Clinical prediction models for serious infections in children: external validation in ambulatory care.

BACKGROUND: Early distinction between mild and serious infections (SI) is challenging in children in ambulatory care. Clinical prediction models (CPMs), developed to aid physicians in clinical decision-making, require broad external validation before clinical use. We aimed to externally validate four CPMs, developed in emergency departments, in ambulatory care. METHODS: We applied the CPMs in a prospective cohort of acutely ill children presenting to general practices, outpatient paediatric practices or emergency departments in Flanders, Belgium. For two multinomial regression models, Feverkidstool and Craig model, discriminative ability and calibration were assessed, and a model update was performed by re-estimation of coefficients with correction for overfitting. For two risk scores, the SBI score and PAWS, the diagnostic test accuracy was assessed. RESULTS: A total of 8211 children were included, comprising 498 SI and 276 serious bacterial infections (SBI). Feverkidstool had a C-statistic of 0.80 (95% confidence interval 0.77-0.84) with good calibration for pneumonia and 0.74 (0.70-0.79) with poor calibration for other SBI. The Craig model had a C-statistic of 0.80 (0.77-0.83) for pneumonia, 0.75 (0.70-0.80) for complicated urinary tract infections and 0.63 (0.39-0.88) for bacteraemia, with poor calibration. The model update resulted in improved C-statistics for all outcomes and good overall calibration for Feverkidstool and the Craig model. SBI score and PAWS performed extremely weak with sensitivities of 0.12 (0.09-0.15) and 0.32 (0.28-0.37). CONCLUSIONS: Feverkidstool and the Craig model show good discriminative ability for predicting SBI and a potential for early recognition of SBI, confirming good external validity in a low prevalence setting of SBI. The SBI score and PAWS showed poor diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02024282. Registered on 31 December 2013.

Scoping review of the association between bacterial vaginosis and emotional, sexual and social health.

BACKGROUND: Bacterial vaginosis (BV) is a condition that, if symptomatic, is characterized by discharge and odor, with high recurrence rates even when treated. This study aims to review what literature exists on the association between BV and the emotional, sexual, and social health of women. METHODS: MEDLINE, Embase and Web of Science databases were searched from inception until November 2020. Studies reporting an association between women's emotional, sexual and/or social health and symptomatic BV in a qualitative and/or quantitative manner were included. Selected studies were divided in three categories, i.e. reporting on the emotional, sexual and/or social association. All studies were critically evaluated and discussed. RESULTS: Sixteen studies were included. Concerning emotional health, we found eight studies that calculated the association between stress and BV, in four this was statistically significant. Four qualitative studies on emotional health showed that the severity of the symptoms influenced the impact on women's lives. All studies on sexual health reported that many women experienced an impact on their relationship and sexual intimacy. Results for social life ranged from no association found to most of the study population showing avoidance behavior. CONCLUSION: This review shows that symptomatic BV can be associated with diminished emotional, sexual, and social health, but there is too little evidence to state the extent of this association.

Oral antihistamine-decongestant-analgesic combinations for the common cold.

BACKGROUND: Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over-the-counter in large quantities for the common cold, the evidence for their effectiveness is limited. This is an update of a review first published in 2012. OBJECTIVES: To assess the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo or other active controls (excluding antibiotics) in reducing the duration of symptoms and alleviating symptoms (general feeling of illness, nasal congestion, rhinorrhoea, sneezing, and cough) in children and adults with the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE via EBSCOhost, Embase, CINAHL via EBSCOhost, LILACS, and Web of Science to 10 June 2021. We searched the WHO ICTRP and ClinicalTrials.gov on 10 June 2021. SELECTION CRITERIA: Randomised controlled trials investigating the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo, other active treatment (excluding antibiotics), or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. We categorised the included trials according to the active ingredients. MAIN RESULTS: We identified 30 studies (6304 participants) including 31 treatment comparisons. The control intervention was placebo in 26 trials and an active substance (paracetamol, chlorphenindione + phenylpropanolamine + belladonna, diphenhydramine) in six trials (two trials had placebo as well as active treatment arms). Reporting of methods was generally poor, and there were large differences in study design, participants, interventions, and outcomes. Most of the included trials involved adult participants. Children were included in nine trials. Three trials included very young children (from six months to five years), and five trials included children aged 2 to 16. One trial included adults and children aged 12 years or older. The trials took place in different settings: university clinics, paediatric departments, family medicine departments, and general practice surgeries.  Antihistamine-decongestant: 14 trials (1298 participants). Eight trials reported on global effectiveness, of which six studies were pooled (281 participants on active treatment and 284 participants on placebo). The odds ratio (OR) of treatment failure was 0.31 (95% confidence interval (CI) 0.20 to 0.48; moderate certainty evidence); number needed to treat for an additional beneficial outcome (NNTB) 3.9 (95% CI 3.03 to 5.2). On the final evaluation day (follow-up: 3 to 10 days), 55% of participants in the placebo group had a favourable response compared to 70% on active treatment. Of the two trials not pooled, one showed some global effect, whilst the other showed no effect. Adverse effects: the antihistamine-decongestant group experienced more adverse effects than the control group: 128/419 (31%) versus 100/423 (13%) participants suffered one or more adverse effects (OR 1.58, 95%CI 0.78 to 3.21; moderate certainty of evidence). Antihistamine-analgesic: four trials (1608 participants). Two trials reported on global effectiveness; data from one trial were presented (290 participants on active treatment and 292 participants on ascorbic acid). The OR of treatment failure was 0.33 (95% CI 0.23 to 0.46; moderate certainty evidence); NNTB 6.67 (95% CI 4.76 to 12.5). Forty-three per cent of participants in the control group and 70% in the active treatment group were cured after six days of treatment. The second trial also showed an effect in favour of the active treatment. Adverse effects: there were not significantly more adverse effects in the active treatment group compared to placebo (drowsiness, hypersomnia, sleepiness  10/152 versus 4/120; OR 1.64 (95 % CI 0.48 to 5.59; low certainty evidence). Analgesic-decongestant: seven trials (2575 participants). One trial reported on global effectiveness: 73% of participants in the analgesic-decongestant group reported a benefit compared with 52% in the control group (paracetamol) (OR of treatment failure 0.28, 95% CI 0.15 to 0.52; moderate certainty evidence; NNTB 4.7). Adverse effects: the decongestant-analgesic group experienced significantly more adverse effects than the control group (199/1122 versus 75/675; OR 1.62  95% CI 1.18 to 2.23; high certainty evidence; number needed to treat for an additional harmful outcome (NNTH 17).  Antihistamine-analgesic-decongestant: six trials (1014 participants). Five trials reported on global effectiveness, of which two studies in adults could be pooled: global effect reported with active treatment (52%) and placebo (34%) was equivalent to a difference of less than one point on a four- or five-point scale; the OR of treatment failure was 0.47 (95% CI 0.33 to 0.67; low certainty evidence); NNTB 5.6 (95% CI 3.8 to 10.2). One trial in children aged 2 to 12 years, and two trials in adults found no beneficial effect. Adverse effects: in one trial 5/224 (2%) suffered adverse effects with the active treatment versus 9/208 (4%) with placebo. Two other trials reported no differences between treatment groups. AUTHORS' CONCLUSIONS: We found a lack of data on the effectiveness of antihistamine-analgesic-decongestant combinations for the common cold. Based on these scarce data, the effect on individual symptoms is probably too small to be clinically relevant. The current evidence suggests that antihistamine-analgesic-decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children. In 2005, the US Food and Drug Administration issued a warning about adverse effects associated with the use of over-the-counter nasal preparations containing phenylpropanolamine.

Prospective SARS-CoV-2 cohort study among primary health care providers during the second COVID-19 wave in Flanders, Belgium.

