Clinical Profile, Etiology and Role of Endotherapy in Chronic Calcific Pancreatitis: An Experience from North India.

Background: In recent years, we have witnessed an evolving landscape in the management of chronic pancreatitis (CP). Endoscopy plays a pivotal role in CP management. Because the management of CP is problematic, we aimed to review and evaluate the role of endoscopy in the management of CP. Methods: This study was carried out in patients with painful chronic calcific pancreatitis who were admitted to the Department of Gastroenterology at the Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar. This was an observational prospective study. We included 67 patients with painful chronic calcific pancreatitis and pancreatic duct abnormalities (stones, strictures, or ductal variations) in our study. These patients had to access exocrine and endocrine status before any therapeutic measures. All the patients underwent endoscopic retrograde cholangiopancreatography (ERCP) as a therapeutic measure. After ERCP, the patients were followed up for 2 years to assess improvement in pain (visual analog scale score reduction), endocrine status (HBA1C reduction), or exocrine status (Fecal elastase reduction). Results: 67 patients were included in the study. Among them males were 32 (47.8%), females were 35(52.5%) and the age distribution studied were as in the age group of 15-30 years, patients were 23 (34.3%), in 30-45 years, there was 20 (29.9%), in age group of 45-60 year, patients were 20 (29.9%), and in the age group of 60-75 years, the patients were 4 (6%). Etiology was sought in all patients; alcohol-related CP was seen in three patients (4.5%), genetic in 11 (16.4%), IgG4 in one (1.5%), pancreatic divisum in 6 (9.0%), hyperparathyroidism in on1e (1.5%), and idiopathic in 45 (67.2%). All patients underwent ERCP for their symptoms to reduce ductal pressure, which is postulated as one of the hypotheses for pain in CP. Pancreatic duct (PD) clearance was attempted in all patients (complete in 42 [62.7%], partial in 17 [25.4%], and failed in 8 [11.9%]). These patients were followed for a period of two years after endotherapy, and the important predictors for pain reduction were single PD stones, disease in the head and body, and non-stricturing disease. Conclusion: Endotherapy offers a high rate of success in selected patients, clearance being better in distal disease and CP without PD strictures, suggesting early disease usually gets cleared very easily.

Customized low-cost high-throughput amplifier for electro-fluidic detection of cell volume changes in point-of-care applications.

Physical parameters of the pathogenic cells, like its volume, shape, and stiffness, are important biomarkers for diseases, chemical changes within the cell, and overall cell health. The response of pathogenic bacteria and viruses to different chemical disinfectants is studied widely. Some of the routinely employed techniques to measure these changes require elaborate and expensive equipment which limits any study to a non-mobile research lab facility. Recently, we showed a micropore-based electro-fluidic technique to have great promise in measuring subtle changes in cell volumes at high throughput and resolution. This method, however, requires commercial amplifiers, which makes this technique expensive and incompatible for in-field use. In this paper, we develop a home-built amplifier to make this technique in-field compatible and apply it to measure changes in bacterial volumes upon exposure to alcohol. First, we introduce our low-cost and portable transimpedance amplifier and characterize the maximum range, absolute error percentage, and RMS noise of the amplifier in the measured current signal, along with the amplifier's bandwidth, and compared these characteristics with the commercial amplifiers. Using our home-built amplifier, we demonstrate a high throughput detection of ~1300 cells/second and resolve cell diameter changes down to 1 µm. Finally, we demonstrate measurement of cell volume changes in E. coli bacteria when exposed to ethanol (5% v/v), which is otherwise difficult to measure via imaging techniques. Our low-cost amplifier (~100-fold lower than commercial alternatives) is battery-run, completely portable for point-of-care applications, and the electro-fluidic devices are currently being tested for in-field applications.

Human Fascioliasis: Report of Two Cases from Kashmir Valley.

