[Show abstract][Hide abstract] ABSTRACT: Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.
In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.
In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.
Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).
New England Journal of Medicine 03/2015; 372(12):1114-25. DOI:10.1056/NEJMoa1408544 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives Estimate the efficacy of amoxicillin for acute uncomplicated lower-respiratory-tract infection (LRTI) in primary care and demonstrate the use of randomisation-based efficacy estimators.
Design Secondary analysis of a two-arm individually-randomised placebo-controlled trial.
Setting Primary care practices in 12 European countries.
Participants Patients aged 18 or older consulting with an acute LRTI in whom pneumonia was not suspected by the clinician.
Interventions Amoxicillin (two 500 mg tablets three times a day for 7 days) or matched placebo.
Main outcome measures Clinician-rated symptom severity between days 2–4; new/worsening symptoms and presence of side effects at 4-weeks. Adherence was captured using self-report and tablet counts.
Results 2061 participants were randomised to the amoxicillin or placebo group. On average, 88% of the prescribed amoxicillin was taken. The original analysis demonstrated small increases in both benefits and harms from amoxicillin. Minor improvements in the benefits of amoxicillin were observed when an adjustments for adherence were made (mean difference in symptom severity −0.08, 95% CI −0.17 to 0.01, OR for new/worsening symptoms 0.81, 95% CI 0.66 to 0.98) as well as minor increases in harms (OR for side effects 1.32, 95% CI 1.12 to 1.57).
Conclusions Adherence to amoxicillin was high, and the findings from the original analysis were robust to non-adherence. Participants consulting to primary care with an acute uncomplicated LRTI can on average expect minor improvements in outcome from taking amoxicillin. However, they are also at an increased risk of experiencing side effects.
Trial registration numbers Eudract-CT 2007-001586-15 and ISRCTN52261229.
The trial was registered at EudraCT in 2007 due to an administrative misunderstanding that EudraCT was a suitable registry—which it was not in 2007, but has become since. On discovery of this error, the trial was also registered at ISRCTN (January 2009). Trial procedures did not change between the two registrations.
BMJ Open 03/2015; 5(3):e006160. DOI:10.1136/bmjopen-2014-006160 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The results obtained from various point-of-care (POC) test devices for estimating C-reactive protein (CRP) levels in a laboratory setting differ when compared to a laboratory reference test. We aimed to determine whether such differences meaningfully affect the accuracy and added diagnostic value in predicting radiographic pneumonia in adults presenting with acute cough in primary care.
A nested case control study of adult patients presenting with acute cough in 12 different European countries (the Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe [GRACE] Network). Venous blood samples from 100 patients with and 100 patients without pneumonia were tested with five different POC CRP tests and a laboratory analyzer. Single test accuracy values and the added value of CRP to symptoms and signs were calculated.
Single test accuracy values showed similar results for all five POC CRP tests and the laboratory analyzer. The area under the curve of the different POC CRP tests and the laboratory analyzer (range 0.79-0.80) were all comparable and higher than the clinical model without CRP (0.70). Multivariable odds ratios were the same (1.2) for all CRP tests.
Five POC CRP test devices and the laboratory analyzer performed with similar accuracy in detecting pneumonia both as single test, and when used in addition to clinical findings. Variability in results obtained from standard CRP laboratory and POC test devices do not translate into clinically relevant differences when used for prediction of pneumonia in patients with acute cough in primary care.
Scandinavian Journal of Clinical and Laboratory Investigation 02/2015; 75(4):1-5. DOI:10.3109/00365513.2015.1006136 · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Urinary tract infections (UTI) are the most frequent bacterial infection affecting women and account for about 15% of antibiotics prescribed in primary care. However, some women with a UTI are not prescribed antibiotics or are prescribed the wrong antibiotics, while many women who do not have a microbiologically confirmed UTI are prescribed antibiotics. Inappropriate antibiotic prescribing unnecessarily increases the risk of side effects and the development of antibiotic resistance, and wastes resources.
