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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Antibiotics for acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 1997 and previously updated in 1999, 2005, 2009 and 2013. OBJECTIVES: To assess the effects of antibiotics for children with AOM. SEARCH METHODS: We searched CENTRAL (2015, Issue 3), MEDLINE (1966 to April week 3, 2015), OLDMEDLINE (1958 to 1965), EMBASE (January 1990 to April 2015), Current Contents (1966 to April 2015), CINAHL (2008 to April 2015) and LILACS (2008 to April 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing 1) antimicrobial drugs with placebo and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: For the review of antibiotics against placebo, 13 RCTs (3401 children and 3938 AOM episodes) from high-income countries were eligible and had generally low risk of bias. The combined results of the trials revealed that by 24 hours from the start of treatment, 60% of the children had recovered whether or not they had placebo or antibiotics. Pain was not reduced by antibiotics at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01) but almost a third fewer had residual pain at two to three days (RR 0.70, 95% CI 0.57 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) 20). A quarter fewer had pain at four to seven days (RR 0.76, 95% CI 0.63 to 0.91; NNTB 16) and two-thirds fewer had pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7) compared with placebo. Antibiotics did reduce the number of children with abnormal tympanometry findings at two to four weeks (RR 0.82, 95% CI 0.74 to 0.90; NNTB 11), at six to eight weeks (RR 0.88, 95% CI 0.78 to 1.00; NNTB 16) and the number of children with tympanic membrane perforations (RR 0.37, 95% CI 0.18 to 0.76; NNTB 33) and halved contralateral otitis episodes (RR 0.49, 95% CI 0.25 to 0.95; NNTB 11) compared with placebo. However, antibiotics neither reduced the number of children with abnormal tympanometry findings at three months (RR 0.97, 95% CI 0.76 to 1.24) nor the number of children with late AOM recurrences (RR 0.93, 95% CI 0.78 to 1.10) when compared with placebo. Severe complications were rare and did not differ between children treated with antibiotics and those treated with placebo. Adverse events (such as vomiting, diarrhoea or rash) occurred more often in children taking antibiotics (RR 1.38, 95% CI 1.19 to 1.59; number needed to treat for an additional harmful outcome (NNTH) 14). Funnel plots do not suggest publication bias. Individual patient data meta-analysis of a subset of included trials found antibiotics to be most beneficial in children aged less than two years with bilateral AOM, or with both AOM and otorrhoea.For the review of immediate antibiotics against expectant observation, five trials (1149 children) from high-income countries were eligible and had low to moderate risk of bias. Four trials (1007 children) reported outcome data that could be used for this review. From these trials, data from 959 children could be extracted for the meta-analysis of pain at three to seven days. No difference in pain was detectable at three to seven days (RR 0.75, 95% CI 0.50 to 1.12). One trial (247 children) reported data on pain at 11 to 14 days. Immediate antibiotics were not associated with a reduction in the number of children with pain (RR 0.91, 95% CI 0.75 to 1.10) compared with expectant observation. Additionally, no differences in the number of children with abnormal tympanometry findings at four weeks, tympanic membrane perforations and AOM recurrence were observed between groups. No serious complications occurred in either the antibiotic or the expectant observation group. Immediate antibiotics were associated with a substantial increased risk of vomiting, diarrhoea or rash compared with expectant observation (RR 1.71, 95% CI 1.24 to 2.36; NNTH 9).Results from an individual patient data meta-analysis including data from six high-quality trials (1643 children) that were also included as individual trials in our review showed that antibiotics seem to be most beneficial in children younger than two years of age with bilateral AOM (NNTB 4) and in children with both AOM and otorrhoea (NNTB 3). AUTHORS' CONCLUSIONS: This review reveals that antibiotics have no early effect on pain, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks and at six to eight weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. Therefore clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics. Antibiotics are most useful in children under two years of age with bilateral AOM, or with both AOM and otorrhoea. For most other children with mild disease in high-income countries, an expectant observational approach seems justified.

Antibiotics for preventing recurrent sore throat.

BACKGROUND: Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. OBJECTIVES: To assess the effects of antibiotics in patients with recurrent sore throat. SEARCH METHODS: The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. MAIN RESULTS: We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

Exercise versus no exercise for the occurrence, severity and duration of acute respiratory infections.

