Emergence of extensively drug-resistant tuberculosis (XDR-TB) has significantly threatened to jeopardize global efforts to control TB, especially in HIV endemic regions. XDR-TB is mainly an iatrogenically created issue, and understanding the epidemiological and risk factors associated with it is of paramount importance in curbing this menace. Emergence of this deadly phenomenon can be prevented by prompt diagnosis and effective treatment with second-line drugs in rifampicin-resistant TB (RR-TB) as well as multidrug-resistant TB (MDR-TB) patients. Optimal treatment of RR-TB, MDR-TB and XDR-TB cases alone will not suffice to reduce the global burden. The TB control programmes need to prioritize on policies focusing on the effective as well as rational use of first-line drugs in every newly diagnosed drug susceptible TB patients so as to prevent the emergence of drug resistance.

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Herpes zoster (HZ) is a neurocutaneous disorder due to endogenous reactivation of the varicella-zoster virus (VZV). The typical clinical manifestation is an acute segmental eruption of herpetiform umbilicated vesicles associated with malaise, pain, dysaesthesia, allodynia and probably fever. This review focuses on other possible clinical manifestations of the disease to sensitize physicians not to overlook HZ since only an early antiviral treatment can reduce the risk of post-zosteric neuralgia.

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Background & objectives: District-Level Household Survey-4 (DLHS-4) indicated that during 2012-2013, only 56 per cent of children aged 12-23 months in Tamil Nadu were fully vaccinated, which were lesser than those reported in earlier national surveys. We, therefore, conducted cluster surveys to estimate coverage of childhood vaccination in the State, and also to identify the factors associated with low coverage. Methods: Cross-sectional surveys were conducted in 15 strata [municipal corporation non-slum (n=1), municipal corporation slum (n=1), hilly (n=1), rural (n=6) and urban (n=6)]. From each stratum, 30 clusters were selected using probability proportional to the population size linear systematic sampling; seven children aged 12-23 months were selected from each cluster and their mothers/care-takers were interviewed to collect information about vaccination status of the child. A child was considered fully vaccinated if he/she received bacillus Calmette-Guérin (BCG), three doses of pentavalent, three doses of oral polio vaccine and one dose of measles vaccine, and appropriately vaccinated if all vaccine doses were given at right age and with right interval. Further, coverage of fully vaccinated children (FVC) as per vaccination cards or mothers' recall, validated coverage of FVC (V-FVC) among those having cards, and coverage of appropriately vaccinated children (AVC) were estimated using survey data analysis module with appropriate sampling weights. Results: A total of 3150 children were surveyed, of them 2528 (80.3%) had vaccination card. The weighted coverage of FVC, V-FVC and AVC in the State was 79.9 per cent [95% confidence interval (CI): 78.2-81.5], 78.8 per cent (95% CI: 76.9-80.5) and 69.7 per cent (95% CI: 67.7-71.7), respectively. The coverage of individual vaccine ranged between 84 per cent (measles) and 99.8 per cent (BCG). About 12 per cent V-FVC were not vaccinated as per the vaccination schedule. Interpretation & conclusions: The coverage of FVC in Tamil Nadu was high, with about 80 per cent children completing primary vaccination. Efforts to increase vaccination coverage in the State need to focus on educating vaccinators about the need to adhere to the national vaccination schedule and strengthening supervision to ensure that children are vaccinated appropriately.

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Background & objectives: Although the need for a combination of antiepileptic drugs (AEDs) in the treatment of epilepsy is well justified, but an associated increase in adverse effects (AEs) lends a restriction to polytherapy. The aim of this study was to evaluate AEs and drug load (prescribed daily dose/defined daily doses) of AEDs in patients with epilepsy (PWE). Methods: Consecutive PWEs attending Epilepsy clinic in a tertiary care hospital in New Delhi, India, were enrolled in the study. Demographic variables, such as age, gender, diagnosis, age at onset of seizures, frequency of seizures, use of all AEDs and adverse event profile (AEP) score were noted. Routine laboratory tests including lipid profile, fasting blood glucose, haematological parameters and liver and kidney function tests were done. Results: A total of 697 consecutive patients were included in this study. Of them, 64.4 per cent were male; mean age was 29.6 ± 10.6 yr. Generalized seizures and focal seizures were recorded in n=386 (55.4%) and n=311 (44.6%), respectively. Monotherapy and polytherapy with two and greater than or equal to three AEDs were prescribed in 264 (37.9%), 243 (34.9%) and 190 (27.2%) patients, respectively. The average AED load, duration of treatment as well as AEP score were found to be significantly higher in combination of greater than or equal to three AEDs as compared to both monotherapy and combination of two AEDs, whereas no significant difference was observed between monotherapy and combination of two AEDs. Patients on monotherapy were in good control of seizures as compared to polytherapy. There was no significant change in biochemical parameters between the groups. Interpretation & conclusions: Polytherapy with combination of greater than or equal to three AEDs was associated with higher AEs and lower seizure control as compared to both monotherapy and combination of two AEDs. AEs did not correlate with AED load, seizure type, gender and age of the patients but were associated with both numbers of AEDs as well as seizure frequency in PWE.

