) or dependence (p > .05) between never-deployed/activated reserve veterans and veterans with a history of active duty service/activation. Never-deployed/activated reserve veterans are less likely to be screened for alcohol use than active duty/deployed veterans, despite no significant difference in meeting alcohol abuse/dependence criteria. Providers may not recognize never-deployed reservists as veterans. We recommend systematic screening for military service history and alcohol use for all veterans, regardless of deployment/active duty service. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dengue is a mosquito-borne virus that causes an influenza-like illness ranging in severity from asymptomatic to fatal. Dengue in pregnancy has been associated with adverse outcomes including miscarriage, preterm birth and fetal and neonatal death. We present the case of a multiparous woman who presented at 9 weeks’ gestation with vaginal bleeding and abdominal cramping after a 1 month stay in Mexico. She was initially diagnosed with miscarriage with plan for outpatient follow-up. She was readmitted 3 days later with fever, retro-orbital pain, arthralgia, rash, pancytopenia and transaminitis and managed with intravenous fluids and acetaminophen. Of note, dengue serology was initially negative but retesting 2 days later was positive. It is imperative that clinicians have heightened suspicion for dengue in pregnant women with history of travel to or residence in a dengue-endemic area and consistent clinical evidence.

Objectives The goals of this study were to: 1) evaluate the cardiac magnetic resonance (CMR) characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information. Background After diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric CMR-based diagnostic criteria. Methods CMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis. Results Of 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis. Conclusions CMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.

Background Value-based contracts that tie payments for pharmaceuticals to predefined outcomes aim to promote value through shared risk and aligned incentives between manufacturers and payers. Methods We conducted a Delphi study among diverse stakeholders (patients, providers, payers, pharmacy benefits managers, pharmaceutical company representatives) to identify top meaningful outcomes for inclusion in value-based contracts for atrial fibrillation medications. The final panel (n = 55) rated the importance of each outcome on a 5-point Likert scale and selected their top 3 most meaningful outcomes. Non-patient participants rated the feasibility of collecting each outcome on a 5-point Likert scale. Consensus was defined as ≥75% agreement (Likert scores ≥4/5 or selection of an outcome as most meaningful). Differences between stakeholder groups were examined using Fisher's Exact Test. Results Consensus was achieved for importance of 10 outcomes (Likert scale), where “preventing stroke or mini-stroke” reached 100% agreement (55/55). Eighty-one percent (44/54) of participants selected “preventing stroke or mini-stroke” as the most meaningful outcome (rank order question). The measures rated as most feasibly collected were “reducing hospitalizations” (97%, 36/37) followed by “preventing stroke or mini-stroke” and “reducing emergency department visits” (both 92%, 34/37). There were statistically significant differences between patients and non-patients [0% (0/17) vs 22% (8/37), P = 0.047] and patients and providers [0% (0/17) vs 39% (7/18), P = 0.008] in selection of “improving health-related quality of life” as a most meaningful outcome. Conclusions These findings will inform the design of atrial fibrillation value-based pharmaceutical contracts and provide additional insight into preferences for outcomes which could be used to improve the quality of atrial fibrillation care.

The data on management and outcomes of pelvic sepsis after re-do IPAA are scarce.The aim of this study is to report our management algorithm of pelvic sepsis in the setting of re-do IPAA and compare functional outcomes and quality of life after successful management of pelvic sepsis with a no sepsis control group.This is a retrospective cohort study.This investigation is based on a single academic practice group experience on re-do IPAA.Patients who underwent re-do IPAA for ileal pouch failure between September 2016 and September 2020 were included in the study.Management of pelvic sepsis was reported. Functional outcomes, restrictions, and quality-of-life scores were compared between the sepsis and no sepsis groups.One-hundred ten patients were included in our study, of whom 25 (22.7%) developed pelvic sepsis. Twenty-three patients presented with pelvic sepsis before ileostomy closure, and 2 patients presented with pelvic sepsis after ileostomy closure. There were 6 pouch failures in the study period due to pelvic sepsis. Our management was successful in 79% of the patients with median follow-up of 26 months. Treatments included interventional radiology abscess drainage (n = 7), IV antibiotics alone (n = 5), interventional radiology drainage and mushroom catheter placement (n = 1), mushroom catheter placement (n = 1), and endoluminal vacuum-assisted closure (n = 1). Average number of bowel movements, urgency, incontinence, pad use, and seepage were comparable between the pelvic sepsis and no pelvic sepsis groups ( p0.05). Lifestyle alterations, Cleveland Global Quality of Life scores, and happiness with the results of the surgery were similar ( p0.05).This study is limited by its low study power and limited follow-up time.Pelvic sepsis is common after re-do IPAA, and management varies according to the location and size of the abscess/sinus. If detected early, our management strategy was associated with high pouch salvage rates. See Video Abstract at http://links.lww.com/DCR/B823 .ANTECEDENTES:Los datos sobre el tratamiento y los resultados de la sepsis pélvica después de reconfección de anastomosis anal, de la bolsa ileal son escasos.OBJETIVO:El objetivo de este estudio es informar nuestro algoritmo de manejo de la sepsis pélvica en el contexto de reconfección de anastomosis anal de la bolsa ileal y comparar los resultados funcionales y la calidad de vida después del manejo exitoso de la sepsis pélvica con un grupo de control sin sepsis.DISEÑO:Este es un estudio de cohorte retrospectivo.AJUSTES:Esta investigación se basa en una experiencia de un solo grupo de práctica académica sobre reconfección de IPAA.PACIENTES:Se incluyeron en el estudio pacientes que se sometieron a una nueva anastomosis anal, del reservorio ileal por falla del reservorio ileal entre el 09/2016 y el 09/2020.PRINCIPALES MEDIDAS DE RESULTADO:Se informó el manejo de la sepsis pélvica. Los resultados funcionales, las restricciones y las puntuaciones de calidad de vida, se compararon entre los grupos con sepsis y sin sepsis.RESULTADOS:Se incluyeron 110 pacientes en nuestro estudio, de los cuales 25 (22,7) desarrollaron sepsis pélvica. Veintitrés pacientes presentaron sepsis pélvica antes del cierre de la ileostomía y 2 pacientes presentaron sepsis pélvica después del cierre de la ileostomía. Hubo 6 fallas de la bolsa en el período de estudio debido a sepsis pélvica. Nuestro manejo fue exitoso en el 79% de los pacientes con una mediana de seguimiento de 26 meses. Los tratamientos incluyeron drenaje de abscesos IR (n = 7), antibióticos intravenosos solos (n = 5), drenaje IR y colocación de catéter en forma de hongo (n = 1), colocación de catéter en forma de hongo (n = 1) y cierre endoluminal asistido por vacío (n = 1). El número promedio de evacuaciones intestinales, urgencia, incontinencia, uso de almohadillas y filtraciones fueron comparables entre los grupos con sepsis pélvica y sin sepsis pélvica ( p0,05). Las alteraciones del estilo de vida, las puntuaciones de la Calidad de vida global de Cleveland y la felicidad con los resultados de la cirugía fueron similares ( p0,05).LIMITACIONES:Este estudio está limitado por su bajo poder de estudio y su tiempo de seguimiento limitado.CONCLUSIONES:La sepsis pélvica es común después de la reconfección de anastomosis anal de la bolsa ileal y el manejo varía según la ubicación y el tamaño del absceso / seno. Si se detecta temprano, nuestra estrategia de manejo se asoció con altas tasas de recuperación de la bolsa. Consulte Video Resumen en http://links.lww.com/DCR/B823 . (Traducción-Dr. Mauricio Santamaria ).

