Early-career general practitioners' antibiotic prescribing for acute infections: a systematic review.

BACKGROUND: Antimicrobial resistance is a worldwide threat, exacerbated by inappropriate prescribing. Most antibiotic prescribing occurs in primary care. Early-career GPs are important for the future of antibiotic prescribing and curbing antimicrobial resistance. OBJECTIVES: To determine antibiotic prescribing patterns by early-career GPs for common acute infections. METHODS: A systematic literature search was conducted using PubMed, Embase and Scopus. Two authors independently screened abstracts and full texts for inclusion. Primary outcomes were antibiotic prescribing rates for common acute infections by GPs with experience of 10 years or less. Secondary outcomes were any associations between working experience and antibiotic prescribing. RESULTS: Of 1483 records retrieved, we identified 41 relevant studies. Early-career GPs were less likely to prescribe antibiotics compared with their more experienced colleagues (OR range 0.23-0.67). Their antibiotic prescribing rates for 'any respiratory condition' ranged from 14.6% to 52%, and for upper respiratory tract infections from 13.5% to 33%. Prescribing for acute bronchitis varied by country, from 15.9% in Sweden to 26% in the USA and 63%-73% in Australia. Condition-specific data for all other included acute infections, such as sinusitis and acute otitis media, were limited to the Australian context. CONCLUSIONS: Early-career GPs prescribe fewer antibiotics than later-career GPs. However, there are still significant improvements to be made for common acute conditions, as their prescribing is higher than recommended benchmarks. Addressing antimicrobial resistance requires an ongoing worldwide effort and early-career GPs should be the target for long-term change.

Prevalence and associations of provision of nursing home visits and home visits by early-career specialist general practitioners.

OBJECTIVE: To establish prevalence and associations of provision of nursing home visits (NHV) and home visits (HV) by early-career specialist GPs. Of particular interest were associations of rurality with performing NHVs and HVs. METHODS: A cross-sectional study. DESIGN: A questionnaire-based study. SETTING: Australian general practice. PARTICIPANTS: Early-career specialist GPs, practising in Australia, who attained Fellowship between January 2016 and July 2018, inclusive, having completed GP training in NSW, the ACT, Eastern Victoria or Tasmania. MAIN OUTCOME MEASURES: Current provision of NHV and HV. RESULTS: NHV were provided by 34% of participants (59% in rural areas) and HV by 41% of participants (60% in rural areas). Remote, rural or regional practice location, as compared to major-city practice, was strongly associated with performing NHV as an early-career specialist GP; multivariable OR 5.87 (95% CI: 2.73, 12.6), p < 0.001, and with the provision of HV; multivariable OR 3.64 (95% CI: 1.63, 8.11), p = 0.002. Rurality of GP training (prior to attaining Fellowship) was significantly univariably associated with providing NHV and with providing HV as an early-career specialist GP. On multivariable analyses, these were no longer statistically significant. CONCLUSION: Early-career specialist GPs located in regional/remote areas are more likely than their urban colleagues to provide NHV and HV.

