The feasibility and acceptability of assessing and managing sarcopenia and frailty among older people with upper limb fracture.

BACKGROUND: sarcopenia and frailty are associated with increased risk of falls and fractures. This study evaluated the feasibility of assessing sarcopenia and frailty among older people attending fracture clinics. METHODS: patients aged 65+ years with an arm fracture attending fracture clinics in one UK city were recruited. Sarcopenia was assessed using gait speed, grip strength, skeletal muscle mass index SMI, SARC-F questionnaire and the European Working Group on Sarcopenia in Older People (EWGSOP) I and II criteria. Frailty was assessed using Fried Frailty Phenotype (FFP), FRAIL scale, PRISMA-7, electronic Frailty Index (e-FI), Clinical Frailty Score (CFS) and Study of Osteoporotic Fracture. The sensitivity and specificity of each tool was calculated against the EWGSOP II criteria (sarcopenia) and FFP (frailty). Patients identified to have either condition were referred for Comprehensive Geriatric Assessment (CGA). Interviews with 13 patients and nine staff explored the acceptability of this process. RESULTS: hundred patients (Mean age 75 years) were recruited. Most sarcopenia and frailty assessments were quick with complete data collection and were acceptable to patients and staff. Sarcopenia was identified among 4-39% participants depending on the tool and frailty among 9-25%. Both conditions were more common among men than women with all tools. The SARC-F and PRISMA-7 had the best sensitivity (100 and 93%, respectively) and specificity (96 and 87%). CGA among 80% of referred participants led to three interventions per participant (e.g. medication changes and investigations). CONCLUSION: SARC-F and PRISMA-7 are recommended for use in fracture clinics to screen for sarcopenia and frailty.

Using digital tools in the recruitment and retention in randomised controlled trials: survey of UK Clinical Trial Units and a qualitative study.

BACKGROUND: Recruitment and retention of participants in randomised controlled trials (RCTs) is a key determinant of success but is challenging. Trialists and UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) are increasingly exploring the use of digital tools to identify, recruit and retain participants. The aim of this UK National Institute for Health Research (NIHR) study was to identify what digital tools are currently used by CTUs and understand the performance characteristics required to be judged useful. METHODS: A scoping of searches (and a survey with NIHR funding staff), a survey with all 52 UKCRC CTUs and 16 qualitative interviews were conducted with five stakeholder groups including trialists within CTUs, funders and research participants. A purposive sampling approach was used to conduct the qualitative interviews during March-June 2018. Qualitative data were analysed using a content analysis and inductive approach. RESULTS: Responses from 24 (46%) CTUs identified that database-screening tools were the most widely used digital tool for recruitment, with the majority being considered effective. The reason (and to whom) these tools were considered effective was in identifying potential participants (for both Site staff and CTU staff) and reaching recruitment target (for CTU staff/CI). Fewer retention tools were used, with short message service (SMS) or email reminders to participants being the most reported. The qualitative interviews revealed five themes across all groups: 'security and transparency'; 'inclusivity and engagement'; 'human interaction'; 'obstacles and risks'; and 'potential benefits'. There was a high level of stakeholder acceptance of the use of digital tools to support trials, despite the lack of evidence to support them over more traditional techniques. Certain differences and similarities between stakeholder groups demonstrated the complexity and challenges of using digital tools for recruiting and retaining research participants. CONCLUSIONS: Our studies identified a range of digital tools in use in recruitment and retention of RCTs, despite the lack of high-quality evidence to support their use. Understanding the type of digital tools in use to support recruitment and retention will help to inform funders and the wider research community about their value and relevance for future RCTs. Consideration of further focused digital tool reviews and primary research will help to reduce gaps in the evidence base.

Microbial epidemiology and carriage studies for the evaluation of vaccines.

Respiratory tract infections are responsible for over 2.8 million deaths per year worldwide. Colonization is the first step in the process of microbes occupying the respiratory tract, which may lead to subsequent infection. Carriage, in contrast, is defined as the occupation of microbial species in the respiratory tract. The duration of carriage may be affected by host immunity, the composition and interactions between members of the microbial community, and the characteristics of colonizing bacteria, including physiology associated with being present in a bacterial biofilm. Numerous vaccines have been implemented to control infections caused by bacteria that can colonize and be subsequently carried. Such vaccines are often species-specific and may target a limited number of strains thereby creating a vacant niche in the upper respiratory tract. Epidemiological changes of bacteria found in both carriage and disease have therefore been widely reported, since the vacant niche is filled by other strains or species. In this review, we discuss the use of carriage-prevalence studies in vaccine evaluation and argue that such studies are essential for (1) examining the epidemiology of carriage before and after the introduction of new vaccines, (2) understanding the dynamics of the respiratory tract flora and (3) identifying the disease potential of emerging strains. In an era of increasing antibiotic resistance, bacterial carriage-prevalence studies are essential for monitoring the impact of vaccination programmes.

