Validity of a clinical model to predict influenza in patients presenting with symptoms of lower respiratory tract infection in primary care.

BACKGROUND: Valid clinical predictors of influenza in patients presenting with lower respiratory tract infection (LRTI) symptoms would provide adequate patient information and reassurance. AIM: Assessing the validity of an existing diagnostic model (Flu Score) to detect influenza in LRTI patients. DESIGN AND SETTING: A European diagnostic study recruited 1801 adult primary care patients with LRTI-like symptoms existing ≤7 days between October and April 2007-2010. METHOD: History and physical examination findings were recorded and nasopharyngeal swabs taken. Polymerase chain reaction (PCR) for influenza A/B was performed as reference test. Diagnostic accuracy of the Flu Score (1× onset <48 hours + 2× myalgia + 1× chills or sweats + 2× fever and cough) was expressed as area under the curve (AUC), calibration slopes and likelihood ratios (LRs). RESULTS: A total of 273 patients (15%) had influenza on PCR. The AUC of the Flu Score during winter months was 0.66 [95% CI (95% confidence internal) 0.63-0.70]. During peak influenza season, both influenza prevalence (24%) and AUC were higher [0.71 (95% CI 0.66-0.76], but calibration remained poor. The Flu Score assigned 64% of the patients as 'low-risk' (10% had influenza, LR - 0.6). About 12% were classified as 'high risk' of whom 32% had influenza (LR + 2.7). During peak influenza season, 60% and 14% of patients were classified as low and high risk, respectively, with influenza prevalences being 14% (LR - 0.5) and 50% (LR + 3.2). CONCLUSION: The Flu-Score attributes a small subgroup of patients with a high influenza risk (prevalence 32%). However, clinical usefulness is limited because this group is small and the association between predicted and observed risks is poor. Considerable diagnostic imprecision remains when it comes to differentiating those with influenza on clinical grounds from the many other causes of LRTI in primary care. New point of care tests are required that accurately, rapidly and cost effectively detect influenza in patients with respiratory tract symptoms in primary care.

Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness.

BACKGROUND: Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). METHODS: Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. RESULTS: Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). CONCLUSIONS: This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.

The influenza landscape and vaccination coverage in older adults during the SARS-Cov-2 pandemic: data from Several European Countries and Israel.

INTRODUCTION: The Raise Awareness of Influenza Strategies in Europe (RAISE) group gathered information about the healthcare burden of influenza (hospitalizations, intensive care unit [ICU] admissions, and excess deaths), surveillance systems, and the vaccine coverage rate (VCR) in older adults in 18 European countries and Israel. AREAS COVERED: Published medical literature and official medical documentation on the influenza disease burden in the participating countries were reviewed from 2010/11 until the 2022/23 influenza seasons. Information on the framework for monitoring the disease burden and the provision for ensuring older adults had access to vaccination in their respective countries was provided. Data on influenza VCR in older adults were collected for the 2019/20 to 2022/23 influenza seasons. Data are reported descriptively. EXPERT OPINION: Influenza presents a significant healthcare burden in older adults. Reporting outcomes across participating countries is heterogeneous, highlighting the need for standardized approaches. Although older adults receive free influenza vaccination, vaccine uptake is highly variable among countries. Moreover, hospitalization rates remain high even in countries reporting a high VCR. Increased awareness and education on the burden of disease and the broader use of improved influenza vaccines for older adults may help reduce the disease burden on this population.

Identifying adults with acute rhinosinusitis in primary care that benefit most from antibiotics: protocol of an individual patient data meta-analysis using multivariable risk prediction modelling.

INTRODUCTION: Acute rhinosinusitis (ARS) is a prime reason for doctor visits and among the conditions with highest antibiotic overprescribing rates in adults. To reduce inappropriate prescribing, we aim to predict the absolute benefit of antibiotic treatment for individual adult patients with ARS by applying multivariable risk prediction methods to individual patient data (IPD) of multiple randomised placebo-controlled trials. METHODS AND ANALYSIS: This is an update and re-analysis of a 2008 IPD meta-analysis on antibiotics for adults with clinically diagnosed ARS. First, the reference list of the 2018 Cochrane review on antibiotics for ARS will be reviewed for relevant studies published since 2008. Next, the systematic searches of CENTRAL, MEDLINE and Embase of the Cochrane review will be updated to 1 September 2020. Methodological quality of eligible studies will be assessed using the Cochrane Risk of Bias 2 tool. The primary outcome is cure at 8-15 days. Regression-based methods will be used to model the risk of being cured based on relevant predictors and treatment, while accounting for clustering. Such model allows for risk predictions as a function of treatment and individual patient characteristics and hence gives insight into individualised absolute benefit. Candidate predictors will be based on literature, clinical reasoning and availability. Calibration and discrimination will be evaluated to assess model performance. Resampling techniques will be used to assess internal validation. In addition, internal-external cross-validation procedures will be used to inform on between-study differences and estimate out-of-sample model performance. Secondarily, we will study possible heterogeneity of treatment effect as a function of outcome risk. ETHICS AND DISSEMINATION: In this study, no identifiable patient data will be used. As such, the Medical Research Involving Humans Subject Act (WMO) does not apply and official ethical approval is not required. Results will be submitted for publication in international peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020220108.

A support programme for primary care leads to substantial improvements in the effectiveness of a public hepatitis C campaign.

INTRODUCTION: Because of its lack of clinical signs, the detection of hepatitis C virus (HCV) infection in the Netherlands remains suboptimal. Therefore, the Dutch Health Council proposed an HCV campaign aimed to inform the general public and motivate people at risk to seek medical advice. Because knowledge and awareness of HCV infection is low among primary care workers, the implementation of a support programme for primary care complementary to a HCV campaign seems appropriate. OBJECTIVE: To evaluate the added value of a support programme for primary care complementary to a public HCV campaign. METHODS: We performed a non-randomized controlled intervention study. In two similar regions, a public HCV campaign was organized. In the intervention region, an additional support for primary care was provided by means of brochures, short courses and informative visits. RESULTS: In the intervention region, the proportional increase in anti-HCV tests was 3.02 (57-172 tests). In the control region, this increase was 1.36 (86-118 tests). In the intervention region, the increase in positive anti-HCV tests was 1.7% (95% confidence interval (CI): -0.2% to -3.7%). In the control region, this number decreased by 0.9% (95% CI: -4.1% to 2.3%). CONCLUSIONS: The addition of primary care practice support leads to considerable improvements in medical consciousness regarding HCV infection in primary care. Even though the positive effect on case finding cannot be indisputably demonstrated due to low prevalence, our results indicate such a positive effect. Therefore, future campaigns aimed at hepatitis C should invariably implement additional support for primary care to improve diagnostic uptake and optimize case finding.

Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data.

BACKGROUND: Primary-care physicians continue to overprescribe antibiotics for acute rhinosinusitis because distinction between viral and bacterial sinus infection is difficult. We undertook a meta-analysis of randomised trials based on individual patients' data to assess whether common signs and symptoms can be used to identify a subgroup of patients who benefit from antibiotics. METHODS: We identified suitable trials--in which adult patients with rhinosinusitis-like complaints were randomly assigned to treatment with an antibiotic or a placebo--by searching the Cochrane Central Register of Controlled Trials, Medline, and Embase, and reference lists of reports describing such trials. Individual patients' data from 2547 adults in nine trials were checked and re-analysed. We assessed the overall effect of antibiotic treatment and the prognostic value of common signs and symptoms by the number needed to treat (NNT) with antibiotics to cure one additional patient. FINDINGS: 15 patients with rhinosinusitis-like complaints would have to be given antibiotics before an additional patient was cured (95% CI NNT[benefit] 7 to NNT[harm] 190). Patients with purulent discharge in the pharynx took longer to cure than those without this sign; the NNT was 8 patients with this sign before one additional patient was cured (95% CI NNT[benefit] 4 to NNT[harm] 47). Patients who were older, reported symptoms for longer, or reported more severe symptoms also took longer to cure but were no more likely to benefit from antibiotics than other patients. INTERPRETATION: Common clinical signs and symptoms cannot identify patients with rhinosinusitis for whom treatment is clearly justified. Antibiotics are not justified even if a patient reports symptoms for longer than 7-10 days.