BACKGROUND: Primary health care providers (PHCPs) are assumed to be at high risk of a COVID-19 infection, as they are exposed to patients with usually less personal protective equipment (PPE) than other frontline health care workers (HCWs). Nevertheless, current research efforts focussed on the assessment of COVID-19 seroprevalence rates in the general population or hospital HCWs. OBJECTIVE: We aimed to determine the seroprevalence in PHCPs during the second SARS-CoV-2 wave in Flanders (Belgium) and compared it to the seroprevalence in the general population. We also assessed risk factors, availability of PPE and attitudes towards the government guidelines over time. METHODS: A prospective cohort of PHCPs (n = 698), mainly general practitioners, was asked to complete a questionnaire and self-sample capillary blood by finger-pricking at five distinct points in time (June-December 2020). We analysed the dried blood spots for IgG antibodies using a Luminex multiplex immunoassay. RESULTS: The seroprevalence of PHCPs remained stable between June and September (4.6-5.0%), increased significantly from October to December (8.1-13.4%) and was significantly higher than the seroprevalence of the general population. The majority of PHCPs were concerned about becoming infected, had adequate PPE and showed increasing confidence in government guidelines. CONCLUSIONS: The marked increase in seroprevalence during the second COVID-19 wave shows that PHCPs were more at risk during the second wave compared to the first wave in Flanders. This increase was only slightly higher in PHCPs than in the general population suggesting that the occupational health measures implemented provided sufficient protection when managing patients.

Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries.

BACKGROUND: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. OBJECTIVE: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. METHODS: Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. RESULTS: A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 ± 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). CONCLUSION: Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms.

Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study.

BACKGROUND: Acute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients' characteristics, care setting, preliminary diagnosis, and management. METHODS: A prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium. RESULTS: In this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR < 5-29). Children below 5 years of age and those presenting to a paediatrician had a higher median CRP. Median CRP in patients with serious infections was 21 mg/L (IQR 6 to 63.5). Pneumonia had a median CRP of 48 mg/L (IQR 13-113). In the episodes with antibiotics prescription, median CRP level was 29 mg/L (IQR 10-58) compared to 7 mg/L (IQR < 5-19) when they were not prescribed. CONCLUSION: A low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).

Challenges and opportunities for general practice specific CME in Europe - a narrative review of seven countries.

BACKGROUND: Several changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development. METHODS: Narrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation. RESULTS: General practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented. CONCLUSIONS: Independent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial.

BACKGROUND: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. METHODS: We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. FINDINGS: Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. INTERPRETATION: Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. FUNDING: European Commission's Seventh Framework Programme.

Different antibiotic treatments for group A streptococcal pharyngitis.

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications.  AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.

Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults.

