Severity of Coronary Artery Diseases Among Pre- and Postmenopausal Women With Acute Coronary Syndrome: A Hospital-Based Study in Bangladesh.

BACKGROUND: Postmenopausal women present with more severe coronary artery disease (CAD) in addition to multiple comorbidities. However, there are limited data available to compare the risk factors, clinical characteristics, and angiographic severity of CAD between pre- and postmenopausal women with the acute coronary syndrome (ACS). AIM: This study aimed to assess and compare the severity of CAD in pre- and postmenopausal women with ACS. METHODS: This cross-sectional observational study was conducted at the Department of Cardiology of NHFH RI. A total of 140 female patients with ACS were enrolled and then divided into Group I (premenopausal) and Group II (postmenopausal) on the basis of menopause history. Clinical data and coronary angiographic severity were compared between both groups. RESULTS: The mean age of the premenopausal group was 41.53 ± 5.45 years, and that of the postmenopausal group was 57.23 ± 7.45 years. Family history of premature CAD was significantly more common in the premenopausal group than in the postmenopausal group (35(50%) vs. 23(32.9%); p=0.017)). DM and smokeless tobacco were more prevalent in the postmenopausal group (48(68.6%) vs. 28(40%); p=0.001 and 14(20%) vs. 2(2.9%); p=0.002). Atypical presentation was more common in the premenopausal group (21(30%) vs. 9(12.9%); p=0.013). Most of the patients in both groups presented with unstable angina followed by NSTEMI and STEMI. Mean left ventricular ejection fraction was lower in the postmenopausal group than in the premenopausal group (50.71 ± 8.38% vs. 53.74 ± 7.46%; p=0.026). Normal coronary angiogram and single-vessel disease were more prevalent in the premenopausal group (22(31.4%) vs. 12(17.1%); p=0.04) and (22(31.4%) vs. 11(15.7%); p=0.002), whereas triple-vessel disease was more prevalent in the postmenopausal group (34(48.6% vs. 14(20%); p=0.001). The left anterior descending artery was the most commonly involved vessel in the postmenopausal group (67(95.7%) vs. 60(85.7%); p=0.04). Finally, the mean Gensini score was higher in the postmenopausal group than in the premenopausal group (56.1 ± 43.4 vs. 33.5 ± 36.9; p=0.001). CONCLUSION: Family history of premature CAD and atypical presentation were common in premenopausal ACS patients. DM and smokeless tobacco use were more prevalent in the postmenopausal group than in the premenopausal group. Normal coronary angiogram and single-vessel disease were more prevalent in the premenopausal group, and triple-vessel disease was more common in the postmenopausal group. CAD was more severe in the postmenopausal group.

Safety and effectiveness of percutaneous coronary intervention using rotational atherectomy and new-generation drug-eluting stents for calcified coronary artery lesions in patients with chronic kidney disease.

AIM: Coronary artery calcification is an important factor influencing revascularisation outcomes in patients with chronic kidney disease (CKD). Lesion preparation using rotational atherectomy (RA) may help adequately modify calcified plaques and facilitate the achievement of optimal clinical outcomes in these patients. In this study, we assessed the safety and effectiveness of percutaneous coronary intervention (PCI) using RA followed by new-generation drug-eluting stent (DES) implantation in patients with CKD and calcified coronary artery disease (CAD). METHODS AND RESULTS: From November 2014 to October 2019, a total of 203 patients with calcified CAD who underwent RA followed by second- or third-generation DES implantation at our centre were included in the study. Mild, moderate, and severe CKD was present in 38%, 55.5%, and 6.5% of the patients, respectively. Diffused coronary calcifications were present in 85%. Procedural success was 97.5% with minimal periprocedural complications. In-stent restenosis occurred in one patient (0.5%); major adverse cardiovascular and cerebrovascular events were reported in 22 patients (10.8%); cardiac death occurred in eight patients during follow-up. CONCLUSION: Percutaneous coronary intervention using RA followed by second- or third-generation DES implantation is feasible and safe with high procedural success and low in-stent restenosis in CKD patients with calcified coronary lesions.

