Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Zinc oxide and selenium nanoparticles can improve semen quality and heat shock protein expression in cryopreserved goat (Capra hircus) spermatozoa.

BACKGROUND: Reactive oxygen species (ROS) are strongly linked with oxidative stress (OS) generated during the process of sperm cryopreservation. Indeed, cellular damage from ROS has been implicated during sperm cryopreservation which causes deterioration in sperm quality and antioxidant nanoparticles (NPs) have been successful in preventing such damage. The interaction of NPs with sperm cells has been less frequently explored in farm animals. OBJECTIVE: The present study explored the effect of NP supplementation on sperm ultrastructure, potential interaction with sperm membrane (plasma and acrosome membrane), heat shock protein (HSP) gene expression levels and sperm quality in cryopreserved buck semen. MATERIALS AND METHODS: Thirty-two (32) ejaculates were collected from four (4) adult male bucks and then diluted in Tris- citric acid- fructose- egg yolk (TCFY) extender containing the Zinc-oxide (ZnO) and Selenium (Se) NP treatments (T0: Control; TZn: 0.1 mg/mL ZnO NPs and TSe: 1 µg/mL Se NPs) after initial evaluation. Diluted semen was packed in 0.25 mL French mini straws and then stored in liquid nitrogen (LN2). Sperm parameters, lipid peroxidation (LPO) profile, sperm head morphology ultrastructural classification under transmission electron microscope (TEM), potential interaction of NPs with sperm membrane and expression of HSP genes were evaluated in the different treatment groups. RESULTS: We found a significant (p < 0.05) increase in the percentage of spermatozoa with intact plasma membrane, and intact acrosome in the ZnO (0.1 mg/mL) and Se (1 µg/mL) NP supplemented groups in comparison to the frozen control group. TEM assessment revealed no internalization of both ZnO and Se NPs into the sperm structure. Few occasional contacts of ZnO NPs with the sperm membrane and a few agglomerates of Se NPs around the area of damaged membranes were visualized. HSP70 and HSP90 mRNA levels were significantly (p < 0.001) higher in the NP supplemented groups in comparison to the control. HSP70 and HSP90 mRNA levels had a strong positive association with sperm motility and a weak to moderate association with other sperm parameters. CONCLUSIONS: Current findings indicated that ZnO NPs are more potent than Se NPs in ameliorating peroxidative damages during sperm cryopreservation, increases semen quality parameters possibly by increasing the expression levels of HSP genes in buck semen. Furthermore, NP supplementation may have a potential role in preserving sperm head ultrastructure by acting as an antioxidant and reducing OS during various degrees of cellular insults, which needs to be further explored.

Subjective Global Assessment of Nutritional Status in Head and Neck Cancer Patients Treated with Radiotherapy - A Prospective Observational Study from North East India.

Head and neck cancer (HNC) patients undergoing curative radiotherapy (RT) are at risk of malnutrition due to disease process as well as effects of therapy. Identifying the nutritional status of these patients at the earliest, helps to introduce adequate and timely interventions that can improve compliance and outcomes of treatment. Various tools for nutritional assessment in cancer patients have been proposed. In this prospective observational study we used the Subjective Global Assessment (SGA) questionnaire in a cohort of HNC patients receiving definitive RT at a regional cancer center of North East India. Recording of data was done at baseline, at two weekly intervals during treatment, at end of radiotherapy (EORT) and at follow-up upto 6 months. We observed that despite proper nutrition counseling, our patients suffered from malnutrition throughout their course of RT, which was at its peak by EORT but gradually improved over six months of follow-up. Pain on eating and swallowing were the most debilitating symptoms which caused significant decline of nutrient intake, body fat and muscle mass among patients together with deteriorating SGA ratings. Our results will hopefully help us design better strategies for nutrition management while delivering curative (chemo)radiotherapy for HNC patients of this region- which has one of the highest incidences of HNC in the world.

Significance of Pattern of Invasion in Tongue Squamous Cell Carcinoma-A Retrospective Study from a Regional Cancer Center of North-East India.

Introduction Many multiparametric models and scoring systems had been proposed in oral tongue squamous cell carcinoma (OTSCC) to predict the survival and recurrence, out of which pattern of invasion (POI) is gaining focus recently. Objective We conducted a retrospective study with the aim to see the prognostic significance of the POI and other parameters such as depth of invasion, perineural invasion (PNI), and lymph node status in OTSCC. Materials and Methods The slides of already diagnosed OTSCC cases were prepared from January 2015 to December 2017 records and studied by two pathologists for different patterns using Brandwein-Gensler scoring system. The different clinicopathologic parameters were compared with different POI. Statistical analysis was performed to present cumulative survival outcomes and for comparison. Results Most of our patients were > 40 years of age with male preponderance. Tumor differentiation pattern was assessed using Broders' system of grading that showed 85% of tumors were well, 12.5% tumors were moderately differentiated, and 2.5% tumors were poorly differentiated. The worst POI was predominantly pattern III (50%) followed by pattern II (32.5%) and pattern IV (13.8%). Most patients were in stage II (33.8%) followed by stage III (32.5%), stage IV (26.3%), and stage I (7.5%). There was an inverse relationship between POI with tumor stage and recurrence. A strong statistically significant association was found between POI with perineural infiltration and lymph node metastasis. Conclusion We concluded from our study that worst POI is significantly associated with number of lymph nodes metastasis and perineural infiltration and hence can be used as an independent prognostic factor.

Influence of New FIGO 2018 Staging on Treatment Outcomes in Early-Stage Cervical Cancer: A Single-Center Study.

Satinder KaurPurpose The aim of this article was to study survival outcomes of early-stage cervical cancer patients and impact on survival after restaging them as per International Federation of Gynecology and Obstetrics (FIGO) 2018. Materials and Methods A retrospective study was conducted from June 1, 2013 to May 31, 2018 in a tertiary care hospital in North India. One-hundred patients of early-stage cervical cancer (as per FIGO 2009 staging) who had been treated by surgery followed by risk based tailored adjuvant therapy in our hospital were evaluated. The clinicopathological features and survival outcomes of these patients were analyzed. These patients were then restaged as per new FIGO 2018 staging and survival outcomes between two FIGO classifications were compared. Results The median age of the study population was 52.5 years with median follow-up of 62.1 months. Ninety percent of our patients had more than 2 years follow-up and 59% had more than 5 years follow-up. The overall survival and relapse-free survival were 87.5 and 91.4%, respectively. The study population was then reclassified according to new FIGO 2018 staging. It was seen that the patients with stage IB1and IB2 cervical cancer had overall survival of 91.1 and 90%, respectively. The overall survival of stage IB3 was 80% and the survival of stage IIIC1 was only 60%. Conclusion The new FIGO 2018 classification has a significant effect on survival outcome and in prognostication of patients with cervical cancer.

Cancer in patients of and above 90 years: A hospital-based retrospective study.

BACKGROUND AND OBJECTIVE: Cancers in a nonagenarian patient are rarely seen, and there is always a moral dilemma for the family members and patient of whether to opt for the treatment or not. The main objective was to identify the survival differences between treated and not treated nonagenarian cancer patients. MATERIALS AND METHODS: This was a retrospective study of Hospital-Based Cancer Registry data from 2010 to 2016. The data of all nonagenarian cancer patients were analyzed for gender distribution, leading sites of cancer, stage distribution, types of treatment received, and survival. The survival was calculated from the date of the first diagnosis. Kaplan-Meier analysis was done to present the survival. RESULTS: Of 60,087 patients, 146 (0.2%) patients were of 90 years and above. Hypopharynx in males (20.5%) and tongue (20.5%) in females were the top cancer sites, 60% patient data were in Stages III and IV, 37 (25.3%) patients received treatment, and 86% patients were treated by radiotherapy. The overall survival (OS) was 14.3%. OS in the treatment group was 21.3% versus 7.7% (P = 0.001) in the no treatment group. The unadjusted hazard ratio for no treatment group was 3.8 (P = 0.003, confidence interval = 1.5-9.7). CONCLUSION: Selected nonagenarian cancer patients from our population with a good performance status should receive curative treatments in all possible ways.

Influence of hormone receptors in breast cancer survival with correlation to place of residence.

INTRODUCTION: Breast cancer is commonly diagnosed cancer in women. Tumor receptors estrogen receptor (ER) and progesterone receptor (PR) are well recognized prognostic factors for breast cancer. MATERIALS AND METHOD: Data from the department of pathology for the 5-year period (2010 to 2014) is used for analysis for Kamrup district of Assam, India. Kaplan Meir method was used to evaluate survival rate. RESULT: The overall 5-year survival is observed as 54.6%. There is a 10.6% improvement in survival was recorded among those who living in the urban areas. The risk of death was 40% higher for those who were resides in rural areas compared to urban areas (P = 0.070). There is a 6 fold variation in survival was observed according to their stage at presentation. Hormone receptors found to be play an important role in survival outcome. Patients with ER/PR+ (positive) status have 13.6% higher survival rate than those with ER/PR-. The overall survival for ER/PR positive is 72.1% compared to 58.5% of ER/PR negative. CONCLUSION: From the study it is observed that population with positive hormone receptors (ER/PR +) and living in the urban areas is experiencing survival rate.

A Survival Analysis of Hypopharyngeal Cancer Patients: A Hospital-Cancer registry Based Study.

To study the survival in patients affected with hypopharyngeal cancer among treatment groups and different stages. Data of hypopharyngeal cancer patients diagnosed from 1st January 2010 to 31st December 2010 was used in the present study. The cases were analyzed for gender, age group distribution, sub-sites at presentation, stage at diagnosis and the type of treatments. Survival from the date of first diagnosis was estimated and hazard ratios were calculated. Survival probability and hazards ratios (HR) were calculated by Kaplan-Meier method and Cox-proportional regression analysis respectively. Censoring of patient who survived longer than 5 years was done. Active follow-up was done for the survival analysis. The study cohort included 217 patients and treatment compliance was observed in 46.9% of cases. The median age at diagnosis was 57 years (range 24-90), 86.2% of cases were locally advanced cases (stage III and IV), pyriform sinus was major sub-site (96%), radiotherapy was main treatment modality alone in 84.8% of cases, median survival was 31 months and 5-year overall survival was 36.9%, and HR for stage IV was 1.9 (P = 0.03, 95% CI - 1.04 to 3.7). In developing setting of North East India, radiotherapy was the main modality of treatment for hypopharyngeal cancer patients, and understanding the clinical parameters and survival of this group of cancers is crucial for its control.

Causes of Treatment Abandonment of Pediatric Cancer Patients ­ Experience in a Regional Cancer Centre in North East India

Introduction: Refusal and abandonment of treatment is often considered as an important reason for poor survival of pediatric cancer patients in developing and underdeveloped countries. In this study we analyze the factors responsible for treatment abandonment and refusal in a Regional Cancer Centre (RCC) in North East India. Material and Methods: All histopathologically or cytologically confirmed cases of childhood cancer from below 15 years of age registered from 1st April, 2010 to 31st March, 2017 were included in this study. Parents or caregivers were interviewed thoroughly and a questionnaire was filled up for analysis of demographic and socio-economic factors. Modified Kuppuswamy scale was used to measure socioeconomic status. Results: Of 592 patients 161 (27.1%) abandoned therapy and 23 (3.9%) refused treatment. Factors associated with abandonment of treatment included: lower risk if residing in urban areas (Odds ratio [OR] = 0.8333, 95% CI 0.565-1.228; P=0.36) and higher risk with maternal education less than secondary school (OR = 1.357; 95%CI: 0.553-3.326; P=0.505). Low socioeconomic status and age >5yrs were also associated with abandonment of treatment. In a binary logistic regression analysis, male sex [Odds Ratio (OR) = 0.701; 95% CI 0.48-1.01; P=0.062] have lowest risk of abandoning treatment with trend to statistical significance. Conclusion: There is a need for proper definition of the problem of childhood cancer patients so that appropriate policy can be introduced to improve survival by improving treatment compliance.

A survival study of uterine cervical patients in the North East India: Hospital-cancer registry-based analysis.