BACKGROUND: Depression and anxiety are the most frequent indication for which antidepressants are prescribed. Long-term antidepressant use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that 30% to 50% of long-term antidepressant prescriptions had no evidence-based indication. Unnecessary use of antidepressants puts people at risk of adverse events. However, high-certainty evidence is lacking regarding the effectiveness and safety of approaches to discontinuing long-term antidepressants. OBJECTIVES: To assess the effectiveness and safety of approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. SEARCH METHODS: We searched all databases for randomised controlled trials (RCTs) until January 2020. SELECTION CRITERIA: We included RCTs comparing approaches to discontinuation with continuation of antidepressants (or usual care) for people with depression or anxiety who are prescribed antidepressants for at least six months. Interventions included discontinuation alone (abrupt or taper), discontinuation with psychological therapy support, and discontinuation with minimal intervention. Primary outcomes were successful discontinuation rate, relapse (as defined by authors of the original study), withdrawal symptoms, and adverse events. Secondary outcomes were depressive symptoms, anxiety symptoms, quality of life, social and occupational functioning, and severity of illness. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 33 studies involving 4995 participants. Nearly all studies were conducted in a specialist mental healthcare service and included participants with recurrent depression (i.e. two or more episodes of depression prior to discontinuation). All included trials were at high risk of bias. The main limitation of the review is bias due to confounding withdrawal symptoms with symptoms of relapse of depression. Withdrawal symptoms (such as low mood, dizziness) may have an effect on almost every outcome including adverse events, quality of life, social functioning, and severity of illness. Abrupt discontinuation Thirteen studies reported abrupt discontinuation of antidepressant. Very low-certainty evidence suggests that abrupt discontinuation without psychological support may increase risk of relapse (hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.59 to 2.74; 1373 participants, 10 studies) and there is insufficient evidence of its effect on adverse events (odds ratio (OR) 1.11, 95% CI 0.62 to 1.99; 1012 participants, 7 studies; I² = 37%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of abrupt discontinuation on withdrawal symptoms (1 study) is very uncertain. None of these studies included successful discontinuation rate as a primary endpoint. Discontinuation by "taper" Eighteen studies examined discontinuation by "tapering" (one week or longer). Most tapering regimens lasted four weeks or less. Very low-certainty evidence suggests that "tapered" discontinuation may lead to higher risk of relapse (HR 2.97, 95% CI 2.24 to 3.93; 1546 participants, 13 studies) with no or little difference in adverse events (OR 1.06, 95% CI 0.82 to 1.38; 1479 participants, 7 studies; I² = 0%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of discontinuation on withdrawal symptoms (1 study) is very uncertain. Discontinuation with psychological support Four studies reported discontinuation with psychological support. Very low-certainty evidence suggests that initiation of preventive cognitive therapy (PCT), or MBCT, combined with "tapering" may result in successful discontinuation rates of 40% to 75% in the discontinuation group (690 participants, 3 studies). Data from control groups in these studies were requested but are not yet available. Low-certainty evidence suggests that discontinuation combined with psychological intervention may result in no or little effect on relapse (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies) compared to continuation of antidepressants. Withdrawal symptoms were not measured. Pooling data on adverse events was not possible due to insufficient information (3 studies). Discontinuation with minimal intervention Low-certainty evidence from one study suggests that a letter to the general practitioner (GP) to review antidepressant treatment may result in no or little effect on successful discontinuation rate compared to usual care (6% versus 8%; 146 participants, 1 study) or on relapse (relapse rate 26% vs 13%; 146 participants, 1 study). No data on withdrawal symptoms nor adverse events were provided. None of the studies used low-intensity psychological interventions such as online support or a changed pharmaceutical formulation that allows tapering with low doses over several months. Insufficient data were available for the majority of people taking antidepressants in the community (i.e. those with only one or no prior episode of depression), for people aged 65 years and older, and for people taking antidepressants for anxiety. AUTHORS' CONCLUSIONS: Currently, relatively few studies have focused on approaches to discontinuation of long-term antidepressants. We cannot make any firm conclusions about effects and safety of the approaches studied to date. The true effect and safety are likely to be substantially different from the data presented due to assessment of relapse of depression that is confounded by withdrawal symptoms. All other outcomes are confounded with withdrawal symptoms. Most tapering regimens were limited to four weeks or less. In the studies with rapid tapering schemes the risk of withdrawal symptoms may be similar to studies using abrupt discontinuation which may influence the effectiveness of the interventions. Nearly all data come from people with recurrent depression.   There is an urgent need for trials that adequately address withdrawal confounding bias, and carefully distinguish relapse from withdrawal symptoms. Future studies should report key outcomes such as successful discontinuation rate and should include populations with one or no prior depression episodes in primary care, older people, and people taking antidepressants for anxiety and use tapering schemes longer than 4 weeks.

Antibiotics for acute rhinosinusitis in adults.

