Summary Background Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall ...effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. Methods Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated “moderately bad” or worse. Secondary outcomes were symptom severity in days 2–4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). Findings 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated “moderately bad” or worse (hazard ratio 1·06, 95% CI 0·96–1·18; p=0·229) nor mean symptom severity (1·69 with placebo vs 1·62 with amoxicillin; difference −0·07 95% CI −0·15 to 0·007; p=0·074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 15·9% of 1021 patients vs 194 19·3% of 1006; p=0·043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11–174; p=0·025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595). Interpretation When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms. Funding European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
Summary 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 NNTbenefit 7 to NNTharm 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 NNTbenefit 4 to NNTharm 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.
Abstract Purpose We set out to assess whether a high sense of coherence (SOC) protects from adverse health outcomes in patients aged 80 years and older who have multiple chronic diseases. Methods A ...population-based prospective cohort study in 29 primary care practices throughout Belgium included 567 individuals aged 80 years and older. We plotted the highest tertile of SOC scores in Kaplan-Meier curves representing 3-year mortality and time to first hospitalization. Using Cox proportional hazard regression analyses and multiple logistic regression analyses adjusted for sociodemographic characteristics, depression, cognition, disability, and multimorbidity we examined the relationship between SOC and mortality, hospitalization, and decline in performance of activities of daily living (ADL). Results Subjects with high SOC scores showed a higher cumulative survival than others (Log rank = 0.004) independent of other prognostic characteristics (adjusted hazard ratio 0.62 (95% CI, 0.38–1.00), P = .049). For ADL decline, a high SOC was shown to be protective, and this effect tended to be independent from the covariates under study (adjusted odds ratio 0.56 (95% CI, 0.31–1.0), P = .05). Conclusion Even very elderly persons with high SOC scores were shown to have lower mortality rates and less functional decline. These effects were independent of multimorbidity, depression, cognition, disability, and sociodemographic characteristics.
Abstract Purpose We sought to determine the prevalence of airway obstruction and bronchodilator responsiveness in adults consulting for acute cough in primary care. Methods Family physicians ...recruited 3,105 adult patients with acute cough (28 days or shorter) attending primary care practices in 12 European countries. After exclusion of patients with preexisting physician-diagnosed asthma or chronic obstructive pulmonary disease (COPD), we undertook complete case analysis of spirometry results (n = 1,947) 28 to 35 days after inclusion. Bronchodilator responsiveness was diagnosed if there were recurrent complaints of wheezing, cough, or dyspnea and an increase of the forced expiratory volume in 1 second (FEV1) of 12% or more after bronchodilation. Airway obstruction was diagnosed according to 2 thresholds for the (postbronchodilator) ratio of FEV1 to forced vital capacity (FEV1:FVC): less than 0.7 and less than the lower limit of normal. Results There were 240 participants who showed bronchodilator responsiveness (12%), 193 (10%) had a FEV1 /FVC ratio of less than 0.7, and 126 (6%) had a ratio of less than the lower limit of normal. Spearman's correlation between the 2 definitions of obstruction was 0.71 ( P < .001), with discordance most pronounced among those younger than 30 years and in older participants. Conclusion Both bronchodilator responsiveness and persistent airway obstruction are common in adults without established asthma or COPD who consult for acute cough in primary care, which suggests a high risk of undiagnosed asthma and COPD. Different accepted methods to define airway obstruction detected different numbers of patients, especially at the extremes of age. As both conditions benefit from appropriate and timely interventions, clinicians should be aware and responsive to potential underdiagnosis.
Summary Background Modified vaccinia virus Ankara (MVA) is a promising viral vector platform for the development of an H5N1 influenza vaccine. Preclinical assessment of MVA-based H5N1 vaccines showed ...their immunogenicity and safety in different animal models. We aimed to assess the safety and immunogenicity of the MVA-haemagglutinin-based H5N1 vaccine MVA-H5-sfMR in healthy individuals. Methods In a single-centre, double-blind phase 1/2a study, young volunteers (aged 18–28 years) were randomly assigned with a computer-generated list in equal numbers to one of eight groups and were given one injection or two injections intramuscularly at an interval of 4 weeks of a standard dose (108 plaque forming units pfu) or a ten times lower dose (107 pfu) of the MVA-H5-sfMR (vector encoding the haemagglutinin gene of influenza A/Vietnam/1194/2004 virus H5N1 subtype) or MVA-F6-sfMR (empty vector) vaccine. Volunteers and physicians who examined and administered the vaccine were masked to vaccine assignment. Individuals who received the MVA-H5-sfMR vaccine were eligible for a booster immunisation 1 year after the first immunisation. Primary endpoint was safety. Secondary outcome was immunogenicity. The trial is registered with the Dutch Trial Register, number NTR3401. Findings 79 of 80 individuals who were enrolled completed the study. No serious adverse events were identified. 11 individuals reported severe headache and lightheadedness, erythema nodosum, respiratory illness (accompanied by influenza-like symptoms), sore throat, or injection-site reaction. Most of the volunteers had one or more local (itch, pain, redness, and swelling) and systemic reactions (rise in body temperature, headache, myalgia, arthralgia, chills, malaise, and fatigue) after the first, second, and booster immunisations. Individuals who received the 107 dose had fewer systemic reactions. The MVA-H5-sfMR vaccine at 108 pfu induced significantly higher antibody responses after one and two immunisations than did 107 pfu when assessed with haemagglutination inhibition geometric mean titre at 8 weeks against H5N1 A/Vietnam/1194/2004 (30·2 SD 3·8 vs 9·2 2·3 and 108·1 2·4 vs 15·8 3·2). 27 of 39 eligible individuals were enrolled in the booster immunisation study. A single shot of MVA-H5-sfMR 108 pfu prime immunisation resulted in higher antibody responses after the booster immunisation than did two shots of MVA-H5-sfMR at the ten times lower dose. Interpretation The MVA-based H5N1 vaccine was well tolerated and immunogenic and therefore the vaccine candidates arising from the MVA platform hold great promise for rapid development in response to a future influenza pandemic threat. However, the immunogenicity of this vaccine needs to be compared with conventional H5N1 inactivated non-adjuvanted vaccine candidates in head-to-head clinical trials. Funding European Research Council.
Objectives of this study were to perform a prospective head-to-head comparison between multi-slice computed tomography (MSCT) venography and invasive venography in cardiac resynchronization therapy ...(CRT) candidates as well as to evaluate the relation between left ventricular (LV) lead position and effect on LV dyssynchrony and immediate response to CRT. Twenty-one consecutive heart failure patients scheduled for CRT implantation were prospectively enrolled to undergo 64-slice MSCT to visualize the venous system, invasive venography during device implantation, and tri-plane tissue synchronization imaging (TSI) before and after implantation. Excellent agreement between MSCT and invasive venography was noted. No significant differences were observed between both techniques regarding vessel diameters. In 12 patients, a match was observed between the area of latest mechanical activation (on TSI) and LV lead position. These patients showed a significant decrease in LV dyssynchrony (43 ± 7 ms to 11 ± 9 ms, p <0.0001) with acute reduction in LV end-systolic volume (188 ± 54 ml to 162 ± 48 ml, p <0.01) and improvement in LV ejection fraction (22% ± 9% to 34% ± 9%, p <0.01). Patients with a mismatch between area of latest activation and LV lead position remained dyssynchronous without improvement in LV function. In conclusion, visualization of major tributaries of the coronary sinus was comparable between invasive venography and MSCT venography. Optimal LV lead positioning in a vein draining the area of latest mechanical activation (determined from tri-plane TSI) resulted in acute improvement of LV dyssynchrony and systolic function after CRT implantation.
To report the 2-year cosmetic outcome of a randomized trial comparing prone and supine whole-breast irradiation in large-breasted patients.
One hundred patients with a (European) cup size ≥C were ...included. Before and 2 years after radiation therapy, clinical endpoints were scored and digital photographs were taken with the arms alongside the body and with the arms elevated 180°. Three observers rated the photographs using the 4-point Harvard cosmesis scale. Cosmesis was also evaluated with the commercially available Breast Cancer Conservation Treatment.cosmetic results (BCCT.core) software.
Two-year follow-up data and photographs were available for 94 patients (47 supine treated and 47 prone treated). Patient and treatment characteristics were not significantly different between the 2 cohorts. A worsening of color change occurred more frequently in the supine than in the prone cohort (19/46 vs 10/46 patients, respectively, P=.04). Five patients in the prone group (11%) and 12 patients in the supine group (26%) presented with a worse scoring of edema at 2-year follow-up (P=.06). For retraction and fibrosis, no significant differences were found between the 2 cohorts, although scores were generally worse in the supine cohort. The cosmetic scoring by 3 observers did not reveal differences between the prone and supine groups. On the photographs with the hands up, 7 patients in the supine group versus none in the prone group had a worsening of cosmesis of 2 categories using the BCCT.org software (P=.02).
With a limited follow-up of 2 years, better cosmetic outcome was observed in prone-treated than in supine-treated patients.
To compare in vitro properties of 4 drug-eluting embolic agents loaded with doxorubicin.
DC Bead (100–300 µm), LifePearl (200 µm), HepaSphere (30–60 µm), and Tandem (100 µm) microspheres were loaded ...with 40 mg/20 mL of doxorubicin per milliliter of microspheres. Loading, elution, diameter changes after loading, changes in the amount of doxorubicin loaded over 2 weeks in storage, and time in suspension were evaluated.
All microspheres loaded > 99% doxorubicin within 1 hour. In vitro elution reached a plateau by 6 hours, with 30% ± 5, 21% ± 2, 8% ± 3, and 6% ± 0 of the loaded doxorubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem microspheres, respectively, with at least 1 statistically significant difference between at least 2 of the products in doxorubicin eluted at every time point. The times to elute 75% of the total released doxorubicin were 197, 139, 110, and 77 min for DC Bead, LifePearl, HepaSphere, and Tandem microspheres, respectively. The average diameters of LifePearl, DC Bead, and Tandem microspheres were reduced after loading by 24%, 20%, and 9%, respectively. After suspension in contrast medium, no changes were observed in doxorubicin loading over 2 wk. After loading, times in suspension were 8.4 min ± 0.2, 6.0 min ± 0.1, 3.1 min ± 0.2, and 2.9 min ± 0.3 for Tandem, LifePearl, DC Bead, and HepaSphere microspheres, respectively.
Although drug-eluting embolic agents universally loaded doxorubicin within 1 hour, the elution amounts, rates of release, diameter shrinkage, and times in suspension varied by product.
Abstract Purpose Imaging may produce unexpected or incidental findings with consequences for patients and ordering of future investigations. Chest radiography in patients with acute cough is among ...the most common reasons for imaging in primary care, but data on associated incidental findings are lacking. We set out to describe the type and prevalence of incidental chest radiography findings in primary care patients with acute cough. Methods We report on data from a cross-sectional study in 16 European primary care networks on 3,105 patients with acute cough, all of whom were undergoing chest radiography as part of a research study workup. Apart from assessment for specified signs of pneumonia and acute bronchitis, local radiologists were asked to evaluate any additional finding on the radiographs. For the 2,823 participants with good-quality chest radiographs, these findings were categorized according to clinical relevance based on previous research evidence and analyzed for type and prevalence by network, sex, age, and smoking status. Results Incidental findings were reported in 19% of all participants, and ranged from 0% to 25% by primary care network, with the network being an independent contributor ( P < .001). Of all participants 3% had clinically relevant incidental findings. Suspected nodules and shadows were reported in 1.8%. Incidental findings were more common is older participants and smokers ( P <.001). Conclusion Clinically relevant incidental findings on chest radiographs in primary care adult patients with acute cough are uncommon, and prevalence varies by setting.
Information on exercise capacity and training in patients who underwent valvular surgery is scarce. The aim of this study is to evaluate postoperative exercise capacity and functional improvement ...after exercise training according to the preoperative risk and type of surgery. In this prospective study, 145 patients who underwent aortic valve surgery (AVS) or mitral valve surgery (MVS) and who were referred for cardiac rehabilitation were stratified according to the preoperative risk (European System for Cardiac Operative Risk Evaluation EuroSCORE) and type of surgery (sternotomy vs ministernotomy or port access). Exercise capacity was evaluated at the start and end of cardiac rehabilitation. Postoperative exercise capacity and the benefit from exercise training were compared between the groups. Patients with a higher preoperative risk had a worse postoperative exercise capacity, with a lower load, peak VO2 , anaerobic threshold and 6-minute walking distance (all p <0.001), and a higher VE/VCO2 slope (p = 0.01). In MVS, port access patients performed significantly better at baseline (all p <0.05), but in AVS, ministernotomy patients performed better than sternotomy patients with a concomitant coronary artery bypass graft (p <0.05). Training resulted in an improvement in exercise capacity in each risk group and each type of surgery (all p <0.05). This gain in exercise capacity was comparable for the EuroSCORE risk groups and for the types of surgery, for patients after AVS or MVS. In conclusion, exercise capacity after cardiac surgery is related to the preoperative risk and the type of surgery. Despite these differences in postoperative exercise capacity, a similar benefit from exercise training is obtained, regardless of their preoperative risk or type of surgery.
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