Beyond the Four Walls: The American College of Emergency Physicians 2022 New Practice Models Task Force Report.

Emergency physicians are highly trained to deliver acute unscheduled care. The emergency physician core skillset gained during emergency medicine residency can be applied to many other roles that benefit patients and extend and diversify emergency physician careers. In 2022, the American College of Emergency Physicians (ACEP) convened the New Practice Models Task Force to describe new care models and emergency physician opportunities outside the 4 walls of the emergency department. The Task Force consisted of 21 emergency physicians with broad experience and 2 ACEP staff. Fifty-nine emergency physician roles were identified (21 established clinical roles, 16 emerging clinical roles, 9 established nonclinical roles, and 13 emerging nonclinical roles). A strength-weakness-opportunity-threat (SWOT) analysis was performed for each role. Using the analysis, the Task Force made recommendations for guiding ACEP internal actions, advocacy, education, and research opportunities. Emphasis was placed on urgent care, rural medicine, telehealth/virtual care, mobile integrated health care, home-based services, emergency psychiatry, pain medicine, addiction medicine, and palliative care as roles with high or rising demand that draw on the emergency physician skillset. Advocacy recommendations focused on removing state and federal regulatory and legislative barriers to the expansion of new and emerging roles. Educational recommendations focused on aggregating available resources, developing a centralized resource for career guidance, and new educational content for emerging roles. The Task Force also recommended promoting research on potential advantages (eg, improved outcomes, lower cost) of emergency physicians in certain roles and new care models (eg, emergency physician remote supervision in rural settings).

Can Untrained Patients Perform Their Own Skin and Soft Tissue Ultrasound Examination by Teleguidance?

Objectives: This pilot study aims to determine if patients untrained in performing ultrasound can self-scan to obtain images under remote clinician teleguidance during a simulated telehealth encounter. This study also seeks to describe the patients' comfort level and barriers to performing an ultrasound examination on themselves using a handheld ultrasound device. Methods: This was a single center prospective observational cohort study conducted over a 4-month period in 2021. Patients were eligible if they had no prior training in the use of ultrasound and in the use of teleguidance. They voluntarily consented to participate at a single ambulatory internal medicine clinic. Results: 20 participants were enrolled and underwent teleguidance to ultrasound their own skin and soft tissues at the antecubital fossae. Six second video clips were evaluated by 2 subject matter experts using the Point of Care Ultrasound Image Quality scale. A score >7 was considered adequate for diagnostic interpretation. The average score was 10.15/14, with a minimum score of 5/14, and maximum score of 14/14 and a standard deviation (SD) of 2.39 using a two tailed Z-score. Setting alpha at 0.05 the 95% CI was (5.47-14.83). Conclusion: In a pilot study of 20 participants with no ultrasound experience, untrained healthy volunteers were able to perform technically acceptable and interpretable ultrasound scans using teleguidance by a trained clinician.

Applications, benefits and challenges of telehealth in India during COVID-19 pandemic and beyond: a systematic review.

BACKGROUND: India, the seventh-largest country in the world and the second-most populated faces enormous challenges when it comes to healthcare. The country's healthcare system was close to collapse due to the detrimental effects of the COVID-19 pandemic. Telehealth, which enables treating patients remotely, played a critical role during these challenging times. This systematic review investigates in detail the role of telehealth during COVID-19 and its application beyond the pandemic. METHODS: Database searches on PubMed, Scopus, Science Direct and Web of Science were carried out for studies published on telehealth, and articles were included if they focused on any audio or video telehealth consultation during the pandemic in India. Findings were synthesised into three main themes: applications, benefits and challenges of telehealth services. Methodological quality was assessed using JBI critical appraisal tools. RESULTS: The initial search on databases yielded 1143 articles. Of those, 19 met the eligibility criteria. Findings highlight the effective utilisation of telehealth across multiple medical specialities. Although insufficient technological infrastructure and other barriers due to the virtual consultation challenge the successful implementation of telehealth in India, it has the potential to bridge the rural-urban healthcare divide with cost-effective and easily accessible services. CONCLUSION: High patient/provider satisfaction underscores the need to integrate telehealth into routine healthcare practices in the country. However, the review urges the government and healthcare practitioners to address the telehealth challenges with prime importance to ensure quality healthcare throughout the nation even after the pandemic.

Variants in complement genes are uncommon in patients with anti-factor H autoantibody-associated atypical hemolytic uremic syndrome.