Threat of an influenza pandemic: family physicians in the front line.

BACKGROUND: The chance of an influenza pandemic is real and clinicians should keep themselves informed about the rationale and science behind preventive and therapeutic principles relating to an (impending) influenza pandemic. DISCUSSION: Vaccination is considered the best prevention in case of a pandemic threat and first choice to contain the impact of a pandemic. Pending the availability of an effective pandemic vaccine, antivirals are likely the only effective agents for prevention and treatment. When an influenza pandemic is impending, all interventions aim to prevent people becoming infected and to suppress replication and transmission of the virus as much as possible. Antivirals will be prescribed to patients with laboratory confirmed pre-pandemic influenza as well as to their contacts (post-exposure prophylaxis) which may delay development of or even prevent a pandemic. During a manifest influenza pandemic, however, there is large-scale spreading of the influenza virus. Therefore, preventive use of antivirals is less efficient to prevent transmission. Delaying the pandemic is then important in order to prevent exhausting public health resources and disruption of society. Thus, during a manifest pandemic everyone with influenza symptoms should receive antivirals as quickly as possible, regardless of virological confirmation. To ensure optimal effectiveness of antivirals and to minimize development of drug resistant viral strains, the use of antivirals for annual influenza should be restrictive. The crucial position of family physicians during an (impending) influenza pandemic necessitates the development of primary health care guidelines on this topic for all countries. SUMMARY: Family physicians will play a key role in assessing and treating victims of a new influenza virus, and in reassuring the worried well. We outline various possible interventions in the event of an impending and a manifest influenza pandemic, such as non-medial measures, prescription of antivirals, and vaccination, and emphasize the need for pandemic influenza preparedness.

Vaccination of healthcare personnel in Europe: Update to current policies.

We investigated and compared current national vaccination policies for health-care personnel (HCP) in Europe with results from our previous survey. Data from 36 European countries were collected using the same methodology as in 2011. National policies for HCP immunization were in place in all countries. There were significant differences in terms of number of vaccinations, target HCP and healthcare settings, and implementation regulations (recommended or mandatory vaccinations). Vaccination policies against hepatitis B and seasonal influenza were present in 35 countries each. Policies for vaccination of HCP against measles, mumps, rubella and varicella existed in 28, 24, 25 and 19 countries, respectively; and against tetanus, diphtheria, pertussis and poliomyelitis in 21, 20, 19, and 18 countries, respectively. Recommendations for hepatitis A immunization existed in 17 countries, and against meningococcus B, meningococcus C, meningococcus A, C, W, Y, and tuberculosis in 10, 8, 17, and 7 countries, respectively. Mandatory vaccination policies were found in 13 countries and were a pre-requisite for employment in ten. Comparing the vaccination programs of the 30 European countries that participated in the 2011 survey, we found that more countries had national vaccination policies against measles, mumps, rubella, hepatitis A, diphtheria, tetanus, poliomyelitis, pertussis, meningococcus C and/or meningococcus A, C, W, Y; and more of these implemented mandatory vaccination policies for HCP. In conclusion, European countries now have more comprehensive national vaccination programs for HCP, however there are still gaps. Given the recent large outbreaks of vaccine-preventable diseases in Europe and the occupational risk for HCP, vaccination policies need to be expanded and strengthened in several European countries. Overall, vaccination policies for HCP in Europe should be periodically re-evaluated in order to provide optimal protection against vaccine-preventable diseases and infection control within healthcare facilities for HCP and patients.

Familiarity between patient and general practitioner does not influence the content of the consultation.