Vaccine Against Covid-19 Disease - Present Status of Development.

The pandemic declaration of Covid-19 disease by World Health Organization (WHO) and subsequent widespread morbidities and mortalities in almost all countries of the world led to the research and development to find out a vaccine against SARS-CoV2 virus. Normally any new vaccine development takes 10-15 y time but the search for vaccine against SARS-CoV2 is going on at a very fast pace resulting in almost breakthrough in vaccine development by several research institutions and vaccine manufacturers. In pandemic situation, however, the entire process of vaccine development including clinical trials gets shortened and may be fast tracked to 15-18 mo time. It is expected that there shall be simultaneous marketing of several vaccines by the beginning of 2021. There are more than 164 candidate vaccines which are in the process of development and among them 24 vaccines are in advanced stages of development. This review aims at highlighting the present stages of development of vaccines and discussing the challenges that may be faced with these novel vaccines.

A Comprehensive Review of Meningococcal Disease Burden in India.

INTRODUCTION: Meningococcal disease caused by Neisseria meningitidis has a high case fatality rate. Of 12 distinct serogroups, A, B, C, W-135 (W) and Y cause the majority of infections. The meningococcal disease burden and epidemiology in India are not reliably known. Hence, we performed a narrative review with a systematically conducted search to summarize information on meningococcal disease burden and epidemiology and vaccination recommendations for meningococcal disease in India. METHODS: A search of Medline and Embase databases was undertaken to identify relevant publications published in the last 25 years. RESULTS: Results from 32 original publications, 11 of which were case reports, suggest a significant burden of meningococcal disease and related complications. Meningococcal disease is increasingly reported among adolescents and adults, and large outbreaks have been reported in this population. Meningococcal disease in India is caused almost exclusively by serogroup A; serogroups B, C, W and Y have also been documented. Meningococcal disease burden data remain unreliable because of limited disease surveillance, insufficient laboratory capacity, misdiagnosis and prevalence of extensive antibiotic use in India. Lack of access to healthcare also increases under-reporting, thus bringing the reliability of the data into question. Conjugate meningococcal vaccines are being used for disease prevention by national governments and immunization programs globally. In India, meningococcal vaccination is recommended only for certain high-risk groups, during outbreaks and for international travelers such as Hajj pilgrims and students pursuing studies abroad. CONCLUSION: Meningococcal disease is prevalent in India but remains grossly underestimated and under-reported. Available literature largely presents outbreak data related to serogroup A disease; however, non-A serogroup disease cases have been reported. Reliable epidemiologic data are urgently needed to inform the true burden of endemic disease. Further research into the significance of meningococcal disease burden can be used to improve public health policy in India. Fig. 1 Plain language summary.

Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway.

Natural killer (NK) cells provide the first line of defense against malaria parasite infection. However, the molecular mechanisms through which NK cells are activated by parasites are largely unknown, so is the molecular basis underlying the variation in NK cell responses to malaria infection in the human population. Here, we compared transcriptional profiles of responding and non-responding NK cells following exposure to Plasmodium-infected red blood cells (iRBCs) and identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be differentially expressed. Knockout of MDA5 in responding human NK cells by CRISPR/cas9 abolished NK cell activation, IFN-γ secretion, lysis of iRBCs. Similarly, inhibition of TBK1/IKKε, an effector molecule downstream of MDA5, also inhibited activation of responding NK cells. Conversely, activation of MDA5 by liposome-packaged poly I:C restored non-responding NK cells to lyse iRBCs. We further show that microvesicles containing large parasite RNAs from iRBCs activated NK cells by fusing with NK cells. These findings suggest that NK cells are activated through the MDA5 pathway by parasite RNAs that are delivered to the cytoplasm of NK cells by microvesicles from iRBCs. The difference in MDA5 expression between responding and non-responding NK cells following exposure to iRBCs likely contributes to the variation in NK cell responses to malaria infection in the human population.

