Summary Background In an open-label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) was well tolerated and seemed to improve motor function ...in patients with advanced Parkinson's disease. We aimed to assess the safety and efficacy of AAV2-neurturin in a double-blind, phase 2 randomised trial. Methods We did a multicentre, double-blind, sham-surgery controlled trial in patients with advanced Parkinson's disease. Patients were randomly assigned (2:1) by a central, computer generated, randomisation code to receive either AAV2-neurturin (5·4×1011 vector genomes) injected bilaterally into the putamen or sham surgery. All patients and study personnel with the exception of the neurosurgical team were masked to treatment assignment. The primary endpoint was change from baseline to 12 months in the motor subscore of the unified Parkinson's disease rating scale in the practically-defined off state. All randomly assigned patients who had at least one assessment after baseline were included in the primary analyses. This trial is registered at ClinicalTrials.gov , NCT00400634. Results Between December, 2006, and November, 2008, 58 patients from nine sites in the USA participated in the trial. There was no significant difference in the primary endpoint in patients treated with AAV2-neurturin compared with control individuals (difference −0·31 SE 2·63, 95% CI −5·58 to 4·97; p=0·91). Serious adverse events occurred in 13 of 38 patients treated with AAV2-neurturin and four of 20 control individuals. Three patients in the AAV2-neurturin group and two in the sham surgery group developed tumours. Interpretation Intraputaminal AAV2-neurturin is not superior to sham surgery when assessed using the UPDRS motor score at 12 months. However, the possibility of a benefit with additional targeting of the substantia nigra and longer term follow-up should be investigated in further studies. Funding Ceregene and Michael J Fox Foundation for Parkinson's Research.
Summary Background Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect ...of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. Methods Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT02295033. Findings Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17·2 years (IQR 13·0–19·0). 20-year overall survival was 59·7% (99% CI 56·3–63·0) in the boost group versus 61·1% (57·6–64·3) in the no boost group, hazard ratio (HR) 1·05 (99% CI 0·92–1·19, p=0·323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0·65 (99% CI 0·52–0·81, p<0·0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16·4% (99% CI 14·1–18·8) in the no boost group versus 12·0% (9·8–14·4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1·8% (99% CI 1·1–2·5) in the no boost group versus 5·2% (99% CI 3·9–6·4) in the boost group (p<0·0001). Interpretation A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. Funding Fonds Cancer, Belgium.
The purpose of this analysis was to revise the model for perioperative risk for esophagectomy for cancer utilizing The Society of Thoracic Surgeons General Thoracic Surgery Database to provide ...enhanced risk stratification and quality improvement measures for contributing centers.
The Society of Thoracic Surgeons General Thoracic Surgery Database was queried for all patients treated for esophageal cancer with esophagectomy between July 1, 2011, and June 30, 2014. Multivariable risk models for major morbidity, perioperative mortality, and combined morbidity and mortality were created with the inclusion of surgical approach as a risk factor.
In all, 4,321 esophagectomies were performed by 164 participating centers. The most common procedures included Ivor Lewis (32.5%), transhiatal (21.7%), minimally invasive esophagectomy, Ivor Lewis type (21.4%), and McKeown (10.0%). Sixty-nine percent of patients received induction therapy. Perioperative mortality (inpatient and 30-day) was 135 of 4,321 (3.4%). Major morbidity occurred in 1,429 patients (33.1%). Major morbidities include unexpected return to operating (15.6%), anastomotic leak (12.9%), reintubation (12.2%), initial ventilation beyond 48 hours (3.5%), pneumonia (12.2%), renal failure (2.0%), and recurrent laryngeal nerve paresis (2.0%). Statistically significant predictors of combined major morbidity or mortality included age more than 65 years, body mass index 35 kg/m(2) or greater, preoperative congestive heart failure, Zubrod score greater than 1, McKeown esophagectomy, current or former smoker, and squamous cell histology.
Thoracic surgeons participating in The Society of Thoracic Surgeons General Thoracic Surgery Database perform esophagectomy with low morbidity and mortality. McKeown esophagectomy is an independent predictor of combined postoperative morbidity or mortality. Revised predictors for perioperative outcome were identified to facilitate quality improvement processes and hospital comparisons.
Abstract The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third ...Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
An international definition for "nursing home" Sanford, Angela M; Orrell, Martin; Tolson, Debbie ...
Journal of the American Medical Directors Association,
03/2015, Letnik:
16, Številka:
3
Journal Article
Recenzirano
There is much ambiguity regarding the term "nursing home" in the international literature. The definition of a nursing home and the type of assistance provided in a nursing home is quite varied by ...country. The International Association of Gerontology and Geriatrics and AMDA foundation developed a survey to assist with an international consensus on the definition of "nursing home."
Objectives This study sought to relate imaging findings on positron emission tomography (PET) to adverse cardiac events in patients referred for evaluation of known or suspected cardiac sarcoidosis. ...Background Although cardiac PET is commonly used to evaluate patients with suspected cardiac sarcoidosis, the relationship between PET findings and clinical outcomes has not been reported. Methods We studied 118 consecutive patients with no history of coronary artery disease, who were referred for PET, using 18 Ffluorodeoxyglucose (FDG) to assess for inflammation and rubidium-82 to evaluate for perfusion defects (PD), following a high-fat/low-carbohydrate diet to suppress normal myocardial glucose uptake. Blind readings of PET data categorized cardiac findings as normal, positive PD or FDG, positive PD and FDG. Images were also used to identify whether findings of extra-cardiac sarcoidosis were present. Adverse events (AE)—death or sustained ventricular tachycardia (VT)—were ascertained by electronic medical records, defibrillator interrogation, patient questionnaires, and telephone interviews. Results Among the 118 patients (age 52 ± 11 years; 57% males; mean ejection fraction: 47 ± 16%), 47 (40%) had normal and 71 (60%) had abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were 31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were predictive of AE, and the presence of both a PD and abnormal FDG (29% of patients) was associated with hazard ratio of 3.9 (p < 0.01) and remained significant after adjusting for left ventricular ejection fraction (LVEF) and clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated with AE. Conclusions The presence of focal PD and FDG uptake on cardiac PET identifies patients at higher risk of death or VT. These findings offer prognostic value beyond Japanese Ministry of Health and Welfare clinical criteria, the presence of extra-cardiac sarcoidosis and LVEF.
Summary Patients with chronic kidney failure—defined as a glomerular filtration rate persistently below 15 mL/min per 1·73 m2 —have an unacceptably high mortality rate. In developing countries, ...mortality results primarily from an absence of access to renal replacement therapy. Additionally, cardiovascular and non-cardiovascular mortality are several times higher in patients on dialysis or post-renal transplantation than in the general population. Mortality of patients on renal replacement therapy is affected by a combination of socioeconomic factors, pre-existing medical disorders, renal replacement treatment modalities, and kidney failure itself. Characterisation of the key pathophysiological contributors to increased mortality and cardiorenal risk staging systems are needed for the rational design of clinical trials aimed at decreasing mortality. Policy changes to improve access to renal replacement therapy should be combined with research into low-cost renal replacement therapy and optimum clinical care, which should include multifaceted approaches simultaneously targeting several of the putative contributors to increased mortality.
Summary Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative ...to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 95% CI 0·14–0·23 vs 0·53 0·46–0·61, p<0·0001) and fingolimod (0·15 0·10–0·20 vs 0·34 0·26–0·41, p<0·0001), and was associated with a similar annualised relapse rate as natalizumab (0·20 0·14–0·26 vs 0·19 0·15–0·23, p=0·78). For the disability outcomes, alemtuzumab was associated with similar probabilities of disability accumulation as interferon beta (hazard ratio HR 0·66 95% CI 0·36–1·22, p=0·37), fingolimod (1·27 0·60–2·70, p=0·67), and natalizumab (0·81 0·47–1·39, p=0·60). Alemtuzumab was associated with similar probabilities of disability improvement as interferon beta (0·98 0·65–1·49, p=0·93) and fingolimod (0·50 0·25–1·01, p=0·18), and a lower probability of disability improvement than natalizumab (0·35 0·20–0·59, p=0·0006). Interpretation Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles. Funding National Health and Medical Research Council, and the University of Melbourne.
Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). ...Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring.
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