BACKGROUND: Personal continuity in general practice is considered to be a prerequisite of high quality patient care based on shared knowledge and mutual understanding. Not much is known about how personal continuity is reflected in the content of GP - patient communication. We explored whether personal continuity of care influences the content of communication during the consultation. METHODS: Personal continuity was defined as the degree of familiarity between GP and patient, rated by both the GP and the patient. 394 videotaped consultations between GPs and patients aged 18 years and older were analyzed. GP - patient communication was evaluated with an observation checklist, which rated the following topics of conversation: (1) medical issues, (2) psychological themes, and (3) the social environment of the patient. For each of these topics we coded whether or not it received attention, and was built upon prior knowledge. Data were analyzed using multilevel logistic regression analyses. RESULTS: No relationship was found between GP - patient familiarity and the discussion of medical issues, psychological themes, or the social environment of the patient. But if the patient and the GP knew each other very well, the GP more often displayed prior knowledge with the topic in question. Few patient and GP characteristics were associated with differences in content of communication. CONCLUSION: Given the relatively small sample size, we carefully conclude that familiarity between a GP and a patient does not influence the content of the communication (medical issues, psychological themes nor topics relating to the social environment). This is remarkable because we expected that familiarity would 'open up the communication' for more psychological and social themes. GPs seem to have the communication skills to put both familiar and non-familiar patients at ease enabling them to freely raise any issue they think necessary.

The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial.

BACKGROUND: Postherpetic neuralgia is the most frequent complication of herpes zoster. Treatment of this neuropathic pain syndrome is difficult and often disappointing. We assessed the effectiveness of a single epidural injection of steroids and local anaesthetics for prevention of postherpetic neuralgia in older patients with herpes zoster. METHODS: We randomly assigned 598 patients older than 50 years, with acute herpes zoster (rash <7 days) below dermatome C6, to receive either standard therapy (oral antivirals and analgesics) or standard therapy with one additional epidural injection of 80 mg methylprednisolone acetate and 10 mg bupivacaine. The primary endpoint was the proportion of patients with zoster-associated pain 1 month after inclusion. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN32866390. FINDINGS: At 1 month, 137 (48%) patients in the epidural group reported pain compared with 164 (58%) in the control group (relative risk [RR] 0.83, 95% CI 0.71-0.97, p=0.02). After 3 months these values were 58 (21%) and 63 (24%) respectively (0.89, 0.65-1.21, p=0.47) and, at 6 months, 39 (15%) and 44 (17%; 0.85, 0.57-1.13, p=0.43). We detected no subgroups in which the relative risk for pain 1 month after inclusion substantially differed from the overall estimate. No patient had major adverse events related to epidural injection. INTERPRETATION: A single epidural injection of steroids and local anaesthetics in the acute phase of herpes zoster has a modest effect in reducing zoster-associated pain for 1 month. This treatment is not effective for prevention of long-term postherpetic neuralgia.

Clinical diagnosis of herpes zoster in family practice.

PURPOSE: Family physicians usually diagnose herpes zoster on clinical grounds only, possibly resulting in false-positive diagnoses and unnecessary treatment. We wanted to determine the positive predictive value of the physicians' judgment in diagnosing herpes zoster and to assess the applicability of dried blood spot analysis for diagnosis of herpes zoster in family practice. METHODS: Our study population consisted of 272 patients older than 50 years with herpes zoster (rash for less than 7 days). Dried blood spot samples were collected from all patients and sent by mail to the laboratory. Baseline measurements included clinical signs (localization, severity, and duration of rash) and symptoms (duration and severity of pain). Varicella-zoster virus antibodies were determined at baseline and 5 to 10 days later. Multivariate logistic regression was used to assess independent associations between clinical variables and serological confirmation of herpes zoster. RESULTS: Dried blood spot analysis was possible in 260 patients (96%). In 236 the diagnosis of herpes zoster was confirmed serologically (positive predictive value of clinical judgment 90.8%; 95% confidence interval, 87.3%-94.3%). Independent clinical variables for serologically confirmed herpes zoster were severity and duration of rash at first examination. CONCLUSION: Family physicians have good clinical judgment when diagnosing herpes zoster in older patients. Dried blood spot analysis is a logistically convenient method for serological investigation of patients in family practice, but it is rarely needed for diagnosing herpes zoster.

