Influenza epidemic surveillance and prediction based on electronic health record data from an out-of-hours general practitioner cooperative: model development and validation on 2003-2015 data.

BACKGROUND: Annual influenza epidemics significantly burden health care. Anticipating them allows for timely preparation. The Scientific Institute of Public Health in Belgium (WIV-ISP) monitors the incidence of influenza and influenza-like illnesses (ILIs) and reports on a weekly basis. General practitioners working in out-of-hour cooperatives (OOH GPCs) register diagnoses of ILIs in an instantly accessible electronic health record (EHR) system. This article has two objectives: to explore the possibility of modelling seasonal influenza epidemics using EHR ILI data from the OOH GPC Deurne-Borgerhout, Belgium, and to attempt to develop a model accurately predicting new epidemics to complement the national influenza surveillance by WIV-ISP. METHOD: Validity of the OOH GPC data was assessed by comparing OOH GPC ILI data with WIV-ISP ILI data for the period 2003-2012 and using Pearson's correlation. The best fitting prediction model based on OOH GPC data was developed on 2003-2012 data and validated on 2012-2015 data. A comparison of this model with other well-established surveillance methods was performed. A 1-week and one-season ahead prediction was formulated. RESULTS: In the OOH GPC, 72,792 contacts were recorded from 2003 to 2012 and 31,844 from 2012 to 2015. The mean ILI diagnosis/week was 4.77 (IQR 3.00) and 3.44 (IQR 3.00) for the two periods respectively. Correlation between OOHs and WIV-ISP ILI incidence is high ranging from 0.83 up to 0.97. Adding a secular trend (5 year cycle) and using a first-order autoregressive modelling for the epidemic component together with the use of Poisson likelihood produced the best prediction results. The selected model had the best 1-week ahead prediction performance compared to existing surveillance methods. The prediction of the starting week was less accurate (±3 weeks) than the predicted duration of the next season. CONCLUSION: OOH GPC data can be used to predict influenza epidemics both accurately and fast 1-week and one-season ahead. It can also be used to complement the national influenza surveillance to anticipate optimal preparation.

Clinical prediction rules combining signs, symptoms and epidemiological context to distinguish influenza from influenza-like illnesses in primary care: a cross sectional study.

BACKGROUND: During an influenza epidemic prompt diagnosis of influenza is important. This diagnosis however is still essentially based on the interpretation of symptoms and signs by general practitioners. No single symptom is specific enough to be useful in differentiating influenza from other respiratory infections. Our objective is to formulate prediction rules for the diagnosis of influenza with the best diagnostic performance, combining symptoms, signs and context among patients with influenza-like illness. METHODS: During five consecutive winter periods (2002-2007) 138 sentinel general practitioners sampled (naso- and oropharyngeal swabs) 4597 patients with an influenza-like illness (ILI) and registered their symptoms and signs, general characteristics and contextual information. The samples were analysed by a DirectigenFlu-A&B and RT-PCR tests. 4584 records were useful for further analysis.Starting from the most relevant variables in a Generalized Estimating Equations (GEE) model, we calculated the area under the Receiver Operating Characteristic curve (ROC AUC), sensitivity, specificity and likelihood ratios for positive (LR+) and negative test results (LR-) of single and combined signs, symptoms and context taking into account pre-test and post-test odds. RESULTS: In total 52.6% (2409/4584) of the samples were positive for influenza virus: 64% (2066/3212) during and 25% (343/1372) pre/post an influenza epidemic. During and pre/post an influenza epidemic the LR+ of 'previous flu-like contacts', 'coughing', 'expectoration on the first day of illness' and 'body temperature above 37.8°C' is 3.35 (95%CI 2.67-4.03) and 1.34 (95%CI 0.97-1.72), respectively. During and pre/post an influenza epidemic the LR- of 'coughing' and 'a body temperature above 37.8°C' is 0.34 (95%CI 0.27-0.41) and 0.07 (95%CI 0.05-0.08), respectively. CONCLUSIONS: Ruling out influenza using clinical and contextual information is easier than ruling it in. Outside an influenza epidemic the absence of cough and fever (> 37,8°C) makes influenza 14 times less likely in ILI patients. During an epidemic the presence of 'previous flu-like contacts', cough, 'expectoration on the first day of illness' and fever (>37,8°C) increases the likelihood for influenza threefold. The additional diagnostic value of rapid point of care tests especially for confirming influenza still has to be established.

