Summary Background Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve ...thrombolysis use and clinical outcome in patients. Methods In 2008–09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010–13). Findings We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1–14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8–19·0) in 2013 (ptrend 2010–13 <0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2–22·6%) were reduced by 2013 (12·1–22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35–60) in 2010 to 44 min (29–60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8–5·9) during 2010–13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9–17·9). Although the 3-month mortality was not affected by our programme (137 13% of 1060 patients in 2010 vs 143 13% of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0–1 in 375 40% of 944 patients in 2010 vs 493 53% of 939 in 2013; score 0–2 in 531 56% patients in 2010 and 615 65% in 2013; ptrend 2010–13 <0·0001). Interpretation During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke. Funding Reformpool of the Tyrolean Health Care Fund.
Stereotactic radiosurgery (SRS) dose is limited by brain metastasis (BM) size. The study goal was to retrospectively determine whether there is a benefit for intracranial outcomes and overall ...survival (OS) for gross total resection with single-fraction SRS versus SRS alone for patients with large BMs.
A large BM was defined as ≥4 cm
(2 cm in diameter) prior to the study. We reviewed the records of consecutive patients treated with single-fraction SRS alone or surgery with preoperative or postoperative SRS between 2005 and 2013 from 2 institutions.
Overall, 213 patients with 223 treated large BMs were included; 66 BMs (30%) were treated with SRS alone and 157 (70%) with surgery and SRS (63 preoperatively and 94 postoperatively). The groups (SRS vs surgery and SRS) were well balanced except regarding lesion volume (median, 5.9 cm
vs 9.6 cm
; P<.001), median number of BMs (1.5 vs 1, P=.002), median SRS dose (18 Gy vs 15 Gy, P<.001), and prior whole-brain radiation therapy (33% vs 5%, P<.001). The local recurrence (LR) rate was significantly lower with surgery and SRS (1-year LR rate, 36.7% vs 20.5%; P=.007). There was no difference in radiation necrosis (RN) by resection status, but there was a significantly increased RN rate with postoperative SRS versus with preoperative SRS and with SRS alone (1-year RN rate, 22.6% vs 5% and 12.3%, respectively; P<.001). OS was significantly higher with surgery and SRS (2-year OS rate, 38.9% vs 19.8%; P=.01). Both multivariate adjusted analyses and propensity score-matched analyses demonstrated similar results.
In this retrospective study, gross total resection with SRS was associated with significantly reduced LR compared with SRS alone for patients with large BMs. Postoperative SRS was associated with the highest rate of RN. Surgical resection with SRS may improve outcomes in patients with a limited number of large BMs compared with SRS alone. Further studies are warranted.
Background The purpose of this study is to help define the indications for rotator cuff repair by identifying predictors of failure of nonoperative treatment. Methods A prospective, multicenter, ...cohort study design was used. All patients with full-thickness rotator cuff tears on magnetic resonance imaging were offered participation. Baseline data from this cohort were used to examine risk factors for failing a standard rehabilitation protocol. Patients who underwent surgery were defined as failing nonoperative treatment. A Cox proportional hazards model was fit to determinethe baseline factors that predicted failure. The dependent variable was time to surgery. The independent variables were tear severity and baseline patient factors: age, activity level, body mass index, sex, Single Assessment Numeric Evaluation score, visual analog scale score for pain, education, handedness, comorbidities, duration of symptoms, strength, employment, smoking status, and patient expectations. Results Of the 433 subjects in this study, 87 underwent surgery with 93% follow-up at 1 year and 88% follow-up at 2 years. The median age was 62 years, and 49% were female patients. Multivariate modeling, adjusted for the covariates listed previously, identified patient expectations regarding physical therapy ( P < .0001) as the strongest predictor of surgery. Higher activity level ( P = .011) and not smoking ( P = .023) were also significant predictors of surgery. Conclusion A patient's decision to undergo surgery is influenced more by low expectations regarding the effectiveness of physical therapy than by patient symptoms or anatomic features of the rotator cuff tear. As such, patient symptoms and anatomic features of the chronic rotator cuff tear may not be the best features to use when deciding on surgical intervention.
Background Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial. Objective We sought to study the effect of a vitamin D intervention in ...pregnancy between subjects of different races and the association between 25-hydroxyvitamin D3 (25OHD) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring. Methods The Vitamin D Antenatal Asthma Reduction Trial is a randomized trial of pregnant women at risk of having children with asthma randomized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and recurrent wheezing until age 3 years were recorded. Results African American (AA) women (n = 312) had lower initial levels of 25(OH)D (mean SD, 17.6 ng/mL 8.3 ng/mL) compared with non-AA women (n = 400; 27.1 ng/mL 9.7 ng/mL, P < .001). No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring ( P for interaction = .77). Having an initial level of greater than 30 ng/mL and being randomized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo (adjusted odds ratio, 0.42; 95% CI, 0.19-0.91). Conclusions We did not find differences between AA and non-AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years. Maternal supplementation of vitamin D, particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL, reduced asthma/recurrent wheeze in the offspring through age 3 years, suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life.
Background Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been ...explored. Objective Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. Methods We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. Results We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone ( P < .0001) or additional controller medications ( P = .001), as well as longitudinal differences in pulmonary function ( P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide ( P = .02) and nedocromil ( P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide ( P = .12) and nedocromil ( P = .56) compared with placebo. Conclusion Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.
Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined ...by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology—pressure and flow—as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.
Background Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can ...identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4+ lymphocytes for association with asthma. Methods eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3 / GSDMB variants with asthma (combined P = 2.9 × 10−8 ). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 ( FADS2 ; P = .002), N-acetyl-α-D-galactosaminidase ( NAGA ; P = .0002), and Factor XIII, A1 ( F13A1 ; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4+ lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2 , NAGA , and F13A1 in the pathogenesis of asthma.
Hypothesis The purpose of this cross-sectional study is to determine whether the duration of symptoms influences the features seen in patients with atraumatic, full-thickness rotator cuff tears. Our ...hypothesis is that an increasing duration of symptoms will correlate with more advanced findings of rotator cuff tear severity on magnetic resonance imaging, worse shoulder outcome scores, more pain, decreased range of motion, and less strength. Methods We enrolled 450 patients with full-thickness rotator cuff tears in a prospective cohort study to assess the effectiveness of nonoperative treatment and factors predictive of success. The duration of patient symptoms was divided into 4 groups: 3 months or less, 4 to 6 months, 7 to 12 months, and greater than 12 months. Data collected at patient entry into the study included (1) demographic data, (2) history and physical examination data, (3) radiographic imaging data, and (4) validated patient-reported measures of shoulder status. Statistical analysis included a univariate analysis with the Kruskal-Wallis test and Pearson test to identify statistically significant differences in these features for different durations of symptoms. Results A longer duration of symptoms does not correlate with more severe rotator cuff disease. The duration of symptoms was not related to weakness, limited range of motion, tear size, fatty atrophy, or validated patient-reported outcome measures. Conclusions There is only a weak relationship between the duration of symptoms and features associated with rotator cuff disease.
Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory ...diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies.
PDF
