Beth Stuart

Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis

Introduction Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuān Xīn Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs). Materials and methods English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data. Results Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor. Conclusions A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.

Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial

Summary Background High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems. Methods After a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214. Results The baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 [55·3%]) and upper-respiratory-tract infections (1416 [20·9%]), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42–0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54–0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36–0·74, p<0·0001; enhanced communication 0·68, 0·50–0·89, p=0·003; combined 0·38, 0·25–0·55, p<0·0001). Interpretation Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries. Funding European Commission Framework Programme 6, National Institute for Health Research, Research Foundation Flanders.

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 χ2 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 χ2 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.

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.

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial

BackgroundTo reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners’ (GPs’) and patients’ attitudes.MethodsGPs were cluster randomised to one of three intervention groups or a control group. The intervention groups received web-based training in either use of the C-reactive protein (CRP) test, communication skills and use of a patient booklet, or training in both. GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Questionnaire. Effects of the interventions on patients were assessed by a post-intervention questionnaire assessing patient enablement, satisfaction with the consultation, and beliefs about the risks and need for antibiotics.ResultsGPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training, and felt that taking part had helped them to reduce prescribing. All GPs perceived reducing prescribing as more important and less risky following the intervention, and GPs in the communication groups reported increased confidence to reduce prescribing. Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful.ConclusionsOur findings suggest that the interventions should be broadly acceptable to both GPs and patients, as well as feasible to roll out more widely across Europe. There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term, such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them. Given the positive effects of the booklet on patient beliefs and attitudes, it seems logical to extend the use of the patient booklet to all patients.

Does Brief Telephone Support Improve Engagement With a Web-Based Weight Management Intervention? Randomized Controlled Trial

Background Recent reviews suggest Web-based interventions are promising approaches for weight management but they identify difficulties with suboptimal usage. The literature suggests that offering some degree of human support to website users may boost usage and outcomes. Objective We disseminated the POWeR (“Positive Online Weight Reduction”) Web-based weight management intervention in a community setting. POWeR consisted of weekly online sessions that emphasized self-monitoring, goal-setting, and cognitive/behavioral strategies. Our primary outcome was intervention usage and we investigated whether this was enhanced by the addition of brief telephone coaching. We also explored group differences in short-term self-reported weight loss. Methods Participants were recruited using a range of methods including targeted mailouts, advertisements in the local press, notices on organizational websites, and social media. A total of 786 adults were randomized at an individual level through an online procedure to (1) POWeR only (n=264), (2) POWeR plus coaching (n=247), or (3) a waiting list control group (n=275). Those in the POWeR plus coaching arm were contacted at approximately 7 and 28 days after randomization for short coaching telephone calls aimed at promoting continued usage of the website. Website usage was tracked automatically. Weight was assessed by online self-report. Results Of the 511 participants allocated to the two intervention groups, the median number of POWeR sessions completed was just one (IQR 0-2 for POWeR only, IQR 0-3 for POWeR plus coach). Nonetheless, a substantial minority completed at least the core three sessions of POWeR: 47 participants (17.8%, 47/264) in the POWeR-only arm and 64 participants (25.9%, 64/247) in the POWeR plus coaching arm. Participants in the POWeR plus coaching group persisted with the intervention for longer and were 1.61 times more likely to complete the core three sessions than the POWeR-only group (χ2 1=4.93; OR 1.61, 95% CI 1.06-2.47; n=511). An intention-to-treat analysis showed between-group differences in weight loss (F 2,782=12.421, P<.001). Both intervention groups reported more weight loss than the waiting list control group. Weight loss was slightly, but not significantly, greater in the POWeR plus coaching group. A large proportion of participants assigned to POWeR plus coaching refused phone calls or were not contactable (57.9%, 143/247). Exploratory analyses identified health and sociodemographic differences between those who did and did not engage in coaching when it was made available to them. Users who engaged with coaching used the intervention more and lost more weight than those who did not. Conclusions In common with most Web-based intervention studies, usage of POWeR was suboptimal overall. However, our findings suggest that supplementing Web-based weight management with brief human support could improve usage and outcomes in those who take it up. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 98176068; http://www.controlled-trials.com/ISRCTN98176068 (Archived by WebCite at http://www.webcitation.org/6OKRjM2oy).

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.

Supporting Self-Care for Families of Children With Eczema With a Web-Based Intervention Plus Health Care Professional Support: Pilot Randomized Controlled Trial

Background Childhood eczema, or childhood atopic dermatitis, causes significant distress to children and their families through sleep disturbance and itch. The main cause of treatment failure is nonuse of prescribed treatments. Objective The objective of this study was to develop and test a Web-based intervention to support families of children with eczema, and to explore whether support from a health care professional (HCP) is necessary to engage participants with the intervention. Methods We followed the PRECEDE-PROCEED model: regular emollient use was the target behavior we were seeking to promote and we identified potential techniques to influence this. LifeGuide software was used to write the intervention website. Carers of children with eczema were invited through primary care mail-out and randomized to 3 groups: (1) website only, (2) website plus HCP support, or (3) usual care. Patient-Oriented Eczema Measure (POEM) scores were measured online by carer report at baseline and at 12 weeks. Qualitative interviews were carried out with 13 HCPs (primarily practice nurses) and 26 participants to explore their experiences of taking part in the study. Results A total of 143 carers were recruited through 31 practices. We found a decrease of ≥2 in follow-up compared with baseline POEM score in 23 of 42 (55%) participants in the website only group, 16 of 49 (33%) in the usual care group, and 18 of 47 (38%) in the website plus HCP group. Website use data showed that 75 of 93 (81%) participants allocated to the website groups completed the core modules, but less than half used other key components (videos: 35%; regular text reminders: 39%). There were no consistent differences in website use between the website only or the website plus HCP groups. Qualitative feedback showed that most HCPs had initial concerns about providing support for eczema self-care because this was not a condition that they felt expert in. However, HCPs reported productive consultations and that they found it helpful to use the website in consultations, while observing that some participants seemed to need more support than others. Qualitative interviews with participants suggested that HCP support was valued highly only by a minority, generally those who were less confident in their management of eczema or less confident using the Internet. Conclusions Our pilot trial demonstrated the potential for greater improvements in POEM scores in both website intervention groups and that a full-scale trial is feasible. Such a trial would quantify the effectiveness and cost-effectiveness of this intervention to determine whether it should be widely promoted to families of children with newly diagnosed eczema. In this study population, HCP support was not strongly valued by participants and did not lead to better outcomes or website use than use of the Web-based intervention alone. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 98560867; http://www.controlled-trials.com/ISRCTN98560867 (Archived by WebCite at http://www.webcitation.org/6NcxvMtgN).

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial

BACKGROUND The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. METHODS We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. FINDINGS Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6-2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34-2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96-2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31-2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI -129 to 195) for POWeR+F and -£25 (-268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. INTERPRETATION Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year. FUNDING Health Technology Assessment Programme of the National Institute for Health Research.

Asthma Trajectories in Early Childhood: Identifying Modifiable Factors

Background There are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories. Data and Methods The Millennium Cohort Study is a large, representative birth cohort of British children born in 2000–2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema) reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity. Results Our model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample); a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%); a trajectory with high prevalence of both wheeze and other atopic symptoms (9%); and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%). These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation. Conclusion Using data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles. We identified correlated intervenable pathways in infancy, including household damp and breastfeeding initiation.