Association of rotavirus strains and severity of gastroenteritis in Indian children.

Rotavirus is the leading cause of severe and dehydrating diarrhea in children aged under 5 years. We undertook this hospital-based surveillance study to examine the possible relationship between the severity of diarrhea and the various G-group rotaviruses circulating in India. Stool samples (n = 2,051) were systematically collected from 4,711 children aged <5 years admitted with severe acute gastroenteritis to 12 medical school centers from April 2011 to July 2012. Rotavirus testing was undertaken using a commercially available enzyme immunoassay kit for the rotavirus VP6 antigen (Premier Rotaclone Qualitative ELISA). Rotavirus positive samples were genotyped for VP7 and VP4 antigens by reverse-transcription polymerase chain reaction at a central laboratory. Of the stool samples tested for rotavirus antigen, 541 (26.4%) were positive for VP6 antigen. Single serotype infections from 377 stool samples were compared in terms of gastroenteritis severity. Among those with G1 rotavirus infection, very severe diarrhea (Vesikari score ≥ 16) was reported in 59 (33.9%) children, severe diarrhea (Vesikari score 11-15) in 104 (59.8%), moderate (Vesikari score 6-10) and mild diarrhea (Vesikari score 0-5) in 11 (6.3%). Among those with G2 infection, very severe diarrhea was reported in 26 (27.4%) children, severe diarrhea in 46 (48.4%), and moderate and mild diarrhea in 23 (24.2 %). Among those with G9 infection, very severe diarrhea was reported in 47 (54.5%) children, severe diarrhea in 29 (33.6%), and moderate and mild diarrhea in 10 (11.9%). Among those with G12 infection, very severe diarrhea was reported in 9 (40.9%) children and severe diarrhea in 13 (59.1%). The results of this study indicate some association between rotavirus serotypes and severity of gastroenteritis.

Isotonic versus Hypotonic Parenteral Maintenance Fluids in Very Severe Pneumonia.

OBJECTIVE: To compare the risk of hyponatremia between hypotonic and isotonic parenteral maintenance solutions (PMS) administered to children with very severe pneumonia, admitted in the general pediatric ward. METHODS: A randomized controlled open label trial was conducted in the pediatrics department of a tertiary care medical college hospital including euvolemic children 2 mo to 5 y of age, fulfilling the WHO clinical definition of very severe pneumonia and requiring PMS. They were randomized to receive either isotonic PMS (0.9% saline in 5% dextrose and potassium chloride 20 meq/L) or hypotonic PMS (0.18% saline in 5% dextrose and potassium chloride 20 meq/L) at standard rates for next 24 h. RESULTS: A total of 119 children were randomized (59: Isotonic; 60: Hypototonic PMS). Nine (15%) children in the isotonic PMS group and 29 (48%) in the hypotonic PMS group developed hyponatremia during the study period, (p <0.001) with a relative risk being 3.16 (95% CI 1.64 to 6.09). Mean serum sodium was significantly lower in the hypotonic group compared to the isotonic group (p < 0.001 each at 6, 12 and 24 h). The difference in mean change in serum sodium from baseline was also significant at 12 and 24 h (5.4 and 5.8 meq/L respectively; p < 0.001 each). CONCLUSIONS: This study demonstrates the rationality of the use of isotonic PMS in children with respiratory infections, a condition regularly encountered by most pediatricians.

Isotonic intravenous maintenance fluid reduces hospital acquired hyponatremia in young children with central nervous system infections.