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Background & objectives: Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections. Methods: Relevant research questions were identified. An extensive electronic and manual search methodology was used. Potentially eligible articles were screened for eligibility. The relevant data were extracted independently in a pre-specified data extraction form. Pooling of data was planned. Results: Of the 340 records screened, 24 studies were included for data extraction and incorporation in the review [carbapenems - imipenem and meropenem (n=7); aminoglycosides - amikacin and gentamicin (n=9); piperacillin-tazobactam (n=2); quinolones (n=2); third- and fourth-generation cephalosporins (n=4) and colistin nil]. For each of the drug categories, the information for all the questions that the review sought to answer was incomplete. There was a wide variability in the covariates assessed, and pooling of results could not be undertaken. Interpretation & conclusions: There is a wide knowledge gap for determining the doses of antimicrobials used for Gram-negative infections in neonates. A different profile of newborns in the developing countries could affect the disposition of antimicrobials for Gram negative infections, necessitating the generation of PK-PD data of antimicrobials in neonates from developing countries. Further, guidelines for treatment of neonatal conditions may incorporate the evidence-based PK-PD-guided dosing regimens.

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Background & objectives: Securing long-term venous access is an essential part of sick newborn care. The malposition of central line tip leads to several complications. There is a need for an easily available bedside investigating tool to diagnose these malpositions. This study was done to compare the effectiveness of real-time ultrasound (RTUS) with X-ray in identifying the peripherally inserted central catheter (PICC) line tip. Methods: This pilot observational study was conducted in a level III Neonatal Intensive Care Unit of a tertiary care hospital in India, from June 2012 to June 2013. A total of 33 PICC lines in 31 infants were included in the study. After insertion of PICC line, X-ray and RTUS were done to locate the tip of the PICC line. Results: In this study, PICC line tip could be identified by bedside RTUS in 94 per cent of line insertions. Standard X-ray identified the tip in all cases. RTUS has been shown to have good diagnostic utility in comparison with X-ray with sensitivity and specificity being 96.55 and 100 per cent, respectively. In our study, majority of malpositions were identified and manipulated by RTUS, thus second X-rays were avoided. Interpretation & conclusions: The result of this pilot study shows that RTUS may be a reliable and safe bedside tool for determining the tip of PICC lines. However, studies with large sample size need to be done to confirm these findings.

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Background & objectives: The interactions between HIV and malaria co-infection have been shown to influence each other in their clinical outcomes in Sub-Saharan Africa. This study was carried out in the two States of north east India endemic for both HIV and malaria infections, to study the interactions between the two diseases in the HIV-infected population. Methods: In this prospective study, a total of 333 HIV-infected individuals were followed up for a period of 6-18 months in Mizoram and Manipur during 2010-2011. The study assessed the changes in viral load and also the therapeutic efficacy of artesunate plus sulphadoxine-pyrimethamine (AS+SP) combination therapy in HIV-infected and HIV-uninfected individuals with Plasmodium falciparum malaria. Results: Viral load in HIV-infected malaria patients on day zero (D0) ranged from 1110 to 147,000 copies/ml. The log transformation of the geometric means of HIV viral loads revealed no significant difference on different days of follow up. There was 100 per cent adequate clinical and parasitological response (ACPR) after treating with artemisinin based combination therapy (ACT) both in HIV-infected and HIV-uninfected P. falciparum-positive individuals. Similarly, chloroquine showed 100 per cent ACPR in P. vivax HIV-infected individuals. Interpretation & conclusion: The study showed no significant increase in HIV viral load in malaria cases. All HIV-infected and HIV-uninfected P. falciparum malaria-positive cases responded to the treatment with 100 per cent ACPR.

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Background & objectives: Celiac disease (CD) and type 1 diabetes mellitus (T1DM) share a common genetic locus and clinical manifestations. The present study was planned to compare clinical, biochemical and hormonal profiles of patients with CD and CD with T1DM. Methods: Records of CD patients with age ≤20 yr, available anthropometric measurements, haematological, biochemical and hormonal workup with tissue transglutaminase IgA antibody and duodenal biopsy (Marsh grade) were screened. The patients were divided into two groups i.e., CD alone (Group A) and concurrent CD with T1DM (Group B). Results: One hundred and nine patients of CD (57 male) with a mean age of 14.9±2.9 yr were evaluated. Of these, 86 (78.9%) patients had CD alone and 23 (13 females) (21.1%) patients had CD with T1DM. The age at diagnosis and the lag duration for the diagnosis of CD were 11.5±4.6 versus 13.8±3.4 yr (P<0.05) and 48.8 ±43.3 versus 20.2±31.8 months (P<0.05) in groups A and B, respectively. The most common histopathological grade was type 3b (59.2%) in group A and type 2 (42.1%) in group B. Short stature (87% vs. 40.9%; P<0.01), anaemia (80.9% vs. 45%, P<0.01) and delayed puberty (61.9% vs. 29.4%; P<0.01) were more common in group A. Interpretation & conclusions: Patients with CD alone have a longer lag time to diagnosis and consequent sequel in the form of anaemia, short stature and delayed puberty, as compared to patients with concurrent CD and T1DM.

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Background & objectives: Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. Methods: This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. Results: The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Interpretation & conclusions: Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

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Background & objectives: The reference radioactive iodine uptake (RAIU) values established in the 1970s in the era of widespread iodine deficiency were relatively high. Now, after four decades of successful Universal Salt Iodization (USI) programme in India, there is a need to re-establish these reference ranges. The present study was aimed to quantify the two-hour and 24-h RAIU values in iodine sufficient euthyroid individuals and validate the results in Graves' and Hashimoto's thyroiditis patients. Methods: In this prospective study conducted from April 2012 to September 2013, euthyroid volunteers who consented for the investigations were enrolled in the study. Treatment-naive Graves' disease and Hashimoto's thyroiditis patients were recruited from the outpatient clinic. The investigations included neck ultrasonography, thyroid function tests, thyroglobulin (Tg), anti-Tg and anti-thyroid peroxidase antibody and urinary iodine concentration. Results: Three different groups comprising 110 euthyroid volunteers, 38 Graves' and 17 Hashimoto's thyroiditis patients were enrolled in the study. The mean 2-h RAIU values for the euthyroid group, Hashimoto's thyroiditis and Graves' patients were 3.83±2.77, 4.22±3.41 and 32.67±15.93 per cent, and mean 24-h RAIU values were 12.75±5.51, 11.66±9.55 and 61.85±12.9 per cent, respectively. The mean thyroid volumes were 7.63±2.72, 7.81±1.67 and 20.76±12.56 ml for the euthyroid, Hashimoto's thyroiditis and Graves' disease groups and the mean spot urinary iodine concentrations were 9.0, 7.8 and 13.9 μg/dl in the three groups, respectively. The new reference range (95% confidence interval) for two-hour was 1-7 per cent and 24-h was 7-18 per cent. Interpretation & conclusions: Compared to the previous values, there was a considerable decrease in the RAIU values in euthyroid individuals. This was further corroborated with increase in the urinary iodine concentration and decrease in thyroid volume, attributed to successful USI programme. Further studies with a large sample from different parts of India need to be done to confirm these findings.

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Background & objectives: Obesity is known for low-grade inflammatory state with enhanced production of inflammatory mediators in children and adolescents. Soluble urokinase plasminogen activator receptor (suPAR) can be generated as a pro-inflammatory marker. This study was conducted to evaluate the role of suPAR, and its association with leptin, adiponectin, interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP) and fibrinogen in adolescent obesity. Methods: A total of 98 participants, 55 obese individuals and 43 healthy controls, aged between 10 and 17 yr, were included in the study. Serum suPAR, IL-6, leptin and adiponectin were measured using ELISA method. Results: Serum suPAR, IL-6, fibrinogen, hsCRP and leptin levels in obese individuals were significantly higher than those of controls (P<0.05 & P<0.001). Serum adiponectin levels in obese individuals were significantly lower than those of controls (P<0.01). Interpretation & conclusions: Our findings showed that suPAR, IL-6, fibrinogen, hsCRP and leptin were significantly higher in the obese individuals than those of controls. suPAR may be a good novel biomarker for systemic subclinical inflammation and immune activation linked to adolescent obesity.

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Background & objectives: Acute rheumatic fever and rheumatic heart disease (RHD) are important public health problems in developing countries. In this study, peptidomic analyses on RHD patients and healthy individuals were performed to characterize variations in serum peptide levels using label-free quantitation approaches. Methods: Blood samples were obtained from 160 healthy controls and 160 RHD patients. Of the 448 identified peptides, 272 were analyzed by two label-free mass spectrometry methods, the spectral count and spectral index. Results: There were 38 proteins and 95 peptides with significant (adjusted P<0.001) differences in the abundance of peptides between healthy controls and RHD patients, including multiple peptides derived from histone H2B, villin-like protein, complement C4-B and motile sperm domain containing protein-2. The levels of 10 peptides were upregulated, and 85 peptides were downregulated in patients compared to controls. In addition, in patients, the levels of four proteins were upregulated and 34 were downregulated compared to controls. Interpretation & conclusions: This study shows that detection of significant changes in serum peptides reflects the difference between RHD patients and healthy controls. This label-free method may be helpful for clinicians to treat RHD patients during the perioperative period.

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Background & objectives: The Broselow tape has been validated in both ambulatory and simulated emergency situations in the United States and is believed to reduce complications arising from inaccurate drug dosing and equipment sizing in paediatric population. This study was conducted to determine the relationship between the actual weight and weight determined by Broselow tape in the Indian children and to derive an equation for determination of weight based on height in the Indian children. Methods: This cross-sectional study was conducted at a tertiary care hospital in Mumbai, India. The participants' weights were divided into three groups <10 kg, 10-18 kg and >18 kg with a total sample size estimated to be 210 (70 in each group). Using the tape, the measured weight was compared to Broselow-predicted weight and percentage weight was calculated. Accuracy was defined as agreement on Broselow colour-coded zones, as well as agreement within 10 per cent between the measured and Broselow-predicted weights. The resulting data were compared with weights estimated by advanced paediatric life support (APLS) and updated APLS formulae using Pearson's correlation coefficient. Results: The mean percentage differences were −11.78, −17.09 and −14.27 per cent for <10, 10-18 and >18 kg weight-based groups, respectively. The Broselow colour-coded zone agreement was 33.3 per cent in children weighing <10 kg, but only 7.4 per cent in the 10-18 kg group and 33.9 per cent in the >18 kg group. Agreement within 10 per cent was 53.13 per cent for the <10 kg group, but only 21.08 per cent for the 10-18 kg group and 33.9 per cent for the >18 kg group. Application of 10 per cent weight correction factor improved the percentages to 79.2 per cent for the <10 kg category, to 55.70 per cent for the 10-18 kg group and to 61.0 per cent for the >18 kg group. The correlation coefficient between actual weight and weights estimated by Broselow tape (r=0.89) was higher than that between actual weight and weight estimated by APLS method or updated APLS formulae (r=0.68) in 12-60 months age group as well as in >60 months age group (r=0.76). Interpretation & conclusions: Broselow weight overestimated weight by >10 per cent in majority of Indian children. The weight overestimation was greater in children belonging to over 18 and 10-18 kg weight groups. Applying 10 per cent weight correction factor to the Broselow-predicted weight may provide a more accurate estimation of actual weight in children attending public hospital. Weights estimated using Broselow tape correlated better with actual weights than those calculated using APLS and updated APLS formulae.

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Background & objectives: Foot length of the newborn has a good correlation with the birth weight and is recommended to be used as a proxy measure. There can be variations in the measurement of foot length. A study was, therefore, carried out to develop a foot length calliper for accurate foot length measurement and to find cut-off values for birth weight and gestational age groups to be used by primary healthcare workers. Methods: This study was undertaken on 645 apparently healthy newborn infants with known gestational age. Nude birth weight was taken within 24 h of birth on a standard electronic weighing machine. A foot length calliper was developed. Correlation between foot length and birth weight as well as gestational age was calculated. Correctness of cut-off values was tested using another set of 133 observations on the apparently healthy newborns. Action-oriented colour coding was done to make it easy for primary healthcare workers to use it. Results: There was a significant correlation of foot length with birth weight (r=0.75) and gestational age (r=0.63). Cut-off values for birth weight groups were 6.1, 6.8 and 7.3 cm and for gestational age of 6.1, 6.8 and 7.0 cm. Correctness of these cut-off values ranged between 77.1 and 95.7 per cent for birth weight and 60-93.3 per cent for gestational age. Considering 2.5 kg as cut-off between normal birth weight and low birth weight (LBW), cut-off values of 6.1, 6.8 and 7.3 were chosen. Action-oriented colour coding was done by superimposing the colours on the scale of the calliper, green indicating home care, yellow indicating supervised home care, orange indicating care at newborn care units at primary health centres and red indicating Neonatal Intensive Care Unit care for infants. Interpretation & conclusions: A simple device was developed so that the primary health care workers and trained Accredited Social Health Activist workers can identify the risk of LBW in the absence of accurate weighing facilities and decide on the type of care needed by the newborn and take action accordingly.

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