What drives the 'August effect'?: an observational study of the effect of junior doctor changeover on out of hours work

Objective: To investigate whether measurements of junior doctor on-call workload and performance can clarify the mechanisms underlying the increase in morbidity and mortality seen after junior doctor changeover: the ‘August effect’. Design: Quantitative retrospective observational study of routinely collected data on junior doctor workload. Setting: Two large teaching hospitals in England. Participants: Task level data from a wireless out of hours system (n = 29,885 requests) used by medical staff, nurses, and allied health professionals. Main outcome measures: Number and type of tasks requested by nurses, time to completion of tasks by junior doctors. Results: There was no overall change in the number of tasks requested by nurses out of hours around the August changeover (median requests per hour 15 before and 14 after, p = 0.46). However, the number of tasks classified as urgent was greater (p = 0.016) equating to five more urgent tasks per day. After changeover, doctors took less time to complete tasks overall due to a reduction in time taken for routine tasks (median 74 vs. 66 min; p = 3.9 × 10−9). Conclusion: This study suggests that the ‘August effect’ is not due to new junior doctors completing tasks more slowly or having a greater workload. Further studies are required to investigate the causes of the increased number of urgent tasks seen, but likely factors are errors, omissions, and poor prioritization. Thus, improved training and quality control has the potential to address this increased duration of unresolved patient risk. The study also highlights the potential of newer technologies to facilitate quantitative study of clinical activity

A Randomized, Placebo Controlled, Double Masked Phase IB Study Evaluating the Safety and Antiviral Activity of Aprepitant, a Neurokinin-1 Receptor Antagonist in HIV-1 Infected Adults

Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic.We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3) and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days.Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20), -0.05(-0.21,+0.10), and +0.04(-0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred.Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity.ClinicalTrials.gov NCT00428519

The impact of a team-based intervention on the lifestyle risk factor management practices of community nurses: outcomes of the community nursing SNAP trial

BackgroundLifestyle risk factors like smoking, nutrition, alcohol consumption, and physical inactivity (SNAP) are the main behavioural risk factors for chronic disease. Primary health care is an appropriate setting to address these risk factors in individuals. Generalist community health nurses (GCHNs) are uniquely placed to provide lifestyle interventions as they see clients in their homes over a period of time. The aim of the paper is to examine the impact of a service-level intervention on the risk factor management practices of GCHNs.MethodsThe trial used a quasi-experimental design involving four generalist community nursing services in NSW, Australia. The services were randomly allocated to either an intervention group or control group. Nurses in the intervention group were provided with training and support in the provision of brief lifestyle assessments and interventions. The control group provided usual care. A sample of 129 GCHNs completed surveys at baseline, 6 and 12&thinsp;months to examine changes in their practices and levels of confidence related to the management of SNAP risk factors. Six semi-structured interviews and four focus groups were conducted among the intervention group to explore the feasibility of incorporating the intervention into everyday practice.ResultsNurses in the intervention group became more confident in assessment and intervention over the three time points compared to their control group peers. Nurses in the intervention group reported assessing physical activity, weight and nutrition more frequently, as well as providing more brief interventions for physical activity, weight management and smoking cessation. There was little change in referral rates except for an improvement in weight management related referrals. Nurses&rsquo; perception of the importance of &lsquo;client and system-related&rsquo; barriers to risk factor management diminished over time.ConclusionsThis study shows that the intervention was associated with positive changes in self-reported lifestyle risk factor management practices of GCHNs. Barriers to referral remained. The service model needs to be adapted to sustain these changes and enhance referral

Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

10.1371/journal.pntd.0002373PLoS Neglected Tropical Diseases78

Reduced prefrontal gyrification in obsessive–compulsive disorder

Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessive–compulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal pole. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (p = 0.021) and a trend for a decreased A-GI in the right hemisphere (p = 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease

Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression

BACKGROUND: Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. METHODS: Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. RESULTS: Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. CONCLUSION: The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features

Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women

Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αβ)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND.This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND

Deficit of social cognition in subjects with surgically treated frontal lobe lesions and in subjects affected by schizophrenia

The ability of humans to predict and explain other people’s behaviour by attributing independent mental states such as desires and beliefs to them, is considered to be due to our ability to construct a “Theory of Mind”. Recently, several neuroimaging studies have implicated the medial frontal lobes as playing a critical role in a dedicated “mentalizing” or “Theory of Mind” network in the human brain. In this study we compare the performance of patients with right and left medial prefrontal lobe lesions in theory of mind and in social cognition tasks, with the performance of people with schizophrenia. We report a similar social cognitive profile between patients with prefrontal lobe lesions and schizophrenic subjects in terms of understanding of false beliefs, in understanding social situations and in using tactical strategies. These findings are relevant for the functional anatomy of “Theory of Mind”