BACKGROUND: Coexisting genetic variants in patients with anti-factor H (FH)-associated atypical hemolytic uremic syndrome (aHUS) have implications for therapy. We estimated the prevalence of complement genetic variants in children with anti-FH aHUS from a prospective nationwide cohort and determined if significant genetic variants impact long-term kidney outcomes. METHODS: Of 436 patients in the database, 77 consecutive patients, 21 with a relapse and 9 with kidney failure and/or death were included. Targeted sequencing, using a 27-gene panel including CFH, CFI, CFB, C3, CD46, PLG, DGKE, and THBD and multiplex ligation-dependent probe amplification of CFH-CFHR region, was performed. The adverse outcome was eGFR < 30 ml/min/1.73 m2 or death. RESULTS: Patients had high anti-FH titers 5670 (2177-13,545) AU/ml, relapsing course (42.1%), and adverse outcomes (19.6%). Variants, chiefly of unknown significance, were found in 7 (6.5%; 95% CI 3.1-13.2%); a pathogenic variant was found in one patient. Homozygous deletion of CFHR1 was present in 91.6% compared to 9.8% in 184 healthy controls. Plasma exchanges and immunosuppression showed a trend of improving outcomes, independent of genetic defects (HR 0.32; P = 0.070). Meta-analysis of 18 studies (384 patients) showed that the pooled prevalence of pathogenic and likely pathogenic variants was 3% (95% CI 0-8%). Of 37 total variants in the meta-analysis, 7 (18.9%) each were pathogenic and likely pathogenic; others were variants of unknown significance. CONCLUSIONS: Significant variants in complement regulatory genes are rare in patients with anti-FH-associated aHUS. Irrespective of genetic defects, plasma exchanges and immunosuppression showed a statistical trend to improved outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Genotype-phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India.

Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies. We analysed a retrospective cohort of patients with dysferlinopathy from a single quaternary care centre in India. A total of 124 patients with dysferlinopathy were included (40 females). Median age at onset and duration of illness were 21 years (range, 13-50) and 48 months (range, 8-288), respectively. The average follow-up period was 60 months (range, 12-288). Fifty-one percent had LGMD pattern of weakness at onset; 23.4% each had Miyoshi and proximo-distal type while isolated hyperCKemia was noted in 1.6%. About 60% were born to consanguineous parents and 26.6% had family history of similar illness. Twenty-three patients (18.6%) lost ambulation at follow-up; the median time to loss of independent ambulation was 120 months (range, 72-264). Single-nucleotide variants (SNVs) constituted 78.2% of patients; INDELs 14.5% and 7.3% had both SNVs and INDELs. Earlier age at onset was noted with SNVs. There was no correlation between the other clinical parameters and ambulatory status with the genotype. Thirty-seven (45.7%) novel pathogenic/likely pathogenic (P/LP) variants were identified out of a total of 81 variations. The c.3191G > A variant was the most recurrent mutation. Our cohort constitutes a clinically and genetically heterogeneous group of dysferlinopathies. There is no significant correlation between the clinico-genetic profile and the ambulatory status.

Comparison of EPDS Scores Among Women with Good Neonatal Outcomes and Adverse Neonatal Outcomes.

A comparative, questionnaire-based study among postpartum patients was conducted using the Edinburgh Postpartum Depression Scale. 80 women who had good neonatal outcomes were compared with 80 women who had adverse neonatal outcomes. Demographic characteristics were similar between the groups. The average EPDS score in those with good neonatal outcomes was lesser than that of those with adverse neonatal outcome (10.07 vs11.04, p 0.045). Using the cut-off value of 9, the proportion of women who tested positive (higher chance of PPD) was statistically significantly higher (p value 0.0488) in adverse neonatal outcomes group (45% vs 28.75%). This result showed that women who have experienced stillbirth/ neonatal mortality or had neonates who needed NICU care have a higher propensity for PPD. This implies that women who have experienced stillbirth/neonatal mortality should be considered for prioritization in screening for PPD. PPD screening, even if not done routinely, should be done in this selected group (adverse perinatal outcomes group) on priority.

Pre-prosthetic Physiotherapy Rehabilitation in Post-operative Transtibial Amputation in a Patient With Congenital Talipes Equinovarus.

Amputation is more common in men than women, a lot of studies suggest this. It is the complete or partial removal of an extremity through a surgical process and is said to be a life-saving procedure performed in various critical conditions. The main objective of amputating a limb or any part at a level is that it should be carried out in a way that will give a stump of optimum length to facilitate the prosthetic fitting at later stages. After amputation, the patients are usually trained with prostheses so that they can carry on with functional activities without any restrictions. One of the disorders seen in infants and children is congenital talipes equinovarus (CTEV). It is characterized by plantarflexion at the ankle joint, inversion at the subtalar joint, and adduction at the forefoot. There are various factors and causes associated with CTEV. The treatment should be done as early as possible, if delayed, it can lead to deformities in the joint. Here is a case of a 12-year-old male, who, a neglected case of bilateral clubfoot, now underwent wedge tarsectomy surgery for the left foot and below knee amputation of the right leg due to the formation of infectious gangrene. Post-surgery, the patient was referred to the physiotherapy department for further treatment and rehabilitation.

Effectiveness of Early Physical Therapy Rehabilitation in Patient With Juvenile Rheumatoid Arthritis.

A diverse group of idiopathic inflammatory arthritis that affects children under the age of 16 and lasts six weeks or longer is known as juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA). It causes joint pain and morning stiffness, and the affected joints swell and become difficult to move. During flares, patients may experience flu-like symptoms such as muscle aches and fatigue. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of rheumatoid arthritis (RA) treatment. If necessary, immunosuppressive medications can be administered in stages. Nonsteroidal anti-inflammatory drugs (NSAIDs) are pain relievers for joints. Physical therapy treatment aims to reduce pain, improve joint range, correct movement patterns, strengthen weak structures, improve cardiovascular endurance, and improve patients' quality of life. We present a case of a 12-year-old boy who presented to the hospital with knee pain and an inability to walk without assistance after falling on the ground one month prior. Medical history revealed that the patient had juvenile rheumatoid arthritis, which was confirmed on investigations. The consultant physician referred the patient for pre-rehabilitation physiotherapy before corrective surgery.

Co-infections in Hospitalized COVID-19 Patients- A Prospective Observational Study.

INTRODUCTION: SARS -CoV-2 was first reported in Wuhan and declared a pandemic in March 2020. Co-infections during other pandemics have been associated with severe outcomes, but data are scarce regarding co-infections in COVID-19 patients. Our study evaluated co-infections prevalence and its impact on morbidity and mortality in hospitalized COVID -19 patients. METHODS: This prospective observational study included 100 patients admitted to a high-dependency unit at a tertiary care hospital in India. Prevalence of co-infections and clinical outcome-related data were analyzed in COVID-19 patients satisfying the inclusion criteria. RESULTS: 14% of patients had co-infections, out of which urinary tract infection was found in 9%. Patients with co-infections had a higher mortality rate (p<0.0004). Urinary co-infection emerged as an independent risk factor for mortality (p <0.001). CONCLUSION: Co-infections associated with COVID-19 infections are an essential risk factor for morbidity and mortality. Early identification and timely treatment of co-infections may help in improving clinical outcomes.

Effectiveness of Myofascial Release (MFR) vs. High-Frequency Transcutaneous Electrical Nerve Stimulation (TENS) for Pain Relief and Functional Improvement in College Students With Trapezius Myalgia.

The pain in the trapezius muscle is known as trapezius myalgia. The patient often complains of trapezius muscle soreness and tightness. Muscle soreness usually lasts for a few days, if not longer. This muscular rigidity and stiffness cause spasms in upper trapezius fibres, culminating in neck discomfort in the posterior side of the neck and shoulder area. This protocol was designed to describe the study to evaluate the effect of myofascial release (MFR) versus high-frequency transcutaneous electrical nerve stimulation (TENS) for pain relief and functional improvement in subjects with trapezius myalgia. Methods: Forty-five subjects with trapezius myalgia meeting inclusion criteria were selected for the study. Two groups were created, with group A undergoing MFR therapy and group B undergoing high-frequency TENS. The procedure was completed within four weeks. Regular assessments were carried out in the first week and fourth week of the rehabilitation. Throughout the recovery process, we evaluated pain, functional improvement, and range of motion of the neck at regular intervals. The outcome measures taken were the Numerical Pain Rating Scale (NPRS) and Neck Disability Index (NDI). Discussion: The intervention's efficacy was assessed by looking at pain alleviation using the outcome measures. The study's findings strongly supported the application of these approaches and modalities in the rehabilitation of myalgia patients.

RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice.

The receptor for advanced glycation endproducts (RAGE) is involved in multiple inflammatory processes. RAGE participates in adaptive and innate immune responses but its role in human immune cell responses has not been directly tested in vivo. We treated humanized mice (NSG) with the small molecule antagonist of RAGE, azeliragon, (AZ), and measured effects on xenogeneic (B6) skin graft rejection. AZ delayed the median time to xenograft rejection (22 vs 56 days, P = 0.0001). PD-1 expression on CD4+ and CD8+ T cells was lower following AZ therapy. Transcriptome studies showed inhibition of pathways in splenocytes with AZ including IL-23, IL-17A and IL-1ß signaling. The serum levels of IL-1ß and IL-17A in AZ treated mice were reduced in mice that did not reject skin grafts. The RAGE antagonist prevented xenograft rejection by human immune cells in a murine model. A RAGE antagonist may be a useful inhibitor of adaptive human immune responses.

A Review on Treatment Approaches for Chronic Low Back Pain via Mulligans Movement With Mobilization and Physical Therapy.

Low back pain is a leading cause of functional disability. Low back pain is a problem that every one of all age groups faces and there are various methods used to correct low back pain. Manual therapy is a specialized area in physiotherapy which manages neuromuscular pain. Manual therapy techniques include the Maitland mobilization technique, Kaltenborn mobilization technique, Mulligan technique, Active release technique, and many more. Manual therapy mainly works on arthrokinematics and osteokinematics of the joint. It is one of the main strategies used to manage low back pain. Low back pain can be because by spinal dysfunction, Sacroiliac dysfunction, muscle pathology, or any ligamentous strain. The cause of the low back pain should be identified and treated accordingly. Articles using keywords - chronic low back pain, Mulligan, and non-specific low back pain were searched on the database of Pubmed and Scopus a total of 30 articles from the timeframe of 2011 to 2021 were included in the study. From this review, we can conclude that Mulligan mobilization with movement is an effective way to reduce low back pain. Further studies need to be conducted to check the effectiveness of manual therapy techniques in chronic low back pain.

The Impact of Physical Therapy Rehabilitation on Pain and Function in a Patient With Cauda Equina Syndrome.

The human spine is a complex and robust structure. Injury to the spine may contribute to limitations in activities of daily living. In the lumbar and sacral regions, the nerve roots continue as the cauda equina. These nerves communicate with the lower limbs and pelvic organs by sending and receiving messages. Cauda equina syndrome is a rare but potentially life-threatening illness caused by spinal canal compression of the cauda equina. Cauda equina syndrome occurs when there is dysfunction of multiple lumbar and sacral nerve roots of the cauda equina. Here is a case of a 25-year-old male, who visited the hospital with complaints of low back pain, weakness in the bilateral lower limb and urinary incontinence. He had a history of a fracture at lumbar vertebrae 10 years ago for which internal fixation was done. The patient was diagnosed with cauda equina syndrome post investigations and underwent implant removal surgery. He was further referred to the physiotherapy department for management of the same.

Impact of Early Physiotherapy Rehabilitation for Pleural Empyema in a Geriatric Patient.

Empyema is the accumulation of pus in the pleural cavity which can be linked to lung abscesses, trauma, septicemia, or spinal osteomyelitis. It is usually caused by a lung infection that extends to the pleural space and causes pus to accumulate. Here, we present the case of a 70-year-old male who complained of dry cough for 15 days, breathlessness on walking for 20 days, right-sided chest and upper back pain, and high-grade fever for 15 days. On investigation, pleural empyema was diagnosed. He underwent a thoracoscopy to drain the fluid and an intercostal drainage tube was inserted. Along with medical management, physiotherapy was also required to help the patient to perform his daily activities with ease. A physiotherapy protocol was developed for the patient to improve his condition.

Determinants of COVID-19 Breakthrough Infections and Severity in ChAdOx1 nCoV-19-Vaccinated Priority Groups.

The current analysis is a part of an ongoing observational study that began in February 2021 in the Sir Sunder Lal Hospital (Varanasi, Uttar Pradesh) in northern India and is expected to continue until June 2022. This analysis aimed to delineate the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The study enrolled health-care workers and the elderly receiving the COVID-19 vaccine at one of three centers linked to the study hospital. The participants received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine based on the chimpanzee adenovirus platform (manufactured in India by the Serum Institute of India). The adenovirus codes for the spike (S) protein of SARS-CoV-2. Participants were contacted by phone at pre-decided intervals and questioned about the occurrence of COVID-19, clinical presentation, severity, and persistence of symptoms. A logistic regression analysis was performed to predict the risk factors of occurrence and severity of COVID-19. Of the 1,500 participants included in the analysis, 418 developed COVID-19 (27.9%). Fever was the most common symptom (72%), followed by cough (34%) and rhinitis (26%). Cardiovascular involvement was seen in more than 2% of individuals, and 11% had post-COVID-19 complaints. Regression analysis showed 1.6 times greater odds of contracting the disease in females and in those younger than 40 years, 1.4 times greater odds in individuals who were overweight, and 2.9 times greater odds in those receiving only one dose, compared with respective comparators. Individuals receiving two doses at a gap of ≤ 30 days had 6.7 times greater odds of infection than those receiving at a > 60-day interval. There was no association between COVID-19 occurrence in the vaccinees and pre-vaccination history of SARS-CoV-2 infection. Males were at a 3.6 times greater risk, and persons with preexisting lung disease-mainly asthma-had a 5.9 times greater risk of experiencing moderate to severe COVID-19 than comparators. While an extended interval between the two vaccine doses seems to be a better strategy, gender differences and an association of asthma phenotypes with COVID-19 need to be explored.

