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Background At many trauma centers in the United States, one acute care surgeon is responsible for overnight coverage of both the emergency general surgery (EGS) and trauma services. The impact of this scheduling phenomenon on the quality and safety of trauma care has not been studied. Methods Overnight (12:00 AM to 7:00 AM) trauma admissions to an academic Level 1 trauma center from 2013-2015 were studied after the institution adopted this scheduling phenomenon. Admissions were divided into two groups based on whether the admitting surgeon covered only the trauma service, or both the trauma and EGS services ("multi-service coverage"). Four major outcomes (e.g., mortality and complications), six quality metrics (e.g., time to first odds ratio visit and unplanned transfers to the ICU), and procedural utilization patterns were compared. Results A total of 1046 admissions were included. There were no differences in any major outcomes between the two exposure groups, including any National Trauma Data Bank-defined complication (OR 1.1, 95% CI 0.8-1.5, P= 0.5). Quality metrics dependent on the admitting surgeon remained unchanged, including attending presence at the highest-level trauma activations within 15 min of arrival (93% versus 86%, P= 0.07) and time to urgent operative intervention (68 min versus 82 min, P= 0.9). There were no differences in the number of laboratory and imaging studies (4.1 versus 4.1, P= 0.9) or bedside interventions (1.8 versus 2.1, P= 0.4) performed per patient by the admitting surgeon. Multivariate logistic regression did not identify multi-service coverage as an independent risk factor for adverse patient outcomes or quality metrics. Conclusions Trauma admissions under a surgeon covering multiple services simultaneously had similar outcomes, quality metrics, and procedural utilization patterns compared to trauma admissions under surgeons covering only the trauma service. Despite concerns that multiple-service coverage may overburden one acute care surgeon, time-dependent quality metrics and studies done during the initial workup of trauma patients remained unchanged. These findings suggest that simultaneous trauma and EGS service coverage by one acute care surgeon does not adversely impact trauma patient care.

Introduction: Screening for coronavirus disease 2019 (COVID-19) exposure, coupled with engaged decision making to prioritize cancer treatment in parallel with reducing risk of exposure and infection, is crucial in the management of COVID-19 during cancer treatment. After two reported case studies of imaging findings during daily computed tomography (CT)-based image-guided radio-therapy (RT) scans, a call for submission of anonymized case reports was published with the objective of rapidly determining if there was a correlation between the onset of new pulmonary infiltrates found during RT and COVID-19. We hereby report the results of the aggregate analysis. Methods: Data of deidentified case reports for patients who developed biochemically confirmed COVID-19 during RT were submitted through an online portal. Information requested included a patient's sex, age, cancer diagnosis and treatment, and COVID-19 diagnosis and outcome. Coplanar CT-based imaging was requested to reveal the presence or absence of ground-glass opacities or infiltrates. Results: A total of seven reports were submitted from Turkey, Spain, Belgium, Egypt, and the United States. Results and imaging from the patients reported by Suppli et al. and McGinnis et al. were included for a total of nine patients for analysis. All patients were confirmed COVID-19 positive using polymerase chain reaction-based methods or nasopharyngeal swabs. Of the nine patients analyzed, abnormalities consistent with ground-glass opacities or in- filtrates were observed in eight patients. Conclusions: This is the largest case series revealing the potential use of CT-based image guidance during RT as a tool for identifying patients who need further workup for COVID-19. Considerations for reviewing image guidance for new pulmonary infiltrates and immediate COVID-19 testing in patients who develop new infiltrates even without COVID-19 symptoms are strongly encouraged. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Review of the effects of SARS-CoV2 infection and COVID-19 on common pediatric psychiatric illnesses

To evaluate the efficacy of daily supplementation of 200 mL milk fortified with 240 IU of vitamin D2 (ergocalciferol). Double-blind randomized controlled trial. School-based study in Delhi between October and December, 2019. 235 healthy children aged 10–14 years. Daily supplementation of 200 mL milk fortified with 240 IU of ergocalciferol in intervention group (n=119) and 200 mL of plain milk in control group (n =116) for 3 months. Change in serum 25 hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), bone formation and resorption markers, and urinary calcium creatinine ratio (U-Ca/CrR). The mean (SD) baseline serum 25(OH) D level in control and fortification groups was 11.9 (3.8) and 11.4 (3.6) ng/mL (P=0.23), respectively. The serum 25(OH)D levels did not increase post-intervention with the dose used for fortification, but were significantly higher in intervention group as compared to control group [10.8 (3.4) vs 6.7 (3.5) ng/mL; P

Malignant ovarian germ cell tumors (MOGCTs) are rare but disproportionately affect young women and adolescent girls. Although clinical presentation varies, these tumors can present with an adnexal mass and raised serum beta-human chorionic gonadotrophin (beta-hCG), mimicking an ectopic pregnancy. We present the case of a 20-year-old nulliparous woman, who was initially treated both medically and surgically as an ectopic pregnancy, and was eventually diagnosed with a malignant mixed germ cell tumor (MMGCT) following laparoscopy. We highlight the diagnostic challenges of ectopic pregnancies versus MOGCTs, and the importance of adopting a fertility-sparing approach in young nulliparous women. J Clin Gynecol Obstet. 2021;10(2):55-58 doi: https://doi.org/10.14740/jcgo743

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus (SARS-CoV2) infection rates are currently occurring at alarmingly accelerated rates. There is also a long-standing and concurrent rise in the prevalence and severity of substance use disorders (SUD). Therefore, the intersection between these two conditions needs to be carefully considered to ensure a more effective delivery of healthcare. RECENT FINDINGS: Generally, those with SUDs are more likely to have higher risk social determinants of health factors. Therefore, these patients are more likely to have barriers that can create difficulties in following appropriate infection control measures which in turn increases the risk of exposure to SARS-CoV2. In addition, these individuals have higher rates of medical comorbidities which increases the risk of all adverse outcomes, including mortality, from SARS-CoV2 infection. SUMMARY: Individuals with SUDs are at increased risk of both contracting SARS-CoV2 infection and suffering from worse outcomes afterwards. Though these risks of adverse outcomes are specific of SARS-CoV2 infection, the risk of exposure to other infectious diseases is increased in this population too. Healthcare providers and policymakers should then consider how to better protect this at-risk population and alleviate this increased disease burden.

