Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney ...disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 11·3% simvastatin plus ezetimibe vs 619 13·4% placebo; rate ratio RR 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 4·6% vs 230 5·0%; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 2·8% vs 174 3·8%; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 6·1% vs 352 7·6%; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 0·2% vs 5 0·1%). There was no evidence of excess risks of hepatitis (21 0·5% vs 18 0·4%), gallstones (106 2·3% vs 106 2·3%), or cancer (438 9·4% vs 439 9·5%, p=0·89) and there was no significant excess of death from any non-vascular cause (668 14·4% vs 612 13·2%, p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
Background The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain. Study Design Observational study. Settings & Participants 6,245 ...nondialysis participants in the Study of Heart and Renal Protection (SHARP). Predictor Baseline cause of kidney disease was categorized into 4 groups: cystic kidney disease, diabetic nephropathy, glomerulonephritis, and other recorded diagnoses. Outcomes End-stage renal disease (ESRD; dialysis or transplantation) and death. Results During an average 4.7 years' follow-up, 2,080 participants progressed to ESRD, including 454 with cystic kidney disease (23% per year), 378 with glomerulonephritis (10% per year), 309 with diabetic nephropathy (12% per year), and 939 with other recorded diagnoses (8% per year). By comparison with patients with cystic kidney disease, other disease groups had substantially lower adjusted risks of ESRD (relative risks of 0.28 95% CI, 0.24-0.32, 0.40 95% CI, 0.34-0.47, and 0.29 95% CI, 0.25-0.32 for glomerulonephritis, diabetic nephropathy, and other recorded diagnoses, respectively). Albuminuria and baseline estimated glomerular filtration rate were associated more weakly with risk of ESRD in patients with cystic kidney disease than the 3 other diagnostic categories ( P for interaction, <0.001 and 0.01, respectively). Death before ESRD was uncommon in patients with cystic kidney disease, but was a major competing risk for participants with diabetic nephropathy, whose adjusted risk of death was 2-fold higher than that of the cystic kidney disease group (relative risk, 2.35 95% CI, 1.73-3.18). Limitations Exclusion of patients with prior myocardial infarction or coronary revascularization. Conclusions The cause of kidney disease has substantial prognostic implications. Other things being equal, patients with cystic kidney disease are at much higher risk of ESRD (and much lower risk of death before ESRD) than other patients. Patients with diabetic nephropathy are at particularly high risk of death prior to reaching ESRD.
Abstract Objective To evaluate the outcomes of a randomized controlled trial, which assigned patients with post-cancer fatigue (PCF) to education, or 12-weeks of integrated cognitive-behavioral ...therapy (CBT) and graded exercise therapy (GET). Methods Three months post treatment for breast or colon cancer, eligible patients had: clinically-significant fatigue; no co-morbid medical or psychiatric conditions which explained the fatigue; and no evidence of recurrence. The CBT/GET arm included individually tailored consultations at approximately two weekly intervals. The education arm included a single visit with clinicians describing the principles of CBT/GET and a booklet. The primary outcome was clinically-significant improvement in self-reported fatigue (SPHERE, 0–12), designated a priori as greater than one standard deviation of improvement in fatigue score. The secondary outcome was associated improvement in function (Role limitation due to physical health problems–SF-36, 0–100) comparing baseline, end-treatment (12-weeks), and follow-up (24-weeks). Results There were 46 patients enrolled, including 43 women (94%), with a mean age of 51 years. Fatigue severity improved in all subjects from a mean of 5.2 (±3.1) at baseline to 3.9 (±2.8) at 12-weeks, suggesting a natural history of improvement. Clinically-significant improvement was observed in 7 of 22 subjects in the intervention group compared to 2 of 24 in the education group (p<0.05, χ2 ). These subjects also had improvement in functional status compared to non-responders (p<0.01, t-test). Conclusions Combined CBT/GET improves fatigue and functional outcomes for a subset of patients with PCF. Further studies to improve the response rate and the magnitude of the benefit are warranted.
Stroke Risk in Maintenance Hemodialysis Herrington, William G., MRCP; Lewis, David A., MRCP
American journal of kidney diseases,
06/2012, Letnik:
59, Številka:
6
Journal Article
The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital ...(RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques.
Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer PIVOTAL trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVs were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage.
In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm(3), 326.7 cm(3), 310.3 cm(3), and 256.7 cm(3), respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm(3) (with 0 mm BEM), 17.4 cm(3) (1-mm BEM), 10.8 cm(3) (2-mm BEM), 6.9 cm(3) (3-mm BEM), 5.0 cm(3) (4-mm BEM), and 1.4 cm(3) (5-mm BEM) in comparison with an overlap of 9.2 cm(3) seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage.
Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.
Summary Background Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal ...quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18–24-year-olds. Methods In this phase 3, observer-blind, randomised controlled trial, university students aged 18–24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov , registration number NCT01214850. Findings Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control 984 analysed, 979 assigned to 4CMenB 974 analysed, 988 assigned to MenACWY-CRM 983 analysed); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8–1·7) or MenACWY-CRM (0·9, 0·6–1·3) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% 95% CI 3·4–30·8 carriage reduction), capsular groups BCWY (26·6% 10·5–39·9 carriage reduction), capsular groups CWY (29·6% 8·1–46·0 carriage reduction), and serogroups CWY (28·5% 2·8–47·5 carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3–55·0) carriage reduction for serogroup Y and 36·2% (15·6–51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified. Interpretation Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented. Funding Novartis Vaccines.
Background Refractory variceal bleeding is associated with a high mortality. Existing salvage techniques such as transjugular intrahepatic portosystemic shunt (TIPS) and balloon tamponade (BT) have ...important limitations and may not be appropriate for all patients. Objective To evaluate the safety and efficacy of a novel removable self-expanding metal stent in the management of refractory variceal bleeding. Design Case series. Setting Tertiary referral liver center. Patients Ten patients with variceal hemorrhage with contraindications to TIPS insertion or BT. Interventions Insertion of a self-expanding metal stent (SX-Ella DANIS stent). Main Outcome Measures Survival, failure to control bleeding, and complications. Results Stent insertion was successful in 9 of 10 patients. Failure to control bleeding was observed in 3 patients (2 with gastric varices), with control of bleeding in the remainder. Overall survival at 42 days was 50%. Six patients survived the acute bleeding episode and had stents removed endoscopically at a median of 9 days after insertion. One patient had a minor ulceration of the esophagus caused by stent insertion. Conclusions Insertion of the SX-Ella DANIS stent in patients with refractory variceal bleeding or complications of previous therapy is effective for the control of bleeding. Stent insertion can be achieved in the majority of patients without fluoroscopic control and without major complications. In selected patients, SX-Ella DANIS stent insertion offers an alternative to other methods of salvage such as BT and TIPS and could be considered a substitute for BT after a prospective trial.
We report 2 cases of mucosa-associated lymphoid tissue lymphoma of the salivary glands, complicating Sjoegren's syndrome. The sonographic and histological features are described in depth. The use of ...sonography as a diagnostic aid in such patients is discussed.
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