Short-Term Adverse Drug Reactions to Antiretroviral Therapy in Children with HIV: A Cohort Study.

OBJECTIVES: To carry out an active surveillance for adverse drug reactions (ADRs) in children with HIV infection newly initiated on antiretroviral therapy (ART), determine risk factors for their occurrence, and assess their influence on adherence to ART. METHODS: All children newly initiated on ART from 1st March 2014 to 30th June 2019 at a tertiary care children's hospital in New Delhi, were actively monitored for ADRs to ART for a period of 6 mo after ART initiation. The frequency, spectrum, and severity of ADRs, their influence on adherence, and risk factors for their occurrence were analyzed. RESULTS: Among the 174 enrolled children, ADRs were observed in 78 (44.8%) children during the first 6 mo after ART initiation. Total numbers of episodes of ADR observed were 108 (0.62 episodes of ADR/child). Sixty percent of events were of grade 1 severity, 19.4% events were of grade 2 and 3 each, while 1 (0.9%) event was of grade 4 severity. Adherence to ART was adversely affected in 21.8% of ADRs. Gastrointestinal symptoms (49.1%) were most frequent among all the events observed. Zidovudine, lopinavir/ritonavir, efavirenz and nevirapine based regimes were significantly associated with hematological, gastrointestinal, neurological, and dermatological ADRs, respectively. Children with immunological suppression were at a higher risk of developing ADRs as compared to those without it [RR 1.9 (95% CI (1.1-3.2)]. CONCLUSIONS: ADRs to ART are very frequent; most of them are mild and self-limiting. However, they can adversely impact adherence to ART. Anticipatory guidance, ongoing monitoring, and provision of symptomatic treatment will help tide over most ADRs and reduce their adverse impact upon ART adherence.

Predictors of mortality in children admitted with SARS-CoV-2 infection to a tertiary care hospital in North India.

AIM: To compare the demographic, clinical, laboratory and radiological parameters of patients with different clinical outcomes (death or discharge) and analyse them to find out the potential predictors for mortality in children hospitalised with SARS-CoV-2 infection. METHODS: Retrospective chart review of all patients less than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and requiring hospital admission between 16 April 2020 and 31 October 2020. RESULTS: Of 255 children with SARS-CoV-2 infection, 100 patients (median age 62.5 months, 59% males, 70% with moderate to severe disease) were hospitalised, of whom 27 died (median age 72 months, 59% males and 30% severely underweight). The subgroup with comorbidities (n = 14) was older (median age 126 months) and had longer duration of stay (median 10 days). Fever and respiratory symptoms were comparable while gastrointestinal symptoms were more common among non-survivors. Hypoxia at admission (odds ratio (OR) 5.48, P = 0.001), multiorgan dysfunction (OR 75.42, P = 0.001), presence of acute kidney injury (OR 11.66, P = 0.001), thrombocytopenia (OR 4.40, P = 0.003) and raised serum C-reactive protein (CRP) (OR 4.69, P = 0.02) were independently associated with mortality. The median time from hospitalisation to death was 3 days. The deceased group had significantly higher median levels of inflammatory parameters and a higher incidence of complications (myocarditis, encephalitis, acute respiratory distress syndrome and shock). CONCLUSIONS: Hypoxia at admission, involvement of three or more organ systems, presence of acute kidney injury, thrombocytopenia and raised serum C-reactive protein were found to be independently associated with increased odds of in-hospital mortality in children admitted with SARS-CoV-2 infection.

Acute Kidney Injury in Hospitalized Children with COVID19.

BACKGROUND: Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection. AIM: The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting. METHODS: Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste's equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan-Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group. RESULTS: A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p < 0.01), nephrotic syndrome (OR 95% CI, 1.13-115.5, p < 0.01), vasopressor support (OR 3.59, 95% CI, 1.37-9.40, p value< 0.007), shock at presentation (OR 2.98, 95% CI, 1.16-7.60, p value 0.01) and mechanical ventilation (OR 2.64, 95% CI, 1.04-6.71, p value< 0.03). Mortality (25.71%) was higher in the AKI group (OR 95% CI, 1.14-8.35, p < 0.023) with shock (OR 45.92; 95% CI, 3.44-612.0, p value <0.004) and ventilation (OR 46.24; 95% CI, 1.6-1333.0 p value< 0.02) as significant risk factors for mortality. CONCLUSION: AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.