BACKGROUND: Acute rhinosinusitis is an acute infection of the nasal passages and paranasal sinuses that lasts less than four weeks. Diagnosis of acute rhinosinusitis is generally based on clinical signs and symptoms in ambulatory care settings. Technical investigations are not routinely performed, nor are they recommended in most countries. Some trials show a trend in favour of antibiotics, but the balance of benefit versus harm is unclear.We merged two Cochrane Reviews for this update, which comprised different approaches with overlapping populations, resulting in different conclusions. For this review update, we maintained the distinction between populations diagnosed by clinical signs and symptoms, or imaging. OBJECTIVES: To assess the effects of antibiotics versus placebo or no treatment in adults with acute rhinosinusitis in ambulatory care settings. SEARCH METHODS: We searched CENTRAL (2017, Issue 12), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1950 to January 2018), Embase (January 1974 to January 2018), and two trials registers (January 2018). We also checked references from identified trials, systematic reviews, and relevant guidelines. SELECTION CRITERIA: Randomised controlled trials of antibiotics versus placebo or no treatment in people with rhinosinusitis-like signs or symptoms or sinusitis confirmed by imaging. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data about cure and side effects and assessed the risk of bias. We contacted trial authors for additional information as required. MAIN RESULTS: We included 15 trials involving 3057 participants. Of the 15 included trials, 10 appeared in our 2012 review, and five (631 participants) are legacy trials from merging two reviews. No new studies were included from searches for this update. Overall, risk of bias was low. Without antibiotics, 46% of participants with rhinosinusitis, whether or not confirmed by radiography, were cured after 1 week and 64% after 14 days. Antibiotics can shorten time to cure, but only 5 to 11 more people per 100 will be cured faster if they receive antibiotics instead of placebo or no treatment: clinical diagnosis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.02 to 1.54; number needed to treat for an additional beneficial outcome (NNTB) 19, 95% CI 10 to 205; I² = 0%; 8 trials; high-quality evidence) and diagnosis confirmed by radiography (OR 1.57, 95% CI 1.03 to 2.39; NNTB 10, 95% CI 5 to 136; I² = 0%; 3 trials; moderate-quality evidence). Cure rates with antibiotics were higher when a fluid level or total opacification in any sinus was found on computed tomography (OR 4.89, 95% CI 1.75 to 13.72; NNTB 4, 95% CI 2 to 15; 1 trial; moderate-quality evidence). Purulent secretion resolved faster with antibiotics (OR 1.58, 95% CI 1.13 to 2.22; NNTB 10, 95% CI 6 to 35; I² = 0%; 3 trials; high-quality evidence). However, 13 more people experienced side effects with antibiotics compared to placebo or no treatment (OR 2.21, 95% CI 1.74 to 2.82; number needed to treat for an additional harmful outcome (NNTH) 8, 95% CI 6 to 12; I² = 16%; 10 trials; high-quality evidence). Five fewer people per 100 will experience clinical failure if they receive antibiotics instead of placebo or no treatment (Peto OR 0.48, 95% CI 0.36 to 0.63; NNTH 19, 95% CI 15 to 27; I² = 21%; 12 trials; high-quality evidence). A disease-related complication (brain abscess) occurred in one participant (of 3057) one week after receiving open antibiotic therapy (clinical failure, control group). AUTHORS' CONCLUSIONS: The potential benefit of antibiotics to treat acute rhinosinusitis diagnosed either clinically (low risk of bias, high-quality evidence) or confirmed by imaging (low to unclear risk of bias, moderate-quality evidence) is marginal and needs to be seen in the context of the risk of adverse effects. Considering antibiotic resistance, and the very low incidence of serious complications, we conclude there is no place for antibiotics for people with uncomplicated acute rhinosinusitis. We could not draw conclusions about children, people with suppressed immune systems, and those with severe sinusitis, because these populations were not included in the available trials.

Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia.

