The performance of methods for correcting measurement error in case-control studies

BACKGROUND: It is generally agreed that adjustment for measurement error (when feasible) can substantially increase the validity of epidemiologic analyses. Although a broad variety of methods for measurement error correction has been developed, application in practice is rare. One reason may be that little is known about the robustness of these methods against violations of their restrictive assumptions. METHODS: We carried out a simulation study to assess the performance of two error correction methods (a regression calibration method and a semiparametric approach) as compared with standard analyses without measurement error correction in case-control studies with internal validation data. Performance was assessed over a wide range of model parameters including varying degrees of violations of assumptions. RESULTS: In nearly all the settings assessed, the semiparametric estimate performed better than all alternatives under investigation. The regression calibration method is sensitive to violations of the assumptions of nondifferential error and small error variance. CONCLUSIONS: The semiparametric method is a very robust method to correct for measurement error in case-control studies, but lack of functional software hinders widespread use. If the assumptions for the regression calibration method are fulfilled, application of this method, originally developed for cohort studies, in case-control studies may be a useful alternative that is easy to implement.     

Sirolimus/cyclosporine/tacrolimus interactions on bile flow and biliary excretion of immunosuppressants in a subchronic bile fistula rat model

The new immunosuppressive agent sirolimus generally is combined in transplant patients with cyclosporine and tacrolimus which both exhibit cholestatic effects. Nothing is known about possible cholestatic effects of these combinations which might be important for biliary excretion of endogenous compounds as well as of immunosuppressants. Rats were daily treated with sirolimus (1 mg kg(-1) p.o.), cyclosporine (10 mg kg(-1) i.p.), tacrolimus (1 mg kg(-1) i.p.), or a combination of sirolimus with cyclosporine or tacrolimus. After 14 days a bile fistula was installed to investigate the effects of the immunosuppressants and their combinations on bile flow and on biliary excretion of bile salts, cholesterol, and immunosuppressants. Cyclosporine as well as tacrolimus reduced bile flow (-22%; -18%), biliary excretion of bile salts (-15%;-36%) and cholesterol (-15%; -47%). Sirolimus decreased bile flow by 10%, but had no effect on cholesterol or bile salt excretion. Combination of sirolimus/cyclosporine decreased bile flow and biliary bile salt excretion to the same extent as cyclosporine alone, but led to a 2 fold increase of biliary cholesterol excretion. Combination of sirolimus/tacrolimus reduced bile flow only by 7.5% and did not change biliary bile salt and cholesterol excretion. Sirolimus enhanced blood concentrations of cyclosporine (+40%) and tacrolimus (+57%). Sirolimus blood concentration was increased by cyclosporine (+400%), but was not affected by tacrolimus. We conclude that a combination of sirolimus/tacrolimus could be the better alternative to the cotreatment of sirolimus/cyclosporine in cholestatic patients and in those facing difficulties in reaching therapeutic ranges of sirolimus blood concentration.     

Lysyl oxidase transcripts in peritoneal adhesions and incisional scars

OBJECTIVE: To evaluate the role of lysyl oxidase in postsurgical adhesion formation and incision wound repair. STUDY DESIGN: Female New Zealand rabbits underwent a pelvic-peritoneum adhesion-inducing operation under sterile conditions. In brief, the uterine horns were removed from the abdomen and abraded with surgical gauze and a scalpel blade. The horns were then replaced into the abdominal cavity, the incision was sutured, and the animals were allowed to recover. The animals were killed before lesion development and after 2, 4, 8, and 14 days of postsurgical recovery. The abraded uterine horns, abdominal wall incisional wound and a portion of the sidewall peritoneum were then removed. Total RNA was extracted using the guanidinium thiocyanate-phenol-chloroform method. Northern blot analysis was performed with an [alpha-32P]-labeled lysyl oxidase probe. RESULTS: Lysyl oxidase was expressed during abdominal wall incision repair on days 2 and 4 of postsurgical recovery, declining thereafter (days 8 and 14). In contrast, no increase in lysyl oxidase expression was noted in the uterine horns as compared to the control sidewall peritoneum. CONCLUSION: Lysyl oxidase plays a differential role in the early stages of abdominal wall and uterine horn repair.     

Five years of ankle fractures grouped by stability

Categories of displaced and undisplaced stable ankle fracture are well recognised. We report on a further group of ankle fractures which are undisplaced at presentation, but do not fulfil criteria for stable injuries, and therefore, may be at risk of displacement. The Blackburn Foot and Ankle Service operates evidence-based guidelines for ankle fractures, introduced in 1998. These were prospectively applied to 306 skeletally mature patients (308 fractures) following classification of the ankle fracture based upon clinical examination and radiography (mortise and lateral views). One hundred and forty-eight (48.4%) of fractures were stable, including 63 male and 85 women, median age 53 years (14-92). Eighty-eight (28.8%) of fractures were undisplaced but potentially unstable based on criteria, including 53 men and 35 women, median age 42 years (14-93). Seventy (22.9%) of fractures were displaced, including 41 men and 29 women, median age 44 years (16-94). Undisplaced, unstable fractures were treated mostly in below-knee casts with immediate weight-bearing and follow-up radiography. Two fractures in this group subsequently displaced requiring fixation according to AO principles. The risk of displacement in potentially unstable fractures is 2.3%. The unstable fracture groups, whether displaced or not, were similar in age/sex profile.     

Early psychological intervention for auditory hallucinations: an exploratory study of young people's voices groups

Twenty to fifty percent of people with a diagnosis of schizophrenia continue to hear voices despite taking neuroleptic medication. Trials of group cognitive behavioral therapy for adults with auditory hallucinations have shown promising results. Auditory hallucinations may be most amenable to psychological intervention during a 3-year critical period after symptom onset. This study evaluates the effectiveness of group cognitive behavioral therapy (CBT) for young people with recent-onset auditory hallucinations (N = 22), using a waiting list control. Outcome measures were administered at four separate time points. Significant reductions in auditory hallucinations occurred over the total treatment phase, but not over the waiting period. Further investigations in the form of randomized controlled trials are warranted.     

Epidural ropivacaine versus epidural morphine and the catabolic response to colonic surgery: stable isotope kinetic studies in the fasted state and during infusion of glucose

BACKGROUND: The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose. METHODS: Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg.kg(-1).min(-1) glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by L-[L-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured. RESULTS: Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused. CONCLUSION: Epidural analgesia achieved with ropivacaine or morphine does not suppress the catabolic response to surgery, either under fasting conditions or in the presence of an energy supply.     

Membrane-association and the sensitivity of guanylyl cyclase-coupled receptors to nitric oxide

Nitric oxide (NO) signal transduction occurs through guanylyl cyclase-coupled receptors, which exist in both cytosolic and membranous locations. It has recently been reported from experiments using heart tissue that the membrane-associated receptor has enhanced sensitivity to NO. Owing to its potential importance, we tested this finding using a method of applying NO in known, constant concentrations. The results showed that the concentration-response curves for receptor activation in cytosolic and membrane preparations of two different tissues (cerebellum and platelets) were indistinguishable. In all cases, half-maximal activation required about 1 nM NO and the curves had Hill coefficients of close to 1. The differential sensitivity reported for the heart is attributed to NO being scavenged by myoglobin in the cytosol, but not in the membrane fraction.