Objective: To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19.Design: An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.Setting: Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.Patients: Critically and noncritically ill patients.Interventions: Randomized to ivermectin or no ivermectin (control).Measurements and Main Results: The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors. Analyses used a Bayesian cumulative logistic model. Enrollment was closed for operational futility, following external evidence suggesting no benefit with ivermectin in nonhospitalized patients with COVID-19. Among 61 critically ill patients, the median number of organ support-free days was -1, indicating death was the most common vital outcome (interquartile range [IQR], -1 to 17), for the ivermectin group and -1 (IQR, -1 to 17.25) for the control group (adjusted proportional odds ratio [OR], 0.94; 95% credible interval [CrI], 0.40-2.07) and the posterior probability of superiority to control was 44.2%. Among 89 noncritically ill patients, the median number of organ support-free days was 22 (IQR, 18.5-22) for ivermectin and 22 (IQR, 16-22) for control (adjusted proportional OR, 1.04; 95% CrI, 0.48-2.34) and the posterior probability of superiority was 53.7%. Among critically ill patients, hospital survival was 35.1% (13/37) for ivermectin and 37.5% (9/24) for control (adjusted OR, 1.00; 95% CrI, 0.39-2.32), posterior probability of superiority was 50.0%. Among noncritically ill patients, hospital survival was 84.1% (37/44) for ivermectin and 77.8% (35/45) for control (adjusted OR, 1.16; 95% CrI, 0.5-3.07), posterior probability of superiority was 63.3%.Conclusions: For critically and noncritically ill hospitalized patients with COVID-19, ivermectin was unlikely to improve the primary composite outcome of organ support-free days and hospital survival.
Cardiac metastases are an uncommon clinical entity and are rarely associated with head and neck squamous cell carcinomas, particularly those originating in the buccal mucosa. We report a rare case of a 28-year-old male with previously treated buccal mucosa squamous cell carcinoma who presented with fatigue, dizziness and dyspnoea and was found to have complete atrioventricular block on electrocardiography, prompting further cardiac evaluation. Transthoracic echocardiography demonstrated multiple intracardiac masses with septal involvement, which were further characterised by computed tomography pulmonary angiography and high-resolution computed tomography of the chest, confirming extensive cardiac infiltration. Histopathological examination of metastatic cervical lymph nodes confirmed squamous cell carcinoma. Owing to persistent symptomatic complete atrioventricular block, the patient underwent single-chamber permanent pacemaker implantation following multidisciplinary discussion. This case highlights the importance of considering cardiac metastases in patients with advanced head and neck malignancies presenting with new-onset conduction abnormalities. A focussed review of the literature is also presented.
Objectives: The spectrum of metabolic disease, including obesity, prediabetes and Type 2 diabetes mellitus (T2DM), is increasing globally at an alarming rate. In addition to the vascular complications classically associated with diabetes, other ‘non-classical’ comorbidities like psychological distress, osteoporosis and sarcopenia are getting increasingly reported with diabetes. Hypogonadism in males has been reported to be associated with diabetes from the early 1990s. Around one-fourth of male subjects with diabetes mellitus were found to have decreased testosterone levels by several studies from both India and other countries. There is apparently a bidirectional link between T2DM and hypogonadism, with each contributing to and adversely affecting the other. This article briefly reviews the literature related to diabetes and hypogonadism, including the burden in an Indian setting, the pathophysiological link between the two, clinical evaluation and the evidence for and against testosterone replacement therapy. Methodology: Literature and information regarding this topic were collected from various original articles, review articles, systematic reviews and meta-analyses available on various platforms such as Google Scholar and PubMed. Results: The caveat here for clinicians is whether this low testosterone in a diabetic male who is more than 50 years old is due to late-onset hypogonadism (andropause) or is it a consequence per se due to diabetes. Physicians should remind themselves that a diabetic patient may also harbour other conditions directly leading to hypogonadism (like hypothalamo-pituitary lesions or primary testicular conditions). Thus, it is imperative that a thorough history and physical examination are mandatory in all diabetes suspected to have hypogonadism. Judicious use of relevant hormonal tests, including FSH, LH, testosterone and sex hormone binding globulin (SHBG), may be warranted to confirm hypogonadism. Conclusions: Appropriate referral to endocrine specialists for further endocrine evaluation of aetiology and management may be required in a subset of patients. In these patients with diabetes with a clear organic aetiology of hypogonadism, the latter is managed with testosterone replacement at age-appropriate doses. However, in the larger group of diabetes patients with functional hypogonadism with or without symptoms of androgen deficiency, testosterone replacement therapy is controversial. There are studies that show improvement in metabolic metrics of body composition, glucose, lipid and inflammatory parameters. However, the main concern of aggravating an underlying androgen-dependent occult malignancy (prostate), rise in haematocrit-related potential thrombotic tendencies, including cardio- and cerebrovascular events, is to be weighed against the potential benefits. Thus, the Endocrine Society guidelines currently recommend against testosterone treatment for improving the metabolic status (glucose levels, dyslipidaemia) alone in a diabetic patient. However, the Indian consensus (Integrated Diabetes and Endocrine Academy [IDEA] group) suggests individualising testosterone replacement after discussing it with the patient.
ABSTRACT 48XXXY is considered a variant of Klinefelter syndrome (47XXY) manifesting with different neuropsychiatric and phenotypic findings. It is quite rare with an incidence of 1 per 50,000 male births. This is a case of a 17-year-old boy referred to endocrinology for elevated plasma glucose levels with delayed milestones, facial dysmorphism, seizure disorder, and intellectual disability. Evaluation revealed hypergonadotropic hypogonadism with a karyotype of 48XXXY and early-onset type 2 diabetes mellitus. This is the fourth reported case of 48XXXY in India. This case report discusses distinctive clinical features of 48XXXY and also the need for its early recognition to create a multidisciplinary approach for optimal care.
Background: Global developmental delay can lead to long term impairment in academic performance, social interactions, and overall quality of life. Prevalence of global developmental delay ranges from 1-3%. Early identification and intervention of developmental delay limits disability and improves outcome. Methods: The aim of this cross-sectional study was assessment of developmental delay among children aged 0-3 years attending the well-baby clinic in Dr Kamakshi Memorial Hospital, a tertiary care pediatric centre in south Chennai using Trivandrum development screening chart (TDSC) (0-3 years) and Language evaluation scale Trivandrum (LEST) (0-3 years). We also aimed to describe the socio-demographic factors associated with developmental delay. Results: Developmental delay was defined as TDSC and/or LEST delay. 21 children out of 251 children had developmental delay i.e., TDSC and /or LEST delay. Prevalence of developmental delay in our study was 8.4%. 13 children (5.2%) had delay only in TDSC scale, 14 children (5.6%) had delay only using LEST scale and 6 children (2.4%) had delay in both TDSC and LEST. 7 children had only motor delay, 8 children had only language delay and 6 children had delay in both motor and language domains. IVF conception was found to have statistically significant association (p=0.002) with developmental delay. Conclusions: The prevalence of 8.4% developmental delay emphasizes need for early developmental screening programme as a routine clinical practice. Early recognition of developmental delay enables early intervention practices. It is recommended to use both TDSC and LEST scales for screening developmental delay in children.