BACKGROUND: Acute respiratory infections (ARIs) last for less than 30 days and are the most common acute diseases affecting people worldwide. Exercise has been shown to improve health generally and may be effective in reducing the occurrence, severity and duration of acute respiratory infections. OBJECTIVES: To evaluate the effectiveness of exercise for altering the occurrence, severity or duration of acute respiratory infections. SEARCH METHODS: We searched CENTRAL (2014, Issue 6), MEDLINE (1948 to July week 1, 2014), EMBASE (2010 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014), SPORTDiscus (1985 to July 2014), PEDro (searched on 11 July 2014), OTseeker (searched on 11 July 2014), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (searched on 11 July 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of exercise for ARIs in the general population. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials using a standard form. We contacted trial authors to request missing data. One review author entered data and a second review author checked this. There were sufficient differences in the populations trialled and in the nature of the interventions to use the random-effects model (which makes fewer assumptions than the fixed-effect model) in the analysis. MAIN RESULTS: We included 11 trials involving 904 adults, published between 1990 and 2014. Eight studies were conducted in the USA, and one each in Canada, Spain and Turkey. Sample sizes ranged from 20 to 154 participants aged between 18 and 85 years old. The proportion of female participants varied between 52% and 100%. The duration of follow-up in the studies varied from seven days to 12 months. The exercise type most prescribed for the intervention was aerobic (walking in 70% of the studies, or bicycle riding or treadmill) at least five times a week. Duration was 30 to 45 minutes at moderate intensity. Participants were supervised in 90% of the studies.For four of the primary outcomes the results did not differ significantly and all were low-quality evidence (number of ARI episodes per person per year, rate ratio 0.91 (95% confidence interval (CI) 0.59 to 1.42); proportion of participants who experienced at least one ARI over the study period, risk ratio 0.76 (95% CI 0.57 to 1.01); severity of ARI symptoms, mean difference (MD) -110 (95% CI -324 to 104); and number of symptom days in the follow-up period, MD -2.1 days (95% CI -4.4 to 0.3)). However, one primary outcome, the number of symptom days per episode of illness, was reduced in those participants who exercised (MD -1.1 day, 95% CI -1.7 to -0.5, moderate-quality evidence).We found no significant differences for the secondary outcomes (laboratory parameters (blood lymphocytes, salivary secretory immunoglobulin and neutrophils); quality of life outcomes; cost-effectiveness and exercise-related injuries).There was good adherence to the intervention with no difference between the exercise and non-exercise groups.We rated the quality of evidence for the primary outcomes as low for most outcomes using the GRADE criteria: allocation concealment was not reported and there was a lack of blinding; in addition, there was imprecision (the CI is very wide because of a small number of participants) and inconsistency, which may be due to differences in study design. AUTHORS' CONCLUSIONS: We cannot determine whether exercise is effective at altering the occurrence, severity or duration of acute respiratory infections. One analysis of four trials suggests that the number of days of illness per episode of infection might be reduced by exercise. The small size of the studies, risk of bias and heterogeneous populations trialled all contribute to the uncertainty. Larger studies, with less risk of bias from patient selection, blinding of outcomes assessors, reporting of all outcomes measured and with registration of study protocols, are required to settle the question.

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.

Antibiotics for bronchiolitis in children under two years of age.

BACKGROUND: Bronchiolitis is a serious, potentially life-threatening respiratory illness commonly affecting babies. It is often caused by respiratory syncytial virus (RSV). Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia or respiratory failure. Nevertheless, they are often used. OBJECTIVES: To evaluate the effectiveness of antibiotics for bronchiolitis in children under two years of age compared to placebo or other interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 6), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register, and the Database of Abstracts of Reviews of Effects, MEDLINE (1966 to June 2014), EMBASE (1990 to June 2014) and Current Contents (2001 to June 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics to placebo in children under two years diagnosed with bronchiolitis, using clinical criteria (including respiratory distress preceded by coryzal symptoms with or without fever). Primary clinical outcomes included time to resolution of signs or symptoms (pulmonary markers included respiratory distress, wheeze, crepitations, oxygen saturation and fever). Secondary outcomes included hospital admissions, length of hospital stay, readmissions, complications or adverse events and radiological findings. DATA COLLECTION AND ANALYSIS: Two review authors independently analysed the search results. MAIN RESULTS: We included seven studies with a total of 824 participants. The results of these seven included studies were often heterogeneous, which generally precluded meta-analysis, except for deaths, length of supplemental oxygen use and length of hospital admission.In this update, we included two new studies (281 participants), both comparing azithromycin with placebo. They found no significant difference for length of hospital stay, duration of oxygen requirement and readmission. These results were similar to an older study (52 participants) that demonstrated no significant difference comparing ampicillin and placebo for length of illness.One small study (21 participants) with higher risk of bias randomised children with proven RSV infection to clarithromycin or placebo and found a trend towards a reduction in hospital readmission with clarithromycin.The three studies providing adequate data for days of supplementary oxygen showed no difference between antibiotics and placebo (pooled mean difference (MD) (days) -0.20; 95% confidence interval (CI) -0.72 to 0.33). The three studies providing adequate data for length of hospital stay, similarly showed no difference between antibiotics (azithromycin) and placebo (pooled MD (days) -0.58; 95% CI -1.18 to 0.02).Two studies randomised children to intravenous ampicillin, oral erythromycin and control and found no difference for most symptom measures.There were no deaths reported in any of the arms of the seven included studies. No other adverse effects were reported. AUTHORS' CONCLUSIONS: This review did not find sufficient evidence to support the use of antibiotics for bronchiolitis, although research may be justified to identify a subgroup of patients who may benefit from antibiotics. Further research may be better focused on determining the reasons that clinicians use antibiotics so readily for bronchiolitis, how to reduce their use and how to reduce clinician anxiety about not using antibiotics.

Systemic corticosteroids for acute sinusitis.

BACKGROUND: Acute sinusitis is the inflammation and swelling of the nasal and paranasal mucous membranes and is a common reason for patients to seek primary care consultations. The related impairment of daily functioning and quality of life is attributable to symptoms such as facial pain and nasal congestion. OBJECTIVES: To assess the effects of systemic corticosteroids on clinical response rates and to determine adverse effects and relapse rates of systemic corticosteroids compared to placebo or standard clinical care in children and adults with acute sinusitis. SEARCH METHODS: We searched CENTRAL (2014, Issue 1), MEDLINE (1966 to February week 1, 2014) and EMBASE (January 2009 to February 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing systemic corticosteroids to placebo or standard clinical care for patients with acute sinusitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the methodological quality of the trials and extracted data. MAIN RESULTS: Five RCTs with a total of 1193 adult participants met our inclusion criteria. We judged methodological quality to be moderate in four trials and high in one trial. Acute sinusitis was defined clinically in all trials. However, the three trials performed in ear, nose and throat (ENT) outpatient clinics also used radiological assessment as part of their inclusion criteria. All participants were assigned to either oral corticosteroids (prednisone 24 mg to 80 mg daily or betamethasone 1 mg daily) or the control treatment (placebo in four trials and non-steroidal anti-inflammatory drugs (NSAIDs) in one trial). In four trials antibiotics were prescribed in addition to oral corticosteroids or control treatment, while one trial investigated the effects of oral corticosteroids as a monotherapy.When combining data from the five trials, participants treated with oral corticosteroids were more likely to have short-term resolution or improvement of symptoms than those receiving the control treatment: at days three to seven (risk ratio (RR) 1.3, 95% confidence interval (CI) 1.1 to 1.6; risk difference (RD) 17%, 95% CI 6% to 29%) and at days four to 14 (RR 1.2, 95% CI 1.0 to 1.5; RD 14%, 95% CI 1% to 27%). A sensitivity analysis including the four trials with placebo as a control treatment showed similar results but with a lesser effect size: at days three to seven (RR 1.2, 95% CI 1.1 to 1.3; RD 11%, 95% CI 4% to 17%) and days four to 14 (RR 1.1, 95% CI 1.0 to 1.2; RD 8%, 95% CI 2% to 13%). Statistical heterogeneity was high for many analyses. Subgroup analyses revealed that corticosteroid monotherapy had no beneficial effects. Furthermore, scenario analysis showed that outcomes missing from the trial reports might have introduced attrition bias (a worst-case scenario showed no statistically significant beneficial effect of oral corticosteroids). No trial reported effects on relapse or recurrence rates. Reported side effects in patients treated with oral corticosteroids were mild (nausea, vomiting, gastric complaints) and did not significantly differ from those receiving placebo. AUTHORS' CONCLUSIONS: Oral corticosteroids as a monotherapy appear to be ineffective for adult patients with clinically diagnosed acute sinusitis. Current data on the use of oral corticosteroids as an adjunctive therapy to oral antibiotics are limited: almost all trials are performed in secondary care settings and there is a significant risk of bias. This limited evidence suggests that oral corticosteroids in combination with antibiotics may be modestly beneficial for short-term relief of symptoms in acute sinusitis, with a number needed to treat to benefit of seven for resolution or symptom improvement. A large primary care factorial trial is needed to establish whether oral corticosteroids offer additional benefits over antibiotics in acute sinusitis.