BackgroundO’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Aim: Depression experienced by people with colorectal cancer (CRC) is an important clinical problem affecting quality of life. Recognition of depression at key points in the pathway enables timely referral to support. This study aimed to examine depression before and 5 years after surgery to examine its prevalence and identify determinants. \ud \ud Method: The ColoREctal Wellbeing (CREW) study is a prospective UK cohort study involving 872 adults with nonmetastatic CRC recruited before surgery with curative intent. Questionnaires completed before surgery and 3, 9, 15, 24, 36, 48 and 60 months after surgery captured socio‐demographics and assessed depression (Centre for Epidemiologic Studies Depression Scale, CES‐D) and other psychosocial factors. Clinical details were also gathered. We present the prevalence of clinically significant depression (CES‐D ≥ 20) over time and its predictors assessed before and 2 years after surgery. \ud \ud Results: Before surgery, 21.0% of the cohort reported CES‐D ≥ 20 reducing to 14.7% 5 years after surgery. Presurgery risk factors predicting subsequent depression were clinically significant depression and anxiety, previous mental health service use, low self‐efficacy, poor health, having neoadjuvant treatment and low social support. Postsurgery risk factors at 2 years predicting subsequent depression were clinically significant depression, negative affect, cognitive dysfunction, accommodation type and poor health. \ud \ud Conclusion: Depression is highly pervasive in people with CRC, exceeding prevalence in the general population across follow‐up. Our findings emphasize the need to screen and treat depression across the pathway. Our novel data highlight key risk factors of later depression at important and opportune time points: before surgery and at the end of routine surveillance. Early recognition and timely referral to appropriate support is vital to improve long‐term psychological outcomes.

Pleomorphic adenoma, otherwise called as benign mixed tumour, is the most common salivary gland tumour which accounts for 60% of all benign salivary gland tumours. The clinical, radiological and histopathological presentations are varied. The tumour occurs in diverse anatomical sites and can consist of epithelial and mesenchymal components. In this case report, the patient reported with an asymptomatic swelling on the face. CT scan with contrast was advised. The clinical, roentgenographic findings and Fine Needle Aspiration Cytology were indicative of pleomorphic adenoma of the parotid gland. Treatment included partial superficial parotidectomy under general anaesthesia using the modified Blair’s incision. The facial nerve was not involved. Part of the gland along with the tumour was resected completely superficial to the facial nerve with a margin of normal tissue all around. Histopathologic examination of tissue specimen confirmed the lesion as pleomorphic adenoma. The patient was asymptomatic at 6-month follow-up.

Gestational and pregestational diabetes during pregnancy are substantial and growing public health issues. Low-income individuals and individuals who identify as racial and ethnic minorities are disproportionately affected. Food security, which is defined as the degree to which individuals have capacity to access and obtain food, is at the center of nutritional resources and decisions for individuals with diabetes. While increasingly recognized as an important mediator of health disparities in the United States, food insecurity is understudied during pregnancy and specifically among pregnant individuals with diabetes, for whom the impact of food-related resources may be even greater. Previous research has suggested that food insecurity is associated with type 2 diabetes mellitus diagnoses and disease exacerbation in the general adult population. An emerging body of research has suggested that food insecurity during pregnancy is associated with gestational diabetes mellitus diagnoses and adverse diabetes-related outcomes. Additionally, food insecurity during pregnancy may be associated with adverse maternal and neonatal outcomes. Future research and clinical work should aim to further examine these relationships and subsequently develop evidence-based interventions to improve diabetes-related outcomes among pregnant individuals with food insecurity. The purpose of this article is to offer a working definition of food security, briefly review issues of food insecurity and diabetes, summarize research on food insecurity and diabetes-related pregnancy health, and discuss clinical recommendations and areas for future investigation. KEY POINTS: · Research on food insecurity and diabetes-related health is limited.. · The impact of food security on diabetes management and obstetric outcomes is likely significant.. · Future work to evaluate perinatal food security screening is warranted..

