Influenza-like Illness In Primary Care Research Articles

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.

Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. 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. 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. 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). 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.

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 Points Predicting 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.

Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC4E Trial.

Background and ObjectiveInfluenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone.MethodsResource use data were extracted from participants’ daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed.ResultsPatients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: €17 [0–95% Crl: 16–19] vs. €24 [5–100% Crl: 18–29]; healthcare provider: €37 [28–67] vs. €44 [25–55]; healthcare payers: €54 [45–85] vs. €68 [45–81]; and society: €423 [399–478] vs. €451 [390–478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences.ConclusionThe average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-021-01057-y.

Association between Influenza Vaccine Administration and Primary Care Consultations for Respiratory Infections: Sentinel Network Study of Five Seasons (2014/2015-2018/2019) in the UK.

Influenza, a vaccine preventable disease, is a serious global public health concern which results in a considerable burden on the healthcare system. However, vaccine hesitancy is increasingly becoming a global problem. One prevalent misconception is that influenza vaccinations can cause the flu. We carried out this study to determine whether people undertaking influenza vaccination presented less with acute respiratory tract infection (ARTI) and influenza-like-illness (ILI) following vaccination. We utilised the Oxford Royal College of General Practitioners Research and Surveillance Centre sentinel database to examine English patients who received vaccination between 2014/2015 and 2018/2019. Of the 3,841,700 influenza vaccinations identified, vaccination details and primary care respiratory consultation counts were extracted to calculate the relative incidence (RI) per exposure risk period using the self-controlled case series methodology. Results showed a significant increase in the RI of respiratory consultation rates within fourteen days of vaccination across all five years. Less than 6.2% of vaccinations led to consultations for ARTI or ILI in primary care (crude consultation rate 6196 per 100,000). These findings, particularly if confirmed in further research, may reduce the risk of cross-infection between waiting patients and increase uptake of influenza vaccine.

Consultations for Influenza-Like Illness in Primary Care in The Netherlands: A Regression Approach

ObjectivesTo estimate the general practitioner (GP) consultation rate attributable to influenza in The Netherlands. MethodsRegression analysis was performed on the weekly numbers of influenza-like illness (ILI) GP consultations and laboratory reports for influenza virus types A and B and 8 other pathogens over the period 2003–2014 (11 influenza seasons; week 40–20 of the following year). ResultsIn an average influenza season, 27% and 11% of ILI GP consultations were attributed to infection by influenza virus types A and B, respectively. Influenza is therefore responsible for approximately 107 000 GP consultations (651/100 000) each year in The Netherlands. GP consultation rates associated with influenza infection were highest in children under 5 years of age, at 667 of 100 000 for influenza A and 258 of 100 000 for influenza B. Influenza virus infection was found to be the predominant cause of ILI-related GP visits in all age groups except children under 5, in which respiratory syncytial virus (RSV) infection was found to be the main contributor. ConclusionsThe burden of influenza in terms of GP consultations is considerable. Overall, influenza is the main contributor to ILI. Although ILI symptoms in children under 5 years of age are most often associated with RSV infection, the majority of visits related to influenza occur among children under 5 years of age.

Performance and ease of use of a molecular point-of-care test for influenza A/B and RSV in patients presenting to primary care

Annual influenza epidemics cause substantial morbidity and mortality, and the majority of patients with influenza-like illness present to primary care. Point-of-care influenza tests could support treatment decisions. It is critical to establish analytic performance of these platforms in real-life patient samples before uptake can be considered. We aimed to assess the analytical performance and ease of use of the cobas® Liat® PCR POCT in detecting influenza A/B and RSV in samples collected from patients with influenza-like illness in primary care. Sensitivity and specificity of the cobas® Liat® POCT are calculated in comparison with a commercial laboratory-based PCR test (Fast-Track Respiratory Pathogens 21 Plus kit (Fast-Track Diagnostics)). Samples with discordant results were analysed additionally by the RespiFinder 2Smart (PathoFinder) using an Extended Gold Standard (EGS). Acceptability was scored on a five-point Likert scale as well as a failure mode analysis of the cobas® Liat® POCT was performed. Nasal and oropharyngeal swabs were obtained from 140 children and nasopharyngeal swabs from 604 adults (744 patients). The cobas® Liat® POCT had a sensitivity and specificity of 100% (95% CI 99–100%) and 98.1% (95%CI 96.3–99%) for influenza A, 100% (95% CI 97.7–100%) and 99.7% (95%CI 98.7–99.9%) for influenza B and 100% (95% CI 87.1–100%) and 99.4% (95%CI 98.6–99.8%) for RSV, respectively. According to trained lab technicians, the cobas® Liat® POCT was considered easy-to-use, with a fast turn-around-time. Cobas® Liat® POCT is a promising decentralised test platform for influenza A/B and RSV in primary care as it provides fairly rapid results with excellent analytic performance. Point-of-care influenza tests could support treatment decisions in primary care. Cobas® Liat® POCT is a promising decentralised test platform for influenza A/B and RSV in primary care as it provides fairly rapid results with excellent analytic performance.

