Adaptation and content validation of measure yourself medical outcomes profile (MYMOP) for 7-11 year-old children.

BACKGROUND: The Measure Yourself Medical Outcome Profile (MYMOP) is an individualised tool designed for adults but used with children without any evidence of validation in this population. Individualised instruments are patient-specific rather than disease-specific and therefore can be applied across various health conditions. This study sought to adapt, and content validate the MYMOP for application in 7-11 year old children. METHODS: There were two main phases of the four iterations: expert consultation (three rounds) and interviews with child-parent pairs at the Outpatient clinics of a Children's Hospital. Thematic analysis was undertaken using an inductive, interpretative approach. RESULTS: Four paediatricians completed the first survey, five paediatricians participated in the focus group, and four paediatric health-related quality of life (HRQOL) research experts completed the second survey. Several changes were recommended to the MYMOP by the expert groups. Twenty-five children (17 general medicine, and 8 diabetes/endocrine clinic) aged 7-11 years completed the draft paediatric MYMOP (P-MYMOP) and were interviewed. Results demonstrated that the majority of participants were able to identify their own problems and activity limitations, and all participants understood the 7-point faces scale. Most parents and children perceived that the P-MYMOP would be useful to complete before clinic appointments. CONCLUSIONS: The P-MYMOP is the first content-validated generic individualised HRQOL measure for children 7-11 years old. Given that validation is an iterative process, further research to assess its feasibility, reliability, and construct validity is required.

Development of a cell-line model to mimic the pro-survival effect of nurse-like cells in chronic lymphocytic leukemia.

The interaction between Chronic lymphocytic leukemia (CLL) cells and monocyte-derived nurse-like cells (NLCs) is fundamentally important to CLL biology. However, studies of how CLL cells and NLCs interact have been hampered by the need for freshly obtained CLL blood samples, coupled with wide variation in the number of monocytes present in the blood of individual patients. Here, we report the development and validation of a cell-line model of NLCs which overcomes these difficulties. Co-culture of primary CLL cells with THP-1 cells induced to differentiate into macrophages by phorbol 12-myristate 13-acetate (PMA) significantly reduced both spontaneous and fludarabine-induced cell death of leukemic cells. Furthermore, compared with their M1-polarized counterparts, M2-polarized macrophages derived from PMA-differentiated THP-1 cells conferred to CLL cells greater protection from spontaneous and fludarabine-induced apoptosis. Since NLCs resemble M2 tumor-associated macrophages, this cell-line model could be useful for investigating the mechanisms through which NLCs protect CLL cells from spontaneous and drug-induced apoptosis.

A systematic review of randomised controlled trials evaluating the use of patient-reported outcome measures (PROMs).

BACKGROUND: Patient-reported outcome measures (PROMs) could play an important role in identifying patients' needs and goals in clinical encounters, improving communication and decision-making with clinicians, while making care more patient-centred. Comprehensive evidence that PROMS are an effective intervention is lacking in single randomised controlled trials (RCTs). METHODS: A systematic search was performed using controlled vocabulary related to the terms: clinical care setting and patient-reported outcome. English language studies were included if they were a RCT with a PROM as an intervention in a patient population. Included studies were analysed and their methodologic quality was appraised using the Cochrane Risk of Bias tool. The protocol was registered with PROSPERO (CRD42016034182). RESULTS: Of 4302 articles initially identified, 115 underwent full-text review resulting in 22 studies reporting on 25 comparisons. The majority of included studies were conducted in USA (11), among cancer patients (11), with adult participants only (20). Statistically significant and robust improvements were reported in the pre-specified outcomes of the process of care (2) and health care (3). Additionally, five, eight and three statistically significant but possibly non-robust findings were reported in the process of care, health and patient satisfaction outcomes, respectively. CONCLUSIONS: Overall, studies that compared PROM to standard care either reported a positive effect or were not powered to find pre-specified differences. There is justification for the use of a PROM as part of standard care, but further adequately powered studies on their use in different contexts are necessary for a more comprehensive evidence base.

Delineating the distinct role of AKT in mediating cell survival and proliferation induced by CD154 and IL-4/IL-21 in chronic lymphocytic leukemia.

