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Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) often remain undiagnosed in older individuals, although both disorders inhibit functionality and impair health. The aim of the study was to assess the effectiveness of a case-finding strategy of these disorders. Methods This is a clustered randomized trial; 18 general practices from the vicinity of Utrecht, the Netherlands, were randomly allocated to a case-finding strategy or usual care. Multimorbid community subjects (≥65 years) with dyspnea or reduced exercise tolerance were eligible for inclusion. The case-finding strategy consisted of history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. Subsequent treatment decisions were at the discretion of the general practitioner. Questionnaires regarding health status and functionality were filled out at baseline and after 6 months of follow-up. Information regarding changes in medication and health care use during the 6 months follow-up was extracted. Results A total of 829 participants were randomized: 389 in the case-finding strategy group and 440 in the usual care group. More patients in the case-finding group received a new diagnosis of HF or COPD than the usual care group (cumulative incidence 34% vs 2% and 17% vs. 2%, respectively). Scores for health status, functionality, and health care use were similar between the 2 strategies after 6 months of follow-up. Conclusions A case-finding strategy applied in primary care to multimorbid older people with dyspnea or reduced exercise tolerance resulted in a number of new diagnoses of HF and COPD but did not result in short-term improvement of health status compared to usual care.

Background The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. Design Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction Methods Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. Results Increased age and β-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60–0.75) and women (c-statistics range 0.51–0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61–0.80 in women and 0.68–0.80 in men). Conclusions We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions.

Background: Reduced exercise tolerance and dyspnea are common in older people, and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the main causes. We want to determine the prevalence of previously unrecognized HF, COPD, and other chronic diseases in frail older people using a nearhome targeted screening strategy. Methods: Community-dwelling frail persons aged >65 years underwent a 2-step screening strategy. First, they received a questionnaire inquiring about dyspnea and exercise tolerance. Those with exercise intolerance and/or dyspnea were invited to visit their primary care physician’s office for a screening program, including medical history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. The final diagnosis of every patient was determined by a panel consisting of 3 physicians. Results:tk;2 Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127 (33.5%, 95% confidence interval, 28.9 –38.4%) were newly diagnosed with HF (mainly HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD was detected in 16.8% (95% confidence interval, 13.4 – 20.9%). In total, 165 patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new diagnoses (in 32.7% of the screening program patients) included atrial fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of 47 patients (12.2%) was found using our strategy. Conclusion: Unrecognized chronic diseases might be detected in community-dwelling frail elderly using a near-home screening strategy that is simple to implement. It remains to be proven, however, whether optimizing treatment of the newly detected diagnoses in this fragile population with multimorbidities and polypharmacy improves quality of life and reduces morbidity and mortality. (J Am Board Fam Med 2014;27:811– 821.)

Background: chronic dyspnoea is common in older people and is often of cardiac or pulmonary aetiology. Information on the exact prevalence and distribution of underlying causes is scarce. Our aim was to review the literature on prevalence and underlying causes of dyspnoea in the older population. Methods: two MEDLINE searches were conducted: the first on studies on the prevalence of dyspnoea in older persons aged ≥65 years using the Medical Research Council (MRC) dyspnoea scale and the second on the underlying causes of dyspnoea in this population. Quality assessment was performed for all included studies. Random effects models based on the logit transformed prevalences were used to calculate pooled prevalence with 95% confidence intervals (95% CI). Results: a total of 21 articles from 20 different populations reported the prevalence in the general older population with a median sample size of 600 (Interquartile range 262–1289). The pooled prevalence was 36% (95% CI: 27–47%) for an MRC of ≥2, 16% (95% CI: 12–21%) for an MRC of ≥3 and 4% (95% CI: 2–9%) for an MRC of ≥4. Prevalence rates were higher in women than in men. Only one article investigated the underlying causes of dyspnoea in older persons; in 70% of these patients, the dyspnoea was considered to be of cardiac or pulmonary origin. Conclusion: dyspnoea is very common in older people, but estimates vary considerably between studies. Only one study describes the underlying causes.