Use of Ambulance Dispatch Calls for Surveillance of Severe Acute Respiratory Infections

Ambulance dispatches for respiratory syndromes reflect incidence of influenza-like illness in primary care. Associations are highest in children (15%–34% of respiratory calls attributable to influenza), out-of-office hours (9%), and highest urgency-level calls (9%–11%). Ambulance dispatches might be an additional source of data for severe influenza surveillance.

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

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. 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. 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. 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. European Commission's Seventh Framework Programme.

Neuraminidase inhibitors for influenza-like illness in primary care

Neuraminidase inhibitors for influenza-like illness in primary care

Oseltamivir Plus Usual Care versus Usual Primary Care for Influenza-Like-Illness: An Open-Label, Pragmatic, Randomized Controlled Trial

Background: Antivirals are infrequently prescribed in primary care for influenza-like-illness (ILI), mostly because of perceived ineffectiveness in real world primary care, and as 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 ILI reduces time to recovery overall and in key subgroups. Methods: We conducted an open-label, pragmatic, randomized controlled trial of adding oseltamivir to usual care in patients aged one year and older consulting with ILI in primary care. The primary endpoint was time to recovery (return to usual activities, with fever, head- and muscle-ache minor/absent), following a Bayesian piece-wise exponential model. Baseline nasopharyngeal swabs were analyzed after study completion. Findings: We ascertained the primary outcome for 3059 of the 3266 participants recruited in 15 European countries during three seasonal influenza seasons (2015-2018); 52.0% (1590/3059) had PCR-confirmed influenza infection. Time to recovery was shorter in those given oseltamivir by 1.02 days (95% Bayesian CI: 0.73-1.32). Hazard ratios of proportional benefit were similar across pre-specified subgroups; absolute benefit in time to recovery varied, with an estimated benefit of >2 days in older patients, more severe illness, comorbidity, or longer prior illness duration. The effect was independent of influenza status. Fewer antibiotics were prescribed in the oseltamivir arm (9.3% vs 13.2%, mean difference 4.0; 95% CI: 1.7-6.3), while nausea and/or vomiting was shorter in usual care patients (HR 0.92; 95% CI: 0.85-1.00). Interpretation: Primary care patients with ILI treated with oseltamivir recovered sooner than those managed by usual care alone, irrespective of influenza virus test results. Older, sicker, patients with comorbidities and longer prior illness duration showed greater absolute benefit. Trial Registration: The trial is registered with the ISRCTN Registry, number ISRCTN27908921. Funding Statement: CB reports receiving advisory board fees from Roche Molecular Systems and grant support from Roche Molecular Diagnostics; CB was supported by funding from an NIHR Protection Research Unit on Health Care Associated Infections and Antimicrobial Resistance, by the NIHR MedTech and In Vitro Diagnostics Co-Operative at Oxford NHS Foundation Trust, and by an NIHR Senior Investigator Award. TV is PI in a project that is funded by Innovative Medicines Initiative (IMI) of the European Union, in which Janssen Pharmaceutica is a partner and researcher in another IMI project in which Biocartis, Janssen, Biomerieux and Berry Consultants are partners. In addition he is co PI of a NIHR funded RCT, and PI in several studies funded by the Netherlands Organization of Health Research and Development. CL has received advisory boards fees from MSD and grant support from GILEAD, Global Bridges, Servier, Galenica-Olvos. Declaration of Interests: CB reports receiving advisory board fees from Roche Molecular Systems and grant support from Roche Molecular Diagnostics; CB was supported by funding from an NIHR Protection Research Unit on Health Care Associated Infections and Antimicrobial Resistance, by the NIHR MedTech and In Vitro Diagnostics Co-Operative at Oxford NHS Foundation Trust, and by an NIHR Senior Investigator Award. TV is PI in a project that is funded by Innovative Medicines Initiative (IMI) of the European Union, in which Janssen Pharmaceutica is a partner and researcher in another IMI project in which Biocartis, Janssen, Biomerieux and Berry Consultants are partners. In addition he is co PI of a NIHR funded RCT, and PI in several studies funded by the Netherlands Organization of Health Research and Development. CL has received advisory boards fees from MSD and grant support from GILEAD, Global Bridges, Servier, Galenica-Olvos. All other authors declare no conflict of interest. Ethics Approval Statement: All participating countries gained national research ethics committees and CTA approval as required. Ethics Ref: 15/SC/0138.