BACKGROUND: Uterine cervical cancer constitutes a major proportion of cancer in females of our population. The objective of this study was to conduct a clinical study of uterine cervical cancers including their survival from hospital-cancer registry data. MATERIALS AND METHODS: Data of uterine cervical cancer patients diagnosed from January 1, 2010 to December 31, 2010 and that were treated at a regional cancer center in North East (NE) India was recruited. The cases were analyzed for age group distribution, stage, and treatment types. Survival from the date of first diagnosis and hazard ratios (HRs) was estimated. Survival probability and HRs were calculated by Kaplan-Meier method and Cox-proportional regression analysis, respectively. Active follow-up was done for the survival analysis. RESULTS: One hundred and ninety-three patients (53.4%) were included for the analysis. Median age was 48 years, 56.5% (108/193) of patients were in the age group of 45-64 years, 56.5% (109/193) were Stage II patients, radiotherapy alone was the main treatment modality in 65.8% (127/193) of cases, 5-year overall survival (OS) was 40.7%, median survival was 44 months, early staged and advanced stage patients had 47.7%, and 29.4% 5-year OS (P = 0.002), respectively, and HR for advanced stages was 1.8 (P = 0.003, confidence interval (CI) = 1.2 to 2.7). CONCLUSION: Describing the clinical characteristics and survival of uterine cervical cancer patients is important for planning and identifying the gaps for its control in the NE India.

Patterns of tobacco use in patients with upper aero digestive tract cancers: A hospital-based study.

BACKGROUND: Tobacco use is a major risk factor for increasing the burden of upper aero digestive tract (UADT) cancer in the population of Northeast India. OBJECTIVE: The objective of this study was to investigate the pattern of tobacco use in different UADT cancer. MATERIALS AND METHODS: This was a retrospective study of electronically recorded data of the Hospital Cancer Registry for the period of May 2014 to December 2014. The UADT cancers were evaluated for gender and age-group distribution, their relative proportion, and association with tobacco use and tobacco-associated risk in males to develop UADT cancers. The type of tobacco usage was clustered as chewable, smoking, and both. Relative risk (RR) of UADT with tobacco usage was identified for males. RESULTS: A total of 1965 (n) UADT cancer patients were identified, male:female was 2.9, tobacco habits was in 1608 (81.8%) patients, both forms of tobacco use in 705 (43.8%), chewable tobacco use in 588 (36.6%) and smoking in 315 (19.6%) patients, tobacco habits in males ranges from 67.3% to 94.3% and in females range from 5.7% to 32.7%, RR of UADT cancer in males for tongue cancer was 1.5 (confidence interval [CI] =1.2-1.9), oropharynx was 1.4 (CI = 1.0-1.8), hypopharynx 1.4 (CI = 1.1-1.7), esophageal cancer was 1.4 (CI = 1.3-1.7), and for laryngeal cancer RR was 1.7 (CI = 1.0-3.0). CONCLUSION: Consumption of chewable tobacco is the major form of tobacco use alone or in combination in UADT cancer patients of our population.

Quality assessment and improvement of cancer registration system in Kamrup Urban District: A report.

INTRODUCTION: The global burden of cancer incidence and mortality are rising continuously worldwide. As per the GLOBOCAN 2012 estimates, about 14.1 million cancer cases and 8.2 million cancer deaths occurred and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide. Reliable data on the magnitude and the pattern of cancer are essential for monitoring the health of the community, assessing the performance of the health care system. Cancer registries should pay great attention to quality of their data. The completeness of cancer registry data- the extent to which all of the incident cancers occurring in the population are included in the registry database- is an extremely important attribute of a cancer registry. There are mainly four aspects influencing the quality of data namely, comparability, completeness, validity and timeliness. MATERIALS AND METHODS: Data regarding incidence and mortality with methods of diagnosis for individual years were obtained from the National Cancer Registry Program database of the Indian Council of Medical Research for 2009 to 2014 periods and recalculated for combined years (2009-2014). RESULTS: In males in 2009-11, 77.1% were microscopically confirmed cases which are improved in the later years and for the year 2012-2014, it is 81.4%. In females also the percentage of microscopically confirmed cases were increased from 80.2% to 82.9%. An improvement in mortality to incidence ratio was observed over the years. MI ratio in males was improved to 32.9%. for the year 2012-14 as compared to 28.6% for the year 2009-11 while in female MI ratio is also increased from 18.8% to 21.8% over the period from 2009-11 to 2012-14. Whereas DCO was decreased from 12% to 10.7% in males and 7.3% to 6.6% in females respectively from the period 2009-11 to 2012-14. CONCLUSION: Although there is a slight improvement in data quality till date, there is an enormous scope for population based cancer registry Guwahati to improve the data quality.

Cancer statistics in Kamrup urban district: Incidence and mortality in 2007-2011.

PURPOSE: The aim of this study was to report cancer statistics in Kamrup Urban District, including incidence and, mortality. INTRODUCTION: In the last five year PBCR-Guwahati witnessed a remarkable growth in cancer incidence cases. The number of new cases of all cancer was increased from 155.3 to 188.5 and 102.7 to 165.3 per 100,000 men and women respectively from the year 2007 to 2011 in KUD. The data from KUD also have shown that for some of the specific types of cancer are highest or some of the highest incidence in rates in the world; particularly cancers of upper aero-digestive tract consist of anatomical sites such as oral cavity, hypopharynx, larynx gallbladder, stomach, lung, prostate and oesophageal cancer. MATERIALS AND METHODS: Age-standardized rates (ASR) (per 100,000 person-years) for incidence, mortality were calculated using the World Standard Population as proposed by Segi and modified by Doll et al. Descriptive statistics were presented by tables and figures. RESULTS: A total of 6623 number of cases (male = 3809, female = 2814) were diagnosed with cancer in the last five years (2007-2011) period of time. The overall age standardized cancer incidence rate is almost 21% higher in men than in women. The pooled ASR for the five year period is 175.2 and 144.7 per 100,000 men and women. CONCLUSION: Overall cancer incidence and mortality rates have increased since 2007.

Denominators: An attempt to adjust for cancer incidence and mortality rates and its role in cancer registries.

Cancer is an important public health burden in India and around the Globe. Incident cases of cancer are reported continuously, and trends in incidence rates vary among five yearly age group. In India National census is carried out after every 10 years since 1951, the latest census is carried out in 2011. As Incident cases of cancer are reported continuously for 5 year age group and estimation of rates and trends for a given year of interest fall in-between two census period population estimation of five yearly age group, which serves as Denominator sense importance. Denominator serves as the most essential part of any cancer registry program as it used for calculation of various rates for five yearly age group such as age-standardized rate, crude rate, truncated rate, cumulative risk etc., Calculated by different registries and Individual Researchers, Government organizations, etc. Currently most of the registries used individual exponential growth rate and differential distribution method to estimate the growth rate. However, it is found that the calculated rates and risk be suffering from bias most of the time since some method over and underestimate the growth rate while some does not able to maintain consistency. Here, an attempt is made to adjust the world standard population with two census period to estimate the five yearly age group for a given year of interest of a geographical region falls in-between two census period. It is also shown here that how the proposed model "age-adjusted population growth model" maintain the overall growth as in exponential growth model and difference distribution method also maintains the estimated growth rate is as found in difference distribution method. Further, it is tried to highlight the points how these method overcomes the problems compared with other methods that are currently used by registries.

Role of environmental pollutants in liver physiology: special references to peoples living in the oil drilling sites of Assam.

The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4-1.6) and 12 times (95% CI 10.74-13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862-3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites.

Community based intervention for tobacco cessation: a pilot study experience, north East India.

BACKGROUND: North East India has a high prevalence of tobacco consumption, but only few individualsseek help for tobacco cessation. Impact of community based tobacco cessation intervention in this part needs more research. MATERIALS AND METHODS: Retrospective analysis was done on the dataset from a community-based tobacco cessation intervention pilot project conducted in Guwahati metro during 2009-10. Subjects, both male and female tobacco users, age>15 years, permanent residents of these blocks giving consent were included in the study. RESULTS: The sample was 800 tobacco users, of whom 25% visited any health care provider during last 12 months and 3% received tobacco cessation advice. An 18% quit rate was observed at six weeks follow up, more than the National average, with a 47% quit rate at eight months, while 52% of subjects reduced use. CONCLUSIONS: Higher tobacco quit rate and reduced tobacco use, no loss to follow up and negligible relapse was observed with this community based intervention design. Such designs should be given more emphasis for implementation in specified communities with very high tobacco consumption rates, cultural acceptance of tobacco and less motivation towards quitting.