Implementation of a general practitioner cooperative adjacent to the emergency department of a hospital increases the caseload for the GPC but not for the emergency department.

BACKGROUND: The implementation of general practitioner cooperatives (GPC) for out-of-hours (OOH) primary care, raises the question if the location of a GPC adjacent to a hospital reduces the OOH caseload of the emergency department (ED). METHODS: Two natural experiments were used in this before-after study, the effect of the implementation of two GPCs in two different regions on the out-of-hours caseload of the local EDs was compared. One GPC was located adjacent to the ED of a general hospital, the other was not. GPCs (or rota systems) and EDs in comparable regions were selected as control groups during the same study period. The study was performed in Flanders (Belgium) with no gatekeeping function for general practitioners (GPs). RESULTS: After implementation of the GPC there was a significantly increase in caseload at the GPC in the two regions, mainly due to an increase of consultations with small children. There were no significant changes in caseload at the ED services. Self-referrals' to the ED did not change significantly. For the GPs the number of home visits decreased during out-of-hours in one region. CONCLUSION: In a country with no gatekeeping role for GPs, implementing a GPC increased the out-of-hours caseload of the GPCs. The caseload of the EDs stabilised during the study period.

The effect of giving influenza vaccination to general practitioners: a controlled trial [NCT00221676].

BACKGROUND: No efficacy studies of influenza vaccination given to GPs have yet been published. Therefore, our purpose was to assess the effect of an inactivated influenza vaccine given to GPs on the rate of clinical respiratory tract infections (RTIs) and proven influenza cases (influenza positive nose and throat swabs and a 4-fold titre rise), while adjusting for important covariates. METHODS: In a controlled trial during two consecutive winter periods (2002-2003 and 2003-2004) we compared (77 and 100) vaccinated with (45 and 40) unvaccinated GPs working in Flanders, Belgium. Influenza antibodies were measured immediately prior to and 3-5 weeks after vaccination, as well as after the influenza epidemic. During the influenza epidemic, GPs had to record their contact with influenza cases and their own RTI symptoms every day. If they became ill, the GPs had to take nose and throat swabs during the first 4 days. We performed a multivariate regression analysis for covariates using Generalized Estimating Equations. RESULTS: One half of the GPs (vaccinated or not) developed an RTI during the 2 influenza epidemics. During the two influenza periods, 8.6% of the vaccinated and 14.7% of the unvaccinated GPs had positive swabs for influenza (RR: 0.59; 95%CI: 0.28 - 1.24). Multivariate analysis revealed that influenza vaccination prevented RTIs and swab-positive influenza only among young GPs (ORadj: 0.35; 95%CI: 0.13 - 0.96 and 0.1; 0.01 - 0.75 respectively for 30-year-old GPs). Independent of vaccination, a low basic antibody titre against influenza (ORadj 0.57; 95%CI: 0.37 - 0.89) and the presence of influenza cases in the family (ORadj 9.24; 95%CI: 2.91 - 29) were highly predictive of an episode of swab-positive influenza. CONCLUSION: Influenza vaccination was shown to protect against proven influenza among young GPs. GPs, vaccinated or not, who are very vulnerable to influenza are those who have a low basic immunity against influenza and, in particular, those who have family members who develop influenza.

Antibiotic prescribing for acute cough: the effect of perceived patient demand.

