The optimal diagnostic strategy for patients with chest pain and detectable to mildly elevated serum troponin is not known. The objective was to compare clinical outcomes among an early decision for ...a noninvasive versus an invasive-based care pathway.
The CMR-IMPACT trial (Cardiac Magnetic Resonance Imaging Strategy for the Management of Patients with Acute Chest Pain and Detectable to Elevated Troponin) was conducted at 4 United States tertiary care hospitals from September 2013 to July 2018. A convenience sample of 312 participants with acute chest pain symptoms and a contemporary troponin between detectable and 1.0 ng/mL were randomized early in their care to 1 of 2 care pathways: invasive-based (n=156) or cardiac magnetic resonance (CMR)-based (n=156) with modification allowed as the patient condition evolved. The primary outcome was a composite including death, myocardial infarction, and cardiac-related hospital readmission or emergency visits.
Participants (N=312, mean age, 60.6 years, SD 11.3; 125 women 59.9%), were followed over a median of 2.6 years (95% CI, 2.4-2.9). Early assigned testing was initiated in 102 out of 156 (65.3%) CMR-based and 110 out of 156 (70.5%) invasive-based participants. The primary outcome (CMR-based versus invasive-based) occurred in 59% versus 52% (hazard ratio, 1.17 95% CI, 0.86-1.57), acute coronary syndrome after discharge 23% versus 22% (hazard ratio, 1.07 95% CI, 0.67-1.71), and invasive angiography at any time 52% versus 74% (hazard ratio, 0.66 95% CI, 0.49-0.87). Among patients completing CMR imaging, 55 out of 95 (58%) were safely identified for discharge based on a negative CMR and did not have angiography or revascularization within 90 days. Therapeutic yield of angiography was higher in the CMR-based arm (52 interventions in 81 angiographies 64.2% versus 46 interventions in 115 angiographies 40.0% in the invasive-based arm
=0.001).
Initial management with CMR or invasive-based care pathways resulted in no detectable difference in clinical and safety event rates. The CMR-based pathway facilitated safe discharge, enriched the therapeutic yield of angiography, and reduced invasive angiography utilization over long-term follow-up.
URL: https://www.
gov; Unique identifier: NCT01931852.
Summary
Depression and insomnia commonly co‐occur, resulting in greater morbidity for patients, and difficult diagnostic and treatment decisions for clinicians.
When patients report symptoms of both ...depression and insomnia, it is common for medical practitioners to conceptualise the insomnia as a secondary symptom of depression. This implies that there is little purpose in treating insomnia directly, and that management of depression will improve both the depression and insomnia symptoms.
In this review, we present an overview of research investigating the comorbidity and treatment approaches for patients presenting with depression and insomnia in primary care.
Evidence shows that clinicians should avoid routinely conceptualising insomnia as a secondary symptom of depression. This is because insomnia symptoms: (i) often occur before mood decline and are independently associated with increased risk of future depression; (ii) commonly remain unchanged following depression treatment; and (iii) predict relapse of depression after treatment for depression only. Furthermore, compared with control, cognitive behaviour therapy for insomnia improves symptoms of both depression and insomnia.
It is critical that primary care clinicians dedicate specific diagnostic and treatment attention to the management of both depression (eg, psychotherapy, antidepressants) and insomnia (eg, cognitive behaviour therapy for insomnia administered by trained therapists or psychologists through a mental health treatment plan referral, by online programs, or by a general practitioner or nurse) when they co‐occur. These treatments may be offered concurrently or sequentially (eg, insomnia treatment followed by depression treatment, or vice versa), depending on presenting symptoms, history, lifestyle factors and other comorbidities.
To evaluate the utility of F-FDG-PET in predicting response to concomitant chemoradiation in locally-advanced esophageal cancer.
Approximately 25% of esophageal cancer patients experience a ...pathologic complete response (pCR) to preoperative chemoradiation therapy. Computed tomography, endoscopy, and endoscopic ultrasound are unable to identify patients experiencing a pCR. Growing evidence supports the use of F-FDG-PET in the staging of esophageal cancer in its ability to detect occult metastatic and lymph nodal disease. The identification of patients with a pCR to chemoradiation could potentially spare those patients the morbidity associated with a resection.
Eligibility criteria included T3-T4N0M0 or T1-T4N1M0 esophageal cancer. Patients underwent an initial F-FDG-PET before treatment and then repeated 4 to 6 weeks after chemoradiation, prior to the esophagectomy. Chemoradiation consisted of: cisplatinum, 5-fluorouracil, and radiation to a median dose of 50.4 Gy. Pathologic response was determined from a systematic review of the esophagectomy specimens.
Sixty-four patients have completed therapy to date. Response was as follows: pCR 27%, pathologic residual microscopic (pCRmicro) 14.5%, partial response 19%, and stable or progressive disease 39.5%. A pretreatment standardized uptake value (SUVmax1hour) > or = 15 was associated with an observed 77.8% significant response (pCR + pCRmicro) compared with 24.2% for patients with a pretreatment SUVmax1hour < 15 (P = 0.005). Significant response was observed in 71.4% of patients with a decrease in SUVmax1hour > or = 10 compared with 33.3% when the SUVmax1hour decreased <10 (P = 0.004).
Pretreatment and posttreatment F-FDG-PET can be useful for predicting significant response to chemoradiation in esophageal cancer. These data should be considered in evaluation of patients for esophagectomy after chemoradiation.
Background Shift work is characterised by displaced sleep opportunities and associated sleep disturbance. Shift workers often report sleepiness and other wake time symptoms associated with poor ...sleep. However, clinical sleep disorders are also prevalent in shift workers. Although prevalence rates are similar or higher in shift workers compared with the general population, help seeking in shift workers with sleep disorders is low.
Objective This article aims to provide general practitioners with a contemporary overview of the prevalence rates for sleep disorders in shift workers, to clarify the existing evidence relating to mental and physical health consequences of sleep disorders in shift workers and to highlight the need to consider undiagnosed sleep disorders before attributing sleep-related symptoms solely to work schedules.
Discussion Symptoms of sleep loss associated with shift work overlap with symptoms experienced by individuals living with sleep disorders. Although >40% of middle-aged Australians live with a sleep disorder that requires investigation and management, symptoms in shift workers are often attributed to the work schedule and, as a result, might not be investigated for appropriate diagnosis and treatment. We argue that screening for sleep disorders in shift workers with sleep complaints should be a priority.
In healthy populations, irregular sleep patterns are associated with delayed sleep and poor functional/mood outcomes. Currently, it is unknown whether irregular sleep contributes to poor ...functional/mood outcomes in individuals with Delayed Sleep-Wake Phase Disorder (DSWPD).
In 170 patients with DSWPD, we collected sleep-wake patterns, dim light melatonin onset (DLMO), and functional/mood outcomes. The Sleep Regularity Index (SRI) and other sleep timing metrics were computed. Correlations of SRI were computed with phase angle (difference between DLMO and desired bedtime), sleep timing and quality variables, daytime function, sleep-related daytime impairment, mood, and insomnia symptom severity. Path analyses assessed whether SRI or total sleep time mediated the associations between sleep onset time and phase angle with daytime functioning, sleep-related impairment, and mood outcomes.
Higher SRI was associated with earlier sleep and longer total sleep time, but did not relate to sleep quality, daytime function, or mood outcomes. Path analysis showed that phase angle was directly associated with all outcome variables, whereas sleep onset time was not directly associated with any. SRI mediated the effects of sleep onset time and phase angle on daytime function. Total sleep time mediated the effects of sleep onset time and phase angle on sleep-related impairment.
Individuals with DSWPD who have more delayed sleep and a greater phase angle also have more irregular sleep. This suggests that it is not delayed sleep timing per se that drives poor functional outcomes in DSWPD, but rather the timing of sleep relative to circadian phase and resultant irregular sleep patterns.
•Irregular sleep is associated with later sleep onset time and shorter sleep duration.•Individuals with more delayed sleep have more circadian misalignment have more irregular sleep.•Sleep regularity mediates the effects of sleep onset time and phase angle on daytime function.
Background
Schizophrenia is associated with significant economic burden. In Brazil, antipsychotic drugs and outpatient and hospital services are provided by the Brazilian National Health System (SUS) ...for patients with schizophrenia. However, few studies capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems.
Objective
Our objective was to use real-world data to describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010.
Methods
We integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. We assessed only direct medical costs and the study was conducted from a public-payer perspective. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables.
Results
We identified 174,310 patients with schizophrenia, with mean ± standard deviation (SD) annual costs of $US1811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of total costs, with a mean annual cost per patient of $US1578.74 ± 240.40. Mean annual costs per patient were $US2482.90 ± 302.92 for psychiatric hospitalization and $US862.96 ± 160.18 for outpatient psychiatric care. Olanzapine was used by 47.7% of patients and represented 62.8% of the total costs of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient for outpatient psychiatric care and psychiatric hospitalization.
Conclusions
Atypical antipsychotics were responsible for the majority of the schizophrenia treatment costs, and psychiatric hospitalization costs were the highest mean annual cost per patient. Authorities should ensure efficient use of atypical antipsychotics and encourage outpatient psychiatric care over psychiatric hospitalization where possible.
Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome of inflammatory diseases and malignancies. Crohn's disease is a chronic ...inflammatory bowel disease of unknown etiology. Perturbation of the intestinal cytokine homeostasis is believed to play a pivotal role, but the pathogenesis of Crohn's disease is not fully understood. Here, we study intestinal T cells from Crohn's disease and healthy volunteers. We show that STAT3 and STAT4 are constitutively activated in Crohn's patients but not in healthy volunteers. The activation is specific, because other STAT proteins are not constitutively activated. Furthermore, the STAT3 regulated protein, SOCS3, is also constitutively expressed in Crohn's patients but not in healthy volunteers. Taken together, these data provide evidence of abnormal STAT/SOCS signaling in Crohn's disease. This aberrant activation, so far noted only in malignant cells, establish a new critical approach for better understanding the immunopathogenesis of Crohn's disease.
The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively ...straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6<Q^{2}<2.9 GeV^{2}, where existing measurements give inconsistent results. The precision and Q^{2} range of these data allow for a better understanding of the current world's data and suggest a path toward further improvement of our overall understanding of the neutron's magnetic form factor.
In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell ...infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.
Background. For patients with metastatic prostate cancer, treatment is primarily palliative, relying mainly on the suppression of systemic androgen hormone levels. To help document the achievement of ...palliation and to characterize positive and negative effects of treatment, we evaluated qualityof-life (QOL) parameters in patients with metastatic prostate cancer who were randomly assigned to two methods of androgen deprivation. Methods: Patients (n = 739) with stage M1 (bone or soft tissue metastasis) prostate cancer were enrolled in a QOL protocol that was a companion to Southwest Oncology Group INT-0105, a randomized doubleblind trial comparing treatment with bilateral orchiectomy (surgical castration) plus either flutamide or placebo. Patients completed a comprehensive battery of QOL questionnaires at random assignment to treatment and at 1, 3, and 6 months later. Data were collected on three treatment-specific symptoms (diarrhea, gas pain, and body image), on physical functioning, and on emotional functioning. All P values are two-sided. Results: Questionnaire return rates for this study never dropped below 80%; only 2% of the patients did not submit baseline QOL assessments. Cross-sectional analyses (corrected for multiple testing) identified statistically significant differences that favored orchiectomy plus placebo for two of the five primary QOL parameters as follows: patients receiving flutamide reported more diarrhea at 3 months (P = .001) and worse emotional functioning at 3 and 6 months (both P<.003). Longitudinal analyses replicated these findings. Other analyzed QOL parameters favored the group receiving placebo but were not statistically significant after adjustment for multiple testing. Conclusions: We found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo. J Nall Cancer Inst 1998;90:1537-44
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