Berna Dl Broekhuizen

Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study

Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool. Design Diagnostic study performed between 2007 and 2010. Participants had their history taken, underwent physical examination and measurement of C reactive protein (CRP) and procalcitonin in venous blood on the day they first consulted, and underwent chest radiography within seven days. Setting Primary care centres in 12 European countries. Participants Adults presenting with acute cough. Main outcome measures Pneumonia as determined by radiologists, who were blind to all other information when they judged chest radiographs. Results Of 3106 eligible patients, 286 were excluded because of missing or inadequate chest radiographs, leaving 2820 patients (mean age 50, 40% men) of whom 140 (5%) had pneumonia. Re-assessment of a subset of 1675 chest radiographs showed agreement in 94% (κ 0.45, 95% confidence interval 0.36 to 0.54). Six published “symptoms and signs models” varied in their discrimination (area under receiver operating characteristics curve (ROC) ranged from 0.55 (95% confidence interval 0.50 to 0.61) to 0.71 (0.66 to 0.76)). The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever, with an ROC area of 0.70 (0.65 to 0.75). Addition of CRP at the optimal cut off of >30 mg/L increased the ROC area to 0.77 (0.73 to 0.81) and improved the diagnostic classification (net reclassification improvement 28%). In the 1556 patients classified according to symptoms, signs, and CRP >30 mg/L as “low risk” (<2.5%) for pneumonia, the prevalence of pneumonia was 2%. In the 132 patients classified as “high risk” (>20%), the prevalence of pneumonia was 31%. The positive likelihood ratio of low, intermediate, and high risk for pneumonia was 0.4, 1.2, and 8.6 respectively. Measurement of procalcitonin added no relevant additional diagnostic information. A simplified diagnostic score based on symptoms, signs, and CRP >30 mg/L resulted in proportions of pneumonia of 0.7%, 3.8%, and 18.2% in the low, intermediate, and high risk group respectively. Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation. Addition of CRP concentration at the optimal cut off of >30 mg/L improved diagnostic information, but measurement of procalcitonin concentration did not add clinically relevant information in this group.

Diagnosing pneumonia in patients with acute cough: clinical judgment compared to chest radiography

Pneumonia is often diagnosed and treated empirically. We set out to determine the diagnostic accuracy of clinical judgment based on signs and symptoms to detect radiographic pneumonia in patients presenting with acute cough in primary care. In 2810 European patients with acute cough, general practitioners (GPs) recorded whether they considered pneumonia to be present (“yes” or “no”) immediately after history and physical examination. Chest radiography was performed within 1 week by local radiologists blind to other patient characteristics. 140 patients had radiographic pneumonia (5%), of whom 41 (29%) had been diagnosed as such. 31 (1%) patients had a clinical diagnosis that was not confirmed by radiography (n=2670). In clinically suspected pneumonia, 57% of subjects were subsequently diagnosed with radiographic pneumonia. Negative predictive value (NPV), sensitivity and specificity of GPs’ clinical judgment were 96%, 29% and 99%, respectively. Compared to patients with a clinical diagnosis of pneumonia, less severe symptoms were found in radiographic pneumonia cases not suspected clinically (p<0.05). The predictive values of GPs’ clinical judgment, particularly the high NPVs, are helpful in routine care. Nonetheless, the majority of diagnoses of radiographic pneumonias was not suspected on clinical grounds. There is a need to further support the detection of clinically relevant pneumonia in primary care. There is a need to further support the detection of clinically relevant pneumonia in primary care http://ow.ly/mxw6Z

Analytical performance, agreement and user-friendliness of five C-reactive protein point-of-care tests

