Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease.

BACKGROUND: The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. METHODS: Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. RESULTS: Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). CONCLUSIONS: Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

A Bibliometric Study of the Pediatric Inguinal Hernia Publication Landscape from the Web of Science Database.

Background: The number of times a research work gets cited by another article is one of the article-level metrics for assessing the quality of a research publication. Citation analysis by bibliometric review has been performed in several disciplines. The current study was aimed to systematically review the literature available on pediatric inguinal hernia since 1960 in terms of the 25 most cited articles in this field and analyze the bibliometric variables author and organizational collaborative patterns. Methods: Thomson Reuters Web of Science citation indexing database and research platform were used to retrieve the most cited articles in pediatric inguinal hernia (PIH) using appropriate search strings. The characteristics (name of authors, the total number of authors, the title of publication, journal of publication, year of publication, etc.) of the 25 top-cited articles were recorded. Specific bibliographical parameters were derived and analyzed. Visualization maps were generated using VOSviewer software. Results: The analysis revealed that the Journal of Pediatric Surgery was leading the choice of journal for publication. While most of the publications originated from the United States of America, Schier was the most influential author. Five of the eight top-productive authors are also the most connected. Conclusion: Articles on laparoscopic repair in PIH have been heavily cited. Following the United States of America, Turkey stands out as the topmost productive country in PIH. The publications on PIH show that "collaboration" is the bridging force between productivity and influence on the academic community.

Fifty Most Influential Articles on Anorectal Malformations: A Tribute through Bibliometric Ranking.

Background: With the global assimilation of "publish and perish" culture into institutional academics, there has been an exponential rise in the publication numbers. There are ~2500 PUBMED entries related to "anorectal malformation (ARM)." The young clinician in his pursuit to translate experimental research to bedside often finds himself lost "in the midst of plenty." This bibliometric analysis has been conducted to codify the seminal work on ARM for future reference and pay tribute to the most impactful articles. Materials and Methods: Thomson Reuters Web of Science citation indexing database and research platform was used to retrieve the most cited articles in ARM using appropriate search strings. The characteristics (name of authors, the total number of authors, the title of publication, journal of publication, year of publication, etc.,) of the 50 top-cited articles were analyzed. Results: The analysis revealed that the Journal of Paediatric Surgery was leading the choice of journal for publication. While most of the publications originated from the United States of America, Alberto Pena was the most influential author. The most studied topic was on associated malformations, and the most common study design was cohort studies. Conclusion: The approach of citation analysis provided us an opportunity to retrieve the most influential articles on ARM. The trends in research in ARM have also been analyzed, spreading over five decades.

Diversity in substance use behaviour among street children of Delhi under Bayesian paradigm.

BACKGROUND: Shannon's index is one of the measures of biodiversity, which is intended to quantify both richness and evenness of the species/individuals in the ecosystem or community. However, application of Shannon's index in the field of substance use among the street children has not been done till date. METHODS: This paper is concerned with methods of estimating Shannon's diversity index (SDI), which can be used to capture the variation in the population due to certain characteristics. Under the consideration that the probability of abundance, based on certain characteristics in the population, is a random phenomenon, we derive a Bayesian estimate in connection with Shannon's information measure and their properties (mean and variance), by using a probability matching prior, through simulation and compared it with those of the classical estimates of Shannon. The theoretical framework has been applied to the primary survey data of substance use among the street children in Delhi, collected during 2015. The measure of diversity was estimated across different age profiles and districts. RESULTS: The results unrevealing the diversity estimate for street children corresponding to each region of Delhi, under both the classical and Bayesian paradigms. Although the estimates were close to one another, a striking difference was noted in the age profile of children. CONCLUSIONS: The Bayesian methodology provided evidence for a greater likelihood of finding substance-using street children, belonging to the lower age group (7-10, maximum Bayesian entropy-3.73), followed by the middle (11-14) and upper age group (15-18). Moreover, the estimated variance under the Bayesian paradigm was lesser than that of the classical estimate. There is ample scope for further refinement in these estimates, by considering more covariates that may have a possible role in initiating substance use among street children in developing countries like India.

