Contact With Young Children Increases the Risk of Respiratory Infection in Older Adults in Europe-the RESCEU Study.

BACKGROUND: Knowledge about how older adults get a respiratory infection is crucial for planning preventive strategies. We aimed to determine how contact with young children living outside of the household affects the risk of acute respiratory tract infections (ARTI) in community-dwelling older adults. METHODS: This study is part of the European RESCEU older adult study. Weekly surveillance was performed to detect ARTI throughout 2 winter seasons (2017-2018, 2018-2019). Child exposure, defined as having regular contact with children under 5 living outside of the subject's household, was assessed at baseline. The average attributable fraction was calculated to determine the fraction of ARTI explained by exposure to these children. RESULTS: We prospectively established that 597/1006 (59%) participants experienced at least 1 ARTI. Child exposure increased the risk of all-cause ARTI (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.21 -2.08; P = .001). This risk was highest in those with the most frequent contact (aOR, 1.80; 95% CI, 1.23-2.63; P = .003). The average attributable fraction of child exposure explaining ARTI was 10% (95% CI, 5%-15%). CONCLUSIONS: One of 10 ARTI in community-dwelling older adults is attributable to exposure to preschool children living outside of the household. CLINICAL TRIALS REGISTRATION: NCT03621930.

World Health Organization Influenza-Like Illness Underestimates the Burden of Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) surveillance is heavily dependent on the influenza-like illness (ILI) case definition from the World Health Organization (WHO). Because ILI includes fever in its syndromic case definition, its ability to accurately identify acute respiratory tract infections (ARTI) caused by RSV in older adults is uncertain. METHODS: The accuracy of the WHO ILI and a modified ILI (requiring only self-reported fever) case definitions in identifying patients with PCR-confirmed RSV-ARTI was evaluated in community-dwelling older adults (≥60 years) from the prospective European RESCEU cohort study. RESULTS: Among 1040 participants, 750 ARTI episodes were analyzed including 36 confirmed RSV-ARTI. Due to a general lack of fever, sensitivity for RSV-ARTI was 33% for modified ILI and 11% for ILI. The area under the curve for both ILI definitions was 0.52 indicating poor discrimination for RSV. RSV-ARTI could not be distinguished from all other ARTI based on clinical symptoms. CONCLUSIONS: The use of ILI underestimated the occurrence of RSV-ARTI in community-dwelling older adults up to 9-fold (11% sensitivity). Because worldwide RSV surveillance depends largely on ILI, there is an urgent need for a better approach to measure the occurrence of RSV disease and the impact of future RSV vaccine introduction. Clinical Trials Registration. NCT03621930.

Performance Assessment of a Rapid Molecular Respiratory Syncytial Virus Point-of-Care Test: A Prospective Community Study in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) causes a substantial burden in older adults. Viral load in RSV-infected adults is generally lower compared to young children, which could result in suboptimal sensitivity of RSV diagnostics. Although the Xpert® Xpress Flu/RSV assay has been used in routine clinical care, its sensitivity to diagnose RSV infection in older adults is largely unknown. We aimed to compare the performance of the Xpert® Xpress Flu/RSV assay with real-time reverse-transcription polymerase chain reaction (RT-PCR) in home-dwelling older adults (≥60 years of age). METHODS: Nasopharyngeal swabs were tested with Xpert® Xpress Flu/RSV and compared to RSV RT-PCR in older adults with acute respiratory tract infections with different levels of disease severity. RESULTS: We studied 758 respiratory samples from 561 older adults from 2 consecutive RSV seasons. Thirty-five (4.6%) samples tested positive for RSV by at least 1 of the assays, of which 2 samples were negative by Xpert® Xpress Flu/RSV and 3 samples by real-time RT-PCR. The positive percentage agreement (PPA) was 90.9% (95% confidence interval [CI], 76.4%-96.8%) and negative percentage agreement was 99.7% (95% CI, 99.0%-99.9%). Viral loads were low (≤103 copies/mL or cycle threshold value ≥34) in all cases with discordant results for the 2 assays. CONCLUSIONS: The PPA of Xpert® Xpress Flu/RSV compared to routine RT-PCR is high for RSV detection in home-dwelling older adults. The assay is fast and easy to use at the point of care. CLINICAL TRIALS REGISTRATION: NCT03621930.

Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries.

BACKGROUND: a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. OBJECTIVES: (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. METHODS: we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. RESULTS: participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. CONCLUSIONS: decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.

Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries.

BACKGROUND: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. OBJECTIVE: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. METHODS: Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. RESULTS: A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 ± 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). CONCLUSION: Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms.

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial.

BACKGROUND: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. METHODS: We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. FINDINGS: Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. INTERPRETATION: Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. FUNDING: European Commission's Seventh Framework Programme.

Diagnosing serious infections in older adults presenting to ambulatory care: a systematic review.

OBJECTIVES: to summarise all available evidence on the accuracy of clinical features and blood tests for diagnosing serious infections in older patients presenting to ambulatory care. METHODS: systematic review, searching seven databases using a comprehensive search strategy. We included cross-sectional prospective diagnostic studies on (1) clinical features, (2) diagnostic prediction rules based on clinical features alone, (3) blood tests and (4) diagnostic prediction rules combining clinical features and blood tests. Study participants had to be community-dwelling adults aged ≥65 years, in whom a physician suspected an infection. We used QUADAS-2 to assess risk of bias. We calculated measures of diagnostic accuracy and present descriptive statistics. RESULTS: out of 13,757 unique articles, only six studies with a moderate to high risk of bias were included. There was substantial clinical heterogeneity across these studies. Clinical features had LR- ≥0.61 and LR+ ≤4.94. Twelve prediction rules using clinical features had LR- ≥0.30 and LR+ ≤2.78. There was evidence on four blood tests of which procalcitonin was the most often investigated: levels <0.37 ng/ml (LR- = 0.20; 95%CI 0.10-0.42) were suitable to rule out sepsis in moderately high prevalence situations. Two diagnostic prediction rules combining clinical features and procalcitonin had LR- of ≤0.12 (95%CI 0.05-0.33) and LR+ of maximum 1.39 (95%CI 1.30-1.49). CONCLUSIONS: we found few studies on the diagnostic accuracy of clinical features and blood tests to detect serious infections in older people presenting to ambulatory care. The risk of bias was mostly moderate to high, leading to substantial uncertainty.

Incidence and management of acute otitis media in adults: a primary care-based cohort study.

BACKGROUND: Although primarily considered a childhood disease, acute otitis media (AOM) also occurs in adults. Data on the burden of this condition in adults are, however, scarce. OBJECTIVE: To explore the primary care incidence and current management of AOM in adults. METHODS: All patients aged 15 and older included in the routine health care database of the Julius General Practitioners' Network were followed from 2015 to 2018 (contributing to a total of 1 261 575 person-years). We extracted data on AOM episodes, AOM-related consultations, comorbidities, and antibiotic and analgesic prescriptions. RESULTS: Five thousand three hundred and fifty-eight patients experienced one or more AOM episodes (total number of AOM episodes: 6667; mean 1.2 per patient). The overall AOM incidence was 5.3/1000 person-years and was fairly stable over the study period. Incidence was particularly high in atopic patients (7.3/1000 person-years) and declined with age (from 7.1 in patients 15-39 years of age to 2.7/1000 person-years in those aged 64 years and older). Oral antibiotics, predominantly amoxicillin, were prescribed in 46%, and topical antibiotics in 21% of all episodes. CONCLUSION: Over the past years, the incidence of AOM in adults in primary care has been stable. Oral antibiotic prescription rates resemble those in children with AOM, whereas a remarkably high topical antibiotic prescription rate was observed. Future prognostic research should inform on the need and feasibility of prospective studies into the best management strategy in this condition.

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis.

OBJECTIVE: Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. DESIGN: Secondary analysis of randomized controlled trial data. SETTING: Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. SUBJECTS: A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. MAIN OUTCOME MEASURES: Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. RESULTS: At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0-210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). CONCLUSION: There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.Key PointsPredicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians.• There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care.• There was no association between CRP concentration at baseline and benefit from oseltamivir treatment.• We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

Molecular epidemiology and clinical impact of rhinovirus infections in adults during three epidemic seasons in 11 European countries (2007-2010).