Abstract Background. Point-of-care (POC) C-reactive protein (CRP) testing is increasingly used in primary care to assist general practitioners (GPs) in the diagnostic workup for various complaints. The present study compares analytical performance, agreement and user-friendliness of five of these POC CRP tests. Methods. The following five POC CRP tests were evaluated: Afinion and NycoCard Reader II (both Alere), Eurolyser Smart 700/340 (Eurolyser), QuikRead go and QuikRead 101 (both Orion Diagnostica). Results were compared with those of a standard immunoturbidimetric method performed on a routine analyzer (Olympus AU 2700, Beckman Coulter). Analytical performance and agreement with the laboratory standard for the five different POC tests were analyzed. Subsequently, user-friendliness of the POC tests was assessed. Results. Within-day CVs varied from 2.6% (QuikRead go) to 19.4% (Eurolyser Smart 700/340) for low CRP values (< 20 mg/L), and 1.1% (QuikRead go) to 17.5% (Eurolyser Smart 700/340) for high values (> 100 mg/L). Between-day CVs varied from 4.6% (Afinion) to 30.5% (Eurolyser Smart 700/340) for low values and 4.0% (QuikRead go) to 18.0% (Eurolyser Smart 700/340) for high values. With high CRP values (> 100 mg/L) agreement with the laboratory standard systematically decreased for all POC tests. Regarding user-friendliness Afinion and Eurolyser Smart 700/340 were judged easiest to operate. Conclusions. Analytical performance, agreement, and user-friendliness of the POC CRP tests varied considerably, yet overall four devices showed adequate analytical performance and agreement.

The diagnostic value of history and physical examination for COPD in suspected or known cases: a systematic review

BACKGROUND According to current guidelines, spirometry should be performed in patients suspected of chronic obstructive pulmonary disease (COPD) by the results of history taking and physical examination. However, little is known about the diagnostic value of patient history and physical examination for COPD. OBJECTIVES To review the existing evidence on the diagnostic value of history taking and physical examination in recognizing COPD in patients suspected of COPD. METHODS A systematic literature search was performed in electronic medical databases. Studies were included after using defined inclusion and exclusion criteria and judged on their methodological quality by using the Quality Assessment of Diagnostic Accuracy Studies criteria. A formal meta-analysis was not performed because all studied items of history and physical examination were investigated in only in a maximum of three studies. RESULTS Six studies were included. The history items dyspnoea, wheezing, previous consultation for wheezing or cough, self-reported COPD, age and smoking and the physical examination items wheezing, forced expiratory time, laryngeal height and prolonged expiration were found to have diagnostic value for COPD. These items were studied in maximally three studies and study population studies were heterogenic. The reference test for COPD in five of the six studies concerned obstructive lung disease in general and not COPD. CONCLUSION There is insufficient evidence to assess the value of history taking and physical examination for diagnosing COPD.

Undetected chronic obstructive pulmonary disease and asthma in people over 50 years with persistent cough

BACKGROUND Chronic obstructive pulmonary disease (COPD) and asthma are underdiagnosed in primary care. AIM To determine how often COPD or asthma are present in middle-aged and older patients who consult their GP for persistent cough. DESIGN OF STUDY A cross-sectional study in 353 patients older than 50 years, visiting their GP for persistent cough and not known to have COPD or asthma. SETTING General practice in the Netherlands. METHOD All participants underwent extensive diagnostic work-up, including symptoms, signs, spirometry, and body plethysmography. All results were studied by an expert panel to diagnose or exclude COPD and/or asthma. The reproducibility of the panel diagnosis was assessed by calculation of Cohens kappa statistic in a sample of 41 participants. RESULTS Of the 353 participants, 102 (29%, 95% confidence interval [CI] = 24 to 34%) were diagnosed with COPD. In 14 of these 102 participants, both COPD and asthma were diagnosed (4%, 95% CI = 2 to 7%). Asthma (without COPD) was diagnosed in 23 (7%, 95% CI = 4 to 10%) participants. Mean duration of cough was 93 days (median 40 days). The reproducibility of the expert panel was good (Cohens kappa = 0.90). CONCLUSION In patients aged over 50 years who consult their GP for persistent cough, undetected COPD or asthma is frequently present.

Development and validation of a model to predict the risk of exacerbations in chronic obstructive pulmonary disease

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.

Spirometric thresholds for diagnosing COPD: 0.70 or LLN, pre- or post-dilator values?

Abstract In absence of a gold standard for chronic obstructive pulmonary disease (COPD) it remains difficult to compare the true diagnostic characteristics of the forced expiratory volume in 1 second to the forced vital capacity (FEV1/FVC) <0.70 and < lower limit of normal (LLN). COPD is a clinical diagnosis, based on symptoms signs and lung function results combined, and an expert panel assessment would be an adequate reference standard. We compared the diagnostic properties of FEV1/FVC <LLN and <0.70 against this panel diagnosis: 342 participants, aged >50, consulting for persistent cough, but without physician-diagnosed COPD, were prospectively enrolled. All underwent extensive history taking, physical examination, spirometry and diffusion testing. An expert panel, including a board certified respiratory physician, assessed all diagnostic information to determine the presence or absence of COPD and served as reference standard. Then, 104 participants were diagnosed with COPD by the panel. The reproducibility of the panel diagnosis was high (kappa of 0.94). Sensitivity estimates of <0.70 were significantly higher than that of <LLN (0.73 and 0.47, respectively, p < 0.001). The fixed approach was less specific than the LLN (0.95 and 0.99, respectively, p < 0.001). There was no significant difference in diagnostic property when using pre- or post-bronchodilator FEV1/FVC (p = 0.615). In a symptomatic primary care population, the FEV1/FVC <0.70 was more accurate to detect COPD.

Prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care

Background Most cases of adult pertussis probably remain undiagnosed. Aim To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. Design and setting Prospective observational study between 2007 and 2010 in primary care in 12 European countries. Method Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days. Results Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation. Conclusion Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation.

COPD in patients with stable heart failure in the primary care setting

Background Presence of chronic obstructive pulmonary disease (COPD) in heart failure (HF) has prognostic and therapeutic implications. Exact prevalence estimates are lacking because most previous studies estimated the prevalence of COPD among HF patients while unstable and in the presence of pulmonary congestion. Methods Community-dwelling patients with an established diagnosis of HF and in a stable phase of their disease were invited for spirometry. COPD was defined according to the Global initiative for chronic Obstructive Lung Disease (GOLD) classification and considered present if the ratio of the post-bronchodilator forced expiratory volume in 1 second and forced vital capacity was below 0.7. Results Thirty of the 106 patients with HF (mean age 76 [standard deviation] 11.9 years, 57% male) had COPD (prevalence 28.3% [95% confidence interval (CI) 19.7%–36.9%]), with similar rates among those with HF and a reduced ejection fraction (18 individuals; prevalence 28.6% [95% CI 20.0%–37.2%]) and HF with preserved ejection fraction (12 individuals; prevalence 27.9% [95% CI 19.4–36.4]). Twenty-one (70%) of the 30 participants were newly detected cases of COPD. Conclusion More than a quarter of the patients with HF concomitantly have COPD, with the large majority being previously unrecognized. Coexistence of COPD should be considered more often in these patients.

Medication use in European primary care patients with lower respiratory tract infection: an observational study

BACKGROUND It is largely unknown what medication is used by patients with lower respiratory tract infection (LRTI). AIM To describe the use of self-medication and prescribed medication in adults presenting with LRTI in different European countries, and to relate self-medication to patient characteristics. DESIGN AND SETTING An observational study in 16 primary care networks in 12 European countries. METHOD A total of 2530 adult patients presenting with LRTI in 12 European countries filled in a diary on any medication used before and after a primary care consultation. Patient characteristics related to self-medication were determined by univariable and multivariable logistic regression analysis. RESULTS The frequency and types of medication used differed greatly between European countries. Overall, 55.4% self-medicated before consultation, and 21.5% after consultation, most frequently with paracetamol, antitussives, and mucolytics. Females, non-smokers, and patients with more severe symptoms used more self-medication. Patients who were not prescribed medication during the consultation self-medicated more often afterwards. Self-medication with antibiotics was relatively rare. CONCLUSION A considerable amount of medication, often with no proven efficacy, was used by adults presenting with LRTI in primary care. There were large differences between European countries. These findings should help develop patient information resources, international guidelines, and international legislation concerning the availability of over-the-counter medication, and can also support interventions against unwarranted variations in care. In addition, further research on the effects of symptomatic medication is needed.