The Past, Present and Future of Literature Pertaining to Betel (Areca) Nut: A Citation Analysis.

Objective and method: Betel (areca) nut has recently received interest from researchers and policy makers for its role as a psychoactive substance. It was historically limited to Asia-pacific region, but with the advent of globalization, it has become an equally challenging public health problem across the globe. Previously published literature can give us valuable insights in terms of historical interest and understanding related to betel nut. With the expansion of biomedical research a huge number of articles have been published on the same. In terms of understanding the impact of an article, citations are considered a proxy estimate measure. Thus we decided to analyze the top 100 cited articles (till November 2018) related to betel nut. The search in Google scholar database was done with the help of freely available software, Publish or Perish. Results: Overall we found that most articles were published from the fields of dentistry and oncology, with relatively minimal contribution from the field of Addiction Psychiatry. Hence, most articles have addressed the issue of epidemiology and mechanism with lesser share of treatment related publications. Various important information related to these articles have been discussed including the institutions, countries, journals and impactful authors in the field. Subsequently, original research articles are further classified into descriptive/epidemiology, mechanism, management, scale/measurement, imaging and medical psychiatry. Importance: This citation analysis provides valuable information with regards to the emphasis of researchers in the field, and areas where more emphasis is required from contemporary world.

Predictive role of serum and urinary cytokines in invasion and recurrence of bladder cancer.

Urothelial cancer patients are prone to recurrence, and there is no marker to predict which cases become refractory to the immunotherapy given to these patients. Tumour behaviour is decided by the dynamics between the pro- and anti-tumorigenic cytokines. In this study, 27 cytokines were estimated in serum and urine of 72 urothelial cancer patients and 42 healthy volunteer controls. Serum cytokines IL-1RA, IL-4 and RANTES were in significantly higher concentration in serum of patients compared to controls, while IL-2 was significantly less in concentration. Patients were found to have significantly high concentrations of 12 urinary cytokines (IL-2, IL-4, IL-8, IL-10, GM-CSF, IFN-γ, IP-10, MIP-1a, PDGF, MIP-1b, RANTES and VEGF) in comparison to healthy controls. Serum VEGF and urinary IL-1ra, IL-4, IL-10, GM-CSF, IP-10, MIP-1a and MIP-1b concentrations were found significantly higher in concentration in high-grade tumours compared to low-grade tumours. There was no difference in either the serum or urinary cytokines between non-invasive and muscle-invasive cases. Serum IL-1ra, IL-6, IL-10, TNF-α and VEGF and urinary IL-1ra, IL-4, IL-8, IL-10, GM-CSF, IP-10, MIP-1a, PDGF, MIP-1b and VEGF were found to be significantly higher in recurrent patients compared to non-recurrent patients. Of these, high concentrations of urinary IL-1RA, IL-4, IL-10, IP-10, PDGF and VEGF and serum IL-1ra, IL-6, IL-10, VEGF and TNF-α were associated with poor recurrence-free survival. Poor recurrence-free survival was also seen with increasing number of cytokines showing high concentrations. The study shows that the estimation of a combination of these cytokines in minimally or non-invasive samples may act as a prognostic indicator.

Prevalence and determinants of depression among elderly persons in a rural community from northern India.

BACKGROUND: Globally, more than 350 million people of all ages suffer from depression. Elderly persons are more vulnerable to depression. We conducted this study to estimate the prevalence of depression, and to study the association of depression with sociodemographic and clinical variables among elderly persons in a rural community. METHODS: We conducted a community-based cross-sectional study among 395 randomly selected elderly persons aged 60 years and above in a rural area of Ballabgarh, Haryana, India. The participants were screened by using the Geriatric Depression Scale, and diagnosis was confirmed by the Mini International Neuropsychiatric Interview. Multivariate analysis was done for independent predictors of depression. RESULTS: The prevalence of depression was 11.4% (95% CI 8.6%-14.9%). Living in a nuclear family (adjusted odds ratio [AOR] 8.98, 95% CI 3.40-23.71), lack of physical activity (AOR 4.95, 95% CI 2.00-12.27), whole-time involvement in household work (AOR 4.47, 95% CI 1.18-16.93), presence of two or more chronic diseases (AOR 4.45, 95% CI 1.60-12.35), having no role in family decision-making (AOR 2.77, 95% CI 1.19-6.42), sleep problems in past one year (AOR 2.97, 95% CI 1.32-6.69) and bilateral hearing impairment (AOR 4.00, 95% CI 1.80-8.88) were factors associated with depression in elderly persons. CONCLUSIONS: Depression is common among elderly persons in rural areas. Individuals providing healthcare to elderly persons need to be trained to identify depression and take appropriate action; elderly persons with chronic diseases and hearing impairment deserve special attention.

