SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 mol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 ؎ 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.

We attempted to assess compliance using both a pharmacologic indicator (low-dose phenobarbital) and a return tablet count in 225 patients who were taking part in three separate studies. There were 216 patients (96%) who kept a follow-up appointment after 28 days; 161 patients appeared to have good compliance (90% to 109%) by return tablet count. Of these 161 patients, 51 (32%) had plasma phenobarbital concentrations (corrected for dose and weight) that were less than 90% of the lowest value previously found in normal volunteers, which suggested poorer compliance. When compared with the age-related volunteer values, 77 (48%) had values that were less than 90% of the lowest volunteer value. There were 6 of 10 patients with apparently excessive (greater than or equal to 110%) compliance by return tablet count and 4 of 12 who failed to return their container who also had phenobarbital concentrations that were less than 90% of the lowest volunteer value. We concluded that return tablet count grossly overestimates compliance.

Summary:A patient is described who became poikilothermic following surgery for removal of a craniopharyngioma. Episodes of disturbed behaviour, neurological abnormilities, pancytopenia and deranged liver function could be correlated with episodes of more profound hypothermia on a background of a chronically lowered core temperature. The association of pancytopenia and neuropsychiatric disturbances with hypothermia is discussed with reference to reported cases of periodic spontaneous hypothermia.

Glomerular and tubular microproteinuria precede the development of overt nephropathy in Type 1 diabetes mellitus. However, in Type 2 diabetes urinary protein excretion and its relationship to diabetic nephropathy has not been clearly characterized. Twenty consecutive, newly diagnosed patients with Type 2 diabetes, whose urine was Albustix-negative and sterile on culture, were studied. Two timed overnight urine samples were collected at diagnosis, and after 2 months and 2 years, and excretion rates of albumin, alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase were calculated. HbA1c fell from 12.1 +/- 2.4% at diagnosis to 9.5 +/- 1.5% at 2 months and 9.6 +/- 2.2% at 2 years. Albumin excretion rate fell marginally from 6.5 (2.1-242.5) micrograms min-1 at diagnosis to 5.5 (1.7-274.0) micrograms min-1 at 2 months (p less than 0.05) rising again to 6.1 (1.9-201.7) micrograms min-1 at 2 years. alpha-1-Microglobulin excretion rate fell from 13.5 (3.6-59.9) micrograms min-1 at diagnosis to 8.4 (2.9-16.1) micrograms min-1 at 2 months and 8.8 (1.8-54.1) micrograms min-1 at 2 years (both p less than 0.05). Albumin excretion rate was found to correlate significantly with creatinine clearance at diagnosis (rs = 0.61, p less than 0.005), though not subsequently. In contrast, excretion rates of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase correlated with HbA1c (rs = 0.68 and 0.66, respectively, p less than 0.005 at diagnosis and rs = 0.57 and 0.53, p less than 0.05 subsequently in both cases).(ABSTRACT TRUNCATED AT 250 WORDS)