Antibiotics for treatment of sore throat in children and adults.

BACKGROUND: Sore throat is a common reason for people to present for medical care and to be prescribed antibiotics. Overuse of antibiotics in primary medicine is a concern, hence it is important to establish their efficacy in treating sore throat and preventing secondary complications.  OBJECTIVES: To assess the effects of antibiotics for reducing symptoms of sore throat for child and adult patients. SEARCH METHODS: We searched CENTRAL 2021, Issue 2, MEDLINE (January 1966 to April week 1, 2021), Embase (January 1990 to April 2021), and two trial registries (searched 6 April 2021). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of antibiotics versus control assessing typical sore throat symptoms or complications amongst children and adults seeking medical care for sore throat symptoms. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. Two review authors independently screened studies for inclusion and extracted data, resolving any differences in opinion by discussion. We contacted the trial authors from three studies for additional information. We used GRADE to assess the certainty of the evidence for the efficacy of antibiotics on our primary outcomes (sore throat at day three and one week) and secondary outcomes (fever and headache symptoms and incidence of acute rheumatic fever, acute glomerulonephritis, acute otitis media, acute sinusitis, and quinsy). MAIN RESULTS: We included 29 trials with 15,337 cases of sore throat. The majority of included studies were conducted in the 1950s, during which time the rates of serious complications (especially acute rheumatic fever) were much higher than today. Although clinical antibiotic trials for sore throat and respiratory symptoms are still being conducted, it is unusual for them to include placebo or 'no treatment' control arms, which is a requirement for inclusion in the review. The age of participants ranged from younger than one year to older than 50 years, but most participants across all studies were adults. Although all studies recruited patients presenting with symptoms of sore throat, few of them distinguished between bacterial and viral aetiology. Bias may have been introduced through non-clarity in treatment allocation procedures and lack of blinding in some studies. Harms from antibiotics were poorly or inconsistently reported, and were thus not quantified for this review. 1. Symptoms Throat soreness and headache at day three were reduced by using antibiotics, although 82% of participants in the placebo or no treatment group were symptom-free by one week. The reduction in sore throat symptoms at day three (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.60 to 0.80; 16 studies, 3730 participants; moderate-certainty evidence) was greater than at one week in absolute numbers (RR 0.50, 95% CI 0.34 to 0.75; 14 studies, 3083 participants; moderate-certainty evidence) due to many cases in both treatment groups having resolved by this time. The number needed to treat for an additional beneficial outcome (NNTB) to prevent one sore throat at day three was less than six; at week one it was 18. Compared with placebo or no treatment, antibiotics did not significantly reduce fever at day three (RR 0.75, 95% CI 0.53 to 1.07; 8 studies, 1443 participants; high-certainty evidence), but did reduce headache at day three (RR 0.49, 95% CI 0.34 to 0.70; 4 studies, 1020 participants; high-certainty evidence). 2. Suppurative complications Whilst the prevalence of suppurative complications was low, antibiotics reduced the incidence of acute otitis media within 14 days (Peto odds ratio (OR) 0.21, 95% CI 0.11 to 0.40; 10 studies, 3646 participants; high-certainty evidence) and quinsy within two months (Peto OR 0.16, 95% CI 0.07 to 0.35; 8 studies, 2433 participants; high-certainty evidence) compared to those receiving placebo or no treatment, but not acute sinusitis within 14 days (Peto OR 0.46, 95% CI 0.10 to 2.05; 8 studies, 2387 participants; high-certainty evidence). 3. Non-suppurative complications There were too few cases of acute glomerulonephritis to determine whether there was a protective effect of antibiotics compared with placebo against this complication (Peto OR 0.07, 95% CI 0.00 to 1.32; 10 studies, 5147 participants; low-certainty evidence). Antibiotics reduced acute rheumatic fever within two months when compared to the control group (Peto OR 0.36, 95% CI 0.26 to 0.50; 18 studies, 12,249 participants; moderate-certainty evidence). It should be noted that the overall prevalence of acute rheumatic fever was very low, particularly in the later studies. AUTHORS' CONCLUSIONS: Antibiotics probably reduce the number of people experiencing sore throat, and reduce the likelihood of headache, and some sore throat complications. As the effect on symptoms can be small, clinicians must judge on an individual basis whether it is clinically justifiable to use antibiotics to produce this effect, and whether the underlying cause of the sore throat is likely to be of bacterial origin. Furthermore, the balance between modest symptom reduction and the potential hazards of antimicrobial resistance must be recognised. Few trials have attempted to measure symptom severity. If antibiotics reduce the severity as well as the duration of symptoms, their benefit will have been underestimated in this meta-analysis. Additionally, more trials are needed in low-income countries, in socio-economically deprived sections of high-income countries, as well as in children.

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.

Corticosteroids as standalone or add-on treatment for sore throat.

BACKGROUND: Sore throat is a common condition associated with a high rate of antibiotic prescriptions, despite limited evidence for the effectiveness of antibiotics. Corticosteroids may improve symptoms of sore throat by reducing inflammation of the upper respiratory tract. This review is an update to our review published in 2012. OBJECTIVES: To assess the clinical benefit and safety of corticosteroids in reducing the symptoms of sore throat in adults and children. SEARCH METHODS: We searched CENTRAL (Issue 4, 2019), MEDLINE (1966 to 14 May 2019), Embase (1974 to 14 May 2019), the Database of Abstracts of Reviews of Effects (DARE, 2002 to 2015), and the NHS Economic Evaluation Database (inception to 2015). We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared steroids to either placebo or standard care in adults and children (aged over three years) with sore throat. We excluded studies of hospitalised participants, those with infectious mononucleosis (glandular fever), sore throat following tonsillectomy or intubation, or peritonsillar abscess. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included one new RCT in this update, for a total of nine trials involving 1319 participants (369 children and 950 adults). In eight trials, participants in both corticosteroid and placebo groups received antibiotics; one trial offered delayed prescription of antibiotics based on clinical assessment. Only two trials reported funding sources (government and a university foundation). In addition to any effect of antibiotics and analgesia, corticosteroids increased the likelihood of complete resolution of pain at 24 hours by 2.40 times (risk ratio (RR) 2.4, 95% confidence interval (CI) 1.29 to 4.47; P = 0.006; I² = 67%; high-certainty evidence) and at 48 hours by 1.5 times (RR 1.50, 95% CI 1.27 to 1.76; P < 0.001; I² = 0%; high-certainty evidence). Five people need to be treated to prevent one person continuing to experience pain at 24 hours. Corticosteroids also reduced the mean time to onset of pain relief and the mean time to complete resolution of pain by 6 and 11.6 hours, respectively, although significant heterogeneity was present (moderate-certainty evidence). At 24 hours, pain (assessed by visual analogue scales) was reduced by an additional 10.6% by corticosteroids (moderate-certainty evidence). No differences were reported in recurrence/relapse rates, days missed from work or school, or adverse events for participants taking corticosteroids compared to placebo. However, the reporting of adverse events was poor, and only two trials included children or reported days missed from work or school. The included studies were assessed as moderate quality evidence, but the small number of included studies has the potential to increase the uncertainty, particularly in terms of applying these results to children. AUTHORS' CONCLUSIONS: Oral or intramuscular corticosteroids, in addition to antibiotics, moderately increased the likelihood of both resolution and improvement of pain in participants with sore throat. Given the limited benefit, further research into the harms and benefits of short courses of steroids is needed to permit informed decision-making.

Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection.

BACKGROUND: Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin is sometimes used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licenced for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital.  OBJECTIVES: To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections in children aged up to three years, admitted to hospital.  SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 6 November 2018) with no restrictions. We searched two trial registries for ongoing trials (to 30 March 2018) and checked the reference lists of reviews and included articles for additional studies. SELECTION CRITERIA: Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence quality using GRADE. MAIN RESULTS: We included seven trials involving 486 infants and children aged up to three years. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. We assessed the primary outcomes of mortality, length of hospital stay, and adverse events as providing low- or very low-certainty evidence due to risk of bias and imprecision. All trials were conducted at sites in high-income countries (USA, Chile, New Zealand, Australia), with two studies including a site in a middle-income country (Panama). Five of the seven studies were "supported" or "sponsored" by the trial drug manufacturers. We found no evidence of a difference between immunoglobulins and placebo for mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 3 trials; 196 children; 4 deaths; 2 deaths amongst 98 children receiving immunoglobulins, and 2 deaths amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however, the study group of the child was not known and the data were not included in the analysis; very low-certainty evidence), and length of hospitalisation (mean difference -0.70, 95% CI -1.83 to 0.42; 5 trials; 324 children; low-certainty evidence). There was no evidence of a difference between immunoglobulins and placebo in adverse events of any severity or seriousness (reported in five trials) or serious adverse events (four trials) (RR for any severity 1.18, 95% CI 0.78 to 1.78; 340 children; low-certainty evidence, and for serious adverse events 1.08, 95% CI 0.65 to 1.79; 238 children; low-certainty evidence).We found no evidence of a significant difference between immunoglobulins and placebo for any of our secondary outcomes. We identified one ongoing trial. AUTHORS' CONCLUSIONS: We found insufficient evidence of a difference between immunoglobulins and placebo for any review outcomes. We assessed the evidence for the effects of immunoglobulins when used as a treatment for RSV lower respiratory tract infection in hospitalised infants and young children as of low or very low certainty due to risk of bias and imprecision. We are uncertain of the effects of immunoglobulins on these outcomes, and the true effect may be substantially different from the effects reported in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.

Probiotics for preventing acute otitis media in children.

BACKGROUND: Acute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority. OBJECTIVES: To assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD). MAIN RESULTS: We included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95% confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95% CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95% CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).None of the included trials reported on the severity of AOM.The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95% CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95% CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.There was no difference in the mean number of school days lost (MD -0.95, 95% CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95% CI 0.99 to 1.05; 5 trials; 990 participants).Probiotics decreased the proportion of children having other infections (RR 0.75, 95% CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias. AUTHORS' CONCLUSIONS: Probiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.

Adverse events in people taking macrolide antibiotics versus placebo for any indication.

BACKGROUND: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. OBJECTIVES: To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. SELECTION CRITERIA: We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. MAIN RESULTS: We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin.Most studies (89%) reported some adverse events or at least stated that no adverse events were observed.Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low-quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low-quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate-quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate-quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate-quality evidence) were also reported more often in participants taking macrolides compared to placebo.The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000.The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting.There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration.Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; I² = 46%; low-quality evidence).Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; I² = 0%; low-quality evidence).We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low-quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low-quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low-quality evidence) compared to placebo.We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo.Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate-quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate-quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate-quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non-significant.There was no increase in mortality in participants taking macrolides compared with placebo (OR 0.96, 95% 0.87 to 1.06; I² = 11%; low-quality evidence).Only 24 studies (13%) provided useful data on macrolide-resistant bacteria. Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic. However, differences in resistance thereafter were inconsistent.Pharmaceutical companies supplied the trial medication or funding, or both, for 91 trials. AUTHORS' CONCLUSIONS: The macrolides as a group clearly increased rates of gastrointestinal adverse events. Most trials made at least some statement about adverse events, such as "none were observed". However, few trials clearly listed adverse events as outcomes, reported on the methods used for eliciting adverse events, or even detailed the numbers of people who experienced adverse events in both the intervention and placebo group. This was especially true for the adverse event of bacterial resistance.

Educational interventions to improve people's understanding of key concepts in assessing the effects of health interventions: a systematic review.

BACKGROUND: Health information is readily accessible but is of variable quality. General knowledge about how to assess whether claims about health interventions are trustworthy is not common, so people's health decisions can be ill-informed, unnecessarily costly and even unsafe. This review aims to identify and evaluate studies of educational interventions designed to improve people's understanding of key concepts for evaluating claims about the effects of health interventions. METHODS/DESIGN: We searched multiple electronic databases and sources of grey literature. Inclusion criteria included all study types that included a comparison, any participants (except health professionals or health professional students) and educational interventions aimed at improving people's understanding of one or more of the key concepts considered necessary for assessing health intervention claims. Knowledge and/or understanding of concepts or skills relevant to evaluating health information were our primary outcome measures. Secondary outcomes included behaviour, confidence, attitude and satisfaction with the educational interventions. Two authors independently screened search results, assessed study eligibility and risk of bias and extracted data. Results were summarised using descriptive synthesis. RESULTS: Among 24 eligible studies, 14 were randomised trials and 10 used other study designs. There was heterogeneity across study participants, settings and educational intervention type, content and delivery. The risk of bias was high in at least one domain for all randomised studies. Most studies measured outcomes immediately after the educational intervention, with few measuring later. In most of the comparisons, measures of knowledge and skills were better among those who had received educational interventions than among controls, and some of these differences were statistically significant. The effects on secondary outcomes were inconsistent. CONCLUSIONS: Educational interventions to improve people's understanding of key concepts for evaluating health intervention claims can improve people's knowledge and skills, at least in the short term. Effects on confidence, attitude and behaviour are uncertain. Many of the studies were at moderate or greater risk of bias. Improvements in study quality, consistency of outcome measures and measures of longer-term effects are needed to improve confidence in estimates of the effects of educational interventions to improve people's understanding of key concepts for evaluating health intervention claims. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033103.