Southampton Arm Fracture Frailty and Sarcopenia Study (SAFFSS): a study protocol for the feasibility of assessing frailty and sarcopenia among older patients with an upper limb fracture.

INTRODUCTION: Falls are a major health problem for older people; 35% of people aged 65+ years fall every year, leading to fractures in 10%-15%. Upper limb fractures are often the first sign of osteoporosis and routine screening for osteoporosis is recommended by the National Institute for Health and Care Excellence to prevent subsequent hip fractures. However, both frailty and sarcopenia (muscle weakness) are associated with increased risk of falling and fracture but are not routinely identified in this group. The aim of this study is to evaluate the feasibility of assessing and managing frailty and sarcopenia among people aged 65+ years with an upper limb fracture. METHODS AND ANALYSIS: This study will be conducted in three fracture clinics in one acute trust in England. 100 people aged 65+ years with an upper arm fracture will be recruited and assessed using six validated frailty measures and two sarcopenia tools. The prevalence of the two conditions and the best tools to use will be determined. Those with either condition will be referred to geriatric clinical teams for comprehensive geriatric assessment (CGA). We will document the proportion who are referred for CGA and those who receive CGA. Other outcome measures including falls, fractures and healthcare resource use over 6 months will be collected. In-depth interviews with a purposive sample of patients who undergo the frailty and sarcopenia assessments and healthcare professionals in fracture clinics and geriatric services will be carried out to their acceptability of assessing frailty and sarcopenia in a busy environment. ETHICS AND DISSEMINATION: The study was given the relevant ethical approvals from NHS Research Ethics Committee (REC No: 18/NE/0377), the University Hospital Southampton NHS Foundation Trust, and the University of Southampton, Faculty of Medicine Ethics Committee and Research Governance Office. Findings will be published in scientific journals and presented to local, national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN13848445.

Antibiotic Prescribing for Acute Respiratory Tract Infections 12 Months After Communication and CRP Training: A Randomized Trial.

PURPOSE: C-reactive-protein (CRP) is useful for diagnosis of lower respiratory tract infections (RTIs). A large international trial documented that Internet-based training in CRP point-of-care testing, in enhanced communication skills, or both reduced antibiotic prescribing at 3 months, with risk ratios (RRs) of 0.68, 0.53, 0.38, respectively. We report the longer-term impact in this trial. METHODS: A total of 246 general practices in 6 countries were cluster-randomized to usual care, Internet-based training on CRP point-of-care testing, Internet-based training on enhanced communication skills and interactive booklet, or both interventions combined. The main outcome was antibiotic prescribing for RTIs after 12 months. RESULTS: Of 228 practices providing 3-month data, 74% provided 12-month data, with no demonstrable attrition bias. Between 3 months and 12 months, prescribing for RTIs decreased with usual care (from 58% to 51%), but increased with CRP training (from 35% to 43%) and with both interventions combined (from 32% to 45%); at 12 months, the adjusted RRs compared with usual care were 0.75 (95% CI, 0.51-1.00) and 0.70 (95% CI, 0.49-0.93), respectively. Between 3 months and 12 months, the reduction in prescribing with communication training was maintained (41% and 40%, with an RR at 12 months of 0.70 [95% CI, 0.49-0.94]). Although materials were provided for free, clinicians seldom used booklets and rarely used CRP point-of-care testing. Communication training, but not CRP training, remained efficacious for reducing prescribing for lower RTIs (RR = 0.7195% CI, 0.45-0.99, and RR = 0.76; 95% CI, 0.47-1.06, respectively), whereas both remained efficacious for reducing prescribing for upper RTIs (RR = 0.60; 95% CI, 0.37-0.94, and RR = 0.58; 95% CI, 0.36-0.92, respectively). CONCLUSIONS: Internet-based training in enhanced communication skills remains effective in the longer term for reducing antibiotic prescribing. The early improvement seen with CRP training wanes, and this training becomes ineffective for lower RTIs, the only current indication for using CRP testing.

