Factors Associated With Recurrent Ischemic Stroke in the Medical Group of the SAMMPRIS Trial.

Abstract

IMPORTANCE:

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial showed that aggressive medical therapy was more effective than stenting for preventing stroke in patients with symptomatic intracranial stenosis. However, 15% of patients in the medical group still experienced a primary end point during a median follow-up of 32.7 months.

OBJECTIVE:

To determine baseline features that were associated with a high rate of a primary end point in the medical arm of the SAMMPRIS Trial.

DESIGN, SETTING, AND PARTICIPANTS:

A post hoc analysis of patients in the medical arm only of the SAMMPRIS trial. Enrollment occurred between October 2008 and April 2013 and included 227 patients randomized to medical management alone. Baseline demographic features, vascular risk factors, qualifying event, brain imaging, and angiographic features were analyzed. Bivariate and multivariable proportional hazard regression modeling was performed to relate baseline features to the time until a primary end point. The post hoc analysis was conducted from November 2014 to June 2015.

INTERVENTIONS:

The SAMMPRIS Trial compared stenting with aggressive medical management in patients with a stroke or transient ischemic attack attributed to 70% to 99% stenosis of a major intracranial artery.

MAIN OUTCOMES AND MEASURES:

The primary outcome was any of the following: stroke or death within 30 days of enrollment, ischemic stroke in the territory of the symptomatic intracranial artery beyond 30 days after enrollment, or any stroke or death within 30 days after stenting a patient in the medical group during follow-up.

RESULTS:

A total of 227 patients were included in the study, 82 of whom were female, and the mean (SD) age was 59.5 (11.8) years. Being female (hazard ratio [HR], 1.9; 95% CI, 0.96-3.7), having diabetes mellitus (HR, 1.8; 95% CI, 0.9-3.5), not taking a statin at enrollment (HR, 2.6; 95% CI, 1.2-5.7), stroke as the qualifying event (HR, 2.5; 95% CI, 1.03-6.0), Rankin grade of 1 or greater (HR, 2.3; 95% CI, 0.9-5.5), old infarct in the territory of the stenotic artery (HR, 2.6; 95% CI, 1.3-5.1), and greater than 80% stenosis (HR, 1.9; 95% CI, 0.9-3.7) were associated (P?<?.10) with higher risk on bivariate analysis. Factors that were significantly associated with a primary end point on multivariable analyses were old infarct in the territory (HR, 2.6; 95% CI, 1.3-5.3; P?=?.006), stroke as the qualifying event (HR, 3.0; 95% CI, 1.1-7.7; P?=?.03), and no statin use at enrollment (HR, 2.4; 95% CI, 1.1-5.2; P?=?.03).

CONCLUSIONS AND RELEVANCE:

Old infarct in the territory of the stenosis, new stroke presentation, and absence of statin use at enrollment were independently associated with high rates of the primary end point in the medical group in the SAMMPRIS Trial. These features may be useful for selecting high-risk patients for future clinical trials evaluating alternative therapies for intracranial stenosis.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier:NCT00576693.

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High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis.

Abstract

BACKGROUND:

Exercise or physical activity is recommended for improving pain and functional status in people with knee or hip osteoarthritis. These are complex interventions whose effectiveness depends on one or more components that are often poorly identified. It has been suggested that health benefits may be greater with high-intensity rather than low-intensity exercise or physical activity.

OBJECTIVES:
To determine the benefits and harms of high- versus low-intensity physical activity or exercise programs in people with hip or knee osteoarthritis.

SEARCH METHODS:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; issue 06, 2014), MEDLINE (194 8 to June 2014) , EMBASE (198 0 to June 2014), CINAHL (1982 to June 2014), PEDro (1929 to June 2014), SCOPUS (to June 2014) and the World Health Organization (WHO) International Clinical Registry Platform (to June 2014) for articles, without a language restriction. We also handsearched relevant conference proceedings, trials, and reference lists and contacted researchers and experts in the ?eld to identify additional studies.

SELECTION CRITERIA:

We included randomized controlled trials of people with knee or hip osteoarthritis that compared high- versus low-intensity physical activity or exercise programs between the experimental and control group.High-intensity physical activity or exercise programs training had to refer to an increase in the overall amount of training time (frequency, duration, number of sessions) or the amount of work (strength, number of repetitions) or effort/energy expenditure (exertion, heart rate, effort).

DATA COLLECTION AND ANALYSIS:

Two review authors independently assessed study eligibility and extracted data on trial details. We contacted authors for additional information if necessary. We assessed the quality of the body of evidence for these outcomes using the GRADE approach.

MAIN RESULTS:

We included reports for six studies of 656 participants that compared high- and low-intensity exercise programs; five studies exclusively recruited people with symptomatic knee osteoarthritis (620 participants), and one study exclusively recruited people with hip or knee osteoarthritis (36 participants). The majority of the participants were females (70%). No studies evaluated physical activity programs. We found the overall quality of evidence to be low to very low due to concerns about study limitations and imprecision (small number of studies, large confidence intervals) for the major outcomes using the GRADE approach. Most of the studies had an unclear or high risk of bias for several domains, and we judged five of the six studies to be at high risk for performance, detection, and attrition bias.Low-quality evidence indicated reduced pain on a 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale (mean difference (MD) -0.84, 95% confidence interval (CI) -1.63 to -0.04; 4% absolute reduction, 95% CI -8% to 0%; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 14 to 22) and improved physical function on the 68-point WOMAC disability subscale (MD -2.65, 95% CI -5.29 to -0.01; 4% absolute reduction; NNTB 10, 95% CI 8 to 13) immediately at the end of the exercise programs (from 8 to 24 weeks). However, these results are unlikely to be of clinical importance. These small improvements did not continue at longer-term follow-up (up to 40 weeks after the end of the intervention). We are uncertain of the effect on quality of life, as only one study reported this outcome (0 to 200 scale; MD 4.3, 95% CI -6.5 to 15.2; 2% absolute reduction; very low level of evidence).Our subgroup analyses provided uncertain evidence as to whether increased exercise time (duration, number of sessions) and level of resistance (strength or effort) have an impact on the exercise program effects.Three studies reported withdrawals due to adverse events. The number of dropouts was small. Only one study systematically monitored adverse effects, but four studies reported some adverse effects related to knee pain associated with an exercise program. We are uncertain as to whether high intensity increases the number of adverse effects (Peto odds ratio 1.72, 95% CI 0.51 to 5.81; – 2% absolute risk reduction; very low level of evidence). None of the included studies reported serious adverse events.

AUTHORS’ CONCLUSIONS:

We found very low-quality to low-quality evidence for no important clinical benefit of high-intensity compared to low-intensity exercise programs in improving pain and physical function in the short term. There was insufficient evidence to determine the effect of different types of intensity of exercise programs.We are uncertain as to whether higher-intensity exercise programs may induce more harmful effects than those of lower intensity; this must be evaluated by further studies. Withdrawals due to adverse events were poorly monitored and not reported systematically in each group. We downgraded the evidence to low or very low because of the risk of bias, inconsistency, and imprecision.The small number of studies comparing high- and low-intensity exercise programs in osteoarthritis underscores the need for more studies investigating the dose-response relationship in exercise programs. In particular, further studies are needed to establish the minimal intensity of exercise programs needed for clinical effect and the highest intensity patients can tolerate. Larger studies should comply with the Consolidated Standards of Reporting Trials (CONSORT) checklist and systematically report harms data to evaluate the potential impact of highest intensities of exercise programs in people with joint damage.

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The Risk of Cancer in Patients With Psoriasis: A Population-Based Cohort Study in the Health Improvement Network.

Abstract

IMPORTANCE:

The risk of cancer in patients with psoriasis remains a cause of special concern due to the chronic inflammatory nature of the disease, the use of immune-suppressive treatments and UV therapies, and the increased prevalence of comorbid, well-established risk factors for cancer, such as smoking and obesity, all of which may increase the risk of carcinogenesis.

OBJECTIVE:

To compare the overall risk of cancer, and specific cancers of interest, in patients with psoriasis compared with patients without psoriasis.

DESIGN, SETTING, AND PARTICIPANTS:

Population-based cohort study of patients ages 18 to 89 years with no medical history of human immunodeficiency virus, cancer, organ transplants, or hereditary disease (albinism and xeroderma pigmentosum), prior to the start date, conducted using The Health Improvement Network, a primary care medical records database in the United Kingdom. The data analyzed had been collected prospectively from 2002 through January 2014. The analysis was completed in August 2015.

EXPOSURES OF INTEREST:

Patients with at least 1 diagnostic code for psoriasis were classified as having moderate-to-severe disease if they had been prescribed psoralen, methotrexate, cyclosporine, acitretin, adalimumab, etanercept, infliximab, or ustekinumab or phototherapy for psoriasis. Patients were classified as having mild disease if they never received treatment with any of these agents.
MAIN OUTCOMES AND MEASURES:
Incident cancer diagnosis.