BACKGROUND: Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in people with dementia although there is uncertainty about the effectiveness of their long-term use for this indication and concern that they may cause harm, including higher mortality. When behavioural strategies have failed and treatment with antipsychotic drugs is instituted, regular attempts to withdraw them have been recommended in guidelines. Physicians, nurses and families of older people with dementia may be reluctant to stop antipsychotics, fearing deterioration of NPS.This is an update of a Cochrane Review published in 2013. OBJECTIVES: To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia and NPS in primary care or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older participants with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on participants' behaviour and assess safety. SEARCH METHODS: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), theCochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources up to 11 January 2018. SELECTION CRITERIA: We included all randomised, controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia who had been treated with an antipsychotic drug for at least three months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 10 studies involving 632 participants. One new trial (19 participants) was added for this update.One trial was conducted in a community setting, eight in nursing homes and one in both settings. Different types of antipsychotics at varying doses were discontinued in the studies. Both abrupt and gradual withdrawal schedules were used. Reported data were predominantly from studies at low or unclear risk of bias.We included nine trials with 575 randomised participants that used a proxy outcome for overall success of antipsychotic withdrawal. Pooling data was not possible due to heterogeneity of outcome measures used. Based on assessment of seven studies, discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence).Two trials included only participants with psychosis, agitation or aggression who had responded to antipsychotic treatment. In these two trials, stopping antipsychotics was associated with a higher risk of leaving the study early due to symptomatic relapse or a shorter time to symptomatic relapse.We found low-quality evidence that discontinuation may make little or no difference to overall NPS, measured using various scales (7 trials, 519 participants). There was some evidence from subgroup analyses in two trials that discontinuation may reduce agitation for participants with less severe NPS at baseline, but may be associated with a worsening of NPS in participants with more severe NPS at baseline.None of the studies assessed withdrawal symptoms. Adverse effects of antipsychotics (such as falls) were not systematically assessed. Low-quality evidence showed that discontinuation may have little or no effect on adverse events (5 trials, 381 participants), quality of life (2 trials, 119 participants), or cognitive function (5 trials, 365 participants).There were insufficient data to determine whether discontinuation of antipsychotics has any effect on mortality (very low-quality evidence). AUTHORS' CONCLUSIONS: There is low-quality evidence that antipsychotics may be successfully discontinued in older people with dementia and NPS who have been taking antipsychotics for at least three months, and that discontinuation may have little or no important effect on behavioural and psychological symptoms. This is consistent with the observation that most behavioural complications of dementia are intermittent and often do not persist for longer than three months. Discontinuation may have little or no effect on overall cognitive function. Discontinuation may make no difference to adverse events and quality of life. Based on the trials in this review, we are uncertain whether discontinuation of antipsychotics leads to a decrease in mortality.People with psychosis, aggression or agitation who responded well to long-term antipsychotic drug use, or those with more severe NPS at baseline, may benefit behaviourally from continuation of antipsychotics. Discontinuation may reduce agitation for people with mild NPS at baseline. However, these conclusions are based on few studies or small subgroups and further evidence of benefits and harms associated with withdrawal of antipsychotic is required in people with dementia and mild and severe NPS.The overall conclusions of the review have not changed since 2013 and the number of available trials remains low.

Point-of-care CRP matters: normal CRP levels reduce immediate antibiotic prescribing for acutely ill children in primary care: a cluster randomized controlled trial.

OBJECTIVE: Antibiotics are prescribed too often in acutely ill children in primary care. We examined whether a Point-of-Care (POC) C-reactive Protein (CRP) test influences the family physicians' (FP) prescribing rate and adherence to the Evidence Based Medicine (EBM) practice guidelines. DESIGN: Cluster randomized controlled trial. SETTING: Primary care, Flanders, Belgium. INTERVENTION: Half of the children with non-severe acute infections (random allocation of practices to perform POC CRP or not) and all children at risk for serious infection were tested with POC CRP. SUBJECTS: Acutely ill children consulting their FP. MAIN OUTCOME MEASURE: Immediate antibiotic prescribing. RESULTS: 2844 infectious episodes recruited by 133 FPs between 15 February 2013 and 28 February 2014 were analyzed. A mixed logistic regression analysis was performed. Compared to episodes in which CRP was not tested, the mere performing of POC CRP reduced prescribing in case EBM practice guidelines advise to prescribe antibiotics (adjusted odds ratio (aOR) 0.54 (95% Confidence Interval (CI) 0.33-0.90). Normal CRP levels reduced antibiotic prescribing, regardless of whether the advice was to prescribe (aOR 0.24 (95%CI 0.11-0.50) or to withhold (aOR 0.31 (95%CI 0.17-0.57)). Elevated CRP levels did not increase antibiotic prescribing. CONCLUSION: Normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. Key points What is previously known or believed on this topic •Antibiotics are prescribed too often for non-severe conditions. Point-of-care (POC) C-reactive Protein (CRP) testing without guidance does not reduce immediate antibiotic prescribing in acutely ill children in primary care. What this research adds •FPs clearly consider CRP once available: normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. •Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing.

Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial.

BACKGROUND: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. METHODS: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. RESULTS: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP < 5 mg/L. CONCLUSIONS: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282 (registered on 14th September 2012).

A High Sense of Coherence as Protection Against Adverse Health Outcomes in Patients Aged 80 Years and Older.

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.

Nasal decongestants in monotherapy for the common cold.

