Frequency and Quality of Exposure to Adaptive Cruise Control and Impact on Trust, Workload, and Mental Models.

Advanced Driver Assistance Systems (ADAS) support drivers with some driving tasks. However, drivers may lack appropriate knowledge about ADAS resulting in inadequate mental models. This may result in drivers misusing ADAS, or mistrusting the technologies, especially after encountering edge-case events (situations beyond the capability of an ADAS where the system may malfunction or fail) and may also adversely affect driver workload. Literature suggests mental models could be improved through exposure to ADAS-related driving situations, especially those related to ADAS capabilities and limitations. The objective of this study was to examine the impact of frequency and quality of exposure on drivers' understanding of Adaptive Cruise Control (ACC), their trust, and their workload after driving with ACC. Sixteen novice ACC users were recruited for this longitudinal driving simulator study. Drivers were randomly assigned to one of two groups - the 'Regular Exposure' group encountering 'routine' edge-case events, and the 'Enhanced Exposure' group encountering 'routine' and 'rare' events. Each participant undertook four different simulator sessions, each separated by about a week. Each session comprised a simulator drive featuring five edge-case scenarios. The study followed a mixed-subject design, with exposure frequency as the within-subject variable, and quality of exposure (defined by two groups) as the between-subject variable. Surveys measured drivers' trust, workload, and mental models. The results from the analyses using linear regression models revealed that drivers' mental models about ACC improve with frequency of exposure to ACC and associated edge-case driving situations. This was more the case for drivers who experienced 'rare' ACC edge cases. The findings also indicate that for those who encountered 'rare' edge cases, workload was higher and trust was lower than those who did not. These findings are significant since they underline the importance of experience and familiarity with ADAS for safe operation. While these findings indicate that drivers benefit from increased exposure to ACC and edge cases in terms of appropriate use of ADAS, and ultimately promise crash reductions and injury prevention, a challenge remains regarding how to provide drivers with appropriate exposure in a safe manner.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

BACKGROUND: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, may increase the risk of death, and impacts kidney transplant outcomes. Direct-acting antivirals have replaced interferons because of better efficacy and tolerability. This is an update of a review first published in 2015. OBJECTIVES: We aimed to look at the benefits and harms of interventions for HCV in CKD patients on dialysis: death, disease relapse, treatment response/discontinuation, time to recovery, quality of life (QoL), cost-effectiveness, and adverse events. We aimed to study comparisons of available interventions, compared with placebo, control, with each other and with newer treatments. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 23 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register Portal (ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Three studies were included in this update, therefore 13 studies (997 randomised participants) met our inclusion criteria. Overall, the risk of bias was judged low in seven studies, unclear in four, low to unclear in one, and high in one study. Interventions included standard interferon, pegylated (PEG) interferon, standard or PEG interferon plus ribavirin; direct-acting antivirals, and direct-acting antivirals plus PEG interferon plus ribavirin. Compared to placebo or control, standard interferon may make little or no difference to death (5 studies, 134 participants: RR 0.89, 95% CI 0.06 to 13.23) or relapse (low certainty evidence), probably improves end-of-treatment response (ETR) (5 studies, 132 participants: RR 8.62, 95% CI 3.03 to 24.55; I² = 0%) (moderate certainty evidence), and probably makes little or no difference to sustained virological response (SVR) (4 studies, 98 participants: RR 3.25, 95% CI 0.81 to 13.07; I² = 53%), treatment discontinuation (4 studies, 116 participants: RR 4.59, 95% CI 0.49 to 42.69; I² = 63%), and adverse events (5 studies, 143 participants: RR 3.56, 95% CI 0.98 to 13.01; I² = 25%) (moderate certainty evidence). In low certainty evidence, PEG interferon (1 study, 50 participants) may improve ETR (RR 1.53, 95% CI 1.09 to 2.15) but may make little or no difference to death (RR 0.33, 95% CI 0.01 to 7.81), SVR (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96), adverse events (RR 0.11, 95% CI 0.01 to 1.96) and relapses (21/38 relapsed) (RR 0.72, 95% CI 0.41 to 1.25) compared to standard interferon. In moderate certainty evidence, high-dose PEG interferon (alpha-2a and alpha-2b) may make little or no difference to death (2 studies, 97 participants: RR 4.30, 95% CI 0.76 to 24.33; I² = 0%), ETR (RR 1.42, 95% CI 0.51 to 3.90; I² = 20%), SVR (RR 1.19, 95% CI 0.68 to 2.07; I² = 0%), treatment discontinuation (RR 1.20, 95% CI 0.63 to 2.28; I² = 0%) or adverse events (RR 1.05, 95% CI 0.61 to 1.83; I² = 27%) compared to low-dose PEG interferon. High-dose PEG interferon may make little or no difference to relapses (1 study, 43 participants: RR 1.11, 95% CI 0.45 to 2.77; low certainty evidence). There were no significant subgroup differences. Standard interferon plus ribavirin may lead to higher treatment discontinuation (1 study, 52 participants: RR 2.97, 95% CI 1.19 to 7.36; low certainty evidence) compared to standard interferon alone.  In low certainty evidence, PEG interferon plus ribavirin (1 study, 377 participants) may improve SVR (RR 1.80, 95% CI 1.46 to 2.21), reduce relapses (RR 0.33, 95% CI 0.23 to 0.48), slightly increase the number with adverse events (RR 1.10, 95% CI 1.01 to 1.19), and may make little or no difference to ETR (RR 1.01, 95% CI 0.94 to 1.09) compared to PEG interferon alone. The evidence is very uncertain about the effect of PEG interferon plus ribavirin on treatment discontinuation (RR 1.71, 95% CI 0.69 to 4.24) compared to PEG interferon alone. One study reported grazoprevir plus elbasvir improved ETR (173 participants: RR 174.99, 95% CI 11.03 to 2775.78; low certainty evidence) compared to placebo. It is uncertain whether telaprevir plus ribavirin (high versus low initial dose) plus PEG interferon for 24 versus 48 weeks (1 study, 35 participants) improves ETR (RR 1.02, 95% CI 0.67 to 1.56) or SVR (RR 1.02, 95% CI 0.67 to 1.56) because the certainty of the evidence is very low.  Data on QoL, cost-effectiveness, cardiovascular outcomes and peritoneal dialysis were not available. AUTHORS' CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.

Simulator evaluation of an intersection maneuver assist system with connected and automated vehicle technologies.

Intersection crashes can be potentially mitigated through vehicle-to-infrastructure (V2I) and vehicle-to-vehicle (V2V) safety management systems. It is important, however, to consider some of the human factors related aspects of such systems to maximise potential safety benefits. In this study, Intersection Manoeuvre Assistance Systems were conceptualised and evaluated in a driving simulator. The systems were designed to assist drivers with intersection manoeuvres by making use of connected infrastructure and providing real-time feedback, guidance, and active vehicle controls. The study compared drivers' confidence, workload, glances at the instrument panel, and hazard anticipation when driving using three systems-System A (no alert or assist); System B (alert only); and System C (alert and assist). Study results show differences in drivers' confidence in such systems and potentially degraded visual gaze behaviours.Practitioner summary: Connected infrastructure-based intersection management assistance systems can potentially reduce crashes. This experimental driving simulation study evaluated drivers' perceptions and reactions to intersection management systems. Results indicate reduced confidence in automated systems, reduced visual scanning for external hazards at intersections, and increased off-road glances towards the instrument panel.

The role of precautions: Organising a medical conference during COVID-19 pandemic-Lessons from IADVL MIDDERMACON 2021.

Background: The use of virtual platforms for clinical meetings has become the default approach during this pandemic era. Organising an offline conference during a pandemic is a challenge and is possible if the participating crowd is vaccinated and is willing to follow appropriate pandemic protocols. Objective: To determine the feasibility of conducting a conference among mostly vaccinated delegates using standard precautionary protocols. Methods: This study was conducted at IADVL MIDDERMACON 2021, held in Mangalore, India, in late October 2021, during the phase of decline of the Delta variant of SARS-CoV-2. The study population included all conference attendees, including support staff. Details were collected about their vaccination status, comorbidities, and mode of travel to the conference venue. An reverse-transcription polymerase chain reaction (RT-PCR) test was done randomly among the attendees for COVID-19 infection. A post-conference assessment and RT-PCR tests were done at the end of 2 weeks to assess the occurrence of infections among study participants. Results: A total of 1744 people were present at the venue, of which 576 (33.03%) participated in the study. The percentage of fully vaccinated was 88.88% (512/576). The majority had taken the vaccine Covishield (manufactured by AstraZeneca), that is, 85.06% (490/576). Infection post the conference was reported in 0.195% (1/576). Conclusions: Holding large gatherings like medical conferences pose a challenge during a pandemic. However, to increase the benefits of the conference, it is advisable to hold them offline with vaccinated delegates, follow the advice of the conference organising committee, and practise safe precautionary measures.