Systemic corticosteroids for acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti-inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics. OBJECTIVES: To assess the effects of systemic corticosteroids (oral or parenteral), with or without antibiotics, for AOM in children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane ARI Group's Specialised Register, MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Thomson Reuters), and LILACS (BIREME) for published studies, and ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing studies, to 20 February 2018. We checked the reference lists of all primary studies and review articles for additional references and contacted experts in the field to identify additional unpublished materials. SELECTION CRITERIA: We included randomised controlled trials of children with AOM that compared any systemic corticosteroid (oral or parenteral) with placebo, either with antibiotics (corticosteroid plus antibiotic versus placebo plus antibiotic) or without antibiotics (corticosteroid versus placebo). DATA COLLECTION AND ANALYSIS: Three review authors (EDS, RR, YP) independently screened the titles and abstracts and retrieved the full texts of potentially relevant studies. We independently extracted study characteristics and outcome data from the included studies, and assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed study quality using the GRADE method. MAIN RESULTS: We included two studies involving 252 children with AOM aged from three months to six years receiving hospital ambulatory care who were treated with intramuscular ceftriaxone, and who were then randomised to the corticosteroid group (corticosteroid and corticosteroid plus antihistamine) or the placebo group (antihistamine and double placebo). In one study, children also had a needle aspiration of middle ear fluid. Both studies were at unclear risk of bias for allocation concealment, and unclear to high risk of bias for selective reporting.One study (N = 179) included pain as an outcome, but we were unable to derive the proportion of children with persistent pain at Day 5 and Day 14. Reduction of overall or specific symptoms was presented as improvement in clinical symptoms and resolution of inflamed tympanic membranes without the need for additional antibiotic treatment: at Day 5 (94% of children in the treatment group (N = 89) versus 89% in the placebo group (N = 90); risk ratio (RR) 1.06, 95% confidence interval (CI) 0.97 to 1.16) and Day 14 (91% versus 87%; RR 1.05, 95% CI 0.95 to 1.17). Low-quality evidence meant that we are uncertain of the effectiveness of corticosteroids for this outcome.The second study (N = 73) reported a reduction of overall or specific symptoms without additional antibiotic treatment during the first two weeks as a favourable outcome. Children in the treatment group had more favourable outcomes (adjusted odds ratio 65.9, 95% CI 1.28 to 1000; P = 0.037), although the numbers were small. We were unable to pool the results with the other study because it did not report the proportion of children with this outcome by treatment group. Only one study reported adverse effects of corticosteroids (e.g. drowsiness, nappy rash), but did not quantify incidence, so we were unable to draw conclusions about adverse effects. Neither study reported a reduction in overall or specific symptom duration. AUTHORS' CONCLUSIONS: The evidence for the effect of systemic corticosteroids on AOM is of low to very low quality, meaning the effect of systemic corticosteroids on important clinical outcomes in AOM remains uncertain. Large, high-quality studies are required to resolve the question.

Clinician-targeted interventions to influence antibiotic prescribing behaviour for acute respiratory infections in primary care: an overview of systematic reviews.