Variations in influenza vaccination coverage among the high-risk population in Sweden in 2003/4 and 2004/5: a population survey.

BACKGROUND: In Sweden, the vaccination campaign is the individual responsibility of the counties, which results in different arrangements. The aim of this study was to find out whether influenza vaccination coverage rates (VCRs) had increased between 2003/4 and 2004/5 among population at high risk and to find out the influence of personal preferences, demographic characteristics and health care system characteristics on VCRs. METHODS: An average sample of 2500 persons was interviewed each season (2003/4 and 2004/5). The respondents were asked whether they had had an influenza vaccination, whether they suffered from chronic conditions and the reasons of non-vaccination. For every county the relevant health care system characteristics were collected via a questionnaire sent to the medical officers of communicable diseases. RESULTS: No difference in VCR was found between the two seasons. Personal invitations strongly increased the chance of having had a vaccination. For the elderly, the number of different health care professionals in a region involved in administering vaccines decreased this chance. CONCLUSION: Sweden remained below the WHO-recommendations for population at high risk due to disease. To meet the 2010 WHO-recommendation further action may be necessary to increase vaccine uptake. Increasing the number of personal invitations and restricting the number of different administrators responsible for vaccination may be effective in increasing VCRs among the elderly.

Effectiveness and cost-effectiveness of nationwide campaigns for awareness and case finding of hepatitis C targeted at people who inject drugs and the general population in the Netherlands.

BACKGROUND: Hepatitis C virus infection (HCV) is a serious, but underdiagnosed disease that can generally be treated successfully. Therefore, a nationwide HCV awareness campaign was implemented in the Netherlands targeting people who inject drugs (PWID) in addiction care ('PWID intervention') and high-risk groups in the general population ('public intervention'). The objective of this study is to assess the effectiveness and cost-effectiveness of the interventions used in this campaign. METHODS: For the 'PWID' intervention, all addiction care centres in the Netherlands provided proactive individual HCV consultation and testing. The 'public intervention' consisted of health education through mass media and instruction of health care professionals. A Markov chain model was used to estimate incremental cost-effectiveness ratios (ICER, cost per QALY gained). We included a 'DAA treatment' scenario to estimate the effect of these treatment strategies on cost-effectiveness. RESULTS: The 'PWID intervention' identified 257 additional HCV-carriers. The ICER was €9056 (95% CI: €6043-€13,523) when compared to 'no intervention'. The 'public intervention' identified 38 additional HCV-carriers. The ICER was €18,421 (95% CI: €7376-€25,490,119) when compared to 'no intervention'. Probabilistic sensitivity analysis showed that the probability that the 'PWID intervention' was cost-effective was 100%. It also showed a probability of 34% that the 'public intervention' did not exceed the Dutch threshold for cost-effectiveness (€20,000). New treatment regimens are likely to improve cost-effectiveness of this strategy. CONCLUSION: In a nationwide HCV awareness and case finding campaign, the intervention targeting PWID was effective and cost-effective. An intervention targeting risk groups in the general population showed only a modest effect and is therefore less likely to be cost-effective.

Gender as an independent risk factor for herpes zoster: a population-based prospective study.

PURPOSE: Several studies reported a difference in herpes zoster (HZ) incidence between males and females, but limitations in design and analysis impeded the assessment of gender as an independent risk factor for HZ. This study examines the independent etiologic association between gender and HZ. METHODS: A total of 335,714 persons were observed prospectively during 2001. We registered gender and HZ occurrence, as well as other risk factors for HZ. We calculated overall crude and adjusted odds ratios (ORs) and stratified to age. RESULTS: The HZ incidence in females was 3.9/1000 patients/year (95% confidence interval [CI], 3.6-4.2), and in males, 2.5/1000 patients/year (95% CI, 2.3-2.8), with a crude OR of 1.53 (95% CI, 1.36-1.74). After adjustment for potential confounders, the adjusted OR was 1.38 (95% CI, 1.22-1.56). The incidence was greater in females in the middle-aged (age, 25 to 64 years; OR range, 1.36 to 1.83) and youngest group (OR, 1.31; 95% CI, 0.90-1.89). Gender effect was inverse in young adults (age, 15 to 24 years; OR, 0.64; 95% CI, 0.41-1.03). CONCLUSION: Female gender is an independent risk factor for HZ in the 25- to 64-year-old age groups.

Clinical effectiveness of influenza vaccination in persons younger than 65 years with high-risk medical conditions: the PRISMA study.

BACKGROUND: Influenza vaccination has consistently been shown to prevent all-cause death and hospitalizations during influenza epidemics among seniors. However, such benefits have not yet been demonstrated among younger individuals with high-risk medical conditions. In the present study, we evaluated the effectiveness of influenza vaccine in persons recommended for vaccination of any age during an epidemic. METHODS: We conducted a case-control study during the 1999-2000 influenza A epidemic nested in a cohort of 75,227 primary care patients. End points were all-cause mortality and episodes of hospitalizations or general practitioner (GP) visits for influenza, pneumonia, other acute respiratory disease, acute otitis media, myocardial infarction, heart failure, and stroke. The effectiveness of vaccination was evaluated by means of logistic regression analysis with adjustments for age, sex, prior health care use, medication use, and comorbid conditions. RESULTS: Among high-risk children and adolescents younger than 18 years (n=5933; 8% of the study population), 1 death, 3 hospitalizations for pneumonia, and 160 GP visits occurred. After adjustments, 43% (95% confidence interval [CI], 10%-64%) of visits were prevented. Among high-risk adults aged between 18 and 64 years (n=24 928; 33% of the study population), 47 deaths, 23 hospitalizations, and 363 GP visits occurred. After adjustments, vaccination prevented 78% of deaths (95% CI, 39%-92%), 87% of hospitalizations (95% CI, 39%-97%), and 26% of GP visits (95% CI, 7%-47%). Among elderly persons (n=44 366; 59% of the study population), 272 deaths and 166 hospitalizations occurred, and after adjustments the vaccine prevented these end points by 50% (95% CI, 23%-68%) and 48% (95% CI, 7%-71%), respectively. CONCLUSION: Persons with high-risk medical conditions of any age can substantially benefit from annual influenza vaccination during an epidemic.

Influenza vaccination: key facts for general practitioners in Europe-a synthesis by European experts based on national guidelines and best practices in the United Kingdom and the Netherlands.

Currently there is no influenza vaccination guidance for European general practitioners. Furthermore, although the European Council recommends a target seasonal influenza vaccination rate of 75% in the elderly (65 years and above) and in anyone aged >6 months with a chronic medical condition, there remain wide discrepancies throughout Europe. A harmonised guideline regarding not only vaccination strategy but also for the consistent diagnosis of influenza across Europe is essential to support a common approach for the implementation of seasonal influenza vaccination across Europe. This document is based on pre-existing guidelines available in the UK and Netherlands and has been approved by a group of European experts for use throughout Europe. As well as providing a standardised influenza diagnosis, it also reviews the current recommendations for influenza vaccination, the types of vaccine available, the contraindications, vaccine use in special populations (in pregnancy, children, and in those with egg allergy), and concomitant administration with other vaccines. The effectiveness, safety, and timing of the seasonal influenza vaccine are also reviewed. A second section provides practical guidance for general practitioners for the implementation of a seasonal influenza vaccination program, including the selection and notification of those eligible for vaccination, as well as suggestions for the organisation of a vaccination programme. Finally, suggested responses to common patient misconceptions and frequently asked questions are included. The aim of this article is to harmonise the diagnosis of seasonal influenza and the approach of European general practitioners to seasonal influenza vaccination in order to better identify influenza outbreaks and to move towards reaching the target vaccination rate of 75% throughout Europe.

Immunogenicity of AS03-adjuvanted and non-adjuvanted trivalent inactivated influenza vaccines in elderly adults: A Phase 3, randomized trial and post-hoc correlate of protection analysis.

