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).

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.

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.

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.

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.

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.

Next Generation Sequencing and Cytogenetic Based Evaluation of Indian Pierre Robin Sequence Families Reveals CNV Regions of Modest Effect and a Novel LOXL3 Mutation.

BACKGROUND: Pierre Robin Sequence (PRS) affects approximately 1 per 8500 to 14000 new-borns worldwide. Although the clinical entity is well defined, the pathogenesis of PRS is debated. The present study aims to understand the contribution of genomic imbalances and genetic variants in patients clinically diagnosed of PRS. METHODOLOGY: A total of 7 independent patients with nonsyndromic PRS thoroughly evaluated by a medical geneticist at a tertiary care hospital, were included in the study. Blood samples were collected from these patients and their family members. Array CGH was performed on all 7 patients and their respective family members for detection of underlying cytogenetic defects. Whole exome sequencing (WES) was performed for 5 families to capture single nucleotide variants or small indels. RESULTS: Cytogenetic analyses did not detect any previously reported gross chromosomal aberrations for PRS in the patient cohort. However, copy number variations (CNVs) of size <1 Mb were detected in patients which may have implications in PRS. The present study provided evidence for the occurrence of de novo deletions at 7p14.1 locus in PRS patients: further validating the candidate loci susceptibility in oral clefts. WES data identified LOXL3 as candidate gene, carrying novel deleterious variant, which is suggestive of the role of point mutations in the pathogenesis of PRS. CONCLUSION: The present study offered considerable insight into the contribution of cytogenetic defects and novel point mutation in the etiology of nonsyndromic PRS. Studies comprising large number of cases are required to fully elucidate the genetic mechanisms underlying the PRS phenotype.

National Estimates of Workplace Telehealth Use Among Emergency Nurses and All Registered Nurses in the United States.

INTRODUCTION: The goal of this research was to quantify the baseline status of prepandemic workplace emergency nursing telehealth as a key consideration for ongoing telehealth growth and sustainable emergency nursing care model planning. The purpose of this research was to: (1) generate national estimates of prepandemic workplace telehealth use among emergency and other inpatient hospital nurses and (2) map the geographic distribution of prepandemic workplace emergency nurse telehealth use by state of nurse residence. METHODS: We generated national estimates using data from the 2018 National Sample Survey of Registered Nurses. Data were analyzed using jack-knife estimation procedures coherent with the complex sampling design selected as representative of the population and requiring analysis with survey weights. RESULTS: Weighted estimates of the 161 865 emergency nurses, compared with 1 191 287 other inpatient nurses revealed more reported telehealth in the workplace setting (49% vs 34%) and individual clinical practice telehealth use (36% vs 15%) among emergency nurses. The geographic distribution of individual clinical practice emergency nurse telehealth use indicates greatest adoption per 10 000 state residents in Maine, Alaska, and Missouri with more states in the Midwest demonstrating emergency nurse adoption of telehealth into clinical practice per population than other regions in the United States. DISCUSSION: By quantifying prepandemic national telehealth use, the results provide corroborating evidence to the potential long-term adoptability and sustainability of telenursing in the emergency nursing specialty. The results also implicate the need to proactively define emergency nursing telehealth care model standards of practice, nurse competencies, and reimbursement.

A founder mutation in the GMPPB gene [c.1000G > A (p.Asp334Asn)] causes a mild form of limb-girdle muscular dystrophy/congenital myasthenic syndrome (LGMD/CMS) in South Indian patients.

Twelve patients from seven unrelated South Indian families with a limb-girdle muscular dystrophy-congenital myasthenic syndrome (LGMD/CMS) phenotype and recessive inheritance underwent deep clinical phenotyping, electrophysiological evaluation, muscle histopathology, and next-generation sequencing/Sanger sequencing-based identification of the genetic defect. Homozygosity mapping was performed using high-throughput genome-wide genotyping for mapping the mutation and to evaluate the founder effect. The age of disease onset among patients ranged from childhood to 40 years of age. The key clinical manifestations observed were progressive fatigable limb-girdle weakness, muscle hypertrophy/atrophy, and preferential weakness in a dystrophic pattern. The ages at last follow-up ranged from 30 to 64 years; nine were independently ambulant, two required assistance, and one was wheelchair-bound. Lower limb muscle MRI showed varying degrees of fat replacement in the glutei, hamstrings, anterior leg muscles, and medial gastrocnemius. All patients showed significant decrement on repetitive nerve stimulation (RNS). Muscle biopsy in 7 patients revealed varying degrees of dystrophic and neurogenic changes. Treatment with pyridostigmine and/or salbutamol resulted in variable improvement in 10 patients. Genetic analysis showed an identical homozygous GMPPB mutation c.1000G > A (p.Asp334Asn) in all affected patients. A region of homozygosity (6Mbp) was observed flanking the c.1000G > A change in carrier chromosomes. This study identifies c.1000G > A in GMPPB as a common founder mutation in an ethnic community of South Indian descent with milder yet variable degree of clinical presentation of GMPPB-associated LGMD-CMS.

An Indian child with Coats plus syndrome due to mutations in STN1.

The role of the CTC1-STN1-TEN1 (CST) complex in Coats plus syndrome (CP), as well as other telomeropathy-phenotypes and disorders of genome instability is well documented. We report an Indian child with a clinical diagnosis of CP who presented to us with retinal exudates, extensive cerebral calcification, developmental delay and severe anemia consequent upon chronic gastrointestinal (GI) bleeding. Whole exome sequencing revealed compound heterozygous variants in STN1 as the probable genetic cause leading to CP in the present case. Of the two variants, the nonsense variant c.397C>T (p.Arg133*) was a truncating variant leading to loss of full protein length whereas the second variant c.985G>C (p.Ala329Pro) was novel and neither reported in ExAC, 1KGP or gnomAD. The deleteriousness of the novel variant was explored through molecular dynamics simulation analysis where p.Ala329Pro mutation affected C-terminal domain interaction between STN1 and TEN1 complex. Hormonal therapy using ethinyl estradiol and norethisterone was apparently associated with a clinically useful, although poorly sustained, decrease in blood transfusion requirement in the proband.

