Clinical profile and prognostic factors of leptospirosis: a study of 50 cases from North Kerala, India

Background: Leptospirosis is the most common zoonosis in the world. In humans it is caused by leptospira interrogans group of organism. It is an emerging disease in various part of the Kerala since 1980 and frequent epidemic with high mortality is being reported. Severe leptospirosis is characterized by jaundice, renal dysfunction, and hemorrhagic manifestation and with high mortality. Studies on assessing the prognostic factors in leptospirosis is only few from this area. This study was conducted to assess the clinical profile and prognostic factors of icteric leptospirosis.Methods: This is a prospective study conducted at academy of medical sciences Pariyaram involving 50 cases from the medical intensive care unit and wards with clinical features of leptospirosis and confirmed by the ELISA. All the patients were investigated and assessed for the complications and out come.Results: 50 cases of clinically and serologically confirmed cases of leptospirosis were included in this study of which 39 (78%) were males and 11(22)% were females. Among males maximum cases were reported in 40 to 44 age group and that females 30-34 age group. Of the 50 cases 7 patients expired and most common cause of mortality among this were acute respiratory distress syndrome (90%). Five patients had residual renal failure at the time of discharge.Conclusions: Leptospirosis was a common cause of hepatorenal failure in this area and important cause of mortality among agriculture workers during monsoon and post monsoon period. Acute respiratorydistress syndrome, and renal failure was the most common cause of mortality. Out of the 50 patients studied, 36 patient got cured and severn patient died and and five patients got discharged with residual renal and hepatic dysfunction. The mortality rate was 14% higher than noticed in other studies. patient who had early dialysis, plasma transfusion had a better prognosis.

Observational study on pharmacoinvasive strategy and primary angioplasty in a tertiary care centre in acute myocardial infarction patients

AIMS AND OBJECTIVE : To compare the efficacy of Pharmacoinvasive therapy and Primary Angioplasty in STEMI patients. The objective was to to study whether the incidence of composite end points (mortality, cardiogenic shock and re-myocardial infarction) in Pharmacoinvasive strategy is non inferior to Primary Angioplasty in patients with STEMI. BACKGROUND : In STEMI patients the treatment of choice is primary PCI. (ACC/AHA Class IA recommendation). But in real world situations, timely PCI remains a challenge especially in developing countries like India where the number of centres performing PCI are few. Timely transfer to such centres also remains a huge challenge considering the dearth of emergency ambulance services and the state of our road infrastructure. Pharmacoinvasive strategy refers to routine angiography with a view to revascularize the infarct related vessel 3-24 hours after fibrinolysis. ACC/AHA has given a classIIa recommendation, while European society of Cardiology has given a class I recommendation for this strategy. We will look whether pharmacoinvasive strategy is non inferior to primary PCI (as proved in various trials) in a setting like ours where streptokinase is used as a fibrinolytic agent as compared to the western countries where these trials were conducted using tenecteplase as a fibrinolytic agent. METHODS : 137 patients were included in this study. All patients admitted with a diagnosis of STEMI at our centre, within a window period of 24 hours. Over a period of 9 months, who underwent PCI or pharmacoinvasive therapy was included in this study. Primary end points (death within 30 days, re-MI within 30 days, and cardiogenic shock) and secondary endpoints (arrhythmias, bleeding manifestations, ischemic stroke, ejection fraction, mechanical complications, duration of hospital stay) were looked into. RESULTS : Though the hypothesis was non-inferiority, analysis of composite of primary endpoint and mortality outcome suggested equivalence. There was no significant difference between the secondary outcomes between the two groups. Use of thrombus aspiration device and in turn the thrombus burden was significantly lower in the pharmacoinvasive group than in primary PCI arm. Pharmacoinvasive arm had significantly greater number of patients who presented with Anterior wall MI. CONCLUSION : This is a small study, which showed that pharmacoinvasive therapy is as effective as primary PCI in the setting of STEMI. It can also be further inferred that, pharmacoinvasive strategy using streptokinase, is an effective alternative to tenecteplase, in our setting with no associated increase in adverse events

Clinical, hemodynamic, echocardiographic, angiographic profiles and post-operative outcomes among DCRV patients from a tertiary care referral center in India

Background: This retrospective study of data from 2006 to 2018 at a tertiary care referral center in India aims to document the contemporary clinical and hemodynamic profile of patients who were diagnosed with double chamber right ventricle (DCRV) based on echocardiography and cardiac  catheterization. Patients were followed up and their outcomes were studied to document their short and long term outcomes.Methods: It is a retrospective observational study of patients diagnosed with DCRV in a tertiary care hospital in India. The diagnosis of DCRV was based on the following criteria: an echocardiographic diagnosis of DCRV with doppler evidence of a mid ventricular gradient; cardiac catheterization revealing a systolic pressure gradient between right ventricular inflow and outflow tracts; a right ventricular angiogram demonstrating an anomalous muscle bundle causing obstruction well below the infundibulum. All the patients were followed up for their long term outcomes.Results: All the patients underwent echocardiography and cardiac catheterization for confirmation of the diagnosis. Sixty percent of our patients presented during adulthood, which is very unusual presentation of this disease entity. Median age of our patient cohort was 23.5 years. Patients presenting during adulthood have atypical symptoms. Dyspnea was the most common presenting symptom in this study. Right ventricular hypertrophy (73.3%)and right bundle branch pattern (26.6%) were the common electrocardiographic findings in our patients. DCRV is commonly associated with other anomalies. Ventricular septal defect (VSD) was the commonest associated anomaly, which was seen in 80% of our patients. Mean gradient cross the anomalous muscle bundle was 67.5 mmHg. Three of our patients (20%) had no associated anomaly, which is very rare in DCRV. Eight patients underwent surgical correction with significant reduction in gradients in all and no perioperative mortality. Median follow up of 8 years showed no adverse outcomes and no progression of gradients.Conclusions: This study describes in detail the clinical profile, echocardiographic and angiographic identification of anomalous muscle bundles in DCRV patients, which will help the young readers in identifying this often missed diagnosis. It highlights the unusual presentation during adulthood with atypical symptoms in DCRV patients with excellent long-term outcomes on follow up

A clinical study of factors predicting prognosis in acute ischemic stroke in a tertiary care center in north Kerala

Background: Stroke is the second most common cause of death and third most common cause of disability in the world. Knowledge of prognostic factors is necessary for the clinician to make a reasonable prediction of outcome for individual patients, to provide rational approach to management and to help patients and their families understand course of the disease. Hence, this study to determine the prognostic factors in acute ischemic stroke with special emphasis on atrial fibrillation, hyperglycemia and fever was undertaken.Methods: This is a prospective and hospital based observational study of 70 patients with acute ischemic stroke. The diagnosis of acute ischemic stroke was based on history, physical examination and CT imaging. The severity was assessed based on Scandinavian Stroke Scale (SSS). The prognostic factors with special emphasis on atrial fibrillation, hyperglycemia and fever were studied based on the standard diagnostic criteria.Results: Prevalence of Atrial Fibrillation was 20% in present study. Mortality and dependency rates were significantly higher in AF group. Fever during the first few days of acute ischemic stroke was a statistically significant predictor of poor outcome. Neuronal damage in brain is directly proportional to its temperature. The results of the study confirm that hyperglycemia at stroke onset is an adverse prognostic factor with 33.33% mortality in hyperglycemic stroke.Conclusions: Atrial fibrillation, hyperglycemia and fever were found to be poor prognostic factors in acute ischemic stroke. Prompt recognition and correction of these poor prognostic factors improve the outcome for such patients

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant