Visalakshi Jeyaseelan

Insight, psychopathology, explanatory models and outcome of schizophrenia in India: a prospective 5-year cohort study

BackgroundThe sole focus of models of insight on bio-medical perspectives to the complete exclusion of local, non-medical and cultural constructs mandates review. This study attempted to investigate the impact of insight, psychopathology, explanatory models of illness on outcome of first episode schizophrenia.MethodPatients diagnosed to have DSM IV schizophrenia (n = 131) were assessed prospectively for insight, psychopathology, explanatory models of illness at baseline, 6, 12 and 60 months using standard instruments. Multiple linear and logistic regression and generalized estimating equations (GEE) were employed to assess predictors of outcome.ResultsWe could follow up 95 (72.5%) patients. Sixty-five of these patients (68.4%) achieved remission. There was a negative relationship between psychosis rating and insight scores. Urban residence, fluctuating course of the initial illness, and improvement in global functioning at 6 months and lower psychosis rating at 12 months were significantly related to remission at 5 years. Insight scores, number of non-medical explanatory models and individual explanatory models held during the later course of the illness were significantly associated with outcome. Analysis of longitudinal data using GEE showed that women, rural residence, insight scores and number of non-medical explanatory models of illness held were significantly associated with BPRS scores during the study period.ConclusionsInsight, the disease model and the number of non-medical model positively correlated with improvement in psychosis arguing for a complex interaction between the culture, context and illness variables. These finding argue that insight and explanatory models are secondary to psychopathology, course and outcome of the illness. The awareness of mental illness is a narrative act in which people make personal sense of the many challenges they face. The course and outcome of the illness, cultural context, acceptable cultural explanations and the prevalent social stigma interact to produce a complex and multifaceted understanding of the issues. This complexity calls for a nuanced framing of insight.

A limited sampling strategy for tacrolimus in renal transplant patients

AIMS To develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC(0-12)) in renal transplant patients. METHODS Twenty-nine renal transplant patients (3-6 months post transplant) who were at steady state with respect to tacrolimus kinetics were included in this study. The blood samples starting with the predose (trough) and collected at fixed time points for 12 h were analysed by microparticle enzyme immunoassay. Linear regression analysis estimated the correlations of tacrolimus concentrations at different sampling time points with the total measured AUC(0-12). By applying multiple stepwise linear regression analysis, LSS equations with acceptable correlation coefficients (R(2)), bias and precision were identified. The predictive performance of these models was validated by the jackknife technique. RESULTS Three models were identified, all with R(2) > or = 0.907. Two point models included one with trough (C(0)) and 1.5 h postdose (C(1.5)), another with trough and 4 h postdose. Increasing the number of sampling time points to more than two increased R(2) marginally (0.951 to 0.990). After jackknife validation, the two sampling time point (trough and 1.5 h postdose) model accurately predicted AUC(0-12). Regression coefficient R(2) = 0.951, intraclass correlation = 0.976, bias [95% confidence interval (CI)] 0.53% (-2.63, 3.69) and precision (95% CI) 6.35% (4.36, 8.35). CONCLUSION The two-point LSS equation [AUC(0-12) = 19.16 + (6.75.C(0)) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC(0-12) in stable renal transplant patients prescribed prednisolone and mycophenolate.

Genital syndromes and syndromic management of vaginal discharge in a community setting

The objective of the study was to determine the community prevalence of genital syndromes in women and evaluate the syndromic management of vaginal discharge in this setting. A representative sample for the state of Tamilnadu was chosen using probability proportional to size cluster technique. Thirty clusters were selected from three districts. Demographic, sexual behaviour, risk factors, clinical and laboratory data were collected from the selected population using a structured questionnaire. Direct smear examination for Trichomonas vaginalis, culture for Neisseria gonorrhoeae and Haemophilus ducreyi, serological tests for syphilis (RPR and TPHA), hepatitis B (Hbs Ag ELISA), IgM and IgG antibodies to HSV2 (Novum diagnostics, Germany) and PCR test for detection of C. trachomatis from urine were done. There were 1157 women in the selected population. On examination, vaginal discharge was the most common genital syndrome (38.4%). The sensitivity, specificity, positive and negative predictive value of vaginal discharge as a marker for STD in women was found to be 43.3%, 61.6%, 10.7% and 91.1%, respectively. We concluded that treatment on the basis of syndromic management would result in over-treatment of 90% of women with vaginal discharge.

High cost burden and health consequences of antibiotic resistance: the price to pay

INTRODUCTION Rising antibiotic resistance may negatively affect the health and cost of care for patients. This study aimed to determine the impact of antibiotic resistance on costs and health consequences for patients. METHODOLOGY A one-year observational study was conducted at Christian Medical College, Vellore, a tertiary care hospital, on patients admitted into medical wards with a preliminary diagnosis of suspected sepsis. Patients with confirmed bacteremia were analysed in two groups - resistant and susceptible - based on susceptibility of causative bacteria to the empiric antibiotics administered. Clinical data and details about costs incurred were collected from hospital records. Costs and health consequences were compared using Mann-Whitney U test and Fishers exact test. For median difference in costs, 95% bootstrap confidence interval was determined. RESULTS Overall, 220 patients were included. The median difference between resistant and susceptible groups in overall costs, antibiotic costs, and pharmacy costs was rupees (INR)/USD 41,993/700 (p = 0.001), 8,315/139 (p < 0.001) and 21,492/358 (p < 0.001), respectively. Health consequences such as intensive care admissions, complications, mortality, and length of stay were significantly higher in the resistant group as compared to susceptible group: 44% vs. 21% (p < 0.001), 56% vs. 37% (p = 0.006), 12% vs. 2% (p = 0.011), and 14 vs. 11 days (p = 0·027), respectively. CONCLUSIONS Antibiotic resistance has a significant impact on cost and health consequences. These findings provide a key message for policymakers and other stakeholders to initiate feasible strategies to tackle resistance and reduce the burden.

Predictors of insight in first-episode schizophrenia: A 5-year cohort study from India

Background and aims: There is a dearth of data on the predictors of insight in schizophrenia. This study attempted to assess the predictors of insight in a cohort of first-episode schizophrenia followed up over 5 years. Methods: Patients diagnosed to have Diagnostic and statistical manual of mental disorders (4th ed.; DSM-IV) schizophrenia (n = 131) were assessed prospectively for insight, psychopathology and explanatory models of illness over a 5-year period using standard instruments. Multiple linear regression and generalized estimating equations (GEE) were employed to assess predictors of insight. Results: We could follow up 95 (72.5%) patients, 5 years after recruitment. A total of 65 of these patients interviewed at 60 months (68.4%) achieved remission. Cross-sectional evaluations suggest a relationship between insight, psychosis rating and explanatory models of illness with good insight and medical models associated with good outcome. However, baseline and early illness data do not predict insight scores at 5 years. Serial longitudinal assessment of insight is negatively associated with Brief Psychiatric Rating Scale (BPRS) scores and positively associated with the number of nonmedical explanatory models of illness held by patients. Conclusion: These findings argue that insight and explanatory models of illness are secondary to psychopathology, course and outcome. They are dependent on the trajectory of the person’s illness, are not independent of the condition and call for multifaceted understanding of the issues.

The Impact of Policy Guidelines on Hospital Antibiotic Use over a Decade: A Segmented Time Series Analysis

Introduction Antibiotic pressure contributes to rising antibiotic resistance. Policy guidelines encourage rational prescribing behavior, but effectiveness in containing antibiotic use needs further assessment. This study therefore assessed the patterns of antibiotic use over a decade and analyzed the impact of different modes of guideline development and dissemination on inpatient antibiotic use. Methods Antibiotic use was calculated monthly as defined daily doses (DDD) per 100 bed days for nine antibiotic groups and overall. This time series compared trends in antibiotic use in five adjacent time periods identified as ‘Segments,’ divided based on differing modes of guideline development and implementation: Segment 1– Baseline prior to antibiotic guidelines development; Segment 2– During preparation of guidelines and booklet dissemination; Segment 3– Dormant period with no guidelines dissemination; Segment 4– Booklet dissemination of revised guidelines; Segment 5– Booklet dissemination of revised guidelines with intranet access. Regression analysis adapted for segmented time series and adjusted for seasonality assessed changes in antibiotic use trend. Results Overall antibiotic use increased at a monthly rate of 0.95 (SE = 0.18), 0.21 (SE = 0.08) and 0.31 (SE = 0.06) for Segments 1, 2 and 3, stabilized in Segment 4 (0.05; SE = 0.10) and declined in Segment 5 (−0.37; SE = 0.11). Segments 1, 2 and 4 exhibited seasonal fluctuations. Pairwise segmented regression adjusted for seasonality revealed a significant drop in monthly antibiotic use of 0.401 (SE = 0.089; p<0.001) for Segment 5 compared to Segment 4. Most antibiotic groups showed similar trends to overall use. Conclusion Use of overall and specific antibiotic groups showed varied patterns and seasonal fluctuations. Containment of rising overall antibiotic use was possible during periods of active guideline dissemination. Wider access through intranet facilitated significant decline in use. Stakeholders and policy makers are urged to develop guidelines, ensure active dissemination and enable accessibility through computer networks to contain antibiotic use and decrease antibiotic pressure.

Role of conventional and diffusion weighted MRI in predicting treatment response after low dose radiation and chemotherapy in locally advanced carcinoma cervix.

BACKGROUND AND PURPOSE To assess the diagnostic performance of conventional and diffusion weighted (DWI) magnetic resonance imaging (MRI) in predicting response in locally advanced cervical cancer. MATERIALS AND METHODS Total 24 patients with stage IIB-IIIB squamous cell carcinoma cervix were treated with initial two cycles of paclitaxel and carboplatin and concurrent low dose radiotherapy prior to standard chemoradiation. Response was assessed clinically and radiologically after 3 weeks of initial treatment. Volumetric and functional parameters derived from conventional and diffusion weighted MRI, due to treatment were measured. RESULTS Significant reduction of GTV was noted in MRI (54 cm(3) vs. 11 cm(3), p < 0.01) and DWI (44 cm(3) vs. 6 cm(3), p < 0.01, ΔADC = 0.49 × 10(-3)mm(2)/sec, p < 0.01) after treatment. Tumor volume reduction rate (TVRR) in DWI was significantly higher in pathological good responders (p = 0.03). In this group both mean post treatment apparent diffusion coefficient (ADC) value and ΔADC were significantly higher (p = 0.01 and p = 0.03). ADC was a good predictor for pathological response (area under receiver operating characteristic curve (ROC) 0.814). CONCLUSION TVRR (DWI) and ΔADC can be used as a predictor of early pathological response. Complete response based on DWI, could be a useful predictor of long term disease control.

Misoprostol versus Foley catheter insertion for induction of labor in pregnancies affected by fetal growth restriction.

To compare 25 μg of vaginal misoprostol with a Foley catheter for induction of labor (IOL) for fetal growth restriction.

Concurrent chemo-irradiation with weekly cisplatin and paclitaxel in the treatment of locally advanced squamous cell carcinoma of cervix: A phase II study

BACKGROUND Cervical cancer is the most common gynecological cancer in Indian women. This study was initiated to assess whether the combination of paclitaxel and cisplatin with radiation was feasible in Indian women. AIMS AND OBJECTIVES The aim of this study was to assess the immediate tumor response and toxicity of weekly cisplatin and paclitaxel along with radiotherapy in the treatment of cervical cancer. MATERIALS AND METHODS Women with primary untreated squamous cell carcinoma of the cervix with FIGO stages IB2 to IIIB were treated with weekly injections of cisplatin 30 mg/m2 and paclitaxel 40 mg/m2 for 4 weeks along with radiotherapy. A total of 25 patients were enrolled in this study. Disease was assessed prior to treatment by pelvic examination and contrast enhanced computed tomography scan of the abdomen and pelvis. Response was assessed 6 weeks after completion of treatment using the same parameters. Clinical and radiological response was documented. The toxicity was assessed and was graded using the common toxicity criteria Version 3.0. Intention to treat analysis was used when reporting results. RESULTS A total of 23 patients completed the intended treatment. There was a complete response rate of 88%, 12% were not available for response assessment. The major toxicity was Grade 3 diarrhea (48%). The mean duration of treatment was 58 days. CONCLUSIONS Combination chemotherapy with cisplatin and paclitaxel along with radiotherapy in patients with locally advanced squamous cell carcinoma of cervix had a high incidence of acute toxicity. There was no increase in immediate tumor response and progression free survival with this treatment regimen. Hence, this regimen offers no added benefit when compared to the chemo radiation with cisplatin alone.

Indomethacin inhibits activation of endothelial nitric oxide synthase in the rat kidney: possible role of this effect in the pathogenesis of indomethacin-induced renal damage.

The clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with adverse effects in the kidney. Indomethacin, an NSAID that has been shown to induce oxidative stress in the kidney, was used to study the pathogenesis of renal damage induced by the drug in a rat model. Experimental animals were given indomethacin (20mg/kg) by oral gavage, sacrificed 1, 12 or 24h (h) later and the kidneys studied. Evidence of glomerular and tubular damage in the kidney was found in response to the drug. Renal tissue nitrite levels, a surrogate marker of nitric oxide (NO) synthesis, were significantly decreased at 12 and 24h. Indomethacin did not affect protein and mRNA levels of endothelial nitric oxide synthase (eNOS) or inducible NOS (iNOS). However, it significantly reduced the ratio of dimeric (active) to monomeric (inactive) eNOS in the kidney, 12 and 24h after drug administration. This was associated with reductions in heme content, both in renal tissue and in NOS. Heme oxygenase 1 (HO-1) mRNA (at 1 and 12h), protein (at 12 and 24h) and activity (at 1, 12 and 24h) were elevated in response to indomethacin. Nuclear translocation of Nrf2 (at 12h) and p38 MAPK signaling (at 12h and 24h), both of which are known to induce HO-1, also occurred in response to the drug. In summary, our results show that indomethacin reduced levels of activated eNOS in the kidney. This effect is possibly mediated by heme depletion, secondary to HO-1 induction that occurred downstream of Nrf2 and p38 MAPK signaling. We postulate that reduced renal eNOS activity may result in decreased NO levels, and hence reduced renal perfusion, leading to glomerular and tubular injury with subsequent renal damage.