Baseline characteristics and clinical symptoms related to respiratory viruses identified among patients presenting with influenza-like illness in primary care

ObjectivesWe aimed to identify patients' clinical characteristics associated with respiratory viruses identified among patients presenting with influenza-like illness (ILI). MethodsA sample of patients of all ages presenting with ILI was included by physicians of the French Sentinelles network during two seasons (2015/16 and 2016/17). Nasopharyngeal samples were tested for the presence of influenza virus (IV), respiratory syncytial virus (RSV), human rhinovirus (HRV) and human metapneumovirus (HMPV). Patients' characteristics associated with each of the four virus classes were studied using multivariate logistic regressions. ResultsA total of 5859 individuals were included in the study: 48.0% tested positive for IV, 7.9% for HRV, 7.5% for RSV and 4.1% for HMPV. Cough was associated with IV (OR 2.14, 95% CI 1.81–2.52) RSV (OR 2.52, 95% CI 1.75–3.74) and HMPV detection (OR 2.15, 95% CI 1.40–3.45). Rhinorrhoea was associated mainly with HRV detection (OR 1.75, 95% CI 1.34–2.32). Headache was associated with IV detection (OR 1.75, 95% CI 1.34–2.32), whereas absence of headache was associated with RSV and HMPV detection. Dyspnoea was associated with RSV detection (OR 2.33, 95% CI 1.73–3.12) and absence of dyspnoea with IV detection. Conjunctivitis was associated with IV detection (OR 1.27, 95% CI 1.08–1.50). Some associations were observed only in children: dyspnoea and cough with RSV detection (age <5 years), conjunctivitis with IV detection (age <15 years). Period of onset of symptoms differed among aetiological diagnoses. Seasonal influenza vaccination decreased the risk of IV detection (OR, 0.67, 95% CI 0.51–0.86). ConclusionsThis study allowed the identification of symptoms associated with several viral aetiologies in patients with ILI. A proper knowledge and understanding of these clinical signs may improve the medical management of patients.

Estimating severity of influenza epidemics from severe acute respiratory infections (SARI) in intensive care units

BackgroundWhile influenza-like-illness (ILI) surveillance is well-organized at primary care level in Europe, few data are available on more severe cases. With retrospective data from intensive care units (ICU) we aim to fill this current knowledge gap. Using multiple parameters proposed by the World Health Organization we estimate the burden of severe acute respiratory infections (SARI) in the ICU and how this varies between influenza epidemics.MethodsWe analyzed weekly ICU admissions in the Netherlands (2007–2016) from the National Intensive Care Evaluation (NICE) quality registry (100% coverage of adult ICUs in 2016; population size 14 million) to calculate SARI incidence, SARI peak levels, ICU SARI mortality, SARI mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score, and the ICU SARI/ILI ratio. These parameters were calculated both yearly and per separate influenza epidemic (defined epidemic weeks). A SARI syndrome was defined as admission diagnosis being any of six pneumonia or pulmonary sepsis codes in the APACHE IV prognostic model. Influenza epidemic periods were retrieved from primary care sentinel influenza surveillance data.ResultsAnnually, an average of 13% of medical admissions to adult ICUs were for a SARI but varied widely between weeks (minimum 5% to maximum 25% per week). Admissions for bacterial pneumonia (59%) and pulmonary sepsis (25%) contributed most to ICU SARI. Between the eight different influenza epidemics under study, the value of each of the severity parameters varied. Per parameter the minimum and maximum of those eight values were as follows: ICU SARI incidence 558–2400 cumulated admissions nationwide, rate 0.40–1.71/10,000 inhabitants; average APACHE score 71–78; ICU SARI mortality 13–20%; ICU SARI/ILI ratio 8–17 cases per 1000 expected medically attended ILI in primary care); peak-incidence 101–188 ICU SARI admissions in highest-incidence week, rate 0.07–0.13/10,000 population).ConclusionsIn the ICU there is great variation between the yearly influenza epidemic periods in terms of different influenza severity parameters. The parameters also complement each other by reflecting different aspects of severity. Prospective syndromic ICU SARI surveillance, as proposed by the World Health Organization, thereby would provide insight into the severity of ongoing influenza epidemics, which differ from season to season.