BACKGROUND: GPs decide whether or not to prescribe antibiotics for acute cough. Apart from clinical signs and symptoms, non-medical reasons influence this decision as well. AIM: To obtain a valid estimate of the effect of perceived patient demand. DESIGN OF STUDY: Secondary analysis of cluster randomised controlled trial data. SETTING: Eighty-five Flemish GPs. METHOD: GPs completed a preprinted form with medical as well as non-medical information and their prescription for 20 consecutive adult patients consulting with acute cough in the periods February to April 2000 and 2001. The effect of perceived patient demand on antibiotic prescribing was estimated by performing alternating logistic regression analysis. A hierarchical backwards elimination procedure, described by Kleinbaum, was used. RESULTS: Seventy-two GPs participated, including 1448 patients eligible for analysis; 500 (34.5%) were prescribed an antibiotic and, according to the GP, 218 (15.1%) asked for an antibiotic. In cases of perceived patient demand antibiotics were prescribed significantly more often (odds ratio [OR] = 4.64, 95% confidence interval [CI] = 2.96 to 7.26). In the final model (n = 819; OR = 4.60, 2.59 to 8.17); Hosmer-Lemeshow goodness-of-fit P = 0.72), the effect of perceived patient demand for an antibiotic depended on the outcome of the lung auscultation. When patient demand was perceived, antibiotics were prescribed significantly more often only in the case of a normal lung auscultation or in the case of only one abnormal auscultatory finding (adjusted OR = 20.83, 95% CI = 8.86 to 48.99; adjusted OR = 4.79; 95% CI = 2.16 to 10.60, respectively). CONCLUSIONS: Perceived patient demand has a significant, independent and clinically relevant effect on antibiotic prescribing for acute cough with negative findings on the lung auscultation. Practice guidelines and interventions to optimise antibiotic prescribing have to take this effect into account.

Improving Care And Research Electronic Data Trust Antwerp (iCAREdata): a research database of linked data on out-of-hours primary care.

BACKGROUND: Primary out-of-hours care is developing throughout Europe. High-quality databases with linked data from primary health services can help to improve research and future health services. METHODS: In 2014, a central clinical research database infrastructure was established (iCAREdata: Improving Care And Research Electronic Data Trust Antwerp, www.icaredata.eu ) for primary and interdisciplinary health care at the University of Antwerp, linking data from General Practice Cooperatives, Emergency Departments and Pharmacies during out-of-hours care. Medical data are pseudonymised using the services of a Trusted Third Party, which encodes private information about patients and physicians before data is sent to iCAREdata. RESULTS: iCAREdata provides many new research opportunities in the fields of clinical epidemiology, health care management and quality of care. A key aspect will be to ensure the quality of data registration by all health care providers. CONCLUSIONS: This article describes the establishment of a research database and the possibilities of linking data from different primary out-of-hours care providers, with the potential to help to improve research and the quality of health care services.

Staphylococcus aureus, Including Meticillin-Resistant Staphylococcus aureus, among General Practitioners and Their Patients: A Cross-Sectional Study.

BACKGROUND: The role of general practitioners (GPs) as reservoir and potential source for Staphylococcus aureus (SA) transmission is unknown. Our primary objective was to evaluate the prevalence of SA and community-acquired methicillin resistant SA (CA-MRSA) carrier status (including spa typing) among GPs and their patients in Belgium. The secondary objective was to determine the association between SA/CA-MRSA carriage in patients and their characteristics, SA carriage in GPs, GP and practice characteristics. METHODS: The Belgian GPs, who swabbed their patients in the APRES study (which assessed the prevalence of SA nasal carriage in nine European countries; November 2010 -June 2011), were asked to swab themselves as well (May-June 2011). GPs and their patients had to complete a questionnaire on factors related to SA carriage and transmission. SA isolation including CA-MRSA and spa typing was performed on the swabs. RESULTS: In eighteen practices 34 GPs swabbed patients of which 25 GPs provided personal swabs. The analysis was performed on 3008 patient records. Among GPs SA carriage (28%) was more prevalent than among their patients (19.2%), but CA-MRSA carriage was not present. SA was more prevalent among younger patients and those living with cattle. Spa typing SA and MRSA strains did not suggest correlation within practices or between patients and GPs, but chronic skin conditions of GPs and always handshaking patients by SA positive GPs were associated with more SA among patients, and hand washing after every patient contact with less SA among patients in practices with high antibiotic prescribing rates. CONCLUSION: No MRSA was found among GPs, although their SA carriership was higher compared to their patients'. Spa types did not cluster within practices, possibly due to difference in timing of swabbing. To minimise SA transmission to their patients GPs should consider taking appropriate care of their chronic skin diseases, antibiotic prescribing behaviour, handshaking and hand washing habits.

Antibiotics for coughing in general practice: a questionnaire study to quantify and condense the reasons for prescribing.

BACKGROUND: Antibiotics are being overprescribed in ambulant care, especially for respiratory tract infections (RTIs). Gaining insight into the actual reasons for prescribing remains important for the design of effective strategies to optimise antibiotic prescribing. We aimed to determine items of importance for the antibiotic prescribing decision and to make them operational for an intervention trial. METHODS: A postal questionnaire based upon focus group findings was sent to 316 Flemish general practitioners (GPs). On a verbal rating scale the GPs scored to what extent they consider the questionnaire items in decision making in case of suspected RTI in a coughing patient and how strongly the items support or counter antibiotic treatment. Factor analysis was used to condense the data. The relative importance of the yielded operational factors was assessed using Wilcoxon Matched Pairs test. RESULTS: 59.5% completed the study. Response group characteristics (mean age: 42.8 years; 65.9% men) approximated that of all Flemish GPs. Participants considered all the items included in the questionnaire: always the operational factor 'lung auscultation', often 'whether or not there is something unusual happening' - both medical reasons - and to a lesser extent 'non-medical reasons' (P < 0.001). Non-medical as well as medical reasons support antibiotic treatment, but non-medical reasons to a lesser extent (P < 0.001). CONCLUSION: This study quantified, condensed and confirmed the findings of previous focus group research. Practice guidelines and interventions to optimise antibiotic prescribing have to take non-medical reasons into account.

The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.

Controversy has arisen regarding the effectiveness of neuraminidase inhibitors (NIs), especially against influenza-related complications. A literature search was performed to critically assess the evidence collected by the available systematic reviews (SRs) regarding the benefits and disadvantages of NIs (oseltamivir, zanamivir) compared to placebos in healthy and at-risk individuals of all ages for prophylaxis and treatment of seasonal influenza. A SR was done using the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects, and Medline (January 2006-July 2012). Two reviewers selected SRs based on randomized clinical trials, which were restricted to intention-to-treat results, and they assessed review (AMSTAR) and study quality indicators (GRADE). The SRs included (N = 9) were of high quality. The efficacy of NIs in prophylaxis ranged from 64% (16-85) to 92% (37-99); the absolute risk reduction ranged from 1.2% to 12.1% (GRADE moderate to low). Clinically relevant treatment benefits of NIs were small in healthy adults and children suffering from influenza-like illness (GRADE high to moderate). Oseltamivir reduced antibiotic usage in healthy adults according to one SR, but this was not confirmed by other reviews (GRADE low). Zanamivir showed a preventive effect on antibiotic usage in children (95% (77-99);GRADE moderate) and on the occurrence of bronchitis in at-risk individuals (59% (30-76);GRADE moderate). No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality. In oseltamivir trials, nausea, vomiting and diarrhea were significant side-effects. For zanamivir trials, no adverse effects have been reported. The combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of oseltamivir or zanamivir for the prophylaxis and treatment of healthy individuals. No relevant benefits of these NIs on complications in at-risk individuals have been established.

Efficacy of daily intake of Lactobacillus casei Shirota on respiratory symptoms and influenza vaccination immune response: a randomized, double-blind, placebo-controlled trial in healthy elderly nursing home residents.

BACKGROUND: Age is associated with immune dysregulation, which results in an increased infection rate and reduced effectiveness of vaccination. OBJECTIVE: We assessed whether an intervention with Lactobacillus casei Shirota (LcS) in elderly nursing home residents reduced their susceptibility to respiratory symptoms and improved their immune response to influenza vaccination. DESIGN: Between October 2007 and April 2008, a randomized, double-blind, placebo-controlled trial was conducted in 737 healthy people aged ≥ 65 y in 53 nursing homes in Antwerp, Belgium. Volunteers were randomly assigned to receive a probiotic (n = 375; 2 bottles of fermented milk that contained ≥ 6.5 × 10(9) live LcS/bottle) or a placebo (n = 362; similar drink with no bacteria) for 176 d. After 21 d, all subjects received an influenza vaccination. Primary outcome parameters were the number of days with respiratory symptoms, the probability of respiratory symptoms, and antiinfluenza antibody titer by hemagglutination inhibition after vaccination. RESULTS: Univariate and multivariate modeling showed no effect of the probiotic on clinical outcome parameters. Generalized linear mixed modeling showed no effect of the probiotic itself on the probability of respiratory symptoms [OR of probiotic: 0.8715; 95% CI: 0.6168, 1.2887). No significant difference regarding the influenza-vaccination immune response was shown. CONCLUSION: The results of this study show that daily consumption of a fermented milk drink that contains LcS has no statistically or clinically significant effect on the protection against respiratory symptoms. This trial was registered at clinicaltrials.gov as NCT00849277.

A systematic review of the evidence on the effectiveness and risks of inactivated influenza vaccines in different target groups.

PURPOSE: To systematically review the evidence regarding the efficacy, effectiveness and risks of the use of inactivated influenza vaccines in children, healthy adults, elderly individuals and individuals with co-morbidities such as diabetes, chronic lung disease, cardiovascular disease, kidney or liver disease and immune suppression. METHODS: The Cochrane database of systematic reviews was searched for relevant reviews and supplemented with searches of the Cochrane Central Register of Controlled Trials database and Medline. Two reviewers independently assessed review and trial quality and extracted data. RESULTS AND CONCLUSIONS: The inactivated influenza vaccine has been proven effective in preventing laboratory-confirmed influenza among healthy adults (16-65 years) and children (≥6 years) (GRADE A evidence). However, there is strikingly limited good-quality evidence (all GRADE B, C or not existing) of the effectiveness of influenza vaccination on complications such as pneumonia, hospitalisation and influenza-specific and overall mortality. Inconsistent results are found in studies among children younger than 6 years, individuals with COPD, institutionalised elderly (65 years or older), elderly with co-morbidities and healthcare workers in elderly homes, which can only be explained by bias of unknown origin. The vaccination of pregnant women might be beneficial for their newborns, and vaccination of children might be protective in non-recipients of the vaccine of all ages living in the same community (one RCT, Grade B evidence).

Serum antibodies against circulating influenza strains among vaccinated and unvaccinated general practitioners during two consecutive years (2002-2003).

Efficacy studies have not answered the question whether influenza vaccination among general practitioners (GPs) has a substantial additive effect on their immunity. To evaluate this effect the influenza antibody titres in vaccinated and unvaccinated GPs were compared in a controlled trial during two consecutive winter periods (2002-2003 and 2003-2004). The seroprotection rates against the circulating A/H3N2 influenza virus amount to 80% and 42% in the unvaccinated group in 2002 and 2003, respectively. In the vaccinated GPs the seroprotection rate increases from 91% to 96% in 2002 and from 70% to 83% in 2003 after vaccination. Besides vaccination, the (high) basic antibody titre before vaccination and working in a child and family preventive medicine unit were predicting a protective antibody level in GPs.

Optimizing antibiotic prescribing for acute cough in general practice: a cluster-randomized controlled trial.

OBJECTIVES: To assess the effect of a tailored professional intervention, including academic detailing, on antibiotic prescribing for acute cough. METHODS: In a cluster-randomized controlled before and after study 85 Flemish GPs included adult patients with acute cough consulting in the periods February-April 2000 and 2001. The intervention consisted of a clinical practice guideline for acute cough, an educational outreach visit and a postal reminder to support its implementation in January 2001. Antibiotic prescribing rates and patients' symptom resolution were the main outcome measures. RESULTS: Thirty-six of 42 GPs received the intervention and 35 of 43 GPs served as controls; 1503 patients were eligible for analysis. Only in the intervention group were patients less likely to receive antibiotics after the intervention [OR(adj) (95% CI)=0.56 (0.36-0.87)]. Prescribed antibiotics were also more in line with the guideline in the intervention group [1.90 (0.96-3.75)] and less expensive from the perspective of the National Sickness and Invalidity Insurance Institute [MD(adj) (95% CI)= Euro -6.89 [-11.77-(-2.02)]]. No significant differences were found between the groups for the time to symptom resolution. CONCLUSIONS: An (inter)actively delivered tailored intervention implementing a guideline for acute cough is successful in optimizing antibiotic prescribing without affecting patients' symptom resolution. Further research efforts should be devoted to cost-effectiveness studies of such interventions.