OBJECTIVES: We developed a nomogram to facilitate the interpretation and presentation of results from multinomial logistic regression models. STUDY DESIGN AND SETTING: We analyzed data from 376 frail elderly with complaints of dyspnea. Potential underlying disease categories were heart failure (HF), chronic obstructive pulmonary disease (COPD), the combination of both (HF and COPD), and any other outcome (other). A nomogram for multinomial model was developed to depict the relative importance of each predictor and to calculate the probability for each disease category for a given patient. Additionally, model performance of the multinomial regression model was assessed. RESULTS: Prevalence of HF and COPD was 14% (n = 54), HF 24% (n = 90), COPD 20% (n = 75), and Other 42% (n = 157). The relative importance of the individual predictors varied across these disease categories or was even reversed. The pairwise C statistics ranged from 0.75 (between HF and Other) to 0.96 (between HF and COPD and Other). The nomogram can be used to rank the disease categories from most to least likely within each patient or to calculate the predicted probabilities. CONCLUSIONS: Our new nomogram is a useful tool to present and understand the results of a multinomial regression model and could enhance the applicability of such models in daily practice.

ObjectiveHeart failure (HF) often coexists in atrial fibrillation (AF) but is frequently unrecognised due to overlapping symptomatology. Furthermore, AF can cause elevated natriuretic peptide levels, impairing its diagnostic value for HF detection. We aimed to assess the prevalence of previously unknown HF in community-dwelling patients with AF, and to determine the diagnostic value of the amino-terminal pro B-type natriuretic peptide (NTproBNP) for HF screening in patients with AF.MethodsIndividual participant data from four HF-screening studies in older community-dwelling persons were combined. Presence or absence of HF was in each study established by an expert panel following the criteria of the European Society of Cardiology. We performed a two-stage patient-level meta-analysis to calculate traditional diagnostic indices.ResultsOf the 1941 individuals included in the four studies, 196 (10.1%) had AF at baseline. HF was uncovered in 83 (43%) of these 196 patients with AF, versus 381 (19.7%) in those without AF at baseline. Median NTproBNP levels of patients with AF with and without HF were 744 pg/mL and 211 pg/mL, respectively. At the cut-point of 125 pg/mL, sensitivity was 93%, specificity 35%, and positive and negative predictive values 51% and 86%, respectively. Only 23% of all patients with AF had an NTproBNP level below the 125 pg/mL cut-point, with still a 13% prevalence of HF in this group.ConclusionsWith a prevalence of nearly 50%, unrecognised HF is common among community-dwelling patients with AF. Given the high prior change, natriuretic peptides are diagnostically not helpful, and straightforward echocardiography seems to be the preferred strategy for HF screening in patients with AF.

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64–0.76) to 0.82 (95% CI 0.78–0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70–0.81) to 0.89 (95% CI 0.86–0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.

It is uncertain whether screening of older persons for chronic obstructive pulmonary disease (COPD) is worthwhile because the effects on patient management and prognosis are unknown.We aimed to assess the short-term consequences of detecting COPD in frail elderly subjects with dyspnoea, considering pulmonary drug use, hospitalisations and all-cause mortality.Community-dwelling frail elderly subjects, aged 65 years and older, with dyspnoea, participating in a screening study on COPD and heart failure were included. Final diagnoses were assigned by an expert panel based on all data from the screening strategy, including spirometry. Follow-up data were collected from the general practitioners.Of the 386 patients, 84 (21.8%) were received a new diagnosis of COPD. Overall, changes in pulmonary drug prescription during 6 months of follow-up were infrequent (n = 53, 13.7%; among new cases of COPD, 15 (17.9%) out of 84). Of all participants, 25.9% were hospitalised in the first year of follow-up, with the highest rate in patients with newly detected COPD (32.1%).Many new cases of COPD could be detected by screening frail elderly subjects with dyspnoea, but the impact on patient management seems limited. Our study underlines the importance of obtaining follow-up data to assess the true impact of a (screen-detected) diagnosis of COPD on patient management and outcome.

Loes C. M. Bertens and colleagues survey the published diagnostic research literature for use of expert panels to define the reference standard, characterize components and missing information, and recommend elements that should be reported in diagnostic studies. Please see later in the article for the Editors' Summary, Background In diagnostic studies, a single and error-free test that can be used as the reference (gold) standard often does not exist. One solution is the use of panel diagnosis, i.e., a group of experts who assess the results from multiple tests to reach a final diagnosis in each patient. Although panel diagnosis, also known as consensus or expert diagnosis, is frequently used as the reference standard, guidance on preferred methodology is lacking. The aim of this study is to provide an overview of methods used in panel diagnoses and to provide initial guidance on the use and reporting of panel diagnosis as reference standard. Methods and Findings PubMed was systematically searched for diagnostic studies applying a panel diagnosis as reference standard published up to May 31, 2012. We included diagnostic studies in which the final diagnosis was made by two or more persons based on results from multiple tests. General study characteristics and details of panel methodology were extracted. Eighty-one studies were included, of which most reported on psychiatry (37%) and cardiovascular (21%) diseases. Data extraction was hampered by incomplete reporting; one or more pieces of critical information about panel reference standard methodology was missing in 83% of studies. In most studies (75%), the panel consisted of three or fewer members. Panel members were blinded to the results of the index test results in 31% of studies. Reproducibility of the decision process was assessed in 17 (21%) studies. Reported details on panel constitution, information for diagnosis and methods of decision making varied considerably between studies. Conclusions Methods of panel diagnosis varied substantially across studies and many aspects of the procedure were either unclear or not reported. On the basis of our review, we identified areas for improvement and developed a checklist and flow chart for initial guidance for researchers conducting and reporting of studies involving panel diagnosis. Please see later in the article for the Editors' Summary, Editors' Summary Background Before any disease or condition can be treated, a correct diagnosis of the condition has to be made. Faced with a patient with medical problems and no diagnosis, a doctor will ask the patient about their symptoms and medical history and generally will examine the patient. On the basis of this questioning and examination, the clinician will form an initial impression of the possible conditions the patient may have, usually with a most likely diagnosis in mind. To support or reject the most likely diagnosis and to exclude the other possible diagnoses, the clinician will then order a series of tests and diagnostic procedures. These may include laboratory tests (such as the measurement of blood sugar levels), imaging procedures (such as an MRI scan), or functional tests (such as spirometry, which tests lung function). Finally, the clinician will use all the data s/he has collected to reach a firm diagnosis and will recommend a program of treatment or observation for the patient. Why Was This Study Done? Researchers are continually looking for new, improved diagnostic tests and multivariable diagnostic models—combinations of tests and characteristics that point to a diagnosis. Diagnostic research, which assesses the accuracy of new tests and models, requires that each patient involved in a diagnostic study has a final correct diagnosis. Unfortunately, for most conditions, there is no single, error-free test that can be used as the reference (gold) standard for diagnosis. If an imperfect reference standard is used, errors in the final disease classification may bias the results of the diagnostic study and may lead to a new test being adopted that is actually less accurate than existing tests. One widely used solution to the lack of a reference standard is “panel diagnosis” in which two or more experts assess the results from multiple tests to reach a final diagnosis for each patient in a diagnostic study. However, there is currently no formal guidance available on the conduct and reporting of panel diagnosis. Here, the researchers undertake a systematic review (a study that uses predefined criteria to identify research on a given topic) to provide an overview of the methodology and reporting of panel diagnosis. What Did the Researchers Do and Find? The researchers identified 81 published diagnostic studies that used panel diagnosis as a reference standard. 37% of these studies reported on psychiatric diseases, 21% reported on cardiovascular diseases, and 12% reported on respiratory diseases. Most of the studies (64%) were designed to assess the accuracy of one or more diagnostic test. Notably, one or more critical piece of information on methodology was missing in 83% of the studies. Specifically, information on the constitution of the panel was missing in a quarter of the studies and information on the decision-making process (whether, for example, a diagnosis was reached by discussion among panel members or by combining individual panel member's assessments) was incomplete in more than two-thirds of the studies. In three-quarters of the studies for which information was available, the panel consisted of only two or three members; different fields of expertise were represented in the panels in nearly two-thirds of the studies. In a third of the studies for which information was available, panel members made their diagnoses without access to the results of the test being assessed. Finally, the reproducibility of the decision-making process was assessed in a fifth of the studies. What Do These Findings Mean? These findings indicate that the methodology of panel diagnosis varies substantially among diagnostic studies and that reporting of this methodology is often unclear or absent. Both the methodology and reporting of panel diagnosis could, therefore, be improved substantially. Based on their findings, the researchers provide a checklist and flow chart to help guide the conduct and reporting of studies involving panel diagnosis. For example, they suggest that, when designing a study that uses panel diagnosis as the reference standard, the number and background of panel members should be considered, and they provide a list of options that should be considered when planning the decision-making process. Although more research into each of the options identified by the researchers is needed, their recommendations provide a starting point for the development of formal guidelines on the methodology and reporting of panel diagnosis for use as a reference standard in diagnostic research. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001531. Wikipedia has a page on medical diagnosis (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) The Equator Network is an international initiative that seeks to improve the reliability and value of medical research literature by promoting transparent and accurate reporting of research studies; its website includes information on a wide range of reporting guidelines, including the STAndards for the Reporting of Diagnostic accuracy studies (STARD), an initiative that aims to improve the accuracy and completeness of reporting of studies of diagnostic accuracy

Background Exercise reduced tolerance and breathlessness are common in the elderly and can result in substantial loss in functionality and health related quality of life. Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common underlying causes, but can be difficult to disentangle due to overlap in symptomatology. In addition, other potential causes such as obesity, anaemia, renal dysfunction and thyroid disorders may be involved. We aim to assess whether screening of frail elderly with reduced exercise tolerance leads to high detection rates of HF, COPD, or alternative diagnoses, and whether detection of these diseases would result in changes in patient management and increase in both functionality and quality of life. Methods/Design A cluster randomized diagnostic trial. Primary care practices are randomized to the diagnostic-treatment strategy (screening) or care as usual. Patient population: Frail (defined as having three or more chronic or vitality threatening diseases and/or receiving five or more drugs chronically during the last year) community-dwelling persons aged 65 years and older selected from the electronic medical files of the participating general practitioners. Those with reduced exercise tolerance or moderate to severe dyspnoea (≥2 score on the Medical Research Counsel dyspnoea scale) are included in the study. The diagnostic screening in the intervention group includes history taking, physical examination, electrocardiography, spirometry, blood tests, and echocardiography. Subsequently, participants with new diagnoses will be managed according to clinical guidelines. Participants in the control arm receive care as usual. All participants fill out health status and other relevant questionnaires at baseline and after 6 months of follow-up. Discussion This study will generate information on the yield of screening for previously unrecognized HF, COPD and other chronic diseases in frail elderly with reduced exercise tolerance and/or exercise induced dyspnoea. The cluster randomized comparison will reveal whether this yield will result in subsequent improvements in functional health and/or health related quality of life. Trial registration ClinicalTrials.gov NCT01148719

Objectives To assess differences between three different decision-making approaches in the method of panel diagnosis as reference standard in diagnostic research. Study Design and Setting Within a diagnostic study, the prevalence of heart failure (HF) and chronic obstructive pulmonary disease (COPD) was compared using three approaches of decision making in panel diagnosis. These were (1) a plenary discussion among experts followed by a consensus decision (plenary); (2) a predefined decision rule based on final diagnoses made by each member individually (individual); and (3) a staged procedure in which first the final diagnosis per individual member is generated followed by a plenary discussion of those cases with disagreement (staged). Results Prevalence of HF and COPD according to plenary approach was 46% and 28%, respectively. Individual approach diagnosed 28% of patients with HF and 31% with COPD and revealed 28 and 8 discordant diagnoses, respectively, compared with plenary approach. Staged approach revealed a prevalence of 43% and 28% for HF and COPD, respectively, with eight discordant diagnoses for HF and none for COPD. Conclusion The staged approach is an attractive choice as it produces very similar results to the full plenary approach, while having the advantage of being less time consuming. Additionally, it provides insights into the decision-making process of the panel, and the “difficult-to-diagnose” patients can easily be identified.

Loes CM Bertens,1 Johannes B Reitsma,1 Karel GM Moons,1 Yvonne van Mourik,1 Jan Willem J Lammers,2 Berna DL Broekhuizen,1 Arno W Hoes,1 Frans H Rutten1 1Julius Center for Health Sciences and Primary Care, 2Department of Pulmonology, Heart-Lung Center, University Medical Center Utrecht, Utrecht, the Netherlands Purpose: Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce. Our aim was to develop and validate a new model to predict exacerbations in patients with COPD. Patients and methods: The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months. The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over. Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization. Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting. The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics. Results: The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up. The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69–0.82). Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61–0.71]). Conclusion: Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. Keywords: exacerbation of COPD, risk prediction, external validation, vascular disease