The functional significance of AKT in chronic lymphocytic leukemia (CLL) remains unclear. Given the importance of non-malignant T cells in regulating clonal expansion in CLL, we investigated the role of AKT in T cell-mediated cytoprotection and proliferation using an established co-culture system in which primary CLL cells were incubated on a monolayer of transfected mouse fibroblasts expressing human CD40L (CD154). Stimulation of CLL cells via CD40 induced activation of AKT, which was closely associated with downregulation of its negative regulator PTEN, and protected CLL cells from killing by bendamustine. This cytoprotective effect of CD40 stimulation was prevented by a selective inhibitor of AKT. Stimulation of CLL cells with CD154 + IL-4 or IL-21 induced proliferation detected as reduced fluorescence of cells pre-stained with CFSE. AKT inhibition produced a significant, consistent reduction in proliferation induced by CD154 + IL-4 and a reduction in proliferation induced by CD154 + IL-21 in most but not all cases. In contrast, AKT inhibition had no effect on the proliferation of normal B cells induced by CD154 + IL-4 or IL-21. These findings indicate that AKT contributes in a significant way to T-cell mediated survival and proliferation signalling in CLL and support the clinical evaluation of AKT inhibitors in this disease.

Disease extent and local complication of ulcerative colitis in Bangladeshi population.

Ulcerative colitis may involve anywhere from the rectum alone to the entire colon. Local complications like perforation, life threatening haemorrhage, toxic megacolon, pseudo polyps, stricture, and carcinoma of colon are seen. Patients who were diagnosed as Ulcerative Colitis in Departmental Ulcerative Colitis record book from January 1990 to June 2010 was considered as study population. Information regarding the extent of the disease and local complications were taken from earliest documented Lower GIT Endoscopy. Out of 164 patients disease extent were seen in 126(76.83%) patients and among them proctitis/proctosigmoiditis were seen in 57(45.24%) patients, left sided colitis were seen in 11(8.73%) patients, extensive/pan colitis were seen in 58(46.03%) patients. Complication were seen in 164 patients and 1(0.60%) patient had life threatening haemorrhage, 25(15.24%) patients developed pseudo polyps. There was no report of perforation, toxic megacolon, stricture or carcinoma of colon. The differences found between our study and studies from other Western and Asian countries in terms of complication rate and disease extent for were probably due to low index of suspicion, incomplete workup, or incomplete records, and influence of various environmental factors. So, further large scale prospective evaluation is suggested.

Clinical, biochemical, virological and sonographic profile of incidentally detected asymptomatic HBsAg positive subjects, in Bangladesh.

Chronic hepatitis B virus (HBV) is known to be the significant cause of Liver related morbidity and mortality, affecting 400 million people worldwide and a major public health problem in Bangladesh where carrier rates of HBV infection varies from 7.5 to 10%. In Bangladesh prevalence of asymptomatic HBV infection and incidentally detected HBsAg positive subjects were not well studied. The aim of this study is to evaluate the disease activity, replicative status of the virus and to find out the stages of chronic liver disease among incidentally detected asymptomatic HBsAg positive Bangladeshi subjects. Two hundred (200) incidentally detected healthy HBsAg positive subject were evaluated clinically, biochemically, serologically and ultrasonographically from January 2004 to June 2008. HBeAg was found positive in 17(8.5%), anti-HBe was positive in 174(87%), raised serum ALT (>45iu/L) in 45(22.5%), prothrombine time (PT) >3 sec of control in 33(16.5%). Ultrasonography showed coarse hepatic echotexture in 13(6.5%). Evidence of active viral replication and signs of chronic liver disease were observed among incidentally detected healthy HBsAg positive subjects. Such individuals should be followed up at regular interval to evaluate the replicative status of the virus and disease activity so that appropriate measures could be initiated in time.

Comparative efficacy and safety of trimebutine versus mebeverine in the treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional disorder characterized by chronic or recurrent abdominal pain or discomfort with bowel disturbances. This prospective, randomized clinical trial has been conducted on IBS patients, using trimebutine and Mebeverine in separate group in parallel design to compare the efficacy and safety of Trimebutine 100mg twice daily with mebeverine 135mg twice daily. Patients of 15 to 60 years old and both sexes were included from the out patient department (OPD) of gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from June 2010 to December 2011. A validated IBS-QOL instrument consisted of 34 questions used to assess improvement of quality of life before and after treatment. A total of 140 patients were enrolled in this study. Eighteen patients dropped out. One hundred twenty two patients completed the trial. In this study at the end of 6 weeks therapy, improvement of symptoms was statistically significant. However, differences of improvement between the two groups in relieving various symptoms were not statistically significant. Mean QOL score before treatment was 103 in Trimebutine group and 106 in Mebeverine group. After 6 weeks of treatment mean QOL score was 82 in Trimebutine group and 95 in Mebeverine group indicating improvement in both groups was statistically significant. The difference between the two groups was also significant. No worsening of symptoms and no side effects of the therapeutic agents was observed in any patient during the trial.

Bioavailability and plasma concentration of omeprazole in healthy bangladeshi population after ingestion.

This cross-sectional observational study was conducted in the department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Plasma concentration of omeprazole was assayed in the quality control laboratory of Novartis (Bangladesh) Limited, Tongi, Gazipur, Bangladesh. The study was conducted from January 2006 to April 2007 and was designed to find out the bioavailability of omeprazole in capsule form in healthy Bangladeshi population and to compare this with that of the other population in the world. Twelve healthy volunteers were included in this study. The subjects were divided into two groups; six of them were randomly selected in each. One group received 40mg omeprazole intact capsule of one trade and other group received 40mg omeprazole intact capsule of another trade once daily for consecutive 8 days at 8.00 hours on each day. On the first and eight days of dosing, 10ml of blood sample was collected from each subject at 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 and 6.0 hours after dosing. Blood samples were centrifuged at 2500rpm for 15 minutes and plasma was stored at 20°C. Omeprazole concentration in plasma was determined using a reverse phase high performance liquid chromatography (HPLC). From the concentration, the area under the curve (AUC) of omeprazole was determined for each subject by the trapezoidal rule. From the result it was observed that the plasma concentration of omeprazole was increased up to 6 hours in both trade-A and trade-B in day 1 and 8. Thus the AUC of omeprazole was also increased. But most of the studies in western population showed that the maximum plasma concentration was within 0.5 to 2.0hours indicating a difference from that of western studies. In this study all the subjects exhibited increased plasma concentration and AUC which may be due to genetic variation of omeprazole metabolism as an Asian which may be due to slow or "Poor metabolizers" (PMs), of the study population, who are deficient in CYP2C19. It is revealed that the plasma concentration and AUCs of both the products after single and repeated doses of omeprazole capsule were higher in comparison to other studies in western population.

Sustained virological response after treatment in patients with chronic hepatitis C infection--a five year follow up.

Peginterferon alpha-2a and ribavirin combination therapy achieves a sustained virological response (SVR) in patients with chronic hepatitis C. Little is know about long-term durability of hepatitis C virus--Ribonucleic acid (HCV-RNA) negativity in patient treated with pegylated interferon and ribavirin therapy. Aim of this study was to evaluate the durability of virologic response in patients with SVR to anti-viral therapy treated at our centre. A total of 52 patients with chronic hepatitis C virus infection who had obtained SVR after Peginterferon alpha-2a and ribavirin combination therapy were followed up to 5 years with annual HCV-RNA testing. During this follow up period, 4 of 52 patients with initial SVR developed late relapse of hepatitis C virus infection. Relapse was more common in patients who has cirrhosis (3/6 [50%]) vs (1/46 [2.17%]) without cirrhosis. In conclusion, SVR is durable in most patients, but some patients do have late relapse; long-term follow up may be particularly important in a subset of patients with hepatitis C virus infection who have liver cirrhosis.

Role of Saccharomyces boulardii in diarrhea predominant irritable bowel syndrome.

Several studies with probiotics have shown promising results in the treatment of IBS. One of the probiotics used was saccharomyces boulardii. This is a randomized double blind placebo controlled clinical trial of S. boulardii in diarrhoea predominant IBS and was carried out in the hospital of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from June 2004 to July 2005. Thirty five (35) patients were included in each of the control and study groups. The study group was treated with S. boulardii 250 mg twice daily orally for one month. Patients were evaluated before therapy, at the end of therapy and 30 days after end of therapy by a scoring system which included symptoms as well as personal and professional life. No significant difference between the two groups was found in any of the parameters evaluated on any of the observation days. S. boulardii treatment for 30 days in diarrhoea predominant IBS patients did not result in any improvement in this study.

Sero-epidemiology of sporadic acute hepatitis in Bangladesh: high prevalences of infection with type-B, type-E and multiple types of hepatitis virus.

In a recent investigation of hepatitis in Bangladesh, the sera from 74 adult patients (aged 15-67 years) who had been clinically diagnosed as cases of sporadic acute hepatitis were collected at various hospitals in and around Dhaka. Five cases were positive for IgM antibody against the hepatitis A virus and 30 were positive both for the surface antigen of the hepatitis B virus (HBV) and for IgM antibody against the HBV core (HBc). The six cases found positive for antibodies against the hepatitis D virus were all also positive for the HBV surface antigen but negative for anti-HBc IgM. Thirteen patients harboured hepatitis C virus RNA and 29 were positive for IgM antibody against the hepatitis E virus (HEV). There were 14 non-A-to-E subjects, whose illness was of unknown aetiology. Of the 83 infections with hepatitis viruses detected in the other 60 patients, 6%, 36%, 16%, 7% and 35% were of types A, B, C, D and E, respectively. Each of 28 of the patients (47% of those confirmed to have viral hepatitis) had concomitant infection with more than one type of hepatitis virus. The predominance of HBV and HEV infections and the high prevalence of multiple infection seen among these Bangladeshi cases have not been observed among hepatitis cases in developed countries.