Linezolid-induced lactic acidosis.

Linezolid is a commonly prescribed antibiotic in clinical practice. Although thrombocytopenia and peripheral neuropathy are frequently encountered following prolonged administration of linezolid, lactic acidosis is a rare adverse drug reaction. We present the case of a patient on linezolid for disseminated multidrug-resistant tuberculosis who presented with vomiting, dyspnoea, hypotension and high anion gap metabolic acidosis. The initial presentation mimicked sepsis syndrome. Ketoacidosis and renal dysfunction were ruled out. There was no history of ingestion of toxins/toxic alcohols. Sepsis was unlikely because extensive radiological and microbiological testing could not identify an infection. Given the possibility of linezolid-induced lactic acidosis (LILA), linezolid was discontinued on admission. The patient's lactic acidosis resolved, and his overall condition improved. A retrospective diagnosis of LILA was thus established. LILA should be considered when patients on linezolid present with lactic acidosis and other causes for the lactic acidosis have been ruled out.

Factors associated with stigma and manifestations experienced by Indian health care workers involved in COVID-19 management in India: A qualitative study.

Healthcare personnel who deal with COVID-19 experience stigma. There is a lack of national-level representative qualitative data to study COVID-19-related stigma among healthcare workers in India. The present study explores factors associated with stigma and manifestations experienced by Indian healthcare workers involved in COVID-19 management. We conducted in-depth interviews across 10 centres in India, which were analysed using NVivo software version 12. Thematic and sentiment analysis was performed to gain deep insights into the complex phenomenon by categorising the qualitative data into meaningful and related categories. Healthcare workers (HCW) usually addressed the stigma they encountered when doing their COVID duties under the superordinate theme of stigma. Among them, 77.42% said they had been stigmatised in some way. Analyses revealed seven interrelated themes surrounding stigma among healthcare workers. It can be seen that the majority of the stigma and coping sentiments fall into the mixed category, followed by the negative sentiment category. This study contributes to our understanding of stigma and discrimination in low- and middle-income settings. Our data show that the emergence of fear of the virus has quickly turned into a stigma against healthcare workers.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Background: Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Materials and methods: Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. Results: A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Conclusion: Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. How to cite this article: Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Efficacy of recurrent transcutaneous magnetic stimulation in the treatment of diabetic peripheral neuropathy: Multicenter randomized trial.

AIMS: Transcutaneous magnetic stimulation (TCMS) is successful in decreasing pain in several neurologic conditions. This multicenter parallel double-blind phase II clinical trial is a follow-up to a pilot study that demonstrated pain relief in patients with diabetic peripheral neuropathy (DPN) treated with TCMS. METHODS: Thirty-four participants with confirmed DPN and baseline pain score ≥ 5 were randomized to treatment at two sites. Participants were treated with either TCMS (n = 18) or sham (n = 16) applied to each foot once a week for four weeks. Pain scores using the Numeric Pain Rating Scale after 10 steps on a hard floor surface and answers to Patient-Reported Outcomes Measurement Information System pain questions were recorded by participants daily for 28 days. RESULTS: Thirty-one participants completed the study and were analyzed. Average pain scores decreased from baseline in both the groups. The difference in pain scores between TCMS and sham treatments was -0.55 for morning, -0.13 for evening, and -0.34 overall, below the pre-determined clinically relevant difference of -2. Moderate adverse events that resolved spontaneously were experienced in both treatment arms. CONCLUSION: In this two-arm trial, TCMS failed to demonstrate a significant benefit over sham in patient reported pain suggesting a substantial placebo effect in our previous pilot study. TRIAL REGISTRATION: TCMS for the Treatment of Foot Pain Caused By Diabetic Neuropathy, https://clinicaltrials.gov/ct2/show/NCT03596203, ID-NCT03596203.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.

Evaluation of a Hospitalized Pediatric COVID-19 Cohort from Indian National Clinical Registry of COVID-19.