Ecology and diversity in upper respiratory tract microbial population structures from a cross-sectional community swabbing study.

PURPOSE: Respiratory tract infections (RTIs) are responsible for over 2.8 million deaths per year worldwide with pathobiont carriage a required precursor to infection. We sought to determine carriage epidemiology for both bacterial and viral respiratory pathogens as part of a large population-based cross-sectional carriage study. METHODOLOGY: Nose self-swab samples were collected in two separate time-points, May to August 2012 (late spring/summer) and February to April 2013 (winter/early spring). The presence of six bacterial species: S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, P. aeruginosa and N. meningitidis in addition to respiratory syncytial virus, influenza viruses A and B, rhinovirus/enterovirus, coronavirus, parainfluenza viruses 1-3 and adenovirus was determined using culture and PCR methods.Results/Key findings. Carriage was shown to vary with age, recent RTI and the presence of other species. Spatial structures of microbial communities were more disordered in the 0-4 age group and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2=20.42, P=0.002), indicating spatial clumping of species consistent with facilitative relationships. Deviations from a neutral model of ecological niches were observed in summer samples and from older individuals but not in the winter or younger individuals (0-4 years), suggesting the presence of seasonal and age-dependent niche processes in respiratory community assembly. CONCLUSION: The application of epidemiological methods and ecological theory to respiratory tract samples has yielded novel insights into the factors that drive microbial community composition.

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.

Influence of the duration of penicillin prescriptions on outcomes for acute sore throat in adults: the DESCARTE prospective cohort study in UK general practice.

BACKGROUND: Guidelines recommend 10-day treatment courses for acute sore throat, but shorter courses may be used in practice. AIM: To determine whether antibiotic duration predicts adverse outcome of acute sore throat in adults in routine care. DESIGN AND SETTING: A secondary analysis of the DESCARTE (Decision rule for the Symptoms and Complications of Acute Red Throat in Everyday practice) prospective cohort study of 12 829 adults presenting in UK general practice with acute sore throat. METHOD: A brief clinical proforma was used to collect symptom severity and examination findings at presentation. Outcomes were collected by notes review, a sample also completed a symptom diary. The primary outcome was re-consultation with new/non-resolving symptoms within 1 month. The secondary outcome was 'global' poorer symptom control (longer than the median duration or higher than median severity). RESULTS: Antibiotics were prescribed for 62% (7872/12 677) of participants. The most commonly prescribed antibiotic was phenoxymethylpenicillin (76%, 5656/7474) and prescription durations were largely for 5 (20%), 7 (57%), or 10 (22%) days. Compared with 5-day courses, those receiving longer courses were less likely to re-consult with new or non-resolving symptoms (5 days 15.3%, 7 days 13.9%, 10 days 12.2%, 7-day course adjusted risk ratio (RR) 0.92 [95% confidence interval [CI] = 0.76 to 1.11] and 10-days RR 0.86 [95% CI = 0.59 to 1.23]) but these differences did not reach statistical significance. CONCLUSION: In adults prescribed antibiotics for sore throat, the authors cannot rule out a small advantage in terms of reduced re-consultation for a 10-day course of penicillin, but the effect is likely to be small.

Symptom response to antibiotic prescribing strategies in acute sore throat in adults: the DESCARTE prospective cohort study in UK general practice.

BACKGROUND: A delayed or 'just in case' prescription has been identified as having potential to reduce antibiotic use in sore throat. AIM: To determine the symptomatic outcome of acute sore throat in adults according to antibiotic prescription strategy in routine care. DESIGN AND SETTING: A secondary analysis of the DESCARTE (Decision rule for the Symptoms and Complications of Acute Red Throat in Everyday practice) prospective cohort study comprising adults aged ≥16 years presenting with acute sore throat (≤2 weeks' duration) managed with treatment as usual in primary care in the UK. METHOD: A random sample of 2876 people from the full cohort were requested to complete a symptom diary. A brief clinical proforma was used to collect symptom severity and examination findings at presentation. Outcome details were collected by notes review and a detailed symptom diary. The primary outcome was poorer 'global' symptom control (defined as longer than the median duration or higher than median symptom severity). Analyses controlled for confounding by indication (propensity to prescribe antibiotics). RESULTS: A total of 1629/2876 (57%) of those requested returned a symptom diary, of whom 1512 had information on prescribing strategy. The proportion with poorer global symptom control was greater in those not prescribed antibiotics 398/587 (68%) compared with those prescribed immediate antibiotics 441/728 (61%) or delayed antibiotic prescription 116/197 59%); adjusted risk ratio (RR) (95% confidence intervals [CI]): immediate RR 0.87 (95% CI = 0.70 to 0.96), P = 0.006; delayed RR 0.88 (95% CI = 0.78 to 1.00), P = 0.042. CONCLUSION: In the routine care of adults with sore throat, a delayed antibiotic strategy confers similar symptomatic benefits to immediate antibiotics compared with no antibiotics. If a decision is made to prescribe an antibiotic, a delayed antibiotic strategy is likely to yield similar symptomatic benefit to immediate antibiotics.

Effectiveness of steam inhalation and nasal irrigation for chronic or recurrent sinus symptoms in primary care: a pragmatic randomized controlled trial.

BACKGROUND: Systematic reviews support nasal saline irrigation for chronic or recurrent sinus symptoms, but trials have been small and few in primary care settings. Steam inhalation has also been proposed, but supporting evidence is lacking. We investigated whether brief pragmatic interventions to encourage use of nasal irrigation or steam inhalation would be effective in relieving sinus symptoms. METHODS: We conducted a pragmatic randomized controlled trial involving adults (age 18-65 yr) from 72 primary care practices in the United Kingdom who had a history of chronic or recurrent sinusitis and reported a "moderate to severe" impact of sinus symptoms on their quality of life. Participants were recruited between Feb. 11, 2009, and June 30, 2014, and randomly assigned to 1 of 4 advice strategies: usual care, daily nasal saline irrigation supported by a demonstration video, daily steam inhalation, or combined treatment with both interventions. The primary outcome measure was the Rhinosinusitis Disability Index (RSDI). Patients were followed up at 3 and 6 months. We imputed missing data using multiple imputation methods. RESULTS: Of the 961 patients who consented, 871 returned baseline questionnaires (210 usual care, 219 nasal irrigation, 232 steam inhalation and 210 combined treatment). A total of 671 (77.0%) of the 871 participants reported RSDI scores at 3 months. Patients' RSDI scores improved more with nasal irrigation than without nasal irrigation by 3 months (crude change -7.42 v. -5.23; estimated adjusted mean difference between groups -2.51, 95% confidence interval -4.65 to -0.37). By 6 months, significantly more patients maintained a 10-point clinically important improvement in the RSDI score with nasal irrigation (44.1% v. 36.6%); fewer used over-the-counter medications (59.4% v. 68.0%) or intended to consult a doctor in future episodes. Steam inhalation reduced headache but had no significant effect on other outcomes. The proportion of participants who had adverse effects was the same in both intervention groups. INTERPRETATION: Advice to use steam inhalation for chronic or recurrent sinus symptoms in primary care was not effective. A similar strategy to use nasal irrigation was less effective than prior evidence suggested, but it provided some symptomatic benefit. TRIAL REGISTRATION: ISRCTN, no. 88204146.

Primary care randomised controlled trial of a tailored interactive website for the self-management of respiratory infections (Internet Doctor).

