Deciding what is possible and impossible following hippocampal damage in humans

There is currently much debate about whether the precise role of the hippocampus in scene processing is predominantly constructive, perceptual or mnemonic. Here, we developed a novel experimental paradigm designed to control for general perceptual and mnemonic demands, thus enabling us to specifically vary the requirement for constructive processing. We tested the ability of patients with selective bilateral hippocampal damage and matched control participants to detect either semantic (e.g., an elephant with butterflies for ears) or constructive (e.g., an endless staircase) violations in realistic images of scenes. Thus, scenes could be semantically or constructively 'possible' or 'impossible'. Importantly, general perceptual and memory requirements were similar for both types of scene. We found that the patients performed comparably to control participants when deciding whether scenes were semantically possible or impossible, but were selectively impaired at judging if scenes were constructively possible or impossible. Post-task debriefing indicated that control participants constructed flexible mental representations of the scenes in order to make constructive judgements, whereas the patients were more constrained and typically focused on specific fragments of the scenes, with little indication of having constructed internal scene models. These results suggest that one contribution the hippocampus makes to scene processing is to construct internal representations of spatially coherent scenes, which may be vital for modelling the world during both perception and memory recall. This article is protected by copyright. All rights reserved

Hippocampal Damage Increases Deontological Responses during Moral Decision Making

Complex moral decision making is associated with the ventromedial prefrontal cortex (vmPFC) in humans, and damage to this region significantly increases the frequency of utilitarian judgments. Since the vmPFC has strong anatomical and functional links with the hippocampus, here we asked how patients with selective bilateral hippocampal damage would derive moral decisions on a classic moral dilemmas paradigm. We found that the patients approved of the utilitarian options significantly less often than control participants, favoring instead deontological responses-rejecting actions that harm even one person. Thus, patients with hippocampal damage have a strikingly opposite approach to moral decision making than vmPFC-lesioned patients. Skin-conductance data collected during the task showed increased emotional arousal in the hippocampal-damaged patients and they stated that their moral decisions were based on emotional instinct. By contrast, control participants made moral decisions based on the integration of an adverse emotional response to harming others, visualization of the consequences of one's action, and the rational re-evaluation of future benefits. This integration may be disturbed in patients with either hippocampal or vmPFC damage. Hippocampal lesions decreased the ability to visualize a scenario and its future consequences, which seemed to render the adverse emotional response overwhelmingly dominant. In patients with vmPFC damage, visualization might also be reduced alongside an inability to detect the adverse emotional response, leaving only the utilitarian option open. Overall, these results provide insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions. SIGNIFICANCE STATEMENT: The ventromedial prefrontal cortex (vmPFC) is closely associated with the ability to make complex moral judgements. When this area is damaged, patients become more utilitarian (the ends justify the means) and have decreased emotional arousal during moral decision making. The vmPFC is closely connected with another brain region-the hippocampus. In this study we found that patients with selective bilateral hippocampal damage show a strikingly opposite response pattern to those with vmPFC damage when making moral judgements. They rejected harmful actions of any kind (thus their responses were deontological) and showed increased emotional arousal. These results provide new insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions

Defining emergency department episodes by severity and intensity: A 15-year study of Medicare beneficiaries

Background. Episodes of Emergency Department (ED) service use among older adults previously have not been constructed, or evaluated as multi-dimensional phenomena. In this study, we constructed episodes of ED service use among a cohort of older adults over a 15-year observation period, measured the episodes by severity and intensity, and compared these measures in predicting subsequent hospitalization. Methods. We conducted a secondary analysis of the prospective cohort study entitled the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD). Baseline (1993) data on 5,511 self-respondents 70 years old were linked to their Medicare claims for 1991-2005. Claims then were organized into episodes of ED care according to Medicare guidelines. The severity of ED episodes was measured with a modified-NYU algorithm using ICD9-CM diagnoses, and the intensity of the episodes was measured using CPT codes. Measures were evaluated against subsequent hospitalization to estimate comparative predictive validity. Results. Over 15 years, three-fourths (4,171) of the 5,511 AHEAD participants had at least 1 ED episode, with a mean of 4.5 episodes. Cross-classification indicated the modified-NYU severity measure and the CPT-based intensity measure captured different aspects of ED episodes (kappa = 0.18). While both measures were significant independent predictors of hospital admission from ED episodes, the CPT measure had substantially higher predictive validity than the modified-NYU measure (AORs 5.70 vs. 3.31; p < .001). Conclusions. We demonstrated an innovative approach for how claims data can be used to construct episodes of ED care among a sample of older adults. We also determined that the modified-NYU measure of severity and the CPT measure of intensity tap different aspects of ED episodes, and that both measures were predictive of subsequent hospitalization. © 2010 Kaskie et al; licensee BioMed Central Ltd

The crossroads of evidence-based medicine and health policy: implications for urology

As healthcare spending in the United States continues to rise at an unsustainable rate, recent policy decisions introduced at the national level will rely on precepts of evidence-based medicine to promote the determination, dissemination, and delivery of “best practices” or quality care while simultaneously reducing cost. We discuss the influence of evidence-based medicine on policy and, in turn, the impact of policy on the developing clinical evidence base with an eye to the potential effects of these relationships on the practice and provision of urologic care

Imaging glial activation in patients with post-treatment Lyme disease symptoms: A pilot study using [ ¹¹ C]DPA-713 PET

The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain's resident immune cells, microglia. Here we used [ 11 C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls. Genotyping for the TSPO rs6971 polymorphism was completed, and individuals with the rare, low affinity binding genotype were excluded. Data from eight brain regions demonstrated higher [ 11 C]DPA-713 binding in 12 patients relative to 19 controls. [ 11 C]DPA-713 PET is a promising tool to study cerebral glial activation in PTLDS and its link to cognitive symptoms

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treating Uncomplicated Malaria: A Randomized Trial to Guide Policy in Uganda

BACKGROUND: Uganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission. METHODOLOGY/PRINCIPAL FINDINGS: Patients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0-28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI -0.2-7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated. CONCLUSIONS/SIGNIFICANCE: DP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN75606663

What effect does physician "profiling" have on inpatient physician satisfaction and hospital length of stay?

BACKGROUND: 2002 marked the first time that the rate of hospital spending in the United States outpaced the overall health care spending rate of growth since 1991. As hospital spending continues to grow and as reimbursement for hospital expenses has moved towards the prospective payment system, there is still increasing pressure to reduce costs. Hospitals have a major incentive to decrease resource utilization, including hospital length of stay. We evaluated whether physician profiling affects physician satisfaction and hospital length of stay, and assessed physicians' views concerning hospital cost containment and the quality of care they provide. METHODS: To determine if physician profiling affects hospital length of stay and/or physician satisfaction, we used quasi-experimental with before-versus-after and intervention-versus-control comparisons of length of stay data collected at an intervention and six control hospitals. Intervention hospital physicians were informed their length of stay would be compared to their peers and were given a questionnaire assessing their experience. RESULTS: Nearly half of attending pre-profiled physicians felt negative about the possibility of being profiled, while less than one-third of profiled physicians reported feeling negative about having been profiled. Nearly all physicians greatly enjoyed their ward month. Length of stay at the profiled site decreased by an additional 1/3 of a day in the profiling year, compared to the non-profiled sites (p < 0.001). CONCLUSION: A relatively non-instrusive profiling intervention modestly reduced length of stay without adversely affecting physician satisfaction