Background Amid a Canadian opioid crisis, many have turned to natural health products, such as kratom (Mitragyna speciosa), to manage their opioid withdrawal. Kratom has also been reported to relieve anxiety, improve stamina, and heighten physical performance. Given that kratom is not authorized for sale by Health Canada, many have turned to online retailers to purchase kratom due to its easy accessibility online. This study investigated the quality of consumer health information provided on the websites of online vendors selling kratom to consumers in Canada. Methods Following searches on Google.ca using search terms designed to simulate the information-seeking behaviour of a typical patient-user online, eligible websites were assessed using the 16-question DISCERN instrument, a tool designed to assess the quality of consumer health information. Searches were conducted on March 27, 2020 and only websites presenting information in English were included. Results A total of 200 webpages were identified; after screening based on eligibility criteria and combining different webpages that belonged to the same website, 51 websites were found to be eligible. The mean summed DISCERN score across all 51 websites was 36.95 (SD = 2.44) out of 75, which reflects poor quality consumer health information across the subset of websites. The overall quality of websites was poor, as 78% (n = 40) of vendors received a score of 2 or less out of 5. Conclusions Individuals who seek information about kratom online are frequently exposed to poor quality consumer health information. Those looking to purchase kratom online are not provided with the critical information necessary to make an informed decision regarding its use, such as the complete details about the risks and side effects or a description of how kratom affects the body. Given the growing interest in kratom, knowledge of the quality of information available can lead to improved dialogue between healthcare providers and patients.

Background Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues’ experiences and published evidence. Methods In late 2020, BJS contacted colleagues across the global surgical community and asked them to describe how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had affected their practice. In addition to this, the Commission undertook a literature review on the impact of COVID-19 on surgery and perioperative care. A thematic analysis was performed to identify the issues most frequently encountered by the correspondents, as well as the solutions and ideas suggested to address them. Results BJS received communications for this Commission from leading clinicians and academics across a variety of surgical specialties in every inhabited continent. The responses from all over the world provided insights into multiple facets of surgical practice from a governmental level to individual clinical practice and training. Conclusion The COVID-19 pandemic has uncovered a variety of problems in healthcare systems, including negative impacts on surgical practice. Global surgical multidisciplinary teams are working collaboratively to address research questions about the future of surgery in the post-COVID-19 era. The COVID-19 pandemic is severely damaging surgical training. The establishment of a multidisciplinary ethics committee should be encouraged at all surgical oncology centres. Innovative leadership and collaboration is vital in the post-COVID-19 era.

Background: Ribociclib is an oral selective CDK4/6 inhibitor approved for use in combination with an aromatase inhibitor (AI) or fulvestrant, in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in several countries, including the UK. Ribociclib plus endocrine therapy (ET) significantly improved PFS outcomes in phase III registration studies (MONALEESA-2, -3, and-7) compared with placebo plus ET; and significantly increased OS in combination with AI in premenopausal women (MONALEESA-7), and in combination with fulvestrant in postmenopausal women (MONALEESA-3). This analysis aims to report the final efficacy and safety results for the UK cohort of CompLEEment-1, a phase 3b trial evaluating ribociclib plus letrozole in an expanded patient population.Methods: Patients with HR+, HER2- ABC, ≤1 line of prior chemotherapy (CT), and no prior ET in the advanced setting, received ribociclib + letrozole. Baseline characteristics and interim results of the UK cohort have been reported previously (Ring et al. SABCS 2019. Poster 443).Results: A total of 139 UK patients received ≥1 dose of study treatment at UK sites. At the cut-off date, November 8th 2019, 53 patients (38.1%) had completed treatment and 86 discontinued due to disease progression (30.9%), adverse events (24.5%), physician or subject/guardian decision (2.9% each), and protocol deviation (0.7%). The mean age of patients was 61.3 (SD10.67). 138 (99.3%) patients were female, 125 (89.9%) were post-menopausal and 50 (35.9%) had an ECOG status of ≥1. 85 (61.1%) patients had received prior chemotherapy in any setting.89 (64.0%) patients had measurable disease at baseline. 80 (60.4%) patients presented with visceral disease, 35 (25.2%) with bone-only metastases and 4 (2.9%) had CNS metastases. 59 (42.5%) of patients had ≥3 metastatic sites. The median duration of exposure to study treatment was 18.4 months with a median time to progression of 27.6 months. The overall response rate was 25.9% (95% CI: 18.8, 34.0) and clinical benefit rate was 74.1% (95% CI: 66.0, 81.2). Overall, the adverse event (AE) profile was consistent with previous phase III trials. Neutropenia (68.3%), nausea (59.7%), and fatigue (54%) and neutropenia (48.9%) were the most common adverse events (all grades). Neutropenia was the most common AE leading to dose reduction (12.2%) or interruption (33.8%), with ALT increase the most common cause for treatment discontinuation (10.1%). QT prolongation (all grades) led to 3 (2.2%) dose interruptions and 2 (1.4%) dose reductions, but no treatment discontinuations. Conclusions: This subgroup analysis of the COMPLEEMENT-1 study provides further clinically meaningful outcomes on first-line ribociclib and letrozole treatment in a UK cohort. This treatment combination showed consistent efficacy and side effect profile in UK HR+, HER2- ABC patients, consistent with the overall ITT population as well as results observed in the other pivotal ribociclib registration studies. NCT02941926. Citation Format: Mark Tuthill, Hardeep Marwaha, Christoph EA Hartmann. Phase 3b CompLEEment-1 study of ribociclib plus letrozole in the treatment of HR+/HER2- advanced breast cancer: Final results from the UK cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-49.

Computer-assisted pattern recognition platforms, such as Face2Gene® (F2G), can facilitate the diagnosis of children with rare genetic syndromes by comparing a patient's features to known genetic diagnoses. Our work designed, implemented, and evaluated an innovative model of care in clinical genetics in a heterogeneous and multicultural patient population that utilized this facial phenotyping software at the point-of-care. We assessed the performance of F2G by comparing the suggested diagnoses to the patient's confirmed molecular diagnosis. Providers' overall experiences with the technology and trainees' educational experiences were assessed with questionnaires. We achieved an overall diagnostic yield of 57%. This increased to 82% when cases diagnosed with syndromes not recognized by F2G were removed. The mean rank of a confirmed diagnosis in the top 10 was 2.3 (CI 1.5-3.2) and the mean gestalt score 37.6%. The most commonly suggested diagnoses were Noonan syndrome, mucopolysaccharidosis, and 22q11.2 deletion syndrome. Our qualitative assessment revealed that clinicians and trainees saw value using the tool in practice. Overall, this work helped to implement an innovative patient care delivery model in clinical genetics that utilizes a facial phenotyping tool at the point-of-care. Our data suggest that F2G has utility in the genetics clinic as a clinical decision support tool in diverse populations, with a majority of patients having their eventual diagnosis listed in the top 10 suggested syndromes based on a photograph alone. It shows promise for further integration into clinical care and medical education, and we advocate for its continued use, adoption and refinement along with transparent and accountable industrial partnerships.

Background Corticosteroids (CS) have been used extensively to induce remission in Crohn’s disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. Aim The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN Methods The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. Results A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. Conclusion The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Regular exercise has multiple benefits for physical and mental health, including the body’s ability to combat infections. The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers. The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period. The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes.