BACKGROUND: Many treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited. OBJECTIVES: To assess the efficacy, and short- and long-term safety, of nasal decongestants used in monotherapy to alleviate symptoms of the common cold in adults and children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi-RCTs. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient well-being score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi-dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together. MAIN RESULTS: We included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta-analyses. Eleven studies used oral decongestants; four studies used topical decongestants.Participants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single-dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow-up in multi-dose studies ranged between one and 10 days.Most studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear.There were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (≥ 0.8).Single-dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well-being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group.Multi-dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well-being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta-analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low-quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low-quality evidence). AUTHORS' CONCLUSIONS: We were unable to draw conclusions on the effectiveness of single-dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good-quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.

Different antibiotic treatments for group A streptococcal pharyngitis.

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although effectiveness increases in participants with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. OBJECTIVES: To assess the evidence on the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing relapse; and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched CENTRAL (2016, Issue 3), MEDLINE Ovid (1946 to March week 3, 2016), Embase Elsevier (1974 to March 2016), and Web of Science Thomson Reuters (2010 to March 2016). We also searched clinical trials registers. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics and reporting at least one of the following: clinical cure, clinical relapse, or complications or adverse events, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion, and extracted data using standard methodological procedures as recommended by Cochrane. We assessed risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and used the GRADE tool to assess the overall quality of evidence for the outcomes. MAIN RESULTS: We included 19 trials (5839 randomised participants); seven compared penicillin with cephalosporins, six compared penicillin with macrolides, three compared penicillin with carbacephem, one trial compared penicillin with sulphonamides, one trial compared clindamycin with ampicillin, and one trial compared azithromycin with amoxicillin in children. All included trials reported clinical outcomes. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. The overall quality of the evidence assessed using the GRADE tool was low for the outcome 'resolution of symptoms' in the intention-to-treat (ITT) analysis and very low for the outcomes 'resolution of symptoms' of evaluable participants and for adverse events. We downgraded the quality of evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals (CIs).There was a difference in symptom resolution in favour of cephalosporins compared with penicillin (evaluable patients analysis odds ratio (OR) for absence of resolution of symptoms 0.51, 95% CI 0.27 to 0.97; number needed to treat to benefit (NNTB) 20, N = 5, n = 1660; very low quality evidence). However, this was not statistically significant in the ITT analysis (OR 0.79, 95% CI 0.55 to 1.12; N = 5, n = 2018; low quality evidence). Clinical relapse was lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; NNTB 50, N = 4, n = 1386; low quality evidence), but this was found only in adults (OR 0.42, 95% CI 0.20 to 0.88; NNTB 33, N = 2, n = 770). There were no differences between macrolides and penicillin for any of the outcomes. One unpublished trial in children found a better cure rate for azithromycin in a single dose compared to amoxicillin for 10 days (OR 0.29, 95% CI 0.11 to 0.73; NNTB 18, N = 1, n = 482), but there was no difference between the groups in ITT analysis (OR 0.76, 95% CI 0.55 to 1.05; N = 1, n = 673) or at long-term follow-up (evaluable patients analysis OR 0.88, 95% CI 0.43 to 1.82; N = 1, n = 422). Children experienced more adverse events with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; N = 1, n = 673). Compared with penicillin carbacephem showed better symptom resolution post-treatment in adults and children combined (ITT analysis OR 0.70, 95% CI 0.49 to 0.99; NNTB 14, N = 3, n = 795), and in the subgroup analysis of children (OR 0.57, 95% CI 0.33 to 0.99; NNTB 8, N = 1, n = 233), but not in the subgroup analysis of adults (OR 0.75, 95% CI 0.46 to 1.22, N = 2, n = 562). Children experienced more adverse events with macrolides compared with penicillin (OR 2.33, 95% CI 1.06 to 5.15; N = 1, n = 489). Studies did not report on long-term complications so it was unclear if any class of antibiotics was better in preventing serious but rare complications. AUTHORS' CONCLUSIONS: There were no clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Limited evidence in adults suggests cephalosporins are more effective than penicillin for relapse, but the NNTB is high. Limited evidence in children suggests carbacephem is more effective than penicillin for symptom resolution. Data on complications are too scarce to draw conclusions. Based on these results and considering the low cost and absence of resistance, penicillin can still be regarded as a first choice treatment for both adults and children. All studies were in high-income countries with low risk of streptococcal complications, so there is need for trials in low-income countries and Aboriginal communities where risk of complications remains high.