OBJECTIVE: To assess an internet-delivered intervention providing advice to manage respiratory tract infections (RTIs). DESIGN: Open pragmatic parallel group randomised controlled trial. SETTING: Primary care in UK. PARTICIPANTS: Adults (aged ≥18) registered with general practitioners, recruited by postal invitation. INTERVENTION: Patients were randomised with computer-generated random numbers to access the intervention website (intervention) or not (control). The intervention tailored advice about the diagnosis, natural history, symptom management (particularly paracetamol/ibuprofen use) and when to seek further help. OUTCOMES: Primary: National Health Service (NHS) contacts for those reporting RTIs from monthly online questionnaires for 20 weeks. Secondary: hospitalisations; symptom duration/severity. RESULTS: Results 3044 participants were recruited. 852 in the intervention group and 920 in the control group reported one or more RTIs, among whom there a modest increase in NHS Direct contacts in the intervention group (intervention 44/1734 (2.5%) versus control 24/1842 (1.3%); multivariate Risk Ratio (RR) 2.53 (95% CI 1.10 to 5.82, p=0.029)). Conversely reduced contact with doctors occurred (283/1734 (16.3%) vs 368/1845 (20.0%); risk ratio 0.71, 0.53 to 0.95, p=0.019). Reduction in contacts occurred despite slightly longer illness duration (11.3 days versus 10.9 days respectively; multivariateestimate 0.48 days longer (-0.16 to 1.12, p=0.141) and more days of illness rated moderately bad or worse illness (0.53 days; 0.12 to 0.94, p=0.012). The estimate of slower symptom resolution in the intervention group was attenuated when controlling for whether individuals had used webpages which advocated ibuprofen use (length of illness 0.22 days, −0.51 to 0.95, p=0.551; moderately bad or worse symptoms 0.36 days, −0.08 to 0.80, p=0.105). There was no evidence of increased hospitalisations (risk ratio 0.13; 0.02 to 1.01; p=0.051). CONCLUSIONS: An internet-delivered intervention for the self-management of RTIs modifies help-seeking behaviour, and does not result in more hospital admissions due to delayed help seeking. Advising the use of ibuprofen may not be helpful. TRIAL REGISTRATION NUMBER: ISRCTN91518452.

An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial.

BACKGROUND: Handwashing to prevent transmission of respiratory tract infections (RTIs) has been widely advocated, especially during the H1N1 pandemic. However, the role of handwashing is debated, and no good randomised evidence exists among adults in non-deprived settings. We aimed to assess whether an internet-delivered intervention to modify handwashing would reduce the number of RTIs among adults and their household members. METHODS: We recruited individuals sharing a household by mailed invitation through general practices in England. After consent, participants were randomised online by an automated computer-generated random number programme to receive either no access or access to a bespoke automated web-based intervention that maximised handwashing intention, monitored handwashing behaviour, provided tailored feedback, reinforced helpful attitudes and norms, and addressed negative beliefs. We enrolled participants into an additional cohort (randomised to receive intervention or no intervention) to assess whether the baseline questionnaire on handwashing would affect handwashing behaviour. Participants were not masked to intervention allocation, but statistical analysis commands were constructed masked to group. The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of randomly assigned participants who completed follow-up at 16 weeks. This trial is registered with the ISRCTN registry, number ISRCTN75058295. FINDINGS: Across three winters between Jan 17, 2011, and March 31, 2013, we enrolled 20,066 participants and randomly assigned them to receive intervention (n=10,040) or no intervention (n=10,026). 16,908 (84%) participants were followed up with the 16 week questionnaire (8241 index participants in intervention group and 8667 in control group). After 16 weeks, 4242 individuals (51%) in the intervention group reported one or more episodes of RTI compared with 5135 (59%) in the control group (multivariate risk ratio 0·86, 95% CI 0·83-0·89; p<0·0001). The intervention reduced transmission of RTIs (reported within 1 week of another household member) both to and from the index person. We noted a slight increase in minor self-reported skin irritation (231 [4%] of 5429 in intervention group vs 79 [1%] of 6087 in control group) and no reported serious adverse events. INTERPRETATION: In non-pandemic years, an effective internet intervention designed to increase handwashing could have an important effect in reduction of infection transmission. In view of the heightened concern during a pandemic and the likely role of the internet in access to advice, the intervention also has potential for effective implementation during a pandemic. FUNDING: Medical Research Council.

Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators.

OBJECTIVES: Estimate the efficacy of amoxicillin for acute uncomplicated lower-respiratory-tract infection (LRTI) in primary care and demonstrate the use of randomisation-based efficacy estimators. DESIGN: Secondary analysis of a two-arm individually-randomised placebo-controlled trial. SETTING: Primary care practices in 12 European countries. PARTICIPANTS: Patients aged 18 or older consulting with an acute LRTI in whom pneumonia was not suspected by the clinician. INTERVENTIONS: Amoxicillin (two 500 mg tablets three times a day for 7 days) or matched placebo. MAIN OUTCOME MEASURES: Clinician-rated symptom severity between days 2-4; new/worsening symptoms and presence of side effects at 4-weeks. Adherence was captured using self-report and tablet counts. RESULTS: 2061 participants were randomised to the amoxicillin or placebo group. On average, 88% of the prescribed amoxicillin was taken. The original analysis demonstrated small increases in both benefits and harms from amoxicillin. Minor improvements in the benefits of amoxicillin were observed when an adjustments for adherence were made (mean difference in symptom severity -0.08, 95% CI -0.17 to 0.01, OR for new/worsening symptoms 0.81, 95% CI 0.66 to 0.98) as well as minor increases in harms (OR for side effects 1.32, 95% CI 1.12 to 1.57). CONCLUSIONS: Adherence to amoxicillin was high, and the findings from the original analysis were robust to non-adherence. Participants consulting to primary care with an acute uncomplicated LRTI can on average expect minor improvements in outcome from taking amoxicillin. However, they are also at an increased risk of experiencing side effects. TRIAL REGISTRATION NUMBERS: Eudract-CT 2007-001586-15 and ISRCTN52261229. The trial was registered at EudraCT in 2007 due to an administrative misunderstanding that EudraCT was a suitable registry--which it was not in 2007, but has become since. On discovery of this error, the trial was also registered at ISRCTN (January 2009). Trial procedures did not change between the two registrations.

Perceptions of weight, diabetes and willingness to participate in randomised controlled trials of bariatric surgery for patients with type 2 diabetes mellitus and body mass index 30-39.9 kg/m(2).

PURPOSE: Evidence from high-quality randomised controlled trials (RCTs) is needed to establish the long-term benefit of bariatric surgery in people with type 2 diabetes mellitus (T2DM) and body mass index (BMI) 30-39.9 kg/m(2). However, willingness amongst this group to be randomised and undergo surgery is uncertain. This study assessed UK patients' perceptions of their weight and diabetes, and associations with willingness to participate in RCTs involving bariatric surgery, amongst this population. MATERIALS AND METHODS: Postal survey of 1820 patients from four regions in England. Eligible patients were as follows: BMI 30-39.9 kg/m(2), 18-74 years, diagnosis of T2DM ≥2 years. A reminder survey was sent after 4 weeks. Independent predictors influencing patients' willingness to consider RCT participation were identified using multiple logistic regression analysis. RESULTS: Thirty-four per cent (614/1820) of patients responded. Weight was considered to be harder to control than diabetes [468/584 (80 %) vs. 107/600 (17 %)]. More people reported a negative impact on life for weight rather than diabetes [379/579 (63 %) vs. 180/574 (31 %)]. Feeling unsatisfied/very unsatisfied with weight loss ability was common 261/578 (45 %). Sixty-four per cent (379/594, CI = 60-68) were willing to consider participating in an RCT. In multivariate analysis, negative impact of weight on life (OR = 2.55, 95 % CI = 1.68-3.89, P < 0.001) and feeling unsatisfied with weight loss ability (OR = 2.47, 95 % CI = 1.55-3.95, P < 0.001) positively influenced patients' willingness to participate in an RCT. CONCLUSION: Strong patient interest supports the feasibility of such trials for this group. Perceptions of obesity negatively impacting on life and difficulties in achieving weight loss were common and influenced attitudes to potential participation in bariatric surgery RCTs.

A pilot randomised controlled trial to compare changes in quality of life for participants with early diagnosis dementia who attend a 'Living Well with Dementia' group compared to waiting-list control.

OBJECTIVES: The aim of this paper is to report a pilot study in which participants who had recently received a diagnosis of dementia were randomised to either a 10-week group intervention or a waiting-list control. METHOD: Memory clinic staff with limited previous experience of group therapy were trained to lead a 10-week group therapy intervention called 'Living Well with Dementia'. Fifty-eight participants, all of whom had received a diagnosis of Alzheimer's disease, vascular or Lewy body dementia within the previous 18 months, were randomised to receive either the intervention or treatment as usual (waiting-list control). Data collection occurred at baseline, within two weeks after the intervention finished and at 10-week follow-up. RESULTS: The study met its recruitment targets, with a relatively low attrition rate for the intervention arm. The acceptability of the intervention and research methods was examined qualitatively and will be reported on elsewhere. For the primary outcome, measure of quality of life in Alzheimer's disease (QoL-AD), and secondary outcome, self-esteem, there was some evidence of improvement in the intervention group compared to the control group. There was, also, evidence of a reduction in cognitive functioning in the treatment group compared to the control. Such reported differences should be treated with caution because they are obtained from a pilot and not a definitive study. CONCLUSION: This pilot study succeeded in collecting data to inform a future definitive cost effectiveness clinical trial of Living Well with Dementia group therapy.