BACKGROUND: Antibiotic resistance is a worldwide health threat. Interventions that reduce antibiotic prescribing by clinicians are expected to reduce antibiotic resistance. Disparate interventions to change antibiotic prescribing behaviour for acute respiratory infections (ARIs) have been trialled and meta-analysed, but not yet synthesised in an overview. This overview synthesises evidence from systematic reviews, rather than individual trials. OBJECTIVES: To systematically review the existing evidence from systematic reviews on the effects of interventions aimed at influencing clinician antibiotic prescribing behaviour for ARIs in primary care. METHODS: We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Science Citation Index to June 2016. We also searched the reference lists of all included reviews. We ran a pre-publication search in May 2017 and placed additional studies in 'awaiting classification'.We included both Cochrane and non-Cochrane reviews of randomised controlled trials evaluating the effect of any clinician-focussed intervention on antibiotic prescribing behaviour in primary care. Two overview authors independently extracted data and assessed the methodological quality of included reviews using the ROBIS tool, with disagreements reached by consensus or by discussion with a third overview author. We used the GRADE system to assess the quality of evidence in included reviews. The results are presented as a narrative overview. MAIN RESULTS: We included eight reviews in this overview: five Cochrane Reviews (33 included trials) and three non-Cochrane reviews (11 included trials). Three reviews (all Cochrane Reviews) scored low risk across all the ROBIS domains in Phase 2 and low risk of bias overall. The remaining five reviews scored high risk on Domain 4 of Phase 2 because the 'Risk of bias' assessment had not been specifically considered and discussed in the review Results and Conclusions. The trials included in the reviews varied in both size and risk of bias. Interventions were compared to usual care.Moderate-quality evidence indicated that C-reactive protein (CRP) point-of-care testing (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92, 3284 participants, 6 trials), shared decision making (odds ratio (OR) 0.44, 95% CI 0.26 to 0.75, 3274 participants, 3 trials; RR 0.64, 95% CI 0.49 to 0.84, 4623 participants, 2 trials; risk difference -18.44, 95% CI -27.24 to -9.65, 481,807 participants, 4 trials), and procalcitonin-guided management (adjusted OR 0.10, 95% CI 0.07 to 0.14, 1008 participants, 2 trials) probably reduce antibiotic prescribing in general practice. We found moderate-quality evidence that procalcitonin-guided management probably reduces antibiotic prescribing in emergency departments (adjusted OR 0.34, 95% CI 0.28 to 0.43, 2605 participants, 7 trials). The overall effect of these interventions was small (few achieving greater than 50% reduction in antibiotic prescribing, most about a quarter or less), but likely to be clinically important.Compared to usual care, shared decision making probably makes little or no difference to reconsultation for the same illness (RR 0.87, 95% CI 0.74 to 1.03, 1860 participants, 4 trials, moderate-quality evidence), and may make little or no difference to patient satisfaction (RR 0.86, 95% CI 0.57 to 1.30, 1110 participants, 2 trials, low-quality evidence). Similarly, CRP testing probably has little or no effect on patient satisfaction (RR 0.79, 95% CI 0.57 to 1.08, 689 participants, 2 trials, moderate-quality evidence) or reconsultation (RR 1.08, 95% CI 0.93 to 1.27, 5132 participants, 4 trials, moderate-quality evidence). Procalcitonin-guided management probably results in little or no difference in treatment failure in general practice compared to normal care (adjusted OR 0.95, 95% CI 0.73 to 1.24, 1008 participants, 2 trials, moderate-quality evidence), however it probably reduces treatment failure in the emergency department compared to usual care (adjusted OR 0.76, 95% CI 0.61 to 0.95, 2605 participants, 7 trials, moderate-quality evidence).The quality of evidence for interventions focused on clinician educational materials and decision support in reducing antibiotic prescribing in general practice was either low or very low (no pooled result reported) and trial results were highly heterogeneous, therefore we were unable draw conclusions about the effects of these interventions. The use of rapid viral diagnostics in emergency departments may have little or no effect on antibiotic prescribing (RR 0.86, 95% CI 0.61 to 1.22, 891 participants, 3 trials, low-quality evidence) and may result in little to no difference in reconsultation (RR 0.86, 95% CI 0.59 to 1.25, 200 participants, 1 trial, low-quality evidence).None of the trials in the included reviews reported on management costs for the treatment of an ARI or any associated complications. AUTHORS' CONCLUSIONS: We found evidence that CRP testing, shared decision making, and procalcitonin-guided management reduce antibiotic prescribing for patients with ARIs in primary care. These interventions may therefore reduce overall antibiotic consumption and consequently antibiotic resistance. There do not appear to be negative effects of these interventions on the outcomes of patient satisfaction and reconsultation, although there was limited measurement of these outcomes in the trials. This should be rectified in future trials.We could gather no information about the costs of management, and this along with the paucity of measurements meant that it was difficult to weigh the benefits and costs of implementing these interventions in practice.Most of this research was undertaken in high-income countries, and it may not generalise to other settings. The quality of evidence for the interventions of educational materials and tools for patients and clinicians was either low or very low, which prevented us from drawing any conclusions. High-quality trials are needed to further investigate these interventions.

Delayed antibiotic prescriptions for respiratory infections.

