Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

Background: Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT<sub>2A</sub> receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT<sub>2A</sub>/D<sub>4</sub> antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. Method: An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. Results: The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (S.D.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). Conclusions: Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week

Diagnosing serious infections in acutely ill children in ambulatory care (ERNIE 2 study protocol, part A): diagnostic accuracy of a clinical decision tree and added value of a point-of-care C-reactive protein test and oxygen saturation

Background: Acute illness is the most common presentation of children to ambulatory care. In contrast, serious infections are rare and often present at an early stage. To avoid complications or death, early recognition and adequate referral are essential. In a recent large study children were included prospectively to construct a symptom-based decision tree with a sensitivity and negative predictive value of nearly 100%. To reduce the number of false positives, point-of-care tests might be useful, providing an immediate result at bedside. The most probable candidate is C-reactive protein, as well as a pulse oximetry. Methods: This is a diagnostic accuracy study of signs, symptoms and point-of-care tests for serious infections. Acutely ill children presenting to a family physician or paediatrician will be included consecutively in Flanders, Belgium. Children testing positive on the decision tree will get a point-of-care C-reactive protein test. Children testing negative will randomly either receive a point-of-care C-reactive protein test or usual care. The outcome of interest is hospital admission more than 24 hours with a serious infection within 10 days. Aiming to include over 6500 children, we will report the diagnostic accuracy of the decision tree (+/- the point-of-care C-reactive protein test or pulse oximetry) in sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values. New diagnostic algorithms will be constructed through classification and regression tree and multiple logistic regression analysis. Discussion: We aim to improve detection of serious infections, and present a practical tool for diagnostic triage of acutely ill children in primary care. We also aim to reduce the number of investigations and admissions in children with non-serious infections

The necessary shift from diagnostic to prognostic research

Background: Do doctors really need to establish an etiological diagnosis each time a patient presents? Or might it often be more effective to treat simply on the basis of symptoms and signs alone, relying on research and on our experience of outcomes for patients who presented in similar ways in the past? Discussion: At a time of increase health care costs especially in pharmaceuticals and expensive diagnostic tests, this article uses examples from recent research to address this question. Our examples come from general practice, because that is where doctors frequently see patients presenting with a yet undifferentiated disease which is consequently difficult to diagnose. The examples include respiratory tract infections, low back pain and shoulder pain. Finally we discuss the 'something is wrong' feeling. Summary: We conclude that, in addition to diagnostic research, a renewed focus on prognostic research is needed. </p

Chronic Diseases among Older Cancer Survivors

Objective. To compare the occurrence of pre-existing and subsequent comorbidity among older cancer patients (≥60 years) with older non-cancer patients. Material and Methods. Each cancer patient (n=3835, mean age 72) was matched with four non-cancer patients in terms of age, sex, and practice. The occurrence of chronic diseases was assessed cross-sectionally (lifetime prevalence at time of diagnosis) and longitudinally (incidence after diagnosis) for all cancer patients and for breast, prostate, and colorectal cancer patients separately. Cancer and non-cancer patients were compared using logistic and Cox regression analysis. Results. The occurrence of the most common pre-existing and incident chronic diseases was largely similar in cancer and non-cancer patients, except for pre-existing COPD (OR 1.21, 95% CI 1.06–1.37) and subsequent venous thrombosis in the first two years after cancer diagnosis (HR 4.20, 95% CI 2.74–6.44), which were significantly more frequent (P<0.01) among older cancer compared to non-cancer patients. Conclusion. The frequency of multimorbidity in older cancer patients is high. However, apart from COPD and venous thrombosis, the incidence of chronic diseases in older cancer patients is similar compared to non-cancer patients of the same age, sex, and practice

GPs' reasons for referral of patients with chest pain: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Prompt diagnosis of an acute coronary syndrome is very important and urgent referral to a hospital is imperative because fast treatment can be life-saving and increase the patient's life expectancy and quality of life. The aim of our study was to identify GPs' reasons for referring or not referring patients presenting with chest pain.</p> <p>Methods</p> <p>In a semi-structured interview, 21 GPs were asked to describe why they do or do not refer a patient presenting with chest pain. Interviews were taped, transcribed and qualitatively analysed.</p> <p>Results</p> <p>Histories of 21 patients were studied. Six were not referred, seven were referred to a cardiologist and eight to the emergency department. GPs' reasons for referral were background knowledge about the patient, patient's age and cost-benefit estimation, the perception of a negative attitude from the medical rescue team, recent patient contact with a cardiologist without detection of a coronary disease and the actual presentation of signs and symptoms, gut feeling, clinical examination and ECG results.</p> <p>Conclusion</p> <p>This study suggests that GPs believe they do not exclusively use the 'classical' signs and symptoms in their decision-making process for patients presenting with chest pain. Background knowledge about the patient, GPs' personal ideas and gut feeling are also important.</p

Diagnosing dementia: No easy job

<p>Abstract</p> <p>Background</p> <p>From both clinical experience and research we learned that in complex progressive disorders such as dementia, diagnosis includes multiple steps, each with their own clinical and research characteristics.</p> <p>Discussion</p> <p>Diagnosing starts with a trigger phase in which the GP gradually realizes that dementia may be emerging. This is followed by a disease-oriented diagnosis and subsequently a care -oriented diagnosis. In parallel the GP should consider the consequences of this process for the caregiver and the interaction between both. As soon as a comprehensive diagnosis and care plan are available, monitoring follows.</p> <p>Summary</p> <p>We propose to split the diagnostic process into four diagnostic steps, followed by a monitoring phase. We recommend to include these steps when designing studies on screening, diagnosis and monitoring of patients with dementia and their families.</p

Incident somatic comorbidity after psychosis: Results from a retrospective cohort study based on Flemish general practice data

Background: Psychotic conditions and especially schizophrenia, have been associated with increased morbidity and mortality. Many studies are performed in specialized settings with a strong focus on schizophrenia. Somatic comorbidity after psychosis is studied, using a general practice comorbidity registration network. Methods. Hazard ratios are presented resulting from frailty models to assess the risk of subsequent somatic disease after a diagnosis of psychosis compared to people without psychosis matched on practice, age and gender. Diseases studied are cancer, physical trauma, diabetes mellitus, gastrointestinal disorders, joint disorders, irritable bowel syndrome, general infections, metabolic disorders other than diabetes, hearing and vision problems, anemia, cardiovascular disease, alcohol abuse, lung disorders, mouth and teeth problems, sexually transmitted diseases. Results: Significant higher risks after a diagnosis of psychosis were found for the emergence of diabetes, physical trauma, gastrointestinal disorders, alcohol abuse, chronic lung disease and teeth and mouth problems. With regard to diabetes, by including the type of antipsychotic medication it is clear that the significant overall effect was largely due to the use of atypical antipsychotic medication. No significant higher risk was seen for cancer, joint conditions, irritable bowel syndrome, general infections, other metabolic conditions, hearing/vision problems, anaemia, cardiovascular disease or diabetes, in case no atypical antipsychotic medication was used. Conclusion: Significantly higher morbidity rates for some somatic conditions in patients with psychosis are apparent. People with a diagnosis of psychosis benefit from regular assessments for the emergence of somatic disorders and risk factors, including diabetes in case of atypical antipsychotic medication