Psychometric validation of the SF-36<Superscript>®</Superscript> Health Survey in ulcerative colitis: results from a systematic literature review

Purpose

To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36^® Health Survey (SF-36) in patients with ulcerative colitis (UC).

Methods

We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed.

Results

Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach’s α ≥ 0.70) for all SF-36 scales and test–retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales.

Conclusions

Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

     

A focus group study of patient’s perspective and experiences of type 2 diabetes and its management in Jordan

Background

Diabetes is increasingly becoming a major health problem in Jordan and glycemic goals are often not achieved.

Circulating microRNA 122 in the methionine and choline‐deficient mouse model of non‐alcoholic steatohepatitis

Non‐alcoholic steatohepatitis (NASH) is a progressive form of non‐alcoholic fatty liver disease (NAFLD) and is a major cause of liver cirrhosis and hepatic failure. The methionine choline‐deficient diet (MCD) is a frequently used hepatotoxicity animal model of NASH that induces hepatic transaminase (ALT, AST) elevations and hepatobiliary histological changes similar to those observed in human NASH. Liver‐specific microRNA‐122 (miR‐122) has been shown as a key regulator of cholesterol and fatty acid metabolism in adult liver, and has recently been proposed as a sensitive and specific circulating biomarker of hepatic injury. The purpose of this study was to assess miR‐122 serum levels in mice receiving an MCD diet for 0, 3, 7, 14, 28 and 56 days and compare the performance vs. routine clinical chemistry when benchmarked against the histopathological liver findings. MiR‐122 levels were quantified in serum using RT‐qPCR. Both miR‐122 and ALT/AST levels were significantly elevated in serum at all timepoints. MiR‐122 levels increased on average by 40‐fold after 3 days of initiating the MCD diet, whereas ALT and AST changes were 4.8‐ and 3.3‐fold, respectively. In general, miR‐122 levels remained elevated across all time points, whereas the ALT/AST increases were less robust but correlated with the progressive severity of NASH as assessed by histopathology. In conclusion, serum levels of miR‐122 can potentially be used as a sensitive biomarker for the early detection of hepatotoxicity and can aid in monitoring the extent of NAFLD‐associated liver injury in mouse efficacy models. Copyright © 2013 John Wiley & Sons, Ltd.     

Human cytomegalovirus-specific immunity following haemopoietic stem cell transplantation

The herpesvirus Human Cytomegalovirus (HCMV) is an important opportunistic infection in recipients of allogeneic haemopoietic stem cell transplants, in whom HCMV-specific CD8+ and CD4+ T-cell responses are impaired. The nature of the HCMV-specific T-cell response in healthy virus carriers has been characterised in detail. High frequencies of circulating CD8+ T-cells that recognise defined viral peptides are maintained for years, and include individual CD8+ clones that have undergone extensive clonal expansion and phenotypic diversification in vivo. Following stem cell transplantation, the kinetics of HCMV-specific CD8+ T-cell reconstitution in the recipient are related to the presence or absence of antigen-experienced CD8+ T-cells transferred via the allograft, and to the presence of the virus in the recipient. We discuss recent progress in our understanding of HCMV-specific immunity in healthy virus carriers and in recipients after alloSCT.     

Cimetidine vs placebo in duodenal ulcer therapy

We studied the healing efficacy of cimetidine or placebo in 23 endoscopically proven duodenal ulcer outpatients in a randomized, controlled, prospective, double-blind trial. There were 11 patients in the cimetidine (1200 mg daily) treatment group and 12 patients in the placebo-treated group. No antacid was allowed, but a placebo antacid with no neutralizing capacity was given as needed for pain. The incidence of complete endoscopic healing at 2, 4, and 6 weeks was 54%, 63%, and 72% in the cimetidine-treated patients and 8%, 50%, and 67% in the placebo-treated patients. There was a statistically significant difference (P<0.05) in complete duodenal ulcer healing between both treatment groups after 2 weeks of therapy, but there was no significant difference at the 4- and 6-week observation periods. The incidence of complete pain relief at 2 and 4 weeks was 64% and 82% in the cimetidine-treated patients and 67% and 75% in the placebo-treated patients. At 6 weeks of treatment there was no increase in the number of patients with complete pain relief in either group. There was no significant difference between the two groups in the incidence of ulcer pain relief at any of the three observation periods. Duodenal ulcer healing rates and duodenal ulcer pain relief were compared at 2, 4, and 6 weeks. There was no statistical association between ulcer healing and complete pain relief in the placebo treatment group at the 2-week evaluation period, but there was statistical association (P<0.05) in the cimetidine treatment group at 2 weeks and both treatment groups at the 4- and 6-week evaluation periods. The results of this study demonstrate that in duodenal ulcer outpatients treated for 6 weeks: (1) cimetidine increases the incidence of duodenal ulcer healing during the first 2 weeks of treatment; (2) more than 50% of duodenal ulcers will spontaneously heal during a 4 to 6-week observation period which is not statistically modified by cimetidine treatment; (3) the complete relief of duodenal ulcer pain is not influenced by treatment with cimetidine when compared to placebo.     

Phosphotyrosine-containing proteins are concentrated in focal adhesions and intercellular junctions in normal cells.

We have used a high-affinity polyclonal antibody directed against phosphotyrosine (P-Tyr) to localize P-Tyr-containing proteins in normal and transformed cells in culture by immunofluorescence microscopy experiments. The distribution of the proteins with modified tyrosine was compared with that of F-actin in these cells. Cells infected with Abelson murine leukemia virus were found to contain elevated levels of P-Tyr, as expected. Various permanent lines of fibroblastic and epithelial cells exhibited lower, but easily detectable, levels of P-Tyr. The P-Tyr in fibroblasts was concentrated at the focal contacts at the termini of actin-containing microfilament bundles and, in the epithelial cells examined, at the intercellular junctions. Early passages of primary cultures of chicken embryo fibroblasts and chicken embryo heart cells also showed detectable levels of P-Tyr in focal contacts and cell-cell junctions. However, P-Tyr was not detectable in later passages of chicken embryo fibroblasts. The concentration of P-Tyr-containing proteins in intercellular junctions in normal cells suggests that these are sites of significant biochemical regulatory activities which may be important in the control of normal cell adhesivity, motility, and shape.     

Reduced in vivo skeletal muscle oxygen consumption in patients with chronic heart failure--a study using Near Infrared Spectrophotometry (NIRS)

AIM: We used Near Infrared Spectrophotometry (NIRS) during arterial occlusion to measure resting skeletal muscle oxygen consumption in chronic heart failure (CHF) patients and in age-matched healthy volunteers (HVs). METHODS: Fifteen CHF patients (ten males) and eleven HVs (six males) had echocardiographic evaluation followed by measurement of the oxygen consumption of the brachioradialis muscle using NIRS. This involved continuous measurement of the oxygenated haemoglobin concentration ([Oxy-Hb]) and deoxy-haemoglobin concentration ([Deoxy-Hb]) with an Oxiplex TS NIRS probe first under basal overnight fasted resting conditions followed by 1 min of forearm arterial occlusion. A linear decline was observed in [Oxy-Hb-Deoxy-Hb] during the arterial occlusion and the oxygen consumption rate was calculated from the initial slope observed. RESULTS: CHF patients were 59+/-2.8 years old with Left Ventricular Ejection Fraction (LVEF) 31%+/-2.2 and the HVs were 52+/-4.8 years old with LVEF 62%+/-2.5. The resting muscle oxygen consumption rate was significantly reduced in CHF patients versus HVs (0.04+/-0.01 mlO(2)/min/100 g versus 0.07+/-0.01 mlO(2)/min/100 g) p<0.005. CONCLUSIONS: There is a significant reduction in resting oxygen consumption per gram of tissue in skeletal muscle of patients with CHF.     

On the translocation of proteins across membranes.

Many proteins of intracellular organelles are first synthesized in the cytoplasm and are then specifically transferred across the membranes of the organelles. On the assumption that these transfers all occur by the same basic mechanism, we enumerate the rather stringent requirements that the mechanism must satisfy. A unitary molecular mechanism is then proposed that meets these requirements.