Obsessive‐compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence ...links these conditions with underlying dysregulation of fronto‐striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of ‘false alarms’ for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.
LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
CONTEXT Suicide attempts constitute a major risk factor for completed suicide,
yet few interventions specifically designed to prevent suicide attempts have
been evaluated. OBJECTIVE To determine the ...effectiveness of a 10-session cognitive therapy intervention
designed to prevent repeat suicide attempts in adults who recently attempted
suicide. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial of adults (N = 120) who attempted
suicide and were evaluated at a hospital emergency department within 48 hours
of the attempt. Potential participants (N = 350) were consecutively
recruited from October 1999 to September 2002; 66 refused to participate and
164 were ineligible. Participants were followed up for 18 months. INTERVENTION Cognitive therapy or enhanced usual care with tracking and referral
services. MAIN OUTCOME MEASURES Incidence of repeat suicide attempts and number of days until a repeat
suicide attempt. Suicide ideation (dichotomized), hopelessness, and depression
severity at 1, 3, 6, 12, and 18 months. RESULTS From baseline to the 18-month assessment, 13 participants (24.1%) in
the cognitive therapy group and 23 participants (41.6%) in the usual care
group made at least 1 subsequent suicide attempt (asymptotic z score, 1.97; P = .049). Using the Kaplan-Meier
method, the estimated 18-month reattempt-free probability in the cognitive
therapy group was 0.76 (95% confidence interval CI, 0.62-0.85) and in the
usual care group was 0.58 (95% CI, 0.44-0.70). Participants in the cognitive
therapy group had a significantly lower reattempt rate (Wald χ21 = 3.9; P = .049)
and were 50% less likely to reattempt suicide than participants in the usual
care group (hazard ratio, 0.51; 95% CI, 0.26-0.997). The severity of self-reported
depression was significantly lower for the cognitive therapy group than for
the usual care group at 6 months (P= .02), 12
months (P = .009), and 18 months (P = .046). The cognitive therapy group reported
significantly less hopelessness than the usual care group at 6 months (P = .045). There were no significant differences
between groups based on rates of suicide ideation at any assessment point. CONCLUSION Cognitive therapy was effective in preventing suicide attempts for adults
who recently attempted suicide.
Telehealth is a care delivery model that promises to increase the flexibility and reach of health services. Our objective is to describe patient experiences with video visits performed with their ...established primary care clinicians.
We constructed semistructured, in-depth qualitative interviews with adult patients following video visits with their primary care clinicians at a single academic medical center. Data were analyzed with a content analysis approach.
Of 32 eligible patients, 19 were successfully interviewed. All patients reported overall satisfaction with video visits, with the majority interested in continuing to use video visits as an alternative to in-person visits. The primary benefits cited were convenience and decreased costs. Some patients felt more comfortable with video visits than office visits and expressed a preference for receiving future serious news via video visit, because they could be in their own supportive environment. Primary concerns with video visits were privacy, including the potential for work colleagues to overhear conversations, and questions about the ability of the clinician to perform an adequate physical examination.
Primary care video visits are acceptable in a variety of situations. Patients identified convenience, efficiency, communication, privacy, and comfort as domains that are potentially important to consider when assessing video visits vs in-person encounters. Future studies should explore which patients and conditions are best suited for video visits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Data are limited regarding how to effectively and efficiently identify patient priorities for research or clinical care. Our goal was to compare the comprehensiveness and efficiency of group concept ...mapping (GCM), a group participatory method, to interviews for identifying patient goals when seeking care.
We engaged patients with moderately- to poorly-controlled diabetes mellitus in either GCM or an individual interview. The primary outcome was the comprehensiveness of GCM brainstorming (the first stage of GCM) as compared to interviews for eliciting patient-important outcomes (PIOs) related to seeking care. Secondary outcomes included 1) comprehensiveness of GCM brainstorming and interviews compared to a master list of PIOs and 2) efficiency of GCM brainstorming, the entire GCM process and interviews.
We engaged 89 interview participants and 52 GCM participants (across 3 iterations of GCM) to identify outcomes most important to patients when making decisions related to diabetes management. We identified 26 PIOs in interviews, 33 PIOs in the first GCM brainstorming session, and 38 PIOs across all three GCM brainstorming sessions. The initial GCM brainstorming session identified 77% (20/26) of interview PIOs, and all 3 GCM brainstorming sessions combined identified 88% (23/26). When comparing GCM brainstorming and interviews to the master list of PIOs, the initial GCM brainstorming sessions identified 80% (33/41), all 3 GCM brainstorming sessions identified 93% (38/41) and interviews identified 63% (26/41) of all PIOs. Compared to interviews, GCM brainstorming required less research team time, more patient time, and had a lowest cost. The entire GCM process still required less research team time than interviews, though required more patient time and had a higher cost than interviews.