BACKGROUND: Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost, and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010 and 2013. OBJECTIVES: To evaluate the effects on clinical outcomes, antibiotic use, antibiotic resistance, and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. SEARCH METHODS: For this 2017 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4, 2017), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (2013 to 25 May 2017); Ovid Embase (2013 to 2017 Week 21); EBSCO CINAHL Plus (1984 to 25 May 2017); Web of Science (2013 to 25 May 2017); WHO International Clinical Trials Registry Platform (1 September 2017); and ClinicalTrials.gov (1 September 2017). SELECTION CRITERIA: Randomised controlled trials involving participants of all ages defined as having an RTI, where delayed antibiotics were compared to immediate antibiotics or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Three review authors independently extracted and collated data. We assessed the risk of bias of all included trials. We contacted trial authors to obtain missing information. MAIN RESULTS: For this 2017 update we added one new trial involving 405 participants with uncomplicated acute respiratory infection. Overall, this review included 11 studies with a total of 3555 participants. These 11 studies involved acute respiratory infections including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study), and a variety of RTIs (one study). Five studies involved only children, two only adults, and four included both adults and children. Six studies were conducted in a primary care setting, three in paediatric clinics, and two in emergency departments.Studies were well reported, and appeared to be of moderate quality. Randomisation was not adequately described in two trials. Four trials blinded the outcomes assessor, and three included blinding of participants and doctors. We conducted meta-analysis for antibiotic use and patient satisfaction.We found no differences among delayed, immediate, and no prescribed antibiotics for clinical outcomes in the three studies that recruited participants with cough. For the outcome of fever with sore throat, three of the five studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and three found no difference. One study compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes.Three studies included participants with acute otitis media. Of the two studies with an immediate antibiotic arm, one study found no difference for fever, and the other study favoured immediate antibiotics for pain and malaise severity on Day 3. One study including participants with acute otitis media compared delayed antibiotics with no antibiotics and found no difference for pain and fever on Day 3.Two studies recruited participants with common cold. Neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study favoured delayed antibiotics over no antibiotics for pain, fever, and cough duration (moderate quality evidence for all clinical outcomes - GRADE assessment).There were either no differences for adverse effects or results favoured delayed antibiotics over immediate antibiotics (low quality evidence - to GRADE assessment) with no significant differences in complication rates. Delayed antibiotics resulted in a significant reduction in antibiotic use compared to immediate antibiotics prescription (odds ratio (OR) 0.04, 95% confidence interval (CI) 0.03 to 0.05). However, a delayed antibiotic was more likely to result in reported antibiotic use than no antibiotics (OR 2.55, 95% CI 1.59 to 4.08) (moderate quality evidence - GRADE assessment).Patient satisfaction favoured delayed over no antibiotics (OR 1.49, 95% CI 1.08 to 2.06). There was no significant difference in patient satisfaction between delayed antibiotics and immediate antibiotics (OR 0.65, 95% CI 0.39 to 1.10) (moderate quality evidence - GRADE assessment).None of the included studies evaluated antibiotic resistance. AUTHORS' CONCLUSIONS: For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%) (moderate quality evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (31% versus 93%) (moderate quality evidence). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (14% versus 28%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with respiratory infections, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delaying prescription of antibiotics. Where clinicians are not confident in using a no antibiotic strategy, a delayed antibiotics strategy may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, and thereby reduce antibiotic resistance, while maintaining patient safety and satisfaction levels.Editorial note: As a living systematic review, this review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

A qualitative study exploring high school students' understanding of, and attitudes towards, health information and claims.

BACKGROUND: Exposure to health claims, particularly in the media and social media, is pervasive, and the information conveyed is often inaccurate, incomplete or misleading. Some young people of high school ages are already making decisions about using readily available health interventions (such as sports drinks and beauty products).Although previous research has assessed adults' understanding of health claims, no research has examined this issue in young adults who are attending high school. OBJECTIVE: To explore high school students' understanding of, and attitudes towards, concepts relevant to assessing health information and claims. DESIGN: A qualitative study involving semi-structured interviews with 27 Australian high school students. Responses were recorded, transcribed and a thematic analysis performed. Three themes emerged as follows: (i) Variability in sources of health information and claims, and general understanding of their creation and accuracy of content, (ii) The use of substitute indicators to assess health information and claims and make judgements about their trustworthiness, (iii) Uncertainty about, and literal interpretation of, the language of health claims. Despite general scepticism of health claims and admitted uncertainty of research terminology, many students were generally convinced. Students had poor understanding about how health claims are generated and tended to rely on substitute indicators, such as endorsements, when evaluating the believability of claims. CONCLUSION: School students' lack of awareness of basic health research processes and methods of assessing the accuracy of health information and claims makes them vulnerable to distorted and misleading health information. This restricts their ability to make informed health decisions - a skill that increases in importance as they become adults.

Preparing Parents to Make An Informed Choice About Antibiotic Use for Common Acute Respiratory Infections in Children: A Randomised Trial of Brief Decision Aids in a Hypothetical Scenario.

BACKGROUND: Childhood acute respiratory infections (ARIs) are one of the most common reasons for primary care consultations and for receiving an antibiotic. Public awareness of antibiotic benefit and harms for these conditions is low. To facilitate informed decision making, ideally in collaboration with their doctor, parents need clear communication about benefits and harms. Decision aids may be able to facilitate this process. OBJECTIVE: The aim of this study was to evaluate the effectiveness of three decision aids about antibiotic use for common ARIs in children. METHODS: Adult parents of children aged 1-16 years (n = 120) were recruited from community settings and then randomised using a computer-generated randomisation sequence to receive a decision aid (n = 60) or fact sheet (n = 60). Allocation was concealed and used sealed and opaque sequentially numbered envelopes. Participants self-completed questionnaires at baseline and immediately post-intervention. The primary outcome was informed choice (conceptual and numerical knowledge; attitudes towards, and intention to use, antibiotics for a future ARI). Secondary outcomes were decisional conflict, decisional self-efficacy, and material acceptability. RESULTS: After reading the information, significantly more intervention group participants made an informed choice [57%] compared with control group participants [29%] [difference 28, 95% confidence interval (CI) 11-45%, p < 0.01], and had higher total knowledge [mean difference (MD) 2.8, 95% CI 2.2-3.5, p < 0.01], conceptual knowledge (MD 0.7, 95% CI 0.4-1.1, p < 0.01) and numerical knowledge (MD 2.1, 95% CI 1.6-2.5, p < 0.01). Between-group differences in attitudes or intention to use antibiotics were not significant. Most intervention group participants found the information understandable and liked the aids' format and features. CONCLUSION: The decision aids prepared parents to make an informed choice about antibiotic use more than fact sheets, in a hypothetical situation. Their effect within a consultation needs to be evaluated. Clinical Trials Registration Number: ACTRN12615000843550.

