This study in 8 countries across Europe found that about 75% of elderly women seen in primary care who were at high risk of osteoporosis-related fractures were not receiving appropriate medication. Lack of osteoporosis diagnosis appeared to be an important contributing factor. Introduction Treatment rates in osteoporosis are documented to be low. We wished to assess the osteoporosis treatment gap in women ≥ 70 years in routine primary care across Europe. Methods This cross-sectional observational study in 8 European countries collected data from women 70 years or older visiting their general practitioner. The primary outcome was treatment gap: the proportion who were not receiving any osteoporosis medication among those at increased risk of fragility fracture (using history of fracture, 10-year probability of fracture above country-specific Fracture Risk Assessment Tool [FRAX] thresholds, T-score ≤ − 2.5). Results Median 10-year probability of fracture (without bone mineral density [BMD]) for the 3798 enrolled patients was 7.2% (hip) and 16.6% (major osteoporotic). Overall, 2077 women (55%) met one or more definitions for increased risk of fragility fracture: 1200 had a prior fracture, 1814 exceeded the FRAX threshold, and 318 had a T-score ≤ − 2.5 (only 944 received a dualenergy x-ray absorptiometry [DXA] scan). In those at increased fracture risk, the median 10-year probability of hip and major osteoporotic fracture was 11.2% and 22.8%, vs 4.1% and 11.5% in those deemed not at risk. An osteoporosis diagnosis was recorded in 804 patients (21.2%); most (79.7%) of these were at increased fracture risk. The treatment gap was 74.6%, varying from 53% in Ireland to 91% in Germany. Patients with an osteoporosis diagnosis were found to have a lower treatment gap than those without a diagnosis, with an absolute reduction of 63%. Conclusions There is a large treatment gap in women aged ≥ 70 years at increased risk of fragility fracture in routine primary care across Europe. The gap appears to be related to a low rate of osteoporosis diagnosis.

Background: Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.

Background. Elderly persons often experience a reduced immune response to influenza vaccination. We evaluated the usual dose of AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004-like strain) compared with a double dose in an elderly population.Methods. This phase 2, open-label study (NCT00397215; http://www.clinicaltrials.gov) randomized participants (age, ≥61 years) to receive, on days 0 and 21: (1) a single dose of AS03A-adjuvanted vaccine (n = 152), (2) a single dose of nonadjuvanted vaccine (n = 54), (3) a double dose of AS03A-adjuvanted vaccine (n = 145), or (4) a double dose of nonadjuvanted vaccine (n = 44). The primary end point was hemagglutination inhibition (HI) and neutralizing antibody response against vaccine antigen (according-to-protocol cohort).Results. Day 42 geometric mean titers for HI antibodies were 126.8 and 237.3 for single and double doses of the AS03A-adjuvanted vaccine, respectively. Corresponding values for neutralizing antibodies were 447.3 and 595.8. Although the immune response was higher with the double dose, European Committee for Human Medicinal Products criteria for seroconversion and seroprotection rates were achieved in both AS03A-adjuvanted groups. Antigen-specific CD4 T cell responses were elicited. Immune response persistence at 6 months was high. Immune response in the non-adjuvanted groups was considerably less.Conclusions. The AS03A-adjuvanted H5N1 vaccine can be administered elderly persons at the same dose and schedule as in younger adults.

Seasonal influenza vaccine formulations must be updated annually to correspond to the influenza viruses in circulation. This was an uncontrolled, open-label, multi-center phase IV study conducted in Belgium to comply with interim European Medicines Agency (EMA) guidelines for rapidly evaluating the safety of newly formulated seasonal influenza vaccines. Adult volunteers received one dose of the 2014-2015 Northern Hemisphere formulation of licensed intradermal trivalent influenza vaccine at either the standard dose (9µg hemagglutinin/strain for 18−59 year-olds) or the high dose (15µg hemagglutinin/strain for ≥ 60 year-olds). Vaccinees recorded their solicited reactions and unsolicited adverse events for 7 d after vaccination. Solicited reaction frequencies were compared to historical reference values obtained from previous clinical trials to determine if the new formulations were excessively reactogenic or allergenic. A total of 210 participants (105 per age group) were included and vaccinated in October 2014. In both groups, pain, erythema, and pruritus were the most common solicited injection site reactions, and headache and myalgia were the most common solicited systemic reactions. Although the frequencies of shivering in 18−59 year-olds and malaise in ≥ 60 year-olds were higher than historical reference values, they were not considered indicative of excessive reactogenicity because almost all of these reactions were mild. The study design was endorsed by the EMA and permitted the reactogenicity of both vaccine formulations to be assessed within one month by collecting adverse events for 7 d. Both formulations exhibited acceptable safety profiles although this should be confirmed through forthcoming enhanced post-marketing safety surveillance systems.

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BackgroundOlder individuals often have a reduced immune response to influenza vaccination, which might be improved by administering a higher vaccine dose. We compared the immune response to two single doses of the AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004) with that of two double vaccine doses (7.5 μg hemagglutinin) in adults aged ≥61 years. Here we report the 2-year persistence of the humoral and cellular immune response.MethodsIn this phase II, open-label study, healthy participants aged 61 to 88 years (median 68 years) were randomised (3:1:3:1) to receive two single doses of the AS03A-adjuvanted vaccine (1xH5N1-AS) or the non-adjuvanted vaccine (1xH5N1), or two double doses of the AS03A-adjuvanted vaccine (2xH5N1-AS) or the non-adjuvanted vaccine (2xH5N1), 21 days apart. Serum haemagglutination inhibition antibodies and cellular immune responses against A/Vietnam/1194/2004 were measured in all groups at months 12 and 24; neutralising antibodies were assessed in a subset of the adjuvanted groups. Serious adverse events and adverse events of specific interest were recorded.ResultsAt month 24, haemagglutination inhibition antibody seroprotection rates were 37.2% (95% CI 27.0% to 48.3%) for 1xH5N1-AS, 30.9% (95% CI 21.1% to 42.1%) for 2xH5N1-AS, 16.2% (95% CI 6.2% to 32.0%) for 1xH5N1, and 8.3% (95% CI 1.0% to 27.0%) for 2xH5N1. Haemagglutination inhibition antibody geometric mean titres were 17.6 (95% CI 13.7 to 22.5) for 1xH5N1-AS, 18.4 (95% CI 14.2 to 23.8) for 2xH5N1-AS, 12.3 (95% CI 8.9 to 16.9) for 1xH5N1 and 9.8 (95% CI 6.7 to 14.4) for 2xH5N1. The median frequency of antigen-specific CD4+ T cells per 106 T cells (25th quartile; 75th quartile) was 852 (482; 1477) for 1xH5N1-AS, 1147 (662; 1698) for 2xH5N1-AS, 556 (343; 749) for 1x-H5N1 and 673 (465; 1497) for 2xH5N1. Neutralising antibody geometric mean titres were 391.0 (95% CI 295.5 to 517.5) in the 1xH5N1-AS group and 382.8 (95% CI 317.4 to 461.6) in the 2xH5N1-AS group.ConclusionsAntibody levels declined substantially in all groups. Seroprotection rates, geometric mean titres for haemagglutination inhibition antibodies, and CD4+ T-cell responses tended to be higher in the AS03A-adjuvanted groups. There was no clear benefit, in terms of long-term persistence of the immune response, of doubling the dose of the adjuvanted vaccine. No safety concern was observed up to 24 months post-primary vaccination.Trial registrationNCT00397215 (7 November 2006).Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-15-419) contains supplementary material, which is available to authorized users.

BackgroundSerious lower respiratory tract infections (SLRTIs), especially Streptococcus pneumoniae (SP)-related pneumonia cause considerable morbidity and mortality. Chest imaging, sputum and blood culture are not routinely obtained by general practitioners (GPs). Antibiotic therapy is usually started empirically. The BinaxNOW® and Urine Antigen Detection (UAD) assays have been developed respectively to detect a common antigen from all pneumococcal strains and the 13 pneumococcal serotypes present in the vaccine Prevenar 13® (PCV13).MethodsOPUS-B was a multicentre, prospective, case-control, observational study of patients with SLRTI in primary care in Belgium, conducted during two winter seasons (2011–2013). A urine sample was collected at baseline for the urine assays. GPs were blinded to the results. All patients with a positive BinaxNOW® test and twice as much randomly selected BinaxNOW® negative patients were followed up. Recorded data included: socio-demographics, medical history, vaccination history, clinical symptoms, CRB-65 score, treatments, hospitalization, blood cultures, healthcare use, EQ-5D score. The objectives were to evaluate the percentage of SP SLRTI within the total number of SLRTIs, to assess the percentage of SP serotypes and to compare the burden of disease between pneumococcal and non-pneumococcal SLRTIs.ResultsThere were 26 patients with a BinaxNOW® positive test and 518 patients with a BinaxNOW® negative test. The proportion of pneumococcal SLRTI was 4.8 % (95 % CI: 3.1 %–7.2 %). Sixty-eight percent of positive cases showed serotypes represented in PCV13. In the BinaxNOW-positive patients, women were more numerous, there was less exposure to young children, seasonal influenza vaccination was less frequent, COPD was more frequent, the body temperature and the number of breaths per minute were higher, the systolic blood pressure was lower, the frequency of sputum, infiltrate, chest pain, muscle ache, confusion/disorientation, diarrhoea, pneumonia and exacerbations of COPD was more frequent, EQ-5D index and VAS scale were lower, the number of visits to the GP, of working days lost and of days patients needed assistance were higher.ConclusionsSP was responsible for approximately 5 % of SLRTIs observed in primary care in Belgium. Pneumococcal infection was associated with a significant increase in morbidity. Sixty-eight percent of serotypes causing SLRTI were potentially preventable by PCV13.

Summary We studied whether elderly women at risk for fractures receive primary care treatment to prevent fracture. We found that across Europe, women at risk are often not identified, and less than half of such women receive appropriate treatment. Finally, women diagnosed with osteoporosis are much more likely to receive treatment. Purpose To examine the relationship between risk factors for fragility fracture (FF) and osteoporosis (OP) treatment gap in elderly women across Europe, and compare the prevalence of risk factors between countries. Methods Demographic and clinical information was collected from women ≥ 70 years visiting primary care physicians in Belgium, France, Germany, Ireland, Poland, Slovakia, Switzerland, and the UK. Increased risk of FF was defined by the presence of 1 or more criteria (history of fracture, 10-year fracture probability, or T-score ≤  − 2.5). Results There were 3798 women in total. Treatment gap (proportion at increased risk of FF not receiving treatment for OP) varied from 53.1 to 90.8% across countries, and the proportion of patients at increased risk of FF varied from 41.2 to 76.1%. Across countries, less than 50% of patients with increased risk of FF had a diagnosis of OP. Previous fracture was the most common risk factor, with similar prevalence across most countries; other risk factors varied widely. The treatment gap was reduced in patients with an OP diagnosis in all countries, but this reduction varied from 36.5 to 79.4%. The countries with the lowest rates of bone densitometry scans (Poland, France, and Germany; 8.3–12.3%) also had the highest treatment gap (82.2 to 90.8%). Conclusions This study highlights differences across Europe in clinical risk factors for fracture, rates of densitometry scanning, and the rates of OP diagnosis. More emphasis is needed on risk assessment to improve the identification and treatment of elderly women at risk for fracture.