614 adult female patients will be recruited from four primary care research networks (Wales, England, Spain, the Netherlands) and individually randomised to either POCT guided care or the guideline-informed 'standard care' arm. Urine and stool samples (where possible) will be obtained at presentation (day 1) and two weeks later for microbiological analysis. All participants will be followed up on the course of their illness and their quality of life, using a 2 week self-completed symptom diary. At 3 months, a primary care notes review will be conducted for evidence of further evidence of treatment failures, recurrence, complications, hospitalisations and health service costs.
Although the Flexicult™ POCT is used in some countries in routine primary care, it's clinical and cost effectiveness has never been evaluated in a randomised clinical trial. If shown to be effective, the use of this POCT could benefit individual sufferers and provide evidence for health care authorities to develop evidence based policies to combat the spread and impact of the unprecedented rise of infections caused by antibiotic resistant bacteria in Europe.
Trial registration number:
ISRCTN65200697 (Registered 10 September 2013).
BMC Family Practice 11/2014; 15(1):187. DOI:10.1186/s12875-014-0187-4 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence shows a high rate of unnecessary antibiotic prescriptions in primary care in Europe and the United States. Given the costs of widespread use and associated antibiotic resistance, reducing inappropriate use is a public health priority.
Journal of General Internal Medicine 11/2014; 30(4). DOI:10.1007/s11606-014-3076-6 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antimicrobial use in farm animals might contribute to the development of antimicrobial resistance in humans and animals, and there is an urgent need to reduce antimicrobial use in farm animals. Veterinarians are typically responsible for prescribing and overseeing antimicrobial use in animals. A thorough understanding of veterinarians' current prescribing practices and their reasons to prescribe antimicrobials might offer leads for interventions to reduce antimicrobial use in farm animals. This paper presents the results of a qualitative study of factors that influence prescribing behaviour of farm animal veterinarians. Semi-structured interviews with eleven farm animal veterinarians were conducted, which were taped, transcribed and iteratively analysed. This preliminary analysis was further discussed and refined in an expert meeting. A final conceptual model was derived from the analysis and sent to all the respondents for validation. Many conflicting interests are identifiable when it comes to antimicrobial prescribing by farm animal veterinarians. Belief in the professional obligation to alleviate animal suffering, financial dependency on clients, risk avoidance, shortcomings in advisory skills, financial barriers for structural veterinary herd health advisory services, lack of farmers' compliance to veterinary recommendations, public health interests, personal beliefs regarding the veterinary contribution to antimicrobial resistance and major economic powers are all influential determinants in antimicrobial prescribing behaviour of farm animal veterinarians. Interventions to change prescribing behaviour of farm animal veterinarians could address attitudes and advisory skills of veterinarians, as well as provide tools to deal with (perceived) pressure from farmers and advisors to prescribe antimicrobials. Additional (policy) measures could probably support farm animal veterinarians in acting as a more independent animal health consultant.
Zoonoses and Public Health 11/2014; 62(s1). DOI:10.1111/zph.12168 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
General public views and expectations around the use of antibiotics can influence general practitioners' antibiotic prescribing decisions. We set out to describe the knowledge, attitudes and beliefs about the use of antibiotics for respiratory tract infections in adults in Poland, and explore differences according to where people live in an urban-rural continuum.
Material and Methods
Face to face survey among a stratified random sample of adults from the general population.
1,210 adults completed the questionnaire (87% response rate); 44.3% were rural; 57.9% were women. 49.4% of rural respondents and 44.4% of urban respondents had used an antibiotic in the last 2 years. Rural participants were less likely to agree with the statement “usually I know when I need an antibiotic,” (53.5% vs. 61.3% respectively; p = 0.015) and reported that they would consult with a physician for a cough with yellow/green phlegm (69.2% vs. 74.9% respectively; p = 0.004), and were more likely to state that they would leave the decision about antibiotic prescribing to their doctor (87.5% vs. 85.6% respectively; p = 0.026). However, rural participants were more likely to believe that antibiotics accelerate recovery from sore throat (45.7% vs. 37.1% respectively; p = 0.017). Use of antibiotic in the last 2 years, level of education, number of children and awareness of the problem of developing antimicrobial resistance predicted accurate knowledge about antibiotic effectiveness.
