Complicated Alcohol Withdrawal-An Unintended Consequence of COVID-19 Lockdown.

AIM: To assess the impact of COVID-19-related lockdown in India on alcohol-dependent persons. METHOD: We examined the change in the incidence of severe alcohol withdrawal syndrome presenting to hospitals in the city of Bangalore. RESULTS: A changepoint analysis of the time series data (between 01.01.20 to 11.04.20) showed an increase in the average number of cases from 4 to 8 per day (likelihood ratio test: χ2 = 72, df = 2, P < 0.001). CONCLUSION: An unintended consequence of the lockdown was serious illness in some patients with alcohol use disorders.

Reversible central adrenal insufficiency in survivors of COVID19: results from a 24-month longitudinal study.

OBJECTIVE: We studied the temporal course of hypothalamic-pituitary-adrenal (HPA) dysfunction in patients with corona-virus disease (COVID19). METHODS: Three-hundred and two patients (median age 54 years [IQR 42-64], 76% males) were recruited. HPA axis was evaluated by morning cortisol and adrenocorticotrophic hormone (ACTH) at admission (n=232). Adrenal insufficiency (AI) during acute illness was defined using a morning cortisol <83 nmol/L. AI at 12-months follow-up was defined using a peak cortisol <406 nmol/L in the ACTH-stimulation test (APST) (n=90). Those with AI at 12-months were further assessed by APST 6-monthly for recovery of hypoadrenalism. RESULTS: The median morning cortisol and ACTH during COVID19 were 295 (IQR 133-460) nmol/L and 3.9 (0.8-6.9) pmol/L, respectively. AI was present in 33 (14%) patients; ACTH was elevated in three, and low or inappropriately normal in the rest 30 patients. At 12-months, AI was seen in 13% (12/90) patients and hypothalamic-pituitary in origin in all; five (42%) of them had not met the diagnostic criteria for AI during COVID19. AI diagnosed at admission persisted at 12-months in seven patients and recovered in seven; the remaining 19 patients were lost to follow-up. The presence of AI at 12-months was independent of severity, and steroid use during COVID19. A morning cortisol <138 nmol/L during COVID19 predicted presence of AI at 12-months. All patients showed recovery of HPA axis in the ensuing 12-months. CONCLUSION: Central AI was common during acute COVID19 and at 12-months of follow-up. AI can be late-onset, developing after recovery from COVID19 and was transient in nature.

Novel Mutation in CYP2R1 Causing Vitamin D-Dependent Rickets Type 1b.

Monogenic forms of rickets are being increasingly recognized. However, vitamin D-dependent rickets 1b (VDDR1b) due to CYP2R1 gene mutation is exceedingly rare. We report a 4.5-year-old girl and her younger sibling who presented with clinical, radiological, and biochemical features suggestive of nutritional rickets that did not resolve despite repeated therapeutic doses of vitamin D3. This led to evaluation for resistant rickets, which revealed a novel homozygous CYP2R1 c.50_51insTCGGCGGCGC; p.Leu18ArgfsTer79 variant in the affected siblings. The children were treated with oral calcium and cholecalciferol, dose titrated to maintain serum alkaline phosphatase, 25 hydroxy vitamin D, and parathyroid hormone levels in the normal range, with good clinical and radiological response. This case highlights the importance of genetic evaluation in patients with suspected nutritional rickets who have a family history of similar illness and require higher than usual doses of vitamin D for healing or relapse on stopping treatment. To the best of our knowledge this is the first case of VDDR1b reported from Asia.

High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Relapse prevention.

Addiction and related disorders are chronic lapsing and relapsing disorders where the combination of long term pharmacological and psychosocial managements are the mainstay approaches of management. Among the psychosocial interventions, the Relapse Prevention (RP), cognitive-behavioural approach, is a strategy for reducing the likelihood and severity of relapse following the cessation or reduction of problematic behaviours. Here the assessment and management of both the intrapersonal and interpersonal determinants of relapse are undertaken. This article discusses the concepts of relapse prevention, relapse determinants and the specific interventional strategies.