CLINICAL PROFILE AND THE OUTCOME OF COVID-19 IN PATIENTS WITH HEMATOLOGICAL MALIGNANCY: A SINGLE CENTRE EXPERIENCE

Objective: In the present study, we are reporting the clinical profile; and outcomes of COVID-19 in patients with hematological malignancy at tertiary care hospitals. Methods: Data from laboratory-confirmed 40 COVID-19 patients diagnosed between January 1, 2021 and July 31, 2021, were analyzed retrospectively. All COVID-19 patients with hematological malignancy (n=40) were included in the study. Results: In the present study, a total of 40 patients were included. Of 40, 25 (62.5%) were males, and 15 (37.5%) were females. The median age in this study was 43 years (Range, 8–70). Of these 40 patients, acute myeloid leukemia was the most common malignancy 11 (27.5%), followed by acute lymphoblastic leukemia 9 (22.5%) than non-Hodgkin lymphoma 5 (12.5%), plasma cell dyscrasia 4 (10%), chronic myeloid leukemia 4 (10%), chronic lymphocytic leukemia 3 (7.5%), acute promyelocytic leukemia 2 (5%), chronic myelomonocytic leukemia 2 (5%). Mean hemoglobin was (8.04 g/dl), white blood cell count was (10.14×109/l), platelet count was (77.7×109/l) creatinine was (0.86 mg/dl), bilirubin was (1.24 mg/dl). The overall case-fatality rate was 8 (22.5%). Conclusion: Patients with hematological malignancy are immunocompromised, and our study reveals that there is an increased case fatality rate among these patients. Hence, physicians should be aggressive in the management of COVID‐19 patients with hematological malignancy

Bone marrow aspiration in haematological disorders: study at a tertiary care centre

Background: The bone marrow examination is an essential investigation for the diagnosis and management of many disorders of the blood and bone marrow. Bone marrow aspiration (BMA) alone is usually sufficient to diagnose nutritional anaemias, and most of the acute leukaemias. Aim was to study the spectrum of haematological disorders diagnosed on bone marrow aspiration.Methods: This study was conducted in the Department of Clinical Haematology in Sher e Kashmir Institute of Medical Sciences, Kashmir for a period of 2 years from December 2015 to December 2017. Bone marrow examination of 2131 cases of suspected hematological disorders was carried out. Bone marrow was aspirated from posterior superior iliac spine under local anaesthesia. Aspirates of dry tap were excluded from the study. Aspiration smears where stained with Leishmann stain for morphological examination.Results: A total of 2131 cases were included in this study. Male to female ratio in our study was 1.9:1. The age range of cases was from 1-80 years and the mean age was 47.3 years. Anemia was the most common haematological disorder in our study accounting for 25.6% of cases followed by acute leukaemia accounting for 22.3% and multiple myeloma (13.3%). Among anemias, megaloblastic anemia was most common followed by dual deficieny anemia. Among leukaemias, acute myeloid leukaemia (13.2%) was more common than acute lymphoblastic leukaemia (9.1%).Conclusions: Bone marrow aspiration cytology is a mildly invasive technique which can diagnose many hematological and non-hematologic diseases that can be confirmed by more advanced investigations viz. serological, biochemical or molecular. It is a highly informative test procedure performed for evaluating blood and blood related diseases in our environment

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Hereditary stomatocytosis: First case report from Valley of Kashmir

Stomatocytes are erythrocytes with a central slit or mouth-shaped (stoma) area of central pallor when examined on dried smears. In wet preparations, they are uniconcave rather than biconcave, giving them a bowllike appearance. In vitro, stomatocytes are produced by drugs that intercalate into the inner half of the lipid bilayer, thereby expanding the inner lipid surface area relative to that of the outer half of the bilayer. Hereditary stomatocytosis (also known as hereditary hydrocytosis, or overhydrated stomatocytosis) refers to a heterogeneous group of autosomal dominant hemolytic anemias caused by altered sodium permeability of the red cell membrane. We present the first case report of hereditary stomatocytosis in a 10-year-old male from the valley of Kashmir. Only eight families with this condition have been described worldwide

Dapsone as a cheap and safe second-line drug for chronic immune thrombocytopenia in developing countries: A prospective cohort study

Objective: The aim was to evaluate the efficacy and safety profile of dapsone as a cheap second-line treatment for chronic immune thrombocytopenia (ITP) in developing countries. Materials and Methods: A prospective study on 100 chronic ITP patients. These patients were put on dapsone after ruling out glucose 6 phosphate dehydrogenase deficiency and secondary causes of ITP. Results: The basic work up for secondary causes of ITP was negative. All these patients had been treated with steroids in the past. Anti-D had been given acutely in 20 patients, and intravenous immunoglobulin G had been given in 10 patients. Vincristine had been given to 20 of these patients. Dapsone was started in these patients, and 44% patients showed a response to treatment. The mean time to onset of response was 21 days. Out of these 44 patients, 21 (47.7%) went into remission and had platelet count >100,000/μl at 2 years post tapering of the treatment. Remaining 23 patients were kept on low dose dapsone and maintained their platelet counts. Adverse drug reactions included mild skin eruptions in 5% of patients, pruritus in 10% of patients, dose-related hemolysis in 1% of patients, methemoglobinemia in 1% of patients and Stevens Johnson syndrome in 1% of patients. 56 patients were nonresponders to the available, affordable conventional medical treatment and were referred to the surgical department for splenectomy, with a cure rate of 86% postsurgery. Conclusions: Dapsone is a safe, cheap and effective treatment option for patients with chronic ITP, who cannot afford the usual costlier second-line drugs

Melorheostosis with renal arterio-venous malformation: A case report with review of literature

Melorheostosis, also known as Leri′s disease and flowing periosteal hyperostosis, is a rare cause of pain and stiffness in a limb. The appearance is of "candle greasing" down one side of one or several bones of the body. We describe a case referred to tertiary care center with suspicion of renal cell carcinoma with diffuse bone metastasis. After reassessment, the patient was diagnosed melorheostosis with renal AV malformation. He was reassured about the benign nature of the disease and is asymptomatic

Data_Sheet_1_Seroprevalence of SARS-CoV-2-specific anti-spike IgM, IgG, and anti-nucleocapsid IgG antibodies during the second wave of the pandemic: A population-based cross-sectional survey across Kashmir, India.docx

BackgroundWithin Kashmir, which is one of the topographically distinct areas in the Himalayan belt of India, a total of 2,236 cumulative deaths occurred by the end of the second wave. We aimed to conduct this population-based study in the age group of 7 years and above to estimate the seropositivity and its attributes in Kashmir valley.MethodsWe conducted a community-based household-level cross-sectional study, with a multistage, population-stratified, probability-proportionate-to-size, cluster sampling method to select 400 participants from each of the 10 districts of Kashmir. We also selected a quota of healthcare workers, police personnel, and antenatal women from each of the districts. Households were selected from each cluster and all family members with age 7 years or more were invited to participate. Information was collected through a standardized questionnaire and entered into Epicollect 5 software. Trained healthcare personnel were assigned for collecting venous blood samples from each of the participants which were transferred and processed for immunological testing. Testing was done for the presence of SARS-CoV-2-specific anti-spike IgM, IgG antibodies, and anti-nucleocapsid IgG antibodies. Weighted seropositivity was estimated along with the adjustment done for the sensitivity and specificity of the test used.FindingsThe data were collected from a total of 4,229 participants from the general population within the 10 districts of Kashmir. Our results showed that 84.84% (95% CI 84.51–85.18%) of the participants were seropositive in the weighted imputed data among the general population. In multiple logistic regression, the variables significantly affecting the seroprevalence were the age group 45–59 years (odds ratio of 0.73; 95% CI 0.67–0.78), self-reported history of comorbidity (odds ratio of 1.47; 95% CI 1.33–1.61), and positive vaccination history (odds ratio of 0.85; 95% CI 0.79–0.90) for anti-nucleocapsid IgG antibodies. The entire assessed variables showed a significant role during multiple logistic regression analysis for affecting IgM anti-spike antibodies with an odds ratio of 1.45 (95% CI 1.32–1.57) for age more than 60 years, 1.21 (95% CI 1.15–1.27) for the female gender, 0.87 (95% CI 0.82–0.92) for urban residents, 0.86 (95% CI 0.76–0.92) for self-reported comorbidity, and an odds ratio of 1.16 (95% CI 1.08–1.24) for a positive history of vaccination. The estimated infection fatality ratio was 0.033% (95% CI: 0.034–0.032%) between 22 May and 31 July 2021 against the seropositivity for IgM antibodies.InterpretationDuring the second wave of the SARS-CoV-2 pandemic, 84.84% (95% CI 84.51–85.18%) of participants from this population-based cross-sectional sample were seropositive against SARS-CoV-2. Despite a comparatively lower number of cases reported and lower vaccination coverage in the region, our study found such high seropositivity across all age groups, which indicates the higher number of subclinical and less severe unnoticed caseload in the community.</p

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FindingsGlobal all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.InterpretationGlobal adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic