C-reactive protein point-of-care testing and complementary strategies to improve antibiotic stewardship in children with acute respiratory infections in primary care.

This paper provides the perspective of an international group of experts on the role of C-reactive protein (CRP) point-of-care testing (POCT) and complementary strategies such as enhanced communication skills training and delayed prescribing to improve antibiotic stewardship in the primary care of children presenting with an acute illness episode due to an acute respiratory tract infection (ARTI). To improve antibiotics prescribing decisions, CRP POCT should be considered to complement the clinical assessment of children (6 months to 14 years) presenting with an ARTI in a primary care setting. CRP POCT can help decide whether a serious infection can be ruled out, before deciding on further treatments or management, when clinical assessment is unconclusive. Based on the evidence currently available, a CRP value can be a valuable support for clinical reasoning and facilitate communication with patients and parents, but the clinical assessment should prevail when making a therapy or referral decision. Nearly half of children tested in the primary care setting can be expected to have a CRP value below 20 mg/l, in which case it is strongly suggested to avoid prescribing antibiotics when the clinical assessment supports ruling out a severe infection. For children with CRP values greater than or equal to 20 mg/l, additional measures such as additional diagnostic tests, observation time, re-assessment by a senior decision-maker, and specialty referrals, should be considered.

Guidance on C-reactive protein point-of-care testing and complementary strategies to improve antibiotic prescribing for adults with lower respiratory tract infections in primary care.

The world faces the threat of increasing antimicrobial resistance, and there is growing consensus that swift action must be taken to improve the rational use of antibiotics and increase the stewardship of antibiotics to safeguard this key resource in modern healthcare. This paper provides the perspective of an international group of experts on the role of C-reactive protein point-of-care testing (CRP POCT) and other complementary strategies to improve antibiotic stewardship in primary care, with regards to the diagnosis and treatment of adult patients presenting symptoms of lower respiratory tract infections (LRTIs). It provides guidance regarding the clinical assessment of symptoms in combination with C-reactive protein (CRP) results, at the point of care, to support the management decision, and discusses enhanced patient communication and delayed prescribing as complementary strategies to decrease the inappropriate use of antibiotics. Recommendation: CRP POCT should be promoted to improve the identification of adults presenting with symptoms of LRTIs in primary care who might gain additional benefit from antibiotic treatment. Appropriateness of antibiotic use can be maximized when CRP POCT is used together with complementary strategies such as enhanced communication skills training and delayed prescribing in addition to routine safety netting.

Diagnostic accuracy of heart auscultation for detecting valve disease: a systematic review.

OBJECTIVE: The objective of this study was to determine the diagnostic accuracy in detecting valvular heart disease (VHD) by heart auscultation, performed by medical doctors. DESIGN/METHODS: A systematic literature search for diagnostic studies comparing heart auscultation to echocardiography or angiography, to evaluate VHD in adults, was performed in MEDLINE (1947-November 2021) and EMBASE (1947-November 2021). Two reviewers screened all references by title and abstract, to select studies to be included. Disagreements were resolved by consensus meetings. Reference lists of included studies were also screened. The results are presented as a narrative synthesis, and risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. MAIN OUTCOME MEASURES: Sensitivity, specificity and likelihood ratios (LRs). RESULTS: We found 23 articles meeting the inclusion criteria. Auscultation was compared with full echocardiography in 15 of the articles; pulsed Doppler was used as reference standard in 2 articles, while aortography and ventriculography was used in 5 articles. One article used point-of-care ultrasound. The articles were published from year 1967 to 2021. Sensitivity of auscultation ranged from 30% to 100%, and specificity ranged from 28% to 100%. LRs ranged from 1.35 to 26. Most of the included studies used cardiologists or internal medicine residents or specialists as auscultators, whereas two used general practitioners and two studied several different auscultators. CONCLUSION: Sensitivity, specificity and LRs of auscultation varied considerably across the different studies. There is a sparsity of data from general practice, where auscultation of the heart is usually one of the main methods for detecting VHD. Based on this review, the diagnostic utility of auscultation is unclear and medical doctors should not rely too much on auscultation alone. More research is needed on how auscultation, together with other clinical findings and history, can be used to distinguish patients with VHD. PROSPERO REGISTRATION NUMBER: CRD42018091675.

The Role of CRP POC Testing in the Fight against Antibiotic Overuse in European Primary Care: Recommendations from a European Expert Panel.

Tackling antibiotic resistance represents one of the major challenges in modern medicine, and limiting antibiotics' overuse represents the first step in this fight. Most antibiotics are prescribed in primary care settings, and lower respiratory tract infections (LRTIs) are one of the most common indications for their prescription. An expert panel conducted an extensive report on C-reactive protein point-of-care (CRP POC) testing in the evaluation of LRTIs and its usefulness to limit antibiotic prescriptions. The expert panel stated that CRP POC testing is a potentially useful tool to limit antibiotic prescriptions for LRTI in a community setting. CRP POC must be used in conjunction with other strategies such as improved communication skills and the use of other molecular POC testing. Potential barriers to the adoption of CRP POC testing are financial and logistical issues. Moreover, the efficacy in limiting antibiotic prescriptions could be hampered by the fact that, in some countries, patients may gain access to antibiotics even without a prescription. Through the realization of a better reimbursement structure, the inclusion in standardized procedures in local guidelines, and better patient education, CRP point-of-care testing can represent a cornerstone in the fight against antimicrobial resistance.

Algorithm for predicting valvular heart disease from heart sounds in an unselected cohort.

Objective: This study aims to assess the ability of state-of-the-art machine learning algorithms to detect valvular heart disease (VHD) from digital heart sound recordings in a general population that includes asymptomatic cases and intermediate stages of disease progression. Methods: We trained a recurrent neural network to predict murmurs from heart sound audio using annotated recordings collected with digital stethoscopes from four auscultation positions in 2,124 participants from the Tromsø7 study. The predicted murmurs were used to predict VHD as determined by echocardiography. Results: The presence of aortic stenosis (AS) was detected with a sensitivity of 90.9%, a specificity of 94.5%, and an area under the curve (AUC) of 0.979 (CI: 0.963-0.995). At least moderate AS was detected with an AUC of 0.993 (CI: 0.989-0.997). Moderate or greater aortic and mitral regurgitation (AR and MR) were predicted with AUC values of 0.634 (CI: 0.565-703) and 0.549 (CI: 0.506-0.593), respectively, which increased to 0.766 and 0.677 when clinical variables were added as predictors. The AUC for predicting symptomatic cases was higher for AR and MR, 0.756 and 0.711, respectively. Screening jointly for symptomatic regurgitation or presence of stenosis resulted in an AUC of 0.86, with 97.7% of AS cases (n = 44) and all 12 MS cases detected. Conclusions: The algorithm demonstrated excellent performance in detecting AS in a general cohort, surpassing observations from similar studies on selected cohorts. The detection of AR and MR based on HS audio was poor, but accuracy was considerably higher for symptomatic cases, and the inclusion of clinical variables improved the performance of the model significantly.

Challenges and opportunities for general practice specific CME in Europe - a narrative review of seven countries.

BACKGROUND: Several changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development. METHODS: Narrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation. RESULTS: General practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented. CONCLUSIONS: Independent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

Associations with Post-Consultation Health-Status in Primary Care Managed Acute Exacerbation of COPD.

BACKGROUND: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing. AIM: To investigate the factors associated with post-consultation COPD health status in patients presenting with AECOPD in this setting. DESIGN AND SETTING: A cohort study of patients enrolled in a randomised controlled trial. Patients aged 40+ years with a clinical diagnosis of COPD who presented in primary care across England and Wales with an AECOPD were included. METHODS: Participants were contacted for follow-up at one- and two-weeks by phone and attended the practice four weeks after the index consultation. The outcome of interest was the Clinical COPD Questionnaire (CCQ) score. Multivariable multilevel linear regression models fitted to examine the factors associated with COPD health status in the four-weeks following consultation for an AECOPD. RESULTS: A total of 649 patients were included, with 1947 CCQ total scores analysed. Post-consultation CCQ total scores were significantly higher (worse) in participants with diabetes (adjusted mean difference [AMD]=0.26; 95% confidence interval (CI) 0.08-0.45), obese patients compared to those with normal body mass index (AMD = 0.25, 95% CI 0.07-0.43), and those who were prescribed oral antibiotics in the prior 12 months (AMD = 0.26; 95% CI 0.11-0.41), but only the two latter associations remained after adjusting for other sociodemographic variables. CONCLUSION: COPD health status was worse in the four weeks following primary care consultation for AECOPD in patients with obesity and those prescribed oral antibiotics in the preceding year.

Interrater and intrarater agreement on heart murmurs.

OBJECTIVE: To investigate interrater and intrarater agreement between physicians and medical students on heart sound classification from audio recordings, and factors predicting agreement with a reference classification. DESIGN: Intra- and interrater agreement study. SUBJECTS: Seventeen GPs and eight cardiologists from Norway and the Netherlands, eight medical students from Norway. MAIN OUTCOME MEASURES: Proportion of agreement and kappa coefficients for intrarater agreement and agreement with a reference classification. RESULTS: The proportion of intrarater agreement on the presence of any murmur was 83% on average, with a median kappa of 0.64 (range k = 0.09-0.86) for all raters, and 0.65, 0.69, and 0.61 for GPs, cardiologist, and medical students, respectively.The proportion of agreement with the reference on any murmur was 81% on average, with a median kappa of 0.67 (range 0.29-0.90) for all raters, and 0.65, 0.69, and 0.51 for GPs, cardiologists, and medical students, respectively.Distinct murmur, more than five years of clinical practice, and cardiology specialty were most strongly associated with the agreement, with ORs of 2.41 (95% CI 1.63-3.58), 2.19 (1.58-3.04), and 2.53 (1.46-4.41), respectively. CONCLUSION: We observed fair but variable agreement with a reference on heart murmurs, and physician experience and specialty, as well as murmur intensity, were the factors most strongly associated with agreement.Key points:Heart auscultation is the main physical examination of the heart, but we lack knowledge of inter- and intrarater agreement on heart sounds.• Physicians identified heart murmurs from heart sound recordings fairly reliably compared with a reference classification, and with fair intrarater agreement.• Both intrarater agreement and agreement with the reference showed considerable variation between doctors• Murmur intensity, more than five years in clinical practice, and cardiology specialty were most strongly linked to agreement with the reference.

Chronic Obstructive Pulmonary Disease (COPD) in Population Studies in Russia and Norway: Comparison of Prevalence, Awareness and Management.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Despite a high prevalence of smoking and respiratory symptoms, two recent population-based studies in Russia found a relatively low prevalence of obstructive lung function. Here, we investigated the prevalence of both obstructive lung disease and respiratory symptoms in a population-based study conducted in two Russian cities and compared the findings with a similar study from Norway conducted in the same time period. METHODS: The study population was a sub-sample of participants aged 40-69 years participating in the Know Your Heart (KYH) study in Russia in 2015-18 (n=1883) and in the 7th survey of the Tromsø Study (n=5271) carried out in Norway in 2015-16 (Tromsø 7) who participated in spirometry examinations. The main outcome was obstructive lung function (FEV1/FVC ratio< lower limit of normal on pre-bronchodilator spirometry examination) with and without respiratory symptoms (chronic cough and breathlessness). In those with obstructive lung function, awareness (known diagnosis) and management (use of medications, smoking cessation) were compared. RESULTS: The age-standardized prevalence of obstructive lung function was similar among men in both studies (KYH 11.0% vs Tromsø 7 9.8%, p=0.21) and higher in the Norwegian (9.4%) than Russian (6.8%) women (p=0.006). In contrast, the prevalence of obstructive lung function plus respiratory symptoms was higher in Russian men (KYH 8.3% vs Tromsø 7 4.7%, p<0.001) but similar in women (KYH 5.9% vs Tromsø 7 6.4%, p=0.18). There was a much higher prevalence of respiratory symptoms in Russian than Norwegian participants of both sexes regardless of presence of obstructive lung function. CONCLUSION: The prevalence of respiratory symptoms was strikingly high among Russian participants but this was not explained by a higher burden of obstructive lung function on spirometry testing in comparison with Norwegian participants. Further work is needed to understand the reasons and health implications of this high prevalence of cough and breathlessness.

Inspiratory crackles-early and late-revisited: identifying COPD by crackle characteristics.

BACKGROUND: The significance of pulmonary crackles, by their timing during inspiration, was described by Nath and Capel in 1974, with early crackles associated with bronchial obstruction and late crackles with restrictive defects. Crackles are also described as 'fine' or 'coarse'. We aimed to evaluate the usefulness of crackle characteristics in the diagnosis of chronic obstructive pulmonary disease (COPD). METHODS: In a population-based study, lung sounds were recorded at six auscultation sites and classified in participants aged 40 years or older. Inspiratory crackles were classified as 'early' or 'late and into the types' 'coarse' and 'fine' by two observers. A diagnosis of COPD was based on respiratory symptoms and forced expiratory volume in 1 s/forced inspiratory vital capacity below lower limit of normal, based on Global Lung Function Initiative 2012 reference. Associations between crackle characteristics and COPD were analysed by logistic regression. Kappa statistics was applied for evaluating interobserver agreement. RESULTS: Of 3684 subjects included in the analysis, 52.9% were female, 50.1% were ≥65 years and 204 (5.5%) had COPD. Basal inspiratory crackles were heard in 306 participants by observer 1 and in 323 by observer 2. When heard bilaterally COPD could be predicted with ORs of 2.59 (95% CI 1.36 to 4.91) and 3.20 (95% CI 1.71 to 5.98), annotated by observer 1 and 2, respectively, adjusted for sex and age. If bilateral crackles were coarse the corresponding ORs were 2.65 (95% CI 1.28 to 5.49) and 3.67 (95% CI 1.58 to 8.52) and when heard early during inspiration the ORs were 6.88 (95% CI 2.59 to 18.29) and 7.63 (95%CI 3.73 to 15.62). The positive predictive value for COPD was 23% when early crackles were heard over one or both lungs. We observed higher kappa values when classifying timing than type. CONCLUSIONS: 'Early' inspiratory crackles predicted COPD more strongly than 'coarse' inspiratory crackles. Identification of early crackles at the lung bases should imply a strong attention to the possibility of COPD.

Associations with antibiotic prescribing for acute exacerbation of COPD in primary care: secondary analysis of a randomised controlled trial.

BACKGROUND: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible. AIM: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care. DESIGN AND SETTING: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial). METHOD: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l). RESULTS: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85). CONCLUSION: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions.

Clinical Features and C-Reactive Protein as Predictors of Bacterial Exacerbations of COPD.

Introduction: Identifying predictors of bacterial and viral pathogens in sputum from patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) may help direct management. Methods: We used data from a trial evaluating a C-reactive protein (CRP) point of care guided approach to managing COPD exacerbations in primary care. We used regression analyses to identify baseline clinical features, including CRP value in those randomized to testing, associated with bacterial, viral or mixed infections, defined by the presence of bacterial and viral pathogens in sputum, detected by culture or polymerase chain reaction (PCR), respectively. Results: Of 386 participants with baseline sputum samples, 79 (20.5%), 123 (31.9%), and 91 (23.6%) had bacterial, viral/atypical, and mixed bacterial/viral/atypical pathogens identified, respectively. Increasing sputum purulence assessed by color chart was associated with increased odds of finding bacterial and mixed (bacterial and viral/atypical) pathogens in sputum (area under the ROC curve (AUROC) for bacterial pathogens =0.739 (95% CI: 0.670, 0.808)). Elevated CRP was associated with increased odds of finding bacterial pathogens and mixed pathogens but did not significantly increase the AUROC for predicting bacterial pathogens over sputum color alone (AUROC for combination of sputum color and CRP = 0.776 (95% CI: 0.708, 0.843), p for comparison of models = 0.053). We found no association between the presence of sputum pathogens and other clinical or demographic features. Conclusion: Sputum purulence was the best predictor of sputum bacterial pathogens and mixed bacterial viral/atypical pathogens in patients with COPD exacerbations in our study. Elevated CRP was associated with bacterial pathogens but did not add to the predictive value of sputum purulence.

Prediction of chronic heart failure and chronic obstructive pulmonary disease in a general population: the Tromsø study.

AIMS: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are main causes of dyspnoea, and echocardiography and spirometry are essential investigations for these diagnoses. Our aim was to determine the prevalence of HF and COPD in a general population, also how the diseases may be identified, and to what extent their clinical characteristics differ. METHODS AND RESULTS: In the seventh survey of Tromsø study (2015-16), subjects aged 40 years or more were examined with echocardiography, spirometry, lung sound recordings, questionnaires, including the modified Medical Research Council (mMRC) questionnaire on dyspnoea, and N-terminal pro-brain natriuretic peptide analysis. A diagnosis of HF (HF with reduced ejection fraction, HF with mid-range ejection fraction, or HF with preserved ejection fraction) or COPD was established according to current guidelines. Predictors of HF and COPD were evaluated by logistic regression and receiver operating characteristic curve analysis. A total of 7110 participants could be evaluated for COPD, 1624 for HF, and 1538 for both diseases. Age-standardized prevalence of HF was 6.8% for women and 6.1% for men; the respective figures for COPD were 5.2% and 5.1%. Among the 1538 evaluated for both diseases, 139 subjects fulfilled the HF criteria, but only 17.1% reported to have the disease. Of those fulfilling the COPD criteria, 31.6% reported to have the disease. Shortness of breath at exertion was a frequent finding in HF; 59% of those with mMRC ≥2 had HF, while such shortness of breath was found in 24% among those with COPD. Reporting mMRC ≥2 had an odds ratio for HF of 19.5 (95% confidence interval 11.3-33.7), whereas the odds ratio for COPD was 6.3 (95% confidence interval 3.5-11.6). Current smoking was the strongest predictor of COPD but did not predict HF. Basal inspiratory crackles were significant predictors of HF in multivariable analysis. Among the subtypes of HF, an age <70 years was most frequently found in HF with reduced ejection fraction, in 51.7%. Clinical scores based on the predictive value in multivariable analysis of history, symptoms, and signs predicted HF and COPD with areas under the curve of 0.833 and 0.829, respectively. CONCLUSIONS: Study participants with HF and COPD were in most cases not aware of their condition. In general practice, when an elderly patient present with shortness of breath, both diseases should be considered. Previous cardiovascular disease points at HF, while a history of smoking points at COPD. The threshold should be low for ordering echocardiography or spirometry for verifying the suspected cause of dyspnoea.

C-reactive protein-guided antibiotic prescribing for COPD exacerbations: a qualitative evaluation.