A Prospective Observational Study on BBV152 Coronavirus Vaccine Use in Adolescents and Comparison with Adults: Interim Results of the First Real-World Safety Analysis.

INTRODUCTION: The BBV152 coronavirus disease 2019 (COVID-19) vaccine (COVAXIN) has recently been approved for adolescents. OBJECTIVE: We provide the first real-world safety data of COVAXIN use in adolescents and compare with adults. METHODS: A prospective observational study was initiated in January 2022. Enrolled adolescents and adults were contacted by telephone after 14 days of receiving the BBV152 vaccine. The primary outcome was vaccine safety assessed as rate of adverse events following immunization (AEFIs). Severity grading of AEFIs was done using the Food and Drug Administration (FDA) scale. Interim results are presented. RESULTS: A total of 698 adolescents and 326 adults were enrolled. AEFIs after the first dose developed in 243 out of 670 adolescents (36.3%), with 21% reporting only local AEFIs and 15.2% reporting systemic AEFIs. Among 340 adolescents who had received the second dose of vaccine, 129 (37.9%) developed AEFIs, with only local involvement in 20.3% and systemic involvement in 17.6%. Injection site pain and fever were the common AEFIs. The majority of AEFIs were mild-moderate. Nearly 0.9% of adolescents receiving the first dose reported severe AEFIs. Atypical AEFIs were observed in 0.6-0.9% of adolescents. The majority of the AEFIs resolved in 1-2 days. AEFIs were persistent in > 2% of adolescents at day 14 after the second dose, and also in 3.7% of adults overall at follow-up. No difference was observed in AEFI incidence and patterns between adolescents and adults. Regression analysis showed females and those with a history of allergy to be, respectively, at 1.6 times and 3 times increased risk of AEFIs among adolescents. CONCLUSIONS: COVAXIN carries an overall favorable short-term safety profile in adolescents. The observed AEFI rates in adolescents are much lower than that reported with mRNA vaccines, but head-head comparisons in the same population are required to generate relative vaccine safety data. Female adolescents and those with a history of allergy need watchfulness for severe and persistent AEFIs. With some AEFIs persisting at 14 days, a longer follow-up is recommended to strengthen the safety data of COVAXIN.

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.

Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice.

Girls with obesity are at increased risk of early puberty. Obesity is associated with insulin resistance and hyperinsulinemia. We hypothesized that insulin plays a physiological role in pubertal transition, and super-imposed hyperinsulinemia due to childhood obesity promotes early initiation of puberty in girls. To isolate the effect of hyperinsulinemia from adiposity, we compared pre-pubertal and pubertal states in hyperinsulinemic, lean muscle (M)-insulin-like growth factor 1 receptor (IGF-1R)-lysine (K)-arginine (R) (MKR) mice to normoinsulinemic WT, with puberty onset defined by vaginal opening (VO). Our results show MKR had greater insulin resistance and higher insulin levels (P < 0.05) than WT despite lower body weight (P < 0.0001) and similar IGF-1 levels (P = NS). Serum luteinizing hormone (LH) levels were higher in hyperinsulinemic MKR (P = 0.005), and insulin stimulation induced an increase in LH levels in WT. VO was earlier in hyperinsulinemic MKR vs WT (P < 0.0001). When compared on the day of VO, kisspeptin expression was higher in hyperinsulinemic MKR vs WT (P < 0.05), and gonadotropin-releasing hormone and insulin receptor isoform expression was similar (P = NS). Despite accelerated VO, MKR had delayed, disordered ovarian follicle and mammary gland development. In conclusion, we found that hyperinsulinemia alone without adiposity triggers earlier puberty. In our study, hyperinsulinemia also promoted dyssynchrony between pubertal initiation and progression, urging future studies in girls with obesity to assess alterations in transition to adulthood.

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature.

INTRODUCTION: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. AIM: To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD METHODS: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. RESULTS: The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab. CONCLUSION: In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD.