Human cerebral circuitry related to cardiac control: A neuroimaging meta‐analysis

Serious arrhythmias often follow stroke, highlighting the important role that the cerebral cortex has in neural regulation of the heart. Neuroimaging studies reveal patterns of activation associated with autonomic cardiovascular responses. Using the activation likelihood estimation, a meta‐analysis was performed to identify cortical activation patterns related to heart rate and heart rate variability across studies that used differing stimuli of cardiovascular arousal. Consistent associations with heart rate and heart rate variability were observed in the anterior cingulate, amygdala, insula, and prefrontal cortex, among others. Also, evidence is provided of insular lateralization associated with autonomic cardiac responses. Ann Neurol 2016;79:709–716     

Relationship of depression and medications on incidence of falls among people with late effects of polio

The purpose of this study was to determine if falls in polio survivors, with or without post-polio syndrome (PPS), are related to number of medications taken, use of anti-depressant or psychoactive medications, or self-report of depression. A survey was sent to 300 members of a regional polio support group, asking them to document their fall history, medications used, and the presence of depression. Depression was measured by self-report and with the Geriatric Depression Scale, short form (GDS-15). One hundred and seventy-two usable surveys were returned with 146 of those completing the medication list. Sixty-two percent reported at least one fall in the past year. The multiple logistic regression was significant (p = 0.023), and it indicated depression to be a significant predictor (p = 0.012) of falls in polio survivors with and without PPS. The number of total medications or anti-depressant or psychoactive medications used was not related to fall incidence. Routine screening and treatment for depression may be one aspect of fall prevention which can be implemented through primary care.     

Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer

BACKGROUND.

Previous reports based on small patient numbers suggested that changes in serum HER‐2/neu levels may predict response or lack of response to trastuzumab‐based therapies in metastatic breast cancer (MBC). The objectives of this study were to pool data from 307 patients with MBC from 7 medical institutions to validate that the serum HER‐2/neu profile predicts patient resistance to trastuzumab and to establish a clinically relevant cutoff.

METHODS.

This was an international, multicenter, retrospective analysis of individual pooled data from 307 patients with MBC who were treated with first‐line trastuzumab‐based therapy. Serum was collected at baseline and 30 to 120 days after the initiation of trastuzumab therapy. A serum HER‐2/neu decrease ≥20% (receiver operating curve analysis) was defined as a significant HER‐2/neu change.

RESULTS.

Of the 307 patients with MBC, 191 patients (62%) had a significant decline (>20%) in serum HER‐2/neu and 116 patients (38%) did not. The objective response rate was 57% for patients who achieved this decline in serum HER‐2/neu (>20%) compared with 28% for patients who did not. Patients who achieved this decline in serum HER‐2/neu also had a significantly longer time to disease progression (320 days vs 180 days; P < .0001), longer duration of response (369 days vs 230 days; P = .008), and longer overall survival (898 days vs 593 days; P < .018).

CONCLUSIONS.

In this pooled analysis of 307 patients with MBC, individuals who did not achieve a significant decline (≥20%) in serum HER‐2/neu levels had decreased benefit from trastuzumab‐based therapy, and these patients should be considered for clinical trials evaluating additional HER‐2/neu‐targeted interventions. Cancer 2008. © 2008 American Cancer Society.     

Knowledge, patterns of care, and outcomes of care for generalists and specialists

OBJECTIVE: To critically evaluate the differences between generalist physicians and specialists in terms of knowledge, patterns of care, and clinical outcomes of care. METHODS: English-language articles (January 1981 to January 1998) were identified through a Medline search and examination of bibliographies of identified articles. Systematic evaluation of articles relevant to adult medicine that had a direct comparison between generalist physicians and specialists in terms of knowledge relative to widely accepted standards of care, patterns of care (including use of medications, ancillary services, procedures, and resource utilization), and outcomes of care was performed. MAIN RESULTS: In many survey studies, specialists were reported to be more knowledgeable about conditions encompassed within their specialty. In terms of overall practice patterns, specialists practicing in their area of expertise were more likely to use medications associated with improved survival and to comply with routine health maintenance screening guidelines; they used more resources including diagnostic tests, procedures, and longer hospital stays. In the limited number of studies examining the care of patients with acute myocardial infarction, acute nonhemorrhagic stroke, and asthma, specialists had superior outcomes compared with generalists. CONCLUSIONS: There is evidence in the literature suggesting differences between specialists and generalists in terms of knowledge, patterns of care, and clinical outcomes of care for a broad range of diseases. In published studies, specialists were generally more knowledgeable about their area of expertise and quicker to adopt new and effective treatments than generalists. More research is needed to examine whether these patterns of care translate into superior outcomes for patients. Further work is also needed to delineate the components of care for which generalists and specialists should be responsible, in order to provide the highest quality of care to patients while most effectively utilizing existing physician manpower.     

Randomized Comparison of Direct Thrombin Inhibition Versus Heparin in Conjunction With Fibrinolytic Therapy for Acute Myocardial Infarction: Results From the GUSTO-IIb Trial

Objectives. We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days.

Background. In a large-scale trial of patients with acute coronary syndromes, hirudin provided modest benefit compared with heparin. However, the interaction with thrombolytic agents was not specifically assessed.

Methods. Patients with symptoms of acute myocardial infarction and electrocardiographic ST segment elevation were treated with thrombolytic therapy and randomly assigned to receive hirudin or heparin.

Results. A total of 2,274 patients received t-PA, and 1,015 received SK. Baseline characteristics were balanced by antithrombin assignment. Among SK-treated patients, death or reinfarction at 30 days occurred more often in those treated with adjunctive heparin (14.4%) rather than hirudin (8.6%, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA–treated patients, the rates were 10.9% with heparin and 10.3% with hirudin (OR 1.06, 95% CI 0.81 to 1.38, p = 0.68; for treatment heterogeneity: chi-square 4.20, degrees of freedom [df] 1, p = 0.04). After adjustment for baseline differences between thrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial treatment effect of hirudin was limited to the SK-treated patients.

Conclusions. Hirudin interacts favorably with SK but not t-PA, highlighting the importance of thrombin activity after SK therapy and the potential for simulating the effects of a more potent fibrinolytic agent through direct antithrombin therapy.