There were no major differences in beliefs about antibiotics between urban and rural responders, although rural responders were slightly less confident in their knowledge about antibiotics and self-reported greater use of antibiotics. Despite differences in the level of education between rural and urban responders, there were no significant differences in their knowledge about antibiotic effectiveness.
PLoS ONE 10/2014; 9(10):e109248. DOI:10.1371/journal.pone.0109248 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:In acute cough patients, impaired lung function as present in chronic lung conditions like asthma and chronic obstructive pulmonary disease (COPD) are often thought to negatively influence course of disease, but clear evidence is lacking.Aims:To investigate the influence of lung function abnormalities on course of disease and response to antibiotic therapy in primary care patients with acute cough.Methods:A total of 3,104 patients with acute cough (⩽28 days) were included in a prospective observational study with a within-nested trial, of which 2,427 underwent spirometry 28-35 days after inclusion. Influence of the lung function abnormalities fixed obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) and bronchodilator responsiveness (FEV1 increase of ⩾12% or 200 ml after 400 μg salbutamol) on symptom severity, duration and worsening were evaluated using uni- and multivariable regression models. Antibiotic use was defined as the reported use of antibiotics ⩾5 days in the first week. Interaction terms were calculated to investigate modifying effects of lung function on antibiotic effect.Results:The only significant association was the effect of severe airway obstruction on symptom severity on days 2-4 (difference=0.31, 95% confidence interval (CI)=0.03-0.60, P=0.03). No evidence of a differential effect of lung function on the effect of antibiotics was found. Prior use of inhaled steroids was associated with a 30% slower resolution of symptoms rated 'moderately bad' or worse (hazard ratio=0.75, 95% CI=0.63-0.90, P=0.00).Conclusions:In adult patients with acute cough, lung function abnormalities were neither significantly associated with course of disease nor did they modify the effect of antibiotics.
npj Primary Care Respiratory Medicine 09/2014; 24:14067. DOI:10.1038/npjpcrm.2014.67
[Show abstract][Hide abstract] ABSTRACT: Background: Patient safety culture, described as shared values, attitudes and behavior of staff in a health-care organization, gained attention as a subject of study as it is believed to be related to the impact of patient safety improvements. However, in primary care, it is yet unknown, which effect interventions have on the safety culture. Objectives: To review literature on the use of interventions that effect patient safety culture in primary care. Methods: Searches were performed in PubMed, EMBASE, CINAHL, and PsychINFO on March 4, 2013. Terms defining safety culture were combined with terms identifying intervention and terms indicating primary care. Inclusion followed if the intervention effected patient safety culture, and effect measures were reported. Results: The search yielded 214 articles from which two were eligible for inclusion. Both studies were heterogeneous in their interventions and outcome; we present a qualitative summary. One study described the implementation of an electronic medical record system in general practices as part of patient safety improvements. The other study facilitated 2 workshops for general practices, one on risk management and another on significant event audit. Results showed signs of improvement, but the level of evidence was low because of the design and methodological problems. Conclusions: These studies in general practice provide a first understanding of improvement strategies and their effect in primary care. As the level of evidence was low, no clear preference can be determined. Further research is needed to help practices make an informed choice for an intervention.
