Adverse drug reactions in children and adolescents on daily antitubercular regimen: An observational longitudinal study.

OBJECTIVES: Subsequent to introduction of daily fixed dose combination (FDC) regimen with increased dosages and inclusion of ethambutol in continuation phase of antitubercular therapy (ATT) in India, this study was done to evaluate adverse drug reactions (ADRs) in children and adolescents. METHODS: Longitudinal observational study conducted in tertiary teaching hospital. Children (1 month-18 year), with newly diagnosed drug sensitive tuberculosis, started on daily FDC regimen of ATT, were included. Participants were followed up at 2 weeks, 8 weeks and 6 months. Division of AIDS (DAIDS) severity grading and World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment was done. RESULTS: In 99 participants, 29 experienced ADRs. Most commonly ADRs involved hepatobiliary (11.1%) and gastrointestinal (8.1%) systems. Grade 3 severity noted in 35.5% ADRs. Certain causality classified in 19.3%. Presence of ADRs was significantly higher in participants with vs without malnutrition [40.5% vs 21.1% (p = 0.036)]. Tendency for more severe ADRs noted in participants with vs without malnutrition [Grade 3 ADRs out of all ADRs: 64.7% vs 0% (p < 0.001)]. CONCLUSION: Incidence and severity of ADRs has increased after introduction of daily FDC of ATT. Most common ADR observed were hepatobiliary. Malnutrition and less weight for age were risk factors for occurrence and severity of ADRs.

Assessment of risk factors in pyogenic liver abscesses in children.

Background: Pyogenic liver abscess (LA) is a significant contributor to morbidity and mortality in developing countries like India. The risk factors predisposing to the LA specifically in children are not known. Studies done in the past largely remain inconclusive and have identified only probable causes. The cause of LA in children with no coexisting illness remains unknown. Methodology: This prospective observational study was conducted at a tertiary teaching hospital located in New Delhi, India. All children between 2 months and 12 years of age with sonographically confirmed LA presenting to the hospital were included and managed with appropriate intravenous antibiotics and relevant investigations. Results: A total of 52 children were included. The mean age was 6 years and 4 months, and the male: female ratio was 1.4:1. Around 50% of the patients were malnourished. Fever, abdominal pain and loss of appetite were the most common symptoms. Nine patients (17%) were managed conservatively, 13 (25%) needed percutaneous needle aspiration and 30 (57.69%) required drainage using a pigtail catheter. Poor socioeconomic status and anaemia were found to be the most commonly associated risk factors. Selective immunoglobulin A (IgA) deficiency was the most common primary immunodeficiency disorder followed by T-cell defect. On multivariate analysis, it was seen that in those with clinical icterus, gamma-glutamyl transferases >350 IU/m, and those with impending rupture, the time to defervescence was significantly different (P = 0.05). Conclusion: Poor socioeconomic status causing malnutrition emerged as a significant risk factor for LA in children. Selective IgA deficiency was the most common immunodeficiency seen in a few children. Adopting a conservative approach like aspiration and percutaneous drainage led to lower mortality and good recovery rates.

Filaggrin Gene Mutation in Pediatric Patients with Atopic Dermatitis: A Look into Indian Gene Pool, a Pilot Study.

Background: Mutations in the filaggrin (FLG) gene has been reported to be an indicator of poor prognosis of atopic dermatitis (AD). It has been reported that there is a considerable variation in the mutations detected in the FLG gene in different ethnicities. Aim: To detect the presence of mutations in the FLG gene in pediatric subjects with atopic dermatitis (AD) and to compare the detected mutations with those already reported from different ethnicities. Materials and Methods: Genomic DNA extracted using standard procedure from peripheral venous blood of 30 patient and 15 control samples. Sequence analysis of the FLG gene carried out and detected changes was then cross referenced with those mutations already reported to check for novelty of detected changes. Results: Amino acid changes were detected in 28 of the patient samples and in none of the control samples indicating that changes in the FLG gene were more common in the patient group than the control group (Fishers exact test, P < 0.0001). The most commonly reported mutations R501X and 2282del4 were not detected. Only 5 of the detected 22 amino acid changes H2507Q, L2481S, K2444E, E2398Q, and S2366T have been previously reported and are not clinically significant; however, in one patient a stop codon was detected (S2366STOP). P2238N, R2239W, and V2243L detected in 70% of the samples and S2231E detected in 67% of the patient samples have not been reported so far and their clinical significance is yet to be analyzed. Conclusion: Analyses of mutations already reported showed that the changes detected from this study are novel to Indian traits. While this adds on to the minimal data available from the Indian subcontinent further analyses has to be carried out to analyze the pathogenicity of these detected changes on larger samples sizes. Aim: To detect the presence of mutations in the FLG gene in pediatric subjects with atopic dermatitis (AD) and to compare the detected mutations with those already reported from different ethnicities.