Although few case reports of human fascioliasis have been reported from different parts of India, there is no case reported from the Kashmir valley to date. Herein we report two cases of human fascioliasis. Both patients presented with fever, marked eosinophilia, and liver lesions on imaging. Hepatobiliary imaging showed vague features like mild biliary dilatation and liver lesions representing burrows. A liver biopsy in one of the patients revealed eosinophilic granuloma. Both patients were diagnosed definitively with endoscopic retrograde cholangiopancreatography (ERCP) by demonstrating live adult fasciola worms. Any patient presenting with fever, marked eosinophilia, and liver lesions on imaging should be evaluated for fascioliasis.

Measurement of Alcohol-Dependent Physiological Changes in Red Blood Cells Using Resistive Pulse Sensing.

Alcohol exposure has been postulated to adversely affect the physiology and function of the red blood cells (RBCs). The global pervasiveness of alcohol abuse, causing health issues and social problems, makes it imperative to resolve the physiological effects of alcohol on RBC physiology. Alcohol consumed recreationally or otherwise almost immediately alters cell physiology in ways that is subtle and still unresolved. In this paper, we introduce a high-resolution device for quantitative electrofluidic measurement of changes in RBC volume upon alcohol exposure. We present an exhaustive calibration of our device using model cells to measure and resolve volume changes down to 0.6 fL. We find an RBC shrinkage of 5.3% at 0.125% ethanol (the legal limit in the United States) and a shrinkage of 18.5% at 0.5% ethanol (the lethal limit) exposure. Further, we also measure the time dependence of cell volume shrinkage (upon alcohol exposure) and then recovery (upon alcohol removal) to quantify shrinkage and recovery of RBC volumes. This work presents the first direct quantification of temporal and concentration-dependent changes in red blood cell volume upon ethanol exposure. Our device presents a universally applicable high-resolution and high-throughput platform to measure changes in cell physiology under native and diseased conditions.

Genotype 1 and 3 Response to Velpatasvir and Sofosbuvir in Chronic Hepatitis C in the Kashmiri Population: An Observational Study.

BACKGROUND: Our data is one of the earliest study from the Indian subcontinent on Velpatasvir/Sofosbuvir (VEL/SOF) combination in chronic hepatitis C (CHC). The primary end point was to evaluate sustained virologic response (SVR) 12 in CHC-infected patients and to determine its effect in patients with hepatitis C virus-related cirrhosis. The secondary end point was to observe any adverse events related to treatment. METHODS: All patients with CHC were randomized into two groups: noncirrhotic and cirrhotic. The combination of VEL/SOF was given as recommended. RESULTS: One hundred patients with CHC infection treated with the VEL/SOF regimen were evaluated. A total of 79 (79%) of 100 patients were noncirrhotic, and 21 (21%) were cirrhotic. We achieved SVR12 in 99 (99%) of 100 patients. Among cirrhotics, the mean serum bilirubin (mg/dl), albumin (g/dl), and platelet count (×10³/µL) improved from baseline 1.82 ± 0.87, 3.22 ± 0.69, and 80.19 ± 46.03 to 1.74 ± 0.87, 3.48 ± 0.72, and 85.05 ± 42.50, respectively, at SVR12 (P-value > 0.05). Mean serum alanine aminotransferase (ALT) (U/L) improved from baseline 71.28 ± 59.17 to 35.38 ± 17.39 at SVR12 (P-value < 0.024). Baseline mean liver stiffness measurement (LSM) in cirrhotic patients was 28.24 ± 10.87 kPa, which decreased to 24.04 ± 9.33 kPa at SVR12 (P-value, 0.02). The baseline Model for End-Stage Liver Disease (MELD) score was 13.47 ± 3.66, which decreased to 12.33 ± 5.46 at SVR12 (P-value, 0.28). The Child-Turcotte-Pugh score improved by 1 point in 33.33% (7/21) patients and 2 points in 9.52% (2/21) patients, and in the majority, that is, 38.09% (8/21), the score remained as it is. CONCLUSION: A single daily dose of the tablet SOF/VEL combination is safe and effective in all types of CHC. There was a significant improvement in the mean transaminase level and LSM at SVR12. And the MELD score improved by 1 point at SVR12 among cirrhotics.

Examining the glacial lake dynamics in a warming climate and GLOF modelling in parts of Chandra basin, Himachal Pradesh, India.

The presented study reports applicability of Lake Detection Algorithm (LDA) for an automated extraction of glacial lakes over a large geographical region and dynamics of Samudra Tapu and Gepang Gath glacial lakes. The areal extent of lake boundary extracted through LDA and areal extent of manually interpreted lake boundary exhibit a remarkable agreement (R2~0.99). Glacial lake dynamics is assessed in terms of areal and volumetric expansion for two selected glacial lakes from 1979 to 2017, i.e. Samudra Tapu (0.95 km2), and Gepang Gath (0.67 km2). They show volumetric expansion from 8.52 × 106 m3 (1979) to 80.34 × 106 m3 (2017) and 2.04 × 106 m3 (1979) to 32.44 × 106 m3 (2017) respectively. Statistical analysis (Mann-Kendall and Sen's slope) of climate data indicates rise in mean annual temperature (0.021 °C yr-1; 1961-2015) and fall in annual precipitation (-2.74 mm yr-1; 1951-2015) at different confidence intervals. Further Glacial Lake Outburst Flood (GLOF) is modelled using empirical relationship and Simplified Dam Breach Model (SMPDBK). The SMPDBK demonstrates discharge of 3866.52 and 2100.90 m3 s-1 reaching Chhatru and Sissu village posing threat to life and property. The study also exhibits that glacial shrinkage under the influence of climate change causes expansion of glacial lakes. This expansion is expected to intensify catastrophic GLOF and resultant fatalities and destruction in the downstream region.

Rasmussen Aneurysm.

Angiographic findings in tuberculosis patients presenting with hemoptysis include hypervascularity, hypertrophy of systemic arteries, aneurysm, systemic to pulmonary anastomosis, and rarely, contrast extravasation. Bronchial arteries are the source of hemorrhage in majority of cases with non-bronchial systemic or pulmonary arteries being less common as the source. Rasmussen's Aneurysm is a very rare sequalae of Pulmonary Tuberculosis. We present one such case of Rasmussen's aneurysm and review of the relevant literature.

COMT genotype and response to cognitive remediation in schizophrenia.

BACKGROUND: A functional polymorphism of the catechol-O-methyltransferase (COMT) gene (Val158Met) partially appears to influence cognitive performance in schizophrenia subjects and healthy controls by modulating prefrontal dopaminergic activity. This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation (CRT). METHOD: 145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling. Subjects were evaluated on neurocognitive assessments (MATRICS) and clinical symptoms (PANSS) at baseline and endpoint after 12weeks of CRT. "Improvement" was defined as ≥67% of cognitive domains (≥4) showing performance increases. If ≤67% (≤2) of domains improved, the change was defined as "minimal improvement." A general linear model was conducted for change of each cognitive domain. RESULTS: Of 145 subjects, data from 138 subjects were usable. Distribution of COMT genotype: Met/Met: 28 (20.29%), Val/Met: 61 (44.20%), and Val/Val: 49 (35.51%). No significant differences were seen among genotype groups at baseline or across genotype group for "Improvement" vs. "Minimal Improvement." GLM analysis showed significant differences in Verbal Learning (p=0.003), Visual Learning (p=0.014) and Attention/Vigilance (p=0.011) favoring Met/Met and Val/Met groups. CONCLUSIONS: The low activity Met allele (Met/Met; Val/Met) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT.

Improving social cognition in schizophrenia: a pilot intervention combining computerized social cognition training with cognitive remediation.

BACKGROUND: Social cognition is significantly impaired in schizophrenia and contributes to poor community functioning. This study examined whether cognitive remediation (CR; COGPACK), shown to improve neurocognition, improves an integral component of social cognition, emotion perception, compared with CR combined with a computerized Emotion Perception intervention (Mind Reading: Interactive Guide to Emotions [MRIGE]). METHODS: 59 stable schizophrenia or schizoaffective predominantly inpatients were randomized to either CR (N=27) alone or CR+MRIGE (N=32) for 12 weeks. Assessments included the Facial Emotion Identification Task (FEIT), Facial Emotion Discrimination Task (FEDT), MCCB-MATRICS, Personal and Social Performance Scale, and the Positive and Negative Syndrome Scale. RESULTS: There was a significant group-by-time effect on FEIT (F=11.509, P=.004); CR+MRIGE demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.89, P=.05; CR alone Z=0.57, P=.13). There was significant group-by-time effect on FEDT (F=5.663, P=.022); CR+MRIGE demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.90, P=.05; CR alone Z=0.67, P=.21). There was also a significant group by time effect for social cognition, measured by the Mayer-Salovey-Caruso Emotional Intelligence Test (F=5.473, P=.050): CR+MRIGE demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.98, P=.02; CR alone, Z=1.00, P=.05). CONCLUSIONS: Combined CR with emotion perception remediation produced greater improvements in emotion recognition, emotion discrimination, social functioning, and neurocognition compared with CR alone in chronic schizophrenia.

Relationship between metabolic syndrome and cognition in patients with schizophrenia.

BACKGROUND: The metabolic syndrome (MetS) and cognitive impairments are common in schizophrenia. Both are associated with poor outcomes, which have received increasing medical and mental health attention. Whether MetS is associated with impaired cognitive functions in schizophrenia has not been thoroughly addressed. The aim of this study was to compare the association between patients with and without MetS and its contributing components with neurocognitive performance. We hypothesized that patients with MetS would be associated with more impaired cognitive performance. METHODS: 159 patients with schizophrenia or schizoaffective disorder, with available metabolic data were included in the study. Patients were classified as either having or not having MetS as defined by the NCEP Adult Panel-III criteria. All patients completed neurocognitive and metabolic tests. RESULTS: Of the 159 patients, 43.34% had MetS. Patients without the MetS performed significantly better on tests measuring processing speed (p=0.050), attention/vigilance (p=0.040), working memory (p=0.041) and problem solving/reasoning (p=0.050) compared with those with MetS. Patients with MetS showed significantly lower cognitive domain scores. After Bonferroni correction greater waist circumference was associated with lower scores on attention/vigilance (ß=-0.551; p≤.0083), HDL was positively associated with scores on attention/vigilance (ß=0.900, p≤.0083) and higher triglycerides were associated with lower scores on attention/vigilance (ß=-1.004, p≤.0083). CONCLUSIONS: Schizophrenia patients with MetS showed significant cognitive impairments in three key cognitive domains. Aggressive medical treatment of the constituent components of MetS may provide the potential for important beneficial effects on patients' cognitive functioning.

Ziprasidone's effect on metabolic markers in patients with diabetes and chronic schizophrenia.

BACKGROUND: Despite numerous studies of diabetes mellitus type II (DM-II) in schizophrenia and schizoaffective disorder, there have been no studies on the glycemic effects of switching patients with long-standing symptomatic DM-II from their current antipsychotic regimen to ziprasidone. METHODS: An open-label, prospective inpatient study was conducted with 26 suboptimally responding inpatients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder and comorbid DM-II who were switched to ziprasidone monotherapy and followed for 8 weeks. Outcome measures were fasting glucose, triglycerides, cholesterol, insulin levels, capillary blood glucose levels and weight. After a 3-week cross-titration period, patients were treated with ziprasidone up to a dose of 320 mg daily. RESULTS: Of the 26 study participants, 16 completed the entire study period of 63 days and 10 (38.46%) discontinued participation, primarily due to psychotic relapse. There was a statistically significant reduction in fasting glucose (F=4.43, p=0.05; 14.68 mg/dL mean reduction), capillary blood glucose levels (F=8.90, p=0.01; 25.36 mg/dL mean reduction), weight (F=4.46, p=0.05; 4.68 lb mean weight loss) and Body Mass Index (F=4.40, p=0.05; 3.62 kg/m(2) mean reduction). There was also a reduction in the use of antidiabetic medications after the switch to ziprasidone. Nine (34.62%) patients met criteria for metabolic syndrome (MetS) at baseline, as compared to 4 (15.38%) at endpoint. No change was observed in positive symptoms (F=0.62, p=0.44), negative symptoms (F=1.47, p=0.24) and in total PANSS score (F=0.12, p=0.74). CONCLUSIONS: This study suggests significant improvement in metabolic side effects and MetS in the subset of the patients who were able to tolerate switching from a polypharmacy regimen to ziprasidone. There was a large discontinuation rate, which limited the sustained beneficial effects of ziprasidone. The decision to switch to ziprasidone in patients with prior suboptimal response has to balance the potential metabolic benefits and the potential relapse risks of the individual patient first and foremost.

A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder.

Quetiapine is often prescribed at doses higher than those approved by regulatory authorities, with limited evidence from controlled trials. The objective of this study was to assess the safety, tolerability, and efficacy of high-dose quetiapine (1200 mg/d) compared with a standard dose of 600 mg/d among patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder hospitalized at 2 state-operated psychiatric facilities. In order to be eligible for randomization, subjects were required to prospectively fail to demonstrate an initial therapeutic response during a 4-week run-in phase with quetiapine at 600 mg/d (immediate release and dosed twice a day). Lack of an adequate initial response was defined a 15% or lower decrease in the Positive and Negative Syndrome Scale total score. Patients were then randomized to either continue quetiapine at 600 mg/d for an additional 8 weeks or to receive 1200 mg/d quetiapine instead. No significant differences were observed between the high dose (n = 29) and standard dose (n = 31) groups in change from baseline to endpoint on extrapyramidal symptoms, electrocardiographic changes, or most laboratory measures between groups. There was a significant difference between groups for triglycerides (P = 0.035), and post hoc tests revealed a decrease in triglycerides from baseline (mean [SD], 162.7 [59.3] mg/dL) to endpoint (mean [SD], 134.8 [62.7] mg/dL) for the 600 mg/d group (P = 0.019). The mean change in the Positive and Negative Syndrome Scale total score did not differ between groups. In conclusion, quetiapine at 1200 mg/d, although reasonably tolerated, did not confer any advantages over quetiapine at 600 mg/d among patients who had failed to demonstrate an adequate response to a prospective 4-week trial of 600 mg/d.

Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy.

Despite its superior efficacy, clozapine is helpful in only a subset of patients with schizophrenia unresponsive to other antipsychotics. This lack of complete success has prompted the frequent use of various clozapine combination strategies despite a paucity of evidence from randomized controlled trials supporting their efficacy. Pimozide, a diphenylbutylpiperidine, possesses pharmacological and clinical properties distinct from other typical antipsychotics. An open-label trial of pimozide adjunctive treatment to clozapine provided promising pilot data in support of a larger controlled trial. Therefore, we conducted a double-blind, placebo-controlled, parallel-designed 12-week trial of pimozide adjunctive treatment added to ongoing optimal clozapine treatment in 53 patients with schizophrenia and schizoaffective disorder partially or completely unresponsive to clozapine monotherapy. An average dose of 6.48 mg/day of pimozide was found to be no better than placebo in combination with clozapine at reducing Positive and Negative Syndrome Scale total, positive, negative, and general psychopathology scores. There is no suggestion from this rigorously conducted trial to suggest that pimozide is an effective augmenting agent if an optimal clozapine trial is ineffective. However, given the lack of evidence to guide clinicians and patients when clozapine does not work well, more controlled trials of innovative strategies are warranted.

Outcome evaluation of a structured educational wellness program in patients with severe mental illness.

OBJECTIVE: Obesity is increasing at an alarming rate in the United States, as is the obesity rate in patients with schizophrenia. Our study retrospectively evaluated the effectiveness of the Solutions for Wellness and Team Solutions programs, 2 structured educational patient programs, and evaluated the effects on obesity and other metabolic markers in a large, naturalistic inpatient sample. METHOD: Between September 18, 2006, and September 15, 2007, 275 inpatients with DSM-IV-TR-diagnosed chronic mental illness admitted to a tertiary care psychiatric facility were included in the 36-week comprehensive and manualized educational program for healthy lifestyles for patients with chronic mental illness incorporating psychoeducational small-group curricula. Patients were tested before and after each of three 12-week group periods by 30 knowledge-assessment questions, and metabolic markers were recorded at baseline, midpoint, and endpoint. RESULTS: Of the 275 included inpatients, 50.5% completed more than 5 modules, 20.4% completed less than or equal to 2 or fewer modules, and 5.1% completed all 11 modules. Significant increases in scores were observed for 7 of the 11 modules in the knowledge assessments (P < .001). Eighty-seven patients (43.72%) had a body mass index (BMI) >/=30 (indicating obesity) at the start of the program. There was a significant mean weight loss of 4.88 lb (P = .035) together with a significant decrease in mean BMI (P = .045). Patients with diabetes showed a reduction in mean weight of 5.98 lb. Significant reductions were observed in glucose and triglyceride levels (both P < .05). Patients with impaired glucose tolerance showed a significantly greater decrease in glucose level (P = .000). Sixty-nine patients (25.46%) met criteria for metabolic syndrome at baseline, and this number was reduced to 53 patients (19.56%) at endpoint; this decrease was significant (P = .027). Regarding relationship of change in knowledge after completion of the modules and metabolic changes, we found a significant correlation between reduction in weight and change in Fitness and Exercise score (r = 0.62, P = .001) and a significant correlation between the change score on Nutrition/Healthy Lifestyles and change in glucose values (r = 0.56, P = .001). CONCLUSIONS: We found that a structured wellness program using a psychoeducational curriculum can be successfully implemented in a large, naturalistic psychiatric setting with unselected, chronically mentally ill inpatients. Results may help both clinicians and hospital managers to implement similar programs or to include successful components in existing programs for psychiatric patients.

Interface for electronic data capture systems for clinical trials by optimal utilization of available hospital resources.

We describe Clinical Trials System (CTS), an innovative EDC system utilizing data from existing hospital-based electronic databases that supports information gathering and storing for various clinical trials. The complexities of designing electronic clinical trials systems and their ideal features are outlined. CTS optimally utilizes existing electronic databases in a well-organized and easy-to-reference format. CTS is currently incorporated within a large psychiatric center, allowing easy sharing of information and data among multidisciplinary clinical and research teams.

Early prediction of antipsychotic response in schizophrenia.

OBJECTIVE: The authors' goal was to examine the predictive value of early symptom changes indicating response to antipsychotic medication in schizophrenia. METHOD: One hundred thirty-one acutely ill patients with schizophrenia received 4 weeks of fluphenazine treatment. Brief Psychiatric Rating Scale (BPRS) ratings were obtained at baseline and weekly. The authors examined the relationship between changes in BPRS total score and each factor score following 1 week of treatment and ultimate response status, defined as a reduction of 20% or more in total BPRS score. RESULTS: None of the patients who [corrected] displayed an improvement of less than 20% in total [corrected] BPRS score and only 5% [corrected] of the [corrected] patients who displayed a reduction of less than 20% in BPRS thought disturbance [corrected] score after 4 weeks of treatment had been classified as responders at 1 week (i.e., 100% and 95% specificity) [corrected] CONCLUSIONS: These data suggest that patients with minimal improvement in positive symptoms during the first week of treatment with a typical antipsychotic are unlikely to respond to a 4-week trial. These data require confirmation and extension to studies with second-generation antipsychotics.