Antihistamines for the common cold.

BACKGROUND: The common cold is an upper respiratory tract infection, most commonly caused by a rhinovirus. It affects people of all age groups and although in most cases it is self limiting, the common cold still causes significant morbidity. Antihistamines are commonly offered over the counter to relieve symptoms for patients affected by the common cold, however there is not much evidence of their efficacy. OBJECTIVES: To assess the effects of antihistamines on the common cold. SEARCH METHODS: We searched CENTRAL (2015, Issue 6), MEDLINE (1948 to July week 4, 2015), EMBASE (2010 to August 2015), CINAHL (1981 to August 2015), LILACS (1982 to August 2015) and Biosis Previews (1985 to August 2015). SELECTION CRITERIA: We selected randomised controlled trials (RCTs) using antihistamines as monotherapy for the common cold. We excluded any studies with combination therapy or using antihistamines in patients with an allergic component in their illness. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We collected adverse effects information from the included trials. MAIN RESULTS: We included 18 RCTs, which were reported in 17 publications (one publication reports on two trials) with 4342 participants (of which 212 were children) suffering from the common cold, both naturally occurring and experimentally induced. The interventions consisted of an antihistamine as monotherapy compared with placebo. In adults there was a short-term beneficial effect of antihistamines on severity of overall symptoms: on day one or two of treatment 45% had a beneficial effect with antihistamines versus 38% with placebo (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60 to 0.92). However, there was no difference between antihistamines and placebo in the mid term (three to four days) to long term (six to 10 days). When evaluating individual symptoms such as nasal congestion, rhinorrhoea and sneezing, there was some beneficial effect of the sedating antihistamines compared to placebo (e.g. rhinorrhoea on day three: mean difference (MD) -0.23, 95% CI -0.39 to -0.06 on a four- or five-point severity scale; sneezing on day three: MD -0.35, 95% CI -0.49 to -0.20 on a four-point severity scale), but this effect is clinically non-significant. Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant. Only two trials included children and the results were conflicting. The majority of the trials had a low risk of bias although some lacked sufficient trial quality information. AUTHORS' CONCLUSIONS: Antihistamines have a limited short-term (days one and two of treatment) beneficial effect on severity of overall symptoms but not in the mid to long term. There is no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing. Although side effects are more common with sedating antihistamines, the difference is not statistically significant. There is no evidence of effectiveness of antihistamines in children.

Dissemination and implementation of the ARIA guidelines for allergic rhinitis in general practice.

BACKGROUND: Allergic rhinitis (AR) is a prevalent problem in general practice. The first evidence-based guidelines for AR, the ARIA guidelines, were published and have been updated repeatedly since 2001 in order to improve the care of AR patients. Very limited information, however, is available on the impact of these guidelines on everyday clinical practice. The aim of this study was to evaluate the dissemination and implementation of the ARIA guidelines in general practice. METHODS: Three hundred and fifty Flemish general practitioners (GPs) were recruited to complete a questionnaire covering their demographic and professional characteristics, awareness, perception and implementation of the ARIA guidelines. To assess compliance with the ARIA treatment recommendations, 4 fictitious case scenarios of AR were presented, in which the respondents were asked to select the treatment of choice. RESULTS: Of the 350 GPs included, only 31% were aware of the ARIA guidelines and 10% stated that they implement them. For the diagnosis of AR, 71% of the GPs ask specific IgE tests or perform skin prick tests, whereas only 29% perform an anterior rhinoscopy. ARIA users are more likely to screen for concomitant asthma. In the clinical-case section, there was a large variability in proposed therapeutic strategies. Adherence to the evidence-based ARIA treatment guidelines was low, but recent graduation was a significant predictor of compliance with these recommendations. CONCLUSIONS: The ARIA guidelines remain relatively unknown among Flemish GPs and even those who are aware of them still tend to treat AR independently of the guideline recommendations.