RESULTS:

A total of 937?716 control group patients without psoriasis, matched on date and practice visit, and 198?366 patients with psoriasis (186?076 with mild psoriasis and 12?290 with moderate-to-severe disease) were included in the analysis. The adjusted hazards ratios (aHRs) with 95% CIs for any incident cancer excluding nonmelanoma skin cancer (NMSC) were 1.06 (95% CI, 1.02-1.09), 1.06 (95% CI, 1.02-1.09), and 1.08 (95% CI, 0.96-1.22) in the overall, mild, and severe psoriasis group. The aHRs for incident lymphoma were 1.34 (95% CI, 1.18-1.51), 1.31 (95% CI, 1.15-1.49), and 1.89 (95% CI, 1.25-2.86); for NMSC, 1.12 (95% CI, 1.07-1.16), 1.09 (95% CI, 1.05-1.13), and 1.61 (95% CI, 1.42-1.84); and for lung cancer, 1.15 (95% CI, 1.03-1.27), 1.12 (95% CI, 1.01-1.25), and 1.62 (95% CI, 1.16-2.28) in the overall, mild, and severe psoriasis groups, respectively. No significant association was seen with cancer of the breast, colon, prostate, or leukemia.

CONCLUSIONS AND RELEVANCE:

The association between psoriasis and cancer, albeit small, was present in our cohort of patients with psoriasis. This association was primarily driven by NMSC, lymphoma, and lung cancer.

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Definition and Implications of the Preventable Stroke.

Abstract

IMPORTANCE:

Although patients with acute stroke are routinely evaluated for potential treatment (ie, treatability of the stroke), preventability of the presenting stroke is generally not seriously considered.

OBJECTIVE:

To systematically analyze stroke preventability.
DESIGN, SETTING, AND PARTICIPANTS:
We evaluated medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012, at the University of California Irvine Medical Center. Mean (SE) patient age was 67.2 (0.8) years. Data analysis was conducted from July 3, 2014, to August 4, 2015.

EXPOSURES:

Medical records were systematically examined for demographic information, stroke risk factors, stroke severity, and acute stroke treatment.
MAIN OUTCOMES AND MEASURES:
We defined stroke preventability as the degree to which the patient’s presenting stroke was preventable. Using variables easily determined at onset of stroke, we developed a 10-point scale (0, not preventable; 10, most preventable) to classify the degree of stroke preventability. Our focus was effectiveness of treatment of hypertension (0-2 points), hyperlipidemia (0-2 points), and atrial fibrillation (0-4 points), as well as use of antithrombotic treatment for known prior cerebrovascular and cardiovascular disease (0-2 points).

RESULTS:

Total risk scores ranged from 0 to 8 (mean [SE], 2.2 [0.1]), with 207 patients (75.5%) exhibiting some degree of preventability (score of 1 or higher). Seventy-one patients (25.9%) had scores of 4 or higher, indicating that the stroke was highly preventable. Severity of stroke as determined by the National Institutes of Health Stroke Scale score was not related to preventability of stroke. However, 21 of 71 patients (29.6%) whose stroke was highly preventable were treated with intravenous or intra-arterial acute stroke therapy while these treatments were provided for only 13 of 67 patients (19.4%) with scores of 0 (no preventability) and 19 of 136 patients (14.0%) with scores of 1 to 3 (low preventability) (P?=?.03).

CONCLUSIONS AND RELEVANCE:

Most patients with acute stroke exhibited some degree of preventability. Preventability and treatment of stroke were significantly associated, indicating that the most preventable strokes paradoxically were more likely to receive acute treatment.

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Effect of Diuretic or Calcium-Channel Blocker Plus Angiotensin-Receptor Blocker on Diastolic Function in Hypertensive Patients.

Abstract

BACKGROUND:

Hypertension increases the risk of left ventricular (LV) diastolic dysfunction, and anti-hypertensive therapy may improve LV relaxation. The aim of this study was to investigate whether combining an angiotensin-receptor blocker (ARB) with either hydrochlorothiazide (HCTZ) or a calcium-channel blocker (CCB) improves LV relaxation in patients with hypertension and diastolic dysfunction.Methods?and?Results:Hypertensive patients who had not achieved their target blood pressure with at least 4 weeks of ARB therapy were randomly assigned to receive either a fixed-dose combination of losartan and HCTZ (losartan/HCTZ; n=110) or a combination of amlodipine and a typical ARB dosage (CCB/ARB; n=121) and followed for 24 weeks. The primary endpoint was change in early diastolic mitral annular velocity (e’, cm/s). Systolic blood pressure decreased in both groups after switch to the combination therapies. E’ velocity increased both in the losartan/HCTZ (0.52 cm/s) and in the CCB/ARB (0.59 cm/s) groups. The mean (95% CI) treatment difference was -0.02 (-0.37 to 0.34) cm/s, indicating that improvement in LV relaxation was similar between the groups. The ratio of early mitral inflow velocity to e’ velocity and left atrial volume index were significantly decreased in the losartan/HCTZ group.

CONCLUSIONS:

The combination of losartan and HCTZ is as effective as amlodipine plus ARB in improving LV relaxation in hypertensive patients.

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