BACKGROUND: Differences in clinical impact between rhinovirus (RVs) species and types in adults are not well established. The objective of this study was to determine the epidemiology and clinical impact of the different RV species. METHODS: We conducted a prospective study of RVs infections in adults with acute cough/lower respiratory tract infection (LRTI) and asymptomatic controls. Subjects were recruited from 16 primary care networks located in 11 European countries between 2007 and 2010. RV detection and genotyping was performed by means of real time and conventional reverse-transcriptase polymerase chain reaction assays, followed by sequence analysis. Clinical data were obtained from medical records and patient symptom diaries. RESULTS: RVs were detected in 566 (19%) of 3016 symptomatic adults, 102 (4%) of their 2539 follow-up samples and 67 (4%) of 1677 asymptomatic controls. Genotyping was successful for 538 (95%) symptomatic subjects, 86 (84%) follow-up infections and 62 (93%) controls. RV-A was the prevailing species, associated with an increased risk of LRTI as compared with RV-B (relative risk (RR), 4.5; 95% CI 2.5 to 7.9; p<0.001) and RV-C (RR 2.2; 95% CI 1.2 to 3.9; p=0.010). In symptomatic subjects, RV-A loads were higher than those of RV-B (p=0.015). Symptom scores and duration were similar across species. More RV-A infected patients felt generally unwell in comparison to RV-C (p=0·023). Of the 140 RV types identified, five were new types; asymptomatic infections were associated with multiple types. INTERPRETATION: In adults, RV-A is significantly more often detected in cases with acute cough/LRTI than RV-C, while RV-B infection is often found in asymptomatic patients.

Using point-of-care C-reactive protein to guide antibiotic prescribing for lower respiratory tract infections in elderly nursing home residents (UPCARE): study design of a cluster randomized controlled trial.

BACKGROUND: Antibiotics are over-prescribed for lower respiratory tract infections (LRTI) in nursing home residents due to diagnostic uncertainty. Inappropriate antibiotic use is undesirable both on patient level, considering their exposure to side effects and drug interactions, and on societal level, given the development of antibiotic resistance. C-reactive protein (CRP) point-of-care testing (POCT) may be a promising diagnostic tool to reduce antibiotic prescribing for LRTI in nursing homes. The UPCARE study will evaluate whether the use of CRP POCT for suspected LRTI is (cost-) effective in reducing antibiotic prescribing in the nursing home setting. METHODS/DESIGN: A cluster randomized controlled trial will be conducted in eleven nursing homes in the Netherlands, with the nursing home as the unit of randomization. Residents with suspected LRTI who reside at a psychogeriatric, somatic, or geriatric rehabilitation ward are eligible for study participation. Nursing homes in the intervention group will provide care as usual with the possibility to use CRP POCT, and the control group will provide care as usual without CRP POCT for residents with (suspected) LRTI. Data will be collected from September 2018 for approximately 1.5 year, using case report forms that are integrated in the electronic patient record system. The primary study outcome is antibiotic prescribing for suspected LRTI at index consultation (yes/no). DISCUSSION: This is the first randomised trial to evaluate the effect of nursing home access to and training in the use of CRP POCT on antibiotic prescribing for LRTI, yielding high-level evidence and contributing to antibiotic stewardship in the nursing home setting. The relatively broad inclusion criteria and the pragmatic study design add to the applicability and generalizability of the study results. TRIAL REGISTRATION: Netherlands Trial Register, Trial NL5054. Registered 29 August 2018.

Cost-effectiveness analysis of a GP- and parent-directed intervention to reduce antibiotic prescribing for children with respiratory tract infections in primary care.