OBJECTIVE: To find the appropriate type of intravenous fluid (isotonic vs. hypotonic saline in 5 % dextrose) for empiric maintenance fluid therapy in children with central nervous system (CNS) infections that reduces the incidence of hospital acquired hyponatremia. METHODS: This blinded randomized controlled trial included hospitalized children aged 3 mo to 5 y with suspected CNS infections requiring intravenous maintenance fluid for at least 24 h. The subjects were randomized to receive 0.9 % saline (Group-A), 0.45 % saline (Group-B) and 0.18 % saline (Group-C) at standard maintenance rate. The outcome measures were proportion of patients developing hyponatremia (serum sodium < 135 mmol/L) after 24 h and serum sodium values at 6, 12, 18, 24 h of receiving maintenance fluids. RESULTS: Of the 92 patients enrolled, 31, 30 and 31 patients were randomized to Group A, B and C, respectively. Majority (60.7 %) of the patients in Group-C developed hyponatremia compared with 7.1 % of the children in Group-A and 46.1 % in Group-B. During first 24 h of fluid administration successive fall in the serum sodium values was observed in patients receiving hypotonic fluids. The risk of developing hyponatremia was nearly 6½ (95 % confidence interval (CI) 1.6-26) to 8.5 (95 % CI 2.16-33.39) times more in patients who received hypotonic saline compared to those who received isotonic saline. CONCLUSIONS: Administration of 0.9 % saline in 5 % dextrose as intravenous maintenance fluid in children with CNS infection leads to significantly less incidence of hyponatremia when compared to that with hypotonic fluids.

An overview of meningococcal disease in India: knowledge gaps and potential solutions.

The Global Meningococcal Initiative (GMI) consists of an international group of scientists and clinicians, with expertise in meningococcal immunology, epidemiology, public health and vaccinology that aims to prevent meningococcal disease worldwide through education, research, cooperation and vaccination. In India, there is no national policy on routine meningococcal vaccination to control the disease. The GMI convened a meeting in India, with local medical leaders and public policy personnel, to gain insight into meningococcal disease burden and current surveillance and vaccination practices in the country. Neisseria meningitidis is the third most common cause of sporadic bacterial meningitis in children <5 years, with higher incidence in temperate northern versus tropical southern India. Incidence is not reliably known due to suboptimal surveillance and insufficient microbiological support for diagnosis. Since 2005, there have been a number of outbreaks, all attributable to serogroup A. Outbreak responses were ad hoc and included mandatory case reporting by hospitals in Delhi, temporary strengthening of laboratory diagnostics, chemoprophylaxis of close contacts/high-risk groups and limited reactive use of polysaccharide vaccine. Although a conjugate serogroup A vaccine (MenAfriVac™) is manufactured in India, it is not presently used in India. Epidemiological data on meningococcal disease in India are sparse. Meningococcal disease control efforts should focus on establishing systematic surveillance and educating physicians and officers of the Immunization Division of the Ministry of Health on the importance of N. meningitidis as a cause of morbidity and mortality. Conjugate vaccine should be used for outbreak control and the immunization of high-risk persons.

Role of zinc in severe pneumonia: a randomized double bind placebo controlled study.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children. OBJECTIVE: The aim of study was to evaluate the efficacy of Zinc supplementation in treatment of severe pneumonia in hospitalized children. DESIGN/METHODS: A double blind randomized, placebo- controlled clinical trial conducted at a tertiary care centre of a teaching hospital. Children with diagnosis of severe pneumonia were randomly assigned to receive supplementation with either elemental zinc or placebo by mouth at the time of enrollment. From day 2, they received 10 mg of their assigned treatment by mouth twice a day for 7 days along with standard antimicrobial therapy. RESULTS: The baseline characteristics like age, sex, weight, weight Z score, height, height Z score, weight for height Z score and hemoglobin were comparable in both study groups. The respiratory rate, chest indrawing, cyanosis, stridor, nasal flaring, wheeze and fever in both groups recorded at enrollment and parameters did not differ significantly between the two groups. The outcome measures like time taken for resolution of severe pneumonia, pneumonia, duration of hospital stay, nil per oral, intravenous fluid, oxygen use, treatment requiring 2nd line of drug and 3rd line drug were evaluated and found to be same. CONCLUSION: The present study did not show a statistically significant reduction in duration of severe pneumonia, or reduction in hospital stay for children given daily zinc supplementation along with standard antimicrobial therapy. Therefore, zinc supplementation given during the acute episode does not help in short term clinical recovery from severe pneumonia.

