Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis.

BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.

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.

Feasibility and acceptability of a brief routine weight management intervention for postnatal women embedded within the national child immunisation programme in primary care: randomised controlled cluster feasibility trial.

BACKGROUND: The prevalence of obesity in women continues to rise and pregnancy is a high-risk time for excessive weight gain. The period after childbirth represents an opportunity to offer women support to manage their weight. The primary aim here was to investigate the acceptability and feasibility of delivering a self-management intervention to postnatal women to support weight loss, embedded within the national child immunisation programme. METHODS: The research involved a randomised controlled cluster feasibility trial. Data were collected at baseline and 3 months later. Twenty-eight postnatal women living with overweight or obesity were recruited via Birmingham Women Hospital or general practices. Babies are routinely immunised at 2, 3 and 4 months of age; the intervention was embedded within these appointments. The intervention involved brief motivation/support by practice nurses to encourage participants to make healthier lifestyle choices through self-monitoring of weight and signposting to an online weight management programme, when they attended their practice to have their child immunised. The role of the nurse was to provide external accountability for weight loss. Participants were asked to weigh themselves weekly and record this on a record card or using the online programme. The weight goal was for participants to lose 0.5 to 1 kg per week. Usual care received a healthy lifestyle leaflet. The primary outcome was the feasibility of a phase III trial to test the subsequent effectiveness of the intervention, as assessed against three stop-go traffic light criteria (recruitment, adherence to regular self-weighing and registration with an online weight management programme). RESULTS: The traffic light stop-go criteria results were red for recruitment (28/80, 35% of target), amber for registration with the online weight loss programme (9/16, 56%) and green for adherence to weekly self-weighing (10/16, 63%). Nurses delivered the intervention with high fidelity. DISCUSSION: Whilst participants and nurses followed the trial protocol well and adherence to self-weighing was acceptable, recruitment was challenging and there is scope to improve engagement with the online weight management programme component of the intervention. TRIAL REGISTRATION: ISRCTN 12209332 . Registration date is 04/12/18.

Beliefs about inevitable decline among home-living older adults at risk of malnutrition: a qualitative study.

BACKGROUND: Approximately 14% of free-living adults aged ≥65 years are at risk of malnutrition. Malnutrition screen and treat interventions in primary care are few, show mixed results, and the advice given is not always accepted and followed. We need to better understand the experiences and contexts of older adults when aiming to develop interventions that are engaging, optimally persuasive and relevant. METHODS: Using the Person-based Approach, we carried out 23 semi-structured interviews with purposively selected adults ≥65 years with chronic health or social conditions associated with malnutrition risk. Thematic analysis informed the development of key principles to guide planned intervention development. RESULTS: We found that individuals' beliefs about an inevitable decline in appetite and eating in older age compound the many and varied physical and physiological barriers that they experience. Also, we found that expectations of decline in appetite and physical ability may encourage resignation, reduce self-efficacy to overcome barriers, and reduce motivation to address weight loss and/or recognise it as an issue that needs to be addressed. Fear of loss of independence may also reduce the likelihood of asking general practitioners for advice. CONCLUSIONS: The key findings identified include a sense of resignation, multiple different barriers to eating and a need for independence, each underpinned by the expectation of a decline in older adulthood. Interventions need to address misperceptions about the inevitability of decline, highlight how and why diet recommendations are somewhat different from recommendations for the general population, and suggest easy ways to increase food intake that address common barriers.

Informal trade in livestock and livestock products.

Informal trade in livestock and livestock products is of special concern because of the risk of spreading animal and human diseases. At the same time, informal trade can contribute to people's livelihoods and food security, especially in lowand middle-income countries. Informal trade may involve legal or illegal products. It may be domestic (or internal) or involve neighbouring countries; it may take place within a region or between distant countries. Entrepôt trade (or 're-exports') is a significant form of informal trade in livestock products. Pastoral mobility often entails movement across boundaries for trade and much of this is also informal. There are important economic, social, political, and environmental drivers for informal trade which make it difficult to eliminate. Informal livestock trade may be largely ignored by the authorities, implicitly encouraged, made less attractive, forcibly suppressed, or actively engaged with, in an attempt to mitigate its risks and enhance its benefits. To identify the optimal management approach, it is crucial to understand the importance and characteristics of informal trade, its benefits and risks, and the feasibility and cost-effectiveness of different strategies to address it. The authors describe a case study from East Africa to explore some of the issues raised by informal trade.

Le commerce informel d'animaux d'élevage et de produits d'origine animale est un sujet particulièrement préoccupant en raison du risque de propagation de maladies animales et humaines associé à cette activité. En même temps, le commerce informel apporte aux populations des moyens de subsistance et contribue à leur sécurité alimentaire, en particulier dans les pays à revenu faible et intermédiaire. Le commerce informel peut porter sur des produits licites ou illicites. Il peut être domestique (marché intérieur) ou inclure les pays avoisinants ; il peut se dérouler dans une même région ou bien entre pays distants. La réexportation (ou recours aux entrepôts francs) constitue une modalité importante du commerce informel de produits issus de l'élevage. Le pastoralisme, qui se caractérise par sa mobilité, entraîne souvent des mouvements transfrontaliers en vue de transactions commerciales dont une grande partie est également informelle. Il existe d'importants moteurs économiques, sociaux, politiques et environnementaux qui favorisent le commerce informel et le rendent difficile à éliminer. Les réponses déployées par les pouvoirs publics face au commerce informel d'animaux d'élevage sont diverses : l'ignorer, l'encourager implicitement, le rendre moins attractif, le réprimer par la force, ou l'accompagner de manière active, le but étant d'atténuer les risques ou d'optimiser les bénéfices qui lui sont associés. Pour définir la meilleure approche de gestion, il est indispensable de bien comprendre l'importance et les caractéristiques du commerce informel, ses bénéfices et ses risques, ainsi que la faisabilité des différentes stratégies d'intervention et leur efficacité au regard de leur coût. Les auteurs décrivent une étude menée en Afrique de l'Est qui permet d'analyser certaines questions soulevées par le commerce informel.

El comercio informal de ganado y productos ganaderos suscita especial inquietud porque trae consigo el riesgo de propagación de enfermedades animales y humanas. Al mismo tiempo, puede contribuir al sustento y a la seguridad alimentaria de las personas, especialmente en los países de renta baja y de renta media. Este tipo de comercio puede tratar con productos legales o ilegales. A veces las transacciones son internas (nacionales), a veces interesan a países contiguos y otras veces tienen lugar dentro de una gran región o entre países distantes. El comercio de reexportación (o uso de puertos francos) es una de las formas importantes que reviste el comercio informal de productos ganaderos. La movilidad propia de las poblaciones que viven del pastoreo las lleva a menudo a cruzar fronteras para entablar transacciones comerciales que son mayoritariamente informales. El comercio informal obedece a importantes factores económicos, sociales, políticos y ambientales que lo alimentan y hacen difícil eliminarlo. La postura de las autoridades respecto del comercio informal de ganado es muy variable: a veces se desentienden en gran medida de él, otras veces lo alientan tácitamente, en ocasiones adoptan medidas para restarle atractivo o lo reprimen por la fuerza e incluso a veces participan activamente en él, tratando así de mitigar los riesgos que entraña y de potenciar sus beneficios. Para determinar la forma idónea de manejar el fenómeno del comercio informal es básico aprehender su importancia y características, sus ventajas y riesgos y la viabilidad y relación costo-eficacia de las distintas posturas que se pueden adoptar ante él. Los autores parten de un estudio monográfico realizado en el África Oriental para abordar algunos de los interrogantes que suscita el comercio informal.

Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group.

BACKGROUND: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. METHODS: An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. RESULTS: We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. CONCLUSIONS: Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.

Young people's perceptions of acne and acne treatments: secondary analysis of qualitative interview data.

BACKGROUND: Acne vulgaris is a common skin condition affecting approximately 95% of adolescents to some extent. First-line treatments are topical preparations but nonadherence is common. A substantial proportion of patients take long courses of oral antibiotics, associated with antibiotic resistance. OBJECTIVES: This study aimed to explore young people's views and experiences of acne and its treatments. METHODS: We report a secondary thematic analysis of interview data collected by researchers in the Health Experiences Research Group (HERG), University of Oxford. A total of 25 transcripts from young people aged 13-24 years with acne were included. RESULTS: Acne is often perceived as a short-term self-limiting condition of adolescence and this appears to have implications for seeking treatment or advice. Participants widely perceived topical treatments as being ineffective, which seemed related to unrealistic expectations around speed of onset of action. Many participants felt they had tried all available topical treatments, although were unsure what was in them or unaware of differences between cosmetic and pharmaceutical treatments. They had concerns around how to use topicals 'properly' and how to avoid side-effects. They were also concerned about the side-effects or necessity of oral treatments, although few seemed aware of antibiotic resistance. CONCLUSIONS: People with acne need support to manage their condition effectively, particularly a better understanding of different topicals, how to use them and how to avoid side-effects. Unrealistic expectations about the onset of action of treatments appears to be a common cause of frustration and nonadherence. Directing people towards accessible evidence-based information is crucial. What's already known about this topic? There is a common perception that acne is a short-term condition that will resolve without treatment. Previous research has shown that nonadherence to topical treatments is common and that oral antibiotics are the most commonly prescribed treatment for acne in the U.K. Further research is needed to understand how young people perceive acne treatments and the implications of this for treatment adherence and self-management. What does this study add? People often said they had tried all available topical preparations for acne, but seemed confused between cosmetic and pharmaceutical treatments. People seemed unsure how to use topical treatments 'properly' or how to avoid side-effects. This was rarely discussed with health professionals. People's perception of acne as a short-term condition appeared to influence their expectations around onset of action of treatment and their views about its effectiveness and necessity. What are the clinical implications of the work? The perception of acne as a short-term condition has implications for self-management and motivation to seek and adhere to treatments. Providing advice about onset of action of treatments and how to prevent side-effects is crucial, including directing people towards accessible, written, evidence-based information. People's confusion about the different topical treatments available may be alleviated by such information, or by encouraging photos or other recordings of treatments tried and for how long. Linked Comment: Prior. Br J Dermatol 2020; 183:208-209. Plain language summary available online.

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records.

BACKGROUND: The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. METHODS: We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). RESULTS: From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. CONCLUSIONS: While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management.

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.

BACKGROUND: Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use. METHODOLOGY: Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. RESULTS: Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. CONCLUSIONS: Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.

Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review.

BACKGROUND: Sore throat resulting from pharyngotonsillitis is one of the commonest reasons for primary care consultation and inappropriate antibiotic prescription and finding effective alternative treatments is important. OBJECTIVES: To review the evidence for using the probiotic Streptococcus salivarius K12 (SsK12) for the prevention or treatment of pharyngotonsillitis. DATA SOURCES: PubMed, Embase, CINAHL and Cochrane Library. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs). PARTICIPANTS: Adults or children. INTERVENTIONS: SsK12 as active treatment or prophylaxis, against pharyngotonsillitis. METHODS: Literature search. RESULTS: Four articles were identified (1846 participants). All were deemed to be of poor quality using the Cochrane risk-of-bias assessment. Two trials studied SsK12 prophylaxis for streptococcal pharyngitis (children without history of recurrence). One compared daily administration of SsK12 to no treatment over 6 months (n = 222, age 33-45 months), reporting significantly lower incidence in the SsK12 group (16.2% vs. 48.6%, p < 0.01), whereas another placebo-controlled RCT over four school terms (n = 1314, 5-14 years) found no significant difference (7.8% vs. 8.8%, p 0.34) with SsK12 (administered on school days). Another trial found daily SsK12 to significantly protect children (n = 250, 6-7 years) against chronic adenoiditis exacerbation over 3 months compared to no treatment (71.7% vs. 100%, p < 0.0001). The one placebo-controlled RCT in adults that studied the use of SsK12 for acute pharyngotonsillitis (concurrently with penicillin) showed no significant benefit. In all trials, SsK12 was safe and well tolerated. CONCLUSIONS: SsK12 appears safe and well tolerated. However, further RCTs are required to establish its role as a prophylactic therapy, particularly among patients experiencing frequent exacerbations of pharyngitis. In the acute setting, SsK12 is unlikely to be effective if given concurrently with antibiotics; however, further RCTs should establish its role as an alternative to antibiotics in nonsevere cases or when prescribed after antibiotic therapy for the prevention of disease recurrence and/or secondary infection.

Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Superselective endovascular tissue access using trans-vessel wall technique: feasibility study for treatment applications in heart, pancreas and kidney in swine.

OBJECTIVES: With the emergence of targeted cell transplantation and gene therapy, there is a need for minimally invasive tissue access to facilitate delivery of therapeutic substrate. The objective of this study was to demonstrate the suitability of an endovascular device which is able to directly access tissue and deliver therapeutic agent to the heart, kidney and pancreas without need to seal the penetration site. METHODS: In vivo experiments were performed in 30 swine, including subgroups with follow-up to evaluate complications. The previously described trans-vessel wall (VW) device was modified to be sharper and not require tip detachment to seal the VW. Injections into targets in the heart (n = 13, 24-h follow-up n = 5, 72-h follow-up n = 3), kidney (n = 8, 14-day follow-up n = 3) and pancreas (n = 5) were performed. Some animals were used for multiple organ injections. Follow-up consisted of clinical monitoring, angiography and necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney and pancreas) were used. Injections were targeted towards the subepicardium, endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex. RESULTS: Injections were successful in target organs, visualized by intraparenchymal contrast on fluoroscopy and by necropsy. No serious complications (defined as heart failure or persistent arrhythmia, haemorrhage requiring treatment or acute kidney injury) were encountered over a total of 157 injections. CONCLUSIONS: The trans-VW device can achieve superselective injections to the heart, pancreas and kidney for delivery of therapeutic substances without tip detachment. All parts of these organs including the subepicardium, pancreas tail and renal subcapsular space can be efficiently reached.

If you want to understand what it really means to live with cluster headache, imagine... fostering empathy through European patients' own stories of their experiences.

Cluster headache (CH) is arguably the most severe pain condition that afflicts humans. The severity of the pain has earned it the nickname "suicide headache". Understanding how CH impacts on those who suffer from it is essential, because this understanding creates empathy, which is so valuable to these patients. On the occasion of Cluster Headache Day 2017, we asked CH patients from different European countries to share their experiences, in order to help people to imagine what it means to live with the condition. Here, we look at some extracts from their stories. These CH patients' direct accounts provide an important illustration of the clinical features and consequences of the disease, helping to contextualise it and its psychological and social consequences. Reports of CH patients' first-person accounts might help to underline the physicians' role and responsibility with regard to the psychological and social consequences of this disease.

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.

Protection of sheep by vaccination against experimental challenge with Leptospira borgpetersenii serovar Hardjo and L. interrogans serovar Pomona.

AIMS: To evaluate a multivalent leptospiral and clostridial vaccine for prevention of renal colonisation and urinary shedding in sheep, following experimental challenge with New Zealand strains of Leptospira borgpetersenii serovar Hardjo type Hardjobovis and L. interrogans serovar Pomona. METHODS: Two separate but similarly designed studies were conducted. In both studies, Romney-cross lambs, aged 9-11 weeks, were randomly allocated to a vaccinated group and a control group. Vaccinated lambs each received two 1.5-mL S/C doses of a multivalent leptospiral and clostridial vaccine, 4 weeks apart, and animals in the control groups received the same dose of saline. Groups of 12 vaccinated and 12 control lambs were randomly selected in each study for challenge with serovars Hardjo or Pomona. Challenge was initiated 16 weeks following the second vaccination with three daily doses of live leptospires by intranasal and conjunctival routes. Following challenge, urine samples were collected weekly for 6 weeks, for dark field microscopy and leptospiral culture; 6 weeks after challenge the lambs were slaughtered and kidneys collected for leptospiral culture. RESULTS: In lambs challenged with serovar Hardjo, 8/12 unvaccinated lambs had ≥1 urine or kidney sample that was positive for leptospires following culture, compared with 0/12 lambs in the vaccinated group (p=0.001). In lambs challenged with serovar Pomona, 9/12 unvaccinated lambs had ≥1 urine or kidney sample that was positive following culture, compared with 0/12 lambs in the vaccinated group (p<0.001). Prevention of renal colonisation and urinary shedding, expressed as the prevented fraction, was 100 (95% CI=61.7-100)% and 100 (95% CI=68.3-100)% against challenge with serovars Hardjo and Pomona, respectively, at 4 months after vaccination. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a multivalent leptospiral and clostridial vaccine demonstrated protection against challenge from New Zealand strains of serovars of Hardjo and Pomona 4 months after vaccination in lambs first vaccinated at 9-11 weeks of age. Further studies are required to assess the duration of immunity against challenge in sheep.

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.

General practitioner and nurse prescriber experiences of prescribing antibiotics for respiratory tract infections in UK primary care out-of-hours services (the UNITE study).

Background: Interventions are needed to reduce unnecessary antibiotic prescribing for respiratory tract infections (RTIs). Although community antibiotic prescribing appears to be decreasing in the UK, figures for out-of-hours (OOH) prescribing have substantially increased. Understanding the factors influencing prescribing in OOH and any perceived differences between general practitioner (GP) and nurse prescriber (NP) prescribing habits may enable the development of tailored interventions promoting optimal prescribing in this setting. Objectives: To explore UK GP and NP views on and experiences of prescribing antibiotics for RTIs in primary care OOH services. Methods: Thirty semi-structured interviews were conducted with GPs and NPs working in primary care OOH services. Inductive thematic analysis was used to analyse data. Results: The research shows that factors particular to OOH influence antibiotic prescribing, including a lack of patient follow-up, access to patient GP records, consultation time, working contracts and implementation of feedback, audit and supervision. NPs reported perceptions of greater accountability for their prescribing compared with GPs and reported they had longer consultations during which they were able to discuss decisions with patients. Participants agreed that more complex cases should be seen by GPs and highlighted the importance of consistency of decision making, illness explanations to patients as well as a perception that differences in clinical training influence communication with patients and antibiotic prescribing decisions. Conclusions: Environmental and social factors in OOH services and a mixed healthcare workforce provide unique influences on antibiotic prescribing for RTIs, which would need to be considered in tailoring interventions that promote prudent antibiotic prescribing in OOH services.

Using an Analysis of Behavior Change to Inform Effective Digital Intervention Design: How Did the PRIMIT Website Change Hand Hygiene Behavior Across 8993 Users?

BACKGROUND: In designing digital interventions for healthcare, it is important to understand not just whether interventions work but also how and for whom-including whether individual intervention components have different effects, whether a certain usage threshold is required to change behavior in each intervention and whether usage differs across population subgroups. PURPOSE: We investigated these questions using data from a large trial of the digital PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory tract infection Transmission) (PRIMIT) intervention, which aimed to reduce respiratory tract infections (RTIs) by increasing hand hygiene behavior. METHOD: Baseline and follow-up questionnaires measured behaviors, intentions and attitudes in hand hygiene. In conjunction with objective measures of usage of the four PRIMIT sessions, we analysed these observational data to examine mechanisms of behavior change in 8993 intervention users. RESULTS: We found that the PRIMIT intervention changed behavior, intentions and attitudes, and this change was associated with reduced RTIs. The largest hand hygiene change occurred after the first session, with incrementally smaller changes after each subsequent session, suggesting that engagement with the core behavior change techniques included in the first session was necessary and sufficient for behavior change. The intervention was equally effective for men and women, older and younger people and was particularly effective for those with lower levels of education. CONCLUSIONS: Our well-powered analysis has implications for intervention development. We were able to determine a 'minimum threshold' of intervention engagement that is required for hand hygiene change, and we discuss the potential implications this (and other analyses of this type) may have for further intervention development. We also discuss the application of similar analyses to other interventions.

Understanding the delayed prescribing of antibiotics for respiratory tract infection in primary care: a qualitative analysis.

OBJECTIVE: To identify general practitioner (GP) views and understanding on the use of delayed prescribing in primary care. DESIGN: Qualitative semistructured telephone interview study. SETTING: Primary care general practices in England. PARTICIPANTS: 32 GPs from identified high-prescribing and low-prescribing general practices in England. METHOD: Semistructured telephone interviews were conducted with GPs identified from practices within clinical commissioning groups with the highest and lowest prescribing rates in England. A thematic analysis of the data was conducted to generate themes. RESULTS: All GPs had a good understanding of respiratory tract infection (RTI) management and how the delayed prescribing approach could be used in primary care. However, GPs highlighted factors that were influential as to whether delayed prescribing was successfully carried out during the consultation. These included the increase in evidence of antimicrobial resistance, and GPs' prior experiences of using delayed prescribing during the consultation. The patient-practitioner relationship could also influence treatment outcomes for RTI, and a lack of an agreed prescribing strategy within and between practices was considered to be of significance to GPs. Participants expressed that a lack of feedback on prescribing data at an individual and practice level made it difficult to know if delayed prescribing strategies were successful in reducing unnecessary consumption. GPs agreed that coherent and uniform training and guidelines would be of some benefit to ensure consistent prescribing throughout the UK. CONCLUSIONS: Delayed prescribing is encouraged in primary care, but is not always implemented successfully. Greater uniformity within and between practices in the UK is needed to operationalise delayed prescribing, as well as providing feedback on the uptake of antibiotics. Finally, GPs may need further guidance on how to answer the concerns of patients without interpreting these questions as a demand for antibiotics, as well as educating the patient about antimicrobial resistance and supporting a good patient-practitioner relationship.

Parents' and carers' views about emollients for childhood eczema: qualitative interview study.

OBJECTIVE: Leave-on emollients form the mainstay of eczema treatment, but adherence is poor. We aimed to explore parents'/carers' views on effectiveness and acceptability of leave-on emollients for childhood eczema through secondary analysis of data from 2 qualitative data sets. SETTING: Study 1 recruited through mail-out from 6 general practices in southern England. Study 2 recruited from a feasibility trial of an intervention to support eczema self-care in 31 practices in the same area. PARTICIPANTS: Study 1 included 28 interviews with carers of children aged ≤5 years with eczema. Study 2 included 26 interviews with carers of children aged ≤5 years with eczema. METHODS: Interviews followed semistructured guides: study 1 explored carers' understandings around eczema treatments in order to develop a web-based self-care support intervention; study 2 explored carers' understandings of eczema and eczema treatments after using the intervention. Interviews were carried out face to face or by telephone, audio-recorded and transcribed. Secondary analysis of data from both studies focused on views and experiences of emollient use. Data were analysed using an inductive thematic approach facilitated by NVivo V.10 software. RESULTS: In study 1, most participants felt emollients improved eczema but held mixed views about long-term use to prevent flare-ups. In study 2, where carers had used the web-based intervention, all participants held positive views about long-term emollient use. In both studies, participants expressed a range of preferences about emollient 'thickness'; some felt that 'thick' emollients (ointments) were most effective, while others found these difficult to use. Carers described a process of 'trial and error', trying emollients suggested by professionals, friends and family, or bought over-the-counter. Carers expressed a need for understanding differences between products and their effective use. CONCLUSIONS: Providing a rationale for long-term emollient use and choice of emollients could help improve adherence and help families gain more rapid control of eczema.