Background Patient navigation programs have shown promise for improving health but are not widely used in obstetric care. Our objective was to understand obstetric provider perspectives on how to implement patient navigation to optimize care during the postpartum period for low-income patients. Method Focus groups were conducted with obstetric physicians, nurses, and social workers who care for low-income pregnant and postpartum patients in an academic medical center. Semistructured interview guides were developed to elicit conversations about the potential value of patient navigators, recommendations for navigator training, and how navigators could be most effective in improving postpartum care. Analysis of themes was based on the constant comparative method. Results Twenty-six obstetric providers (six focus groups) discussed elements for a successful obstetric navigation program. Successful implementation themes included selecting navigators with appropriate interpersonal attributes, arranging navigator training, and identifying the most valuable services navigators could render. Desirable navigator attributes included persistence in patient advocacy, consistency, relatability, and a supportive manner. Training recommendations included learning the health care system, identifying where to obtain health system and community resources, and learning how be effective health educators. Suggested services were broad, ranging from traditional care coordination to specific educational and resource-driven tasks. Conclusions Obstetric providers perceive patient navigation to be a potentially beneficial resource to support low-income patients and offered recommendations for navigation implementation. These included suggestions for patient-centered navigators, with specific training and services focused on promoting care continuity and coordination.

Study Design: Retrospective study.Purpose: To report the perioperative and radiological outcomes of single-stage posterior passive correction and fusion (SSPPCF) in adolescent patients who present with congenital scoliosis.Overview of Literature: The surgical treatment for congenital scoliosis is complex. There is no definitive guide on surgical options for skeletally matured adolescent patients who have congenital scoliosis.Methods: Patients with congenital scoliosis who underwent SSPPCF using a pedicle screw system were reviewed. We identified the following three surgical indications: (1) hemivertebra or wedge vertebra over the thoracic or thoracolumbar region with structural lumbar curves, (2) hemivertebra or wedge vertebra at the lumbar region with significant pelvic obliquity or sacral slanting, and (3) mixed or complex congenital scoliosis. The demographic, perioperative, and radiographic data of these patients were collected.Results: Thirty-four patients were reviewed. The mean patient age was 14.6±3.4 years. There were 13 hemivertebrae, three wedged vertebrae, two butterfly vertebrae, three hemivertebrae with butterfly vertebra, eight unsegmented bars, and five multiple complex lesions. The average surgical duration was 219.4±68.8 minutes. The average blood loss was 1,208.4±763.5 mL. Seven patients required allogeneic blood transfusion. The mean hospital stay duration was 6.1±2.5 days. The complication rate was 11.8% (4/34): one patient had severe blood loss, one had rod breakage, and two had distal adding-on. The Cobb angle reduced from 65.9°±17.4° to 36.3°±15.3° (p

Study Objective The purpose of this study was to examine feasibility, acceptability, and preliminary efficacy of a mindfulness-based healthy lifestyle self-management intervention with adolescents and young adults diagnosed with polycystic ovary syndrome (PCOS). Design A pilot randomized controlled trial using a pre-post design was used. Setting Central Texas. Participants: Individuals aged 14-23 with a diagnosis of PCOS. Interventions The PCOS Kind Mind Program integrates a manualized mindfulness training program (Taming the Adolescent Mind) with health education in four key areas of self-management and health promotion; (1) medication adherence, (2) nutrition, (3) physical activity, and (4) sleep. Main Outcome Measures Psychological distress, mindfulness, physical activity strategies, nutrition and exercise self-efficacy. Results Linear regression models revealed that those in the PCOS Kind Mind condition reported significantly higher nutrition self-efficacy (β = 6.50, 95% CI = 1.71 – 11.28, p = 0.013, d = 0.48), physical activity strategies (β = 0.41, 95% CI = 0.04 – 0.79, p = 0.040, d = 0.67), and physical activity self-efficacy (β = 0.48, 95% CI = 0.07 – 0.88, p = 0.028, d = 0.46). Conclusion The PCOS Kind Mind Program improved self-efficacy in the key areas of nutrition and physical activity and increased physical activity strategies in adolescents and young people with PCOS. These findings are encouraging and suggest the need for larger scale, randomized controlled trials with longer-term follow-up in order to more robustly evaluate the PCOS Kind Mind Program on the psychological and physiological health of adolescents and young people with PCOS.

CFTR modulators have dramatically changed the clinical course of CF in those fortunate enough to receive them. Inevitably, randomised controlled trials during the development of these drugs are too short to use mortality as an outcome. Evidence for their effect on life expectancy are best gained from real world registry studies specifically looking at mortality, but these are only available for ivacaftor to date. Therefore, indirect evidence must be obtained by looking at outcomes known to affect mortality and seeing the effect of these drugs on those outcomes.

Decision-making for treatment of rheumatoid arthritis (RA) is complex, with multiple beneficial medication options available, but with the potential for treatment-related adverse effects and significant economic considerations. Indigenous patients make treatment decisions informed by an interplay of clinical, family, and societal factors. Shared decision-making may represent an approach to support treatment decisions in a culturally congruent manner. Our objective was to identify aspects of arthritis care that Indigenous participants found relevant for shared decision-making and to explore preferences for shared decision-making strategies.A purposive sampling from rheumatology clinics that provide services to Indigenous patients in a Canadian urban center was used to recruit participants for interviews. Seven participants were recruited to reach content saturation. Interview content was coded by 2 individuals, including an Indigenous patient with RA, and the data were analyzed via thematic analysis.Participants were all women ages 37-61 years living with RA. Participants supported the idea that shared decision-making would be beneficial, primarily to support decisions around treatment plans and medication changes. Shared decision-making approaches would need to reflect Indigenous-specific content areas, such as benefits and risks of therapy informed by data from Indigenous patient populations and inclusion of traditional modes of healing. All participants were interested in having a decision coach and preferred that decision aids be in both paper and electronic formats for accessibility.This study advances knowledge in the priority areas and specific content needed in the shared decision-making process and the preferences of shared decision-making strategies relevant and appropriate for urban Indigenous women living with RA in Canada.

Background: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. Results: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of 25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be Conclusions: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

Objectives Treatment of hepatitis C virus infection (HCV) with direct acting antiviral therapy is encouraged regardless of substance use status. Patients with substance use disorder are at risk of HCV reinfection after cure. Follow up viral load testing (FUVL) with HCV RNA is recommended. We investigated factors associated with adoption of FUVL in real-world clinical settings. Methods Medical records of all patients with SUD who achieved HCV cure with direct acting antivirals at a multidisciplinary addiction treatment program between 2014 and 2019 were reviewed as part of a quality improvement initiative. Demographic and clinical characteristics including SUD treatment, urine toxicology results, and medical service use were collected. Factors associated with FUVL were analyzed and the rate of HCV reinfection was determined. Results Among 149 patients, 58.4% received FUVL. Receipt of FUVL was associated with engagement in ongoing primary medical care after cure (AOR 4.39, 95% CI [1.67, 11.49]). The HCV reinfection rate among those who received FUVL was 1.95 per 100 person-years of follow up (95% CI [0.64, 5.98]). There was no significant difference in the percentage of negative urine toxicology results before and after cure. Conclusions Over half of a cohort of patients with substance use disorder cured of HCV received FUVL. The relationship between FUVL and engagement in primary medical and substance use treatment highlights the importance of integrated systems in providing longitudinal care for patients cured of HCV. Standardized interventions that facilitate FUVL testing and management of infectious complications of SUD in addiction treatment settings are needed.

Objective To develop an item response theory (IRT)–calibrated, patient-reported outcome measure (the PROMIS Cancer Function Brief 3D Profile) of physical function, including associations with fatigue and social participation, in cancer rehabilitation patients. Design Large-scale field testing, graded response model IRT analyses, and multivariate regression analysis. Setting Six cancer rehabilitation clinics associated with cancer centers across the United States. Participants Adults (N=616) treated in outpatient cancer rehabilitation medicine clinics. Intervention Not applicable. Main Outcome Measures: The PROMIS(r) Cancer Function 3D Profile (including existing items from PROMIS(r) item banks). Results A total of 616 patients completed 21 items in the initial item pool. Nine items were removed because of comparatively lower information that they provide according to the IRT item calibrations, low item-total correlations, or bimodal distributions. The remaining items generated a 12-item short form. Regression analyses determined that the items were responsive to and representative of the patient population across trait ranges and multiple domains and subdomains of function. Conclusions This psychometric investigation supports the use of the PROMIS Cancer Function Brief 3D Profile for evaluating function in outpatient cancer rehabilitation patients.

Background aims The internal tandem duplication of FLT3 (FLT3ITD) and NPM1 mutations (NPM1mut) are well-established prognostic factors in cytogenetically intermediate-risk acute myeloid leukemia (AML) when treated with chemotherapy alone. However, their prognostic value in the setting of allogeneic hematopoietic cell transplantation (HCT) is controversial. Methods FLT3 and NPM1 mutational status was determined at diagnosis using single-gene polymerase chain reaction or next-generation sequencing in 247 adult patients with cytogenetically intermediate-risk AML who underwent myeloablative HCT. Multivariate Fine–Gray and Cox regression was used to analyze the cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS). Results FLT3ITD and NPM1mut were present in 74 of 247 (30%) and 79 of 247 (32%) patients, respectively. There was no significant difference between patients without a FLT3ITD or NPM1mut (FLT3NONITD/NPM1WT) and patients with a FLT3ITD mutation alone (FLT3ITD/NPM1WT) with regard to CIR (P = 0.60), RFS (P = 0.91) or OS (P = 0.66). Similarly, there was no significant difference between FLT3NONITD/NPM1WT and FLT3NONITD/NPM1mut patients with regard to CIR (P = 0.70), RFS (P = 0.75) or OS (P = 0.95). The presence of a concurrent mutation in NPM1 did not appear to modify the impact of having a FLT3ITD mutation. Conclusions In contrast to chemotherapy-only treatment, FLT3 and NPM1 mutational status does not appear to predict outcomes in patients with cytogenetically intermediate-risk AML following HCT. These results suggest that HCT may ameliorate the poor prognostic effect of FLT3ITD mutation and that HCT should be considered over chemotherapy-only treatment in FLT3ITD-mutated AML.

Objective To evaluate the reliability, standard error of measurement, minimum detectable change, and item-level consistency of the Transfer Assessment Instrument (TAI) version 4.0 when used to evaluate transfer quality remotely. Design Participants transferred from their wheelchair to a mat table (transfer 1), repeated this after a 10-minute delay to assess intrarater reliability (transfer 2), and repeated this 1-2 days later to assess test-retest reliability (transfer 3). Each transfer was scored in person by 4 raters and asynchronously by a remote clinician rater. Setting 2017 National Veterans Wheelchair Games. Participants Convenience sample of 44 full-time wheelchair users (N=44). Interventions Not applicable. Main Outcome Measures TAI total score, subscores (wheelchair setup, body setup, flight/landing), and item scores (15 items). Results Moderate to excellent reliability was found when scoring remotely for TAI total and subscores for intrarater (intraclass correlation coefficient (ICC(3,1)=0.687-0.854), test-retest (ICC(3,1)=0.695-0.836), and interrater reliability (ICC(3,5)=0.746-0.962). Remote rater total score and flight/landing subscore were greater (indicating higher transfer quality) compared to the average in-person raters (P=.021 and P=.005, respectively). There were no differences between transfers 1-3 in remote rater scores. Item-level percentage agreement between the remote rater and in-person exceeded the 75% cutoff for clinical utility for all items. Conclusions The TAI is a reliable outcome measure for assessing transfer technique remotely.