Persistent hyperinsulinemic hypoglycemia of infancy.

Congenital hyperinsulinism (CHI) is the most frequent cause of severe, persistent hypoglycemia in infancy and childhood. We report a case of CHI with diffuse pancreatic abnormality diagnosed preoperatively using the 68Ga octreotide (DOTA NOC) positron emission tomography scan. Genetic analysis revealed homozygous ABCC8 splicing mutation. Subtotal (95%) pancreatectomy was done, and the infant remained euglycemic and was discharged on breast feeds. The patient is continuously followed up and is asymptomatic until 9 months.

Plasmodium vivax malaria admissions and risk of mortality in a tertiary-care children's hospital in North India.

BACKGROUND: In 2010, there was an increase in the severity of malaria admissions to Kalawati Saran Children's Hospital, New Delhi and this report describes the morbidity and mortality profile. METHOD: A retrospective chart review of patients admitted with parasitologically confirmed malaria between January and December 2010. RESULTS: There were 156 cases: P. vivax 105 (67.3%), P. falciparum 39 (25%) and mixed infections 12 (7.7%). Thrombocytopenia (platelet count <150×10(9)/L) was present in 90 (85.7%) patients with P. vivax mono-infection. There were 91 (58.3%) patients with severe malaria: P. vivax mono-infection 46 (50.5%), P. falciparum mono-infection 35 (38.5%) and mixed 10 (11%). Severe anaemia and severe thrombocytopenia (platelet count <20×10(9)/L) were detected significantly more often in P. falciparum and P. vivax mono-infection, respectively. Complications including cerebral malaria, acute renal failure, shock, acute respiratory distress syndrome (ARDS) and multiple-organ dysfunction syndrome (MODS) were similar in both groups. The mortality rate of around 20% was similar in severe P. vivax and P. falciparum mono-infection. Risk of mortality in vivax malaria was highest in patients with ARDS followed by MODS and shock. CONCLUSION: Increased morbidity owing to P. vivax malaria was observed and risk of mortality was highest in patients with ARDS and MODS.

Assessment of sexual maturity in a cohort of adolescents with celiac disease on gluten-free diet.

Delayed sexual maturation is a known complication of celiac disease (CD). There is paucity of data regarding the effect of gluten-free diet (GFD) on sexual maturity in patients with CD in India. We did a cross-sectional observational study to assess the sexual maturity in 30 adolescents with CD on GFD for at least 1 year, and evaluated factors which affect their sexual maturity. Sexual maturation was assessed using Tanner's stages of sexual development. All adolescents had completed 2 years of GFD and 53 % had completed 4 years of GFD. Sexual maturation was delayed in 30 %. Age at initiation of GFD was associated with attaining appropriate sexual maturity (p = 0.048). We conclude that delayed sexual maturation is not uncommon in adolescents with CD and may be corrected by early diagnosis and initiation of GFD.

Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Serious bacterial infections are a major cause of death in early infancy in developing countries. Inexpensive and accessible interventions that can add to the effect of standard antibiotic treatment could reduce infant mortality. We measured the effect of zinc as an adjunct to antibiotics in infants with probable serious bacterial infection. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled infants aged 7-120 days with probable serious bacterial infection at three hospitals in New Delhi, India, between July 6, 2005, and Dec 3, 2008. With computer-generated sequences, we randomly assigned infants in permuted blocks of six, stratified by whether patients were underweight or had diarrhoea at enrolment, to receive either 10 mg of zinc or placebo orally every day in addition to standard antibiotic treatment. The primary outcome was treatment failure, which was defined as a need to change antibiotics within 7 days of randomisation, or a need for intensive care, or death at any time within 21 days. Participants and investigators were masked to treatment allocation. All analyses were done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00347386. FINDINGS: 352 infants were randomly assigned to receive zinc and 348 to placebo. 332 given zinc and 323 given placebo could be assessed for treatment failure. Significantly fewer treatment failures occurred in the zinc group (34 [10%]) than in the placebo group (55 [17%]; relative risk reduction 40%, 95% CI 10-60, p=0·0113; absolute risk reduction 6·8%, 1·5-12·0, p=0·0111). Treatment of 15 (95% CI eight to 67) infants with zinc would prevent one treatment failure. Ten infants receiving zinc died compared with 17 given placebo (relative risk 0·57, 0·27-1·23, p=0·15). INTERPRETATION: Zinc could be given as adjunct treatment to reduce the risk of treatment failure in infants aged 7-120 days with probable serious bacterial infection. FUNDING: Department of Biotechnology, Government of India; the European Commission; the Meltzer Foundation; and the Research Council of Norway.

Occupational exposure to human immunodeficiency virus in health care providers: a retrospective analysis.

OBJECTIVES: To determine the population at risk, risk factors, and outcome of occupational exposure to blood and body fluids in health care providers. MATERIALS AND METHODS: Retrospective review of two and half year data of ongoing surveillance of occupational exposure to blood and body fluids in a tertiary care hospital. RESULTS: 103 Health Care Providers (HCP) reported an occupational exposure to blood and body fluids during the period under review. These comprised 72 (69.9%) doctors, 20 (19.4%) nursing personnel, and 11 (10.6%) cleaning staff. Of the doctors, 65% were interns. 53.4% HCP had work experience of less than one year. Circumstances of exposure included clinical procedures (48%), sweeping/handling used sharps (29%), recapping (16%), and surgery (6.9%). 74.3% of the exposures were due to non-compliance with universal precautions and were thus preventable. The device most frequently implicated in causing injury was hollow bore needle (n=85, 82.5%). Human Immunodeficiency Virus (HIV) status of the source was positive in 6.8% cases, negative in 53.4% cases, and unknown in remaining 39.8% cases. Postexposure prophylaxis (PEP) was indicated in 100 (97.08%) cases and was initiated within 2 h of exposure in 26.8% HCP. In 23.2% HCP, PEP initiation was delayed beyond 72 h of exposure due to late reporting. Thirteen HCP received expanded and the remaining received basic regime. Of the 82 HCP followed up, 15 completed the full course, while 55 stopped PEP after the first dose due to negative source status. Twelve HCP with exposure to blood of unknown HIV status discontinued PEP despite counseling. Complete follow-up for seroconversion was very poor among the HCP. HIV status at 6 month of exposure is not known for any HCP. CONCLUSIONS: Failure to follow universal precautions including improper disposal of waste was responsible for majority of occupational exposures. HCP need to be sensitized regarding hospital waste management, management of occupational exposure, need for PEP, and continued follow-up.

Tetanus - still a scourge in the 21st century: a paediatric hospital-based study in India.

Tetanus remains endemic in India. A retrospective hospital-based study was conducted to review the profile of all children admitted with diagnosis of tetanus between January 2009 and December 2010. A total of 140 cases of tetanus were admitted; 45 cases of neonatal tetanus (NT) and 77 cases of post-neonatal tetanus (PNT) were studied. Age of presentation of NT was 9.4 ± 1.2 days. Home-delivered children accounted for 86.7% of cases, with 77.8% being attended by untrained birth attendants. Unimmunized mothers accounted for 93.4%. In PNT, otogenic route of infection and trauma were present in 58.4% and 23.3% of cases, respectively. The rate of hospital admission of tetanus remains high. Unlike previously published reports, otogenic route is the most common mode of PNT infection in this study. Improving immunization, increasing deliveries by skilled birth attendants and prompt treatment of suppurative otitis media are the main areas in which public health initiatives need to be focused.