Lower respiratory tract infection in the community: associations between viral aetiology and illness course.

OBJECTIVES: This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection. METHODS: A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed. RESULTS: The PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65-0.96) and hMPV infections (AHR 0.77, 95% CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration. CONCLUSIONS: In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.

Training general practitioners to improve evidence-based drug treatment of patients with heart failure: a cluster randomised controlled trial.

AIMS: To assess whether a single training session for general practitioners (GPs) improves the evidence-based drug treatment of heart failure (HF) patients, especially of those with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: A cluster randomised controlled trial was performed for which patients with established HF were eligible. Primary care practices (PCPs) were randomised to care-as-usual or to the intervention group in which GPs received a half-day training session on HF management. Changes in HF medication, health status, hospitalisation and survival were compared between the two groups. Fifteen PCPs with 200 HF patients were randomised to the intervention group and 15 PCPs with 198 HF patients to the control group. Mean age was 76.9 (SD 10.8) years; 52.5% were female. On average, the patients had been diagnosed with HF 3.0 (SD 3.0) years previously. In total, 204 had HFrEF and 194 HF with preserved ejection fraction (HFpEF). In participants with HFrEF, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased in 6 months in both groups [5.2%; (95% confidence interval (CI) 2.0-10.0)] and 5.6% (95% CI 2.8-13.4)], respectively [baseline-corrected odds ratio (OR) 1.07 (95% CI 0.55-2.08)], while beta-blocker use increased in both groups by 5.2% (95% CI 2.0-10.0) and 1.1% (95% CI 0.2-6.3), respectively [baseline-corrected OR 0.82 (95% CI 0.42-1.61)]. For health status, hospitalisations or survival after 12-28 months there were no significant differences between the two groups, also not when separately analysed for HFrEF and HFpEF. CONCLUSION: A half-day training session for GPs does not improve drug treatment of HF in patients with established HF.

Physical activity levels of women with breast cancer during and after treatment, a comparison with the Dutch female population.

Background: Physical activity has been shown to reduce side-effects of breast cancer and its treatment. As physical activity levels of patients with breast cancer are largely unknown, we investigated these levels and compared them to women from the general population. Methods: In this prospective cohort study, physical activity levels of women with breast cancer participating in the UMBRELLA cohort were assessed at radiotherapy intake and thereafter every 6 months up to 3 years with the SQUASH questionnaire, which was also used in a random sample of the Dutch population. We compared physical activity levels (no activity, low, moderate or high levels of sports, leisure time or total activity) between patients and the Dutch female population using multinomial logistic regression. Standardized Prevalence Ratios (SPR) were calculated to compare adherence to Dutch physical activity guidelines. Results: Women with breast cancer (nbaseline = 1655, n6 months = 1414, n12 months = 1186, n18 months = 957, n24 months = 744, n30 months = 555, and n36 months = 377) were less likely to spend time in physical activity compared to the general population (n = 11,710) until 3 years post-diagnosis, especially after 6 months (ORhigh-vs.-no activity = 0.34, 95% CI: 0.28-0.41). From 12 months onwards, patients were more likely to perform sports compared to the general population, especially patients who underwent systemic therapy. Guideline adherence was significantly lower in patients at baseline and 6 months (SPRbaseline = 89, 95% CI: 82-97; SPR6 months = 88, 95% CI: 81-96), and comparable to the general population at 12-36 months, especially in older women. Conclusions: Physical activity levels in women with breast cancer during and after treatment were lower compared to the Dutch female population. Three years post-treatment, they were still less physically active, although they spend more time in sport activities. As about half of the patients did not perform any sports, physical activity needs to be stimulated during and after treatment.

Disability in the Individual ADL, IADL, and Mobility among Older Adults: A Prospective Cohort Study.

OBJECTIVES: To examine the risk of disability in 15 individual ADL, IADL, and mobility in older adults by age; and to assess the association of multimorbidity, gender, and education with disability. DESIGN AND SETTING: A prospective cohort study. The sample included 805 community-dwelling older people aged 60+ living in the Netherlands. MEASUREMENTS: Disability was assessed using the Katz-15 Index of Independence in Basic Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and one mobility item. Disability in any of these activities was defined as the inability to perform the activity without assistance. The risk of disability by age for each individual ADL, IADL, and for mobility was assessed using Generalized mixed models. RESULTS: Disability in activities as household tasks, traveling, shopping, and continence had the highest risk and increased rapidly with age. The risk traveling disability among people aged 65 with two comorbidities increase from 9% to 37% at age 85. Disability in using the telephone, managing medications, finances, transferring, and toileting, had a very low risk and hardly increased with age. Compared to those without chronic conditions, those with ≥ 3 chronic conditions had a 3 to 5 times higher risk of developing disability. Males had a higher risk of disability in managing medication (P=0.005), and preparing meals (P=0.019), whereas females had a higher risk of disability with traveling (P=0.001). No association between education and disability on the individual ADL, IADL, and mobility was observed. CONCLUSIONS: Older adults were mostly disabled in physical related activities, whereas disability in more cognitive related activities was less often experienced. The impact of multimorbidity on disability in each activity was substantial, while education was not.

Hippocampal volume and the course of depressive symptoms over eight years of follow-up.

OBJECTIVE: To estimate the association between hippocampal and total brain volume and the course of depressive symptoms over eight years of follow-up in patients with a history of vascular disease. METHOD: Within the SMART-Medea study, 636 participants (62 ± 10 years) had a 1.5-tesla brain MRI obtaining hippocampal and total brain volumes. Depressive symptoms were assessed with the Patient Health Questionnaire-9 biannually during eight-year follow-up. Generalized estimating equation models with robust standard errors were used to assess the associations of hippocampal and total brain volumes with depressive symptoms during follow-up adjusting for age, sex, education, and intracranial volume. An interaction term between volume and time (6-month intervals) was included to examine whether the course of depressive symptoms differed according to hippocampal and total brain volume. RESULTS: The mean PHQ-9 score was 2.8 ± 3.5. Smaller hippocampal volumes were associated with an increasing course of depressive symptom levels, while larger volumes were associated with decreasing levels (P-value interaction = 0.07). Smaller total brain volume was associated with consistently higher levels of depressive symptoms, but not with change in course of depressive symptoms (P-value interaction = 0.45). CONCLUSION: Smaller hippocampal volume but not total brain volume is associated with poorer course of depressive symptoms over eight years of follow-up.

Does integrated training in evidence-based medicine (EBM) in the general practice (GP) specialty training improve EBM behaviour in daily clinical practice? A cluster randomised controlled trial.

OBJECTIVES: Evidence-based medicine (EBM) is an important element in the general practice (GP) specialty training. Studies show that integrating EBM training into clinical practice brings larger benefits than stand-alone modules. However, these studies have neither been performed in GP nor assessed EBM behaviour of former trainees in daily clinical practice. SETTING: GP specialty training in the Netherlands. PARTICIPANTS: All 82 third year GP trainees who started their final third year in 2011 were approached for inclusion, of whom 79 (96%) participated: 39 in the intervention group and 40 in the control group. INTERVENTION: Integrated EBM training, in which EBM is embedded closely within the clinical context by joint assignments for the trainee and supervisor in daily practice, and teaching sessions based on dilemmas from actual patient consultations. COMPARISON: Stand-alone EBM training at the institute only. PRIMARY AND SECONDARY OUTCOMES: Our primary outcome was EBM behaviour, assessed by measuring guideline adherence (incorporating rational, motivated deviation) and information-seeking behaviour. Our secondary outcomes were EBM attitude and EBM knowledge. Data were acquired using logbooks and questionnaires, respectively. Analyses were performed using mixed models. RESULTS: Logbook data were available from 76 (96%) of the participating trainees at baseline (7614 consultations), 60 (76%) at the end of the third year (T1, 4973 consultations) and 53 (67%) 1 year after graduation (T2, 3307 consultations). We found no significant differences in outcomes between the 2 groups, with relative risks for guideline adherence varying between 0.96 and 0.99 (95% CI 0.86 to 1.11) at T1, and 0.99 and 1.10 (95% CI 0.92 to 1.25) at T2, and for information-seeking behaviour between 0.97 and 1.16 (95% CI 0.70 to 1.91) and 0.90 and 1.10 (95% CI 0.70 to 1.32), respectively. CONCLUSIONS: Integrated EBM training compared with stand-alone EBM training does not improve EBM behaviour, attitude or knowledge of (future) GPs.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Cognitive performance and the course of depressive symptoms over 7 years of follow-up: the SMART-MR study.

BACKGROUND: Depressive symptoms and cognitive impairment often co-occur, but their interactive relationship is complex and the direction of causation is still a topic of research. We examined the influence of cognitive performance on the course of depressive symptoms during 7 years of follow-up in patients with vascular disease. METHOD: Within the SMART-MR study, 736 patients (mean age 62 ± 10 years) had neuropsychological assessment on four cognitive domains at baseline [memory (MEM), working memory (WMEM), executive functioning (EXEC), and information processing speed (SPEED)]. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline and every 6 months during 7 years of follow-up. Generalized Estimating Equation (GEE) models were used to assess the association between cognitive performance with depressive symptoms at multiple time points during follow-up. Interaction terms between the respective cognitive domains and time was included to examine if the course of depressive symptoms differed according to baseline cognitive performance. RESULTS: The GEE analyses showed no significant interactions between the respective cognitive domains and time indicating no different course of depressive symptoms according to baseline cognitive performance. Lower MEM, EXEC or SPEED, but not WMEM performance, was significantly associated with more depressive symptoms during follow-up per z score decrease: MEM [B = 0.70, 95% confidence interval (CI) 0.35-1.05]; EXEC (B = 0.88, 95% CI 0.41-1.36), and SPEED (B = 0.57, 95% CI 0.21-0.92). CONCLUSIONS: Poorer cognitive performance on the domains MEM, EXEC and SPEED, but not WMEM, was associated with higher levels of depressive symptoms over 7 years of follow-up, but not with a different course of depressive symptoms over time.

Validity and reliability of the Katz-15 scale to measure unfavorable health outcomes in community-dwelling older people.

OBJECTIVES: To predict the risk of future unfavourable health outcomes in older people it is common to assess the level of both basic and instrumental activities of daily living. To accomplish this, the commonly used Katz-6 and the Lawton IADL questionnaires can be combined to form the 'Modified Katz ADL' scale, also known as the Katz-15 scale. So far, the validity and reliability of the Katz-15 scale is unknown. The objective of the current study is to investigate how well the Katz-15 is able to predict future unfavorable health outcomes and how this is related to the existing Katz-6 scale. DESIGN: We performed a follow-up study using data from a group of 60 year and older participants from a large Dutch clinical trial. PARTICIPANTS: We included 2321 participants in the analysis. The average age of the study population was 74 years and 44% was male. MEASUREMENTS: We studied the relation between the Katz-15 scale and a number of unfavourable health outcomes, such as hospitalization, admission to a nursing home, admission to a home for the aged and death within one year of follow-up. RESULTS: We found the Katz-15 to be both internally consistent and strongly associated with quality of life measures. We observed moderate to strong associations between the Katz-15 and the unfavourable health outcomes All associations studied were stronger for the Katz-15 scale as compared to the Katz-6 scale. CONCLUSION: The results of our study indicate that the Katz-15 scale is able to reliably and validly predict future unfavorable health outcomes. This makes the scale a valuable measure in determining both basic and instrumental activities of daily living.

Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis.

OBJECTIVE: To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. DESIGN: Meta-analysis of individual patient data. DATA SOURCES: Authors of 13 studies (n = 10,002) provided their datasets, and these individual patient data were merged into one dataset. ELIGIBILITY CRITERIA: Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard. MAIN OUTCOME MEASURES: Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result. RESULTS: Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤ 1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe. CONCLUSION: Combined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.

[Attrition and poor performance in general practice training: age, competence and knowledge play a role]. / Uitval en stagnatie in de opleiding tot huisarts. Leeftijd, competenties en kennis spelen een rol.

OBJECTIVE: To investigate which determinants are related to poor performance and forced attrition in the first year residency in general practice (GP). DESIGN: Observational retrospective cohort study. METHOD: We collected data relating to personal characteristics such as age, sex and clinical experience from residents who started the GP training in Utrecht, the Netherlands, in the period March 2005-August 2007. We also collected competence scores from the domains 'medical expertise', 'doctor-patient communication' and 'professionalism', as well as scores on a national GP knowledge test. The outcome measures were 'poor performance' and 'forced attrition'. Multivariate logistic regression was used to analyse correlations between personal characteristics, competence scores on the 3 domains and knowledge scores in the first trimester on the one hand and poor performance or forced attrition on the other. RESULTS: 215 residents started the GP training. In the first trimester a quarter of the residents had an insufficient score in 1 or more of the domains. Competence scores were mutually correlated, but did not correlate with the knowledge score. 18 residents showed poor performance and 3 were forced to stop their training. Poor performance and forced attrition were correlated with age (adjusted odds ratio (OR): 1.1; 95% CI: 1.0-1.3), insufficient knowledge (adjusted OR: 8.9; 3.0-26.3) and medical expertise (adjusted OR: 2.1; 1.1-4.0) at the beginning of the training. CONCLUSION: Age, insufficient knowledge of general practice, and insufficient competence in the domain of 'medical expertise' at the beginning of the training are risk factors for poor performance by residents and attrition from their GP training.

Meta-analysis of the diagnostic accuracy of transesophageal echocardiography for assessment of atherosclerosis in the ascending aorta in patients undergoing cardiac surgery.

BACKGROUND: Stroke after cardiac surgery may be caused by emboli emerging from an atherosclerotic ascending aorta (AA). Epiaortic ultrasound scanning (EUS), the current 'gold' standard for detecting AA atherosclerosis, has not gained widespread use because there is a lack of optimized ultrasound devices, it lengthens the procedure, it endangers sterility, and there is a false belief by many surgeons that palpation is as sensitive as EUS. Furthermore there is no clear evidence proving that the use of epiaortic scanning changes outcome in cardiac surgery. Various researchers investigated the ability of transesophageal echocardiography (TEE) to discriminate between the presence and absence of AA atherosclerosis. It is acknowledged that TEE has limited value in this, but it has never been supported by a meta-analysis estimating the true diagnostic accuracy of TEE based on all quantitative evidence. We aimed to do this using state-of-the-art methodology of diagnostic meta-analyses. METHODS: We searched multiple databases for studies comparing TEE vs. EUS for detection of atherosclerosis. A random-effects bivariate meta-regression model was used to obtain summary estimates of sensitivity and specificity, incorporating the correlation between sensitivity and specificity as well as covariates to explore heterogeneity across studies. RESULTS: We extracted six studies with a total of 346 patients, of whom 419 aortic segments were analyzed, including 100 segments with atherosclerosis [median prevalence 25% (range 17-62%)]. Summary estimates of sensitivity and specificity were 21% (95% CI 13-32%) and 99% (96-99%), respectively. CONCLUSIONS: Because of the low sensitivity of TEE for the detection of AA atherosclerosis, a negative test result requires verification by additional testing using epiaortic scanning. In case of a positive test result, AA atherosclerosis can be considered as present, and less manipulative strategies might be indicated.

Long-term effects of self-management education for patients with Type 2 diabetes taking maximal oral hypoglycaemic therapy: a randomized trial in primary care.

AIMS: Education is an essential part of the management of patients with Type 2 diabetes, but the long-term effects are unclear and not well investigated in primary care. METHODS: Fifty-four patients (39-75 years) treated with maximal dosages of oral hypoglycaemic agents, needing to start insulin (HbA(1c)> or = 7.0%), were randomly allocated to a 6-month educational programme by a diabetes nurse (DN group) or usual care (UC group). Main outcome measures were HbA(1c), number of patients with HbA(1c) < 7.0%, and number of patients treated with insulin 18 months after baseline. RESULTS: Six weeks after the intervention HbA(1c) levels had improved from 8.2 (1.1) to 7.2 (1.3) in the DN group, and from 8.8 (1.5) to 8.4 (1.7) in the UC group. Adjusted for baseline values, at 6 weeks HbA(1c) improved 0.7% (95% confidence interval 0.1, 1.4) more in DN than in UC. Of the patients in DN, 60% reached HbA(1c) < 7.0% compared with 17% in UC (P < 0.01). However, at 18 months there were no significant differences for HbA(1c), number of patients with HbA(1c) < 7.0%, or number treated with insulin. CONCLUSIONS: Education was effective in improving glycaemic control and in delaying the need for insulin therapy in patients treated with maximal oral hypoglycaemic therapy. The reduced effect after 1 year was probably due to the discontinuation of the educational programme. Short-term education should not be offered without regular reinforcements integrated into standard diabetes care.