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data.

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza. METHODS: We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies. RESULTS: Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%). Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65). CONCLUSIONS: Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002245. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Urinary alkalisation for symptomatic uncomplicated urinary tract infection in women.

BACKGROUND: Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women, characterised by dysuria and urinary frequency. Urinary alkalisers are widely used in some countries for the symptomatic treatment of uncomplicated UTI, and they are recommended in some national formularies. However, there is a lack of empirical evidence to support their use for UTI and some healthcare guidelines advise against their use. OBJECTIVES: We aimed to look at the benefits and harms of the use of urinary alkalisers for the treatment of uncomplicated UTIs in adult women. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 19 January 2016 through contact with the Trials Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs on the use of (any) urinary alkalisers (either exclusively or non-exclusively) for the symptomatic treatment of uncomplicated UTI amongst women aged 16 and over, were included. Studies were eligible if they included patients whose diagnosis of UTI was decided by symptoms alone, or positive urine dipstick test or urine culture; and patients with recurrent UTI, provided patients had no symptoms of UTI in the two weeks prior to the onset of symptoms that lead them to seek medical advice. Studies were ineligible if they studied patients with complicated UTIs; immune-compromising conditions; acute pyelonephritis; or chronic conditions such as interstitial cystitis. DATA COLLECTION AND ANALYSIS: Three authors independently assessed and screened papers, and this was repeated by two separate authors (independently). An additional investigator acted as arbitrator, where necessary. There were no papers which fulfilled the inclusion criteria for this review, and therefore no data extraction was performed. MAIN RESULTS: Our search identified 172 potential studies for inclusion. However, following assessment none fulfilled the inclusion criteria for this review. AUTHORS' CONCLUSIONS: Until relevant evidence is generated from randomised trials, the safety and efficacy of urinary alkalisers for the symptomatic treatment of uncomplicated UTI remains unknown.

Educational interventions to improve people's understanding of key concepts in assessing the effects of health interventions: a systematic review protocol.

BACKGROUND: Health information has become readily accessible through mass media, and people are playing a more active and autonomous role in their health. Much of the health information that was previously only available to health professionals is now directly accessible to the public. Consequently, people often navigate vast amounts of health information on their own, typically with little knowledge about how to evaluate it or the need to do so. Health information remains essentially unregulated, and widespread problems and concerns with the quality of health information have been noted. In addition to the variable quality of health information, inconsistent and/or inappropriate use of related terminology (e.g. 'evidence-based' and 'clinically proven') can be confusing to the public, who are ill-prepared to critically examine claims. The general public are not trained in the fundamentals of health research and do not typically possess the knowledge and skills to evaluate the accuracy and completeness of information about health interventions. Without this, the public are vulnerable to acting on inaccurate or incomplete health information and making ill-informed health decisions. With this review, we intend to identify and assess educational interventions which have been designed to improve people's ability to understand key concepts relevant to evaluating claims about the effects of health interventions. METHODS/DESIGN: This systematic review of the literature will use a search strategy that has been developed in conjunction with a Health Sciences Librarian who has expertise in systematic review searching to identify relevant studies. Databases to be searched include the following: the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and ERIC. Attempts to identify unpublished studies and ongoing trials will also be made. Two review authors will independently screen search results and assess studies for eligibility. Studies which aim to improve participants' understanding of the key concepts relevant to evaluating the effects (or the interpretation of results) of health interventions will be included. Randomised trials, non-randomised trials, controlled before and after studies, controlled studies with only post-test measures, and interrupted time series studies will be eligible for inclusion. We will contact study authors to clarify any missing details/data. Due to the nature of the systematic review question and the expectation of heterogeneity in study design, interventions, and outcomes, we intend to take a narrative approach to data synthesis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033103.

Can consumers learn to ask three questions to improve shared decision making? A feasibility study of the ASK (AskShareKnow) Patient-Clinician Communication Model(®) intervention in a primary health-care setting.

