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Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.

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Objective: Assess potential impacts of the COVID-19 pandemic on a subset of Post-9/11 U.S. Veterans included in a study of post-traumatic epilepsy (PTE). Methods: Two measures were added to a structured health interview for Veterans during temporary pandemic research shutdown: a validated health questionnaire [1] previously completed by survey, and a semi-structured instrument developed to assess whether pandemic conditions affected responses to the health questionnaire and identify unique impacts. Interviews were conducted between August 2020 - February 2021. Scaled items were calculated and t-tests used to compare results. Open-ended items were coded using thematic analyses. Results: Veterans identified eight major areas of impact with negative and positive impacts: mental health, family, social, work/employment, access to resources, physical health, finances, and education. Innovation: The temporary shut-down of a large health study for Post-9/11 Veterans provided an opportunity to devise an instrument to assess COVID-19's impact on health and well-being. The instrument was accepted as of the first Veteran instrument in a pandemic SDOH research repository [2], and is being used in other studies. Conclusion: This study highlights the need to assess and understand interrelated relationships of factors impacting health and well-being, especially as COVID-19 moves from pandemic to endemic with reverberating effects across multiple social determinants of health (SDOH).

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Objective: The aim of this study was to identify clinical and laboratory phenotype distribution patterns and their usefulness as prognostic markers in COVID-19 patients admitted to the intensive care unit (ICU) at Tygerberg Hospital, Cape Town. Methods and results: A latent class analysis (LCA) model was applied in a prospective, observational cohort study. Data from 343 COVID-19 patients were analysed. Two distinct phenotypes (1 and 2) were identified, comprising 68.46% and 31.54% of patients, respectively. The phenotype 2 patients were characterized by increased coagulopathy markers (D-dimer, median value 1.73 ng/L vs 0.94 ng/L; p < 0.001), end-organ dysfunction (creatinine, median value 79 µmol/L vs 69.5 µmol/L; p < 0.003), under-perfusion markers (lactate, median value 1.60 mmol/L vs 1.20 mmol/L; p < 0.001), abnormal cardiac function markers (median N-terminal pro-brain natriuretic peptide (NT-proBNP) 314 pg/ml vs 63.5 pg/ml; p < 0.001 and median high-sensitivity cardiac troponin (Hs-TropT) 39 ng/L vs 12 ng/L; p < 0.001), and acute inflammatory syndrome (median neutrophil-to-lymphocyte ratio 15.08 vs 8.68; p < 0.001 and median monocyte value 0.68 × 109/L vs 0.45 × 109/L; p < 0.001). Conclusion: The identification of COVID-19 phenotypes and sub-phenotypes in ICU patients could help as a prognostic marker in the day-to-day management of COVID-19 patients admitted to the ICU.

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Background: Patients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise - Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness. Methods: Neuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching. Conclusion: We are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.

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Background & Aims: Psychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators. Methods: The perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded. Results: Seventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks. Conclusions: MBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT02950077). Lay summary: Autoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis.

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Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort. Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed. Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge. Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge. Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ.

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BACKGROUND: In this follow-up study to previous work, the authors survey the availability of key measures and resources pertaining to residency research in U.S. Accreditation Council for Graduate Medical Education-accredited dermatology residency programs, including potential policy changes following the COVID-19 pandemic. OBJECTIVE: The chief objective of this survey was to evaluate and compare dermatology programs' resident research requirements and guidelines. METHODS: This cross-sectional study employed a 13-item survey administered online in early 2021 to assess the degree to which dermatology residency programs require and support their new physician graduates in scholarly research endeavors. RESULTS: A total of 32 program directors representing 30 dermatology residency programs (30 of 138 accredited programs contacted [22%]) responded to the survey. Almost all programs described quality improvement project requirements for residents and were able to provide funding for resident conference participation. Most programs also reported resident publication requirements and the availability of research electives. However, the vast majority did not have required research rotations or a formal mentorship program. The COVID-19 pandemic did not have a substantial impact on residency research requirements. CONCLUSION: Our survey provides objective data about the current dermatology resident research requirements across the United States. These findings may prove valuable to prospective applicants, residency programs, and accrediting agencies in improving, advancing, and structuring dermatology residency guidelines and resources with the aim of encouraging new physician trainees to pursue research.