Clinico-epidemiological analysis of Post kala-azar dermal leishmaniasis (PKDL) cases in India over last two decades: a hospital based retrospective study.

BACKGROUND: Patients with Post kala-azar dermal leishmaniasis (PKDL) are considered a reservoir of Leishmania donovani. It is imperative to identify and treat them early for control of visceral leishmaniasis (VL), a current priority in the Indian subcontinent. We explored trends in clinico-epidemiological features of PKDL cases over last two decades, for improving management of the disease. METHODS: Clinically suspected cases were diagnosed with rK39 strip test followed by parasitological confirmation by microscopy and/or PCR/qPCR in skin tissue/slit aspirates. Patients were treated with antimonials till 2008 and subsequently with miltefosine. RESULTS: The study indicated higher incidence of PKDL cases in areas of high endemicity for VL, with 20 % cases reporting no history of VL. Approximately 26 % cases of PKDL were initially misdiagnosed at primary health centers. Duration between onset of PKDL and diagnosis was above 12 months in 80 % cases. Diagnostic sensitivity was 32-36 % with microscopy and 96-100 % with PCR/qPCR. Compliance to treatment was over 85 % with miltefosine while 15 % with antimonials. Relapse rate with miltefosine was up to 13.2 %. CONCLUSIONS: PKDL patients tend to delay reporting and are often misdiagnosed. Confirmatory diagnosis using minimally invasive skin slit aspirate samples would help overcome such issues. There was a paradigm shift in compliance with miltefosine; however, increasing relapse rate indicated the need for newer therapies with oral formulations.

Copy number polymorphism of glutathione-S-transferase genes (GSTM1 & GSTT1) in susceptibility to lung cancer in a high-risk population from north-east India.

BACKGROUND & OBJECTIVES: Genetic polymorphisms in glutathione-S-transferase genes ( GSTM1 and GSTT1 ) have been studied intensively for their potential role in lung cancer susceptibility. However, most of the studies on association between the polymorphisms and lung cancer do not distinguish between genotypes with one or two copies of the genes. The present study investigates the gene dosage effects of GSTT1 and GSTM1 copy number and their environmental interactions to examine the association of lung cancer risk with trimodular genotypes of the GSTs in a high-risk population from north-east India. METHODS: A total of 154 lung cancer cases and 154 age and sex matched controls from the high risk region of north-east India were analyzed by multiplex real-time PCR to determine the trimodal genotypes (+/+, +/- and -/-) in both the genes ( GSTM1 and GSTT1 ). RESULTS: No significant association and gene dosage effect of GSTM1 gene copy number with lung cancer risk ( P trend =0.13) were found. However, absence of GSTT1 conferred 68 per cent (OR=0.32;95%CI=0.15-0.71;P=0.005) reduced risk compared to the two copy number of the gene. t0 here was evidence of gene dosage effect of GSTT1 gene ( P trend =0.006). Tobacco smoking was a major environmental risk factor to lung cancer (OR=3.03;95%CI=1.73-5.31;P<0.001). However, its interaction with null genotype of GSTT1 conferred significant reduced risk to lung cancer (OR=0.30;95%CI=0.10-0.91;P=0.03). Further in only tobacco smokers, null genotype was associated with increased reduced risk [0.03(0.001-0.78)0.03; P trend =0.006]. No effect modification of GSTM1 was observed with lung cancer risk by environmental risk factors. INTERPRETATION & CONCLUSIONS: The results suggest that absence of GSTT1 null genotype may be associated with a reduced risk of lung cancer and the effect remains unchanged after interaction with smoking.