OBJECTIVE: To test the feasibility and assess the uptake and acceptability of implementing a consumer questions programme, AskShareKnow, to encourage consumers to use the questions '1. What are my options; 2. What are the possible benefits and harms of those options; 3. How likely are each of those benefits and harms to happen to me?' These three questions have previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement. METHODS: This single-arm intervention study invited participants attending a reproductive and sexual health-care clinic to view a 4-min video-clip in the waiting room. Participants completed three questionnaires: (T1) prior to viewing the intervention; (T2) immediately after their consultation; and (T3) two weeks later. RESULTS: A total of 121 (78%) participants viewed the video-clip before their consultation. Eighty-four (69%) participants asked one or more questions, and 35 (29%) participants asked all three questions. For those making a decision, 55 (87%) participants asked one or more questions, while 27 (43%) participants asked all three questions. Eighty-seven (72%) participants recommended the questions. After two weeks, 47 (49%) of the participants recalled the questions. CONCLUSIONS: Enabling patients to view a short video-clip before an appointment to improve information and involvement in health-care consultations is feasible and led to a high uptake of question asking in consultations. PRACTICE IMPLICATIONS: This AskShareKnow programme is a simple and feasible method of training patients to use a brief consumer-targeted intervention that has previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement and use of evidence-based questions.

Interventions to facilitate shared decision making to address antibiotic use for acute respiratory infections in primary care.

BACKGROUND: Shared decision making is an important component of patient-centred care. It is a set of communication and evidence-based practice skills that elicits patients' expectations, clarifies any misperceptions and discusses the best available evidence for benefits and harms of treatment. Acute respiratory infections (ARIs) are one of the most common reasons for consulting in primary care and obtaining prescriptions for antibiotics. However, antibiotics offer few benefits for ARIs, and their excessive use contributes to antibiotic resistance - an evolving public health crisis. Greater explicit consideration of the benefit-harm trade-off within shared decision making may reduce antibiotic prescribing for ARIs in primary care. OBJECTIVES: To assess whether interventions that aim to facilitate shared decision making increase or reduce antibiotic prescribing for ARIs in primary care. SEARCH METHODS: We searched CENTRAL (2014, Issue 11), MEDLINE (1946 to November week 3, 2014), EMBASE (2010 to December 2014) and Web of Science (1985 to December 2014). We searched for other published, unpublished or ongoing trials by searching bibliographies of published articles, personal communication with key trial authors and content experts, and by searching trial registries at the National Institutes of Health and the World Health Organization. SELECTION CRITERIA: Randomised controlled trials (RCTs) (individual level or cluster-randomised), which evaluated the effectiveness of interventions that promote shared decision making (as the focus or a component of the intervention) about antibiotic prescribing for ARIs in primary care. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. Antibiotic prescribing was the primary outcome, and secondary outcomes included clinically important adverse endpoints (e.g. re-consultations, hospital admissions, mortality) and process measures (e.g. patient satisfaction). We assessed the risk of bias of all included trials and the quality of evidence. We contacted trial authors to obtain missing information where available. MAIN RESULTS: We identified 10 published reports of nine original RCTs (one report was a long-term follow-up of the original trial) in over 1100 primary care doctors and around 492,000 patients.The main risk of bias came from participants in most studies knowing whether they had received the intervention or not, and we downgraded the rating of the quality of evidence because of this.We meta-analysed data using a random-effects model on the primary and key secondary outcomes and formally assessed heterogeneity. Remaining outcomes are presented narratively.There is moderate quality evidence that interventions that aim to facilitate shared decision making reduce antibiotic use for ARIs in primary care (immediately after or within six weeks of the consultation), compared with usual care, from 47% to 29%: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55 to 0.68. Reduction in antibiotic prescribing occurred without an increase in patient-initiated re-consultations (RR 0.87, 95% CI 0.74 to 1.03, moderate quality evidence) or a decrease in patient satisfaction with the consultation (OR 0.86, 95% CI 0.57 to 1.30, low quality evidence). There were insufficient data to assess the effects of the intervention on sustained reduction in antibiotic prescribing, adverse clinical outcomes (such as hospital admission, incidence of pneumonia and mortality), or measures of patient and caregiver involvement in shared decision making (such as satisfaction with the consultation; regret or conflict with the decision made; or treatment compliance following the decision). No studies assessed antibiotic resistance in colonising or infective organisms. AUTHORS' CONCLUSIONS: Interventions that aim to facilitate shared decision making reduce antibiotic prescribing in primary care in the short term. Effects on longer-term rates of prescribing are uncertain and more evidence is needed to determine how any sustained reduction in antibiotic prescribing affects hospital admission, pneumonia and death.

Corticosteroids for the common cold.

BACKGROUND: The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. OBJECTIVES: To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). SELECTION CRITERIA: Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. MAIN RESULTS: We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. AUTHORS' CONCLUSIONS: Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.