Adolescents and young adults (AYA) with sickle cell disease (SCD) experience high rates of acute care utilization and increased morbidity. At this high-risk time, they also face the need to transition from pediatric to adult services, which, if poorly coordinated, adds to heightened morbidity and acute care utilization. The study objective was to characterize the feasibility, acceptability, and short-term efficacy of a protocolized transition navigator (TN) intervention in AYA with SCD.We developed a protocolized TN intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, and to provide disease and pain management education and skills to AYAs with SCD.Ninety-three percent (56/60) of enrolled individuals completed the intervention. Participation in the TN program was associated with significant improvement in mean transition readiness scores (3.58-4.15, P.0001), disease knowledge scale (8.91-10.13, P.0001), Adolescent Medication Barriers Scale (40.05-35.39, P = .003) and confidence in both disease (22.5-23.96, P = .048) and pain management (25.07-26.61, P = .003) for youth with SCD.The TN intervention was acceptable to youth with SCD, feasible to implement at an urban academic medical center, and addressed barriers to transition identified by the youth. Longer-term assessment is needed to determine if the TN intervention improved successful transfer to and retention in adult care.

PURPOSE: Serious Illness Conversations (SICs) are structured conversations between clinicians and patients about prognosis, treatment goals, and end-of-life preferences. Although behavioral interventions may prompt earlier or more frequent SICs, their impact on the quality of SICs is unclear. METHODS: This was a secondary analysis of a randomized clinical trial ( NCT03984773 ) among 78 clinicians and 14,607 patients with cancer testing the impact of an automated mortality prediction with behavioral nudges to clinicians to prompt more SICs. We analyzed 318 randomly selected SICs matched 1:1 by clinicians (159 control and 159 intervention) to compare the quality of intervention vs. control conversations using a validated codebook. Comprehensiveness of SIC documentation was used as a measure of quality, with higher integer numbers of documented conversation domains corresponding to higher quality conversations. A conversation was classified as high-quality if its score was ≥ 8 of a maximum of 10. Using a noninferiority design, mixed effects regression models with clinician-level random effects were used to assess SIC quality in intervention vs. control groups, concluding noninferiority if the adjusted odds ratio (aOR) was not significantly < 0.9. RESULTS: Baseline characteristics of the control and intervention groups were similar. Intervention SICs were noninferior to control conversations (aOR 0.99; 95% CI, 0.91 to 1.09). The intervention increased the likelihood of addressing patient-clinician relationship (aOR = 1.99; 95% CI, 1.23 to 3.27; P < .01) and decreased the likelihood of addressing family involvement (aOR = 0.56; 95% CI, 0.34 to 0.90; P < .05). CONCLUSION: A behavioral intervention that increased SIC frequency did not decrease their quality. Behavioral prompts may increase SIC frequency without sacrificing quality.

PURPOSE: A deep learning artificial intelligence (AI) algorithm has been demonstrated to outperform embryologists in identifying euploid embryos destined to implant with an accuracy of 75.3% (1). Our aim was to evaluate the performance of highly trained embryologists in selecting top quality day 5 euploid blastocysts with and without the aid of a deep learning algorithm. MATERIALS AND METHODS: A non-overlapping series of 200 sets of day 5 euploid embryo images with known implantation outcomes was distributed to 17 highly trained embryologists. One embryo in each set was known to have implanted and one failed implantation. They were asked to select which embryo to transfer from each set. The same 200 sets of embryos, with indication of which embryo in each set had been identified by the algorithm as more likely to implant was then distributed. Chi-squared, t-test, and receiver operating curves were performed to compare the embryologist performeance with and without AI. RESULTS: Fourteen embryologists completed both assessments. Embryologists provided with AI results selected successfully implanted embryos in 73.6% of cases compared to 65.5% for those selected using visual assessments alone (p

The legal profession depends on expert witnesses, and indeed the first time an English Court relied on an expert medical witness was in the 14th century. Asking a specialist to comment on the standard of professional practice expected in their own specialty was first introduced in a 1767 case [1]. This article draws on 20 years of experience in medicolegal work relating to paediatric respiratory medicine. It highlights some of the legal principles that lie behind an expert opinion and what constitutes clinical negligence. It aims to set out lessons for medicolegal experts and clinicians, but also offers some advice to lawyers and parents. Finally, it illustrates some issues that arise more commonly in paediatric respiratory practice.

Contains fulltext : 248781.pdf (Publisher’s version ) (Open Access) BACKGROUND: For patients with chronic myeloid leukemia, a web-based platform CMyLife was developed. Its aim is to enhance patient empowerment, by adequate information provision, among others. Before evaluating its effect, information provision and needs in current care were assessed. OBJECTIVE: To assess patients' evaluation of received information and information needs before CMyLife utilization and whether this information source is used correspondingly. Additionally, we explored predicting patient factors in information perception. PATIENT INVOLVEMENT: CMyLife platform was developed with active patient participation. METHODS: We conducted a cross-sectional survey among 203 CML patients before launch of the CMyLife platform, using validated questionnaires on information provision and predictive factors. We focused on website utilization during the first 3 years, using Google Analytics. Regression analyses were performed to determine influence of patient factors on information perception. RESULTS: Global perceived information provision was scored 42.8 (0-100). Information on other services such as rehabilitation and psychological support, and effects of treatment on sexuality showed room for improvement. One out of 3 knew where to find useful health information online. But more information was desired by 36% of them. Age ≥65 years, time since diagnosis and low education were positively associated with this need. Pages on medication and side effects were visited the most. DISCUSSION: To fill the gap in perceived provision and needs, information should be adjusted more to the individual in content, manner and timing. Age, time since diagnosis, and educational level are of influence in perceived information, and specific needs within these groups should be further explored. PRACTICAL VALUE: CMyLife provides reliable and up-to-date information for low eHealth literacy skilled patients concerning multiple topics indicated by patients.

Research Question To evaluate whether endometrial scratch improved the chance of a live birth in women with PCOS undergoing ovulation induction and trying to conceive. Design An international, multicentre, randomised, sham-controlled trial across six fertility clinics in three countries (New Zealand, United Kingdom and Brazil). Women with a diagnosis of PCOS who were planning to commence ovulation induction cycles (at least three cycles) in order to conceive were randomly assigned to receive the pipelle (scratch) procedure or a sham (placebo) procedure in the first cycle of ovulation induction. Women kept a diary of ovulation induction and sexual intercourse timing over three consecutive cycles and pregnancies were followed-up to live birth. Primary outcome was live birth and secondary outcomes were clinical pregnancy, ongoing pregnancy, multiple pregnancy, adverse pregnancy outcomes, neonatal outcomes, bleeding following procedure and pain score following procedure. Results 117 women were randomised; 58 to the scratch group and 59 to the sham group. Live birth occurred in 11 (19%) women in the scratch group and 14 (24%) in the sham group (OR 0.76, 95% confidence interval of 0.30 to 1.92). Secondary outcomes were similar in each group. Significantly higher pain scores were reported in the scratch group (adjusted mean difference 3.2, 95% confidence interval of 2.5 to 3.9) when measured on a visual-analogue scale. Conclusion We did not detect a difference in live birth rate for women with PCOS who received an endometrial scratch when trying to conceive using ovulation induction, however, uncertainty remains due to the small sample size in our study.

Background HIV and other medical complications of drug use, including overdose, are rising among people who inject drugs (PWID) in the United States (US). Risk of complications and mortality increase with injection behaviors such as syringe sharing, rushing injections, and injecting in isolated places. Studies suggest safe consumption sites (SCS) reduce high-risk injection behaviors by offering sterile syringes and a safe, supervised space to consume drugs, though this has yet to be evaluated in the US. Setting An unsanctioned SCS in an undisclosed US location. Methods From 2018 to 2019, we recruited PWID using targeted sampling methods (N=494) and conducted interviews at baseline, 6-, and 12-months. We sought to determine associations of past-month SCS use with past-month receptive syringe sharing, rushed injections, and injections in isolated places. We analyzed data using inverse probability of treatment weighted Poisson regression models. Generalized estimating equations accounted for repeated measures. Results Fifty-two (11%) participants had past-month SCS use. Participants with past-month SCS use had decreased rates of receptive syringe sharing (IRR 0.17, 95%CI 0.03-1.02) and injecting in an isolated location (IRR 0.77 95%CI 0.54-1.27) compared to those without past-month SCS use, though results were not statistically conclusive. Rate of rushed injections was only slightly lower (IRR 0.94, 95%CI 0.70-1.30). Conclusion SCS may show benefit in reducing high-risk injection practices, and legal sanctioning of an SCS may offer further advantages. SCS implementation should be considered to help reduce the spread of HIV, overdose mortality, and prevent other medical complications of injection drug use.

Postsurgical infections of the shoulder joint involving Cutibacterium acnes are difficult to diagnose and manage. Despite the devastating clinical complications and costly health care burden of joi...

PURPOSE Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD). METHODS This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS). RESULTS Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037). CONCLUSION CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

The aim of this study was to describe genital hair thread tourniquet syndrome (HTTS) and its treatment by pediatric and adolescent health care providers through a systematic literature review.We performed a systematic literature review on pediatric male and female genital HTTS. Studies were included if they involved genital HTTS in males or females 21 years and younger and were published in English. The main outcomes were body parts involved, symptoms, treatment, anesthetic type, providers involved in diagnosis and management, and implications of delayed or missed diagnosis.There were 38 female cases from 33 publications (1973-2020) and 147 male cases from 47 publications (1951-2019). The average age among females and males was 9.1 and 5.1 years, respectively. Among cases involving female patients, 93% of them were premenarchal; patients were circumcised in 90% of reviewed cases of male HTTS. The most commonly involved body parts were clitoris and labia minora in females, and penis and urethra in males. Males most commonly presented with edema and urinary symptoms, whereas females most commonly presented with edema and pain. General anesthesia was used for tourniquet excision in most cases. Male and female genital HTTS were mostly managed by urologists and emergency medicine physicians, respectively.This systematic literature review of more than 150 cases of male and female genital HTTS describes evaluation and management of genital HTTS spanning 7 decades. The main treatment of genital HTTS remains prompt diagnosis and removal of the tourniquet, as well as education on prevention strategies. Delayed diagnosis due to lack of recognition of the HTTS can lead to serious sequelae. Development of national guidelines regarding best practices in management of genital HTTS disseminated to all providers taking care of pediatric and adolescent patients will lead to improved patient care.

When peers rate each other, they may rate inaccurately to boost their own reputation or unfairly lower another’s. This could be mitigated by having a reputation server incentivise accurate ratings with a reward. However, assigning rewards becomes challenging when ratings are anonymous, since the reputation server cannot tell which peers to reward for rating accurately. To address this, we propose an anonymous peer rating system in which users can be rewarded for accurate ratings, and we formally define its model and security requirements. In our system ratings are rewarded in batches, so that users claiming their rewards only reveal they authored one in this batch of ratings. To ensure the anonymity set of rewarded users is not reduced, we also split the reputation server into two entities, the Rewarder, who knows which ratings are rewarded, and the Reputation Holder, who knows which users were rewarded. We give a provably secure construction satisfying all the security properties required. For our construction we use a modification of a Direct Anonymous Attestation scheme to ensure that peers can prove their own reputation when rating others, and that multiple feedback on the same subject can be detected. We then use Linkable Ring Signatures to enable peers to be rewarded for their accurate ratings, while still ensuring that ratings are anonymous. Our work results in a system which allows accurate ratings to be rewarded, whilst still providing anonymity of ratings with respect to the central entities managing the system.