Neuraminidase inhibitors for preventing and treating influenza in adults and children.

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 describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours, 95% CI 12 to 47 hours, P = 0.001). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days, P < 0.00001), equating to a reduction in the mean duration of symptoms from 6.6 to 6.0 days. The effect in children was not significant. In subgroup analysis we found no evidence of a difference in treatment effect for zanamivir on time to first alleviation of symptoms in adults in the influenza-infected and non-influenza-infected subgroups (P = 0.53). Hospitalisations. Treatment of adults with oseltamivir had no significant effect on hospitalisations: risk difference (RD) 0.15% (95% CI -0.78 to 0.91). There was also no significant effect in children or in prophylaxis. Zanamivir hospitalisation data were unreported. Serious influenza complications or those leading to study withdrawal. In adult treatment trials, oseltamivir did not significantly reduce those complications classified as serious or those which led to study withdrawal (RD 0.07%, 95% CI -0.78 to 0.44), nor in child treatment trials; neither did zanamivir in the treatment of adults or in prophylaxis. There were insufficient events to compare this outcome for oseltamivir in prophylaxis or zanamivir in the treatment of children. Pneumonia. Oseltamivir significantly reduced self reported, investigator-mediated, unverified pneumonia (RD 1.00%, 95% CI 0.22 to 1.49); number needed to treat to benefit (NNTB) = 100 (95% CI 67 to 451) in the treated population. The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia. In prophylaxis, zanamivir significantly reduced the risk of self reported, investigator-mediated, unverified pneumonia in adults (RD 0.32%, 95% CI 0.09 to 0.41); NNTB = 311 (95% CI 244 to 1086), but not oseltamivir. Bronchitis, sinusitis and otitis media. Zanamivir significantly reduced the risk of bronchitis in adult treatment trials (RD 1.80%, 95% CI 0.65 to 2.80); NNTB = 56 (36 to 155), but not oseltamivir. Neither NI significantly reduced the risk of otitis media and sinusitis in both adults and children. Harms of treatment. Oseltamivir in the treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90 to 7.39); number needed to treat to harm (NNTH) = 28 (95% CI 14 to 112) and vomiting (RD 4.56%, 95% CI 2.39 to 7.58); NNTH = 22 (14 to 42). The proportion of participants with four-fold increases in antibody titre was significantly lower in the treated group compared to the control group (RR 0.92, 95% CI 0.86 to 0.97, I(2) statistic = 0%) (5% absolute difference between arms). Oseltamivir significantly decreased the risk of diarrhoea (RD 2.33%, 95% CI 0.14 to 3.81); NNTB = 43 (95% CI 27 to 709) and cardiac events (RD 0.68%, 95% CI 0.04 to 1.0); NNTB = 148 (101 to 2509) compared to placebo during the on-treatment period. There was a dose-response effect on psychiatric events in the two oseltamivir "pivotal" treatment trials, WV15670 and WV15671, at 150 mg (standard dose) and 300 mg daily (high dose) (P = 0.038). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75 to 10.29); NNTH = 19 (95% CI 10 to 57). There was a significantly lower proportion of children on oseltamivir with a four-fold increase in antibodies (RR 0.90, 95% CI 0.80 to 1.00, I(2) = 0%). Prophylaxis. In prophylaxis trials, oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals (oseltamivir: RD 3.05% (95% CI 1.83 to 3.88); NNTB = 33 (26 to 55); zanamivir: RD 1.98% (95% CI 0.98 to 2.54); NNTB = 51 (40 to 103)) and in households (oseltamivir: RD 13.6% (95% CI 9.52 to 15.47); NNTB = 7 (6 to 11); zanamivir: RD 14.84% (95% CI 12.18 to 16.55); NNTB = 7 (7 to 9)). There was no significant effect on asymptomatic influenza (oseltamivir: RR 1.14 (95% CI 0.39 to 3.33); zanamivir: RR 0.97 (95% CI 0.76 to 1.24)). Non-influenza, influenza-like illness could not be assessed due to data not being fully reported. In oseltamivir prophylaxis studies, psychiatric adverse events were increased in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07 to 2.76); NNTH = 94 (95% CI 36 to 1538) in the study treatment population. Oseltamivir increased the risk of headaches whilst on treatment (RD 3.15%, 95% CI 0.88 to 5.78); NNTH = 32 (95% CI 18 to 115), renal events whilst on treatment (RD 0.67%, 95% CI -2.93 to 0.01); NNTH = 150 (NNTH 35 to NNTB > 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence.