Neuropsychiatric manifestations of altered thyroid state

The authors assessed the mood and cognitive effects of sequential T4, T3, and withdrawal of thyroid hormone replacement on 25 patients who had had thyroidectomies for thyroid cancer. The patients experienced increased sadness and anxiety when they were without medication, but not significant difference in mood was noted between T4 and T3. The patients who experienced increased affective symptoms when not taking medication were more likely to have histories of affective illness or mood lability.     

Pre-trial evaluation of the potential for unblinding in drug trials: a prototype example

Blinding is an important design feature of randomised trials that may reduce bias in the results, compared to the situation where blinding is not possible or is not maintained. The literature provides some guidance for the evaluation of blinding in ongoing or completed studies, but the question of pre-trial assessment of the potential for unblinding has not been addressed. This paper describes the design and analysis of a prototype experiment for the pre-trial assessment of blinding in a drug trial. This work was motivated by a trial using antibiotic therapy, in which the investigators were concerned about the possibility of subjects being able to differentiate active medication from placebo, and thus become unblinded to their treatment assignment. A small experiment was mounted in which participants had to divide a random mixture of tablets into two groups. Statistical methods were developed to calculate the probability of a given number of similar tablets being classified into the same group by chance, with a modification to allow for some participants having constrained their responses to have equal numbers of tablets in each group. Differentiation of tablets by taste (the initial concern of the investigators) was not statistically different from chance. A smaller set of data on differentiation by appearance (a possibility not originally considered) had borderline statistical significance. After reviewing all these results, the investigators decided to proceed with the study without modifying the tablets, in part because subjects in the study would be unlikely to compare the two types of medication side-by-side. Our results suggest that blinding might sometimes be compromised in unexpected ways. Whenever possible, we suggest that similar and larger such experiments be carried out before the trial to assess whether blinding might be compromised. The methods proposed here could easily be adapted to evaluate the results of such experiments.     

Routine placement of subdural drain after burr hole evacuation of chronic and subacute subdural hematoma: a contrarian evidence based approach

The objective of this paper was to evaluate whether available evidence supporting placement of subdural drain placement after evacuation of chronic subdural haematoma (CSDH) is applicable to a cohort of patients managed by us. In this observational cohort study, clinical follow-up was obtained in 166 patients who underwent burr hole evacuation of CSDH without placement of subdural drain followed by 3 days of bed rest. The primary outcome studied was recurrence requiring reoperation. Factors predicting recurrence were also analysed. We compared the patient characteristics and management protocols in our cohort with that in reports supporting drain placement to determine whether such evidence is relevant to our patient group. The mean age of our patients was 58 ± 17 years (range, 1 to 89 years). Sixteen of the 166 (9.6%) patients presented with symptomatic recurrence. The median time to reoperation for recurrence (15 of 16 patients) after the primary procedure was 17 days (range, 2 to 68 days). Antiplatelet and anticoagulant therapy was the only factor that was significantly associated with recurrence (p = 0.01). There were no infective or non-infective complications in our patient cohort. Our patient cohort and outcomes differed from those reporting drain placements in the following parameters: they were a decade younger, all patients received bed rest for 3 days after surgery and the recurrence rate was similar to that reported in the drained groups but significantly less than that reported in the non-drained groups. Routine placement of drain following burr hole evacuation of CSDH should only be done after careful comparison of the patient cohort under consideration and those reporting superior outcomes with drains. Evidence-based medicine supports such an approach.     

Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy

OBJECTIVE: Raloxifene hydrochloride is a selective estrogen receptor modulator that to date has not been shown to cause hypertriglyceridemia in normal, diabetic, or hypertriglyceridemic women. This study was designed to assess the effect of raloxifene on serum triglycerides in postmenopausal women who have a history of increased hypertriglyceridemia with oral estrogen therapy. RESEARCH DESIGN AND METHODS: This was a single-center, uncontrolled, open-label study investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma lipids. The study subjects were 12 postmenopausal women, ages 49-73 years, with a documented history of oral estrogen-induced hypertriglyceridemia (serum triglycerides > or =3.39 mmol/l [> or =300 mg/dl]). RESULTS: At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (>or =11.3 mmol/l [> or =1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL(2) levels (P = 0.013 and 0.03, respectively). CONCLUSIONS: Patients with a previous history of hypertriglyceridemia on oral estrogen therapy should have serum triglyceride levels monitored closely after beginning raloxifene therapy and may even require fibrate therapy before beginning raloxifene.     

Modulation of AT-1R/CHOP-JNK-Caspase12 pathway by olmesartan treatment attenuates ER stress-induced renal apoptosis in streptozotocin-induced diabetic mice

There is evidence that the activation of renal angiotensin (Ang)-II plays a critical role in the pathogenesis of diabetic kidney diseases (DN) via the ER stress-induced renal apoptosis. Since, the potential negative role of Ang-II in the pathogenesis of ER stress-mediated apoptosis is poorly understood; we evaluated whether treatment of mice with AT-1R specific blocker, olmesartan is associated with the reduction of ER stress-induced renal apoptosis in streptozotocin (STZ)-induced diabetic animal model. We employed western blot analysis to measure the renal protein expressions level of NADPH oxidase subunits, ER chaperone GRP78 and the ER-associated apoptosis proteins. Furthermore, TUNEL staining was used to measure the renal apoptosis. Additionally, dihydroethidium staining and TBARS assay, and immunohistochemistry were performed to measure the renal superoxide radical production and lipid peroxidation, and activation of an Ang-II, respectively. The diabetic kidney mice were found to have increased protein expressions of NADPH oxidase subunits, GRP78 and ER-associated apoptosis proteins, such as TRAF2, IRE-1α, CHOP, p-JNK and procaspase-12, in comparison to normal mice, and which were significantly blunted by the olmesartan treatment in diabetic kidney mice. Furthermore, the diabetic kidney mice were found to have significant increment in renal apoptosis, superoxide radical production, MDA level and activation of an Ang-II and which were also attenuated by the olmesartan treatment. Considering all the findings, it is suggested that the AT-1R specific blocker-olmesartan treatment could be a potential therapy in treating ER stress-induced renal apoptosis via the modulation of AT-1R/CHOP-JNK-Caspase12 pathway in STZ-induced diabetic mice.