[Show abstract][Hide abstract] ABSTRACT: Rhinovirus infections occur frequently throughout life and have been reported in about one-third of asymptomatic cases. The clinical significance of sequential rhinovirus infections remains unclear. To determine the incidence and clinical relevance of sequential rhinovirus detections, nasopharyngeal samples from 2485 adults with acute cough/lower respiratory illness were analysed. Patients were enrolled prospectively by general practitioners from 12 European Union countries during three consecutive years (2007-2010). Nasopharyngeal samples were collected at the initial general practitioner consultation and 28 days thereafter and symptom scores were recorded by patients over that period. Rhinovirus RNA was detected in 444 (18%) out of 2485 visit one samples and in 110 (4.4%) out of 2485 visit two respiratory samples. 21 (5%) of the 444 patients had both samples positive for rhinovirus. Genotyping of both virus detections was successful for 17 (81%) out of 21 of these patients. Prolonged rhinovirus shedding occurred in six (35%) out of 21 and re-infection with a different rhinovirus in 11 (65%) out of 21. Rhinovirus re-infections were significantly associated with chronic obstructive pulmonary disease (p=0.04) and asthma (p=0.02) and appeared to be more severe than prolonged infections. Our findings indicate that in immunocompetent adults rhinovirus re-infections are more common than prolonged infections, and chronic airway comorbidities might predispose to more frequent rhinovirus re-infections.
European Respiratory Journal 07/2014; 44(1):169-77. DOI:10.1183/09031936.00172113 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Canuti and Martin Deijs have contributed equally to this work. Previously unknown or unexpected pathogens may be responsible for that proportion of respiratory diseases in which a causative agent cannot be identified. The application of broad-spectrum, sequence independent virus discovery techniques may be useful to reduce this proportion and widen our knowledge about respiratory pathogens. Thanks to the availability of high-throughput sequencing (HTS) technology, it became today possible to detect viruses which are present at a very low load, but the clinical relevance of those viruses must be investigated. In this study we used VIDISCA-454, a restriction enzyme based virus discovery method that utilizes Roche 454 HTS system, on a nasal swab collected from a subject with respiratory complaints. A γ-papillomavirus was detected (complete genome: 7142 bp) and its role in disease was investigated. Respiratory samples collected both during the acute phase of the illness and 2 weeks after full recovery contained the virus. The patient presented antibodies directed against the virus but there was no difference between IgG levels in blood samples collected during the acute phase and 2 weeks after full recovery. We therefore concluded that the detected γ-papillomavirus is unlikely to be the causative agent of the respiratory complaints and its presence in the nose of the patient is not related to the disease. Although HTS based virus discovery techniques proved their great potential as a tool to clarify the etiology of some infectious diseases, the obtained information must be subjected to cautious interpretations. This study underlines the crucial importance of performing careful investigations on viruses identified when applying sensitive virus discovery techniques, since the mere identification of a virus and its presence in a clinical sample are not satisfactory proofs to establish a causative link with a disease.
Frontiers in Microbiology 07/2014; 5:374. DOI:10.3389/fmicb.2014.00347 · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A positive patient safety culture is considered a main condition for patient safety. Several initiatives have been taken with the intention to improve this culture in healthcare. Because these were mainly implemented in hospitalized care settings not much is known about ameliorating patient safety culture in general practice. Therefore, we aimed at examining the effect of two patient safety culture interventions in general practice.
We conducted a cluster randomized three armed trial, one control group and two intervention groups, in thirty general practices in the Netherlands. The interventions consisted of a Dutch patient safety culture questionnaire solely, or this questionnaire combined with a workshop on practice location. The workshop was based on MaPSaF and processed the practice results of theculture questionnaire. It comprised theory and discussion with the objective to draw a practice specific action plan. After randomisation 10 practices served as controls, 10 practices received the safety culture questionnaire as intervention, and 10 had the combination of the questionnaire and the workshop. All practices were asked to fill out a practice information form before the intervention and one year hereafter. In this form general safety and quality issues were addressed such as whether the practice had a formal incident reporting procedure, the number of incident reports and whether they were analysed; whether there was a complaint procedure and number of registered complaints; whether there were staff meetings and if patient safety (culture) were part of these; whether training was followed in the field of patient safety and whether a safety management system or policy was present. Improvement in patient safety culture was operationalized as an increase in reported number of incident as a primary outcome measure. At follow-up, we also asked all staff of all practices, including the controls, to complete the safety culture questionnaire. In addition, to be able to evaluate the process of patient safety improvements we performed semi-structured interviews.
Thirty practices completed the pre practice information form. During the intervention period two practices in the 'combination' group dropped out. For this, we randomly moved one of the control practices to this intervention group. Up until now, 27 practices filled out this questionnaire post intervention. The SCOPE questionnaire is completed by 171 respondents distributed over the 28 practices with a range of 1 to 13. We conducted 48 interviews with respectively 24 physicians, 21 medical assistants and 3 practice nurses. Data cleaning and analysis about to start and will be finished by the end of 2013.
this study is one of the first attempting to at shed light on the effectiveness of patient safety culture improvement interventions in general practice. With collecting both quantitative and qualitative data, not only the effect of the intervention is examined but also potential underlying grounds for the results in the practices can be clarified. These findings will contribute to our knowledge about patient safety improvements in general practice and may enhance future interventions.
[Show abstract][Hide abstract] ABSTRACT: Patient safety culture, described as shared values, attitudes and behavior of staff in a health-care organization, gained attention as a subject of study as it is believed to be related to the impact of patient safety improvements. However, in primary care, it is yet unknown, which effect interventions have on the safety culture.
To review literature on the use of interventions that effect patient safety culture in primary care.
Searches were performed in PubMed, EMBASE, CINAHL, and PsychINFO on March 4, 2013. Terms defining safety culture were combined with terms identifying intervention and terms indicating primary care. Inclusion followed if the intervention effected patient safety culture, and effect measures were reported.
The search yielded 214 articles from which two were eligible for inclusion. Both studies were heterogeneous in their interventions and outcome; we present a qualitative summary. One study described the implementation of an electronic medical record system in general practices as part of patient safety improvements. The other study facilitated 2 workshops for general practices, one on risk management and another on significant event audit. Results showed signs of improvement, but the level of evidence was low because of the design and methodological problems.
These studies in general practice provide a first understanding of improvement strategies and their effect in primary care. As the level of evidence was low, no clear preference can be determined. Further research is needed to help practices make an informed choice for an intervention.
Journal of Patient Safety 03/2014; Publish Ahead of Print. DOI:10.1097/PTS.0000000000000075 · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Countries generally present their overall use of antibiotics as an indicator of antibiotic prescribing quality. Additional insight is urgently needed for targeted improvement recommendations: first, data on specific clinical indications for which antibiotics are used, and second, on distinguishing whether changes in patient consultation or changes in physician prescribing drive changing antibiotic use for particular indications. The aim of this study was to describe the antibiotic management of infectious diseases in the clinical context, by analysing prescribing by physicians and patient consultation incidences per indication over time.
A database with all contact data for infectious diseases from 45 primary care practices in the Netherlands (2007-10) was used. Consultation incidences, prescribing rates and choice of antibiotic were analysed per International Classification of Primary Care (ICPC) chapter and relevant ICPC codes.
Antibiotics were prescribed in ∼25% of infectious disease episodes, mainly respiratory infections, urinary infections and ear and skin infections. Overall, this resulted in 300 prescribed courses of antibiotics per 1000 patient-years. Given a stable prescription rate, a 19% increase in the number of consultations explained the increased antibiotic prescribing for urinary tract infections. Given a stable consultation incidence, an 8% reduction in prescribing rate explained the decreased antibiotic prescribing for respiratory tract infections. Macrolides were predominantly prescribed for respiratory disease (∼66%), amoxicillin/clavulanate for respiratory disease (∼42%) and urinary illness (∼25%), and fluoroquinolones for urinary and genital indications.
Insight into the reasons for the decreased prescribing for respiratory tract infections and the increased prescribing for urinary tract infections was provided by a detailed analysis of incidences and prescribing rates. For respiratory disease, the second- and third-choice antibiotics were overused. Complete data on infectious disease management, with respect to patient and physician behaviour, are crucial for understanding changes in antibiotic use, and in defining strategies to reduce inappropriate antibiotic use.
[Show abstract][Hide abstract] ABSTRACT: 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.
British Journal of General Practice 01/2014; 64(619):e81-e91. DOI:10.3399/bjgp14X677130 · 2.29 Impact Factor