Summary Background High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it ...frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems. Methods After a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214. Results The baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 55·3%) and upper-respiratory-tract infections (1416 20·9%), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42–0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54–0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36–0·74, p<0·0001; enhanced communication 0·68, 0·50–0·89, p=0·003; combined 0·38, 0·25–0·55, p<0·0001). Interpretation Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries. Funding European Commission Framework Programme 6, National Institute for Health Research, Research Foundation Flanders.
Abstract Purpose C-reactive-protein (CRP) is useful for diagnosis of lower respiratory tract infections (RTIs). A large international trial documented that Internet-based training in CRP ...point-of-care testing, in enhanced communication skills, or both reduced antibiotic prescribing at 3 months, with risk ratios (RRs) of 0.68, 0.53, 0.38, respectively. We report the longer-term impact in this trial. Methods A total of 246 general practices in 6 countries were cluster-randomized to usual care, Internet-based training on CRP point-of-care testing, Internet-based training on enhanced communication skills and interactive booklet, or both interventions combined. The main outcome was antibiotic prescribing for RTIs after 12 months. Results Of 228 practices providing 3-month data, 74% provided 12-month data, with no demonstrable attrition bias. Between 3 months and 12 months, prescribing for RTIs decreased with usual care (from 58% to 51%), but increased with CRP training (from 35% to 43%) and with both interventions combined (from 32% to 45%); at 12 months, the adjusted RRs compared with usual care were 0.75 (95% CI, 0.51–1.00) and 0.70 (95% CI, 0.49–0.93), respectively. Between 3 months and 12 months, the reduction in prescribing with communication training was maintained (41% and 40%, with an RR at 12 months of 0.70 95% CI, 0.49–0.94). Although materials were provided for free, clinicians seldom used booklets and rarely used CRP point-of-care testing. Communication training, but not CRP training, remained efficacious for reducing prescribing for lower RTIs (RR = 0.7195% CI, 0.45–0.99, and RR = 0.76; 95% CI, 0.47–1.06, respectively), whereas both remained efficacious for reducing prescribing for upper RTIs (RR = 0.60; 95% CI, 0.37–0.94, and RR = 0.58; 95% CI, 0.36–0.92, respectively). Conclusions Internet-based training in enhanced communication skills remains effective in the longer term for reducing antibiotic prescribing. The early improvement seen with CRP training wanes, and this training becomes ineffective for lower RTIs, the only current indication for using CRP testing.
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 Data from trials suggest that antibiotics reduce the risk of complications of sore throat by at least 50%, but few trials for complications have been done in modern settings, and ...datasets of delayed antibiotic prescription are underpowered. Observational evidence is important in view of poor compliance with antibiotic treatment outside trials, but no prospective observational cohort studies have been done to date. Methods We generated a large prospective cohort from the DESCARTE study, and the PRISM component of DESCARTE, of 12 829 adults presenting with sore throat (≤2 weeks duration) in primary care. Our follow-up of the cohort was based on a detailed and structured review of routine medical records, and analysis of the comparison of three antibiotic prescription strategies (no antibiotic prescription, immediate antibiotic prescription, and delayed antibiotic prescription) to control for the propensity to prescribe antibiotics. Information about antibiotic prescription was recorded in 12 677 individuals (4805 prescribed no antibiotics, 6088 prescribed antibiotics immediately, and 1784 prescribed delayed antibiotics). We documented by review of patients' notes (n=11 950) the development of suppurative complications (eg, quinsy, impetigo and cellulitis, otitis media, and sinusitis) or reconsultation with new or non-resolving symptoms). We used multivariate analysis to control for variables significantly related to the propensity to prescribe antibiotics and for clustering by general practitioner. Findings 164 (1·4%) of the 11 950 patients with information available developed complications; otitis media and sinusitis were the most common complications (101 patients 62%). Compared with no antibiotic prescription, immediate antibiotic prescription was associated with fewer complications (adjusted risk ratio RR 0·62, 95% CI 0·43–0·91, estimated number needed to treat NNT 193) as was delayed prescription of antibiotics (0·58, 0·34–0·98; NNT 174). 1787 of the 11 950 patients (15%) reconsulted with new or non-resolving symptoms; the risk of reconsultation was also reduced by immediate (0·83, 0·73–0·94; NNT 40) or delayed antibiotics (0·61, 0·50–0·74; NNT 18). Interpretation Suppurative complications are not common in primary care and most are not serious. The risks of suppurative complications or reconsultation in adults are reduced by antibiotics, but not as much as the trial evidence suggests. In most cases, no antibiotic is needed, but a delayed prescription strategy is likely to provide similar benefits to an immediate antibiotic prescription. Funding UK Medical Research Council.
Postinfectious cough is common in primary care, but has no proven effective treatments. Cysteinyl leukotrienes are involved in the pathogenesis of postinfectious cough and whooping cough (pertussis). ...We investigated the effectiveness of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment of postinfectious cough.
In this randomised, placebo-controlled trial, non-smoking adults aged 16-49 years with postinfectious cough of 2-8 weeks' duration were recruited from 25 general practices in England. Patients were tested for pertussis (oral fluid anti-pertussis toxin IgG) and randomly assigned (1:1) to montelukast 10 mg daily or image-matched placebo for 2 weeks. Patients chose whether to continue study drug for another 2 weeks. The randomisation sequence was computer-generated and stratified by general practice. Patients, health-care professionals, and researchers were masked to treatment allocation. Effectiveness was assessed with the Leicester Cough Questionnaire to measure changes in cough-specific quality of life; the primary outcomes were changes in total score between baseline and two follow-up stages (2 weeks and 4 weeks). The primary analysis was by intention to treat with imputation by last observation carried forward. Recruitment closed on Sept 21, 2012, and follow-up has been completed. This trial is registered with EudraCT (2010-019647-19), UKCRN Portfolio (ID 8360), and ClinicalTrials.gov (NCT01279668).
From April 13, 2011, to Sept 21, 2012, we randomly assigned 276 patients to montelukast (n=137) or placebo (n=139). 70 (25%) patients had laboratory-confirmed pertussis. Improvements in cough-specific quality of life occurred in both groups after 2 weeks (montelukast: mean 2·7, 95% CI 2·2-3·3; placebo: 3·6, 2·9-4·3), but the difference between groups did not meet the minimum clinically important difference of 1·3 (mean difference -0·9, -1·7 to -0·04, p=0·04). This difference was not statistically significant in any sensitivity analyses. After 2 weeks, 192 of 259 participants from whom data were available elected to continue study drug (99 77% of 129 participants on montelukast; 93 72% of 130 on placebo). After 4 weeks, there were no significant between-group differences in cough-specific quality of life improvement (montelukast: 5·2, 4·5-5·9; placebo: 5·9, 5·1-6·7; mean difference -0·5, -1·5 to 0·6, p=0·38) or adverse event rates (21 (15%) of 137 patients on montelukast reported one or more adverse events; 31 (22%) of 139 on placebo; p=0·14). The most common adverse events reported were increased mucus production (montelukast, n=6; placebo, n=2), gastrointestinal disturbance (montelukast, n=3; placebo, n=5), and headache (montelukast, n=2; placebo, n=6). One serious adverse event was reported (placebo, n=1), which was unrelated to study drug (shortness of breath and throat tightness after severe coughing bouts).
Montelukast is not an effective treatment for postinfectious cough. However, the burden of postinfectious cough in primary care is high, making it an ideal setting for future antitussive treatment trials.
National Institute for Health Research School for Primary Care Research, UK.
Abstract Purpose Presentation with acute lower respiratory tract infection (LRTI) in primary care is common. The aim of this study was to help clinicians treat patients presenting with LRTI in ...primary care by identifying those at risk of serious adverse outcomes (death, admission, late-onset pneumonia). Methods In a prospective cohort study of patients presenting with LRTI symptoms, patient characteristics and clinical findings were recorded and adverse events identified over 30 days by chart review. Multivariable logistic regression analyses identified predictors of adverse outcomes. Results Participants were recruited from 522 UK practices in 2009–2013. The analysis was restricted to the 28,846 adult patients not referred immediately to the hospital. Serious adverse outcomes occurred in 325/28,846 (1.1%). Eight factors were independently predictive; these characterized symptom severity (absence of coryza, fever, chest pain, and clinician-assessed severity), patient vulnerability (age >65 years, comorbidity), and physiological impact (oxygen saturation <95%, low blood pressure). In aggregate, the 8 features had moderate predictive value (area under the receiver operating characteristic curve 0.71, 95% CI, 0.68–0.74); the 4% of patients with ≥5 features had an approximately 1 in 17 (5.7%) risk of serious adverse outcomes, the 35% with 3 or 4 features had an intermediate risk (1 in 50, 2.0%), and the 61% with ≤2 features had a low (1 in 200, 0.5%) risk. Conclusions In routine practice most patients presenting with LRTI in primary care can be identified as at intermediate or low risk of serious outcome.
Abstract Purpose We aimed to determine the effectiveness of interventions to manage antidepressant discontinuation, and the outcomes for patients. Methods We conducted a systematic review with ...narrative synthesis and meta-analysis of studies published to March 2017. Studies were eligible for inclusion if they were randomized controlled trials, quasi-experimental studies, or observational studies assessing interventions to facilitate discontinuation of antidepressants for depression in adults. Our primary outcomes were antidepressant discontinuation and discontinuation symptoms. Secondary outcomes were relapse/recurrence; quality of life; antidepressant reduction; and sexual, social, and occupational function. Results Of 15 included studies, 12 studies (8 randomized controlled trials, 2 single-arm trials, 2 retrospective cohort studies) were included in the synthesis. None were rated as having high risk for selection or detection bias. Two studies prompting primary care clinician discontinuation with antidepressant tapering guidance found 6% and 7% of patients discontinued, vs 8% for usual care. Six studies of psychological or psychiatric treatment plus tapering reported cessation rates of 40% to 95%. Two studies reported a higher risk of discontinuation symptoms with abrupt termination. At 2 years, risk of relapse/recurrence was lower with cognitive behavioral therapy plus taper vs clinical management plus taper (15% to 25% vs 35% to 80%: risk ratio = 0.34; 95% CI, 0.18-0.67; 2 studies). Relapse/recurrence rates were similar for mindfulness-based cognitive therapy with tapering and maintenance antidepressants (44% to 48% vs 47% to 60%; 2 studies). Conclusions Cognitive behavioral therapy or mindfulness-based cognitive therapy can help patients discontinue antidepressants without increasing the risk of relapse/recurrence, but are resource intensive. More scalable interventions incorporating psychological support are needed.
Abstract Background Respiratory infections cause 7% of deaths globally. Microbial upper respiratory tract (URT) carriage is a precursor to respiratory disease, meningitis, and septicaemia. ...Understanding carriage of URT pathogens is crucial to understanding the spread of respiratory disease. Vaccination against respiratory pathogens has reduced invasive disease rates but also profoundly modified carriage. Previous work shows the importance of individual URT pathogens, especially Streptococcus pneumoniae , and the effects of vaccination on carriage and disease. We aimed to assess carriage of multiple respiratory pathogens within a population benefitting from pneumococcal, Haemophilus influenzae b and meningitis C vaccines. This assessment will enable us to decipher the role of URT community dynamics. Methods We undertook a population-based respiratory carriage pilot study with 1574 participants, 1171 of whom were aged 5 years or older and 385 aged younger than 5 years (18 participants of age unknown because they did not return questionnaire). Patients registered at one of 19 Hampshire general practices, of any age and health status, were randomly selected using the ralloc command in Stata 12. Optimum sample collection method and carriage rates of the above species were assessed in two study groups: a self-swab group, in which participants did their own nose and mouth swabs; and a healthcare professional (HCP) group, in which HCPs did participants' nasopharyngeal and mouth swabs. Participant response rates in each study arm were compared. SPSS and a confidence interval calculator were used in the analysis. Findings Preliminary data suggest that nasal swabbing gave the greatest bacterial recovery at 40%. Nasal carriage rates of S pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, H influenzae , and Neisseria meningitidis were 10·3%, 2·5%, 1·6%, 21·3%, 2·6%, and 1·7%, respectively. Carriage of S pneumoniae and H influenzae were associated with young children whereas S aureus was associated with adults (p<0·0001). Carriage of S pneumoniae and H influenzae were associated with recent respiratory infection (p<0·0001 and p=0·0003, respectively). Co-colonisation of S pneumoniae with other species was common, especially H influenzae . Polymicrobial carriage occurred in 2·5% (n=80) samples. Response rates were higher for self-swabbing (22·3%, 95% CI 21·2–23·4) versus HCP-swabbing (6·6%, 5·9–7·3). However, isolation rates were greater for HCP-swabbing (36·0%, 30·7–41·3) versus self-swabbing (20·2%, 18·0–22·4). Interpretation Preliminary data show URT diversity and will aid continuation of the study in future years. We hope to use molecular methods to further understand the genetic composition and diversity of the URT community. Continuation of such studies will enable us to track changes in the rates of these interacting pathogens with ever-changing use of vaccines and antibiotics within the population. These studies are essential for enabling future improvements in clinical care by informing vaccine and antibiotic development and policy against infections causing meningitis, sepsis, and respiratory disease. Funding Bupa Foundation, The Rosetree's Trust.