OBJECTIVE: To evaluate the factors associated with mortality of a multicentric cohort of hospitalized COVID-19 patients, 0-18 y old, from 42 centers across India. METHODS: The National Clinical Registry for COVID-19 (NCRC) is an on-going prospective data collection platform enrolling COVID-19 patients diagnosed by real-time PCR or rapid antigen test. The data are collected in prestructured e-capture forms. The sociodemographic, clinical, laboratory, and hospital outcome data from 1st September 2020 to 20th February 2022 were analyzed. RESULTS: Of the 1244 enrolled hospitalized COVID-19 patients aged 0-18 y, 98 and 124 were infants and neonates, respectively. Only 68.6% children were symptomatic at admission, with fever being the most common symptom. Diarrhea, rash, and neurological symptoms were also noted. At least 1 comorbidity was present in 260 (21%) children. The in-hospital mortality rate was 6.2% (n = 67), the highest in infants (12.5%). Altered sensorium (aOR: 6.8, CI: 1.9, 24.6), WHO ordinal scale ≥ 4 at admission (aOR: 19.6, CI: 8.0, 47.8), and malignancy (aOR: 8.9, 95% CI: 2.4, 32.3) were associated with higher odds of death. Malnutrition did not affect the outcome. Mortality rates were similar across the three waves of the pandemic, though a significant shift towards the under-five group was observed in the third wave. CONCLUSION: This multicentric cohort of admitted Indian children showed that the COVID-19 was milder in children than adults, and the pattern was consistent across all waves of the pandemic.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

Development of the India COVID-19 vaccine tracker.

COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Since then, efforts were initiated to develop safe and effective vaccines. Till date, 11 vaccines have been included in the WHO's emergency use list. The emergence and spread of variant strains of SARS-CoV-2 has altered the disease transmission dynamics, thus creating a need for continuously monitoring the real-world effectiveness of various vaccines and assessing their overall impact on disease control. To achieve this goal, the Indian Council of Medical Research (ICMR) along with the Ministry of Health and Family Welfare, Government of India, took the lead to develop the India COVID-19 Vaccination Tracker by synergizing three different public health databases: National COVID-19 testing database, CoWIN vaccination database and the COVID-19 India portal. A Vaccine Data Analytics Committee (VDAC) was constituted to advise on various modalities of the proposed tracker. The VDAC reviewed the data related to COVID-19 testing, vaccination and patient outcomes available in the three databases and selected relevant data points for inclusion in the tracker, following which databases were integrated, using common identifiers, wherever feasible. Multiple data filters were applied to retrieve information of all individuals ≥18 yr who died after the acquisition of COVID-19 infection with or without vaccination, irrespective of the time between vaccination and test positivity. Vaccine effectiveness (VE) against the reduction of mortality and hospitalizations was initially assessed. As compared to the hospitalization data, mortality reporting was found to be much better in terms of correctness and completeness. Therefore, hospitalization data were not considered for analysis and presentation in the vaccine tracker. The vaccine tracker thus depicts VE against mortality, calculated by a cohort approach using person-time analysis. Incidence of COVID-19 deaths among one- and two-dose vaccine recipients was compared with that among unvaccinated groups, to estimate the rate ratios (RRs). VE was estimated as 96.6 and 97.5 per cent, with one and two doses of the vaccines, respectively, during the period of reporting. The India COVID-19 Vaccination Tracker was officially launched on September 9, 2021. The high VE against mortality, as demonstrated by the tracker, has helped aid in allaying vaccine hesitancy, augmenting and maintaining the momentum of India's COVID-19 vaccination drive.

Psychosocial impact of COVID-19 pandemic on healthcare workers in India & their perceptions on the way forward - A qualitative study.

Background & objectives: The healthcare system across the world has been overburdened due to the COVID-19 pandemic impacting healthcare workers (HCWs) in different ways. The present study provides an insight into the psychosocial challenges faced by the HCWs related to their work, family and personal well-being and the associated stigmas. Additionally, the coping mechanisms adopted by them and their perceptions on the interventions to address these challenges were also explored. Methods: A qualitative study was conducted between September and December 2020 through in-depth telephonic interviews using an interview guide among 111 HCWs who were involved in COVID-19 management across 10 States in India. Results: HCWs report major changes in work-life environment that included excessive workload with erratic timings accentuated with the extended duration of inconvenient personal protection equipment usage, periods of quarantine and long durations of separation from family. Family-related issues were manifold; the main challenge being separated from family, the challenge of caregiving, especially for females with infants and children, and fears around infecting family. Stigma from the community and peers fuelled by the fear of infection was manifested through avoidance and rejection. Coping strategies included peer, family support and the positive experiences manifested as appreciation and recognition for their contribution during the pandemic. Interpretation & conclusions: The study demonstrates the psychological burden of HCWs engaged with COVID-19 care services. The study findings point to need-based psychosocial interventions at the organizational, societal and individual levels. This includes a conducive working environment involving periodic evaluation of the HCW problems, rotation of workforce by engaging more staff, debunking of false information, community and HCW involvement in COVID sensitization to allay fears and prevent stigma associated with COVID-19 infection/transmission and finally need-based psychological support for them and their families.

Clinical profile of hospitalized COVID-19 patients in first & second wave of the pandemic: Insights from an Indian registry based observational study.