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The quality of life, in itself, in cancer patients or in osteoporotic individuals, without even considering the side effects of the medication in the first place, has a considerable negative impact on the clinical outcome. The Medication Related Osteonecrosis of the Jaw (MRONJ), in the maxillofacial region, although rare, needs to be addressed with the prime importance. One of the key components of any given preventive treatment strategy is to, create awareness about the medication related unwanted effects, among health care professionals and patients. OBJECTIVE: This study is aimed to explore and assess the awareness level among dental patients about MRONJ, the risk factors, and the high-risk category (who are prone to develop MRONJ). MATERIAL AND METHODS: This is a prospective interviewer administered research electronic data capture (REDCap) survey. The sample included 68 patients, who are currently taking or will be taking Bisphosphonate (BP), and/or Denosumab, and anti-Angiogenic agent. Data have been analyzed using IBM SPSS software. RESULTS: Sixty-eight patients (18 males and 50 females), participated in this study. Only 23 subjects (33.82%) were aware about the MRONJ. Females were more aware about the complications than males. The awareness among the subjects with education at college level appears to be higher than the subjects having education less than high school level. Even though, a dental check- up, is mandatory, prior to starting these medications, to see if any dental treatment is required, only slightly more than half of the patients (54.72%) had a dental checkup. CONCLUSION: This is a novel study in the Middle- East, used to assess awareness about the MRONJ including three type of related medications. Low awareness of MRONJ is alarming. The results of the study will help to initiate the process of providing the education materials, about the side effects and importance of oral hygiene maintenance, giving priority to improve the quality of life in such patients. Awareness of patients regarding the complications must be an important part of health care practice guidelines.

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Appropriate patient identification is a critical component of safe health care delivery. With increasing reliance on electronic medical records (EMRs), errors of test ordering and documentation have become commonplace. Incorporating patients' photograph in the EMR has considerably decreased error frequency and improved health care delivery by making it easier for physicians to identify a patient. We conducted a survey of all 35 physicians working in the Executive Health Program to determine the importance of having patient photographs in the EMR. Of the 35 physicians who received the survey, 26 (74.3%) responded, 24 (92.3%) of whom agreed that it was important to improve patient identification, care, and safety. Based on these data, we implemented a quality improvement project to increase the percentage of new patients having a photograph included in the EMR. Our goal was to increase photograph inclusion by more than 20% from baseline within 6 months without any unintended consequences (ie, not slowing down any of the workflow during the intake process). The intervention took place between June 1, 2015, and February 8, 2016. Using Define-Measure-Analyze-Improve-Control models, the baseline rate of photographs in the EMR was 49.5% (302 of 607). We initiated 3 Plan-Do-Study-Act cycles targeting awareness and data sharing campaigns. After the Plan-Do-Study-Act cycles, the weekly rate of patient photographs incorporated into the EMR was at 71.4%, which was significantly improved compared with baseline (F test, P<.001). No unintended consequences were identified. Increased inclusion of patient photographs in the EMR aided in patient identification and improved staff satisfaction with minimal interruption to workflow.

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OBJECTIVE: To apply practice-based evidence to clinical management of cerebral palsy (CP). The process of establishing purpose, structure, logistics, and elements of a multi-institutional registry and the baseline characteristics of initial enrollees are reported. DESIGN: A consensus-building process among consumers, clinicians, and researchers used a participatory action process. SETTING: Community, hospitals, and universities. PARTICIPANTS: More than 100 clinicians, researchers, and consumers and more than 1858 enrollees in the registry. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Consensus was that the purpose of registry was to (1) quantify practice variation, (2) facilitate quality improvement (QI), and (3) perform comparative effectiveness research (CER). Collecting data during routine clinical care using the electronic medical record was determined to be a sustainable plan for data acquisition and management. Clinicians from multiple disciplines defined salient characteristics of individuals and interventions for the registry elements. The registry was central to the clinical research network, and a leadership structure was created. A leading electronic health record platform adopted the registry elements. Twenty-four sites have initiated the data collection process and agreed to export data to the registry. Currently 12 are collecting data. Number of enrollees and characteristics were similar to other population registers. CONCLUSIONS: This is the first multi-institutional CP registry that contains the patient and treatment characteristics needed for QI and CER. The Cerebral Palsy Research Network registry elements are implemented in a versatile electronic platform and minimize burden to clinicians. The resultant registry is available for any institution to participate and is growing rapidly.

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OBJECTIVE: The breadth of technical skills included in general surgery training continues to expand. The current competency-based training model requires assessment tools to measure acquisition, learning, and mastery of technical skill longitudinally in a reliable and valid manner. This study describes a novel skills assessment tool, the Omni, which evaluates performance in a broad range of skills over time. DESIGN: The 5 Omni tasks, consisting of open bowel anastomosis, knot tying, laparoscopic clover pattern cut, robotic needle drive, and endoscopic bubble pop, were developed by general surgery faculty. Component performance metrics assessed speed, accuracy, and quality, which were scaled into an overall score ranging from 0 to 10 for each task. For each task, ANOVAs with Scheffé's post hoc comparisons and Pearson's chi-squared tests compared performance between 6 resident cohorts (clinical years (CY1-5) and research fellows (RF)). Paired samples t-tests evaluated changes in performance across academic years. Cronbach's alpha coefficient determined the internal consistency of the Omni as an overall assessment. SETTING: The Omni was developed by the Department of Surgery at Duke University. Annual assessment and this research study took place in the Surgical Education and Activities Lab. PARTICIPANTS: All active general surgery residents in 2 consecutive academic years spanning 2015 to 2017. RESULTS: A total of 62 general surgery residents completed the Omni and 39 (67.2%) of those residents completed the assessment in 2 consecutive years. Based on data from all residents' first assessment, statistically significant differences (p < 0.05) were observed among CY cohorts for bowel anastomosis, robotic, and laparoscopic task metrics. By pair-wise comparisons, mean bowel anastomosis scores distinguished CY1 from CY3-5 and CY2 from CY5. Mean robotic scores distinguished CY1 from RF, and mean laparoscopic scores distinguished CY1 from RF, CY3, and CY5 in addition to CY2 from CY3. Mean scores in performance on the knot tying and endoscopic tasks were not significantly different. Statistically significant improvement in mean scores was observed for all tasks from year 1 to year 2 (all p < 0.02). The internal consistency analysis revealed an alpha coefficient of 0.656. CONCLUSIONS: The Omni is a novel composite assessment tool for surgical technical skill that utilizes objective measures and scoring algorithms to evaluate performance. In this pilot study, 3 tasks demonstrated discriminative ability of performance by CY, and all 5 tasks demonstrated construct validity by showing longitudinal improvement in performance. Additionally, the Omni has adequate internal consistency for a formative assessment. These results suggest the Omni holds promise for the evaluation of resident technical skill and early identification of outliers requiring intervention.

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Introduction Disasters will continue to occur throughout the world and it is the responsibility of the government, health care systems, and communities to adequately prepare for potential catastrophic scenarios. Unfortunately, low-and-middle-income countries (LMICs) are especially vulnerable following a disaster. By understanding disaster preparedness and risk perception, interventions can be developed to improve community preparedness and avoid unnecessary mortality and morbidity following a natural disaster. Problem The purpose of this study was to assess disaster preparedness and risk perception in communities surrounding Trujillo, Peru. METHODS: After designing a novel disaster preparedness and risk perception survey based on guidelines from the International Federation of Red Cross and Red Crescent Societies (IFRC; Geneva, Switzerland), investigators performed a cross-sectional survey of potentially vulnerable communities surrounding Trujillo, Peru. Data were entered and analyzed utilizing the Research Electronic Data Capture (REDCap; Harvard Catalyst; Boston, Massachusetts USA) database. RESULTS: A total of 230 study participants were surveyed, composed of 37% males, 63% females, with ages ranging from 18-85 years old. Those surveyed who had previously experienced a disaster (41%) had a higher perception of future disaster occurrence and potential disaster impact on their community. Overall, the study participants consistently perceived that earthquakes and infection had the highest potential impact of all disasters. Twenty-six percent of participants had an emergency supply of food, 24% had an emergency water plan, 24% had a first aid kit at home, and only 20% of the study participants had an established family evacuation plan. CONCLUSION: Natural and man-made disasters will remain a threat to the safety and health of communities in all parts of the world, especially within vulnerable communities in LMICs; however, little research has been done to identify disaster perception, vulnerability, and preparedness in LMIC communities. The current study established that selected communities near Trujillo, Peru recognize a high disaster impact from earthquakes and infection, but are not adequately prepared for potential future disasters. By identifying high-risk demographics, targeted public health interventions are needed to prepare vulnerable communities in the following areas: emergency food supplies, emergency water plan, medical supplies at home, and establishing evacuation plans. Stewart M , Grahmann B , Fillmore A , Benson LS . Rural community disaster preparedness and risk perception in Trujillo, Peru. Prehosp Disaster Med. 2017;32(4):387-392.

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Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70-85%HRmax) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke.