Background & objectives: Though studies have reported high prevalence rates of metabolic syndrome among patients with bipolar disorder (BPAD) and schizophrenia, there is lack of data on the impact of the same on the patients' life. This study was aimed to assess the lifestyle related factors associated with metabolic syndrome (MetS) and to study the impact of MetS on functioning and quality of life (QOL) in patients with BPAD and schizophrenia. Methods: A total of 102 patients with BPAD and 72 patients with schizophrenia attending the output unit of a tertiary care hospital in north India were evaluated for MetS. These patients were assessed on Health Promoting Lifestyle Profile scale II (HPLP II), World Health Organization QOL -Bref Version (WHOQOL-Bref), Impact of Weight on Quality of Life- Lite version (IWOQOL -Lite), Body weight, Image and Self-esteem Evaluation questionnaire (BWISE), Obesity-related Problem scale (OP scale) and Global Assessment of Functioning (GAF) scale. Results: MetS was associated with lower scores on domains of health responsibility and nutrition habit domain on HPLP-II scale in both groups, and additionally on physical activity and stress management domain in BPAD group. On WHOQOL-Bref, MetS was associated with lower scores on the domains of physical and psychological health in both groups. On IWQOL–Lite, scores on personal distress and self esteem domains were higher in those with obesity in both groups and also on physical activity domain in schizophrenia group. Those with MetS had lower level of functioning as measured by GAF in schizophrenia group. Fulfillment of higher number of criteria of MetS correlated with poorer quality of life and higher problems in both groups. Interpretation & conclusions: Many modifiable lifestyle factors increase the risk of MetS. MetS was found to be associated with poorer QOL in patients with BPAD and schizophrenia; in addition, obesity led to poor self-esteem and excessive personal distress.

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Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadotropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoimmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI.

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Background & objectives: The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India. Methods: A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform. Results: The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. the HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology. Interpretation & conclusions: A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.

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Background & objectives: In developed countries, efforts have been made to restrict episiotomy practice. However, in developing countries the episiotomy rates continue to be high. This study was conducted to evaluate the pattern of episiotomy use and its immediate complications among women delivering at tertiary level public hospitals in India. Methods: Prospective data of all women undergoing vaginal delivery including instrumental delivery were collected daily from the labour room registers of the 18 tertiary care hospitals on a structured proforma. Weekly data from all sites were sent to a central unit for compilation and analysis. Odds ratio was used to compare the proportion of genital trauma among women with and without episiotomy both in nulliparous and multiparous women. Results: Among 1,20,243 vaginal deliveries, episiotomy was performed in 63.4 per cent (n=76,305) cases. Nulliparaous women were 8.8 times more likely to undergo episiotomy than multiparous women. The various genital tract injuries reported were first degree perineal tear (n=4805, 3.9%), second degree perineal tear (n=1082, 0.9%), third and fourth degree perineal tear (n=186, 0.2%), anterior vaginal trauma requiring suturing (n=490, 0.4%), extension of episiotomy/vaginal laceration/excessive bleeding from episiotomy or tear (n=177, 0.15%), vulval/vaginal haematoma (n=70, 0.06%) and cervical tear (n=108, 0.08%). The combined rate of third and fourth degree perineal tears was observed to be significantly lower (p<0.001) among nullipara who received episiotomy (0.13%) compared to those who delivered without episiotomy (0.62%). Interpretations & conclusions: Significantly lower rates of third or fourth degree perineal tear were seen among nulliparous women undergoing episiotomy. The risk and benefit of episiotomy and its complications need to be evaluated through randomized clinical trials in the Indian context.

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Background & objectives: Mycobacterium tuberculosis (M. tuberculosis) has four homologous mammalian cell entry (mce) operons (mce1-4) that encode exported proteins and have a possible role in the virulence mechanism of this pathogen. The expression of mce operon is considered to be complex and not completely understood. Although expression of mce operon at different in vitro growth phases has been studied earlier, its expression in different M. tuberculosis isolates under different growth phases is not yet studied. The present preliminary study was conducted on a limited number of isolates to know the trend of expression pattern of mce operon genes in different M. tuberculosis isolates under different growth stages. Methods: In this study, we monitored the transcriptional profile of selected mce operon genes (mce1A, mce1D, mce2A, mce2D, mce3A, mce3C) in different M.tuberculosis isolates (MDR1, MDR2, and sensitive isolate) at early exponential and stationary phases using real-time quantitative PCR. Results: The expression ratio of all selected mce operon genes in all M. tuberculosis isolates was reduced at the initial phase and increased substantially at a later phase of growth. Higher expression of mce1 operon genes was found in all M. tuberculosis isolates as compared to other mce operon genes (mce2 and mce3 operons) at stationary growth phase. Interpretation & conclusions: the higher expression of mce operon genes at stationary phase (as compared to early exponential phase) suggested growth phase dependent expression of mce operon genes. This indicated that the mce operon genes might have a role in M. tuberculosis survival and adaptation on the onset of adverse condition like stationary phase. Identification of differentially expressed genes will add to our understanding of the bacilli involved in adaptation to different growth conditions.

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Background & objectives: The changing spectrum of Candida species in causation of oropharyngeal candidiasis and their antifungal susceptibility pattern among the HIV infected individuals has made the identification to species level mandatory and detection of drug resistance necessary for patient care. The present study was carried out to determine the species distribution and antifungal susceptibility profile of oral Candida isolates colonizing or infecting both HIV seropositive and seronegative individuals. Methods: A case-control study was conducted including 141 consecutive, non-repeat HIV-seropositive individuals and an equal number of sex and age matched HIV-seronegative control. Speciation of the oropharyngeal Candida isolates was done using standard yeast identification protocol. Antifungal susceptibility testing was done by the disk-diffusion method as well as by Fungitest method. Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%), C. dubliniensis (n=9, 14.7%), C. parapsilosis (n=2, 3.2%), C. glabrata (n=2, 3.2%), and C. famata (n=1, 1.6%). Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control) group. Antifungal susceptibility testing revealed (n=6, 9.3%) C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country.

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Background & objectives: Limited data are available on prescription patterns of the antidepressants from India. We studied antidepressants' prescription pattern from five geographically distant tertiary psychiatric care centers of the India. Method: In this cross-sectional study, all patients who attended outpatients department or were admitted in the psychiatry wards at Lucknow, Chandigarh, Tiruvalla, Mumbai and Guwahati on a fixed day, who were using or had been prescribed antidepressant medications, were included. The data were collected on a unified research protocol. Results: A total of 312 patients were included. Mean age was 39±14.28 yr and 149 (47.76%) were females, 277 (87.5%) were outpatients. Among the patients receiving antidepressants, 150 (48.1%) were of diagnoses other than depression. Diabetes mellitus 18 (5.78%) was the most common co-morbid medical illness. A total of 194 (62.2%) patients were using selective serotonin reuptake inhibitors (SSRIs) with escitalopram 114 (36.53%) being the most common antidepressant used. Overall, 272 (87.18%) patients were using newer antidepressants. Thirty (9.62%) were prescribed more than one antidepressant; 159 (50.96%) patients were prescribed hypnotic or sedative medications with clonazepam being the most common (n=116; 37.18%). Interpretation & conclusions: About half of the patients with diagnoses other than depression were prescribed antidepressants. SSRIs were the most common group and escitalopram was the most common medication used. Concomitant use of two antidepressants was infrequent. Hypnotic and sedatives were frequently prescribed along with antidepressants.

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Background & objectives: There is a paucity of data available on genetic biodiversity of Mycobacterium tuberculosis isolates from central India. The present study was carried out on isolates of M. tuberculosis cultured from diagnostic clinical samples of patients from Bhopal, central India, using spoligotyping as a method of molecular typing. Methods: DNA was extracted from 340 isolates of M. tuberculosis from culture, confirmed as M. tuberculosis by molecular and biochemical methods and subjected to spoligotyping. The results were compared with the international SITVIT2 database. Results: Sixty five different spoligo international type (SIT) patterns were observed. A total of 239 (70.3%) isolates could be clustered into 25 SITs. The Central Asian (CAS) and East African Indian (EAI) families were found to be the two major circulating families in this region. SIT26/CAS1_DEL was identified as the most predominant type, followed by SIT11/EAI3_IND and SIT288/CAS^[2]. Forty (11.8%) unique (non-clustered) and 61 (17.9%) orphan isolates were identified in the study. There was no significant association of clustering with clinical and demographic characteristics of patients. Interpretation & conclusions: Well established SITs were found to be predominant in our study. SIT26/CAS1_DEL was the most predominant type. However, the occurrence of a substantial number of orphan isolates may indicate the presence of active spatial and temporal evolutionary dynamics within the isolates of M. tuberculosis.

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The sickle cell gene in India represents a separate occurrence of the HbS mutations from those in Africa. Sickle cell disease in India occurs against different genetic and environmental backgrounds from those seen in African patients and there is evidence of clinical differences between the populations. Knowledge of the clinical features of African disease was drawn from the Jamaican Cohort Study, based on prospective follow up of all cases of sickle cell disease detected by the screening of 100,000 consecutive newborns in Kingston, Jamaica, and supplemented by observations from the Cooperative Study of Sickle Cell Disease in the US. Defining the principal causes of early morbidity in African sickle cell disease led to successful interventions including pneumococcal prophylaxis, parental education in the early diagnosis of acute splenic sequestration, and the early detection by trans-cranial Doppler of cerebral vessel stenosis predictive of stroke but their success depended on early diagnosis, ideally at birth. Although reducing mortality among patients with African forms of SS disease, the question remains whether these interventions are appropriate or justified in Indian patients. This dilemma is approached by comparing the available data in African and Indian forms of SS disease seeking to highlight the similarities and differences and to identify the deficiencies in knowledge of Indian disease. These deficiencies could be most readily addressed by cohort studies based on newborn screening and since much of the morbidity of African disease occurs in the first five years of life, these need not be a daunting prospect for Indian health care personnel. Newborn screening programmes for sickle cell disease are already underway in India and appropriate protocols and therapeutic trials could quickly answer many of these questions. Without this knowledge, Indian physicians may continue to use possibly unnecessary and expensive models of care.

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Background & objectives: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. Methods: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. Results: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. Interpretation & conclusions: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

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Background & objectives: Healthcare associated infections (HAIs) increase the length of stay in the hospital and consequently costs as reported from studies done in developed countries. The current study was undertaken to evaluate the impact of HAIs on length of stay and costs of health care in children admitted to Paediatric Intensive Care Unit (PICU) of a tertiary care hospital in north India.Methods: This prospective study was done in the seven bedded PICU of a large multi-specialty tertiary care hospital in New Delhi, India. A total of 20 children with HAI (cases) and 35 children without HAI (controls), admitted to the PICU during the study period (January 2012 to June 2012), were matched for gender, age, and average severity of illness score. Each patient's length of stay was obtained prospectively. Costs of healthcare were estimated according to traditional and time driven activity based costing methods approach. Results: The median extra length of PICU stay for children with HAI (cases), compared with children with no HAI (controls), was seven days (IQR 3-16). The mean total costs of patients with and without HAI were ' 2,04,787 (US$ 3,413) and ' 56,587 (US$ 943), respectively and the mean difference in the total cost between cases and controls was ' 1,48,200 (95% CI 55,716 to 2,40,685, p<0.01). Interpretation & conclusions: This study highlights the effect of HAI on costs for PICU patients, especially costs due to prolongation of hospital stay, and suggests the need to develop effective strategies for prevention of HAI to reduce costs of health care.