Objective The objective of this study was to examine the association of quadriceps strength symmetry and surgical status (ACL reconstruction or nonoperative management) with early clinical knee OA 5 years after ACL injury or reconstruction. Methods 204/300 athletes were analyzed 5 years after ACL injury or reconstruction (ACLR). Quadriceps strength was measured and reported as a limb symmetry index. We identified participants with early clinical knee OA using criteria that two of four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales score ≤85% (Luyten et al. 2018). We calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression, adjusted for age, sex, meniscal injury, and BMI, to examine the associations between quadriceps strength and surgical status with clinical knee OA. Results 21% of participants met KOOS criteria for clinical knee OA (Luyten et al. 2018). For every 1% increase in quadriceps limb symmetry index, there was 4% lower odds of clinical OA (adjusted OR 0.96, 95% CI 0.93-0.99) at 5 years. Surgical status was not associated with clinical knee OA (adjusted OR 0.58, 95% CI 0.23, 1.50). Conclusions More symmetrical quadriceps strength, but not surgical status, 5 years after ACL injury or reconstruction was associated with lower odds of clinical knee OA.

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...

Primary hyperoxaluria (PH) is a metabolic defect that results in oxalate overproduction by the liver and leads to kidney failure due to oxalate nephropathy. As oxalate tissue stores are mobilized after transplantation, the transplanted kidney is at risk of recurrent disease. We evaluated surveillance kidney transplant biopsies for recurrent calcium oxalate (CaOx) deposits in 37 kidney transplants (29 simultaneous kidney and liver [K/L] transplants and eight kidney alone [K]) in 36 PH patients and 62 comparison transplants. Median follow-up posttransplant was 9.2 years (IQR: [5.3, 15.1]). The recurrence of CaOx crystals in surveillance biopsies in PH at any time posttransplant was 46% overall (41% in K/L, 62% in K). Higher CaOx crystal index (which accounted for biopsy sample size) was associated with higher plasma and urine oxalate following transplant (p

Background Understanding the overall variant burden in pediatric patients with left ventricular noncompaction (LVNC) has clinical implications. Whole exome sequencing (WES) allows detection of coding variants in both candidate cardiomyopathy genes and those included on commercial panels. Other lines of evidence, including in silico analysis, are necessary to reduce the overwhelming number of variants to those most likely having a phenotypic impact. Methods Five families, including five pediatric probands with LVNC, 5 other affected, and 10 unaffected family members, had WES performed, followed by bioinformatics filtering and Sanger sequencing. Review of the HGMD, variant classification by ACMG guidelines, and clinical information were used to further refine complex genotypes. Results One nonsense and eleven missense variants were identified. In Family 1, affected siblings carried digenic heterozygous variants: E1350K-MYH7 and A276V-ANKRD1. The proband also carried heterozygous W143X-NRG1. Four affected members of Family 2 carried K184Q-MYH7 while unaffected members did not. In Family 3, homozygous A161T-MYH7 and heterozygous P4935T-OBSCN variants were identified in the proband with the latter being absent in his unaffected brother. In Family 4, proband's father and half-sibling have mild hypertrabeculation and carry T3796I-PLEC. The proband, carrying T3796I-PLEC and V2878A-OBSCN, demonstrated higher trabeculation burden. The proband in Family 5 carried four variants, R3247W-PLEC, C92Y-ERG, T1233M-NCOR2, and E54K-HIST1H4B. Application of ACMG criteria and clinical data revealed that W143X-NRG1, P4935T-OBSCN, and V2878A-OBSCN likely have no phenotypic role. Conclusions We report nine variants, including novel T3796I-PLEC and biallelic A161T-MYH7, likely contributing to phenotypes ranging from asymptomatic hypertrabeculation to severe LVNC with heart failure.

Women who experience HIV seroconversion during pregnancy are missed during early routine pregnancy HIV screening and are at high risk of perinatal HIV transmission. Male partner HIV testing during routine prenatal care may be an effective primary prevention strategy by identifying women at risk of seroconversion and mitigating their risk. Our objective was to assess interest in and uptake of male partner HIV testing services offered during prenatal care. This demonstration project included all pregnant, English-speaking, HIV-negative women receiving publicly funded prenatal care in an urban hospital-based practice located in a high HIV prevalence area. Women were offered free HIV screening for their male sexual partners. From April 2017 to June 2018, enrolled women completed surveys on social demographics, medical access characteristics, and HIV testing history. Women were invited to bring their partners to a prenatal visit where HIV testing was offered to their male partners. Factors associated with women's interest in testing and completion of partner testing were assessed using bivariable and multivariable analyses. Of 392 women approached, 70% (N = 274) completed study surveys. Although the majority (76%, N = 200 of 264 respondents) of women desired their partner undergo HIV testing, testing was underutilized as only 18 (7%) male partners completed testing. While neither maternal characteristics nor male social or attitudinal factors were associated with interest in or completion of partner HIV testing, sensitivity analyses, performed with multiple imputation, demonstrated some association between interest and completion of partner testing and partner medical care access and utilization. In conclusion, although the majority of low-income women in an urban prenatal clinic expressed interest in having their partners undergo HIV testing, uptake of free partner HIV testing services was uncommon. A focused assessment of implementation and uptake barriers is needed to optimize partner testing and eliminate HIV transmission to mothers and their babies.