GATA6 pathogenic variants primarily manifest a phenotype with pancreatic agenesis and cardiac malformations. However, additional congenital malformations affecting the biliary system, congenital diaphragmatic hernia and developmental delay have been reported. We report a newborn, prenatally diagnosed with truncus arteriosus and intrauterine growth restriction, who was postnatally found to have pancreatic agenesis associated with neonatal diabetes and hepatobiliary abnormalities. Whole exome sequencing identified a de novo, heterozygous mutation in the GATA6 gene (c.1366C>T; p.Arg456Cys). Further investigations revealed abnormalities not previously associated with GATA6 mutation, including unilateral thyroid lobe agenesis associated with congenital hypothyroidism, absent gall bladder, possible adrenal insufficiency, thrombocytopenia, and neonatal stroke.

BackgroundCannabis use is a global public health issue associated with increased risks of developing mental health disorders, especially in young people. We aimed to investigate the relationships between cannabis exposure and risks of receiving mental illness diagnoses or treatment as outcomes.MethodsA population based, retrospective, open cohort study using patients recorded in ‘IQVIA medical research data’, a UK primary care database. Read codes were used to confirm patients with recorded exposure to cannabis use who were matched up to two unexposed patients. We examined the risk of developing three categories of mental ill health: depression, anxiety or serious mental illness (SMI).ResultsAt study entry, the exposed cohort had an increased likelihood of having experienced mental ill health [odds ratio (OR) 4.13; 95% confidence interval (CI) 3.99–4.27] and mental ill health-related prescription (OR 2.95; 95% CI 2.86–3.05) compared to the unexposed group. During the study period we found that exposure to cannabis was associated with an increased risk of developing any mental disorder [adjusted hazard ratio (aHR) 2.73; 95% CI 2.59–2.88], also noted when examining by subtype of disorder: anxiety (aHR 2.46; 95% CI 2.29–2.64), depression (aHR 2.34; 95% CI 2.20–2.49) and SMI (aHR 6.41; 95% CI 5.42–7.57). These results remained robust in sensitivity analyses.ConclusionThese findings point to the potential need for a public health approach to the management of people misusing cannabis. However, there is a gross under-recording of cannabis use in GP records, as seen by the prevalence of recorded cannabis exposure substantially lower than self-reported survey records.

Relatively little is known about how to make digital health tools accessible to different populations from a cultural standpoint. Alignment with cultural values and communication styles may affect these tools’ ability to diagnose and treat various conditions. In this Editorial, we highlight the findings of recent work to make digital tools for mental health more culturally accessible, and propose ways to advance this area of study.

Background: Need for Medical devices is very important in the healthcare sector and related processes for global regulation. Medical devices are the apparatus or instruments which are specifically used for diagnostics and therapeutic applications. In the USA, a regulatory body known as FDA (Food and Drug Administration) has its unit called CDRH which looks the manufacture, packaging and use of medical devices in the USA. Objective: In USA, Medical devices are classified into 3 classes: class I which look for the medical devices used for the general control as dental floss and bandages, etc., class II which regulate the medical devices used for the general control as well as special control as powered wheelchairs and pregnancy kits. Class III medical devices look the general control. PMA (Premarket Approval) and Premarket Notification application has been filed to FDA for seeking the market authorization of medical devices. We perform clinical trials for medical device which are quite different from the clinical trials performed for drug analysis. These trials are performed on various age groups such as on paediatrics, adult and old age group commonly called phase 1,2,3,4. Regulatory approval of high-risk medical device is based on clinical studies submitted with pre-market approval. The main objective of this article is to make the researcher aware of the regulation and clinical trials of medical devices in the USA. Conclusion: Every medical device should comply with FDA, QMS and QSR for marketing in the USA. The present article has focused on the regulation of medical devices, clinical trial phases and clinical studies on medical devices.

Introduction: Coronavirus disease-2019 (COVID-19) was announced as a pandemic by the World Health Organization (WHO) on March 11, 2020 According to a WHO report on COVID-19, the disease has nospecific manifestation and the patient's pres-entation can range from completely asymptomatic to severe pneumonia and death Objective: To retrospectively characterize and interpret the spectrum of chest computed tomography (CT) imaging features of Coronavirus disease-19 (COVID-19) in infected Indian population and to correlate CT total severity score with clinical classification and study extra-pulmonary manifestation of Corona-virus disease 2019 (COVID-19) Methods: A retrospective single-centre study was conducted on patients with COVID-19 from May 10, 2020, to July 13, 2020, in tertiary care Max super specialty hospital, Delhi, India A total of 532 patients either laboratory-confirmed or strongly suspected of having COVID-19 underwent CT chest and their imaging features were analyzed and interpreted in detail and studied for extra-pulmonary manifestation of COVID-19 The consistency of observers was evaluated for CT total severity score (TSS) and TSS was compared with clinical classification Result: This study included 532 patients, 10 patients were excluded from the study Among a total of 522 patients in the study, 362 (69 3%) were males and 160 (30 7%) were females with a mean age of 52 75 years (range 14-88) According to the clinical subtype classification there were mild 17 (3 3%), common 355 (68 0%), severe 105 (20 1%) and critical 45 (8 6%) cases 57 (10 9%) patients died and 37 (7 08%) patients showed extra-pulmonary manifestation of COVID-19 There were 17 patients with normal CT chest Only 2 cases had unilateral lung disease and the rest of 503 cases showed bilateral lung involvement with multiple opacities and multiple lobe involvement Diffuse lung involvement i e white lung noted in 10 cases and none of the patient had single lesion Opacities on CT imaging tended to be both peripheral and central in most cases, followed by purely peripheral and rarely are with the purely central distribution According to CT attenuation of opacity, Ground glass opacity (GGO), and the mixture of Ground glass opacity & consolidative opacities and consolidative opacities was the dominant abnormality founded almost in all cases Perilesional or intralesional, thickened small vessel was observed in almost all cases Accompany-ing signs were crazy paving (40 6%), reverse halo sign (10 9 %), subpleural lines (47 9%), air bronchogram (28 4%), bronchiec-tasis (18 6%), pleural effusion (5 6%) and mediastinal lymphadenopathy (4 8%) Follow up scanning was obtained in 28 cases, showed no change in 2 cases, turned better in 12 cases, and became worse in 14 cases on follow up imaging studies Conclusions: The typical pattern of COVID-19 pneumonia in Delhi, India, was ground glass opacity in the form of pure ground glass opacity, ground glass opacity with superimposed crazy paving pattern or Ground glass opacity admixed with consolidation with intralesional vascular enlargement were the most dominant lung parenchymal abnormalities with the peripheral and pos-terior distribution encountered in most of the cases In the short term follow-up, more patients had disease progression rather than absorption Proportion of patients [17 (3 2%)] with normal CT chest in laboratory-confirmed COVID-19 was relatively low;hence chest CT may play a complementary role in the early detection of COVID-19 pneumonia and could be regarded as a diagnotic standard of COVID-19 COVID-19 is progressive viral pneumonia with broad spectrum of clinical manifestations and can also present with extra-pulmonary manifestations © IJCRR

Background: Many studies have proposed the lack of Lewis antigen as a marker for coronary artery disease (CAD); on the contrary, some of the studies found no association in this regard. This study aims to assess the association of the expression of Lewis antigen as an independent risk factor for CAD separately in males and females. Materials and Methods: In this cross-sectional observational study, patients with angiographically proven CAD were taken as test group, and angiographically, negative patients were included as a control group. The individuals were examined for established CAD risk factor and Lewis antigen expression on red cell. Red cell Lewis phenotyping was done using microcolumn gel agglutination technology. Statistical tests were applied to see the association between lack of Lewis antigen expression and CAD. Results: Of these 232 patients included in the study, 161 patients had more than 50% luminal stenosis in a major epicardial artery on coronary angiography (Test Group), and 71 were normal on angiography (Control Group). When males and females were considered together, there was an increased frequency of Lewis-negative phenotype among the angiography-positive group (26.7%) as compared to angiography normal control group (16.9 %), though was not statistically significant (P = 0.19). When males and females were segregated in multivariate analysis, Le (a-b-) females had a higher incidence of CAD (P = 0.03) with the odds ratio of 4.97, though an association was not found significant in males (P = 0.71). Conclusion: The association between Lewis phenotypes and CAD was not significant in males and in among the overall study population, but this association was statistically significant in females. Further studies based on a larger sample size may substantiate as well as delineate the possible hypotheses.

Inherited bleeding disorders are not uncommon in pediatric practice: most of them being chronic, require lifelong replacement therapy. To frame a management policy, it is essential to assess the load and pattern of bleeding disorders in the local population. However, there is paucity of data reporting the clinical spectrum of coagulation and platelet function disorders in Indian children. Hence to find out the exact burden and clinico-investigational profile of these patients we conducted this study. In this retrospective case review, detailed clinical information was extracted from case records in 426 children with a suspected diagnosis of hereditary bleeding disorder registered in the Pediatric Hematology clinic of a tertiary referral centre over a period of 14 years (1998-2011) and pooled for analysis. In our cohort prevalence of hemophilia A, hemophilia B, platelet function disorders, von Willebrand disease and other rare factor deficiencies were 72%, 11%, 7%, 4% and 4% respectively. Common clinical spectrum included skin bleeds, arthropathy, mucosal bleeds. 10% had deeper tissue bleeding and 16% received replacement therapy at the first visit. Nearly 3/4th of cases were lost for follow up after the initial visit. Hemophilia A was the commonest inherited bleeding disorder in our population. Skin bleeds and arthropathy were common clinical presentations. Factor replacement therapy was restricted to a minority. There is an urgent need for establishing centres of excellence with administrative commitment for factor replacement therapy for comprehensive management of such children in resource-limited countries.

Mutations in the torsinA-interacting protein 1 (TOR1AIP1) gene result in a severe muscular dystrophy with minimal literature in the pediatric population. We review a case of TOR1AIP1 gene mutation in a 16-year-old Caucasian female with a long history of muscle weakness. Extensive clinical workup was performed and MRI at time of initial presentation demonstrated no significant muscular atrophy with heterogenous STIR hyperintensity of the lower extremity muscles. MRI findings seven years later included extensive atrophy of the lower extremities, with severe progression, including the gluteal muscles, iliopsoas, rectus femoris, and obturator internus. There was also significant atrophy of the rectus abdominis and internal and external oblique muscles, and iliacus muscles. The MRI findings showed more proximal involvement of lower extremities and no atrophy of the tibialis anterior, making TOR1AIP1 the more likely genetic cause. Muscle biopsy findings supported TOR1AIP1 limb-girdle muscular dystrophy. Though rare, TOR1AIP1 gene mutation occurs in pediatric patients and MRI can aid in diagnosis and help differentiate from other types of muscular dystrophy. Genetic and pathology workup is also crucial to accurate diagnosis and possible treatment of these patients.

Background The effectiveness and value of teledermatology and face-to-face workflows for diagnosing lesions are not adequately understood. Objective We compared the risks of biopsy and cancer diagnosis among 2 face-to-face workflows (direct referral and roving dermatologist) and 4 teledermatology workflows. Methods Retrospective study of 59,279 primary care patients presenting with a lesion from January through June 2017. Results One teledermatology workflow achieved high-resolution images with use of a dermatoscope-fitted digital camera, a picture archiving and communication system, and image retrieval to a large computer monitor (in contrast to a smartphone screen). Compared with direct referral, this workflow was associated with a 9% greater probability of cancer detection (95% confidence interval [CI], 2%-16%), a 4% lower probability of biopsy (relative risk, 0.96; 95% CI, 0.93-0.99), and 39% fewer face-to-face visits (relative risk, 0.61; 95% CI, 0.57-0.65). Other workflows were less effective. Limitations Differing proficiencies across teledermatology workflows and selection of patients for direct referral could have caused bias. Conclusion Implementation is critical to the effectiveness of teledermatology.

Background Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. Methods We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. Results We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. Limitation The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. Conclusions There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.

Anomalous origin of the right coronary artery (RCA) from the ascending aorta above the left Sinus of Valsalva is a very rare coronary anomaly which can pose extreme difficulties for the operator, especially in the setting of an acute myocardial infarction. Herein, we describe a patient in whom this very rare anomaly was encountered in a setting of acute inferior wall myocardial infarction complicated by complete heart block and cardiogenic shock. Since we were aware of this anomaly as we had recently encountered and published a case of a similar anomaly in a relatively elective setting, we could successfully manage this case in the acute emergent setting minimising contrast load and avoiding complications.

Background The Plastic Surgery Milestones Project was implemented in 2014 to establish standards for competency based resident education. In restructuring educational activities under the Milestones, various pedagogical tools have been revised. However, these standards have not yet been applied to the Plastic Surgery In-Service Training Examination. The purpose of this study was to determine the representation of the various components of the Plastic Surgery Milestones Project, on the In-Service Training Examination. Methods All questions from the 2014 ‐ 2018 In-Service Examinations were evaluated within the framework of the current Plastic Surgery Milestones. Using content analysis, each Examination question was mapped to a single Milestone. Descriptive analysis of Milestone subject area and Core Competency breakdown, as well as year to year trends, were performed. Results Of the 1,150 questions analyzed, there was an unequal representation of individual Milestones (0-7.4%). Of the 36 Plastic Surgery Milestones, 10 represented more than 50% of the PSITEs while 8 Milestones had less than 1% representation. The most common subject area was Head and Neck (12.7%) and least common was Reconstruction of the Trunk and Perineum. Among Core Competencies, more than half (50.4%) tested Patient Care while Interpersonal and Communication Skills was the lowest represented, 0.2%. Conclusions The Plastic Surgery In-Service Examination tests a variable proportion of Milestones. Currently, the PSITE is not well integrated with competency based education in spite of a shift towards such a training model. Going forward, the PSITE may include an associated Milestone with each question in order to better incorporate Competencies into this important annual evaluation metric.

Background\ud Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis.\ud \ud Methods\ud CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at least one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045.\ud \ud Results\ud Five hundred fifty-one participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99, 382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group; however, the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group.\ud \ud Conclusions\ud Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered.

It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2–5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6–8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution. A diagnostic tool based on blood RNA-seq is shown to identify causal genes and variants linked to clinical phenotypes in individuals with rare diseases for which whole-exome genetic sequencing was uninformative.

Objective: Diabetic cardiomyopathy (DC) is a myocardial disease characterized by myocyte hypertrophy, interstitial fibrosis, protein glycosylation and intra-myocardial micro-angiopathy due to prolonged exposure of myocardial tissues to hyperglycemia in diabetes mellitus (DM) patients. Alteration in cardiac function can be non-invasively assessed via echocardiography. The early recognition of cardiac dysfunction can prevent the symptomatic heart failure in DM patients. The study aimed at evaluating cardiac function in uncomplicated type 2 diabetes mellitus. Materials And Methods: Sixty Type 2 DM patients without any feature of the coronary arterial disease (CAD), hypertension, nephropathy and respiratory illness were enrolled in the study and compared with the sixty age matched healthy controls. Echocardiographic assessment was done in all subjects to evaluate the cardiac function. Results: Diastolic dysfunction was more common in diabetic patients when compared with normal healthy population. Systolic dysfunction progresses with age of the diabetic patient. Conclusion: Echocardiography is a simple noninvasive cost effective test for detecting cardiac dysfunction in Type 2 DM patients and should be applied to detect early Left ventricular(LV) dysfunction so that corrective measures may be initiated early and cardiac functions may be preserved for long. Bangladesh Journal of Medical Science Vol.18(2) 2019 p.211-215

BACKGROUND Little is known about the relationship between dental caries prevalence and the social risk factors of asylum seekers and refugees in Australia. METHODS An oral health interview and a clinical oral examination were carried out on 201 asylum seekers and refugees patients, aged 18-68, attending Monash Health Dental Services, Melbourne, Victoria. RESULTS Data illustrated that 82% of participants had at least one tooth with untreated decay. Tooth level analysis revealed that white spot lesions were most prevalent in age groups 18-29 and 30-39, with respective mean values of 4.45 ± 4.95 and 3.49 ± 4.74. Binary logistic regression models identified multiple social factors as a barrier to receiving dental care. These included, but were not limited to; medication intake, consumption of soft drinks and long waiting lists. These social factors in addition to oral health factors, such as white spot and hypomineralization lesions, were significant predisposing factors to the presence of cavitated carious lesions. CONCLUSIONS Multiple social and oral health risk factors were identified and significantly associated with dental caries among refugee and asylum seeker patients. Addressing these underlying risks is an integral component to reducing the prevalence of dental caries among this population group and improving their overall general and oral health.

The cardiovascular benefits of regular physical activity and systematic exercise are well-established. Exercise results in a favourable atherosclerotic risk profile and increased cardiorespiratory fitness; both factors are associated with a significantly lower prevalence of adverse cardiovascular events in middle and older age, and increased longevity of life. Genetic diseases include the primary cardiomyopathies such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC); channelopathies such as long-QT syndrome (LQTS), catecholamine polymorphic ventricular tachycardia (CPVT) and Brugada syndrome; aortopathies such as Marfan syndrome and premature atherosclerotic coronary artery disease (CAD) due to familial hypercholesterolaemia. The clinical history pertains to identifying cardiovascular symptoms such as exertional chest discomfort, dyspnoea, palpitations and syncope. The societal impact of a sudden death in an athlete may be considered as an important public health issue. Most deaths in exercising individuals affect middle aged and older athletes.

BackgroundPost-discharge opioid consumption is an important source of data in guiding appropriate opioid prescribing guidelines, but its collection is tedious and requires significant resources. Furthermore, the reliability of post-discharge opioid consumption surveys is unclear. Our group developed an automated short messaging service (SMS)-to-web survey for collecting this data from patients. In this study, we assessed its effectiveness in estimating opioid consumption by performing causal adjustment and comparison to a phone-based survey as reference.MethodsPatients who underwent surgical procedures at our institution from 2019-2020 were sent an SMS message with a link to a secure web survey to quantify opioids consumed after discharge. Several patient factors extracted from the EHR were tested for association with survey response. Following targeted learning (TL) nonresponse adjustment using these EHR-based factors, opioid consumption survey results were compared to a prior telephone-based survey at our institution as a reference.Results6,553 patients were included. Opioid consumption was measured in 2,883 (44%), including 1,342 (20.5%) through survey response. Characteristics associated with inability to measure opioid consumption included age, length of stay, race, tobacco use, and missing preoperative assessment. Among the top 10 procedures by volume, EHR-based TL nonresponse bias adjustment corrected the median opioid consumption reported by an average of 57%, and corrected the 75th percentile of reported consumption by an average of 11%. This brought median estimates for 6/10 procedures closer to telephone survey-based consumption estimates, and 75th percentile estimates for 3/10 procedures closer to telephone survey-based consumption estimates.ConclusionWe found that applying electronic health record (EHR)-based machine learning nonresponse bias adjustment is essential for debiased opioid consumption estimates from patient surveys. After adjustment, post-discharge surveys can generate reliable opioid consumption estimates. Clinical factors from the EHR combined with TL adjustment appropriately capture differences between responders and nonresponders and should be used prior to generalizing or applying opioid consumption estimates to patient care.

Funding Acknowledgements Type of funding sources: None. Background The apical variant of hypertrophic cardiomyopathy (ApHCM) has male predominance and is a relatively rare phenotype in Western population. Characteristics of female and black patients diagnosed with ApHCM are very limited in the existing literature. Purpose We aimed to investigate whether gender and race are associated with a different clinical presentation and CMR findings in apical HCM. Methods We retrospectively analysed 150 patients (113 males and 37 females) with a diagnosis of apical HCM who have been followed in our inherited cardiac conditions (ICC) clinic between 2010 and 2020. Only patients with a CMR study and apical hypertrophy defined as ≥ 13mm at the time of diagnosis were included. Demographics and clinical characteristics were obtained from electronic records. Volumetric CMR data were taken from confirmed reports while other parameters were measured by standard protocol. "Pure" ApHCM was defined as isolated apical hypertrophy and "mixed" with both apical and septal hypertrophy but with the apex thickest (1). Apical displacement of papillary muscles (PM) was defined when the base of PM originated from the apical one-third of the left ventricle (LV) in the apical 4- or 2-chamber views. Giant T-wave inversion was defined as T-wave inversion that is equal or greater than 10 mm (1 mV) in any electrocardiogram lead. Results Our study population included patients of White (55, 37%), Black (37, 25%), Asian (36, 24%) and Mixed/Others (22, 15%) ethnicity. Black patients were more likely to have a diagnosis of hypertension at presentation when compared to White (70% vs 40%, p = 0.01) and to Asian and Mixed/Other patients (70% vs 48%, p = 0.03). Similarly, they were more likely to have "mixed" ApHCM than White (49% vs 20%, p = 0.003) and Asian and Mixed/Other (49% vs 26%, p = 0.02) patients. Females were diagnosed at an older age (63 ± 12 vs 52 ± 14, p Conclusions In our cohort, females with ApHCM presented at an older age and were less likely to have giant T-wave inversion on ECG. Black patients with ApHCM were more likely to have hypertension and the "mixed" type of the disease.

Background Black men and women suffer from disparities in morbidity and mortality from hypertension, cardiovascular disease, and currently, COVID-19. These conditions are associated with social determinants of health and psychosocial stress. While previous trials demonstrated that stress reduction with meditation lowered BP in the grade I range in Black adults, there is a paucity of evidence for high normal and normal BP. Objective This randomized controlled trial was conducted to evaluate the effect of stress reduction with the Transcendental Meditation (TM) technique in Black adults with high normal BP and normal BP using international classifications. Methods A total of 304 Black men and women with high normal (130–139/85–89 mm Hg) and normal BP (120–129/80–84 mm Hg) were randomized to either TM or health education (HE) groups. BP was recorded at 3, 6, 9, 12, 24, 30 and 36 months after baseline. Linear mixed model analysis was conducted to compare the BP change between TM and HE participants in the high-normal BP and normal-BP groups. Survival analysis for hypertensive events was conducted. Results After an average of 19.9 ± 11.1 months follow-up, TM participants in the high-normal BP group showed significantly lower posttest SBP (-3.33 mm Hg, p = 0.045). There was no difference in DBP (-0.785 mm Hg, p = 0.367) compared to HE participants. In the normal BP group, the SBP and DBP were not different between the TM and HE participants. The hazard ratio for hypertensive events was 0.52 (p = 0.15) in the high normal BP group (7 TM vs 13 HE) with no difference in the normal BP group Conclusion This RCT found that meditation lowered systolic BP in Black men and women with high normal BP but not in normal BP participants. These results may be relevant to reducing health disparities in CVD and related co-morbidities.

Background Knowledge is needed about the risk of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens. Objective Evaluate the risk of cSCC in relation to medications used by SOTRs. Methods The cohort and nest case-control study included 3308 SOTRs and 65,883 persons without transplantation during 2009-2019. Incident cSCC was identified from pathology data, and medications were identified from pharmacy data. Adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards analysis, with voriconazole examined as a time-dependent variable. Results The annual incidence of cSCC was 1.69% in SOTRs and 0.30% in persons without transplantation. The adjusted hazard ratio of cSCC associated with lung transplant was 14.83 (95% CI, 9.85-22.33) for lung and 6.53-10.69 for other organs. Risk in Latinx persons was higher than in other non-White groups. Among lung recipients, the hazard ratio was 1.14 for each month of voriconazole use (95% CI, 1.04-1.26). Azathioprine use for ≥7 months, relating to mycophenolate mofetil intolerance, was associated with a 4.22-fold increased risk of cSCC (95% CI, 1.90-9.40). Belatacept and other immunsuppressive medications were not associated with risk. Limitation The number of events was somewhat small. Conclusions The knowledge of risks and benefits in diverse patients can translate to improvements in care.

Objective\ud The extant literature is inconsistent over whether manic symptoms in first‐episode psychosis (FEP) impact on its development and trajectory. This study addressed the following: (1) Does Duration of Untreated Illness (DUI) and Duration of Untreated Psychosis (DUP) differ between FEP patients with and without manic symptoms? (2) Do manic symptoms in FEP have an impact on time to remission over 1 year?\ud \ud Methods\ud We used data from the National EDEN study, a longitudinal cohort of patients with FEP accessing early intervention services (EIS) in England, which measured manic, positive and negative psychotic symptoms, depression and functioning at service entry and 1 year. Data from 913 patients with FEP (639 without manic symptoms, 237 with manic symptoms) were analysed using both general linear modelling and survival analysis.\ud \ud Results\ud Compared to FEP patients without manic symptoms, those with manic symptoms had a significantly longer DUI, though no difference in DUP. At baseline, people with manic symptoms had higher levels of positive and negative psychotic symptoms, depression and worse functioning. At 12 months, people with manic symptoms had significantly poorer functioning and more positive psychotic symptoms. The presence of manic symptoms delayed time to remission over 1 year. There was a 19% reduced rate of remission for people with manic symptoms compared to those without.\ud \ud Conclusions\ud Manic symptoms in FEP are associated with delays to treatment. This poorer trajectory persists over 1 year. They appear to be a vulnerable and under‐recognised group for poor outcome and need more focussed early intervention treatment.

Purpose/Objective(s) Adrenal metastases are commonly identified in the context of primary lung cancer. Recent literature has shown stereotactic body radiation therapy (SBRT) to improve progression free survival (PFS) in the setting of oligometastatic disease. Multiple studies have shown the efficacy and safety of adrenal SBRT. However, patient selection criteria are not well defined. We investigated the various patient selection criteria for adrenal SBRT and their associations with PFS. Materials/Methods We examined a cohort of patients with stage IV oligometastatic primary lung cancer with adrenal metastases who were consecutively treated with 5-fraction SBRT (n = 19). Multiple characteristics were selected for examination prior to data collection and PFS calculation. We considered 1) age 2) performance status 3) size greater than 4cm 4) presence of other metastases at adrenal metastasis diagnosis 5) presence of brain metastases at adrenal metastasis diagnosis 6) time to adrenal metastasis progression from primary diagnoses. Results Eighteen patients completed their treatments of 5-fraction adrenal SBRT with a median dose of 4500 cGy (range from 3500 cGy to 500 cGy). One patient had a course of SBRT to each adrenal gland. Completion rate was 100% and there was no grade two or higher acute toxicities. Small bowel 0.03cc max dose ranged from 230 cGy to 3410 cGy with a median dose of 2350 cGy. Median PFS was 4.7 months. PFS was the same for patients with and without brain metastases at adrenal progression (P = 0.133). There were also no significant differences found in PFS when observing patients with adrenal progression within one year and greater than one year of initial diagnosis (P = 0.474). Similarly, PFS did not change when comparing patients with adrenal lesions greater than 4cm to patients with adrenal lesion less than or equal to 4cm (P = 0.477). PFS trended towards significance for patients older than 70 compared to patients who were 70 or younger (6.6 months vs 12.4 months, P = 0.09). Additionally, PFS was significant for patients with ECOG 2 or higher compared to patients with ECOG less than 2 (1.4 months vs 11.5 months, P = 0.027). Patients without additional metastatic disease at the time of progression had better PFS than patients with additional metastatic disease (18 months vs 7 months, P = 0.016). Conclusion Patients with an ECOG score of 0 or 1 who did not have additional metastases at the time of adrenal metastasis exhibited a higher progression free survival rate after adrenal SBRT. Despite the small sample size, this study showed that appropriate patient selection for adrenal SBRT can lead to good long-term progression free survival with very minimal toxicity if any.

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.64, 0.81) and adequate calibration with intercept alpha of –0.014 (–0.34, 0.31) and slope beta of 0.85 (0.42, 1.27). Our model improved the net-benefit by 16% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 16 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact.

Introduction: The donor vigilance program is intended to collect and assess information on unexpected or undesirable effects or reactions resulting from blood donation. In this report, we discuss the analysis of the blood donor adverse reactions (DARs) reported in the National Blood Donor Vigilance Programme of India during the first 2 years of implementation. Materials and Methods: DAR reporting form prepared and approved by the National Executive Committee of the Haemovigilance Programme of India was used to capture the data by the blood centers and submitted to Donor-Vigil software prepared and hosted by the official website of the National Institute of Biologicals. Data reported for the years 2016 and 2017 were reviewed, analyzed, and validated by independent transfusion medicine experts. Results: During this period, a total of 19,98,101 donations denominator data were reported, in which 1,622,600 (80.9%) were valid. A total of 6091 DARs were reported, out of which 3980 (65.35%) were found valid. Only validated numerator and denominator data were included in the analysis. Generalized DARs were the most common type of DARs reported (83.7%), followed by “others” type (7.7%), localized (7.6%), allergic (0.4%), and complications related to apheresis (0.4%). The overall DAR rate was 2.45/1000 blood donations, which was higher in apheresis donations (3.07/1000) as compared to whole blood donations (2.39/1000). The DARs rates were higher in females (3.5/1000) compared to male donors (2.3/1000) and in the first time (2.5/1000) compared to repeat donors (2.15/1000). Conclusion: In this report, we concluded that younger age, first time, and female donors are more prone to DARs as compared to older age, repeat, and male donors. During the analysis of the data, we found some limitations, which can be improved by upgrading the reporting form and conducting regular continuing medical education (CMEs) of participant blood centers.

Introduction Coordination of care between primary care providers and dermatologists is important to ensure high quality and cost efficiency. In our integrated care setting, we used a retrospective cohort study to assess which patients self-refer to dermatology and which returned for a follow-up visit in dermatology. Methods We identified 107,832 patients with a new rash diagnosis who presented to primary care or dermatology between January and March 2017. We compared patients who self-referred to dermatology with those who used primary care, using multi-level generalized estimating equations with adjustment for patient-level covariables and medical center. We also characterized patients who returned for a follow-up visit in dermatology. Results Among patients with a new rash diagnosis, 99% were originally seen in primary care. Patients with a history of a dermatological condition were more likely to present to dermatology. Patients with a history of a dermatological condition or with psoriasis, pigment, hair, bullous, or multiple conditions were more likely to have a follow-up visit with a dermatologist. For each outcome, initial location of care and return for a follow-up visit, we found minimal clustering by medical center or provider. Conclusion One percent of patients with a new rash diagnosis self-refer to dermatology in this setting. Patients with a history of a dermatological condition were more likely to self-refer to dermatology and to have a follow-up visit with a dermatologist. Individual dermatologists and primary care providers had little impact on a patient's odds of returning for a follow-up visit.

Background: Primary Percutaneous Coronary Intervention (PCI) is the preferred treatment for patients presenting with ST-elevation myocardial infarction (STEMI). Despite multiple randomized clinical trials (RCT) best revascularization strategy (RS) in patients with STEMI and multivessel disease (MVD) remains unknown. We aimed to use network meta-analysis to compare currently used approaches. Methods: We searched for RCT comparing RSs in patients with MVD undergoing PCI for STEMI. We identified and compared RCT with arms evaluating at least two of the following approaches: culprit only revascularization (CoR), complete revascularization during initial intervention (CR) and staged procedure with culprit vessel revascularization followed by non culprit significant lesions intervention during the initial hospitalization. Our primary outcome was all-cause mortality. We combined direct and indirect data to perform a network meta-analysis. Results: A total of 7,779 patients from 13 RCT were included in this analysis (Fig. 1). Overall, this is an unbalanced network with only 1 arm comparing CR and SR. Complete revascularization during initial procedure was associated with a significant reduction in mortality with RR 0.47 (0.34; 0.65), p0.5 (Fig. 2). There was no evidence of a model inconsistency in an overall comparison, p>0.21. There was a design by treatment interaction in SR vs CoR comparison, p Conclusion: Complete revascularization during primary PCI in patients presenting with STEMI and MVD was associated with significant mortality reduction when compared to culprit only lesion revascularization. There may be design by treatment interaction limiting comparison of staged and culprit only strategies.

Bipolar disorder (BD) is a debilitating mood disorder marked by manic, hypomanic and/or mixed or depressive episodes. It affects approximately 1–2% of the population and is linked to high rates of suicide, functional impairment and poorer quality of life. Presently, treatment options for BD are limited. There is a strong evidence base for pharmacological (e.g., lithium) and psychological (e.g., psychoeducation) treatments; however, both of these pose challenges for treatment outcomes (e.g., non-response, side-effects, limited access). Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, is a recommended treatment for unipolar depression, but it is unclear whether rTMS is an effective, safe and well tolerated treatment in people with BD. This article reviews the extant literature on the use of rTMS to treat BD across different mood states. We found 34 studies in total ( N = 611 patients), with most assessing bipolar depression ( n = 26), versus bipolar mania ( n = 5), mixed state bipolar ( n = 2) or those not in a current affective episode ( n = 1). Across all studies, there appears to be a detectable signal of efficacy for rTMS treatment, as most studies report that rTMS treatment reduced bipolar symptoms. Importantly, within the randomised controlled trial (RCT) study designs, most reported that rTMS was not superior to sham in the treatment of bipolar depression. However, these RCTs are based on small samples ( NBD ⩽ 52). Reported side effects of rTMS in BD include headache, dizziness and sleep problems. Ten studies ( N = 14 patients) reported cases of affective switching; however, no clear pattern of potential risk factors for affective switching emerged. Future adequately powered, sham-controlled trials are needed to establish the ideal rTMS treatment parameters to help better determine the efficacy of rTMS for the treatment of BD.

Background There is evidence that repetitive transcranial magnetic stimulation (rTMS) is effective for treating adult depression. However, it remains unclear whether rTMS is an effective treatment for adolescent depression. This systematic review examines the existing literature on the effectiveness and acceptability of rTMS in the treatment of adolescent depression. Methods After protocol registration (PROSPERO), we searched PubMed, Embase, PsycINFO, WoS and CENTRAL databases and the grey literature. We included studies that used rTMS in adolescents aged 12–25 years old who had a clinical diagnosis of depression. Study quality was assessed using the Newcastle-Ottawa Scale. Results Fourteen studies were identified, which included 8 open-trial studies (N = 142 participants) and six studies which performed further post-hoc/follow-up analyses on these open-trial datasets. All studies suffered from multiple biases but reported that rTMS treatment reduced depression scores in adolescents. A single study on theta burst stimulation also found a positive effect. No study to date includes a sham control. Reported side effects of rTMS included scalp pain, headache and dizziness. Limitations Study methodologies precluded a meta-analysis. Conclusions The current literature signals that rTMS could reduce adolescent depressive symptoms. However, sham controlled randomized trials are needed. These findings suggest that rTMS may be a promising treatment option for adolescents with depression.

Background: A subset of encapsulated/circumscribed follicular variant of papillary thyroid carcinoma (FVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reduce overtreatment of a low-risk tumor. Study objectives were to describe the epidemiology and long-term outcomes of NIFTP in a high-volume, urban, tertiary referral center. Methods: Among patients enrolled in the Boston Medical Center (BMC) Thyroid Cancer Registry, 110 cases of FVPTC underwent index thyroid surgery at BMC between 2000 and 2016. Historically, BMC pathologists assess all malignant nodules using sections ≤0.3 cm with evaluation of the entire nodule and capsule. After review of pathology reports to identify potential NIFTPs, slides were rereviewed using criteria established by the NIFTP Working Group in 2016 and 2018. We evaluated interobserver reliability using Cohen's Kappa coefficient. Results: Among 110 FVPTCs, 15 (13%) met NIFTP criteria; 11 women and 4 men, age range 31–64 (mean 47.5) years. Mean tumor diameter was 1.7 cm (compared with 2.2 cm for FVPTC). Among NIFTP cases, there were no lymph node metastases, distant metastases, or tumor recurrences. All NIFTP cases were American Thyroid Association (ATA) low risk compared with only 68% of FVPTC (p = 0.011). Among FVPTCs, 14% had positive lymph nodes at index operation. Four patients (4%) had distant metastases. Mean follow-up time was 46 and 69 months for FVPTC and NIFTP, respectively. Among FVPTCs with an excellent response to therapy (2015 ATA guidelines), there were no recurrences. Just over half (n = 8) of patients with NIFTP received postoperative radioactive iodine (RAI) therapy. Concordance between pathologists was high for ruling out NIFTP (75%), but only 36% for ruling in NIFTP. Overall, for NIFTP designation, Cohen's Kappa was 0.39, which is considered fair. Conclusions: Although this is a relatively small cohort, all NIFTP specimens underwent updated pathology review consistent with current guidelines; mean follow-up was nearly 6 years. NIFTP represents a small fraction of the total papillary neoplasia diagnosed at this tertiary referral center (2.3%). None of the NIFTP cohort experienced an adverse oncologic event, and there were no regional or distant metastases. Over 50% of patients with NIFTP received RAI. Thus, the NIFTP reclassification may substantially reduce the number of patients who require adjuvant therapies, such as completion surgery or RAI.

Recognizing that current frameworks for classification and treatment in psychiatry are inadequate, particularly for use in young people and early intervention services, transdiagnostic clinical staging models have gained prominence. These models aim to identify where individuals lie along a continuum of illness, to improve treatment selection and to better understand patterns of illness continuity, discontinuity and aetiopathogenesis. All of these factors are particularly relevant to help-seeking and mental health needs experienced during the peak age range of onset, namely the adolescent and young adult developmental periods (i.e., ages 12-25 years). To date, progressive stages in transdiagnostic models have typically been defined by traditional symptom sets that distinguish "sub-threshold" from "threshold-level" disorders, even though both require clinical assessment and potential interventions. Here, we argue that staging models must go beyond illness progression to capture additional dimensions of illness extension as evidenced by emergence of mental or physical comorbidity/complexity or a marked change in a linked biological construct. To develop further consensus in this nascent field, we articulate principles and assumptions underpinning transdiagnostic clinical staging in youth mental health, how these models can be operationalized, and the implications of these arguments for research and development of new service systems. We then propose an agenda for the coming decade, including knowledge gaps, the need for multi-stakeholder input, and a collaborative international process for advancing both science and implementation.

Background: Appropriate use criteria recommend against unwarranted cardiac catheterization (caths) in low risk patients. Reporting of risk stratification on non-invasive cardiac stress test reports was implemented at our institution to reduce low risk cardiac cath referrals. Methods: We performed a retrospective study to compare the effect of introduction of risk stratification in cardiac stress test reports. The percentages of low risk patients by nuclear stress, who underwent cardiac cath, before and after application of risk stratification were compared. Chi-square and Mann-Whitney-Wilcoxon tests were used for analysis. Results: There were significantly fewer low risk referrals after risk stratification, 43.2% of patients of low-risk patients were referred for catheterization before, compared to 28.3% of low-risk patients after risk stratification (p value 0.01). There was reduction in the percentage of normal cardiac caths in the low risk category after introduction of risk stratification (61.5% vs 33.3%, p value 0.05). Conclusion: Risk stratification led to a decrease in the percentage of low-risk patients referred for cath following a stress test.

Objectives: Vitamin D is known to play an important role in bone mineral metabolism. Its deficiency may affect growth and status of bone markers in children. Hence, we undertook to study the status of bone markers in children with vitamin D deficiency (VDD) and impact of vitamin D3 supplementation on them. Materials and Methods: Total 468 out of 615 children and adolescents with VDD, who were given either of the three doses (600, 1000, and 2000) of vitamin D supplementation, were included in the study. These 468 children with pre- and postsupplementation preserved samples with available anthropometry, serum biochemistry, 25-hydroxy-vitamin D, and parathormone were evaluated for bone formation (procollagen type 1 amino-terminal propeptide [P1NP]) and resorption (β-cross laps [CTx]) markers. Results: The mean age and body mass index of these children were 11.3 ± 2.3 years (boys: 11.5 ± 2.4; girls: 12.2 ± 1.2 years; P = 0.03) and 18.1 ± 3.8 kg/m2 (boys: 18.2 ± 3.9; girls: 17.6 ± 3.2 kg/m2; P = 0.208), respectively. There were 8.8% subjects with severe, 42.7% with moderate, and 48.5% with mild VDD. There was a significant decline in serum P1NP (from 691 ± 233 ng/ml to 640 ± 259 ng/ml, P < 0.001) and CTx (from 1.67 ± 0.53 ng/ml to 1.39 ± 0.51 ng/ml, P < 0.001) following supplementation. Though decline in serum P1NP and CTx levels was observed in both boys and girls, among all three supplementation groups and VDD categories, the effect was more marked in serum CTx than P1NP levels. Conclusions: Vitamin D supplementation in VDD children resulted in decrease in both bone formation (P1NP) and resorption (CTx). The impact, however, was more marked on bone resorption than bone formation.