Assessment of treatment retention rates and predictors of retention on opioid agonist treatment among adolescents.

INTRODUCTION: Opioid agonist treatment (OAT) is an effective treatment for opioid dependence syndrome in adults. However, studies on effectiveness of OAT in adolescents are limited; existing studies show varying retention rates. The present study aimed to assess OAT retention rates in adolescent patients with opioid dependence syndrome registered in a community drug treatment clinic in Delhi, India, and to analyse factors associated with retention at 1 year. METHODS: Retrospective cohort study. All adolescents (n = 130) aged 10-19 years, started on OAT from January 2020 to July 2022 were included. Baseline and follow-up data was extracted from online record system maintained at the clinic. OAT retention rates at different timepoints were assessed. Multivariable logistic regression was used to discern factors associated with one-year retention. RESULTS: The participants' mean age was 16.9 (SD 1.4) years. Mean age of starting opioids was 14.9 (SD 2.2) years; 29.5% (n = 38) injected opioids. The 6-, 12-, 18- and 24-month retention rate on OAT was 64.4%, 45.6%, 38.7% and 29% respectively. The retention rates with buprenorphine and methadone were comparable. Multivariate logistic regression showed retention for less than 12 months to be significantly associated with younger age of starting heroin, involvement in illegal activities, absenteeism from school and substance use in family. DISCUSSION AND CONCLUSIONS: The 12-month retention rates on OAT in adolescents is comparable to retention rates in adults. Various factors associated with early age of onset of opioid use are also associated with lower retention rates on OAT.

Characteristics Associated with Substance Use and Non-use Among Street Children in Delhi, India: A Community-based Cross-sectional Epidemiological Study.

Background: Street children are vulnerable to adverse health and risk behaviors and drug use. Substance use among street children has been well documented in several countries. This study reports sociodemographic and peer, family, and stress-related factors associated with substance use and non-use in a representative sample of street children of Delhi. Methods: This cross-sectional survey was conducted through six NGOs working with street children, using Respondent Driven Sampling, in nine districts of Delhi (n = 766, 7-18 years). The multivariable model was developed by applying binary logistic regression analysis. Results: The rate of substance use was 49%. Significant association was found between substance use in the past year and increasing age [Odds Ratio: OR (95% Confidence Interval)] [1.22(1.12,1.33)], male sex [4.34 (2.28,8.26)], lacking psychosocial support from family/relatives [3.27(1.84,5.80)], being engaged in earning from illegal sources, [3.04(1.75,5.29)], family use of substance [2.59(1.38,4.89)], presence of substance-using peers [29.86(14.38,62.01)], lack of non-drug-using peers [2.35(1.46,3.79)], and not possessing basic amenities [2.26(1.31,3.93)]. Conclusion: Multiple modifiable factors exist within the family and peer group, including risk and protective factors or a consequence of substance use. Some challenges in the form of difficulty in reaching out to them and poor treatment seeking by those using substances warrant intensification in both primary and secondary prevention initiatives.

Comparison of 1-day versus 3-day intravenous terlipressin in cirrhosis patients with variceal bleeding: A pilot randomised controlled trial.

BACKGROUND: In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS: We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS: In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS: A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS: Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome.

