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1.  Physiotherapy breathing retraining for asthma: a randomised controlled trial 
Summary
Background
Despite effective pharmacotherapy, asthma continues to impair quality of life for most patients. Non-pharmacological approaches, including breathing retraining, are therefore of great interest to patients. However, clinicians rarely advocate breathing retraining and access to this intervention is restricted for most patients due to the limited availability of suitable physiotherapists and poor integration of breathing retraining into standard care. We aimed to assess the effectiveness of a digital self-guided breathing retraining intervention.
Methods
In this randomised controlled trial, we recruited patients from 34 general practices in the UK. Eligibility criteria for patients with asthma were broad, comprising a physician diagnosis of asthma, age of 16–70 years, receipt of at least one anti-asthma medication in the previous year, and impaired asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ] score of <5·5). We developed a self-guided intervention, which was delivered as a DVD plus a printed booklet (DVDB). Participants were randomly assigned to receive either the DVDB intervention, three face-to-face breathing retraining sessions, or standard care, in a 2:1:2 ratio, for 12 months. Randomisation was achieved using the Southampton Clinical Trials Unit telephone randomisation service by use of random number generators. The primary outcome was the AQLQ score in the intention-to-treat population at 12 months. The trial was powered to show equivalence between the two active intervention groups, and superiority of both intervention groups over usual care. Secondary outcomes included patient-reported and physiological measures of asthma control, patient acceptability, and health-care costs. This trial was registered with International Standard Randomised Controlled Trial Number registry, number ISRCTN88318003.
Findings
Between Nov 5, 2012 and Jan 28, 2014, invitations to participate in the study were sent to 15 203 patients with general practitioner-diagnosed asthma, of whom 655 were recruited into the study. AQLQ scores at 12 months were significantly higher in the DVDB group (mean 5·40, SD 1·14) than in the usual care group (5·12, SD 1·17; adjusted mean difference 0·28, 95% CI 0·11 to 0·44), and in the face-to-face group (5·33, SD 1·06) than in the usual care group (adjusted mean difference 0·24, 95% CI 0·04 to 0·44); AQLQ scores were similar between the DVDB group and the face-to-face group (0·04, 95% CI −0·16 to 0·24). There were no significant differences between the randomisation groups in FEV1 or fraction of exhaled nitric oxide. 744 adverse events occurred in 272 patients: 101 (39%) of 261 patients in the DVDB group, 55 (42%) of 132 patients in the face-to-face group, and 132 (50%) of 262 in the usual care group, with patients reporting one or more event. 11 (4%) patients in the DVDB group, four (3%) patients in the face-to-face group, and 20 (8%) patients in the usual care group had a serious adverse event.
Interpretation
Breathing retraining programmes improve quality of life in patients with incompletely controlled asthma despite having little effect on lung function or airway inflammation. Such programmes can be delivered conveniently and cost-effectively as a self-guided digital audiovisual programme, so might also reduce health-care costs.
Funding
UK National Institute of Health Research.
doi:10.1016/S2213-2600(17)30474-5
PMCID: PMC5757422  PMID: 29248433
2.  Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial 
BACKGROUND:
Reducing the use of antibiotics for upper respiratory tract infections is needed to limit the global threat of antibiotic resistance. We estimated the effectiveness of probiotics and xylitol for the management of pharyngitis.
METHODS:
In this parallel-group factorial randomized controlled trial, participants in primary care (aged 3 years or older) with pharyngitis underwent randomization by nurses who provided sequential intervention packs. Pack contents for 3 kinds of material and advice were previously determined by computer-generated random numbers: no chewing gum, xylitol-based chewing gum (15% xylitol; 5 pieces daily) and sorbitol gum (5 pieces daily). Half of each group were also randomly assigned to receive either probiotic capsules (containing 24 × 109 colony-forming units of lactobacilli and bifidobacteria) or placebo. The primary outcome was mean self-reported severity of sore throat and difficulty swallowing (scale 0–6) in the first 3 days. We used multiple imputation to avoid the assumption that data were missing completely at random.
RESULTS:
A total of 1009 individuals consented, 934 completed the baseline assessment, and 689 provided complete data for the primary outcome. Probiotics were not effective in reducing the severity of symptoms: mean severity scores 2.75 with no probiotic and 2.78 with probiotic (adjusted difference −0.001, 95% confidence interval [CI] −0.24 to 0.24). Chewing gum was also ineffective: mean severity scores 2.73 without gum, 2.72 with sorbitol gum (adjusted difference 0.07, 95% CI −0.23 to 0.37) and 2.73 with xylitol gum (adjusted difference 0.01, 95% CI −0.29 to 0.30). None of the secondary outcomes differed significantly between groups, and no harms were reported.
INTERPRETATION:
Neither probiotics nor advice to chew xylitol-based chewing gum was effective for managing pharyngitis. Trial registration: ISRCTN, no. ISRCTN51472596
doi:10.1503/cmaj.170599
PMCID: PMC5738247  PMID: 29255098
3.  Adverse Effects of Amoxicillin for Acute Lower Respiratory Tract Infection in Primary Care: Secondary and Subgroup Analysis of a Randomised Clinical Trial 
Antibiotics  2017;6(4):36.
A European placebo-controlled trial of antibiotic treatment for lower respiratory tract infection (LRTI) conducted in 16 primary care practices networks recruited participants between November 2007 and April 2010, and found adverse events (AEs) occurred more often in patients prescribed amoxicillin compared to placebo. This secondary analysis explores the causal relationship and estimates specific AEs (diarrhoea, nausea, rash) due to amoxicillin treatment for LRTI, and if any subgroup is at increased risk of any or a specific AE. A total of 2061 patients were randomly assigned to amoxicillin (1038) and placebo (1023); 595 (28%) were 60 and older. A significantly higher proportion of any AEs (diarrhoea or nausea or rash) (OR = 1.31, 95% CI 1.05–1.64, number needed to harm (NNH) = 24) and of diarrhoea (OR 1.43 95% CI 1.08–1.90, NNH = 29) was reported in the amoxicillin group during the first week after randomisation. Subgroup analysis showed rash was significantly more often reported in males prescribed amoxicillin (interaction term 3.72 95% CI 1.22–11.36; OR of amoxicillin in males 2.79 (95% CI 1.08–7.22). No other subgroup at higher risk was identified. Although the study was not powered for subgroup analysis, this analysis suggests that most patients are likely to be equally harmed when prescribed antibiotics.
doi:10.3390/antibiotics6040036
PMCID: PMC5745479  PMID: 29236038
adverse effects; antibiotics; respiratory infections; randomized controlled trial; primary care; subgroup analysis
4.  Predictors of pneumonia in lower respiratory tract infections: 3C prospective cough complication cohort study 
The European Respiratory Journal  2017;50(5):1700434.
The aim was to aid diagnosis of pneumonia in those presenting with lower respiratory tract symptoms in routine primary care.
A cohort of 28 883 adult patients with acute cough attributed to lower respiratory tract infections (LRTIs) was recruited from 5222 UK practices in 2009–13. Symptoms, signs and treatment were recorded at presentation and subsequent events followed-up for 30 days by chart review. The predictive value of patient characteristics, presenting symptoms and clinical findings for the diagnosis of pneumonia in the first 7 days was established.
Of the 720 out of 28 883 (2.5.%) radiographed within 1 week of the index consultation, 115 (16.0%; 0.40% of 28 883) were assigned a definite or probable pneumonia diagnosis. The significant independent predictors of radiograph-confirmed pneumonia were temperature >37.8°C (RR 2.6; 95% CI 1.5–4.8), crackles on auscultation (RR 1.8; 1.1–3.0), oxygen saturation <95% (RR 1.7; 1.0–3.1) and pulse >100·min–1 (RR 1.9; 1.1–3.2). Most patients with pneumonia (99/115, 86.1%) exhibited at least one of these four clinical signs; the positive predictive value of having at least one of these signs was 20.2% (95% CI 17.3–23.1).
In routine practice, radiograph-confirmed pneumonia as a short-term complication of LRTI is very uncommon (one in 270). Pulse oximetry may aid the diagnosis of pneumonia in this setting.
Pulse oximetry probably has a role in the diagnosis of pneumonia in the community http://ow.ly/QpWc30fVM2j
doi:10.1183/13993003.00434-2017
PMCID: PMC5724402  PMID: 29167296
5.  Qualitative interview study of antibiotics and self-management strategies for respiratory infections in primary care 
BMJ Open  2017;7(11):e016903.
Objective
To explore perceptions of illness, the decisions to consult and the acceptability of delayed antibiotic prescriptions and self-help treatments for respiratory tract infections (RTIs).
Design
Qualitative semistructured interview study.
Setting
UK primary care.
Participants
20 adult patients who had been participating in the ‘PIPS’ (Pragmatic Ibuprofen Paracetamol and Steam) trial in the South of England.
Method
Semistructured telephone interviews were conducted with participants to explore their experiences and views on various treatments for RTI.
Results
Participants had concerns about symptoms that were not clinically serious and were mostly unaware of the natural history of RTIs, but were aware of the limitations of antibiotics and did not expect them with every consultation. Most viewed delayed prescriptions positively and had no strong preference over which technique is used to deliver the delayed antibiotic, but some patients received mixed messages, such as being told their infection was viral then being given an antibiotic, or were sceptical about the rationale. Participants disliked self-help treatments that involved taking medication and were particularly concerned about painkillers in combination. Steam inhalation was viewed as only moderately helpful for mild symptoms.
Conclusion
Delayed prescribing is acceptable no matter how the delay is operationalised, but explanation of the rationale is needed and care taken to minimise mixed messages about the severity of illnesses and causation by viruses or bacteria. Better access is needed to good natural history information, and the signs and symptoms requiring or not requiring general practitioner advice. Significant concerns about paracetamol, ibuprofen and steam inhalation are likely to need careful exploration in the consultation.
doi:10.1136/bmjopen-2017-016903
PMCID: PMC5719297  PMID: 29180593
antibiotics; prescribing; respiratory tract infection; self-help
6.  ’Well, it literally stops me from having a life when it’s really bad': a nested qualitative interview study of patient views on the use of self-management treatments for the management of recurrent sinusitis (SNIFS trial) 
BMJ Open  2017;7(11):e017130.
Objective
To explore the experience and perceptions of illness, the decision to consult a general practitioner and the use of self-management approaches for chronic or recurrent sinusitis.
Design
Qualitative semistructured interview study.
Setting
UK primary care.
Participants
32 participants who had been participating in the ‘SNIFS’ (Steam inhalation and Nasal Irrigation For recurrent Sinusitis) trial in the South of England.
Method
Thematic analysis of semistructured telephone interviews.
Results
Participants often reported dramatic impact on both activities and their quality of life. Participants were aware of both antibiotic side effects and resistance, but if they had previously been prescribed antibiotics, many patients believed that they would be necessary for the future treatment of sinusitis. Participants used self-help treatments for short and limited periods of time only. In the context of the trial, steam inhalation used for recurrent sinusitis was described as acceptable but is seen as having limited effectiveness. Nasal irrigation was viewed as acceptable and beneficial by more patients. However, some participants reported that they would not use the treatment again due to the uncomfortable side effects they experienced, which outweighed any symptom relief, which may have resulted had they continued.
Conclusions
Steam inhalation is acceptable but seen as having limited effectiveness. Nasal irrigation is generally acceptable and beneficial for symptoms, but detailed information on the correct procedure and potential benefits of persisting may increase acceptability and adherence in those patients who find it uncomfortable.
Trial registration number
ISRCTN 88204146.
doi:10.1136/bmjopen-2017-017130
PMCID: PMC5695339  PMID: 29101134
primary care; qualitative research; sinusitis; antibiotics; self-help
7.  Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults 
JAMA  2017;317(15):1535-1543.
Key Points
Question
Does a single dose of dexamethasone in the absence of antibiotics provide symptom relief for acute sore throat in adults presenting to primary care?
Findings
In this randomized clinical trial including 565 adults, the proportion of participants in the dexamethasone group achieving complete symptom resolution at 24 hours was not significantly different from those taking placebo. But at 48 hours significantly more in the dexamethasone group experienced complete resolution than did those in the placebo group.
Meaning
Among adults presenting to primary care practices with acute sore throat, a single dose of oral dexamethasone did not increase the likelihood of symptom resolution at 24 hours but did increase the likelihood at 48 hours.
This randomized controlled trial compared the effects of a single dose of dexamethasone vs placebo on sore throat symptoms among adults with acute sore throat not requiring immediate antibiotics.
Importance
Acute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment.
Objective
To assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics.
Design, Setting, and Participants
Double-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy.
Interventions
Single oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283).
Main Outcomes and Measures
Primary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events.
Results
Among 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, −1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no significant differences in any other secondary outcomes.
Results
Of 565 eligible randomized participants (median age, 34 years [interquartile range, 26.0-45.5 years]; 75.2% women; 100% completed the intervention), 288 received dexamethasone and 277, placebo. At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. Results were similar among those who were not offered an antibiotic prescription and those who were offered a delayed antibiotic prescription. At 48 hours, more participants receiving dexamethasone than placebo had complete symptom resolution. This difference also was observed in patients not offered delayed antibiotics. There were no significant differences in any other secondary outcomes.
Conclusions and Relevance
Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours.
Trial Registration
isrctn.org Identifier: ISRCTN17435450
doi:10.1001/jama.2017.3417
PMCID: PMC5470351  PMID: 28418482
8.  Antibiotic Prescription Patterns for Acute Diarrhea in a Hospital in Shanghai in 2016: A Cross-sectional Study 
Open Forum Infectious Diseases  2017;4(Suppl 1):S326.
Abstract
Background
Unnecessary antibiotic use increases the risk for antibiotic resistance. The rates of antibiotic use for upper respiratory infections are high in hospitals in China. Although most guidelines advise against the use of antibiotics for acute diarrhea, little is known about antibiotic use practices for acute diarrhea in China.
Methods
A retrospective prescription review from a Shanghai hospital outpatient electronic health records system was conducted from 1 January 2016 to 30 December 2016. Records were included for adult patients. The microbial resistance seasonal data in 2016 were extracted. Chi-squared and multivariable logistic regression and adjusted odd ratio (aOR) were used to assess the relationships between demographic characteristics and antibiotic prescribing.
Results
In total, there were 16,565 prescriptions, 16,060 prescriptions were included in the final analysis after excluding the follow up visits. There were 12,131 (76%) prescriptions with antibiotics prescribed. 5505 (45%) of the antibiotics prescribed were injectable. Of the antibiotics prescribed, levofloxacin was the most frequent (85%), followed by various cephalosporins (14%). Of the cephalosporin prescriptions, third-generation products were the most common (97%). Treatment with oral rehydration salts (ORS) was prescribed 34 (0.2%) times, probiotics were prescribed 3414 (21%) times and smectite was prescribed 2209 (14%) times. Multivariable regression analysis showed that those more likely to receive antibiotics were age 31–50 aOR 1.3 (1.1–1.4), P < 0.001, evaluated in the late evening (11pm to 7am) aOR 2.6 (2.2–2.9) P < 0.001, in the early evening (6pm-11pm) aOR 2.0 (1.8–2.2) P < 0.001, in the summer (June-August) aOR 1.7 (1.5–1.9) P < 0.001. At the same time, the Gram-positive and Gram-negative resistance rates to levofloxacin exceeded 40%, including 50% of E. coliisolates.
Conclusion
High rates of antibiotic use were observed for acute diarrhea in this hospital. Given the inappropriateness of antibiotics for acute diarrhea and the nonsensical high rates of of intravenous levofloxacin use and the concurrent high rates of the levofloxacin resistance, a more effective antibiotic stewardship program is needed to improve patient outcomes, reduce costs, reinforce policy and address the underlying causes of antibiotic abuse.
Disclosures
All authors: No reported disclosures.
doi:10.1093/ofid/ofx163.770
PMCID: PMC5632036
9.  Antibiotic Use Among Future Health Professionals: A Multicentre Cross-Sectional Study of Chinese Medical Student 
Open Forum Infectious Diseases  2017;4(Suppl 1):S257.
Abstract
Background
Antibiotic use leads to antibiotic resistance and antibiotic misuse is high in China and other developing countries. This may arise from beliefs and behaviours of doctors and the pressure they receive from patients. This study aims to understand antibiotic use behaviour for self-limited illness among medical students - the future healthcare professionals.
Methods
This is part of a large cross-sectional study of Chinese university students of science, social science and humanities, and medicine. An electronic survey health belief model (HBM) questionnaire was distributed at six universities in China from September to November 2015. The score assessment was based on the constructs of HBM theory. Chi-squared and multivariable logistic regression and adjusted odd ratios (aOR) were used to assess the relationship between demographic characteristics, antibiotic use knowledge and behavior.
Results
In total, 11455 students were asked to participate and 11192 (97.5%) completed the questionnaires. 1819 medical students completed the survey. In the past month 529 (29%) medical students reported at least one self-limited illness. Of those, 285 (54%) self-medicated and 77 (27%) of them used antibiotics. 111 (21%) saw a doctor among whom 64 (58%) received antibiotics. 133 (25%) did nothing. In the past year, 279 (15%) of students used antibiotics for prophylaxis, 273 (15%) ever demanded an antibiotic from a doctor, 1166 (64%) kept a personal stock of antibiotics, 1034 (57%) bought antibiotics at a pharmacy, 97% of these without a prescription. Students with high HBM scores about antibiotics were significantly less likely to self-medicate with antibiotics (aOR 0.37, 95% CI 0.15-0.91, P = 0.031), to use antibiotics for prophylaxis (aOR 0.35, 95% CI 0.21–0.60, P < 0.0001) or demand an antibiotic (aOR 0.46, 95% CI 0.26-0.81, P = 0.007). Students whose father has a higher education level, whose mother is a doctor or who are from urban areas were more likely to stock antibiotics and self-medicate.
Conclusion
High rates of antibiotic self-medication (54%) and stocking (64%) were found among medical students. Along with the high rates of unnecessarily prescribed antibiotics by doctors (58%), there is clearly a need for effective antibiotic stewardship and training programs in Chinese healthcare institutions and medical schools.
Disclosures
All authors: No reported disclosures.
doi:10.1093/ofid/ofx163.559
PMCID: PMC5632178
10.  Qualitative interview study of parents’ perspectives, concerns and experiences of the management of lower respiratory tract infections in children in primary care 
BMJ Open  2017;7(9):e015701.
Objective
To explore parents’ perspectives, concerns and experiences of the management of lower respiratory tract infections (LRTIs) in children in primary care.
Design
Qualitative semistructured interview study.
Setting
UK primary care.
Participants
23 parents of children aged 6 months to 10 years presenting with LRTI in primary care.
Method
Thematic analysis of semistructured interviews (either in person or by telephone) conducted with parents to explore their experiences and views on their children being prescribed antibiotics for LRTI.
Results
Four major themes were identified and these are perspectives on: (1) infection, (2) antibiotic use, (3) the general practitioner (GP) appointment and (4) decision making around prescribing. Symptomatic relief was a key concern: the most troublesome symptoms were cough, breathing difficulty, fever and malaise. Many parents were reluctant to use self-care medication, tended to support antibiotic use and believed they are effective for symptoms, illness duration and for preventing complications. However, parental expectations varied from a desire for reassurance and advice to an explicit preference for an antibiotic prescription. These preferences were shaped by: (1) the age of the child, with younger children perceived as more vulnerable because of their greater difficulty in communicating, and concerns about rapid deterioration; (2) the perceived severity of the illness; and (3) disruption to daily routine. When there was disagreement with the GP, parents described feeling dismissed, and they were critical of inconsistent prescribing when they reconsult. When agreement between the parent and the doctor featured, parents described a feeling of relief and legitimation for consulting, feeling reassured that the illness did indeed warrant a doctor’s attention.
Conclusion
Symptomatic relief is a major concern for parents. Careful exploration of expectations, and eliciting worries about key symptoms and impact on daily life will be needed to help parents understand when a no antibiotic recommendation or delayed antibiotic recommendation is made.
doi:10.1136/bmjopen-2016-015701
PMCID: PMC5640115  PMID: 28918409
primary care; qualitative research; antibiotics; interviews
11.  Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial 
Trials  2017;18:421.
Background
Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use.
Methods/design
Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below:Group 1 – Uva-ursi + advice to take ibuprofenGroup 2 – Placebo + advice to take ibuprofenGroup 3 – Uva-ursi + no advice to take ibuprofenGroup 4 – Placebo + no advice to take ibuprofen
Patients and physicians will be blinded to the randomised group for the herb.
The main outcome is symptom severity at days 2–4 recorded in a validated, self-report diary used in previous studies.
Secondary outcomes include antibiotic use and symptom duration.
In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint.
In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package.
Discussion
The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics.
Trial registration
ISRCTN registry, ID: ISRCTN43397016. Registered on 11 February 2015.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-017-2145-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-017-2145-7
PMCID: PMC5591533  PMID: 28886751
Antibiotic resistance; Urinary tract infection; Uva-ursi; NSAID; Ibuprofen
12.  Cost effectiveness of amoxicillin for lower respiratory tract infections in primary care: an economic evaluation accounting for the cost of antimicrobial resistance 
The British Journal of General Practice  2016;66(650):e633-e639.
Background
Lower respiratory tract infections (LRTIs) are a major disease burden and are often treated with antibiotics. Typically, studies evaluating the use of antibiotics focus on immediate costs of care, and do not account for the wider implications of antimicrobial resistance.
Aim
This study sought to establish whether antibiotics (principally amoxicillin) are cost effective in patients with LRTIs, and to explore the implications of taking into account costs associated with resistance.
Design and setting
Multinational randomised double-blinded trial in 2060 patients with acute cough/LRTIs recruited in 12 European countries.
Method
A cost-utility analysis from a health system perspective with a time horizon of 28 days was conducted. The primary outcome measure was the quality-adjusted life year (QALY). Hierarchical modelling was used to estimate incremental cost-effectiveness ratios (ICERs).
Results
Amoxicillin was associated with an ICER of €8216 (£6540) per QALY gained when the cost of resistance was excluded. If the cost of resistance is greater than €11 (£9) per patient, then amoxicillin treatment is no longer cost effective. Including possible estimates of the cost of resistance resulted in ICERs ranging from €14 730 (£11 949) per QALY gained — when only multidrug resistance costs and health care costs are included — to €727 135 (£589 856) per QALY gained when broader societal costs are also included.
Conclusion
Economic evaluation of antibiotic prescribing strategies that do not include the cost of resistance may provide misleading results that could be of questionable use to policymakers. However, further work is required to estimate robust costs of resistance.
doi:10.3399/bjgp16X686533
PMCID: PMC5198702  PMID: 27402969
amoxicillin; antibiotic resistance; cost-effectiveness; economic costs; lower respiratory tract infection; quality-adjusted life years
13.  Nappy pad urine samples for investigation and treatment of UTI in young children: the ‘DUTY’ prospective diagnostic cohort study 
The British Journal of General Practice  2016;66(648):e516-e524.
Background
The added diagnostic utility of nappy pad urine samples and the proportion that are contaminated is unknown.
Aim
To develop a clinical prediction rule for the diagnosis of urinary tract infection (UTI) based on sampling using the nappy pad method.
Design and setting
Acutely unwell children <5 years presenting to 233 UK primary care sites.
Method
Logistic regression to identify independent associations of symptoms, signs, and urine dipstick test results with UTI; diagnostic utility quantified as area under the receiver operator curves (AUROC). Nappy pad rule characteristics, AUROC, and contamination, compared with findings from clean-catch samples.
Results
Nappy pad samples were obtained from 3205 children (82% aged <2 years; 48% female), culture results were available for 2277 (71.0%) and 30 (1.3%) had a UTI on culture. Female sex, smelly urine, darker urine, and the absence of nappy rash were independently associated with a UTI, with an internally-validated, coefficient model AUROC of 0.81 (0.87 for clean-catch), which increased to 0.87 (0.90 for clean-catch) with the addition of dipstick results. GPs’ ‘working diagnosis’ had an AUROC 0.63 (95% confidence intervals [CI] = 0.53 to 0.72). A total of 12.2% of nappy pad and 1.8% of clean-catch samples were ‘frankly contaminated’ (risk ratio 6.66; 95% CI = 4.95 to 8.96; P<0.001).
Conclusion
Nappy pad urine culture results, with features that can be reported by parents and dipstick tests, can be clinically useful, but are less accurate and more often contaminated compared with clean-catch urine culture.
doi:10.3399/bjgp16X685873
PMCID: PMC4917055  PMID: 27364678
antibacterial agents; diagnosis; infant; paediatrics; primary health care; urinary tract infections
14.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
15.  What techniques might be used to harness placebo effects in non-malignant pain? A literature review and survey to develop a taxonomy 
BMJ Open  2017;7(6):e015516.
Objectives
Placebo effects can be clinically meaningful but are seldom fully exploited in clinical practice. This review aimed to facilitate translational research by producing a taxonomy of techniques that could augment placebo analgesia in clinical practice.
Design
Literature review and survey.
Methods
We systematically analysed methods which could plausibly be used to elicit placebo effects in 169 clinical and laboratory-based studies involving non-malignant pain, drawn from seven systematic reviews. In a validation exercise, we surveyed 33 leading placebo researchers (mean 12 years’ research experience, SD 9.8), who were asked to comment on and add to the draft taxonomy derived from the literature.
Results
The final taxonomy defines 30 procedures that may contribute to placebo effects in clinical and experimental research, proposes 60 possible clinical applications and classifies procedures into five domains: the patient’s characteristics and belief (5 procedures and 11 clinical applications), the practitioner’s characteristics and beliefs (2 procedures and 4 clinical applications), the healthcare setting (8 procedures and 13 clinical applications), treatment characteristics (8 procedures and 14 clinical applications) and the patient–practitioner interaction (7 procedures and 18 clinical applications).
Conclusion
The taxonomy provides a preliminary and novel tool with potential to guide translational research aiming to harness placebo effects for patient benefit in practice.
doi:10.1136/bmjopen-2016-015516
PMCID: PMC5734496  PMID: 28667217
placebos; placebo effect; nocebo effect; translational research; review; classification
16.  Providing online weight management in Primary Care: a mixed methods process evaluation of healthcare practitioners’ experiences of using and supporting patients using POWeR+ 
Background
An online weight management intervention (POWeR+) combined with a small amount of primary care healthcare practitioner support is effective in helping patients to lose weight, but little is known about how practitioners interact with the POWeR+ intervention or their experiences of providing support for patients using POWeR+. The aim of this study was to explore practitioners’ usage of POWeR+ and their experiences of providing support to patients using POWeR+.
Methods
Set within a randomised controlled trial of POWeR+, practitioners’ usage of POWeR+ was automatically captured and a qualitative process analysis was conducted employing semi-structured telephone interviews with practitioners who provided support to patients using POWeR+. The usage analysis captured how 54 practitioners used the POWeR+ intervention. Thirteen telephone interviews explored practitioners’ experiences of using POWeR+ and providing patients with face-to-face or remote (email and telephone) support. Interview data were analysed using inductive thematic analysis.
Results
Usage analysis indicated that almost all practitioners engaged with POWeR+. Pages which displayed patients’ progress and allowed practitioners to email patients were used the most. Practitioners found POWeR+ straightforward and easy to use. Some practitioners preferred providing support face-to-face, which they enjoyed more than remote support. A small number of nurses found providing non-directive support using the CARe approach (Congratulate, Ask, Remind) challenging, feeling it was the opposite of their normal approach. POWeR+ enabled practitioners to raise the topic of weight loss with patients, and POWeR+ was viewed as a superior alternative to existing weight management support which was limited in most practices. Still some practitioners found it difficult to fit providing support into their busy schedules.
Conclusions
Overall, practitioners engaged well with POWeR+ and perceived providing patients with support whilst using POWeR+ as acceptable and feasible. CARe provides a potentially useful model for how practitioners can combine human and digital support in a cost-effective way, which could be useful for the management of other conditions. Some potential barriers to implementation were identified, which allowed modification of POWeR+. The findings suggest that implementing this cost-effective online weight management intervention in Primary Care would be feasible and acceptable to practitioners.
Trial registration
ClinicalTrial.gov, ISRCTN21244703
doi:10.1186/s13012-017-0596-6
PMCID: PMC5445406  PMID: 28545538
Obesity; Mixed methods; Process analysis; Healthcare practitioners; Weight loss; Digital intervention; E-health
17.  ‘You feel like your whole world is caving in’: A qualitative study of primary care patients’ conceptualisations of emotional distress 
Health (London, England : 1997)  2016;21(3):295-315.
General practitioners are tasked with determining the nature of patients’ emotional distress and providing appropriate care. For patients whose symptoms appear to fall near the ‘boundaries’ of psychiatric disorder, this can be difficult with important implications for treatment. There is a lack of qualitative research among patients with symptoms severe enough to warrant consultation, but where general practitioners have refrained from diagnosis. We aimed to explore how patients in this potentially large group conceptualise their symptoms and consequently investigate lay understandings of complex distinctions between emotional distress and psychiatric disorder. Interviews were conducted with 20 primary care patients whom general practitioners had identified as experiencing emotional distress, but had not diagnosed with major depressive disorder. Participants described severe emotional experiences with substantial impact on their lives. The term ‘depression’ was used in many different ways; however, despite severity, they often considered their emotional experience to be different to their perceived notions of ‘actual’ depression or mental illness. Where anxiety was mentioned, use appeared to refer to an underlying generalised state. Participants drew on complex, sometimes fluid and often theoretically coherent conceptualisations of their emotional distress, as related to, but distinct from, mental disorder. These conceptualisations differ from those frequently drawn on in research and treatment guidelines, compounding the difficulty for general practitioners. Developing models of psychological symptoms that draw on patient experience and integrate psychological/psychiatric theory may help patients understand the nature of their experience and, critically, provide the basis for a broader range of primary care interventions.
doi:10.1177/1363459316674786
PMCID: PMC5439536  PMID: 28177273
depression; emotional distress; mental disorder; primary care; qualitative
18.  Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough 
BMJ Open  2017;7(5):e014506.
Objective
To investigate recruitment and retention, data collection methods and the acceptability of a ‘within-consultation’ complex intervention designed to reduce antibiotic prescribing.
Design
Primary care feasibility cluster randomised controlled trial.
Setting
32 general practices in South West England recruiting children from October 2014 to April 2015.
Participants
Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI).
Intervention
A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record.
Controls
Usual practice, with clinicians recording data on symptoms, signs and treatment decisions.
Results
Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children’s RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm.
Conclusion
Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records.
Trial registration number
ISRCTN 23547970
UKCRN study ID
16891
doi:10.1136/bmjopen-2016-014506
PMCID: PMC5623421  PMID: 28490554
Randomised controlled trial (RCT); Feasibility; Children; Respiratory tract infections (RTIs); Primary care; Cough; Antibiotics (or Anti-microbial agents)
19.  Using digital interventions for self-management of chronic physical health conditions: A meta-ethnography review of published studies 
Patient education and counseling  2016;100(4):616-635.
Objectives
To understand the experiences of patients and healthcare professionals (HCPs) using self-management digital interventions (DIs) for chronic physical health conditions.
Methods
A systematic search was conducted in 6 electronic databases. Qualitative studies describing users’ experiences of self-management DIs were included, and authors’ interpretations were synthesised using meta-ethnography.
Results
30 papers met the inclusion criteria, covering a range of DIs and chronic conditions, including hypertension, asthma and heart disease. The review found that patients monitoring their health felt reassured by the insight this provided, and perceived they had more meaningful consultations with the HCP. These benefits were elicited by simple tele-monitoring systems as well as multifaceted DIs. Patients appeared to feel more reliant on HCPs if they received regular feedback from the HCP. HCPs focused mainly on their improved clinical control, and some also appreciated patients’ increased understanding of their condition.
Conclusions
Patients using self-management DIs tend to feel well cared for and perceive that they adopt a more active role in consultations, whilst HCPs focus on the clinical benefits provided by DIs.
Practice implications
DIs can simultaneously support patient condition management, and HCPs’ control of patient health. Tele-monitoring physiological data can promote complex behaviour change amongst patients.
doi:10.1016/j.pec.2016.10.019
PMCID: PMC5380218  PMID: 28029572
Self-management; Qualitative; Digital; Interventions
20.  The Diagnosis of Urinary Tract Infection in Young Children (DUTY) Study Clinical Rule: Economic Evaluation 
Value in Health  2017;20(4):556-566.
Objective
To estimate the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick testing to guide the diagnosis and antibiotic treatment of urinary tract infection (UTI) in acutely unwell young children presenting to primary care.
Methods
Decision analytic model synthesising data from a multicentre, prospective cohort study (DUTY) and the wider literature to estimate the short-term and lifetime costs and healthcare outcomes (symptomatic days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies. We compared GP clinical judgement with three strategies based on a ‘coefficient score’ combining seven symptoms and signs independently associated with UTI and four strategies based on weighted scores according to the presence/absence of five symptoms and signs. We compared dipstick testing versus laboratory culture in children at intermediate risk of UTI.
Results
Sampling, culture and antibiotic costs were lowest in high-specificity DUTY strategies (£1.22 and £1.08) compared to clinical judgement (£1.99). These strategies also approximately halved urine sampling (4.8% versus 9.1% in clinical judgement) without reducing sensitivity (58.2% versus 56.4%). Outcomes were very similar across all diagnostic strategies. High-specificity DUTY strategies were more cost-effective than clinical judgement in the short- (iNMB = £0.78 and £0.84) and long-term (iNMB =£2.31 and £2.50). Dipstick tests had poorer cost-effectiveness than laboratory culture in children at intermediate risk of UTI (iNMB = £-1.41).
Conclusions
Compared to GPs’ clinical judgement, high specificity clinical rules from the DUTY study could substantially reduce urine sampling, achieving lower costs and equivalent patient outcomes. Dipstick testing children for UTI is not cost-effective.
doi:10.1016/j.jval.2017.01.003
PMCID: PMC5406157  PMID: 28407997
antibacterial agents; diagnosis; economics; medical; pediatrics; urinary tract infections
21.  Determinants of initiation, implementation, and discontinuation of amoxicillin by adults with acute cough in primary care 
Aim
To investigate the determinants of adherence to amoxicillin in patients with acute lower respiratory tract infection.
Materials and methods
Three European data sets were used. Adherence data were collected using self-reported diaries. Candidate determinants included factors relating to patient, condition, therapy, health care system/provider, and the study in which the patient participated. Logistic and Cox regression models were used to investigate the determinants of initiation, implementation, and discontinuation of amoxicillin.
Results
Although initiation differed across samples, implementation and discontinuation were similar. Determinants of initiation were days waited before consulting, duration of prescription, and being in a country where a doctor-issued sick certificate is required for being off work for <7 days. Implementation was higher for older participants or those with abnormal auscultation. Implementation was lower for those prescribed longer courses of amoxicillin (≥8 days). Time from initiation to discontinuation was longer for longer prescriptions and shorter for those from countries where single-handed practices were widespread.
Conclusion
Nonadherence to amoxicillin was largely driven by noninitiation. Differing sets of determinants were found for initiation, implementation, and discontinuation. There is a need to further understand the reasons for these determinants, the impact of poor adherence to antibiotics on outcomes, and to develop interventions to improve antibiotic use when prescribed.
doi:10.2147/PPA.S119256
PMCID: PMC5359137
adherence; antibiotics; general practice; determinants
22.  Intervention planning for a digital intervention for self-management of hypertension: a theory-, evidence- and person-based approach 
Background
This paper describes the intervention planning process for the Home and Online Management and Evaluation of Blood Pressure (HOME BP), a digital intervention to promote hypertension self-management. It illustrates how a Person-Based Approach can be integrated with theory- and evidence-based approaches. The Person-Based Approach to intervention development emphasises the use of qualitative research to ensure that the intervention is acceptable, persuasive, engaging and easy to implement.
Methods
Our intervention planning process comprised two parallel, integrated work streams, which combined theory-, evidence- and person-based elements. The first work stream involved collating evidence from a mixed methods feasibility study, a systematic review and a synthesis of qualitative research. This evidence was analysed to identify likely barriers and facilitators to uptake and implementation as well as design features that should be incorporated in the HOME BP intervention. The second work stream used three complementary approaches to theoretical modelling: developing brief guiding principles for intervention design, causal modelling to map behaviour change techniques in the intervention onto the Behaviour Change Wheel and Normalisation Process Theory frameworks, and developing a logic model.
Results
The different elements of our integrated approach to intervention planning yielded important, complementary insights into how to design the intervention to maximise acceptability and ease of implementation by both patients and health professionals. From the primary and secondary evidence, we identified key barriers to overcome (such as patient and health professional concerns about side effects of escalating medication) and effective intervention ingredients (such as providing in-person support for making healthy behaviour changes). Our guiding principles highlighted unique design features that could address these issues (such as online reassurance and procedures for managing concerns). Causal modelling ensured that all relevant behavioural determinants had been addressed, and provided a complete description of the intervention. Our logic model linked the hypothesised mechanisms of action of our intervention to existing psychological theory.
Conclusion
Our integrated approach to intervention development, combining theory-, evidence- and person-based approaches, increased the clarity, comprehensiveness and confidence of our theoretical modelling and enabled us to ground our intervention in an in-depth understanding of the barriers and facilitators most relevant to this specific intervention and user population.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-017-0553-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s13012-017-0553-4
PMCID: PMC5324312  PMID: 28231840
Intervention planning; Theoretical modelling; Methodological study; Hypertension; Blood pressure; Self-monitoring; Self-management
23.  Comparison of microbiological diagnosis of urinary tract infection in young children by routine health service laboratories and a research laboratory: Diagnostic cohort study 
PLoS ONE  2017;12(2):e0171113.
Objectives
To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory.
Population and methods
We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples. We calculated areas under the receiver-operator curve (AUC) for UTI predicted by pre-specified symptoms, signs and dipstick test results (the “index test”), separately according to whether samples were obtained by clean catch or nappy (diaper) pads.
Results
251 (5.2%) and 88 (1.8%) children were classified as UTI positive by health service and research laboratories respectively. Agreement between laboratories was moderate (kappa = 0.36; 95% confidence interval [CI] 0.29, 0.43), and better for clean catch (0.54; 0.45, 0.63) than nappy pad samples (0.20; 0.12, 0.28). In clean catch samples, the AUC was lower for health service laboratories (AUC = 0.75; 95% CI 0.69, 0.80) than the research laboratory (0.86; 0.79, 0.92). Values of AUC were lower in nappy pad samples (0.65 [0.61, 0.70] and 0.79 [0.70, 0.88] for health service and research laboratory positivity, respectively) than clean catch samples.
Conclusions
The agreement of microbiological diagnosis of UTI comparing routine health service laboratories with a research laboratory was moderate for clean catch samples and poor for nappy pad samples and reliability is lower for nappy pad than for clean catch samples. Positive results from the research laboratory appear more likely to reflect real UTIs than those from routine health service laboratories, many of which (particularly from nappy pad samples) could be due to contamination. Health service laboratories should consider adopting procedures used in the research laboratory for paediatric urine samples. Primary care clinicians should try to obtain clean catch samples, even in very young children.
doi:10.1371/journal.pone.0171113
PMCID: PMC5310769  PMID: 28199403
24.  Effects on Engagement and Health Literacy Outcomes of Web-Based Materials Promoting Physical Activity in People With Diabetes: An International Randomized Trial 
Background
Developing accessible Web-based materials to support diabetes self-management in people with lower levels of health literacy is a continuing challenge.
Objective
The objective of this international study was to develop a Web-based intervention promoting physical activity among people with type 2 diabetes to determine whether audiovisual presentation and interactivity (quizzes, planners, tailoring) could help to overcome the digital divide by making digital interventions accessible and effective for people with all levels of health literacy. This study also aimed to determine whether these materials can improve health literacy outcomes for people with lower levels of health literacy and also be effective for people with higher levels of health literacy.
Methods
To assess the impact of interactivity and audiovisual features on usage, engagement, and health literacy outcomes, we designed two versions of a Web-based intervention (one interactive and one plain-text version of the same content) to promote physical activity in people with type 2 diabetes. We randomly assigned participants from the United Kingdom, Austria, Germany, Ireland, and Taiwan to either an interactive or plain-text version of the intervention in English, German, or Mandarin. Intervention usage was objectively recorded by the intervention software. Self-report measures were taken at baseline and follow-up (immediately after participants viewed the intervention) and included measures of health literacy, engagement (website satisfaction and willingness to recommend the intervention to others), and health literacy outcomes (diabetes knowledge, enablement, attitude, perceived behavioral control, and intention to undertake physical activity).
Results
In total, 1041 people took part in this study. Of the 1005 who completed health literacy information, 268 (26.67%) had intermediate or low levels of health literacy. The interactive intervention overall did not produce better outcomes than did the plain-text version. Participants in the plain-text intervention group looked at significantly more sections of the intervention (mean difference –0.47, 95% CI –0.64 to –0.30, P<.001), but this did not lead to better outcomes. Health literacy outcomes, including attitudes and intentions to engage in physical activity, significantly improved following the intervention for participants in both intervention groups. These improvements were similar across higher and lower health literacy levels and in all countries. Participants in the interactive intervention group had acquired more diabetes knowledge (mean difference 0.80, 95% CI 0.65-0.94, P<.001). Participants from both groups reported high levels of website satisfaction and would recommend the website to others.
Conclusions
Following established practice for simple, clear design and presentation and using a person-based approach to intervention development, with in-depth iterative feedback from users, may be more important than interactivity and audiovisual presentations when developing accessible digital health interventions to improve health literacy outcomes.
ClinicalTrial
International Standard Randomized Controlled Trial Number (ISRCTN): 43587048; http://www.isrctn.com/ISRCTN43587048. (Archived by WebCite at http://www.webcitation.org/6nGhaP9bv)
doi:10.2196/jmir.6601
PMCID: PMC5294369  PMID: 28115299
health literacy; digital intervention; diabetes; quantitative trial; physical activity
25.  Predicting the presence of bacterial pathogens in the airways of primary care patients with acute cough 
BACKGROUND:
Bacterial testing of all patients who present with acute cough is not feasible in primary care. Furthermore, the extent to which easily obtainable clinical information predicts bacterial infection is unknown. We evaluated the diagnostic value of clinical examination and testing for C-reactive protein and procalcitonin for bacterial lower respiratory tract infection.
METHODS:
Through a European diagnostic study, we recruited 3104 adults with acute cough (≤ 28 days) in primary care settings. All of the patients underwent clinical examination, measurement of C-reactive protein and procalcitonin in blood, and chest radiography. Bacterial infection was determined by conventional culture, polymerase chain reaction and serology, and positive results were defined by the presence of Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Bordetella pertussis or Legionella pneumophila. Using multivariable regression analysis, we examined the association of diagnostic variables with the presence of bacterial infection.
RESULTS:
Overall, 539 patients (17%) had bacterial lower respiratory tract infection, and 38 (1%) had bacterial pneumonia. The only item with diagnostic value for lower respiratory tract infection was discoloured sputum (area under the receiver operating characteristic [ROC] curve 0.56, 95% confidence interval [CI] 0.54–0.59). Adding C-reactive protein above 30 mg/L increased the area under the ROC curve to 0.62 (95% CI 0.59–0.65). For bacterial pneumonia, comorbidity, fever and crackles on auscultation had diagnostic value (area under ROC curve 0.68, 95% CI 0.58–0.77). Adding C-reactive protein above 30 mg/L increased the area under the ROC curve to 0.79 (95% CI 0.71–0.87). Procalcitonin did not add diagnostic information for any bacterial lower respiratory tract infection, including bacterial pneumonia.
INTERPRETATION:
In adults presenting with acute lower respiratory tract infection, signs, symptoms and C-reactive protein showed diagnostic value for a bacterial cause. However, the ability of these diagnostic indicators to exclude a bacterial cause was limited. Procalcitonin added no clinically relevant information.
doi:10.1503/cmaj.151364
PMCID: PMC5235925  PMID: 27777252

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