Randomised controlled feasibility trial of a web-based weight management intervention with nurse support for obese patients in primary care.

BACKGROUND: There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity. Automated web-based interventions might provide a solution, but evidence suggests that they may be ineffective without additional human support. The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care, comparing different levels of nurse support, to determine the optimal combination of web-based and personal support to be tested in a full trial. METHODS: This was an individually randomised four arm parallel non-blinded trial, recruiting obese patients in primary care. Following online registration, patients were randomly allocated by the automated intervention to either usual care, the web-based intervention only, or the web-based intervention with either basic nurse support (3 sessions in 3 months) or regular nurse support (7 sessions in 6 months). The main outcome measure (intended as the primary outcome for the main trial) was weight loss in kg at 12 months. As this was a feasibility trial no statistical analyses were carried out, but we present means, confidence intervals and effect sizes for weight loss in each group, uptake and retention, and completion of intervention components and outcome measures. RESULTS: All randomised patients were included in the weight loss analyses (using Last Observation Carried Forward). At 12 months mean weight loss was: usual care group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg. Intervention effect sizes compared with usual care were: d = 0.01 web-based; d = 0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated from protocol by providing considerable weight management support to their usual care patients. CONCLUSIONS: This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care, and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31685626.

Delayed antibiotic prescribing strategies for respiratory tract infections in primary care: pragmatic, factorial, randomised controlled trial.

OBJECTIVE: To estimate the effectiveness of different strategies involving delayed antibiotic prescription for acute respiratory tract infections. DESIGN: Open, pragmatic, parallel group, factorial, randomised controlled trial. SETTING: Primary care in the United Kingdom. PATIENTS: 889 patients aged 3 years and over with acute respiratory tract infection, recruited between 3 March 2010 and 28 March 2012 by 53 health professionals in 25 practices. INTERVENTIONS: Patients judged not to need immediate antibiotics were randomised to undergo four strategies of delayed prescription: recontact for a prescription, post-dated prescription, collection of the prescription, and be given the prescription (patient led). During the trial, a strategy of no antibiotic prescription was added as another randomised comparison. Analysis was intention to treat. MAIN OUTCOME MEASURES: Mean symptom severity (0-6 scale) at days 2-4 (primary outcome), antibiotic use, and patients' beliefs in the effectiveness of antibiotic use. Secondary analysis included comparison with immediate use of antibiotics. RESULTS: Mean symptom severity had minimal differences between the strategies involving no prescription and delayed prescription (recontact, post-date, collection, patient led; 1.62, 1.60, 1.82, 1.68, 1.75, respectively; likelihood ratio test χ(2) 2.61, P=0.625). Duration of symptoms rated moderately bad or worse also did not differ between no prescription and delayed prescription strategies combined (median 3 days v 4 days; 4.29, P=0.368). There were modest and non-significant differences in patients very satisfied with the consultation between the randomised groups (79%, 74%, 80%, 88%, 89%, respectively; likelihood ratio test χ(2) 2.38, P=0.667), belief in antibiotics (71%, 74%, 73%, 72%, 66%; 1.62, P=0.805), or antibiotic use (26%, 37%, 37%, 33%, 39%; 4.96, P=0.292). By contrast, most patients given immediate antibiotics used antibiotics (97%) and strongly believed in them (93%), but with no benefit for symptom severity (score 1.76) or duration (median 4 days). CONCLUSION: Strategies of no prescription or delayed antibiotic prescription result in fewer than 40% of patients using antibiotics, and are associated with less strong beliefs in antibiotics, and similar symptomatic outcomes to immediate prescription. If clear advice is given to patients, there is probably little to choose between the different strategies of delayed prescription. TRIAL REGISTRATION: ISRCTN38551726.

Antibiotic prescription strategies for acute sore throat: a prospective observational cohort study.