BACKGROUND: There is scant literature on hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). AIM: To assess the magnitude, clinical characteristics, feasibility, and outcomes of treatment in BCS-HCC. METHODS: A total of 904 BCS patients from New Delhi, India and 1140 from Mumbai, India were included. The prevalence and incidence of HCC were determined, and among patients with BCS-HCC, the viability and outcomes of interventional therapy were evaluated. RESULTS: In the New Delhi cohort of 35 BCS-HCC patients, 18 had HCC at index presentation (prevalence 1.99%), and 17 developed HCC over a follow-up of 4601 person-years, [incidence 0.36 (0.22-0.57) per 100 person-years]. BCS-HCC patients were older when compared to patients with BCS alone (P = 0.001) and had a higher proportion of inferior vena cava block, cirrhosis, and long-segment vascular obstruction. The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up (13029 ng/mL vs 500 ng/mL, P = 0.01). Of the 35 BCS-HCC, 26 (74.3%) underwent radiological interventions for BCS, and 22 (62.8%) patients underwent treatment for HCC [transarterial chemoembolization in 18 (81.8%), oral tyrosine kinase inhibitor in 3 (13.6%), and transarterial radioembolization in 1 (4.5%)]. The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo (P = 0.0001). In contrast to the New Delhi cohort, the Mumbai cohort of BCS-HCC patients were predominantly males, presented with a more advanced HCC [Barcelona Clinic Liver Cancer C and D], and 2 patients underwent liver transplantation. CONCLUSION: HCC is not uncommon in patients with BCS. Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Does ethyl glucuronide in hair correlate with alcohol consumption? A comparative study with other traditional biomarkers among individuals with alcohol dependence syndrome.

AIM: Ethyl glucuronide (EtG) in hair is a direct biomarker proven to be useful for the detection of chronic excessive alcohol use. This study investigated the association of self-reported alcohol consumption with traditional biomarkers: GGT, AST, ALT, CDT, and MCV in blood and a direct biomarker, hair EtG, in a total of 122 patients with alcohol dependence syndrome. The diagnostic accuracy of the biomarkers to differentiate heavy from non-heavy drinkers was also evaluated. METHOD: GGT, AST, and ALT in serum were measured by Automated Chemistry Analyzer, MCV in blood was measured by Haematology Analyzer, serum CDT was analyzed by ELISA, and EtG in hair was evaluated by gas chromatography-mass spectrometry. The association between the biomarkers and the amount of alcohol consumed (self-reported) was determined using Spearman's rank correlation. RESULTS: All participants showed EtG level above the cut-off (0.03 ng/mg). Hair EtG showed a statistically significant linear and positive correlation with the amounts (in grams) of alcohol consumed (r = 0.60; p < 0.001). No correlation was observed among the traditional biomarkers and the quantity of alcohol consumed. Also, EtG showed an excellent receiver operating characteristic (ROC) curve (98%) with good sensitivity (85%) and specificity (60%) to classify heavy drinkers among individuals with alcohol dependence syndrome. CONCLUSION: Hair EtG can be helpful to estimate retrospective alcohol consumption in long-term chronic alcohol consumption cases. Hair EtG also provides a reliable diagnostic test to detect heavy drinkers among individuals with alcohol dependence syndrome.

A Prospective Three-Months Naturalistic Follow-Up Study of Outcomes of Patients with Opioid Dependence Discharged on Buprenorphine or Oral Naltrexone.

Background: Comparative studies of the naturalistic course of patients of opioid dependence on naltrexone and buprenorphine are likely to be helpful for clinical decision-making. The article aimed to report on the three-months naturalistic outcomes of patients discharged on naltrexone or buprenorphine from the same center. Methods: Patients with opioid dependence who were discharged on either naltrexone (n = 86) or buprenorphine (n = 30) were followed up for three months for retention in treatment. The patients were also followed up telephonically, and the Maudsley Addiction Profile was applied. Results: The days of retention in treatment were significantly higher in the buprenorphine group (69.5 versus 48.7 days, P = 0.009). Heroin use, pharmaceutical opioid use, injection drug use, involvement in illegal activity, and percentage of contact days in conflict with friends in the last 30 days reduced over three months in both the groups, while the physical and psychological quality of life improved in both the groups. Additionally, in the naltrexone group, smoked tobacco use, cannabis use, and percentage of contact days in conflict with family within the last 30 days reduced at three months compared to baseline. Conclusion: With the possible limitations of choice of medication-assisted treatment for opioid dependence being determined by the patient, and prescribing related factors and sample size constraints, the study suggests that retention outcomes may vary between naltrexone and buprenorphine, though both medications may improve several patient-related parameters. However, a true head-to-head comparison of the outcomes of buprenorphine and naltrexone in a naturalistic setting may be difficult.

Trazodone for sleep disturbance in opioid dependent patients maintained on buprenorphine: A double blind, placebo-controlled trial.

BACKGROUND: Sleep disturbances are seen even in individuals on opioid agonist treatment (OAT). Established pharmacotherapy for sleep disturbances such as benzodiazepines have misuse potential and increased mortality risk in patients with OAT. No study has explored the role of trazodone on sleep disturbance in individuals maintained on buprenorphine. We aimed to assess the efficacy of trazodone in improving sleep disturbance among individuals maintained on buprenorphine. METHODS: The study was a double-blind, placebo-controlled, parallel, randomised trial. Adult males (18-60 years) stabilised on buprenorphine with Pittsburgh Sleep Quality Index (PSQI) score of above five, without other psychiatric comorbidity were randomised to receive either trazodone (50-150mg per day) or placebo. Sleep-50 questionnaire, Epworth Sleepiness Scale (ESS), Brief Pain Inventory (BPI), Clinical Opiate Withdrawal Scale (COWS), Depression, Anxiety and Stress Scale (DASS)-21, Visual Analogue Scale (VAS) for opioid craving, and PSQI were assessed at baseline and at the end of six weeks. RESULTS: Fifty-one patients were allocated to trazodone arm and 49 to placebo arm. Side-effects of trazodone were minimal and well-tolerated with comparable discontiuation rates between both groups. Significantly greater proportion of patients on trazodone (82%, mean dose 101.9 mg) had PSQI scores five or less than those on placebo (16%) at the end of six weeks. Sleep improvement was in various components like sleep quality, latency, efficiency, and duration of sleep. CONCLUSION: Trazodone is well-tolerated and effective in improving sleep disturbances in individuals with opioid dependence maintained on buprenorphine over a six-week period.

Does Cognitive Therapy Change the Early Maladaptive Schemas in Individuals with Alcohol Dependence? Evidence from a Randomized Controlled Trial.

Background: Although early maladaptive schemas (EMSs) have been suggested as potential vulnerability markers for alcohol dependence (AD), there is less emphasis on addressing these schemas in substance abuse treatment programs. We thus aimed to examine the change in schemas in response to cognitive therapy in individuals with AD. Methods: In this an open-label randomized controlled study, individuals with alcohol dependence syndrome (ADS, n = 84) were randomized to the intervention group (n = 45), which received six cognitive therapy sessions combined with treatment as usual (TAU), or the control group (n = 39), which was on TAU only. Participants were assessed on the measures of EMSs, alcohol use severity, and perceived stress at baseline and posttreatment. Results: The intervention group showed significant improvement in 5 out of 18 EMSs, that is, emotional deprivation, defectiveness, self-sacrifice, unrelenting standard, and negativity, compared to the control group, at the end of the treatment. There was a significant between-group effect for perceived stress but not for alcohol use severity. Conclusion: EMSs can be changed with cognitive therapy in individuals with AD and could be a crucial area to address in treatment programs. Further studies with long-term follow-up are warranted. The trial was registered with the Clinical Trials Registry-India (CTRI/2015/12/006441) on December 17, 2015.

Whole Exome-Trio Analysis Reveals Rare Variants Associated with Congenital Pouch Colon.

Anorectal malformations (ARM) are individually common, but Congenital Pouch Colon (CPC) is a rare anorectal anomaly that causes a dilated pouch and communication with the genitourinary tract. In this work, we attempted to identify de novo heterozygous missense variants, and further discovered variants of unknown significance (VUS) which could provide insights into CPC manifestation. From whole exome sequencing (WES) performed earlier, the trio exomes were analyzed from those who were admitted to J.K. Lon Hospital, SMS Medical College, Jaipur, India, between 2011 and 2017. The proband exomes were compared with the unaffected sibling/family members, and we sought to ask whether any variants of significant interest were associated with the CPC manifestation. The WES data from a total of 64 samples including 16 affected neonates (11 male and 5 female) with their parents and unaffected siblings were used for the study. We examined the role of rare allelic variation associated with CPC in a 16 proband/parent trio family, comparing the mutations to those of their unaffected parents/siblings. We also performed RNA-Seq as a pilot to find whether or not the genes harboring these mutations were differentially expressed. Our study revealed extremely rare variants, viz., TAF1B, MUC5B and FRG1, which were further validated for disease-causing mutations associated with CPC, further closing the gaps of surgery by bringing intervention in therapies.

Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy.

Resistance to chemotherapy is a major impediment to the successful treatment of acute leukemia (AL). Expression of genes involved in drug resistance and apoptosis may be responsible for this. This study aimed to investigate the expression of drug resistance (MDR1, MRP1, LRP, BCRP, GSTP1, DHFR) and apoptotic genes (p53, BCL-2, Survivin) in adult acute leukemias and compare them with clinical and hematological findings and response to induction chemotherapy. Eighty-five patients with AL [45 with acute myeloid leukemia (AML) and 40 with acute lymphoblastic leukemia (ALL)] were used as a study group. Real-time PCR results showed that expression level of MDR1 was significantly higher in AML whereas expression of DHFR, BCRP and Survivin was significantly higher in ALL patients. In AML, significant correlation was observed between LRP and MRP1 (r(s)=0.44, p=0.016), LRP and DHFR (r(s)=0.41, p=0.02), MDR1 and BCL-2 (r(s)=0.38, p=0.03). Expression of GSTP1 and LRP correlated with high white blood count (p=0.03 and p=0.03) and BCL-2 with high peripheral blast count (p=0.009). MDR1 expression was significantly associated with the expression of immature stem cell marker CD34 (p=0.002). In ALL, significant association was found between LRP gene and female sex (p<0.0001), LRP and B-ALL patients (p=0.04) and LRP and BCR/ABL positive patients (p=0.004). High expression of MDR1 and BCL-2 in AML and MRP1 gene in ALL was associated with response to induction chemotherapy (p=0.001, p=0.02 and p=0.007 respectively). These results showed the potential clinical relevance of MDR1, MRP1 and BCL-2 in adult patients with acute leukemia in the context of induction chemotherapy.

Implication of DNA repair genes in prostate tumourigenesis in Indian males.

BACKGROUND & OBJECTIVES: Prostate cancer (CaP) is the fifth most common cancer among Indian men. Tumour protein p53 (TP53) gene increases the fidelity of DNA replication and homologous recombination by transcriptional transactivation of mismatch repair (MMR) genes. DNA repair thus has a potential role in molecular carcinogenesis of CaP. The aim of the present study was to identify mutations, and polymorphisms in TP53 gene and MMR protein expression in CaP in Indian male population. METHODS: TP53 codon 72 polymorphism was analysed in 105 CaP, 120 benign prostatic hyperplasia (BPH) cases and 106 normal controls. Mutational analysis of TP53 was done in DNA extracted from formalin fixed paraffin embedded tissue of 80 CaP and 24 BPH cases. Expression of MMR proteins viz. hMLH1, hMSH2, hPMS1 and hPMS2 was studied in 80 CaP, 15 prostatic intraepithelial neoplasia (PIN) and 15 BPH cases. RESULTS: A somatic C/A variation at the intronic boundary of exon 7 in TP53 gene was observed in one each biopsy samples from CaP and BPH. A significant association of codon 72 TP53 Pro/Pro genotype was observed with the risk of CaP (OR, 2.59, P=0.02) and BPH (OR, 6.27, P<0.001). Immunohistochemical analysis of MMR proteins showed maximum loss of hPMS1 expression in cases of CaP and PIN while no loss in expression of MMR proteins was observed in BPH cases. The study also identified a significant loss of hPMS2 protein in poorly differentiated tumours (Gleason score >7) than in well differentiated tumours (Gleason score 3-6) (P<0.05). INTERPRETATION & CONCLUSIONS: The results of the present study demonstrate that TP53 codon 72 polymorphism plays significant role in the pathogenesis and susceptibility to CaP and BPH. Also, an aberrant MMR protein expression could be involved in progression of prostate cancer through PIN, early CaP to aggressive CaP. The loss of hPMS2 protein expression may serve as a marker for progression of CaP.