No association between serotonin-2A receptor gene polymorphism and psychotic symptomatology of mood disorders.

Abnormalities of the serotonergic system are involved in the pathophysiology of mood disorders. In the present study, we investigated the possible influence of the T102C polymorphism of the serotonin-2A receptor gene (5-HT2A, 13q14-21) on the symptomatology of mood disorders. Inpatients affected by mood disorders (n = 246, 149 bipolar, 97 major depressive disorder) were assessed with a checklist of operational criteria for psychotic illness (OPCRIT) to score their lifetime psychotic symptomatology. The subjects were also typed for 5-HT2A variants using polymerase chain reaction techniques. No association was found between this polymorphism and psychopathology as defined by the four symptomatologic factors used in phenotype definition (mania, depression, delusion and disorganization). Genetic variation at the 5-HT2A receptor gene does not, therefore, appear to play a major role in the pathogenesis of major mood disorders.     

Serotonin transporter gene (5-HTTLPR) and major psychoses.

Serotoninergic neurotransmitter systems have been implicated in the pathogenesis of major psychoses. A functional polymorphism (5-HTTLPR) in the upstream regulatory region of the gene (SLC6A4) has been associated with a number of psychiatric disturbances, but conflicting replication followed. The aim of this study was to investigate the possibility that the 5-HTTLPR might be associated with major psychoses. One thousand, eight hundred and twenty inpatients (789 bipolars, 667 major depressives, 66 delusionals, 261 schizophrenics, 37 psychotics not otherwise specified-NOS) and 457 control subjects were included in this study. A subsample of 1235 patients (523 bipolars, 359 major depressives, 259 schizophrenics, 66 delusionals, 28 psychotic NOS) were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic illness (OPCRIT) checklist. The subjects were also typed for 5-HTTLPR variants using PCR techniques. 5-HTTLPR allele frequencies were not significantly different between controls and bipolars, major depressives, schizophrenics, delusionals and psychotic NOS; genotype analysis also did not show any association. The analysis of symptomatology did not show significant differences. Consideration of possible stratification factors such as sex and age of onset did not significantly influence results. 5-HTTLPR variants are not therefore a liability factor for major psychoses or for major psychoses symptomatology.     

Chest pain in daily practice: occurrence, causes and management

QUESTIONS UNDER STUDY: We assessed the occurrence and aetiology of chest pain in primary care practice. These features differ between primary and emergency care settings, where most previous studies have been performed. METHODS: 59 GPs in western Switzerland recorded all consecutive cases presenting with chest pain. Clinical characteristics, laboratory tests and other investigations as well as the diagnoses remaining after 12 months of follow-up were systematically registered. RESULTS: Among 24,620 patients examined during a total duration of 300 weeks of observation, 672 (2.7%) presented with chest pain (52% female, mean age 55 +/- 19(SD)). Most cases, 442 (1.8%), presented new symptoms and in 356 (1.4%) it was the reason for consulting. Over 40 ailments were diagnosed: musculoskeletal chest pain (including chest wall syndrome) (49%), cardiovascular (16%), psychogenic (11%), respiratory (10%), digestive (8%), miscellaneous (2%) and without diagnosis (3%). The three most prevalent diseases were: chest wall syndrome (43%), coronary artery disease (12%) and anxiety (7%). Unstable angina (6), myocardial infarction (4) and pulmonary embolism (2) were uncommon (1.8%). Potentially serious conditions including cardiac, respiratory and neoplasic diseases accounted for 20% of cases. A large number of laboratory tests (42%), referral to a specialist (16%) or hospitalisation (5%) were performed. Twentyfive patients died during follow-up, of which twelve were for a reason directly associated with thoracic pain [cancer (7) and cardiac causes (5)]. CONCLUSIONS: Thoracic pain was present in 2.7% of primary care consultations. Chest wall syndrome pain was the main aetiology. Cardio - vascular emergencies were uncommon. However chest pain deserves full consideration because of the occurrence of potentially serious conditions.     

Use of Impella Recover 2.5 left ventricular assist device in patients with cardiogenic shock or undergoing high-risk percutaneous coronary intervention procedures: experience of a high-volume center

AIM: Percutaneous coronary interventions are increasingly applied to high-risk patients. The availability of hemodynamic support devices offers a promising option to prevent and treat low-output syndrome in these patients. The aim of this study was to evaluate the feasibility, safety and efficacy of the Impella Recover' LP 2.5 left ventricular assist device in patients with cardiogenic shock or undergoing high-risk percutaneous coronary interventions. METHODS: Eleven patients presenting cardiogenic shock (N=6) or scheduled for high-risk percutaneous revascularization (N=5) were evaluated. The Impella pump was successfully implanted in all patients, except one. When implanted, the device was correctly positioned in the left ventricle and remained in a stable position. RESULTS: Bleedings occurred in 7 patients (5 of them presented cardiogenic shock), while renal failure and severe thrombocytopenia were observed in 4 and 1 patients respectively, all with cardiogenic shock. During high-risk procedures, the Impella pump succeeded in obtaining hemodynamic stability, while in only two patients with cardiogenic shock the device determined a significant improvement of hemodynamic variables. All elective patients and two patients with cardiogenic shock were discharged from the hospital and were still alive at 30-day follow-up. CONCLUSION: These data, although preliminary due to the limited sample size, demonstrated the feasibility, safety and efficacy of the Impella Recover(R) LP 2.5 during high-risk percutaneous procedures, even though the benefits of prophylactic deployment of such a system have to be further investigated. The use of Impella Recover(R) LP 2.5 in patients with cardiogenic shock is feasible and safe, however it maybe insufficient in reversing an advanced cardiogenic shock which, probably, has to be treated with more powerful left ventricular assist devices.     

Coronary heart disease in primary care: accuracy of medical history and physical findings in patients with chest pain – a study protocol for a systematic review with individual patient data

Background

Within the 52 health districts in South Africa, the family physician is seen as the clinical leader within a multi-professional district health team. Family physicians must be competent to meet 90% of the health needs of the communities in their districts. The eight university departments of Family Medicine have identified five unit standards, broken down into 85 training outcomes, for postgraduate training. The family medicine registrar must prove at the end of training that all the required training outcomes have been attained. District health managers must be assured that the family physician is competent to deliver the expected service. The Colleges of Medicine of South Africa (CMSA) require a portfolio to be submitted as part of the uniform assessment of all registrars applying to write the national fellowship examinations. This study aimed to achieve a consensus on the contents and principles of the first national portfolio for use in family medicine training in South Africa.

Methods

A workshop held at the WONCA Africa Regional Conference in 2009 explored the purpose and broad contents of the portfolio. The 85 training outcomes, ideas from the WONCA workshop, the literature, and existing portfolios in the various universities were used to develop a questionnaire that was tested for content validity by a panel of 31 experts in family medicine in South Africa, via the Delphi technique in four rounds. Eighty five content items (national learning outcomes) and 27 principles were tested. Consensus was defined as 70% agreement. For those items that the panel thought should be included, they were also asked how to provide evidence for the specific item in the portfolio, and how to assess that evidence.

Results

Consensus was reached on 61 of the 85 national learning outcomes. The panel recommended that 50 be assessed by the portfolio and 11 should not be. No consensus could be reached on the remaining 24 outcomes and these were also omitted from the portfolio. The panel recommended that various types of evidence be included in the portfolio. The panel supported 26 of the 27 principles, but could not reach consensus on whether the portfolio should reflect on the relationship between the supervisor and registrar.

Conclusion

A portfolio was developed and distributed to the eight departments of Family Medicine in South Africa, and the CMSA, to be further tested in implementation.     

Coronary heart disease in primary care: accuracy of medical history and physical findings in patients with chest pain - a study protocol for a systematic review with individual patient data

ABSTRACT: BACKGROUND: Chest pain is a common complaint in primary care, with coronary heart disease (CHD) being the most concerning of many potential causes. Systematic reviews on the sensitivity and specificity of symptoms and signs summarize the evidence about which of them are most useful in making a diagnosis. Previous meta-analyses are dominated by studies of patients referred to specialists. Moreover, as the analysis is typically based on study-level data, the statistical analyses in these reviews are limited while meta-analyses based on individual patient data can provide additional information. Our patient-level meta-analysis has three unique aims. First, we strive to determine the diagnostic accuracy of symptoms and signs for myocardial ischemia in primary care. Second, we investigate associations between study- or patient-level characteristics and measures of diagnostic accuracy. Third, we aim to validate existing clinical prediction rules for diagnosing myocardial ischemia in primary care. This article describes the methods of our study and six prospective studies of primary care patients with chest pain. Later articles will describe the main results. METHODS: We will conduct a systematic review and IPD meta-analysis of studies evaluating the diagnostic accuracy of symptoms and signs for diagnosing coronary heart disease in primary care. We will perform bivariate analyses to determine the sensitivity, specificity and likelihood ratios of individual symptoms and signs and multivariate analyses to explore the diagnostic value of an optimal combination of all symptoms and signs based on all data of all studies. We will validate existing clinical prediction rules from each of the included studies by calculating measures of diagnostic accuracy separately by study. DISCUSSION: Our study will face several methodological challenges. First, the number of studies will be limited. Second, the investigators of original studies defined some outcomes and predictors differently. Third, the studies did not collect the same standard clinical data set. Fourth, missing data, varying from partly missing to fully missing, will have to be dealt with. Despite these limitations, we aim to summarize the available evidence regarding the diagnostic accuracy of symptoms and signs for diagnosing CHD in patients presenting with chest pain in primary care. Review registration Centre for Reviews and Dissemination (University of York): CRD42011001170.