Profile of Helicobacter pylori cagA &vacA genotypes and its association with the spectrum of gastroduodenal disease.

PURPOSE: Globally, H. pylori virulence factors cagA and vacA genotypes and its variation is leading to the austere form of the gastroduodenal disease. Our objectives were to detect H. pylori in dyspeptic patients from biopsy samples with the validation of the various existing diagnostic tools and to screen the cagA, vacA genotypes profile from biopsy specimens and how it impacts in progression of gastroduodenal disease in southern India. METHODS: 374 patients who attended endoscopy unit at Kasturba Hospital, Manipal with their consent obtained their biopsies. H. pylori were detected by HPE, Culture, RUT and PCR and its virulence gene were patterned with PCR. RESULTS: The positive rate of H. pylori by HPE, RUT, Culture and PCR were 51.33%, 47.1%, 32.4% and 50.3% respectively and comparison by Bayesian LCMs analysis showed PCR is superior among them. The frequency of H. pylori virulence gene viz cagPAI (cagA) were 80.9%, and vacA alleles-s1m1 (42%), s1m2 (33%) and s2m2 (25%) genotypes by PCR respectively. Four combinations of cagA/vacA genotypes were noted, majority of strains harboured cagA+/vacA s1m1 genotypes (42.6%), interestingly this hyper-virulent strain more frequently seen in severe gastroduodenal disease whereas cagPAI negative strains as well as cagA-/vacA s2m2 combinations (19.1%) are seen most commonly in functional dyspepsia cases and depicted significant association by Chi-square test. CONCLUSIONS: This study validates and compares the existing diagnostic methods for detecting H. pylori in biopsies. Also, it reveals some pattern of virulence gene combination will play a vital role in disease progression.

Best practices of handling, processing, and interpretation of small intestinal biopsies for the diagnosis and management of celiac disease: A joint consensus of Indian association of pathologists and microbiologists and Indian society of gastroenterology.

The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.

Prevalence of low bone mineral density in inflammatory bowel disease and factors associated with it.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have numerous risk factors for low bone mineral density (BMD). We aimed to study the prevalence of low BMD in IBD and the factors associated with it. METHODS: BMD was measured by radial quantitative ultrasound, and clinical and biochemical characteristics were compared in prospectively enrolled patients and healthy age and gender-matched controls. Chi-square test, t test for independent samples, analysis of variance (ANOVA), Mann-Whitney U test and Kruskal-Wallis H tests were used as appropriate for univariate analysis to compare the characteristics between patients with and without abnormal BMD. Binary logistic regression analysis was done to determine the factors associated with low BMD in IBD patients. RESULTS: One hundred and six patients (Crohn's disease [CD] = 35, ulcerative colitis [UC] = 71) and 55 controls were included. Low BMD was equally prevalent in CD, UC and controls (42.9%, 36.6%, 36.4% respectively, p = 0.791). Serum calcium and vitamin D were significantly lower in IBD patients compared to controls (p < 0.001 and p = 0.003, respectively) but not between patients with low and normal BMD. Older age (Odds ratio [OR] = 66.12 [9.299-470.243], p < 0.001), late onset of disease (OR = 4.795 [1.067-21.543], p = 0.041) and absence of steroid usage (OR = 0.272 [0.089-0.832], p = 0.022) were significantly associated with low BMD. CONCLUSIONS: The prevalence of low BMD in patients with IBD was similar to controls and this was associated with increasing age, late onset of disease, and absence of steroid usage. Judicious use of steroids can help preserve bone health in IBD.

A Wizard-of-Oz experimental approach to study the human factors of automated vehicles: Platform and methods evaluation.

OBJECTIVES: Driving simulation is an important platform for studying vehicle automation. There are different approaches to using this platform - with most using scripting or programmatic tools to simulate vehicle automation. A less frequently used approach, the Wizard-of-Oz method, has potential for increased flexibility and efficiency in designing and conducting experiments. This study designed and evaluated an experimental setup to examine the feasibility of this approach as an alternative for conducting automation studies. METHODS: Twenty-four participants experienced simulated vehicle automation in two platforms, one where the automation was controlled by algorithms, and the other where the automation was simulated by an external operator. Surveys were administered after each drive and the drivers' takeover performance after the automation disengaged was measured. RESULTS: Results indicate that while the kinematic parameters of the driving differed significantly for the two platforms, there were no significant differences in the perceptions of participants and in their takeover performance between the two platforms. CONCLUSION: These results provide evidence for the use of alternative approaches for the conduct of human factors studies on vehicle automation, potentially lowering barriers to undertaking such experiments while increasing flexibility in designing more complex studies.

Fractional carbon dioxide laser for facial scarring due to windscreen glass shatter injury.

BACKGROUND: Facial injuries due to flying windscreen glass pieces are common in road accident and require surgical intervention by plastic surgeons to debride, suture, and dress the injuries. Posthealing patients visit dermatologists for further treatment of residual scar tissue. Interestingly, tiny papules or small nodular scars seen on otherwise level background which persists for beyond 3 months (scar modeling time) may actually harbor small fragments of glass. Such lesions can only be treated by fractional CO2 therapy. METHODS: Two patients who had papules and small nodular lesions on the accident scarred areas were subjected to fractional CO2 laser (ultraPulse, Lumenis)with moderate fluence and high density, once and observed over a period of 12 weeks. RESULTS: On targeting the papules and small nodules, tiny particles of glass appeared out of the broken lesions. DISCUSSION: Irrespective of the surgery done on accident victims involving windshield glass injuries, fractional CO2 may be considered at a later stage, especially with presence of papules interspersed in the area of facial scars.

Hair and Humor - 1 - "The Only Problem".

Perhaps the best solution for hair loss is a little bit of philosophy and a lot of humor. Endless trips to trichologists, hair potions and lotions hardly prevent the reluctant march to baldness. Unless of course, the patient agrees to a hair transplant.

Diet and inflammatory bowel disease: The Asian Working Group guidelines.

INTRODUCTION: These Asian Working Group guidelines on diet in inflammatory bowel disease (IBD) present a multidisciplinary focus on clinical nutrition in IBD in Asian countries. METHODOLOGY: The guidelines are based on evidence from existing published literature; however, if objective data were lacking or inconclusive, expert opinion was considered. The conclusions and 38 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. RESULTS: Diet has an important role in IBD pathogenesis, and an increase in the incidence of IBD in Asian countries has paralleled changes in the dietary patterns. The present consensus endeavors to address the following topics in relation to IBD: (i) role of diet in the pathogenesis; (ii) diet as a therapy; (iii) malnutrition and nutritional assessment of the patients; (iv) dietary recommendations; (v) nutritional rehabilitation; and (vi) nutrition in special situations like surgery, pregnancy, and lactation. CONCLUSIONS: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 38 recommendations.

High primary resistance to metronidazole and levofloxacin, and a moderate resistance to clarithromycin in Helicobacter pylori isolated from Karnataka patients.

BACKGROUND: Due to increased prevalence of H. pylori antimicrobial resistance worldwide and more importantly the resistance patterns vary between different geographical regions, it is important to survey local H. pylori antibiotic resistance profile to provide physicians with more informed drug choices to better treat H. pylori infection. To our knowledge, this is the first study to examine the prevalence of antimicrobial resistance of H. pylori in Karnataka state of South India. RESULTS: A total of 113 H. pylori strains were isolated from gastric biopsies and tested: 81.4% were resistant to metronidazole, 54.9% were resistant to levofloxacin, 20.4% were resistant to clarithromycin, 5.3% were resistant to tetracycline and 7.1% were resistant to amoxicillin. Multidrug resistance was detected in 59.3% of total isolated strains, among which 86.6% were resistant to at least both metronidazole and levofloxacin. In this study, 38 out of 113 H. pylori strains had been whole-genome sequenced. Based on the draft genomes, RdxA and/or FrxA inactivation mutations were found to present in 75% of metronidazole-resistant strains. Clarithromycin-resistant strains had mainly A2143G and G2224A mutations in the 23 rRNA gene. While 87.1% levofloxacin-resistant strains had amino acid substitution mutations occurring predominantly at N87 and D91 in GyrA, novel mutations in the same protein including an insertion of five amino acid residues (QDNSV), immediately after the start codon, and a substitution mutation at R295 were identified. CONCLUSION: High primary resistance to metronidazole and levofloxacin, and a modest occurrence of clarithromycin resistance were revealed in H. pylori strains isolated from Karnataka patients. Therefore metronidazole-, levofloxacin- and clarithromycin-based triple therapies are not suitable as first-line treatment in Karnataka. Both amoxicillin and tetracycline can still be used to eradicate H. pylori infection in this region. We also revealed novel mutations in GyrA protein that possibly contribute to H. pylori resistance in levofloxacin, which merit further investigations.

Effect of video-assisted patient education on compliance with therapy, quality of life, psychomorbidity, and cost of illness in irritable bowel syndrome.

OBJECTIVE: Patient education is important in irritable bowel syndrome (IBS), but its effects on outcomes have not been studied extensively. METHODS: Patients were enrolled and prospectively divided into an interventional and usual care group. Both received standard of care, but the former additionally received video-assisted patient education. Self-administered questionnaires IBS-quality of life (QOL), Beck Anxiety-Depression Inventory II (BAI, BDI), and Hospital Anxiety and Depression Scale (HADS) were administered at baseline, 3 months, and 6 months. Compliance was defined as drug intake of >80% of the prescribed dose. COI included prospective, prevalence-based, societal perspective. RESULTS: Of the 107 patients included, 84 [78.5%; male = 66 (78.57%); median age = 44 (range 20-77 years)] completed the follow up. While the median (inter-quartile range; IQR) QOL scores decreased significantly in both the groups (p < 0.001 for either group), the final scores were significantly better in the interventional group [49 (44-52.5) versus 80 (76-103), respectively; p < 0.005]. There was a significant improvement in the BDI; p < 0.001]. However, the rest did not achieve statistical significance. At 6 months, total median (IQR) semi-annual cost per patient was INR 14,639 (8253-17,909) [US $240 (135-294]. CONCLUSION: Video-assisted patient education should be a part of the treatment of IBS since it improves the QOL and depression scores.

Correction to: Diet and inflammatory bowel disease: The Asian Working Group guidelines.

The recommendations 31 which recommend "VSL#3®", refer only to the product used in the cited literature and equivalent products independent from the present product labelings. This product is now known by the generic name "De Simone Formulation".

Resveratrol analogue, trans-4,4'-dihydroxystilbene (DHS), inhibits melanoma tumor growth and suppresses its metastatic colonization in lungs.

The prevalence of melanoma and the lack of effective therapy for metastatic melanoma warrant extensive and systematic evaluations of small molecules in cellular and pre-clinical models. We investigated, herein, the antitumor and anti-metastatic effects of trans-4,4'-dihydroxystilbene (DHS), a natural product present in bark of Yucca periculosa, using in vitro and in vivo melanoma murine models. DHS showed potent melanoma cytotoxicity, as determined by MTT and clonogenic assay. Further, DHS induced cytotoxicity was mediated through apoptosis, which was assessed by annexin V-FITC/PI, sub-G1 and caspase activation assays. In addition, DHS inhibited cell proliferation by inducing robust cell cycle arrest in G1-phase. Imperatively, these inhibitory effects led to a significant reduction of melanoma tumor in pre-clinical murine model. DHS also inhibited cell migration and invasion of melanoma cells, which were examined using wound healing and Transwell migration/invasion assays. Mechanistically, DHS modulated the expressions of several key metastasis regulating proteins e.g., MMP-2/9, N-cadherin, E-cadherin and survivin. We also showed the anti-metastatic effect of DHS in a melanoma mediated lung metastasis model in vivo. DHS significantly reduced large melanoma nodule formation in the parenchyma of lungs. Therefore, DHS may represent a promising natural drug in the repertoire of treatment against melanoma tumor growth and metastasis.

Drinking pattern in persons with alcohol dependence with and without cirrhosis: A hospital-based comparative study.

BACKGROUND: Worldwide, alcohol is the most frequently used and socially accepted hepatotoxin. However, not everyone who has alcohol dependence develops alcoholic cirrhosis, and does quantity/type or pattern of alcohol intake determine the development of cirrhosis? A study of this nature would help in delineating similarities/differences in the drinking pattern between alcohol dependence and alcohol-induced cirrhosis groups. AIM: The aim was to study the drinking pattern of persons with alcohol dependence syndrome (ADS) and alcohol-induced cirrhosis. MATERIALS AND METHODS: Alcohol Intake database and Severity of Alcohol Dependence Questionnaire (SADQ) were administered to eighty male inpatients with a reliable family member of which forty were in ADS group and forty were in alcohol dependence with cirrhosis group. RESULTS: Persons in the cirrhosis group were older with longer duration of drinking. There is no statistically significant difference in the educational status, religion, occupation, socioeconomic class, mean age of onset of drinking, mean age of development of dependence, type of beverage preferred, and initiating/maintaining factors between the two groups. The amount of alcohol consumed was significantly high in the cirrhosis group, with 33.5% in the high severity of dependence. They usually were drinking alone, outside meal times with regular and intermittent binge pattern. CONCLUSION: Alcohol dependence and alcohol-induced cirrhosis may be on a continuum but form a different group of heavy drinkers who may require different approaches to management.

Direct costs for nonsurgical management of Chronic Pancreatitis in a tertiary care teaching hospital.

BACKGROUND: Chronic pancreatitis (CP) is a leading cause of hospitalization among gastrointestinal diseases resulting in considerable financial burden to patients. However the direct costs for nonsurgical management in CP remains unexplored. METHODS: A cross sectional study was carried out (2011-14) in the Department of Gastroenterology, Kasturba Hospital, Manipal, India. Demographic and clinical data on laboratory investigations, interventions and follow up were obtained from the medical records department. Item costs were derived from the hospital electronic billing section. Cost was expressed as median annual cost per patient. RESULTS: 65 (male 48; 73.8%) patients were included. Their median age was 31 (range 12-68) years. The annual median (IQR) total cost per patient was INR 88,892 (70,550.5-116,004); [USD 1410(1119-1841); € 1155(916-1507)], comprising of INR 61,089 (39,102.5-90,360.5) [USD 970 (621-1434); € 793(508-1174)] for outpatient management and INR 32,450 (11,016-46,958) [USD 515 (175-745); €421(143-610)] for hospitalization. 69.5% of the treatment cost was attributed to outpatient treatment. Drugs contributed to 54%, hospitalization incurred 30.5%, investigations 12% and professional fees (3.5%) of the total cost. Pancreatic enzyme replacement therapy (PERT) cost contributed to three-quarters of drug therapy. Use of rabeprazole as against pantoprazole reduced the overall annual cost of therapy by 4%. CONCLUSIONS: This study depicts the first nonsurgical management of accrued direct costs associated with CP due to expensive medications. Due to the high cost for PERT, its usefulness needs proper validation by cost benefit analysis.

trans-4,4'-Dihydroxystilbene (DHS) inhibits human neuroblastoma tumor growth and induces mitochondrial and lysosomal damages in neuroblastoma cell lines.

In view of the inadequacy of neuroblastoma treatment, five hydroxystilbenes and resveratrol (Resv) were screened for their cytotoxic property against human neuroblastoma cell lines. The mechanism of cytotoxic action of the most potent compound, trans-4,4'-dihydroxystilbene (DHS) was investigated in vitro using human neuroblastoma cell lines. DHS was also tested in a mouse xenograft model of human neuroblastoma tumor. The MTT, sub-G1, annexin V and clonogenic assays as well as microscopy established higher cytotoxicity of DHS than Resv to the IMR32 cell line. DHS (20 µM) induced mitochondrial membrane permeabilization (MMP) in the cells, as revealed from JC-1 staining, cytochrome c and ApaF1 release and caspases-9/3 activation. DHS also induced lysosomal membrane permeabilization (LMP) to release cathepsins B, L and D, and the cathepsins inhibitors partially reduced MMP/caspase-3 activation. The ROS, produced by DHS activated the p38 and JNK MAPKs to augment the BAX activity and BID-cleavage, and induce LMP and MMP in the cells. DHS (100 mg/kg) also inhibited human neuroblastoma tumor growth in SCID mice by 51%. Hence, DHS may be a potential chemotherapeutic option against neuroblastoma. The involvement of an independent LMP as well as a partially LMP-dependent MMP by DHS is attractive as it provides options to target both mitochondria and lysosome.