Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [18F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [18F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [18F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen's d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence-a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established

Improving education in primary care: development of an online curriculum using the blended learning model

<p>Abstract</p> <p>Background</p> <p>Standardizing the experiences of medical students in a community preceptorship where clinical sites vary by geography and discipline can be challenging. Computer-assisted learning is prevalent in medical education and can help standardize experiences, but often is not used to its fullest advantage. A blended learning curriculum combining web-based modules with face-to-face learning can ensure students obtain core curricular principles.</p> <p>Methods</p> <p>This course was developed and used at The Case Western Reserve University School of Medicine and its associated preceptorship sites in the greater Cleveland area. Leaders of a two-year elective continuity experience at the Case Western Reserve School of Medicine used adult learning principles to develop four interactive online modules presenting basics of office practice, difficult patient interviews, common primary care diagnoses, and disease prevention. They can be viewed at <url>http://casemed.case.edu/cpcp/curriculum</url>. Students completed surveys rating the content and technical performance of each module and completed a Generalist OSCE exam at the end of the course.</p> <p>Results</p> <p>Participating students rated all aspects of the course highly; particularly those related to charting and direct patient care. Additionally, they scored very well on the Generalist OSCE exam.</p> <p>Conclusion</p> <p>Students found the web-based modules to be valuable and to enhance their clinical learning. The blended learning model is a useful tool in designing web-based curriculum for enhancing the clinical curriculum of medical students.</p

A decision aid to rule out pneumonia and reduce unnecessary prescriptions of antibiotics in primary care patients with cough and fever

BACKGROUND: Physicians fear missing cases of pneumonia and treat many patients with signs of respiratory infection unnecessarily with antibiotics. This is an avoidable cause for the increasing worldwide problem of antibiotic resistance. We developed a user-friendly decision aid to rule out pneumonia and thus reduce the rate of needless prescriptions of antibiotics. METHODS: This was a prospective cohort study in which we enrolled patients older than 18 years with a new or worsened cough and fever without serious co-morbidities. Physicians recorded results of a standardized medical history and physical examination. C-reactive protein was measured and chest radiographs were obtained. We used Classification and Regression Trees to derive the decision tool. RESULTS: A total of 621 consenting eligible patients were studied, 598 were attending a primary care facility, were 48 years on average and 50% were male. Radiographic signs for pneumonia were present in 127 (20.5%) of patients. Antibiotics were prescribed to 234 (48.3%) of patients without pneumonia. In patients with C-reactive protein values below 10 μg/ml or patients presenting with C-reactive protein between 11 and 50 μg/ml, but without dyspnoea and daily fever, pneumonia can be ruled out. By applying this rule in clinical practice antibiotic prescription could be reduced by 9.1% (95% confidence interval (CI): 6.4 to 11.8). CONCLUSIONS: Following validation and confirmation in new patient samples, this tool could help rule out pneumonia and be used to reduce unnecessary antibiotic prescriptions in patients presenting with cough and fever in primary care. The algorithm might be especially useful in those instances where taking a medical history and physical examination alone are inconclusive for ruling out pneumonia

Faculty verbal evaluations reveal strategies used to promote medical student performance

Background: Preceptors rarely follow medical students&#x2019; developing clinical performance over time and across disciplines. This study analyzes preceptors&#x2019; descriptions of longitudinal integrated clerkship (LIC) students&#x2019; clinical development and their identification of strategies to guide students&#x2019; progress. Methods: We used a common evaluation framework, reporter-interpreter-manager-educator, to guide multidisciplinary LIC preceptors&#x2019; discussions of students&#x2019; progress. We conducted thematic analysis of transcripts from preceptors&#x2019; (seven longitudinal ambulatory preceptors per student) quarterly group discussions of 15 students&#x2019; performance over one year. Results: All students&#x2019; clinical development progressed, although most experienced obstacles. Lack of structure in the history and physical exam commonly obstructed progression. Preceptors used templates for data gathering, and modeling or experiences in the inpatient setting to provide time and solidify structure. To advance students&#x2019; knowledge acquisition, many preceptors identified focused learning topics with their students; to promote application of knowledge, preceptors used reasoning strategies to teach the steps involved in synthesizing clinical data. Preceptors shared accountability for helping students advance as the LIC allowed them to follow students&#x2019; response to teaching strategies. Discussion: These results depict preceptors&#x2019; perceptions of LIC students&#x2019; developmental continuum and illustrate how multidisciplinary preceptors can use a common evaluation framework to identify strategies to improve performance and follow students&#x2019; performance longitudinally

Health Alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT) -impact of a non-randomised multifaceted intervention programme

<p>Abstract</p> <p>Background</p> <p>Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance.</p> <p>Methods</p> <p>GPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention.</p> <p>Results</p> <p>A total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%.</p> <p>Conclusion</p> <p>A multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.</p

Health Alliance for Prudent Prescribing, Yield and Use of Antimicrobial Drugs in the Treatment of Respiratory Tract Infections (HAPPY AUDIT)

<p>Abstract</p> <p>Background</p> <p>Excessive and inappropriate use of antibiotics is considered to be the most important reason for development of bacterial resistance to antibiotics. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries.</p> <p>The majority of respiratory tract infections (RTIs) are treated in general practice. Most infections are caused by virus and antibiotics are therefore unlikely to have any clinical benefit. Several intervention initiatives have been taken to reduce the inappropriate use of antibiotics in primary health care, but the effectiveness of these interventions is only modest. Only few studies have been designed to determine the effectiveness of multifaceted strategies in countries with different practice setting. The aim of this study is to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different prevalence of antibiotic resistance: Two Nordic countries (Denmark and Sweden), two Baltic Countries (Lithuania and Kaliningrad-Russia) and two Hispano-American countries (Spain and Argentina).</p> <p>Methods/Design</p> <p>HAPPY AUDIT was initiated in 2008 and the project is still ongoing. The project includes 15 partners from 9 countries. GPs participating in HAPPY AUDIT will be audited by the Audit Project Odense (APO) method. The APO method will be used at a multinational level involving GPs from six countries with different cultural background and different organisation of primary health care. Research on the effect of the intervention will be performed by analysing audit registrations carried out before and after the intervention. The intervention includes training courses on management of RTIs, dissemination of clinical guidelines with recommendations for diagnosis and treatment, posters for the waiting room, brochures to patients and implementation of point of care tests (Strep A and CRP) to be used in the GPs'surgeries.</p> <p>To ensure public awareness of the risk of resistant bacteria, media campaigns targeting both professionals and the public will be developed and the results will be published and widely disseminated at a Working Conference hosted by the World Association of Family Doctors (WONCA-Europe) at the end of the project period.</p> <p>Discussion</p> <p>HAPPY AUDIT is an EU-financed project with the aim of contributing to the battle against antibiotic resistance through quality improvement of GPs' diagnosis and treatment of RTIs through development of intervention programmes targeting GPs, parents of young children and healthy adults. It is hypothesized that the use of multifaceted strategies combining active intervention by GPs will be effective in reducing prescribing of unnecessary antibiotics for RTIs and improving the use of appropriate antibiotics in suspected bacterial infections.</p

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice

Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers

Background: Drug addiction is associated with significant disease and death, but its impact on the ageing process has not been considered. The recent demonstration that many of the items available in routine clinical pathology have applicability as biomarkers of the ageing process implies that routine clinical laboratory parameters would be useful as an initial investigation of this possibility. Methods: 12,093 clinical laboratory results 1995-2006 were reviewed. To make the age ranges of the medical and addicted groups comparable the age range was restricted to 15-45 years. Results: 739 drug addicted (DA) and 5834 general medical (GM) age matched blood samples were compared. Significant elevation of immune parameters was noted in the C-reactive protein, erythrocyte sedimentation rate, total lymphocyte count, serum globulins and the globulin:albumin ratio (P < 0.01). Alanine aminotranferase, creatinine, urea, and insulin like growth factor-1 were also significantly higher (P < 0.01) in the DA group. Albumin, body mass index and dihydroepiandrosterone sulphate were unchanged and cholesterol was lower (all P < 0.05). Conclusion: These data demonstrate for the first time that addiction is associated with an altered profile of common biomarkers of ageing raising the possibility that the ageing process may be altered in this group. Infective and immune processes may be centrally involved. They suggest that addiction forms an interesting model to further examine the contribution of immune suppression and hyperstimulation to the ageing process