Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia

The incidence of retinopathy of prematurity in a neonatal care unit

In India, with advancement in neonatal care units, a large number of low-birth weight premature babies are now surviving and are at risk of developing retinopathy of prematurity (ROP). However, there are not enough reports on the incidence of ROP in this country. To determine the incidence of ROP in a prospective manner, 165 babies weighing ≤ 1700 gm over a period of one year were examined. An incidence of 47.27% of ROP at the mean age of 7.21 ± 0.3 weeks of life was detected. The maximum stage reached was stage 1 in 28 (16.97%), stage 2 in 29 (17.58%), stage 3 in 19 (11.52%) and stage 4b in 2 (1.21%) babies. Plus disease was present in 17 (10.3%) babies. Babies with lower birth weights and lower gestation age at birth had a significantly higher (p = < 0.05) incidence of ROP. However, the difference in mean birth weight and gestation age at birth for various stages of ROP was not significant (p = > 0.05). Thus, we recommend screening for all babies weighing ≤ 1700 gm

Anthropometric analysis of hip joint using Computed Tomography in a tertiary care centre in North India

Background: Hip joint has a significant functional modification on erect bipedal posture. The geometry of the hip joint is determined by genetic and environmental factors such as age, race, sex, and lifestyle. Anthropometric dimensions described for hip joint in Westerners might be quite different from those encountered among Indians. So this study was aimed to do anthropometric study of Hip joint by CT scan. Material and Methods: The study was conducted on a CT pelvis of normal patients who underwent CT pelvis for some other reason and having both hip joints radiologically normal. This study was conducted in Department of Orthopedics, BPS Govt. Medical College, Khanpur Kalan, Sonepat, Haryana. Anthropometric measurements of 162 hips were carried out by CT scan of patient who underwent CT scan of pelvis for some other reason and have normal radiological hip with the age group between 20 years to 70 years. Total 8 parameter HD, NW, NSA, HO, VO, AA, CDLT, AV of each hip joint were measured and compared between males and females and as per the side of the joint. Results: We found in our study that there is statistically significant difference between males and females in parameters like HD, NW, NSA, HO, VO, AA, CDLT, AV. The mentioned parameter has lesser values in females than the males. We also found that there is no statistically significant difference as per the side of the joint in any parameter we studied. At the end of the study, we did a anthropometric study of the various parameter of the hip joint which may help for the better designing of the implants which are being used for hip surgeries and replacement surgeries. Conclusion: However, our study population was small up to 162 hips and large multicentric study may require supporting this finding

WINROP algorithm for prediction of sight threatening retinopathy of prematurity: Initial experience in Indian preterm infants

Purpose: To determine the efficacy of the online monitoring tool, WINROP (https://winrop.com/) in detecting sight-threatening type 1 retinopathy of prematurity (ROP) in Indian preterm infants. Methods: Birth weight, gestational age, and weekly weight measurements of seventy preterm infants (<32 weeks gestation) born between June 2014 and August 2016 were entered into WINROP algorithm. Based on weekly weight gain, WINROP algorithm signaled an alarm to indicate that the infant is at risk for sight-threatening Type 1 ROP. ROP screening was done according to standard guidelines. The negative and positive predictive values were calculated using the sensitivity, specificity, and prevalence of ROP type 1 for the study group. 95% confidence interval (CI) was calculated. Results: Of the seventy infants enrolled in the study, 31 (44.28%) developed Type 1 ROP. WINROP alarm was signaled in 74.28% (52/70) of all infants and 90.32% (28/31) of infants treated for Type 1 ROP. The specificity was 38.46% (15/39). The positive predictive value was 53.84% (95% CI: 39.59–67.53) and negative predictive value was 83.3% (95% CI: 57.73–95.59). Conclusion: This is the first study from India using a weight gain-based algorithm for prediction of ROP. Overall sensitivity of WINROP algorithm in detecting Type 1 ROP was 90.32%. The overall specificity was 38.46%. Population-specific tweaking of algorithm may improve the result and practical utility for ophthalmologists and neonatologists

Retinopathy of prematurity in Asian Indian babies weighing greater than 1250 grams at birth: Ten year data from a tertiary care center in a developing country

Background: Retinopathy of prematurity (ROP) is an important cause of childhood blindness in developing countries. Aim: To report the spectrum of ROP and associated risk factors in babies weighing &gt; 1250 g at birth in a developing country. Setting and Design: Institutional, retrospective, non-randomized, observational clinical case series. Materials and Methods : Retrospective analysis (10 years) of 275 eyes (138 babies) with ROP. Statistical Analysis: Qualitative data with the Chi-square test. Quantitative data using the unpaired t test or the ANOVA and further tested using multivariate logistic regression. Results: The mean birth weight was 1533.9 g (range 1251 to 2750 g) and the mean period of gestation was 30.9 weeks (range 26 to 35). One hundred and twenty-four of 275 eyes (45.1&#x0025;) had threshold or worse ROP. Risk factors for threshold or worse disease were, &#x2032;outborn babies&#x2032; ( P &lt; 0.001), respiratory distress syndrome ( P = 0.007) and exchange transfusion ( P = 0.003). The sensitivity of the American and British screening guidelines to pick up threshold or worse ROP in our study group was 82.4&#x0025; and 77.4&#x0025; respectively. Conclusions : Severe ROP is often encountered in babies weighing greater than 1250 g at birth in developing countries. Western screening guidelines may require modifications before application in developing countries