BACKGROUND: Antibiotics are prescribed to >70% of patients presenting in primary care with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The PACE randomised controlled trial found that a C-reactive protein point-of-care test (CRP-POCT) management strategy for AECOPD in primary care resulted in a 20% reduction in patient-reported antibiotic consumption over 4 weeks. AIM: To understand perceptions of the value of CRP-POCT for guiding antibiotic prescribing for AECOPD; explore possible mechanisms, mediators, and pathways to effects; and identify potential barriers and facilitators to implementation from the perspectives of patients and clinicians. DESIGN AND SETTING: Qualitative process evaluation in UK general practices. METHOD: Semi-structured telephone interviews with 20 patients presenting with an AECOPD and 20 primary care staff, purposively sampled from the PACE study. Interviews were audio-recorded, transcribed, and analysed using framework analysis. RESULTS: Patients and clinicians felt that CRP-POCT was useful in guiding clinicians' antibiotic prescribing decisions for AECOPD, and were positive about introduction of the test in routine care. The CRP-POCT enhanced clinician confidence in antibiotic prescribing decisions, reduced decisional ambiguity, and facilitated communication with patients. Some clinicians thought the CRP-POCT should be routinely used in consultations for AECOPD; others favoured use only when there was decisional uncertainty. CRP-POCT cartridge preparation time and cost were potential barriers to implementation. CONCLUSION: CRP-POCT-guided antibiotic prescribing for AECOPD had high acceptability, but commissioning arrangements and further simplification of the CRP-POCT need attention to facilitate implementation in routine practice.

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. OBJECTIVE: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. DESIGN: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. SETTING: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. PARTICIPANTS: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours' and 21 days' duration. INTERVENTION: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. MAIN OUTCOME MEASURES: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. RESULTS: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI -0.33 to -0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI -£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. CONCLUSIONS: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. FUTURE WORK: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24346473. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information.

People with chronic obstructive pulmonary disease (COPD) often experience flare-ups known as acute exacerbations of chronic obstructive pulmonary disease. Antibiotics are prescribed for most flare-ups, but they do not always benefit patients and may cause harm, such as side effects or subsequent infections that are resistant. Rapid point-of-care tests (POCTs) can be used to help determine when antibiotics are more likely to be needed. C-reactive protein (CRP) is a marker of inflammation that can be measured with a POCT. Patients with flare-ups and a low CRP value are less likely to benefit from antibiotics. The PACE trial asked whether or not measuring CRP with a POCT could lead to fewer antibiotics being consumed for flare-ups, without having negative effects for patients. We aimed to recruit 650 patients with a COPD flare-up from primary care. Patients were randomly assigned to either (1) usual care with the addition of a CRP POCT, or (2) usual care without the addition of the test. Antibiotic use over the first 4 weeks and patients' self-assessment of their health 2 weeks after enrolment were measured in both groups. Patients in the CRP test group used fewer antibiotics than those managed as usual, and had improved patient-reported outcomes. Costs were a little higher in the CRP POCT group. Interviews with patients and clinicians found that they appreciated the CRP test being included in the decision-making process.

The effect of atmospheric pressure on oxygen saturation and dyspnea: the Tromsø study.

A drop in atmospheric pressure, as observed at high altitudes, leads to decreased oxygen saturation. The effect of regular changes in barometric pressure at sea level has never been studied in a general population. A cohort of adults aged 40 years were examined with pulse oximetry at two separate visits, and the local barometric pressure was available from the local weather station. The study aimed at determining the effect of atmospheric pressure on oxygen saturation also called SpO2, as well as on shortness of breath. Based on spirometry, the participants were divided into two groups, with normal and decreased lung function. Decreased lung function was defined as forced expiratory volume in 1 s (FEV1) below lower limit or normal (LLN) or FEV1/FVC (FVC, forced vital capacity) below LLN, with GLI 2012 reference values. The statistical analysis included uni/multivariable linear and logistic regression. A total of 7439 participants of the Tromsø 7 cohort study were included. There was a significant association between barometric pressure and SpO2 < 96%, and we found that a reduction of 166.67 hPa was needed to get a 1% reduction in SpO2. The change in atmospheric pressure was not significantly associated with shortness of breath, also not in subjects with reduced lung function.

Is the Disease Burden from COPD in Norway Falling off? A Study of Time Trends in Three Different Data Sources.

Background: Less smoking should lead to fewer COPD cases. We aimed at estimating time trends in the prevalence and burden of COPD in Norway from 2001 to 2017. Methods: We used pre-bronchodilator spirometry and other health data from persons aged 40-84 years in three surveys of the Tromsø Study, 2001-2002, 2007-2008 and 2015-2016. We applied spirometry lower limits of normal (LLN) according to Global Lung Initiative 2012. Age-standardized prevalence was determined. We defined COPD as FEV1/FVC

Impact of respiratory symptoms and oxygen saturation on the risk of incident venous thromboembolism-the Tromsø study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with risk of venous thromboembolism (VTE). It remains unknown whether individual respiratory symptoms and lowered oxygen saturation (SpO2), individually and in combination with COPD, affect the risk of VTE. OBJECTIVES: To investigate whether measures of respiratory impairments including respiratory symptoms and SpO2, individually and combined with COPD, were associated with an increased risk of VTE. METHODS: Spirometry, SpO2, and self-reported respiratory symptoms were collected in 8686 participants from the fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study. Incident VTE events were registered from the date of inclusion to December 31, 2016. Cox regression models with exposures and confounders as time-varying covariates (for repeated measurements) were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE. RESULTS: During a median follow-up of 9.1 years, 330 participants developed incident VTE. Subjects with SpO2 ≤ 96% (lowest 20th percentile) had a 1.5-fold higher risk of VTE (adjusted HR, 1.48; 95% CI, 1.13-1.93) compared with those with SpO2 ≥ 98%. Severe respiratory symptoms (dyspnea, cough, and phlegm) were associated with a 1.4- to 2.0-fold higher risk of VTE compared with no such symptoms. COPD, combined with respiratory symptoms or lowered SpO2, had an additive effect on the VTE risk. CONCLUSIONS: Lowered SpO2 and severe respiratory symptoms were associated with increased VTE risk. COPD combined with respiratory impairments had an additive effect on VTE risk, and may suggest particular attention on VTE preventive strategies in COPD patients with respiratory impairments.

Chronic Obstructive Pulmonary Disease and Risk of Mortality in Patients with Venous Thromboembolism-The Tromsø Study.

BACKGROUND: Previous studies have shown increased mortality in venous thromboembolism (VTE) patients with chronic obstructive pulmonary disease (COPD), but it is unknown to what extent the association is influenced by the severity of COPD and physical inactivity. OBJECTIVES: This article investigates whether COPD, and stages of COPD, influenced the risk of mortality after a first episode of VTE when physical inactivity was taken into account. METHODS: Patients with a first lifetime VTE (n = 256) were recruited among individuals who participated and performed spirometry in the fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study (n = 9577). All-cause mortality was registered up to December 31, 2015. RESULTS: There were 123 deaths during a median of 2.9 years of follow-up. The overall mortality rate was 11.9 (95% confidence interval [CI] 10.0-14.2) per 100 person-years. The risk of death was twofold higher in COPD patients compared with those with normal airflow (hazard ratio [HR] 2.00, 95% CI 1.30-3.08) after multivariable adjustment. The risk of death increased with the severity of COPD. VTE patients with COPD stage III/IV had a fivefold increased risk of death (HR 5.20, 95% CI 2.65-10.2) compared with those without COPD, and 50% of these patients died within 3.5 months after the incident VTE event. Adjustment for physical inactivity had minor effect on the risk estimates. CONCLUSION: VTE patients with COPD had increased risk of death, particularly patients with severe COPD. The detrimental effect of COPD on mortality in VTE patients was apparently explained by factors other than physical inactivity among patients with COPD.

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations.

BACKGROUND: Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority). RESULTS: A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation. CONCLUSIONS: CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.).