BACKGROUND Although deep inspiratory breath-hold (DIBH) is routinely used for left-sided breast cancers, its benefits for right-sided breast cancer (rBC) have yet to be established. We compared free-breathing (FB) and DIBH treatment plans for a cohort of rBC undergoing regional nodal irradiation (RNI) to determine its potential benefits. METHODS AND MATERIALS rBC patients considered for RNI (internal mammary nodal chains, supraclavicular field, with or without axilla) from October 2017 to May 2020 were included in this analysis. For each patient, FB versus DIBH plans were generated and dose volume histograms evaluated the following parameters: mean lung dose, ipsilateral lung V20/V5 (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V5 (volumes of heart receiving 5 Gy); liver V20 absolute /V30 absolute (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver Dmax, and total liver volume irradiated (TVIliver). The dosimetric parameters were compared using Wilcoxon signed-rank testing. RESULTS Fifty-four patients were eligible for analysis, comparing 108 FB and DIBH plans. DIBH significantly decreased all lung and liver parameters: mean lung dose (19.7 Gy-16.2 Gy, P < .001), lung V20 (40.7%-31.7%, P < .001), lung V5 (61.2%-54.5%, P < .001), TVIliver (1446 cc vs 1264 cc; P = .006) liver Dmax (50.2 Gy vs 48.9 Gy; P = .023), liver V20 (78.8-23.9 cc, P < .001), and liver V30 (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V5Heart trended on significance (1.25-0.6, P = .067). CONCLUSIONS This is the largest cohort to date analyzing DIBH for RNI-rBC. Our findings demonstrate significant improvement in all lung and liver parameters with DIBH, supporting its routine consideration for rBC patients undergoing comprehensive RNI.

Background The Long-ter M O U tcomes after the Multisystem Inflammatory S yndrome I n C hildren (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods This multicenter observational cohort study will enroll at least 600 patients Conclusion The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

INTRODUCTION Neoadjuvant chemotherapy is standard treatment for locally advanced (LABC) or inflammatory breast cancer (IBC). We hypothesized adding sunitinib, a tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2 negative LABC or IBC. PATIENTS AND METHODS We conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2 negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m2 IV weekly x12 followed by doxorubicin 24 mg/m2 IV weekly + cyclophosphamide 60 mg/m2 PO daily with G-CSF support. Response was evaluated using pCR in the breast and the Clinical-pathologic scoring + estrogen receptor (ER) and grade (CPS+EG) score. RESULTS Seventy patients enrolled and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER+ disease and 8 had triple negative disease). When defining response as pCR and/or CPS+EG score ≤ 2, 47% were responders. In ER+ patients, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue. CONCLUSIONS Neoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR. However, 47% were responders using pCR and/or CPS+EG score ≤2. ER+ patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for ER+ patients.

We present the results of our 13th annual horizon scan of issues likely to impact on biodiversity conservation. Issues are either novel within the biological conservation sector or could cause a substantial step-change in impact, either globally or regionally. Our global panel of 26 scientists and practitioners identified 15 issues that we believe to represent the highest priorities for tracking and action. Many of the issues we identified, including the impact of satellite megaconstellations and the use of long-distance wireless energy transfer, have both elements of threats and emerging opportunities. A recent state-sponsored application to commence deep-sea mining represents a significant step-change in impact. We hope that this horizon scan will increase research and policy attention on the highlighted issues.

Background Despite the success rate of Total Knee Arthroplasty (TKA), many patients undergo contralateral TKA. It is possible that altered gait mechanics after unilateral TKA play a role in the progression of contralateral OA progression. Research question The purpose of this study was to identify biomechanical predictors of radiographic OA progression in the contralateral (non-surgical) knee after unilateral (primary/initial) TKA. In addition, this study quantified for patients who had contralateral OA progression. Methods Biomechanical outcomes were collected 6–24 months after unilateral primary TKA and were used to predict changes in contralateral OA severity at follow-up. Participants were divided into “Progressor” and “Non-Progressor” groups based on changes in Kellgren-Lawrence (KL) OA grade and Joint Space Width (JSW) between baseline and follow-up testing sessions. Biomechanical factors during walking were peak knee adduction moment, knee flexion/extension excursions, knee angle at initial foot contact, and peak knee flexion/extension. Multiple independent t-tests were used to examine the magnitude of differences in biomechanical variables between the groups. Logistic regression was used to examine the association between the biomechanical predictors and change in KL scores and JSW. Results The mean time between surgery and follow-up x-rays was 8.8 (2.4) years. Of 40 participants, 62.5–78% had contralateral radiographic knee OA progression by follow-up. There were no significant differences in the biomechanical variables between groups. For the regression analysis, none of the biomechanical variables were found to be predictors for contralateral OA progression. Significance Although abnormal biomechanics are known risk factors for primary knee OA, it is possible that the mechanisms that result in OA progression of the contralateral limb are different than primary knee OA progression. Future work should evaluate other objective measures of OA progression and determine if cumulative measures of joint loading are related to OA worsening.

Background In 2013, the United States Preventive Services Taskforce instituted recommendations for annual lung cancer screening (LCS) with low-dose chest CT imaging for high-risk individuals. LCS reduces lung cancer mortality, with greater reduction observed in Black participants in clinical trials. Although racial disparities in lung cancer mortality have been well documented, less is known about disparities in LCS participation and adherence to follow-up in clinical practice. Research Question What is the association between race and adherence to LCS follow-up? Study Design and Methods A systematic review was conducted through a search of published studies in MEDLINE, PubMed, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health Literature Database from database inception through October 2020. We included studies that examined rates of adherence to LCS follow-up and compared rates by race. Studies were pooled using random-effects meta-analysis. Results We screened 18,300 titles and abstracts, and 229 studies were selected for full-text review. Nine studies met inclusion criteria; seven were included in the meta-analysis. Median adherent follow-up rate was 37% (range, 16%-82%). Notable differences among the studies included the proportion of the Black population (range, 4%-47%) and the structure of the LCS programs. The meta-analyses showed lower adherence to LCS follow-up in the Black population (OR, 0.67; 95% CI, 0.55-0.80). This disparity persisted across all malignancy risk levels determined by initial screening results. Interpretation Lower adherence to LCS follow-up in Black compared with White patients occurs despite the higher potential lung cancer mortality benefit. Literature specifically addressing race-related barriers to LCS adherence remains limited. To ensure equity in LCS benefits, greater outreach to eligible Black patients should be implemented through increased physician education and use of screening program coordinators to focus on this patient population. Trial Registry PROSPERO; No.: CRD42020214213; URL: http://www.crd.york.ac.uk/PROSPERO