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Background & objectives: Early atherosclerosis and vascular complication have been described in thalassaemia patients. There is lack of data or guidelines regarding monitoring of vascular health in thalassaemia. This study was conducted to compare carotid artery structural and functional indices such as carotid artery intima-media thickness (CIMT), stiffness index (SI) and Young's elastic modulus (YEM) in β-thalassemia patients with age and sex matched controls, and to correlate these parameters with serum ferritin, cardiac iron, and hepatic iron. Methods: This cross-sectional study included 53 β-thalassaemia patients receiving regular blood transfusions. Carotid artery indices such as CIMT, SI, and YEM were calculated by duplex ultrasound and colour Doppler. Serum ferritin levels were measured by chemiluminescence. Cardiac and hepatic iron estimation were done using MRI T2* sequences analyzed by a special thalassaemia software. Results: Mean CIMT of cases and controls were 0.48 ± 0.04 and 0.44±0.02 mm, respectively and these were significantly different (P<0.001). Similarly significant differences were noted in SI and YEM of cases (2.45±0.79 and 96.12±34.85, respectively) as compared to controls (1.98±0.54 and 68.60±24.29, respectively) (p<0.001). There was significant inverse correlation between stiffness index and cardiac iron overload assessed by MRI cardiac T2* (p=0.03). Mean SI and YEM of cases were (2.1736 ± 0.2986 and 107.3± 41.6, respectively) significantly higher among non-splenectomized patients compared to splenectomized patients (2.0136 ± 0.263 and 86.9 ± 25.2, respectively) (p<0.05). Interpretation & conclusions: CIMT and arterial stiffness indices were significantly increased in β-thalassaemia patients compared to controls which was indicative of early atherogenic changes. This study supports the hypothesis that iron overload is a risk factor for early atherosclerosis and cardiovascular disease.

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The many benefits of laparoscopy, including smaller incision, reduced length of hospital stay and more rapid return to normal function, have seen its popularity grow in recent years. With concurrent improvements in non-surgical cancer management the importance of accurate staging is becoming increasingly important. There are two main applications of laparoscopic surgery in managing hepato-pancreatico-biliary (HPB) malignancy: accurate staging of disease and resection. We aim to summarize the use of laparoscopy in these contexts. The role of staging laparoscopy has become routine in certain cancers, in particular T^[2] staged, locally advanced gastric cancer, hilar cholangiocarcinoma and non-Hodgkin's lymphoma. For other cancers, in particular colorectal, laparoscopy has now become the gold standard management for resection such that there is no role for stand-alone staging laparoscopy. In HPB cancers, although staging laparoscopy may play a role, with ever improving radiology, its role remains controversial.

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Background & objectives: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including β-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse β-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of β-thalassaemia major and SCA. Methods: a total of 620 samples (420 β-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with β-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. β-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of β-thalassaemia major as well as SCA was evaluated. Results: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in β-thalassaemia major as well as SCA. Interpretation & conclusions: This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of β-thalassaemia as well as SCA.

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Background & objectives: Preventing unintended pregnancies among people living with HIV (PLHIV) is one of the strategies of WHO for preventing parent-to-child transmission (PPTCT). Given the limitation of only condom use, the objective of this study was to improve use of dual contraceptive methods among HIV infected women. Methods: An experimental study among HIV positive women was conducted at two tertiary care level hospitals in Mumbai. Linking HIV with family planning services was the focus of intervention at one site and standard level of care was maintained at the control site. At each site, 150 HIV+ve women attending counselling and testing centres, who did not intend to get pregnant in the next one year and were eligible to use dual methods, were enrolled and followed up to one year. Results: At the end of one year, 60 per cent women in the intervention group reached Family Planning centres compared to eight per cent in the control group. There was three times more acceptance and continuation of use of dual methods along with increase in consistent use of condoms and less number of unplanned pregnancies in the intervention group than the control group. Interpretation & conclusions: The study findings demonstrate that linking HIV and family planning services may facilitate the uptake of dual methods of contraception without reducing consistent condom use among HIV infected women. The PPTCT programmes need to focus on the component of Prong 2 of PPTCT which aims to prevent unintended pregnancies among HIV positive women.

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