'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

What the public think about participation in medical research during an influenza pandemic: an international cross-sectional survey.

OBJECTIVES: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic. STUDY DESIGN: This is an international cross-sectional survey. METHODS: We surveyed the views of nationally representative samples of people in Belgium, Poland, Spain, Ireland, the United Kingdom, Canada, Australia and New Zealand, using a scenario-based instrument during the 2017 regional influenza season. Descriptive and regression analyses were conducted. RESULTS: Of the 6804 respondents, 5572 (81.8%) thought pandemic-relevant research was important, and 5089 (74.8%) thought 'special rules' should be applied to make this research feasible. The respondents indicated willingness to take part in lower risk (4715, 69.3%) and higher risk (3585, 52.7%) primary care and lower risk (4780, 70.3%) and higher risk (4113, 60.4%) intensive care unit (ICU) study scenarios. For primary care studies, most (3972, 58.4%) participants preferred standard enrolment procedures such as prospective written informed consent, but 2327 (34.2%) thought simplified procedures would be acceptable. For ICU studies, 2800 (41.2%) preferred deferred consent, and 2623 (38.6%) preferred prospective third-party consent. Greater knowledge about pandemics, trust in a health professional, trust in the government, therapeutic misconception and having had ICU experience as a patient or carer predicted increased willingness to participate in pandemic-relevant research. CONCLUSIONS: Our study indicates current public support for pandemic-relevant clinical research. Tailored information and initiatives to advance research literacy and maintain trust are required to support pandemic-relevant research participation and engagement.

Risk factors for influenza-related complications in children during the 2009/10 pandemic: a UK primary care cohort study using linked routinely collected data.

Primary care clinicians have a central role in managing influenza/influenza-like illness (ILI) during influenza pandemics. This study identifies risk factors for influenza-related complications in children presenting with influenza/ILI in primary care. We conducted a cohort study using routinely collected linked data from the Clinical Practice Research Datalink on children aged 17 years and younger who presented with influenza/ILI during the 2009/10 pandemic. We calculated odds ratios (ORs) for potential risk factors in relation to influenza-related complications, complications requiring intervention, pneumonia, all-cause hospitalisation and hospitalisation due to influenza-related complications within 30 days of presentation. Analyses were adjusted for potential confounders including age, vaccination and socio-economic deprivation. Asthma was a risk factor for influenza-related complications (adjusted OR 1.48, 95% confidence interval (CI) 1.21-1.80, P < 0.001), complications requiring intervention (adjusted OR 1.44, 95% CI 1.11-1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95% CI 1.07-2.51, P = 0.024) and hospitalisation due to influenza-related complications (adjusted OR 2.46, 95% CI 1.09-5.56, P = 0.031). Neurological conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95% CI 1.50-12.07, P = 0.007) but not influenza-related complications (adjusted OR 1.46, 95% CI 0.83-2.56, P = 0.189). Community-based early interventions to prevent influenza-related clinical deterioration should therefore be primarily targeted at children with asthma and neurological conditions.

The management of acne vulgaris in primary care: a cohort study of consulting and prescribing patterns using the Clinical Practice Research Datalink.

BACKGROUND: Effective management of acne vulgaris in primary care involves support (usually provided over a number of consultations) and prescription of effective treatments. However, consulting and prescribing patterns for acne in primary care are not well described. OBJECTIVES: To describe the rate of primary-care consultations and follow-up consultations; prescribing patterns, including overall use of acne-related medications (ARMs); and initial and follow-up prescription for acne vulgaris in the U.K. METHODS: U.K. primary-care acne consultations and prescriptions for ARMs were identified in the Clinical Practice Research Datalink. Annual consultation rates (between 2004 and 2013) by age and sex, new consultations and consultations in the subsequent year were calculated, along with prescribing trends - during a new consultation and over the subsequent 90 days and year - using the number of registered patients as the denominator. RESULTS: Two-thirds (66·1%) of patients who had a new acne consultation had no further acne consultations in the subsequent year. Overall 26·7%, 24·9%, and 23·6% and 2·8% of patients were prescribed no ARM, an oral antibiotic, a topical antibiotic or an oral plus topical antibiotic, respectively, during a new acne consultation. In total 60·1% and 38·6% of patients prescribed an ARM received no further ARM prescriptions in the following 90 days and 1 year, respectively, despite most prescriptions being for 2 months or less. Prescribing rates for lymecycline and topical combined clindamycin and benzoyl peroxide increased substantially between 2004 and 2013. There were no important changes in consultation rates between 2004 and 2013. CONCLUSIONS: These data suggest that patients with acne are receiving a suboptimal initial choice of ARMs, longitudinal care and prescribing.

Analytic laboratory performance of a point of care urine culture kit for diagnosis and antibiotic susceptibility testing.

Currently available point-of-care (POC) diagnostic tests for managing urinary tract infections (UTIs) in general practice are limited by poor performance characteristics, and laboratory culture generally provides results only after a few days. This laboratory evaluation compared the analytic performance of the POC UK Flexicult(™) (Statens Serum Institut) (SSI) urinary kit for quantification, identification and antibiotic susceptibility testing and routine UK National Health Service (NHS) urine processing to an advanced urine culture method. Two hundred urine samples routinely submitted to the Public Health Wales Microbiology Laboratory were divided and: (1) analysed by routine NHS microbiological tests as per local laboratory standard operating procedures, (2) inoculated onto the UK Flexicult(™) SSI urinary kit and (3) spiral plated onto Colorex Orientation UTI medium (E&O Laboratories Ltd). The results were evaluated between the NHS and Flexicult(™ )methods, and discordant results were compared to the spiral plating method. The UK Flexicult(™) SSI urinary kit was compared to routine NHS culture for identification of a pure or predominant uropathogen at ≥ 10(5) cfu/mL, with a positive discordancy rate of 13.5% and a negative discordancy rate of 3%. The sensitivity and specificity were 86.7% [95% confidence interval (CI) 73.8-93.7] and 82.6% (95% CI 75.8-87.7), respectively. The UK Flexicult(™) SSI urinary kit was comparable to routine NHS urine processing in identifying microbiologically positive UTIs in this laboratory evaluation. However, the number of false-positive samples could lead to over-prescribing of antibiotics in clinical practice. The Flexicult(™) SSI kit could be useful as a POC test for UTIs in primary care but further pragmatic evaluations are necessary.

Predicting benign course and prolonged illness in lower respiratory tract infections: a 13 European country study.

BACKGROUND: Clinicians and patients are often uncertain about the likely clinical course of community-acquired lower respiratory tract infection (LRTI) in individual patients. We therefore set out to develop a prediction rule to identify patients at risk of prolonged illness and those with a benign course. METHODS: We determined which signs and symptoms predicted prolonged illness (moderately bad symptoms lasting >3 weeks after consultation) in 2690 adults presenting in primary care with LRTI in 13 European countries by using multilevel modelling. RESULTS: 212 (8.1%) patients experienced prolonged illness. Illness that had lasted >5 days at the time of presentation, >1 episode of cough in the preceding year, chronic use of inhaled pulmonary medication and diarrhoea independently predicted prolonged illness. Applying a rule based on these four variables, 3% of the patients with ≤ 1 variable present (n = 955, 37%) had prolonged illness. Patients with all four variables present had a 30% chance of prolonged illness (n = 71, 3%). CONCLUSIONS: Most patients with acute cough (>90%) recover within 3 weeks. A prediction rule containing four clinical items had predictive value for the risk of prolonged illness, but given its imprecision, appeared to have little clinical utility. Patients should be reassured that they are most likely to recover within three weeks and advised to re-consult if their symptoms persist beyond that period.

Otitis externa: what is the problem with getting it right? A mixed-methods study in primary and secondary care.

OBJECTIVE: Otitis externa accounts for 1.1-1.3 per cent of patient presentations in primary care and 25 per cent of urgent referrals to ENT. This study aimed to explore otitis externa clinical decision-making at the primary-secondary care interface, otitis externa prevalence and recent trends in antimicrobial resistance in otitis externa related bacterial isolates and ototopical prescribing. METHOD: This is a mixed-methods study drawing on data from primary and secondary care and open National Health Service sources. RESULTS: A total of 101 general practitioner survey respondents reported frequently prescribing oral antibiotics for otitis externa. General practitioner consultations for otitis externa increased 25 per cent over 15 years. General practitioner ototopical preparations cost the National Health Service £7 410 440 in 2006 and £11 325 241 in 2016. A total of 162 consecutive hospital otitis externa-related bacterial isolates yielded 128 pseudomonas species, with 18 that were resistant to gentamicin and 7 that were resistant to ciprofloxacin. Ten guidelines reviewed showed systematic inconsistencies. CONCLUSION: General practitioners reported regularly prescribing oral antibiotics for otitis externa. Antimicrobial drug resistance is common in otitis externa. The available guidance is suboptimal.

Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines.

European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription.

Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection.

We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p = 0.68) or green (coefficient -0.01; p = 0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p = 0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.

[Prevalence of microbiologically-confirmed influenza in patients with influenza-like illness in primary care and clinical and epidemiological characteristics]. / Prevalencia de gripe confirmada microbiológicamente en pacientes con síntomas gripales en atención primaria y características clínico-epidemiológicas.

OBJECTIVE: We evaluated the prevalence of microbiologically-confirmed influenza infection among patients with influenza-like symptoms and compared the clinical and epidemiological characteristics of patients with and without influenza infection. METHODS: Retrospective study of a cohort of patients with influenza-like symptoms from 2016 to 2018 who participated in a clinical trial in thirteen urban primary centres in Catalonia. Different epidemiological data were collected. Patients rated the different symptoms and signs on a Likert scale (absent, little problem, moderate problem and severe problem) and self-reported the measure of health status with the EuroQol visual analogue scale. A nasopharyngeal swab was taken for microbiological isolation of influenza and other microorganisms. RESULTS: A total of 427 patients were included. Microbiologically confirmed influenza was found in 240 patients (56.2%). The percentage of patients with moderate-to-severe cough, muscle aches, tiredness and dizziness was greater among patients with microbiologically confirmed influenza. The self-reported health status was significantly lower among patients with true flu infection (mean of 36.3 ± 18.2 vs 41.7 ± 17.8 in patients without influenza; p<0.001). CONCLUSIONS: Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza when intensity is not considered. However, the presence of moderate-to-severe cough, myalgias, tiredness and dizziness along with a poor health status is more common in patients with confirmed flu infection.

Lower respiratory tract infection in the community: associations between viral aetiology and illness course.

OBJECTIVES: This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection. METHODS: A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed. RESULTS: The PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65-0.96) and hMPV infections (AHR 0.77, 95% CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration. CONCLUSIONS: In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.

Are smokers with acute cough in primary care prescribed antibiotics more often, and to what benefit? An observational study in 13 European countries.

Little is known about actual clinical practice regarding management of smokers compared with ex-smokers and nonsmokers presenting with acute cough in primary care, and whether a lower threshold for prescribing antibiotics benefits smokers. This was a multicentre 13-country European prospective observational study of primary care clinician management of acute cough in consecutive immunocompetent adults presenting with an acute cough of

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis by bacterial and viral aetiology.

OBJECTIVE: We aimed to assess the effects of amoxicillin treatment in adult patients presenting to primary care with a lower respiratory tract infection (LRTI) who were infected with a potential bacterial, viral, or mixed bacterial/viral infection. METHODS: This multicentre randomized controlled trial focused on adults with LRTI not suspected for pneumonia. Patients were randomized to receive either antibiotic (amoxicillin 1 g) or placebo three times daily for 7 consecutive days using computer-generated random numbers (follow-up 28 days). In this secondary analysis of the trial, symptom duration (primary outcome), symptom severity (scored 0-6), and illness deterioration (reconsultation with new or worsening symptoms, or hospital admission) were analysed in pre-specified subgroups using regression models. Subgroups of interest were patients with a (strictly) bacterial, (strictly) viral, or combined infection, and patients with elevated values of procalcitonin, C-reactive protein, or blood urea nitrogen. RESULTS: 2058 patients (amoxicillin n = 1036; placebo n = 1022) were randomized. Treatment did not affect symptom duration (n = 1793). Patients from whom a bacterial pathogen only was isolated (n = 207) benefited from amoxicillin in that symptom severity (n = 804) was reduced by 0.26 points (95% CI -0.48 to -0.03). The odds of illness deterioration (n = 2024) was 0.24 (95% CI 0.11 to 0.53) times lower from treatment with amoxicillin when both a bacterial and a viral pathogen were isolated (combined infection; n = 198). CONCLUSIONS: Amoxicillin may reduce the risk of illness deterioration in patients with a combined bacterial and viral infection. We found no clinically meaningful benefit from amoxicillin treatment in other subgroups.

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries.

OBJECTIVES: To describe the role of bacteria (including bacterial resistance), viruses (including those recently described) and mixed bacterial-viral infections in adults presenting to primary care with lower respiratory tract infection (LRTI). METHODS: In all, 3104 adults with LRTI were enrolled, of whom 141 (4.5%) had community-acquired pneumonia (CAP), and 2985 matched controls in a prospective study in 16 primary care networks in Europe, and followed patients up at 28-35 days. We detected Streptococcus pneumoniae and Haemophilus influenzae and assessed susceptibility, atypical bacteria and viruses. RESULTS: A potential pathogen was detected in 1844 (59%) (in 350 (11%) bacterial pathogens only, in 1190 (38%) viral pathogens only, and in 304 (10%) both bacterial and viral pathogens). The most common bacterial pathogens isolated were S. pneumoniae (5.5% overall, 9.2% in CAP patients) and H. influenzae (5.4% overall, 14.2% in CAP patients). Less than 1% of S. pneumoniae were highly resistant to penicillin and 12.6% of H. influenzae were ß-lactamase positive. The most common viral pathogens detected were human rhinovirus (20.1%), influenza viruses (9.9%), and human coronavirus (7.4%). Influenza virus, human parainfluenza viruses and human respiratory syncytial virus as well as human rhinovirus, human coronavirus and human metapneumovirus were detected significantly more frequently in LRTI patients than in controls. CONCLUSIONS: A bacterial pathogen is identified in approximately one in five adult patients with LRTI in primary care, and a viral pathogen in just under half, with mixed infections in one in ten. Penicillin-resistant pneumococci and ß-lactamase-producing H. influenzae are uncommon. These new findings support a restrictive approach to antibiotic prescribing for LRTI and the use of first-line, narrow-spectrum agents in primary care.

Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children.

BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated developmental delay. Treatment remains controversial. OBJECTIVES: To examine evidence for or against treating children with hearing loss associated with OME with systemic or topical intranasal steroids. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 4 2005, MEDLINE (1966 to 2006), EMBASE (1974 to 2006), and the CINAHL, LILACS, Zetoc, IndMED, SAMED, KoreaMed, MEDCARIB and Cambridge Scientific Abstracts databases in January 2006. SELECTION CRITERIA: Randomised controlled trials of oral and topical intranasal steroids, either alone or in combination with another agent such as an antibiotic, were included. EXCLUSIONS: publications in abstract form only; uncontrolled, non-randomised or retrospective studies; studies reporting outcomes with ears (rather than children). DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by the authors independently using standardised data extraction forms and methods. The methodological quality of the included studies was independently assessed by the authors as described in the Cochrane Handbook. Dichotomous results were expressed as an odds ratio using a fixed-effect model together with the 95% confidence intervals. Continuous data were analysed using the weighted mean difference in a fixed-effect model. Tests for heterogeneity between studies were performed using a Mantel-Haenszel approach. In trials with a cross-over design, post cross-over treatment data were not used. MAIN RESULTS: No study prospectively documented hearing loss associated with OME prior to randomisation. Follow up was mainly short term. The odds ratio for OME persisting after short-term follow up in children treated with oral steroids compared to control was 0.22 (95% CI 0.08 to 0.63). The odds ratio for OME persisting after short-term follow up for children treated with oral steroids plus antibiotic compared to control plus antibiotic was 0.37 (95% CI 0.25 to 0.56). However, there was significant heterogeneity between studies included in the latter comparison (P < 0.01). Trends favoured steroids for most other comparisons, but confidence intervals included unity. There was no evidence of benefit for steroid treatment for OME or hearing loss associated with OME in the longer term. AUTHORS' CONCLUSIONS: Both oral and topical intranasal steroids alone or in combination with an antibiotic lead to a quicker resolution of OME in the short term, however, there is no evidence of longer term benefit.

Interventions for cutaneous molluscum contagiosum.

BACKGROUND: Molluscum contagiosum is a common skin infection, caused by a virus, which will usually resolve within months in people with a normal immune system. Many treatments have been promoted for molluscum contagiosum but a clear evidence base supporting them is lacking. OBJECTIVES: To assess the effects of management strategies (including waiting for natural resolution) for cutaneous, non-genital molluscum contagiosum in healthy people. SEARCH STRATEGY: We searched the Skin Group Specialised Register (March 2004), the Cochrane Central Register of Controlled Trials (2004, Issue 2), MEDLINE (from 1966 to March 2004), EMBASE (from 1980 to March 2004) and LILACS (from 1982 to March 2004) databases. We also searched reference lists and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomised controlled trials for treatment of molluscum contagiosum were investigated. Trials on sexually transmitted molluscum contagiosum and in people with lowered immunity (including those with HIV infection) were excluded. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent authors. As similar comparisons between two interventions were not made in more than one study, statistical pooling was not performed. MAIN RESULTS: Five studies, with a total number of 137 participants, examined the effects of topical (three studies), systemic and homoeopathic interventions (one study each). Limited evidence was found for sodium nitrite co-applied with salicylic acid compared to salicylic acid alone (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.23 to 9.92). No statistically significant differences were found for topical povidone iodine plus salicylic acid compared to povidone iodine alone (RR of cure 1.67, 95% CI 0.81 to 3.41) or compared to salicylic acid alone. Also no statistically significant differences were found for potassium hydroxide compared to placebo; systemic treatment with cimetidine versus placebo or systemic treatment with calcarea carbonica, a homoeopathic drug, versus placebo (RR 5.57, 95% CI 0.93 to 33.54). Study limitations included no blinding (two studies), many dropouts (three studies) and no intention-to-treat analysis (two studies); small study sizes may have led to important differences being missed. None of the evaluated treatment options were associated with serious adverse effects. AUTHORS' CONCLUSIONS: No single intervention has been shown to be convincingly effective in treating molluscum contagiosum.

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common and rises with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular vitamin B12 which is a considerable source of work for health care professionals. Several case control and case series studies have reported equal efficacy of oral administration of vitamin B12 but it is rarely prescribed in this form, other than in Sweden and Canada. Doctors may not be prescribing oral formulations because they are unaware of this option or have concerns regarding effectiveness. OBJECTIVES: To assess the effectiveness of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH STRATEGY: Searches were undertaken of The Cochrane Library, MEDLINE, EMBASE and Lilacs in early 2005. The bibliographies of all relevant papers identified using this strategy were searched. In addition we contacted authors of relevant identified studies and Vitamin B12 research and pharmaceutical companies to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) examining the use of oral or intramuscular vitamin B12 to treat vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: All abstracts or titles identified by the electronic searches were independently scrutinised by two reviewers. When a difference between reviewers arose, we obtained and reviewed a hard copy of the papers and made decisions by consensus. We obtained a copy of all pre-selected papers and two researchers independently extracted the data from these studies using piloted data extraction forms. The whole group checked whether inclusion and exclusion criteria were met, and disagreement was decided by consensus. The methodological quality of the included studies was independently assessed by two researchers and disagreements were brought back to the whole group and resolved by consensus. MAIN RESULTS: Two RCT's comparing oral with intramuscular administration of vitamin B12 met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to four months. High oral doses of B12 (1000 mcg and 2000 mcg) were as effective as intramuscular administration in achieving haematological and neurological responses. AUTHORS' CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.

Steroids for otitis media with effusion: a systematic review.

BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated delayed language development in children. Treatment remains controversial. OBJECTIVE: To examine evidence for or against treating OME with systemic or topical nasal steroids. DATA SOURCES: We searched the Cochrane Controlled Trials Register using the terms otitis media; otitis media with effusion; glue ear; or OME and steroids; glucocorticoids; glucocorticoids, synthetic; glucocorticoids, topical; or anti-inflammatory agents, steroidal; or various combinations of these terms. EMBASE and MEDLINE were also searched. STUDY SELECTION: Randomized controlled trials of oral and topical nasal steroids, either alone or in combination with another agent such as an antibiotic, were included. Ten studies met the inclusion criteria. DATA EXTRACTION: Data extraction and methodological quality assessment were performed by the 2 of us (C.C.B. and J.H.v.d.V.) independently, using standardized methods described in the Cochrane Collaboration Handbook. DATA SYNTHESIS: The odds ratio for OME persisting after short-term follow-up in children treated with oral steroids compared with a control was 0.22 (95% confidence interval, 0.08 = 0.63), and was 0.32 (95% confidence interval, 0.20 = 0.52) for children treated with oral steroids plus an antibiotic compared with a control plus an antibiotic. Trends favored steroids for most other comparisons, but confidence intervals included unity. Trends favored steroids for most other comparisons, but confidence intervals included unity. CONCLUSIONS: Steroids alone or combined with an antibiotic lead to a quicker resolution of OME in the short-term. However, there is no evidence for a long-term benefit from treating hearing loss associated with OME with either oral or topical nasal steroids. These treatments are, therefore, not recommended.