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 2021. 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 Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023. 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 recommended by Cochrane. We assessed the risk of bias in the 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 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). Based on an analysis of evaluable participants, 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). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. 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 at 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. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. 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 disadvantaged populations, where the risk of complications remains high.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review last published in 2020. We include results from studies from the current COVID-19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL, and two trials registers in October 2022, with backwards and forwards citation analysis on the new studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, glasses, and gargling) to prevent respiratory virus transmission.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 11 new RCTs and cluster-RCTs (610,872 participants) in this update, bringing the total number of RCTs to 78. Six of the new trials were conducted during the COVID-19 pandemic; two from Mexico, and one each from Denmark, Bangladesh, England, and Norway. We identified four ongoing studies, of which one is completed, but unreported, evaluating masks concurrent with the COVID-19 pandemic. Many studies were conducted during non-epidemic influenza periods. Several were conducted during the 2009 H1N1 influenza pandemic, and others in epidemic influenza seasons up to 2016. Therefore, many studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID-19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high-income countries; crowded inner city settings in low-income countries; and an immigrant neighbourhood in a high-income country. Adherence with interventions was low in many studies. The risk of bias for the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included 12 trials (10 cluster-RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and 10 in the community). Wearing masks in the community probably makes little or no difference to the outcome of influenza-like illness (ILI)/COVID-19 like illness compared to not wearing masks (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials, 276,917 participants; moderate-certainty evidence. Wearing masks in the community probably makes little or no difference to the outcome of laboratory-confirmed influenza/SARS-CoV-2 compared to not wearing masks (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate-certainty evidence). Harms were rarely measured and poorly reported (very low-certainty evidence). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). We are very uncertain on the effects of N95/P2 respirators compared with medical/surgical masks on the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; 3 trials, 7779 participants; very low-certainty evidence). N95/P2 respirators compared with medical/surgical masks may be effective for ILI (RR 0.82, 95% CI 0.66 to 1.03; 5 trials, 8407 participants; low-certainty evidence). Evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirators compared to medical/surgical masks probably makes little or no difference for the objective and more precise outcome of laboratory-confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; 5 trials, 8407 participants; moderate-certainty evidence). Restricting pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies (very low-certainty evidence).  One previously reported ongoing RCT has now been published and observed that medical/surgical masks were non-inferior to N95 respirators in a large study of 1009 healthcare workers in four countries providing direct care to COVID-19 patients.  Hand hygiene compared to control Nineteen trials compared hand hygiene interventions with controls with sufficient data to include in meta-analyses. Settings included schools, childcare centres and homes. Comparing hand hygiene interventions with controls (i.e. no intervention), there was a 14% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.86, 95% CI 0.81 to 0.90; 9 trials, 52,105 participants; moderate-certainty evidence), suggesting a probable benefit. In absolute terms this benefit would result in a reduction from 380 events per 1000 people to 327 per 1000 people (95% CI 308 to 342). When considering the more strictly defined outcomes of ILI and laboratory-confirmed influenza, the estimates of effect for ILI (RR 0.94, 95% CI 0.81 to 1.09; 11 trials, 34,503 participants; low-certainty evidence), and laboratory-confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials, 8332 participants; low-certainty evidence), suggest the intervention made little or no difference. We pooled 19 trials (71, 210 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. Pooled data showed that hand hygiene may be beneficial with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.83 to 0.94; low-certainty evidence), but with high heterogeneity. In absolute terms this benefit would result in a reduction from 200 events per 1000 people to 178 per 1000 people (95% CI 166 to 188). Few trials measured and reported harms (very low-certainty evidence). We found no RCTs on gowns and gloves, face shields, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions. There were additional RCTs during the pandemic related to physical interventions but a relative paucity given the importance of the question of masking and its relative effectiveness and the concomitant measures of mask adherence which would be highly relevant to the measurement of effectiveness, especially in the elderly and in young children. There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory-confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs.

Temporal patterns of antibiotic prescribing for sore throat, otitis media, and sinusitis: a longitudinal study of general practitioner registrars.

BACKGROUND: Antibiotics provide minimal benefit for sore throat, otitis media, and sinusitis. Antibiotic stewardship, with reduced prescribing, is required to address antibiotic resistance. As most antibiotic prescribing occurs in general practice and prescribing habits develop early, general practitioner (GP) trainees (registrars) are important for effective antibiotic stewardship. OBJECTIVES: To establish temporal trends in Australian registrars' antibiotic prescribing for acute sore throat, acute otitis media, and acute sinusitis. DESIGN: A longitudinal analysis of data from the Registrar Clinical Encounters in Training (ReCEnT) study from 2010 to 2019. PARTICIPANTS: ReCEnT is an ongoing cohort study of registrars' in-consultation experiences and clinical behaviours. Pre-2016, 5 of 17 Australian training regions participated. From 2016, 3 of 9 regions (42% of Australian registrars) participate. MAIN MEASURES: The outcome was prescription of an antibiotic for a new acute problem/diagnosis of sore throat, otitis media, or sinusitis. The study factor was year (2010-2019). KEY RESULTS: Antibiotics were prescribed in 66% of sore throat diagnoses, 81% of otitis media, and in 72% of sinusitis. Prescribing frequencies decreased between 2010 and 2019 by 16% for sore throat (from 76% to 60%) by 11% for otitis media (from 88% to 77%) and by 18% for sinusitis (from 84% to 66%). In multivariable analyses, "Year" was associated with reduced prescribing for sore throat (OR 0.89; 95%CI 0.86-0.92; p < 0.001), otitis media (OR 0.90; 95%CI 0.86-0.94; p < 0.001), and sinusitis (OR 0.90; 95%CI 0.86, 0.94; p < 0.001). CONCLUSIONS: Registrars' prescribing rates for sore throat, otitis media, and sinusitis significantly decreased during the period 2010-2019. However, educational (and other) interventions to further reduce prescribing are warranted.

The prevalence and associations of Australian early-career general practitioners' provision of after-hours care.

INTRODUCTION: Access to after-hours care (AHC) is an important aspect of general practice service provision. OBJECTIVE: To establish the prevalence and associations of early-career GPs' provision of AHC. DESIGN: An analysis of data from the New alumni Experiences of Training and independent Unsupervised Practice (NEXT-UP) cross-sectional questionnaire-based study. Participants were early-career GPs (6-month to 2-year post-Fellowship) following the completion of GP vocational training in NSW, the ACT, Victoria or Tasmania. The outcome factor was 'current provision of after-hours care'. Associations of the outcome were established using multivariable logistic regression. FINDINGS: Three hundred and fifty-four early-career GPs participated (response rate 28%). Of these, 322 had responses available for analysis of currently performing AHC. Of these observations, 128 (40%) reported current provision of AHC (55% of rural participants and 32% of urban participants). On multivariable analysis, participants who provided any AHC during training were more likely to be providing AHC (odds ratio (OR) 5.51, [95% confidence interval (CI) 2.80-10.80], p < 0.001). Current rural location and in-training rural experience were strongly associated with currently providing AHC in univariable but not multivariable analysis. DISCUSSION: Early-career GPs who provided AHC during training, compared with those who did not, were more than five times more likely to provide after-hours care in their first 2 years after gaining Fellowship, suggesting participation in AHC during training may have a role in preparing registrars to provide AHC as independent practitioners. CONCLUSION: These findings may inform future GP vocational training policy and practice concerning registrars' provision of AHC during training.

Value in primary care clinics: a service ecosystem perspective.

In this article, we propose that value is a multidimensional construct, highlighting the need for a multi-actor service ecosystem perspective of value in primary care clinics. We argue that different actors in the service ecosystem - for example, patients, their family members and carers, medical practitioners, practice managers, nurses, allied health workers, receptionists and practice owners - may value different aspects of health service delivery more highly than others. We describe ways in which value is perceived among actors in primary care, and highlight the need for a greater focus on a broader view of value involving the various stakeholders to realise better outcomes.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although most infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most treatments have minimal benefit and may lead to adverse events. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for their effectiveness is established. This is an update of a review first published in 2018. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat ARTIs in children. SEARCH METHODS: We searched CENTRAL (2022, Issue 3), including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 16 March 2022), Embase (2010 to 16 March 2022), CINAHL (1981 to 16 March 2022), AMED (1985 to 16 March 2022), CAMbase (searched 16 March 2022), and British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov (16 March 2022), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included double-blind randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this 2022 update, we identified three new RCTs involving 251 children, for a total of 11 included RCTs with 1813 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for ARTIs. All studies focused on upper respiratory tract infections (URTIs), with only one study including some lower respiratory tract infections (LRTIs). Six treatment studies examined the effect on URTI recovery, and five studies investigated the effect on preventing URTIs after one to four months of treatment. Two treatment and three prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products, with dilutions ranging from 1 x 10-4 to 1 x 10-200. We identified several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many studies had additional domains with unclear risk of bias. Four studies received funding from homeopathy manufacturers; one study support from a non-government organisation; two studies government support; one study was co-sponsored by a university; and three studies did not report funding support. Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products, whilst trials at unclear or high risk of bias reported beneficial effects. For the comparison of individualised homeopathy versus placebo or usual care for the prevention of ARTIs, two trials reported on disease severity; due to heterogeneity the data were not combined, but neither study demonstrated a clinically significant difference. We combined data from two trials for the outcome need for antibiotics (OR 0.79, 95% CI 0.35 to 1.76; low-certainty evidence). For the comparison of non-individualised homeopathy versus placebo or usual care for the prevention of ARTIs, only the outcome recurrence of ARTI was reported by more than one trial; data from three studies were combined for this outcome (OR 0.60, 95% CI 0.21 to 1.72; low-certainty evidence). For the comparison of both individualised and non-individualised homeopathy versus placebo or usual care for the treatment of ARTIs, two studies provided data on short-term cure (OR 1.31, 95% CI 0.09 to 19.54) and long-term cure (OR 1.01, 95% CI 0.10 to 9.96; very low-certainty evidence). The studies demonstrated an opposite direction of effect for both outcomes. Six studies reported on disease severity but were not combined as they used different scoring systems and scales. Three studies reported adverse events (OR 0.79, 95% CI 0.16 to 4.03; low-certainty evidence). AUTHORS' CONCLUSIONS: Pooling of five prevention and six treatment studies did not show any consistent benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We assessed the certainty of the evidence as low to very low for the majority of outcomes. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, and we could not draw conclusions regarding safety.

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.

Treatment for recurrent vulvovaginal candidiasis (thrush).

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) affects up to 5% of women. No comprehensive systematic review of treatments for RVVC has been published. OBJECTIVES: The primary objective was to assess the effectiveness and safety of pharmacological and non-pharmacological treatments for RVVC. The secondary objective was to assess patient preference of treatment options. SEARCH METHODS: We conducted electronic searches of bibliographic databases, including CENTRAL, MEDLINE, Embase, and CINAHL (search date 6 October 2021). We also handsearched reference lists of identified trials and contacted authors of identified trials, experts in RVVC, and manufacturers of products for vulvovaginal candidiasis. SELECTION CRITERIA: We considered all published and unpublished randomised controlled trials evaluating RVVC treatments for at least six months, in women with four or more symptomatic episodes of vulvovaginal candidiasis in the past year. We excluded women with immunosuppressive disorders or taking immunosuppressant medication. We included women with diabetes mellitus and pregnant women. Diagnosis of RVVC must have been confirmed by presence of symptoms and a positive culture and/or microscopy. We included all drug and non-drug therapies and partner treatment, assessing the following primary outcomes: • number of clinical recurrences per participant per year (recurrence defined as clinical signs and positive culture/microscopy); • proportion of participants with at least one clinical recurrence during the treatment and follow-up period; and • adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed titles and abstracts to identify eligible trials. Duplicate data extraction was completed independently by two authors. We assessed risk of bias as described in the Cochrane Handbook for Systematic Reviews of Interventions. We used the fixed-effects model for pooling and expressed the results as risk ratio (RR) with 95% confidence intervals (CI). Where important statistical heterogeneity was present we either did not pool data (I2 > 70%) or used a random-effects model (I2 40-70%). We used the GRADE tool to assess overall certainty of the evidence for the pooled primary outcomes. MAIN RESULTS: Studies: Twenty-three studies involving 2212 women aged 17 to 67 years met the inclusion criteria. Most studies excluded pregnant women and women with diabetes or immunosuppression. The predominant species found on culture at study entry was Candida albicans. Overall, the included studies were small (<100 participants). Six studies compared antifungal treatment with placebo (607 participants); four studies compared oral versus topical antifungals (543 participants); one study compared different oral antifungals (45 participants); two studies compared different dosing regimens for antifungals (100 participants); one study compared two different dosing regimens of the same topical agent (23 participants); one study compared short versus longer treatment duration (26 participants); two studies assessed the effect of partner treatment (98 participants); one study compared a complementary treatment (Lactobacillus vaginal tablets and probiotic oral tablets) with placebo (34 participants); three studies compared complementary medicine with antifungals (354 participants); two studies compared 'dermasilk' briefs with cotton briefs (130 participants); one study examined Lactobacillus vaccination versus heliotherapy versus ciclopyroxolamine (90 participants); one study compared CAM treatments to an antifungal treatment combined with CAM treatments (68 participants). We did not find any studies comparing different topical antifungals. Nine studies reported industry funding, three were funded by an independent source and eleven did not report their funding source. Risk of bias: Overall, the risk of bias was high or unclear due to insufficient blinding of allocation and participants and poor reporting. Primary outcomes: Meta-analyses comparing drug treatments (oral and topical) with placebo or no treatment showed there may be a clinically relevant reduction in clinical recurrence at 6 months (RR 0.36, 95% CI 0.21 to 0.63; number needed to treat for an additional beneficial outcome (NNTB) = 2; participants = 607; studies = 6; I² = 82%; low-certainty evidence) and 12 months (RR 0.80, 95% CI 0.72 to 0.89; NNTB = 6; participants = 585; studies = 6; I² = 21%; low-certainty evidence). No study reported on the number of clinical recurrences per participant per year. We are very uncertain whether oral drug treatment compared to topical treatment increases the risk of clinical recurrence at 6 months (RR 1.66, 95% CI 0.83 to 3.31; participants = 206; studies = 3; I² = 0%; very low-certainty evidence) and reduces the risk of clinical recurrence at 12 months (RR 0.95, 95% CI 0.71 to 1.27; participants = 206; studies = 3; I² = 10%; very low-certainty evidence). No study reported on the number of clinical recurrences per participant per year. Adverse events were scarce across both treatment and control groups in both comparisons. The reporting of adverse events varied amongst studies, was generally of very low quality and could not be pooled. Overall the adverse event rate was low for both placebo and treatment arms and ranged from less than 5% to no side effects or complications. AUTHORS' CONCLUSIONS: In women with RVVC, treatment with oral or topical antifungals may reduce symptomatic clinical recurrences when compared to placebo or no treatment. We were unable to find clear differences between different treatment options (e.g. oral versus topical treatment, different doses and durations). These findings are not applicable to pregnant or immunocompromised women and women with diabetes as the studies did not include or report on them. More research is needed to determine the optimal medication, dose and frequency.

Antibiotic prescribing for upper respiratory tract infections and acute bronchitis: a longitudinal analysis of general practitioner trainees.

BACKGROUND: Most antibiotic prescribing for upper respiratory tract infections (URTIs) and acute bronchitis is inappropriate. Substantive and sustained reductions in prescribing are needed to reduce antibiotic resistance. Prescribing habits develop early in clinicians' careers. Hence, general practice (GP) trainees are an important group to target. OBJECTIVES: We aimed to establish temporal trends in antibiotic prescribing for URTIs and acute bronchitis/bronchiolitis by Australian GP trainees (registrars). METHODS: A longitudinal analysis, 2010-2019, of the Registrars Clinical Encounters in Training (ReCEnT) dataset. In ReCEnT, registrars record clinical and educational content of 60 consecutive consultations, on 3 occasions, 6 monthly. Analyses were of new diagnoses of URTI and acute bronchitis/bronchiolitis, with the outcome variable a systemic antibiotic being prescribed. The independent variable of interest was year of prescribing (modelled as a continuous variable). RESULTS: 28,372 diagnoses of URTI and 5,289 diagnoses of acute bronchitis/bronchiolitis were recorded by 2,839 registrars. Antibiotic prescribing for URTI decreased from 24% in 2010 to 12% in 2019. Prescribing for acute bronchitis/bronchiolitis decreased from 84% to 72%. "Year" was significantly, negatively associated with antibiotic prescribing for both URTI (odds ratio [OR] 0.90; 95% confidence interval [CI]: 0.88-0.93) and acute bronchitis/bronchiolitis (OR 0.92; 95% CI: 0.88-0.96) on multivariable analysis, with estimates representing the mean annual change. CONCLUSIONS: GP registrars' prescribing for URTI and acute bronchitis/bronchiolitis declined over the 10-year period. Prescribing for acute bronchitis/bronchiolitis, however, remains higher than recommended benchmarks. Continued education and programme-level antibiotic stewardship interventions are required to further reduce registrars' antibiotic prescribing for acute bronchitis/bronchiolitis to appropriate levels.

It is well known that antibiotic consumption can cause antibiotic resistance. Most antibiotic prescribing happens in general practice. The common cold (upper respiratory tract infections) and cough (acute bronchitis) are 2 conditions that antibiotics are often prescribed for, but are not needed. There is considerable evidence that antibiotics do not help these conditions improve, and guidelines in Australia state that they are not a treatment option. General practitioners at the beginning of their career form prescribing habits early on. In light of the problem of antibiotic resistance, it is important to know how new doctors prescribe antibiotics, as they may do this for the rest of their career. We investigated their prescribing for the common cold and cough, from 2010 to 2019. We found that overall their prescribing has been declining over the last 10 years, but prescribing for cough is still too high. There needs to be more interventions in this group of doctors to reduce prescribing for this condition.

Socioeconomic status of practice location and Australian GP registrars' training: a cross-sectional analysis.

BACKGROUND: Socioeconomic status (SES) is a major determinant of health. In Australia, areas of socioeconomic disadvantage are characterised by complex health needs and inequity in primary health care provision. General Practice (GP) registrars play an important role in addressing workforce needs, including equitable health care provision in areas of greater socioeconomic disadvantage. We aimed to characterize GP registrars' practice location by level of socioeconomic disadvantage, and establish associations (of registrar, practice, patient characteristics, and registrars' clinical behaviours) with GP registrars training being undertaken in areas of greater socioeconomic disadvantage. METHODS: A cross-sectional analysis from the Registrars' Clinical Encounters in Training (ReCEnT) study. ReCEnT is an ongoing, multi-centre, cohort study that documents 60 consecutive consultations by each GP registrar once in each of their three six-monthly training terms. The outcome factor was the practice location's level of socioeconomic disadvantage, defined using the Index of Relative Socio-economic Disadvantage (SEIFA-IRSD). The odds of being in the lowest quintile was compared to the other four quintiles. Independent variables related to the registrar, patient, practice, and consultation. RESULTS: A total of 1,736 registrars contributed 241,945 consultations. Significant associations of training being in areas of most disadvantage included: the registrar being full-time, being in training term 1, being in the rural training pathway; patients being Aboriginal or Torres Strait Islander, or from a non-English-speaking background; and measures of continuity of care. CONCLUSIONS: Training in areas of greater social disadvantage, as well as addressing community need, may provide GP registrars with richer learning opportunities.

Psychosocial care for cancer survivors: A systematic literature review on the role of general practitioners.

OBJECTIVE: To explore the general practitioners (GP's) role in providing psychosocial care for cancer survivors through a systematic literature review. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and CINAHL and included the studies that complied with the predefined inclusion and exclusion criteria. At least two independent reviewers performed the quality appraisal and data extraction. RESULTS: We included 33 (five qualitative, 19 observational, and nine intervention) studies; the majority of these studies focused on care for depression and anxiety (21/33). Cancer survivors were more likely to contact their GP for psychosocial problems compared with noncancer controls. Survivors were more likely to use antidepressants compared with controls, although 71% of survivors preferred depression treatment to be "talking therapy only." Overall, GPs and patients mostly agreed that GPs are the preferred healthcare provider to manage psychosocial problems. The major exception is a survivor's fear of recurrence-here, the oncologist was the preferred healthcare provider. Only two interventions effectively decreased depression or anxiety; these studies included patients who had a clinical indication for psychosocial care, were specifically designed for decreasing depression/anxiety, and consisted of a multidisciplinary team approach. The other interventions evaluated GP-led follow-up for cancer survivors and found that this did not impact the patients' levels of anxiety, depression, or distress neither negatively nor positively. CONCLUSIONS: Cancer survivors often prefer psychosocial care by their GP, and GPs generally consider they are well placed to provide this care. Although evidence on the effectiveness of psychosocial care by GPs is limited, an active multidisciplinary team approach seems key.

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.

Heliox for croup in children.

BACKGROUND: Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (the benefits of which are often delayed) and nebulised epinephrine (adrenaline) (the benefits of which may be short-lived and which can cause dose-related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation. A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress. This review updates versions published in 2010, 2013, and 2018. OBJECTIVES: To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation. SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, on 15 April 2021. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 15 April 2021. We contacted the British Oxygen Company, a leading supplier of heliox. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo, no treatment, or any active intervention(s) in children with croup. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively. MAIN RESULTS: We included 3 RCTs involving a total of 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months, and all studies were conducted in emergency departments. Two studies were conducted in the USA and one in Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study because of its open-label design. We did not identify any new trials for this 2021 update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) -0.83, 95% confidence interval (CI) -2.36 to 0.70) (Westley croup score, scale range 0 to 16). The mean croup score at 20 minutes postintervention may not differ between groups (MD -0.57, 95% CI -1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI -1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI -8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low certainty, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve Taussig croup scores (scale range 0 to 15) at 60 minutes postintervention (MD -1.10, 95% CI -1.96 to -0.24), but there may be no difference between groups at 120 minutes (MD -0.70, 95% CI -1.56 to 0.16). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD -1.11, 95% CI -2.05 to -0.17) but not at 120 minutes (MD -0.71, 95% CI -1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD -4.94, 95% CI -9.66 to -0.22), but there may be no difference at 120 minutes (MD -3.17, 95% CI -7.83 to 1.49). There may be a difference in hospitalisation rates between groups (odds ratio 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to imprecision and high risk of bias related to an open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup all received continuous cool mist and intramuscular dexamethasone (0.6 mg/kg). They were then randomised to receive either heliox (given as a mixture of 70% helium and 30% oxygen) plus one to two doses of nebulised saline or 100% oxygen plus nebulised epinephrine (adrenaline), with gas therapy administered continuously for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may result in little or no difference overall using repeated-measures analysis. We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study. AUTHORS' CONCLUSIONS: Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate croup treated with dexamethasone. The effect of heliox may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.

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.

'Never change a winning team': GPs' perspectives on discontinuation of long-term antidepressants.

BACKGROUND: Long-term antidepressant use, much longer than recommended by guidelines, can harm patients and generate unnecessary costs. Most antidepressants are prescribed by general practitioners (GPs) but it remains unclear why they do not discontinue long-term use. AIM: To explore GPs' views and experiences of discontinuing long-term antidepressants, barriers and facilitators of discontinuation and required support. DESIGN AND SETTING: Qualitative study in Belgian GPs. METHOD: 20 semi-structured face-to-face interviews with GPs. Interviews were analysed thematically. RESULTS: The first theme, 'Success stories' describes three strong motivators to discontinue antidepressants: patient health issues, patient requests and a new positive life event. Second, not all GPs consider long-term antidepressant use a 'problem' as they perceive antidepressants as effective and safe. GPs' main concern is the risk of relapse. Third, GPs foresee that discontinuation of antidepressants is not an easy and straightforward process. GPs weigh up whether they have the necessary skills and whether it is worth the effort to start this process. CONCLUSION: Discontinuation of long-term antidepressants is a difficult and uncertain process for GPs, especially in the absence of a facilitating life-event or patient demand. The absence of a compelling need for discontinuation and fear of relapse of symptoms in a stable patient are important barriers for GPs when considering discontinuation. In order to increase GPs' motivation to discontinue long-term antidepressants, more emphasis on the futility of the actual effect and on potential harms related to long-term use is needed.KEY POINTSCurrent awareness:Long-term antidepressant use, much longer than recommended by guidelines, can harm patients and generate unnecessary costs.Main statements: • Discontinuation of long-term antidepressants is a difficult and uncertain process for GPs. • More emphasis on the futility of the actual effect of antidepressants and on potential harms related to long-term use is needed.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review published in 2007, 2009, 2010, and 2011. The evidence summarised in this review does not include results from studies from the current COVID-19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL on 1 April 2020. We searched ClinicalTrials.gov, and the WHO ICTRP on 16 March 2020. We conducted a backwards and forwards citation analysis on the newly included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs of trials investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, and gargling) to prevent respiratory virus transmission. In previous versions of this review we also included observational studies. However, for this update, there were sufficient RCTs to address our study aims.   DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. Three pairs of review authors independently extracted data using a standard template applied in previous versions of this review, but which was revised to reflect our focus on RCTs and cluster-RCTs for this update. We did not contact trialists for missing data due to the urgency in completing the review. We extracted data on adverse events (harms) associated with the interventions. MAIN RESULTS: We included 44 new RCTs and cluster-RCTs in this update, bringing the total number of randomised trials to 67. There were no included studies conducted during the COVID-19 pandemic. Six ongoing studies were identified, of which three evaluating masks are being conducted concurrent with the COVID pandemic, and one is completed. Many studies were conducted during non-epidemic influenza periods, but several studies were conducted during the global H1N1 influenza pandemic in 2009, and others in epidemic influenza seasons up to 2016. Thus, studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID-19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high-income countries; crowded inner city settings in low-income countries; and an immigrant neighbourhood in a high-income country. Compliance with interventions was low in many studies. The risk of bias for the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included nine trials (of which eight were cluster-RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and seven in the community). There is low certainty evidence from nine trials (3507 participants) that wearing a mask may make little or no difference to the outcome of influenza-like illness (ILI) compared to not wearing a mask (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.82 to 1.18. There is moderate certainty evidence that wearing a mask probably makes little or no difference to the outcome of laboratory-confirmed influenza compared to not wearing a mask (RR 0.91, 95% CI 0.66 to 1.26; 6 trials; 3005 participants). Harms were rarely measured and poorly reported. Two studies during COVID-19 plan to recruit a total of 72,000 people. One evaluates medical/surgical masks (N = 6000) (published Annals of Internal Medicine, 18 Nov 2020), and one evaluates cloth masks (N = 66,000). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). There is uncertainty over the effects of N95/P2 respirators when compared with medical/surgical masks on the outcomes of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; very low-certainty evidence; 3 trials; 7779 participants) and ILI (RR 0.82, 95% CI 0.66 to 1.03; low-certainty evidence; 5 trials; 8407 participants). The evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirator compared to a medical/surgical mask probably makes little or no difference for the objective and more precise outcome of laboratory-confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; moderate-certainty evidence; 5 trials; 8407 participants). Restricting the pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies. One ongoing study recruiting 576 people compares N95/P2 respirators with medical surgical masks for healthcare workers during COVID-19. Hand hygiene compared to control Settings included schools, childcare centres, homes, and offices. In a comparison of hand hygiene interventions with control (no intervention), there was a 16% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.84, 95% CI 0.82 to 0.86; 7 trials; 44,129 participants; moderate-certainty evidence), suggesting a probable benefit. When considering the more strictly defined outcomes of ILI and laboratory-confirmed influenza, the estimates of effect for ILI (RR 0.98, 95% CI 0.85 to 1.13; 10 trials; 32,641 participants; low-certainty evidence) and laboratory-confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials; 8332 participants; low-certainty evidence) suggest the intervention made little or no difference. We pooled all 16 trials (61,372 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. The pooled data showed that hand hygiene may offer a benefit with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.84 to 0.95; low-certainty evidence), but with high heterogeneity. Few trials measured and reported harms. There are two ongoing studies of handwashing interventions in 395 children outside of COVID-19. We identified one RCT on quarantine/physical distancing. Company employees in Japan were asked to stay at home if household members had ILI symptoms. Overall fewer people in the intervention group contracted influenza compared with workers in the control group (2.75% versus 3.18%; hazard ratio 0.80, 95% CI 0.66 to 0.97). However, those who stayed at home with their infected family members were 2.17 times more likely to be infected. We found no RCTs on eye protection, gowns and gloves, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low compliance with the interventions during the studies hamper drawing firm conclusions and generalising the findings to the current COVID-19 pandemic. There is uncertainty about the effects of face masks. The low-moderate certainty of the evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of randomised trials did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks during seasonal influenza. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, especially in those most at risk of ARIs.

Withdrawal and Misuse Concerns of Consumers regarding Opioid Analgesic and Anxiolytic, Hypnotic and Sedative Medicines.

BACKGROUND: Opioid analgesic (OA) and anxiolytic, hypnotic and sedative (AHS) medicines use raise community concerns about risks of dependence: dose escalation, unintentional misuse. Objectives: We aimed to identify common consumer OA and AHS information gaps and concerns that led to information seeking from a hotline. Methods: We conducted a retrospective, mixed-method observational study of consumers' OA and AHS-related calls to an Australian national medicines call center (September 2002-30 June 2010). We analyzed these medicines' call characteristics compared to their respective rest of calls (ROC) and thematically explored narratives concerning withdrawal and misuse. Results: Of 123,217 calls, 7,395 (6.0%) involved OA and 7,789 (6.2%) AHS, with consistency between call characteristics. While female middle-aged callers predominated, more males called for these medicines than their complementary ROC. Uncertainty about unresolved OA and AHS concerns led to help-seeking that was consistent over eight years. Main motivations were inadequate information (OA 44.5%; AHS 41.2%), seeking a second opinion (OA 24.2%; AHS 24.2%), worrying symptoms (OA 21.6%; AHS 23.1%), and conflicting information (OA 4.9%; AHS 5.1%). Callers focused on withdrawal and issues related to inadvertent overuse or deliberate misuse (OA 9.2% vs. non-OA ROC 2.9%; AHS 12.6% vs. non-AHS ROC 2.7%). Primary themes were similar for both cohorts: concern about harm or aiming to minimize harm by information seeking, requesting a strategy, or reassurance. Conclusions: Consumers have under-recognized perceptions of harm from OA and AHS use, particularly withdrawal and misuse. Resources based on real world consumer concerns can encourage open dialogue between patients and their prescribers.

Configurations for obtaining in-consultation assistance from supervisors in general practice training, and patient-related barriers to trainee help-seeking: a survey study.

BACKGROUND: General practice (GP) trainees may seek supervisor assistance to complete their patient consultations. This in-consultation assistance plays a key role in the supervisory oversight of trainees and in trainee learning. It may be obtained face-to-face, or using phone or messaging systems, and either in front of patients or outside their hearing. Trainee concerns about decreased patient impressions of their competence, and discomfort presenting patients within their hearing, act as barriers to seeking help during consultations. Little is known about the frequency and associations of trainee concerns about these patient-related barriers, or the various trainee-supervisor-patient configurations used to obtain in-consultation assistance. METHODS: Australian GP trainees rated their frequency of use of five specific configurations for obtaining in-consultation assistance, perceived change in patient impressions of their competence after this assistance, and relative trainee comfort presenting patients outside, compared to within, patients' hearing. Statistical analyses included descriptive statistics and multivariable logistic regression. RESULTS: Responses were received from 778 Australian GP trainees (response rate 89%). Help-seeking configurations did not differ between trainees at different training stages, except for greater use of electronic messaging in later stages. In-consultation assistance was most commonly provided by phone between trainee and supervisor consulting rooms, or outside the trainee's patient's hearing. Supervisor assistance in the trainee's room face-to-face with the patient was reported as either never or rarely obtained by 12% of respondents. More trainees (25%) perceived that patient impressions of their competence increased after help-seeking than perceived that these impressions decreased (19%). Most trainees (55%) preferred to present patients outside their hearing. Trainee age was the only variable associated with both patient-related barriers. CONCLUSION: Supervisors appear to have considerable influence over trainee help-seeking, including which configurations are used and trainee perceptions of patient-related barriers. In-consultation supervision may actually increase trainee perceptions of patient impressions of their competence. Many supervisors and trainees may benefit from additional educational and workplace interventions to facilitate comfortable and effective trainee help-seeking in front of patients. More work is required to understand the clinical and educational implications of different help-seeking configurations when trainees require 'just in time' supervisor assistance.