Ternary Cobalt (II)-Metformin-Glycine/Histidine/Proline Complexes: Multispectroscopic DNA, HSA, and BSA Interaction and Cytotoxicity Studies.

The synthesized water-soluble ternary complexes [Co(met)(gly)(Cl)2] (1), [Co(met)(hist)(Cl)2] (2), and [Co(met)(pro)(Cl)2] (3), (met = metformin, gly = glycine, hist = histidine, and pro = proline) were evaluated using spectro-analytical techniques, and the stereochemistry of the complexes was determined to be octahedral. UV-Vis absorption, competitive DNA-binding experiments using ethidium bromide (EB) by fluorescence, fluorescence emission studies, viscosity studies, and gel electrophoresis techniques were all employed to explore the binding characteristics of the cobalt (II) complexes with CT-DNA and groove-binding mechanism established. The salt-dependent association of the complexes to CT-DNA was investigated using UV-Vis spectrophotometric analysis. The association of the cobalt (II) complexes with BSA and HSA was explored by utilizing UV-Vis absorption and fluorescence spectroscopy approaches. The findings show that the complexes exhibit adequate capacity to quench BSA and HSA fluorescence and that the binding response is mostly a static quenching mechanism. The cytotoxicity of the complexes has also been appraised with the human breast adenocarcinoma cell lines (MCF-7) and (MDA-MB-231) by utilizing the MTT assay. For each cell line, the IC50 values were computed. In both cell lines, all the complexes were active.

Metformin-Derived Water-Soluble Cobalt Complexes: Thermal, Spectroscopic, DNA Interaction, and Molecular Docking Studies.

Novel three water-soluble cobalt (II) complexes of type [Co(metf)(o-phen)2]Cl2 (1), [Co(metf)(opda)2]Cl2 (2), and [Co(metf)(2-2'bipy)2]Cl2 (3) (Metf, metformin; o-phen, ortho-phenanthroline; opda, ortho-phenylenediamine; 2,2'-bipy, 2,2'-bipyridine) were synthesized and characterized by various analytical and spectral techniques. Based on these studies, octahedral geometry is assigned to these complexes. The stability of the complexes has been calculated from quantum chemical parameters using HOMO-LUMO energies. Thermal degradation pattern of the compounds was studied and Coats-Redfern method is used to determine kinetic parameters for complexes 1, 2, and 3 from thermal studies. The DNA interaction of these complexes was investigated by absorption, emission, and viscosity studies. From the spectral data, it was concluded that the complexes bind to DNA through groove mode of binding. The intrinsic binding constants (Kb) from absorption spectroscopy were 2.49 × 104, 2.48 × 104, and 2.64 × 104 M-1 for 1, 2, and 3, respectively, and Stern-Volmer quenching constants (Ksv) from emission spectroscopy were 0.21, 0.20, and 0.13, respectively. These complexes were screened for nuclease activity of pUC19 DNA, in the presence of H2O2. Discovery studio 2.1 software was used to evaluate binding affinity and interaction pattern of complexes with B-DNA receptor protein and the maximum dock score is seen for complex 2.

Nickel-Metformin Ternary Complexes: Geometrical, Thermal, DNA Binding, and Molecular Docking Studies.

Novel three nickel(II) complexes of type [Ni(metf)(o-phen)2]Cl2 (1), [Ni(metf)(opda)2]Cl2 (2), [Ni(metf)(2-2'bipy)2]Cl2 (3), (Metf = metformin, o-phen = ortho-phenanthroline, opda = ortho-phenylenediamine, 2-2' bipy = 2-2' bipyridyl) were synthesized and characterized by various analytical and spectral techniques. Based on these studies, octahedral geometry is assigned to these complexes. The DNA binding properties of these complexes were investigated by absorption, emission, and viscosity studies. From the spectral data, it was concluded that the complexes bind to DNA through groove mode of binding. The intrinsic binding constants (Kb) from absorption spectroscopy were 1.60 × 104, 3.57 × 104, and 5.70 × 104 M-1 for 1, 2, and 3, respectively, and Stern-Volmer quenching constants (Ksv) from emission spectroscopy were 0.11, 0.87, and 0.24, respectively. Thermal degradation pattern of the compounds was studied and Coats-Redfern method is used to determine kinetic parameters for complexes 1, 2, and 3 from thermal studies. The software Discovery Studio 2.1 was used to assess the binding affinity and interaction pattern of complexes with the B-DNA receptor protein and complex 1 has the highest dock score.

Unintentional Injuries Among Under-five Children in a Rural Area in Delhi.

OBJECTIVE: To determine the prevalence of unintentional injuries and its associated factors among under-five children in Rural Delhi. METHODS: This community based cross-sectional study was conducted in Pooth Khurd village of Delhi during 2018 among under-five children and their care givers. Primary caregivers of the child in the randomly selected households were interviewed using a semi-structured pretested questionnaire. Data related to unintentional injuries in past 12 months and its associated factors were collected. RESULTS: Unintentional injuries were prevalent in 29.3% (95% CI: 25.8-32.9) of the 650 under-five children included. Male children had 1.4 times increased prevalence of injuries (aPR=1.4, 95% CI: 1.1-1.7). As the age increases from 2 years to 5 years the prevalence of injuries increased constantly from 29% to 50%. The prevalence of unintentional injuries was significantly higher among children of working mothers (aPR=1.7, 95% CI: 1.4-2.1), family with more than 3 children (aPR=1.6, 95% CI:1.1-2.4), household without a separate kitchen (aPR=1.6, 95% CI:1.2-2.2) and household with inadequate lighting (aPR=1.8, 95% CI:1.4-2.3). CONCLUSIONS: The factors significantly associated with unintentional injuries were male gender, higher age of the children, maternal occupation, increased number of children in the family, not having a separate kitchen and inadequate lighting.

Quality of life and its determinants among people living with HIV attending an antiretroviral treatment center in Delhi, India.

BACKGROUND: With universal access to antiretroviral treatment (ART), the management of people living with human immunodeficiency virus (PLHIV) encompasses holistic, comprehensive care. Despite being a vital goal of care, quality of life (QOL) assessment of PLHIV in India is neglected. OBJECTIVES: This study assessed the QOL and its determinants among PLHIV accessing services through ART centers. METHODS: The cross-sectional study was conducted from November 2015 to February 2017 among 109 PLHIV attending an ART center in New Delhi. Sociodemographic and clinical profile characteristics were ascertained. QoL was evaluated using the medical outcomes study HIV health survey questionnaire; physical health summary (PHS), and mental health summary (MHS) scores were calculated. Depression was evaluated with the becks depression inventory and social support using the multidimensional scale of perceived social support. Chi-square test, Student's t-test, and analysis of variance were used as test of significance. RESULTS: The overall QOL was: PHS-48.04 ± 8.27 and MHS 42.43 ± 8.79. PHS scores were significantly higher among PLHIV with older age (P = 0.04), higher formal education (P = 0.022), early HIV disease (P = 0.006), higher CD4 counts (current, peak and nadir: P =0.024, 0.008, and ≤0.001, respectively), receiving ART (P = 0.05), with better social support (P = 0.012) and without depression (P ≤ 0.001). Similarly, MHS scores were better in PLHIV with greater formal education (P = 0.009), early HIV disease (P = 0.046), without depression (P ≤ 0.001). CONCLUSION: Depression and social support mechanisms emerged as two key determinants of QOL. Older age, higher education, less advanced disease, and ART were predictive of better QOL.

Mucormycosis: an unusual masquerader of an endobronchial tumour.

Pulmonary mucormycosis is a life-threatening invasive fungal infection usually seen in the background of immunosuppression, haematological malignancies, or uncontrolled diabetes. Immunocompetent hosts can also be affected. Isolated endobronchial mucormycosis is rare with only a few cases reported in the literature. Here, we present a case of an endobronchial mass masquerading as a tumour that was later diagnosed as invasive mucormycosis by histopathological examination.

'Ease of interpretation' of cytological smears stained with modified ultrafast papanicolaou stain: Interobserver agreement and reproducibility.

BACKGROUND: Since its inception in 1995, the Ultrafast Papanicoloau (UFPAP) cytological stain has undergone a number of modifications to suit the local availability of reagents and cost in different set ups. However, the reported results have been uniformly encouraging. We designed a study to investigate the inter-observer agreement in 'perceived ease of interpretation' of cytological smears stained with Modified Ultrafast Papanicoloau stain (MUFPAP). METHODS: After a small pilot study, we prospectively stained air-dried fine needle aspirate smears (FNACs) and Body Fluid smears with the standardized MUFPAP stain. The MUFPAP stained slides were evaluated in tandem with other routine cytological stains as well as independently by two pathologists. Two rater kappa was used to determine the agreement. RESULTS: The study included 93 fluids and 34 FNACs. A vast majority of the cases stained with MUFPAP were rated 'better' than the routine stains in terms of 'overall ease of interpretation' with considerable agreement. The agreement tended to be better for FNACs than fluid specimens. Cases with malignant pathology demonstrated a perfect agreement (kappa = 1) between the raters in terms of 'overall ease of interpretation' (91.7% cases were rated 'very good' by each pathologist) when compared to cases with benign pathology (kappa = 0.52). Nuclear characteristics were appreciated with a better agreement than other parameters. CONCLUSION: Modified UFPAP stain appears to be quick, reliable, cost-effective alternative in cytology, especially for detecting malignant cells in smears with low cellularity. Its specific advantage is robust nuclear staining against a clear background.

Syringocystadenocarcinoma papilliferum with coexisting trichoblastoma: A case report with review of literature.

We present a unique case of syringocystadenoma with malignant transformation into syringocystadenocarcinoma papilliferum and coexisting trichoblastoma arising de novo in a scalp swelling of long duration in a 78-year-old woman. Syringocystadenocarcinoma papilliferum was described by the World Health Organization as an extremely rare malignant adnexal tumor of apocrine origin with varied histology with some cases reported in literature.

Evaluation of Resting Tongue Position in Recently Extracted and Long Term Completely Edentulous Patients: A Prospective Interventional Study.

INTRODUCTION: Presence of abnormal resting tongue position can lead to poor denture retention and stability. The prevalence of retracted tongue position has been found to be higher in partially edentulous subjects compared to dentate subjects and is greatest in completely edentulous individuals. AIM: To evaluate resting tongue position in recently extracted and long term completely edentulous patients, and to evaluate the efficacy of achieving retracted tongue position by simple modification in complete denture along with certain tongue exercises. MATERIALS AND METHODS: A total of 62 study subjects were classified into two groups based on duration of edentulousness. Group A: Recently extracted completely edentulous subjects (<1 year), Group B: Long term completely edentulous subjects (>1-10 year). The patients with retracted tongue position were subjected to a simple modification in complete denture along with inclusion of certain tongue exercises. After eight months patients were recalled and evaluated. The data was analysed using SPSS statistical tests like mean, standard deviation, proportion, Chi square test and McNemar Test. RESULTS: Among the study subjects, 54.9% had retracted tongue position. Group B showed high proportion of retracted tongue position (68.8%) as compared to Group A. After the intervention, 42.8% study subjects gained normal resting tongue position. CONCLUSION: Long term completely edentulous subjects presented retracted tongue position in higher percentage when compared to the recently extracted group. The interventional method employed for the subjects with retracted tongue position, played a significant role to assume normal resting tongue position and showed improvement in denture stability and retention.

Synchronous Malignant Phyllodes Tumor with Skin Ulceration and Invasive Carcinoma as Collision Tumor.

Phyllodes tumor is a rare fibroepithelial biphasic tumor of the breast composed of hypercellular mesenchymal stroma and double-layered epithelial component, arranged in clefts with leaf-like projections. Phyllodes tumor with coincidental presence of invasive carcinoma or in situ ductal carcinoma in the same or distinct breast is a rare occurrence, documented by some reports. Invasive carcinoma can be seen within or outside the phyllodes tumor. Skin ulceration by malignant phyllodes tumor with coexisting invasive carcinoma as collision tumor is extremely rare. Here, we report an extremely rare presentation of malignant phyllodes tumor as a giant fungating mass with distinct invasive carcinoma in the same breast in a 51-year-old female.

Squamous Cell Carcinoma In situ of the Cervix with Superficial Intraepithelial Extension to the Endometrium of Lower Uterine Segment: A Rare Presentation.

Carcinoma of the cervix is the most common malignancy in women in India. Squamous cell carcinoma accounts for more than 70% of the cervical malignancies. Carcinoma of the cervix generally invades the uterine wall by direct extension with or without parametrial involvement, however, rarely can spread superficially to the inner surface of the uterus replacing the endometrium. It is an uncommon phenomenon for an in situ lesion of the cervix to have contiguous superficial spread to the endometrium. We report a case of cervical in situ squamous cell carcinoma in a 45-year-old female with contiguous extension to the endometrium of the lower uterine segment.

Asymptomatic Cryptococcal Antigenemia in People Living with HIV (PLHIV) with Severe Immunosuppression: Is Routine CrAg Screening Indicated in India?

BACKGROUND: Cryptococcal meningitis (CM) is a common, life-threatening opportunistic infection (OI) among people living with HIV (PLHIV) in India. Serum Cryptococcal antigen (CrAg) positivity is predictive of future occurrence of CM and pre-emptive treatment reduces its mortality. Routine CrAg screening among PLHIV is not adopted by India's national programme. This study evaluated the prevalence of CrAg and assessed CrAg positivity in predicting all-cause mortality among PLHIV. METHODS: This prospective study was conducted in a tertiary care, public health facility in New Delhi, India. Prevalence of CrAg was assessed in 128 ART naive adult PLHIV with CD4 < 100 cells/mm3 using a latex agglutination test. Age, gender, weight, body mass index (BMI), CD4 count, haemoglobin, serum albumin, and presence of other OI were evaluated as determinants of CrAg positivity. Subjects were followed up for occurrence of CM and mortality (all-cause) at 12 weeks and 6 months. RESULTS: The mean age of the subjects was 36.2±9.48 years, 73.4% were men, 21.09% women and 5.46% were transgender. The mean BMI was 18.4±2.53 kg/m2 and 64% of subjects belonged to the lower socio-economic strata. Mean CD4 counts of the subjects was 54.9±26.58 cells/mm3 and 42.97% had CD4 < 50 cells/mm3. The prevalence of CrAg in the subjects was 3.125 % (4/128). None of the factors assessed showed statistically significant difference between the 2 groups, though CD4 count <50 cells/mm3, low serum albumin and presence of oral candidiasis had a stronger association with CrAg positivity. None of the subjects developed CM during follow up. At 12 weeks, 3/4 (75%) CrAg positive patients were alive compared to 118/124 (95.16%) of CrAg negative subjects. At 6 months, 50% (2/4) CrAg positive patients had died compared to 10.48% (13/124) CrAg negative (p<0.01). CONCLUSIONS: Though CrAg prevalence in PLHIV with CD4<100 cells/mm3 is moderate, asymptomatic CrAg positivity among PLHIV with CD4 < 100cells/mm3 is significantly associated with higher all-cause mortality. CrAg testing is very cost effective and India's National AIDS Control Programme should seriously consider routine screening among the severely immunosuppressed PLHIV.

Evaluation of moxifloxacin-hydroxyapatite composite graft in the regeneration of intrabony defects: A clinical, radiographic, and microbiological study.

BACKGROUND: The formation of new connective periodontal attachment is contingent upon the elimination or marked reduction of pathogens at the treated periodontal site. An anti-microbial agent, i.e. moxifloxacin has been incorporated into the bone graft to control infection and facilitate healing during and after periodontal therapy. MATERIALS AND METHODS: By purposive sampling, 15 patients with at least two contralateral vertical defect sites were selected. The selected sites in each individual were divided randomly into test and control sites according to split-mouth design. Test site received moxifloxacin-hydroxyapatite composite graft and control site received hydroxyapatite-placebo gel composite graft. Probing depth (PD) and Clinical attachment level (CAL) were assessed at baseline, 3, 6, 9, and 12 months. Bone probing depth (BPD) and hard tissue parameters such as amount of defect fill, percentage of defect fill, and changes in alveolar crest were assessed at baseline, 6, and 12 months. Changes in subgingival microflora were also assessed by culturing the subgingival plaque samples at baseline and at 3-month follow-up. The clinical, radiographic, and microbiological data obtained were subjected to statistical analysis using descriptive statistics, paired sample t-test, independent t-test, and contingency test. RESULTS: On intragroup comparison at test and control sites, there was a significant improvement in all clinical and radiographic parameters. However, on intergroup comparison of the same, there was no statistically significant difference between test and control sites at any interval. Although test sites showed slightly higher amount of bone fill, it was not statistically significant. There was a significant reduction in the counts of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis at both sites from baseline to 3 months. In addition, there was a significant reduction at test sites as compared to control sites at 3-month follow-up (P = 0.003 and P = 0.013). CONCLUSION: The reduction in microbial counts found in test sites at 3-month follow-up could not bring similar significant improvements in the clinical and radiographic parameters though the test sites showed slightly higher bone fill.

Ectopic parathyroid adenoma presenting as facial expansile growths.

BACKGROUND: Giant cell reparative granuloma of the facial skeleton is a rare presentation of hyperparathyroidism. METHODOLOGY: A 17-year-old girl presented with progressive expansile bony growths of the mandible and maxilla. The case was investigated using biopsies, blood tests, imaging, and surgery. RESULTS: Biopsies confirmed giant cell reparative granuloma. Blood testing revealed very high parathyroid hormone levels, and brown tumours due to primary hyperparathyroidism weresuspected. Surgical removal of an ectopic adenoma led to correction of the endocrine condition. CONCLUSIONS: To our knowledge, this is the first reported case of multiple brown tumours of the facial skeleton due to an ectopic parathyroid adenoma. Diagnostic pitfalls and therapeutic challenges are described.