Advances in medical therapies leading to improved patient outcomes are in large part related to successful conduct of clinical trials that offer critical information regarding the efficacy and safety ...of novel interventions. The conduct of clinical trials in the United States, however, continues to face increasing challenges with recruitment and retention. These trends are paralleled by an increasing shift toward more multinational trials where most participants are enrolled in countries outside the United States, bringing into question the generalizability of the results to the American population. This manuscript presents the perspectives and recommendations from clinicians, researchers, sponsors, and regulators who attended a meeting facilitated by the Food and Drug Administration to improve upon the current clinical trial trends in the United States.
Study objective Allergic reactions are common presentations to the emergency department (ED). An unknown proportion of patients will develop biphasic reactions, and patients are often monitored for ...prolonged periods to manage potential reactions. We seek to determine the incidence of clinically important biphasic reactions. Methods Consecutive adult patients presenting to 2 urban EDs with allergic reactions during a 5-year period were identified. Encounters were dichotomized as “anaphylaxis” or “allergic reaction” with an explicit algorithm. A comprehensive chart review was conducted on each index and all subsequent visits to detail patient presentations, comorbidities, ED management, and predefined clinically important biphasic reactions. Regional and provincial databases were linked to identify subsequent ED visits and deaths within a 7-day period. The primary outcome was the proportion of patients with a clinically important biphasic reaction, and the secondary outcome was mortality. Results Of 428,634 ED visits, 2,819 (0.66%) encounters were reviewed (496 anaphylactic and 2,323 allergic reactions). Overall, 185 patients had at least 1 subsequent visit for allergic symptoms. Five clinically important biphasic reactions were identified (0.18%; 95% confidence interval CI 0.07% to 0.44%), with 2 occurring during the ED visit and 3 postdischarge. There were no fatalities (95% CI 0% to 0.17%). In the anaphylaxis and allergic reaction groups, clinically important biphasic reactions occurred in 2 patients (0.40%; 95% CI 0.07% to 1.6%) and 3 patients (0.13%; 95% CI 0.03% to 0.41%), respectively. Conclusion Among ED patients with allergic reactions or anaphylaxis, clinically important biphasic reactions and fatalities are rare. Our data suggest that prolonged routine monitoring of patients whose symptoms have resolved is likely unnecessary for patient safety.
Study objective Corticosteroids (steroids) are often used to mitigate symptoms and prevent subsequent reactions in emergency department (ED) patients with allergic reactions, despite a lack of ...evidence to support their use. We sought to determine the association of steroid administration with improved clinical outcomes. Methods Adult allergy-related encounters to 2 urban EDs during a 5-year period were identified and classified as “anaphylaxis” or “allergic reaction.” Regional and provincial databases identified subsequent ED visits or deaths within a 7-day period. The primary outcome was allergy-related ED revisits in the steroid- and nonsteroid-exposed groups, adjusting for potential confounders with a propensity score analysis; secondary outcomes included the number of clinically important biphasic reactions and deaths. Results Two thousand seven hundred one encounters (473 anaphylactic) were included; 48% were treated with steroids. Allergy-related ED revisits occurred in 5.8% and 6.7% of patients treated with and without steroids, respectively (adjusted odds ratio OR 0.91; 95% confidence interval CI 0.64 to 1.28), with a number needed to treat (NNT) to benefit of 176 (95% CI NNT to benefit 39 to ∞ to NNT to harm 65). The adjusted OR in the anaphylaxis subgroup was 1.12 (95% CI 0.41 to 3.27). In the allergic reaction group, the adjusted OR was 0.91 (95% CI 0.63 to 1.31), with an NNT to benefit of 173 (95% CI NNT to benefit 38 to ∞ to NNT to harm 58). In the steroid and nonsteroid groups, there were 4 and 1 clinically important biphasic reactions, respectively. There were no deaths. Conclusion Among ED patients with allergic reactions or anaphylaxis, corticosteroid use was not associated with decreased relapses to additional care within 7 days.
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.
Purpose To examine the association of cardiovascular disease (CVD), CVD risk factors, and CVD treatment with age-related macular degeneration (AMD). Design Observational analysis of a randomized ...clinical trial. Methods settings: The Women’s Health Initiative Sight Examination (WHISE), an ancillary study to the Women’s Health Initiative’s clinical trial of hormone replacement therapy. study population: A total of 4,288 women age 63 years and older. observation procedures: Information on CVD and its risk factors were obtained from a standardized questionnaire and examination. main outcome measure: AMD as determined by standardized grading of fundus photographs. Results Prevalence of any AMD was 21.4% (n = 919). Of those with AMD, 5.8% (n = 53) had signs of exudative AMD (n = 39) or pure geographic atrophy (n = 14), limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were (odds ratio OR, 95% confidence interval CI) older age (1.19, 1.13 to 1.27, P < .0001), more pack years smoked (1.02 per pack-year smoked, 1.003 to 1.03, P = .01), systolic blood pressure (0.84 per 10 mm Hg, 0.71 to 0.995, P = .04), report of taking calcium channel blockers (2.49, 1.21 to 5.12, P = .04), self-reported history of diabetes (2.00, 1.01 to 3.96, P = .05), and greater body mass index (1.05 per 1 kg/m , 1.001 to 1.10, P = .05). History of myocardial infarction, stroke, use of statins, or white blood cell count was not associated with AMD. Conclusions Results suggest that smoking, use of calcium channel blockers, diabetes, and obesity are risk factors for late AMD in women. However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored.
Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing ...cardiologists to use. Guidelines should be condensed and their format upgraded, so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on (1) class I recommendations with established benefits that are supported by randomized clinical trials and (2) class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence based but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as “Expert Consensus Statements” or “Task Force Committee Opinions,” so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines.
The hemodynamics and diagnosis of venous disease Meissner, Mark H., MD; Moneta, Gregory, MD; Burnand, Kevin, MD ...
Journal of vascular surgery,
12/2007, Letnik:
46, Številka:
6
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The venous system is, in many respects, more complex than the arterial system and a thorough understanding of venous anatomy, pathophysiology, and available diagnostic tests is required in the ...management of acute and chronic venous disorders. The venous system develops through several stages, which may be associated with a number of development anomalies. A thorough knowledge of lower extremity venous anatomy, anatomic variants, and the recently updated nomenclature is required of all venous practitioners. Effective venous return from the lower extremities requires the interaction of the heart, a pressure gradient, the peripheral muscle pumps of the leg, and competent venous valves. In the absence of pathology, this system functions to reduce venous pressure from approximately 100 mm Hg to a mean of 22 mm Hg within a few steps. The severe manifestations of chronic venous insufficiency result from ambulatory venous hypertension, or a failure to reduce venous pressure with exercise. Although the precise mechanism remains unclear, venous hypertension is thought to induce the associated skin changes through a number of inflammatory mechanisms. Several diagnostic tests are available for the evaluation of acute and chronic venous disease. Although venous duplex ultrasonography has become the standard for detection of acute deep venous thrombosis, adjuvant modalities such as contrast, computed tomographic, and magnetic resonance venography have an increasing role. Duplex ultrasonography is also the most useful test for detecting and localizing chronic venous obstruction and valvular incompetence. However, it provides relatively little quantitative hemodynamic information and is often combined with measurements of hemodynamic severity determined by a number of plethysmographic methods. Finally, critical assessment of venous treatment modalities requires an understanding of the objective clinical outcome and quality of life instruments available.
A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).
Two similarly designed, double-masked, randomized, ...phase 3 trials, VISTA(DME) and VIVID(DME).
We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.
Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.
The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.
Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.
At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.
Summary Oral squamous-cell carcinomas arise in mucosal linings of the oral cavity and frequently metastasise to regional lymph nodes in the neck. The presence of nodal metastases is a determinant of ...prognosis and clinical management. The neck is staged by palpation and imaging, but accuracy of these techniques to detect small metastases is low. In general, 30–40% of patients will have occult nodal disease and will develop clinically detectable lymph-node metastases when the neck is left untreated. The choice at present is either elective treatment or careful observation followed by treatment of the neck in patients who develop manifest metastases. These unsatisfying therapeutic options have been the subject of debate for decades. Recent developments in staging of the neck, including expression profiling and sentinel lymph-node biopsy, will allow more personalised management of the neck.
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.
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