Background & objectives: India witnessed a massive second surge of COVID-19 cases since March 2021 after a period of decline from September 2020. Data collected under the National Clinical Registry for COVID-19 (NCRC) were analysed to describe the differences in demographic and clinical features of COVID-19 patients recruited during these two successive waves. Methods: The NCRC, launched in September 2020, is an ongoing multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized, confirmed COVID-19 patients were captured in an electronic data portal from 41 hospitals across India. Patients enrolled during September 1, 2020 to January 31, 2021 and February 1 to May 11, 2021 constituted participants of the two successive waves, respectively. Results: As on May 11, 2021, 18961 individuals were recruited in the registry, 12059 and 6903 reflecting in-patients from the first and second waves, respectively. Mean age of the patients was significantly lower in the second wave [48.7 (18.1) yr vs. 50.7 (18.0) yr, P<0.001] with higher proportion of patients in the younger age group intervals of <20, and 20-39 yr. Approximately 70 per cent of the admitted patients were ≥ 40 yr of age in both waves of the pandemic. The proportion of males were slightly lower in second wave as compared to the first [4400 (63.7%) vs. 7886 (65.4%), P=0.02]. Commonest presenting symptom was fever in both waves. In the second wave, a significantly higher proportion [2625 (48.6%) vs. 4420 (42.8%), P<0.003] complained of shortness of breath, developed ARDS [422(13%) vs. 880 (7.9%), P<0.001], required supplemental oxygen [1637 (50.3%) vs. 4771 (42.7%), P<0.001], and mechanical ventilation [260 (15.9%) vs. 530 (11.1%), P<0.001]. Mortality also significantly increased in the second wave [OR: 1.35 (95% CI: 1.19, 1.52)] in all age groups except in <20 yr. Interpretation & conclusions: The second wave of COVID-19 in India was slightly different in presentation than the first wave, with a younger demography, lesser comorbidities, and presentation with breathlessness in greater frequency.

A Systematic Review and Meta-analysis of Prevalence of Epilepsy, Dementia, Headache, and Parkinson Disease in India.

BACKGROUND: There are wide variations reported in the prevalence rates of common neurological disorders in India leading to huge treatment gap. There is no comprehensive systematic review reporting prevalence of common neurological conditions affecting Indians which is essential for developing and aligning health services to meet patient care. OBJECTIVES: The aim of this study was to perform a systematic review and meta-analysis of prevalence of epilepsy, dementia, headache, and Parkinson's disease (PD) in India from 1980 to 2019. METHODS AND MATERIALS: We performed a bibliographic systematic search in PubMed and Google Scholar along with manual search for peer-reviewed cross-sectional studies and community-based surveys reporting prevalence of epilepsy, dementia, headache, and PD in India from January 1980 to July 2019. Meta-analysis was performed adopting a random-effects model using "Metafor" package in R. RESULTS: The systematic review and meta-analysis included 50 studies [epilepsy (n = 22), dementia (n = 19), headache (n = 6), and PD (n = 3)] including a total of 179,1541 participants of which 5,890 were diagnosed with epilepsy, 1,843 with dementia, 914 with headache, and 121 were diagnosed with PD. The pooled prevalence of epilepsy was 4.7 per 1,000 population (95% CI: 3.8-5.6) with high heterogeneity (P < 0.01, I2 = 98%). The prevalence of dementia was found to be 33.7 per 1,000 population (95% CI: 19.4-49.8) (P = 0, I2 = 100%). The pooled prevalence of headache and PD were found to be 438.8 per 1,000 population (95% CI: 287.6-602.3) (P < 0.0001, I2 = 97.99%), and 0.8 per 1,000 population (95%CI: 0.4-1.3) (P < 0.01, I2 = 95%), respectively. CONCLUSIONS: The findings could be used for appropriate policy measures and targeted treatments for addressing these conditions.

Comparative Ca2+ channel contributions to intracellular Ca2+ levels in the circadian clock.

Circadian rhythms in mammals are coordinated by the central clock in the brain, located in the suprachiasmatic nucleus (SCN). Multiple molecular and cellular signals display a circadian variation within SCN neurons, including intracellular Ca2+, but the mechanisms are not definitively established. SCN cytosolic Ca2+ levels exhibit a peak during the day, when both action potential firing and Ca2+ channel activity are increased, and are decreased at night, correlating with a reduction in firing rate. In this study, we employ a single-color fluorescence anisotropy reporter (FLARE), Venus FLARE-Cameleon, and polarization inverted selective-plane illumination microscopy to measure rhythmic changes in cytosolic Ca2+ in SCN neurons. Using this technique, the Ca2+ channel subtypes contributing to intracellular Ca2+ at the peak and trough of the circadian cycle were assessed using a pharmacological approach with Ca2+ channel inhibitors. Peak (218 ± 16 nM) and trough (172 ± 13 nM) Ca2+ levels were quantified, indicating a 1.3-fold circadian variance in Ca2+ concentration. Inhibition of ryanodine-receptor-mediated Ca2+ release produced a larger relative decrease in cytosolic Ca2+ at both time points compared to voltage-gated Ca2+channels. These results support the hypothesis that circadian Ca2+ rhythms in SCN neurons are predominantly driven by intracellular Ca2+ channels, although not exclusively so. The study provides a foundation for future experiments to probe Ca2+ signaling in a dynamic biological context using FLAREs.

Knowledge, attitude, and practices of medical clinicians regarding food allergy and anaphylaxis in Hyderabad, India.

BACKGROUND: Food allergy (FA) is a chronic condition of emerging global concern. Surveys have been conducted in numerous countries to assess physician knowledge, attitude, and practices (KAP) pertaining to FA and anaphylaxis, and substantial deficits in their KAP were identified. OBJECTIVE: To assess the KAP of medical clinicians in Hyderabad, India, with respect to FA and anaphylaxis. METHODS: A regionally representative sample of 570 physicians including 113 general practitioners, 123 pediatricians, 110 pulmonologists, 113 dermatologists, and 111 gastroenterologists were recruited from all major institutions in Hyderabad, India. A validated questionnaire was used to assess their KAP. RESULTS: Overall, 90% of questions were correctly answered and differences emerged with respect to specific items, namely the following: (1) the lateral thigh being the preferred location for epinephrine administration (P = .001); (2) a positive skin prick test or radioallergosorbent test is sufficient for FA diagnosis (P = .04); and (3) the appropriate epinephrine dose for a 27-kg child (P = .006). Approximately 95% of the participants in each group were confident in their ability to care for patients with FA, yet 91% desired additional periodic FA training sessions. CONCLUSION: Survey findings suggest that although FA knowledge among South Indian clinicians seems high across all major specialties who care for patients with FA, there are differences in the level of knowledge among them, which in turn reflects the differences in attitude and approach toward their patients. These FA care providers still desire to further participate in continuing medical education efforts in the field of food allergy. Efforts to provide periodic training and education for all FA clinical care providers remain vital in South India.

Secondary Subcutaneous Rhizopus Infection in a Posttransplant Recipient with Calcific Uremic Arteriolopathy.

Calcific uremic arteriolopathy is a rare condition affecting chronic kidney disease (CKD) patients on long-term dialysis. The clinical manifestations include subcutaneous skin necrosis and ulcers secondary to calcification of the subcutaneous blood vessels. The necrotic tissue often becomes a nidus of infection. The prognosis is often poor. We present a case of a renal allograft recipient who developed a subcutaneous necrotic lesion which was subsequently infected by Rhizopus spp. The patient underwent surgical debridement and antifungal therapy. The infection resolved completely. Our case represents agrave underlying condition predisposing a rare and serious posttransplant infection. The outcome was favourable because of early identification and treatment of the infection.

Not always a commensal: A case of mastitis by Corynebacterium amycolatum.

Gram positive rods seen on Gram's stain are often dismissed as skin commensal organisms. Diphtheroids (Non-diphtherial Corynebacterium species), as they are collectively called, are taken as harmless bystanders in a skin and soft tissue infection (SSTI). However, emerging evidence has established virulence factors in some of these species leading to various infections. Here, we describe a case of mastitis in a 43 year old female caused by Corynebacterium amycolatum. The organism was seen as thick Gram positive rods on Gram stain and was isolated as a pure growth on Blood agar. Identification was done on Vitek-2 and confirmed by matrix assisted laser desorption-ionization - Time-offlight (MALDI-TOF). Patient was managed successfully with surgical excision and antibiotics.

Homotransfer of FRET Reporters for Live Cell Imaging.

Förster resonance energy transfer (FRET) between fluorophores of the same species was recognized in the early to mid-1900s, well before modern heterotransfer applications. Recently, homotransfer FRET principles have re-emerged in biosensors that incorporate genetically encoded fluorescent proteins. Homotransfer offers distinct advantages over the standard heterotransfer FRET method, some of which are related to the use of fluorescence polarization microscopy to quantify FRET between two fluorophores of identical color. These include enhanced signal-to-noise, greater compatibility with other optical sensors and modulators, and new design strategies based upon the clustering or dimerization of singly-labeled sensors. Here, we discuss the theoretical basis for measuring homotransfer using polarization microscopy, procedures for data collection and processing, and we review the existing genetically-encoded homotransfer biosensors.