In this study we describe the immunogenicity results from a subset of older people (N = 5187) who participated in a Phase 3 randomized, observer-blinded trial of AS03-TIV versus TIV (Fluarix™) (ClinicalTrials.gov, NCT00753272). Participants received one dose of AS03-TIV or TIV in each study year and antibody titers against the vaccine strains were assessed using hemagglutination-inhibition (HI) assay at 21 d and 180 d post-vaccination in each vaccine group in the 2008/09 (Year 1) and 2009/10 (Year 2) influenza seasons. Manufacturing consistency of 3 lots of AS03-TIV for HI antibody responses in Year 1 was a co-primary objective. In a post-hoc analysis, a statistical regression model included 4830 subjects in whom immunogenicity and laboratory-confirmed attack rate data were available; the analysis was performed to assess HI antibody titers against A/H3N2 as a correlate of protection for laboratory-confirmed A/H3N2 influenza. AS03-TIV and TIV elicited strong HI antibody responses against each vaccine strain 21 d post-vaccination in both years. The manufacturing consistency of 3 lots of AS03-TIV was demonstrated. In both years and each vaccine group, HI antibody responses were lower for A/H1N1 than the other vaccine strains. Day 180 seroconversion rates (proportion with ≥4-fold increase in titer compared with pre-vaccination titer) in Year 1 in the AS03-TIV and TIV groups, respectively, were 87.7% and 74.1% for A/H3N2, 69.7% and 59.6% for influenza B, and 58.3% and 47.4% for A/H1N1. The post-hoc statistical model based on A/H3N2 attack rates and HI antibody titers estimated that a 4-fold increase in post-vaccination titers against A/H3N2 was associated with a 2-fold decrease in the odds of A/H3N2 infection.

Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease.

Background. To investigate the relationship between hemagglutinin-inhibition (HI) antibody levels to the risk of influenza disease, we conducted a correlate of protection analysis using pooled data from previously published randomized trials. Methods. Data on the occurrence of laboratory-confirmed influenza and HI levels pre- and postvaccination were analyzed from 4 datasets: 3 datasets included subjects aged <65 years who received inactivated trivalent influenza vaccine (TIV) or placebo, and 1 dataset included subjects aged ≥65 years who received AS03-adjuvanted TIV (AS03-TIV) or TIV. A logistic model was used to evaluate the relationship between the postvaccination titer of A/H3N2 HI antibodies and occurrence of A/H3N2 disease. We then built a receiver-operating characteristic curve to identify a potential cutoff titer between protection and no protection. Results. The baseline odds ratio of A/H3N2 disease was higher for subjects aged ≥65 years than <65 years and higher in seasons of strong epidemic intensity than moderate or low intensity. Including age and epidemic intensity as covariates, a 4-fold increase in titer was associated with a 2-fold decrease in the risk of A/H3N2 disease. Conclusions. The modeling exercise confirmed a relationship between A/H3N2 disease and HI responses, but it did not allow an evaluation of the predictive power of the HI response.

Measles incidence estimations based on the notification by general practitioners were suboptimal.

OBJECTIVE: The aim of this study was to determine the notification by general practitioners (GPs) to the Municipal Health Service (MHS) and the presentation of measles complaints by patients to the GP during a measles epidemic in a 78% vaccinated population. STUDY DESIGN AND SETTING: Measles cases in children under 13 years were identified via questionnaires, GPs' records, and MHS's records. Consultation rate, notification rate, and completeness of notification were determined. Determinants of consultation were identified by multivariable logistic regression analysis. RESULTS: Among 1654 responders, 164 measles cases were identified. Consultation rate: 30%; notification rate: 30% (range among GPs: 0-62%); completeness of notification: 9%. Determinants of GP consultation: perceived seriousness of illness (adjusted OR 45; 95% CI: 6-347), self-reported complications (adjusted OR 9; 95% CI: 1-70), and need to consult for respiratory tract infections (adjusted OR 8; 95% CI: 1-51). CONCLUSION: Incidence estimations based on the notification by GPs to the MHS are suboptimal for measles in The Netherlands. Perceived seriousness of illness seemed to be the most important factor to consult.