Neurological Deterioration in Three Siblings: Exploring the Spectrum of Argininemia.

Argininemia or hyperargininemia is a urea cycle disorder caused by deficiency of the enzyme arginase 1. It is inherited in an autosomal recessive fashion. It commonly leads to spastic diplegia in childhood, but other important features include cognitive deterioration and epilepsy. Unlike other disorders of the urea cycle, hyperammonemia is not prominent. The authors report three siblings with genetically proven argininemia who presented with diverse phenotypes but with spasticity being a common feature. Sibling 1 developed motor regression in early childhood, sibling 2 developed delayed motor milestones from early infancy, whereas sibling 3 had global developmental delay in late infancy after a period of normal development. All siblings had mild hyperammonemia only. Early recognition is imperative, not only to initiate ammonia scavenging therapy which may lead to definite clinical improvement, but also to provide genetic counselling.

Comparison of Feeding Options for HIV-Exposed Infants: A Retrospective Cohort Study.

OBJECTIVE: To compare growth, anemia prevalence, and sickness frequency in HIV- exposed uninfected infants on different feeding modes. METHODS: In this retrospective cohort study, 109 HIV-exposed uninfected infants registered at our center were categorized into three groups as per their feeding mode during first 6 months viz. exclusively breast fed (n=50), animal milk fed (n=40) and commercial infant formula fed (n=19). Their anthropometric parameters, hemoglobin and frequency of sickness at the age of 6 months were compared. RESULTS: There were no significant inter-group differences in the weight for age, weight for length, length for age z-scores (P=0.16, 0.37 and 0.12, respectively); proportion of infants with underweight (P=0.63), wasting (P=0.82), or stunting (P=0.82), and mean hemoglobin levels among the 3 groups at 6 month of age. Animal milk fed and formula fed infant had increased risk of sickness compared to exclusively breastfed infants (OR 2.5 and 2.49, respectively; P<0.01). CONCLUSIONS: In circumstances where breastfeeding is not feasible or preferred, animal milk feeding offers a viable alternative to commercial infant feeding formula in HIV exposed infants.

Immune Response to Double Dose Hepatitis-B Vaccine using Four Dose Schedule in HIV Infected Children.

OBJECTIVE: To assess the immune response to hepatitis B vaccination in HIV infected children using 4 double dose schedule administered at 0-1-2-6 mo. METHODS: In a prospective observational study, 40 HIV infected children were vaccinated with hepatitis B virus (HBV) vaccine (20 mcg, 1 ml IM at anterolateral aspect of thigh of recombinant DNA vaccine) at 0-1-2-6 mo. Anti-HBsAb titre were assessed 4-8 wk after the last dose. Clinical severity was assessed according to WHO staging. Immune status of the patients was assessed using CD 4+ counts before the vaccination. RESULTS: Of the total 40 patients, 33 (28 boys, 5 girls) completed the study. Six patients were in pre-antiretroviral therapy (ART) care while 27 were receiving ART for a mean duration of 2.06 y. Ten patients belonged to WHO clinical stage 1, and 17, 2 and 4 patients to WHO clinical stage 2, 3 and 4 respectively. Median CD4+ cell count was 738/mm(3) and 28 patients had mild or no immunosuppression. Out of the total 33 patients who completed followup, only 2 patients (6 %) did not seroconvert (Anti HBsAb titre at end of study <10 IU/L), the rest (94 %) achieved different levels of Anti HBsAb titre at end of study. Twenty two (66 %) patients had anti HBsAb titre more than 1000 IU/L, 8 (24 %) had titre between 100 and 1000 IU/L and one (3 %) patient had level of 10-99.99 IU/L. CONCLUSIONS: In HIV-infected children who have no or mild immunosuppression, four dose, double dose schedule of HBV vaccine achieves very high seroconversion rates.

An assessment of rural health care delivery system in some areas of West Bengal-an overview.

A cross sectional observational study was carried out in three districts of West Bengal by following observational, quantitative and qualitative methods during July to December 2006 to find out the extent of utilization, strengths, weaknesses and gap as well as suggest recommendations in connection with health care delivery system for the state of West Bengal, India. A total of 672 episodes of illnesses were reported (2 weeks recall) by the study population of the three selected districts in three geographically separated divisions of West Bengal. None did seek care from any health facilities for treatment in case of 221 (32.89%) episodes; especially from tribal areas where in case of 76.19% none sought any health care from any facilities depended on their home remedies. In rest of episodes the (451), majority preferred government health facilities (38.58%), followed by Unqualified quacks (29.27%) due to low cost as well as living in close proximity, 27.27% preferred qualified Private practitioners and only 4.88% preferred AYUSH, as a first choice. Referral was mostly by self or by close relatives/families (61%) and not by a doctor. Awareness is required to avoid unnecessary referral. Cleanliness of the premises, face-lift, and clean toilet with privacy and availability of safe drinking water facilities could have an improved client satisfaction in rural health care delivery systems. This could be achieved through community participation with the involvement of PRI. However, as observed in the study RCH services including Family Planning as well as immunization services (preventive services) were utilized much better while there was a strong need of improvement of Post Natal Care, otherwise, Neonatal and Maternal mortality and morbidity will continue to be high.

A study on prevalence of bacteria in the hands of children and their perception on hand washing in two schools of Bangalore and Kolkata.

BACKGROUND: Contaminated hands play a major role in fecal-oral transmission of diseases. In 1847, Dr Semmelweis Ignac pointed to the link between infection and unclean hands, and demonstrated that washing hands could reduce transmission of puerperal fever (child birth fever), a dreaded disease with high mortality in those days. MATERIALS AND METHODS: A cross-sectional study was conducted to find out the extent of germs present in hand, and also the students' perception on hand washing. This was assessed by questionnaire as well as by collection of swab from hand and performing bacteriological culture in the laboratory. RESULTS: In regard to students' perception about the dirty areas of the hands, it was observed that majority (78%) felt palm was likely to be more dirty while less than 70% felt that web spaces could harbor dirt. Almost 86% reported that they washed hands before eating lunch, but only 21.3% said they always used soap while 47.3% never used it. Availability of soap all the time in the school was reported by only 18.4% students. The swabs of 61% children showed potential pathogens. The commonest of these was Staphylococcus aureus which was seen in 44% samples. CONCLUSION: The students' hands were contaminated before taking food. Although they washed hands before meals, they hardly used soap due to non-availability of soap. The school authority should be asked to keep soaps in the toilets for hand washing.

Hand washing practices in two communities of two states of Eastern India: an intervention study.

BACKGROUND: Public health importance of hand washing as well as its importance in reduction of communicable diseases such as diarrhea and acute respiratory infections have been highlighted in many studies worldwide. OBJECTIVE: This study was designed to study the hand washing practices followed in two urban slums as well as to assess and compare the status of different components of hand washing at the pre- and post-intervention phases. MATERIALS AND METHODS: A community-based cross-sectional intervention study on hand washing practices was carried out at two urban slums situated in two states of Eastern India with similar sociocultural and linguistic background. The study was carried out by using an interview technique as well as observation of hand washing practices. Interpersonal communication for behavioural change was chosen as a method of intervention. RESULTS: The majority (>90%) practiced hand washing after defecation in both the study areas. However, hand washing following all six steps and for stipulated time period was seen to be poor before intervention. Significant improvement was observed in all the aspects of hand washing after intervention in both the areas. The poor practice of hand washing was observed in some situations and needed attention. Use of soap and clean material for drying hands after hand washing was poor initially followed by improvement after intervention. CONCLUSION: Based on the findings of the study, it could be suggested that Behaviour Change Communication program should be further planned with emphasis on different components of hand washing with a final objective to bring down the incidence of target diseases.

An epidemiological study on incidence, symptoms and complications of measles in bordering districts of West Bengal.

The present study was carried out to find out the incidence of measles in under five children and its complications in four selected urban slums of inter-state border districts of West Bengal. 20 cluster sampling technique was followed and in each cluster 250 under five children were covered. Paramedical workers found out the children of the target age group who had the history of measles in past one year and Medical Officer confirmed the case following standard case definition. Incidence of measles was round to be 3.3% in Purulia, 5.5% in Bankura. 4.6% in Midnapur, 5.7% in Haldia-Tamluk and with an overall rate of 4.8%. Incidence was higher in 0-11 and 12-23 months age group and decreased with increasing age, but no sex difference in incidence of Measles was observed. Only 20% of cases were vaccinated with measles vaccine and 26% received Vitamin A in oil. Diarrhoea was the commonest complications followed by cough and cold, pneumonia and weight loss. The study highlighted the necessity of timely measles vaccine coverage, additional dose at a higher age and Vitamin A oil supplementation through IEC activities.

Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins.

A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2-6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.

National rural health mission--opportunity for Indian Public Health Association.

Indian Public Health Association (IPHA) welcomes the release of National Rural Health Mission (NRHM) documents. It suggests that manpower requirements of the Community Health Centre (CHC) should be rationally determined on the basis of work and patient load of the CHC. Importance should be given on availability of simple & life saving equipment, female staff when male staff is not available. Safe drinking water, an adequate sanitation and excreta disposal facility through Panchayet Raj Institution (PRI) or privatization was proposed. Accredited Social Health Activist (ASHA) has been accepted more streamlining based on the community was suggested. Capacity building or training should be CHC based for grass-root level functionaries with incentive to Medical officer (MO). IPHA proposes to extend support in capacity building, development of manual for ASHA & other categories of health professional as well as Program Implementation Plan (PIP).

Epidemiological study of measles in slum areas of Kolkata.

OBJECTIVE: An epidemiological study on measles was conducted among the under five children in slum areas of Kolkata to assess the incidence of measles. METHODS: 20 cluster sampling technique was followed and in each cluster 250 under five children were covered. Paramedical workers identified children of the target of age group who had history of measles in past one year and the medical officer confirmed the diagnosis following standard case definition. RESULTS: Incidence of measles was found as 5.76%. Incidence was equal in both the sex groups, but found more among infants. The incidence of measles gradually declined with the increase of age strengthening the view in favor of early immunization. Amongst the measles cases only 19.7% were immunized with measles vaccine. 100% of measles cases gave history of rash, 98.9% had history of fever, 82.8% reported that the rash started from face and progressed downwards to abdomen and leg. Cough, redness of eye and discoloration of skin were reported by 97.5%, 83.8% and 65.2% measles cases respectively. Only 16.9% and 8.6% children received Vitamin A oil before and after the illness respectively. 49% gave history of exposure to measles cases and 46.6% cases had measles within 2 weeks incubation period. CONCLUSION: The study highlighted the necessity of timely measles vaccine coverage, additional dose at a higher age and Vitamin A supplementation through IEC activities.

Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray.

To obtain comprehensive information on 17beta-estradiol (E2) sensitivity of genes that are inducible or suppressible by this hormone, we designed a method that determines ligand sensitivities of large numbers of genes by using DNA microarray and a set of simple Perl computer scripts implementing the standard metric statistics. We used it to characterize effects of low (0-100 pM) concentrations of E2 on the transcriptome profile of MCF7/BUS human breast cancer cells, whose E2 dose-dependent growth curve saturated with 100 pM E2. Evaluation of changes in mRNA expression for all genes covered by the DNA microarray indicated that, at a very low concentration (10 pM), E2 suppressed approximately 3-5 times larger numbers of genes than it induced, whereas at higher concentrations (30-100 pM) it induced approximately 1.5-2 times more genes than it suppressed. Using clearly defined statistical criteria, E2-inducible genes were categorized into several classes based on their E2 sensitivities. This approach of hormone sensitivity analysis revealed that expression of two previously reported E2-inducible autocrine growth factors, transforming growth factor alpha and stromal cell-derived factor 1, was not affected by 100 pM and lower concentrations of E2 but strongly enhanced by 10 nM E2, which was far higher than the concentration that saturated the E2 dose-dependent growth curve of MCF7/BUS cells. These observations suggested that biological actions of E2 are derived from expression of multiple genes whose E2 sensitivities differ significantly and, hence, depend on the E2 concentration, especially when it is lower than the saturating level, emphasizing the importance of characterizing the ligand dose-dependent aspects of E2 actions.