Summary Background Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation, but whether this benefit outweighs the increased risk of ...bleeding in elderly patients is unknown. We assessed whether warfarin reduced risk of major stroke, arterial embolism, or other intracranial haemorrhage compared with aspirin in elderly patients. Methods 973 patients aged 75 years or over (mean age 81·5 years, SD 4·2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target international normalised ratio 2–3) or aspirin (75 mg per day). Follow-up was for a mean of 2·7 years (SD 1·2). The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN89345269. Findings There were 24 primary events (21 strokes, two other intracranial haemorrhages, and one systemic embolus) in people assigned to warfarin and 48 primary events (44 strokes, one other intracranial haemorrhage, and three systemic emboli) in people assigned to aspirin (yearly risk 1·8% vs 3·8%, relative risk 0·48, 95% CI 0·28–0·80, p=0·003; absolute yearly risk reduction 2%, 95% CI 0·7–3·2). Yearly risk of extracranial haemorrhage was 1·4% (warfarin) versus 1·6% (aspirin) (relative risk 0·87, 0·43–1·73; absolute risk reduction 0·2%, −0·7 to 1·2). Interpretation These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.
Summary Background Our aim was to identify which clinical features have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings in ...developed countries. Methods In this systematic review, we searched electronic databases (Medline, Embase, DARE, CINAHL), reference lists of relevant studies, and contacted experts to identify articles assessing clinical features of serious infection in children. 1939 potentially relevant studies were identified. Studies were selected on the basis of six criteria: design (studies of diagnostic accuracy or prediction rules), participants (otherwise healthy children aged 1 month to 18 years), setting (ambulatory care), outcome (serious infection), features assessed (assessable in ambulatory care setting), and sufficient data reported. Quality assessment was based on the Quality Assessment of Diagnostic Accuracy Studies criteria. We calculated likelihood ratios for the presence (positive likelihood ratio) or absence (negative likelihood ratio) of each clinical feature and pre-test and post-test probabilities of the outcome. Clinical features with a positive likelihood ratio of more than 5·0 were deemed red flags (ie, warning signs for serious infection); features with a negative likelihood ratio of less than 0·2 were deemed rule-out signs. Findings 30 studies were included in the analysis. Cyanosis (positive likelihood ratio range 2·66–52·20), rapid breathing (1·26–9·78), poor peripheral perfusion (2·39–38·80), and petechial rash (6·18–83·70) were identified as red flags in several studies. Parental concern (positive likelihood ratio 14·40, 95% CI 9·30–22·10) and clinician instinct (positive likelihood ratio 23·50, 95 % CI 16·80–32·70) were identified as strong red flags in one primary care study. Temperature of 40°C or more has value as a red flag in settings with a low prevalence of serious infection. No single clinical feature has rule-out value but some combinations can be used to exclude the possibility of serious infection—for example, pneumonia is very unlikely (negative likelihood ratio 0·07, 95% CI 0·01–0·46) if the child is not short of breath and there is no parental concern. The Yale Observation Scale had little value in confirming (positive likelihood ratio range 1·10–6·70) or excluding (negative likelihood ratio range 0·16–0·97) the possibility of serious infection. Interpretation The red flags for serious infection that we identified should be used routinely, but serious illness will still be missed without effective use of precautionary measures. We now need to identify the level of risk at which clinical action should be taken. Funding Health Technology Assessment and National Institute for Health Research National School for Primary Care Research.
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.
The state of primary-care research Mant, David; Del Mar, Chris; Glasziou, Paul ...
The Lancet (British edition),
09/2004, Letnik:
364, Številka:
9438
Journal Article
Recenzirano
Odprti dostop
In March, 2003, the editor of The Lancet attended an international conference in Kingston, Ontario, Canada, on primary-care research, subsequently running a rather dyspeptic editorial entitled "Is ...primary-care research a lost cause?"1 This article highlighted the unacceptable weakness of primary-care research worldwide. A particular concern of the conference was the shortage of primary care research in less economically developed countries to inform the clinical and public health management of malnutrition, malaria, AIDS, water-borne infection, and other illnesses of poverty.2 However, problems exist even in economically developed countries. In Australia, for example, a crude measure of research productivity with practising physicians as the denominator suggests that primary care is only 1% as productive as internal medicine, 0.5% as productive as public health and 1.6% as productive as surgery.3 But for The Lancet to characterise primary-care research as a "lost cause" is unhelpful. This notion implies either that the field is so weak that it cannot be resuscitated or that it is irrelevant anyway. Both are wrong.
Summary Background The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular ...outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. Methods We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies—further blood pressure measurement in the clinic, at home, and with an ambulatory monitor—in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. Findings Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from −£56 95% CI −105 to −10 in men aged 75 years to −£323 −389 to −222 in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 0·000 to 0·015 for women aged 60 years to 0·022 0·012 to 0·035 for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. Interpretation Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. Funding National Institute for Health Research and the National Institute for Health and Clinical Excellence.
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