GCM brainstorming is a powerful tool for effectively and efficiently identifying PIOs in certain scenarios, though it does not provide the breadth and depth of individual interviews or the higher level conceptual organization of the complete process of GCM. Selection of the optimal method for patient engagement should include consideration of multiple factors including depth of patient input desired, research team expertise, resources, and the population to be engaged.
Registered on ClinicalTrials.gov , NCT02792777. Registration information submitted 6/2/2016, with the registration first posted on the ClinicalTrials.gov website 6/8/2016. Data collection began on 4/29/2016.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The amyloid cascade hypothesis has strongly impacted the Alzheimer's disease research agenda and clinical trial designs over the past decades, but precisely how amyloid-β pathology initiates ...the aggregation of neocortical tau remains unclear. We cannot exclude the possibility of a shared upstream process driving both amyloid-β and tau in an independent manner instead of there being a causal relationship between amyloid-β and tau. Here, we tested the premise that if a causal relationship exists, then exposure should be associated with outcome both at the individual level as well as within identical twin-pairs, who are strongly matched on genetic, demographic and shared environmental background. Specifically, we tested associations between longitudinal amyloid-β PET and cross-sectional tau PET, neurodegeneration and cognitive decline using genetically identical twin-pair difference models, which provide the unique opportunity of ruling out genetic and shared environmental effects as potential confounders in an association.
We included 78 cognitively unimpaired identical twins with 18Fflutemetamol (amyloid-β)-PET, 18Fflortaucipir (tau)-PET, MRI (hippocampal volume) and cognitive data (composite memory). Associations between each modality were tested at the individual level using generalized estimating equation models, and within identical twin-pairs using within-pair difference models. Mediation analyses were performed to test for directionality in the associations as suggested by the amyloid cascade hypothesis.
At the individual level, we observed moderate-to-strong associations between amyloid-β, tau, neurodegeneration and cognition. The within-pair difference models replicated results observed at the individual level with comparably strong effect sizes. Within-pair differences in amyloid-β were strongly associated with within-pair differences in tau (β = 0.68, P < 0.001), and moderately associated with within-pair differences in hippocampal volume (β = −0.37, P = 0.03) and memory functioning (β = −0.57, P < 0.001). Within-pair differences in tau were moderately associated with within-pair differences in hippocampal volume (β = −0.53, P < 0.001) and strongly associated with within-pair differences in memory functioning (β = −0.68, P < 0.001). Mediation analyses showed that of the total twin-difference effect of amyloid-β on memory functioning, the proportion mediated through pathways including tau and hippocampal volume was 69.9%, which was largely attributable to the pathway leading from amyloid-β to tau to memory functioning (proportion mediated, 51.6%).
Our results indicate that associations between amyloid-β, tau, neurodegeneration and cognition are unbiased by (genetic) confounding. Furthermore, effects of amyloid-β on neurodegeneration and cognitive decline were fully mediated by tau. These novel findings in this unique sample of identical twins are compatible with the amyloid cascade hypothesis and thereby provide important new knowledge for clinical trial designs.
Coomans & Tomassen et al. test associations between amyloid-β, tau, neurodegeneration and cognitive decline within pairs of identical twins using within-pair difference models, thereby ruling out potential confounding by genetic and shared environmental factors. The results are compatible with the amyloid cascade hypothesis.
The Thrombolysis in Myocardial Infarction (TIMI) risk score uses clinical data to predict the short-term risk of acute myocardial infarction, coronary revascularization or death from any cause. It ...was originally developed for use in patients with unstable angina or non-ST-elevation myocardial infarction. We sought to expand the clinical application of the TIMI risk score by assessing its prognostic accuracy in patients in the emergency department with potential acute coronary syndromes.
We searched five electronic databases, hand-searched reference lists of included studies and contacted content experts to identify articles for review. We included prospective cohort studies that validated the TIMI risk score in emergency department patients. We performed a meta-regression to determine whether a linear relation exists between TIMI risk score and the cumulative incidence of cardiac events.
We included 10 prospective cohort studies (with a total of 17 265 patients) in our systematic review. Data were available for meta-analysis in 8 of the 10 studies. Of patients with a score of zero, 1.8% had a cardiac event within 30 days (sensitivity 97.2%, 95% CI 96.4-97.8; specificity 25.0%, 95% CI 24.3-25.7; positive likelihood ratio 1.30, 95% CI 1.28-1.31; negative likelihood ratio 0.11, 95% CI 0.09-0.15). Meta-regression analysis revealed a strong linear relation between TIMI risk score (p < 0.001) and the cumulative incidence of cardiac events.
Although the TIMI risk score is an effective risk stratification tool for patients in the emergency department with potential acute coronary syndromes, it should not be used as the sole means of determining patient disposition.
Current treatments for autism spectrum disorders (ASD) are limited in efficacy and are often associated with substantial side effects. These medications typically ameliorate problem behaviors ...associated with ASD, but do not target core symptom domains. As a result, there is a significant amount of research underway for development of novel experimental therapeutics. Endocannabinoids are arachidonic acid-derived lipid neuromodulators, which, in combination with their receptors and associated metabolic enzymes, constitute the endocannabinoid (EC) system. Cannabinoid signaling may be involved in the social impairment and repetitive behaviors observed in those with ASD. In this review, we discuss a possible role of the EC system in excitatory-inhibitory (E-I) imbalance and immune dysregulation in ASD. Novel treatments for the core symptom domains of ASD are needed and phytocannabinoids could be useful experimental therapeutics for core symptoms and associated domains.
•Cannabinoid signaling may be involved in the social impairment observed in those with autism spectrum disorders (ASD).•Novel treatments for the core symptom domains of ASD are needed, and the endocannabinoid (EC) system could be a target for those therapies through the administration of exogenous cannabinoids.•Currently, trials involving cannabidiol (CBD), cannavidivarin (CBDV) and tetrahydrocannabinol (THC) in ASD are underway, but more research is needed to assess their efficacy in symptom improvement.
Objectives
To assess the association between Body Mass Index (BMI) and cause-specific mortality in older adults and to assess which BMI was associated with lowest mortality.
Design
Prospective study.
...Setting
European towns.
Participants
1,980 older adults, aged 70–75 years from the SENECA (Survey in Europe on Nutrition and the Elderly: a concerted action) study.
Measurements
BMI, examined in 1988/1989, and mortality rates and causes of death during 10 years of follow-up.
Results
Cox proportional hazards model including both BMI and BMI2, accounting for sex, smoking status, educational level and age at baseline showed that BMI was associated with all-cause mortality (p<0.01), cardiovascular mortality (p<0.01) and mortality from other causes (p<0.01), but not with cancer or respiratory mortality (p>0.3). The lowest all-cause mortality risk was found at 27.1 (95%CI 24.1, 29.3) kg/m
2
, and this risk was increased with statistical significance when higher than 31.4 kg/m
2
and lower than 21.1 kg/m
2
. The lowest cardiovascular mortality risk was found at 25.6 (95%CI 17.1, 28.4) kg/m
2
, and was increased with statistical significance when higher than 30.9 kg/m
2
.
Conclusion
In this study, BMI was associated with all-cause mortality risk in older people. This risk was mostly driven by an increased cardiovascular mortality risk, as no association was found for mortality risk from cancer or respiratory disease. Our results indicate that the WHO cut-off point of 25 kg/m
2
for overweight might be too low in old age, but more studies are needed to define specific cut-off points.
The cyanoacrylate topical skin adhesives Singer, Adam J., MD; Quinn, James V., MD, MS; Hollander, Judd E., MD
The American journal of emergency medicine,
05/2008, Letnik:
26, Številka:
4
Journal Article
Recenzirano
Abstract Each year there are over 7 million lacerations requiring wound closure in the emergency department. Traditionally, most lacerations have been closed with sutures. Topical cyanoacrylate skin ...adhesives offer many advantages over traditional wound closure devices. Recently, the Food and Drug Administration (FDA) has reclassified the topical skin adhesives. As a result, new topical skin adhesives are expected to enter the market in the near future. This article will review the structure and function of cyanoacrylates as well as their advantages, indications, and usage.
Study objective We seek to determine the impact of emergency department (ED) crowding on delays in antibiotic administration for patients with community-acquired pneumonia. Methods We performed a ...retrospective cohort study of adult patients admitted with community-acquired pneumonia from January 1, 2003, to April 31, 2005, at a single, urban academic ED. The main outcome was a delay (>4 hours from arrival) or nonreceipt of antibiotics in the ED. Eight ED crowding measures were assigned at triage. Multivariable regression and bootstrapping were used to test the adjusted impact of ED crowding measures of delayed (or no) antibiotics. Predicted probabilities were then calculated to assess the magnitude of the impact of ED crowding on the probability of delayed (or no) antibiotics. Results In 694 patients, 44% (95% confidence interval CI 40% to 48%) received antibiotics within 4 hours and 92% (95% CI 90% to 94%) received antibiotics in the ED. Increasing levels of ED crowding were associated with delayed (or no) antibiotics, including waiting room number (odds ratio OR 1.05 for each additional waiting room patient 95% CI 1.01 to 1.10) and recent ED length of stay for admitted patients (OR 1.14 for each additional hour 95% CI 1.04 to 1.25). When the waiting room and recent length of stay were both at the lowest quartiles (ie, not crowded), the predicted probability of delayed (or no) antibiotics within 4 hours was 31% (95% CI 21% to 42%); when both were at the highest quartiles, the predicted probability was 72% (95% CI 61% to 81%). Conclusion ED crowding is associated with delayed and nonreceipt of antibiotics in the ED for patients admitted with community-acquired pneumonia.
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