A trial like ALIC4E: why design a platform, response-adaptive, open, randomised controlled trial of antivirals for influenza-like illness?

ALIC4E is the first publicly funded, multicountry, pragmatic study determining whether antivirals should be routinely prescribed for influenza-like illness in primary care. The trial aims to go beyond determining the average treatment effect in a population to determining effects in patients with combinations of participant characteristics (age, symptom duration, illness severity, and comorbidities). It is one of the first platform, response-adaptive, open trial designs implemented in primary care, and this article aims to provide an accessible description of key aspects of the study design. 1) The platform design allows the study to remain relevant to evolving circumstances, with the ability to add treatment arms. 2) Response adaptation allows the proportion of participants with key characteristics allocated to study arms to be altered during the course of the trial according to emerging outcome data, so that participants' information will be most useful, and increasing their chances of receiving the trial intervention that will be most effective for them. 3) Because the possibility of taking placebos influences participant expectations about their treatment, and determining effects of the interventions on patient help seeking and adherence behaviour in real-world care is critical to estimates of cost-effectiveness, ALIC4E is an open-label trial.

Correction: Prescribing antibiotics to 'at-risk' children with influenza-like illness in primary care: qualitative study.

Correction: Prescribing antibiotics to 'at-risk' children with influenza-like illness in primary care: qualitative study.

Prescribing antibiotics to ‘at-risk’ children with influenza-like illness in primary care: qualitative study

ObjectivesNational Institute for Health and Care Excellence guidelines recommend immediate antibiotic treatment of respiratory tract infections in ‘at-risk’ individuals with comorbidities. Observational evidence suggests that influenza particularly predisposes children to...

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

The ongoing influenza epidemic is characterized by intense activity with most influenza infections due to the A (H3N2) viruses. Using the screening method, mid-season vaccine effectiveness (VE) in preventing influenza-like illness in primary care was estimated to 32% (95% CI; 23 to 40) among risk groups and was 11% (95% CI; −4 to 23) among the elderly (≥ 65 y). The VE in ≥ 65 y was the lowest estimate regarding the 4 previous seasonal influenza epidemics.

Vigilancia sindrómica de la gripe en atención primaria, un instrumento complementario a las redes centinelas para períodos de elevada incidencia de gripe

ObjectiveEpidemiological data on influenza is essential for resource management when the incidence of the disease in the population is very high, but not easily available in real-time. The objective of this study was to evaluate the use of a syndromic surveillance system for influenza-like illness in Primary Care (ILIsPC) and assess its level of agreement with the epidemiological data from the Influenza Sentinel Network. LocalizationHealth centres and deputising medical services in the Balearic Islands. ParticipantsData from 122 epidemiological weeks for each system were included. Main measuresData from January 1, 2007 to January 31, 2010 were compared. ILIsPC rates were obtained from the diagnoses registered in electronic health records of Primary Care clinics and deputising medical services. Data from Sentinel Network were obtained from weekly epidemiological reports. Intraclass correlation coefficient was calculated and Bland – Altman plot constructed. ResultsThere was good agreement between both measures, with an intraclass correlation coefficient of 0.88 (95% CI: 0.83-0.91). After constructing a Bland-Altman plot, the precision between both rates was greater during the periods of the highest influenza incidence. ConclusionsWe believe that the syndromic surveillance system ILIsPC, provides access to very useful data in real-time, especially during periods of high influenza incidence, such as during epidemics or the recent pandemic.