Telehealth in the time of COVID-19.

Telehealth or using technology for a remote medical encounter has become an efficient solution for safe patient care during the severe acute respiratory syndrome coronavirus 2 or COVID-19 pandemic. This medium allows patient immediate healthcare access without the need for an in-person visit. We designed a time-sensitive, practical, effective and innovative scale-up of telehealth services as a response to the demand for COVID-19 evaluation and testing. As more patients made appointments through the institution's telehealth programme, we increased the number of clinicians available. JeffConnect, the acute care telehealth programme, was expanded to increase staffing from a standing staff of 37-187 doctors within 72 hours. Telehealth care clinicians primarily trained in emergency medicine, internal medicine and family medicine followed a patient decision pathway to risk stratify patients into three groups: home quarantine no testing, home quarantine with outpatient COVID-19 testing and referral for in-person evaluation in the ED, for symptomatic and potentially unstable patients.

Hospital Telehealth Adoption Increased in 2014 and 2015 and Was Influenced by Population, Hospital, and Policy Characteristics.

Background: Telehealth can increase value by reducing gaps in care, access, and cost for patients, providers, and payers. Medicare reimbursement policies aim to increase health access in areas with a provider shortage. Introduction: The influences of telehealth adoption over time are not well known, and would be beneficial for further policy discussion. Materials and Methods: Using the Information Technology Supplement to the American Hospital Association Annual Survey of Acute Care Hospitals, we determined several predictors of telehealth adoption in California hospitals from 2012 to 2015. Results: There were 870 hospitals evaluated. Telehealth adoption was more likely in 2014 and 2015. Compared with those not using telehealth, hospitals using telehealth were less likely to be located in more populated areas (odds ratio [OR] = 0.74; 95% confidence interval [CI]: 0.57-0.98), nonrural areas as defined by metropolitan statistical area (OR = 0.37; 95% CI: 0.20-0.70), and have a higher percentage of employed individuals (OR = 0.0001; 95% CI: 0.00-0.010). Hospitals were more likely to adopt telehealth if they had mobile device integration into the electronic health record (EHR) (OR = 2.97; 95% CI: 1.39-6.33) or a higher percentage of commuters in their ZIP code (OR = 20.24; 95% CI: 1.29-317.4). Telehealth reimbursement for health professional shortage areas did not contribute to increased telehealth adoption. Discussion: The findings suggest how addressing current infrastructural and policy barriers may improve value-based care. Conclusion: Our analysis suggests that telehealth has become more prominent since 2014, and factors such as significant commuting population, mobile device/EHR integration, and nonrural location influence adoption.

Whole exome and targeted gene sequencing to detect pathogenic recessive variants in early onset cerebellar ataxia.

Over 100 genetically distinct causal known loci for hereditary ataxia phenotype poses a challenge for diagnostic work-up for ataxia patients in a clinically relevant time and precision. In the present study using next-generation sequencing, we have investigated pathogenic variants in early-onset cerebellar ataxia cases using whole exome sequencing in singleton/family-designed and targeted gene-panel sequencing. A total of 98 index patients were clinically and genetically (whole exome sequencing (WES) in 16 patients and targeted gene panel of 41 ataxia causing genes in 82 patients) evaluated. Four families underwent WES in family based design. Overall, we have identified 24 variants comprising 20 pathogenic and four likely-pathogenic both rare/novel, variations in 21 early onset cerebellar ataxia patients. Among the identified variations, SACS (n = 7) and SETX (n = 6) were frequent, while ATM (n = 2), TTPA (n = 2) and other rare loci were observed. We have prioritized novel pathogenic variants in RARS2 and FA2H loci through family based design in two out of four families.

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population.

INTRODUCTION: Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. AIM: To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. METHODS: Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. RESULTS: Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High-titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1-13-positive cases (RR = 2.04; 95% CI 1.06-3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high-titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4-590 C/T allele (RR = 0.22; 95% CI 0.108-0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. CONCLUSION: The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross-sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.

A novel mutation in SLC39A14 causing hypermanganesemia associated with infantile onset dystonia.

BACKGROUND: Mutations in SLC39A14 cause a recessive disorder of manganese (Mn) metabolism that manifests as childhood onset progressive neurodegeneration characterized by parkinsonism and dystonia. METHODS: The present study genetically investigated a case of hypermanganesemia. We describe a family where an affected child with a history of progressive neurodegeneration showed symptoms of dystonia with increased levels of blood Mn and altered signal intensities in globus pallidus and dentate nucleus. Whole exome sequencing was conducted to genetically investigate the pathology in the child, which allowed us to identify a novel homozygous causal mutation in SLC39A14. RESULTS: Insilico modeling of the novel homozygous causal mutation in SLC39A14 predicted that it was deleterious, affecting Mn binding and transportation of metal by transmembrane instability of the protein structure. The clinical features of other reported mutations in SLC39A14 were also reviewed and the clinical spectrum in our case conforms to the described neurological abnormalities. CONCLUSIONS: We conclude that the mutation identified in SLC39A14 in our case is a novel variation linked to recessive disorders of hypermaganesemia and dystonia.

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.