OBJECTIVES: We evaluated costs and effects of the RAAK (RAtional Antibiotic use Kids) intervention (GP online training and information booklets for parents), aiming to reduce antibiotic prescribing for children with respiratory tract infection (RTI). METHODS: We conducted a trial-based cost-effectiveness analysis from a societal perspective. We included children consulting the GP with RTI for whom parents kept a 2 week (cost) diary. The antibiotic prescribing rate was the percentage of children receiving an antibiotic prescription at the index consultation and during the 2 weeks of follow-up. The cost difference between the intervention and usual care groups per percentage decrease in antibiotic prescribing was calculated. Bootstrapping was used to assess uncertainty surrounding the outcomes. RESULTS: Costs and effects of 153 children in the intervention group and 107 children in the usual care group were available for analysis. Antibiotic prescribing was 12% lower in the intervention group and costs were €10.27 higher in the intervention group compared with the usual care group. This resulted in an incremental cost-effectiveness ratio of €0.85 per percentage decrease in antibiotic prescribing. The probability that the intervention was more effective, but more expensive, was 53%, whereas the probability that the intervention was more effective and less expensive compared with usual care was 41%. CONCLUSIONS: The online training for GPs and the information booklet for parents resulted in a decrease in antibiotic prescribing in children with RTI, at very low cost, and should therefore be considered for implementation in primary care.

Impetigo incidence and treatment: a retrospective study of Dutch routine primary care data.

BACKGROUND: There is a lack of recently published data on impetigo presentation incidence and treatment practices in the routine Western European primary care setting. OBJECTIVES: To investigate impetigo incidence, treatments and recurrence in primary care in the Netherlands. METHODS: A retrospective, observational study. Electronic records of patients treated for impetigo in 2015 at 29 general practices in Utrecht and surrounds were reviewed. An episode of impetigo was defined as one or more patient-doctor contacts within 8 weeks of the index consultation. Within an episode, patient demographics and prescribing patterns were analysed including number of treatments, and the category and sequence of individual medicines. RESULTS: A total of 1761 impetigo episodes were managed, with an incidence rate of 13.6 per 1000 person years. Impetigo peaked in summer. Most patients, the majority children, experienced a single episode (93%), and 25% had eczema as comorbidity. Topical antibiotics (primarily fusidic acid) were the most prescribed initial treatments (85%), followed by oral antibiotics (14%). Topical antibiotics were progressively used less over subsequent treatments, while there was an inverse increase in oral antibiotic use. Topical fusidic acid as the most common first line treatment seemed satisfactory as only 12% of initial treatments with this drug received further therapy. Repeat treatments generally occurred within 7 days. CONCLUSION: This study of impetigo prescribing patterns in primary care highlighted that Dutch general practitioners were generally adherent to national treatment guidelines. Topical treatment, and if needed systemic small-spectrum antibiotic treatment, appeared satisfactory; these findings aid in antimicrobial stewardship.

Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Effectiveness of general practitioner online training and an information booklet for parents on antibiotic prescribing for children with respiratory tract infection in primary care: a cluster randomized controlled trial.

Objectives: Antibiotics are too often prescribed in childhood respiratory tract infection (RTI), despite limited effectiveness, potential side effects and bacterial resistance. We aimed to reduce antibiotic prescribing for children with RTI by online training for general practitioners (GPs) and information for parents. Methods: A pragmatic cluster randomized controlled trial in primary care. The intervention consisted of online training for GPs and an information booklet for parents. The primary outcome was the antibiotic prescription rate for children presenting with RTI symptoms, as registered by GPs. Secondary outcomes were number of reconsultations within the same disease episode, consultations for new episodes, hospital referrals and pharmacy-dispensed antibiotic courses for children. This trial was registered at the Dutch Trial Register (NTR), registration number: NTR4240. Results: After randomization, GPs from a total of 32 general practices registered 1009 consultations. An antibiotic was prescribed in 21% of consultations in the intervention group, compared with 33% in the usual care group, controlled for baseline prescribing (rate ratio 0.65, 95% CI 0.46-0.91). The probability of reconsulting during the same RTI episode did not differ significantly between the intervention and control groups, and nor did the numbers of consultations for new episodes and hospital referrals. In the intervention group antibiotic dispensing was 32 courses per 1000 children/year lower than the control group, adjusted for baseline prescribing (rate ratio 0.78, 95% CI 0.66-0.92). The numbers and proportion of second-choice antibiotics did not differ significantly. Conclusions: Concise, feasible, online GP training, with an information booklet for parents, showed a relevant reduction in antibiotic prescribing for children with RTI.