BACKGROUND: Data from trials suggest that antibiotics reduce the risk of complications of sore throat by at least 50%, but few trials for complications have been done in modern settings, and datasets of delayed antibiotic prescription are underpowered. Observational evidence is important in view of poor compliance with antibiotic treatment outside trials, but no prospective observational cohort studies have been done to date. METHODS: We generated a large prospective cohort from the DESCARTE study, and the PRISM component of DESCARTE, of 12,829 adults presenting with sore throat (≤ 2 weeks duration) in primary care. Our follow-up of the cohort was based on a detailed and structured review of routine medical records, and analysis of the comparison of three antibiotic prescription strategies (no antibiotic prescription, immediate antibiotic prescription, and delayed antibiotic prescription) to control for the propensity to prescribe antibiotics. Information about antibiotic prescription was recorded in 12,677 individuals (4805 prescribed no antibiotics, 6088 prescribed antibiotics immediately, and 1784 prescribed delayed antibiotics). We documented by review of patients' notes (n=11,950) the development of suppurative complications (eg, quinsy, impetigo and cellulitis, otitis media, and sinusitis) or reconsultation with new or non-resolving symptoms). We used multivariate analysis to control for variables significantly related to the propensity to prescribe antibiotics and for clustering by general practitioner. FINDINGS: 164 (1.4%) of the 11,950 patients with information available developed complications; otitis media and sinusitis were the most common complications (101 patients [62%]). Compared with no antibiotic prescription, immediate antibiotic prescription was associated with fewer complications (adjusted risk ratio [RR] 0.62, 95% CI 0.43-0.91, estimated number needed to treat [NNT 193) as was delayed prescription of antibiotics (0.58, 0.34-0.98; NNT 174). 1787 of the 11,950 patients (15%) reconsulted with new or non-resolving symptoms; the risk of reconsultation was also reduced by immediate (0.83, 0.73-0.94; NNT 40) or delayed antibiotics (0.61, 0.50-0.74; NNT 18). INTERPRETATION: Suppurative complications are not common in primary care and most are not serious. The risks of suppurative complications or reconsultation in adults are reduced by antibiotics, but not as much as the trial evidence suggests. In most cases, no antibiotic is needed, but a delayed prescription strategy is likely to provide similar benefits to an immediate antibiotic prescription.

PRImary care Streptococcal Management (PRISM) study: in vitro study, diagnostic cohorts and a pragmatic adaptive randomised controlled trial with nested qualitative study and cost-effectiveness study.

BACKGROUND: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. OBJECTIVE: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. DESIGN: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. SETTING: The setting was UK primary care general practices. PARTICIPANTS: Participants were patients aged ≥ 3 years with acute sore throat. INTERVENTIONS: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. MAIN OUTCOME MEASURES: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2-4 days). RESULTS: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (-0.33; 95% confidence interval -0.64 to -0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (-0.30; -0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals' concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. CONCLUSIONS: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals' concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians' perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32027234. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 6. See the NIHR Journals Library website for further project information.

Predictors of suppurative complications for acute sore throat in primary care: prospective clinical cohort study.

OBJECTIVE: To document whether elements of a structured history and examination predict adverse outcome of acute sore throat. DESIGN: Prospective clinical cohort. SETTING: Primary care. PARTICIPANTS: 14,610 adults with acute sore throat (≤ 2 weeks' duration). MAIN OUTCOME MEASURES: Common suppurative complications (quinsy or peritonsillar abscess, otitis media, sinusitis, impetigo or cellulitis) and reconsultation with new or unresolving symptoms within one month. RESULTS: Complications were assessed reliably (inter-rater κ=0.95). 1.3% (177/13,445) of participants developed complications overall and 14.2% (1889/13,288) reconsulted with new or unresolving symptoms. Independent predictors of complications were severe tonsillar inflammation (documented among 13.0% (1652/12,717); odds ratio 1.92, 95% confidence interval 1.28 to 2.89) and severe earache (5% (667/13,323); 3.02, 1.91 to 4.76), but the model including both variables had modest prognostic utility (bootstrapped area under the receiver operator curve 0.61, 0.57 to 0.65), and 70% of complications (124/177) occurred when neither was present. Clinical prediction rules for bacterial infection (Centor criteria and FeverPAIN) also predicted complications, but predictive values were also poor and most complications occurred with low scores (67% (118/175) scoring ≤ 2 for Centor; 126/173 (73%) scoring ≤ 2 for FeverPAIN). Previous medical problems, sex, temperature, and muscle aches were independently but weakly associated with reconsultation with new or unresolving symptoms. CONCLUSION: Important suppurative complications after an episode of acute sore throat in primary care are uncommon. History and examination and scores to predict bacterial infection cannot usefully identify those who will develop complications. Clinicians will need to rely on strategies such as safety netting or delayed prescription in managing the uncertainty and low risk of complications.