Analytical performance of a platform for point-of-care CRP testing in adults consulting for lower respiratory tract infection in primary care.

C-reactive protein (CRP) is a biomarker widely used for disease severity assessment and treatment of inflammatory conditions. Point-of-care testing (POCT) devices should ideally be rapid and provide similar results to standard tests done in laboratories. Two thousand nine hundred twenty-two serum samples were obtained from adult patients presenting to primary care with symptoms of lower respiratory infection in a European diagnostic study. The analytic performance of the CRP QuikRead POCT device (Orion Diagnostica) was evaluated by comparing results with a central laboratory method (Dimension Vista, Siemens), with both tests performed in a laboratory setting. For a CRP cut-off concentration of ≥ 30 mg/L, the QuikRead test had a sensitivity of 92.2%, and specificity of 99.4%. The mean difference between the QuikRead and the central lab test was 0.4 mg/L. The slope of the Passing-Bablok regression was 0.94 (95% CI 0.93-0.95) indicating an underestimation of CRP levels of 6% by QuikRead. CRP estimates obtained from the QuikRead test correlate well with a central laboratory assay and the measurement displays low inter-assay variation. Therefore, the QuikRead test is a good candidate for CRP testing in primary care.

Predicting the presence of bacterial pathogens in the airways of primary care patients with acute cough.

BACKGROUND: Bacterial testing of all patients who present with acute cough is not feasible in primary care. Furthermore, the extent to which easily obtainable clinical information predicts bacterial infection is unknown. We evaluated the diagnostic value of clinical examination and testing for C-reactive protein and procalcitonin for bacterial lower respiratory tract infection. METHODS: Through a European diagnostic study, we recruited 3104 adults with acute cough (≤ 28 days) in primary care settings. All of the patients underwent clinical examination, measurement of C-reactive protein and procalcitonin in blood, and chest radiography. Bacterial infection was determined by conventional culture, polymerase chain reaction and serology, and positive results were defined by the presence of Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Bordetella pertussis or Legionella pneumophila. Using multivariable regression analysis, we examined the association of diagnostic variables with the presence of bacterial infection. RESULTS: Overall, 539 patients (17%) had bacterial lower respiratory tract infection, and 38 (1%) had bacterial pneumonia. The only item with diagnostic value for lower respiratory tract infection was discoloured sputum (area under the receiver operating characteristic [ROC] curve 0.56, 95% confidence interval [CI] 0.54-0.59). Adding C-reactive protein above 30 mg/L increased the area under the ROC curve to 0.62 (95% CI 0.59-0.65). For bacterial pneumonia, comorbidity, fever and crackles on auscultation had diagnostic value (area under ROC curve 0.68, 95% CI 0.58-0.77). Adding C-reactive protein above 30 mg/L increased the area under the ROC curve to 0.79 (95% CI 0.71-0.87). Procalcitonin did not add diagnostic information for any bacterial lower respiratory tract infection, including bacterial pneumonia. INTERPRETATION: In adults presenting with acute lower respiratory tract infection, signs, symptoms and C-reactive protein showed diagnostic value for a bacterial cause. However, the ability of these diagnostic indicators to exclude a bacterial cause was limited. Procalcitonin added no clinically relevant information.

The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data.

BACKGROUND: C-reactive protein (CRP) is increasingly being included in the diagnostic work-up for community-acquired pneumonia in primary care. Its added diagnostic value beyond signs and symptoms, however, remains unclear. We conducted a meta-analysis of individual patient data to quantify the added value of CRP measurement. METHODS: We included studies of the diagnostic accuracy of CRP in adult outpatients with suspected lower respiratory tract infection. We contacted authors of eligible studies for inclusion of data and for additional data as needed. The value of adding CRP measurement to a basic signs-and-symptoms prediction model was assessed. Outcome measures were improvement in discrimination between patients with and without pneumonia in primary care and improvement in risk classification, both within the individual studies and across studies. RESULTS: Authors of 8 eligible studies (n = 5308) provided their data sets. In all of the data sets, discrimination between patients with and without pneumonia improved after CRP measurement was added to the prediction model (extended model), with a mean improvement in the area under the curve of 0.075 (range 0.02-0.18). In a hypothetical cohort of 1000 patients, the proportion of patients without pneumonia correctly classified at low risk increased from 28% to 36% in the extended model, and the proportion with pneumonia correctly classified at high risk increased from 63% to 70%. The number of patients with pneumonia classified at low risk did not change (n = 4). Overall, the proportion of patients assigned to the intermediate-risk category decreased from 56% to 51%. INTERPRETATION: Adding CRP measurement to the diagnostic work-up for suspected pneumonia in primary care improved the discrimination and risk classification of patients. However, it still left a substantial group of patients classified at intermediate risk, in which clinical decision-making remains challenging.

Antibiotic management of children with infectious diseases in Dutch Primary Care.

Background: Childhood infections are common in general practice. Although clinical guidelines recommend restrictive antibiotic use for children, antibiotics are too often prescribed. Objective: The aim of this study was to obtain insight in antibiotic prescribing for children related to clinical diagnoses. This is pivotal to define improvement strategies in the antibiotic management. Methods: In this observational study, we used consultation data collected from 45 general practices in the Netherlands in 2012. Infectious disease episode incidences, the number of antibiotic prescriptions per 1000 person-years, the proportion of episodes with an antibiotic prescription and the choice of antibiotic subclass were analysed for the most relevant diagnoses over different ages. Results: A total of 262 antibiotic courses were prescribed per 1000 person-years on average, with the highest number among children of 1 year (714/1000 person-years). Antibiotics were prescribed in 24% of infectious disease episodes. Acute upper respiratory tract infection (RTI) was the most common reason to visit the GP (173/1000 person-years), and the second most frequent indication to prescribe antibiotics. Antibiotics were most often prescribed for acute otitis media (58/1000 person-years). Amoxicillin dominated prescribing (55%), followed by macrolides (14%) and amoxicillin/clavulanate (10%), prescribing of narrow-spectrum antibiotics was low (10%). Conclusion: This detailed insight in antibiotic management of childhood infections shows targets for Dutch improvement strategies: (i) prevent antibiotic prescribing for acute upper RTI and bronchitis; (ii) stimulate the use of narrow-spectrum antibiotics; and (iii) reduce the use of macrolides and amoxicillin/clavulanate. Furthermore, this information is helpful to compare antibiotic policy between countries.

Clinicians' interpretations of point of care urine culture versus laboratory culture results: analysis from the four-country POETIC trial of diagnosis of uncomplicated urinary tract infection in primary care.

Background: Urine culture at the point of care minimises delay between obtaining the sample and agar inoculation in a microbiology laboratory, and quantification and sensitivity results can be available more rapidly in primary care. Objective: To identify the degree to which clinicians' interpretations of a point-of-care-test (POCT) urine culture (Flexicult™ SSI-Urinary Kit) agrees with laboratory culture in women presenting to primary care with symptoms of uncomplicated urinary tract infections (UTI). Methods: Primary care clinicians used the Flexicult™-POCT, recorded their findings and took a photograph of the result, which was interpreted by microbiology laboratory technicians. Urine samples were additionally processed in routine care laboratories. Cross tabulations were used to identify important differences in organism identification, quantification and antibiotic susceptibility between these three sources of data. The influence of various laboratory definitions for UTI on culture were assessed. Results: Primary care clinicians identified 202/289 urine samples (69.9%) as positive for UTI using the Flexicult™-POCT, whereas laboratory culture identified 94-190 (32.5-65.7%) as positive, depending on definition thresholds. 82.9% of samples identified positive for E. coli on laboratory culture were also considered positive for E. coli using the Flexicult™ -POCT, and susceptibilities were reasonably concordant. There were major discrepancies between laboratory staff interpretation of Flexicult™ photographs, clinicians' interpretation of the Flexicult™ test, and laboratory culture results. Conclusion: Flexicult™-POCT overestimated the positivity rate of urine samples for UTI when laboratory culture was used as the reference standard. However, it is unclear whether point-of-care or laboratory based urine culture provides the most valid diagnostic information.