Eliciting and prioritising determinants of improved care in multimorbidity: A modified online Delphi study.

Background: Multimorbidity is a major challenge to health and social care systems around the world. There is limited research exploring the wider contextual determinants that are important to improving care for this cohort. In this study, we aimed to elicit and prioritise determinants of improved care in people with multiple conditions. Methods: A three-round online Delphi study was conducted in England with health and social care professionals, data scientists, researchers, people living with multimorbidity and their carers. Results: Our findings suggest a care system which is still predominantly single condition focused. 'Person-centred and holistic care' and 'coordinated and joined up care', were highly rated determinants in relation to improved care for multimorbidity. We further identified a range of non-medical determinants that are important to providing holistic care for this cohort. Conclusions: Further progress towards a holistic and patient-centred model is needed to ensure that care more effectively addresses the complex range of medical and non-medical needs of people living with multimorbidity. This requires a move from a single condition focused biomedical model to a person-based biopsychosocial approach, which has yet to be achieved.

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

Use of antibiotics and other treatments in Chinese adults with acute cough: An online survey.

Background: This study aimed to identify use of various treatments and their association with the use of antibiotics and patient reported clinical recovery in Chinese adults with acute cough. Methods: An online survey recruiting people who had recently experienced cough was conducted. Their sociodemographic, clinical characteristics, treatments received and their perceived changes in symptoms were collected. Factors influencing avoidance of antibiotics and improvement in symptoms were explored. Results: A total of 22,787 adults with recent acute cough completed the questionnaire, covering all 34 province-level administrative units in China. Most respondents were male (68.0%), young (89.4%, aged 18-45), educated to university/degree or postgraduate level (44.6%), with a median cough severity of 6/10 on a numerical rating scale. Nearly half of the participants (46.4%) reported using antibiotics, among which 93.1% were for presumed upper respiratory tract infections (URTIs). Pharmacies (48.8%) were the most common source of antibiotics. Fewer patients took antibiotics after taking CHM (14.9%), compared to those who started with home remedies (18.0%), or allopathic non-antibiotic medication (25.0%). Antibiotics, allopathic non-antibiotic medications, CHM and home remedies were all perceived beneficial in relieving cough. Conclusions: Chinese adult responders report use of a considerable variety of treatments alone or in combination for acute cough. Patient-reported clinical recovery was similar regardless of treatment. There is likely a high proportion of inappropriate use of antibiotics for treatment of simple acute cough. As the majority of respondents did not use antibiotics as a first-line, and use of CHM was associated with relief of cough symptoms and reduction in the use of antibiotics, this presents an important opportunity for prudent antibiotic stewardship in China.

Treating Acute EXacerbations of COPD with Chinese HerbAL MedIcine to aid AntiBiotic Use Reduction (EXCALIBUR): study protocol of a randomised double-blind, placebo-controlled feasibility trial.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major reason for consultations in primary care, hospital admissions, deterioration in function, and mortality. Despite the majority of exacerbations not being caused by bacteria, as many as 70% of patients who present in UK primary care with AECOPD are prescribed antibiotics as part of standard care. However, finding effective non-antibiotic treatments for COPD exacerbations is a priority to reduce antibiotic use. The Chinese herbal medicine Shufeng Jiedu® (SFJD) has the potential to reduce treatment failure and duration of hospital stay. This study aims to determine the feasibility of conducting a fully powered randomised, double blind, placebo-controlled clinical trial on SFJD for AECOPD in UK primary care. METHODS: This study is a phase III, two-arm individually double blind, randomised, placebo-controlled feasibility trial with nested qualitative study, coordinated by the Southampton Clinical Trial Unit (SCTU). Patients aged ≥ 40 years, with a current AECOPD, presenting with increased sputum purulence/volume, or breathlessness, and for whom the GP is considering use of antibiotics, will be eligible to participate. We aim to recruit seven eligible participants per month and randomise them to receive either the patent Chinese herbal medicine SFJD capsules or placebo for 14 consecutive days and to follow-up for 12 weeks. The primary outcomes include the feasibility of recruitment, study retention, and the percentage of diary completion. DISCUSSION: If this trial demonstrates the feasibility of recruitment, delivery, and follow-up, we will seek funding for a fully powered placebo-controlled trial of SFJD for the treatment of AECOPD in primary care. TRIAL REGISTRATION: This trial is registered via ISRCTN on 1 July 2021, identifier: ISRCTN26614726.

Development and Validation of Population Clusters for Integrating Health and Social Care: Protocol for a Mixed Methods Study in Multiple Long-Term Conditions (Cluster-Artificial Intelligence for Multiple Long-Term Conditions).

BACKGROUND: Multiple long-term health conditions (multimorbidity) (MLTC-M) are increasingly prevalent and associated with high rates of morbidity, mortality, and health care expenditure. Strategies to address this have primarily focused on the biological aspects of disease, but MLTC-M also result from and are associated with additional psychosocial, economic, and environmental barriers. A shift toward more personalized, holistic, and integrated care could be effective. This could be made more efficient by identifying groups of populations based on their health and social needs. In turn, these will contribute to evidence-based solutions supporting delivery of interventions tailored to address the needs pertinent to each cluster. Evidence is needed on how to generate clusters based on health and social needs and quantify the impact of clusters on long-term health and costs. OBJECTIVE: We intend to develop and validate population clusters that consider determinants of health and social care needs for people with MLTC-M using data-driven machine learning (ML) methods compared to expert-driven approaches within primary care national databases, followed by evaluation of cluster trajectories and their association with health outcomes and costs. METHODS: The mixed methods program of work with parallel work streams include the following: (1) qualitative semistructured interview studies exploring patient, caregiver, and professional views on clinical and socioeconomic factors influencing experiences of living with or seeking care in MLTC-M; (2) modified Delphi with relevant stakeholders to generate variables on health and social (wider) determinants and to examine the feasibility of including these variables within existing primary care databases; and (3) cohort study with expert-driven segmentation, alongside data-driven algorithms. Outputs will be compared, clusters characterized, and trajectories over time examined to quantify associations with mortality, additional long-term conditions, worsening frailty, disease severity, and 10-year health and social care costs. RESULTS: The study will commence in October 2021 and is expected to be completed by October 2023. CONCLUSIONS: By studying MLTC-M clusters, we will assess how more personalized care can be developed, how accurate costs can be provided, and how to better understand the personal and medical profiles and environment of individuals within each cluster. Integrated care that considers "whole persons" and their environment is essential in addressing the complex, diverse, and individual needs of people living with MLTC-M. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/34405.

A feasibility trial of a digital mindfulness-based intervention to improve asthma-related quality of life for primary care patients with asthma.

Asthma outcomes remain suboptimal, despite effective pharmacotherapy. Psychological dysfunction (such as anxiety) is common, and associated with poorer outcomes. We evaluated a digital mindfulness programme as an intervention to improve asthma-related quality of life for primary care patients, in a prospectively registered randomized-controlled feasibility study. We offered 'Headspace', a widely-used digital mindfulness intervention, to adults with asthma through 16 UK GP practices. Participants were randomized on a 2:1 basis to the mindfulness intervention, or waitlist control. Participants completed questionnaires (including asthma symptom control, asthma-related quality of life, anxiety, depression) at baseline, 6-week and 3-month follow-up. 116 participants completed primary outcomes at 3-month follow-up: intervention 73 (79%), control 43 (84%). Compared to baseline, the intervention group but not the control group reported significantly improved asthma-related quality of life, with a between-group difference favoring the intervention group that was not significant (Mean difference = 0.15, 95%CI - 0.13 to 0.42). Intervention use varied (ranging from 0 to 192 times) but was generally high. Digital mindfulness interventions are feasible and acceptable adjunct treatments for mild and moderate asthma to target quality of life. Further research should adapt 'generic' mindfulness-based stress-reduction to maximize effectiveness for asthma, and validate our findings in a fully-powered randomized controlled trial.Trial registration Prospectively registered: ISRCTN52212323.

Diarrhoea Management using Over-the-counter Nutraceuticals in Daily practice (DIAMOND): a feasibility RCT on alternative therapy to reduce antibiotic use.

BACKGROUND: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomised, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. METHODS: Adults with acute uncomplicated diarrhoea aged 18 to 70 were randomised to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 h if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2-week follow-up period. Semi-structured interviews were conducted following recruitment and were analysed thematically. Recruiting doctors, delivery pharmacists and research assistants were blinded to treatment allocation. RESULTS: Only 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and were entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only three participants used rescue antibiotics compared to 67% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was 14 h in group B (interquartile range (IQR) 10-22), 16 h in group D (IQR 10-22), 18 h in group A (IQR 10-33) and 20 h in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said that although they had believed antibiotics to be effective for diarrhoea, they were surprised by their quick recovery without antibiotics in this trial. CONCLUSION: Although recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted trying an alternative. The three nutraceuticals therapy require further evaluation in a fully powered, randomised controlled trial among a broader sample. TRIAL REGISTRATION: ChiCTR-IPR-17014107.

Direct and mediated effects of treatment context on low back pain outcome: a prospective cohort study.

OBJECTIVES: Contextual components of treatment previously associated with patient outcomes include the environment, therapeutic relationship and expectancies. Questions remain about which components are most important, how they influence outcomes and comparative effects across treatment approaches. We aimed to identify significant and strong contextual predictors of patient outcomes, test for psychological mediators and compare effects across three treatment approaches. DESIGN: Prospective cohort study with patient-reported and practitioner-reported questionnaire data (online or paper) collected at first consultation, 2 weeks and 3 months. SETTING: Physiotherapy, osteopathy and acupuncture clinics throughout the UK. PARTICIPANTS: 166 practitioners (65 physiotherapists, 46 osteopaths, 55 acupuncturists) were recruited via their professional organisations. Practitioners recruited 960 adult patients seeking treatment for low back pain (LBP). PRIMARY AND SECONDARY OUTCOMES: The primary outcome was back-related disability. Secondary outcomes were pain and well-being. Contextual components measured were: therapeutic alliance; patient satisfaction with appointment systems, access, facilities; patients' treatment beliefs including outcome expectancies; practitioners' attitudes to LBP and practitioners' patient-specific outcome expectancies. The hypothesised mediators measured were: patient self-efficacy for pain management; patient perceptions of LBP and psychosocial distress. RESULTS: After controlling for baseline and potential confounders, statistically significant predictors of reduced back-related disability were: all three dimensions of stronger therapeutic alliance (goal, task and bond); higher patient satisfaction with appointment systems; reduced patient-perceived treatment credibility and increased practitioner-rated outcome expectancies. Therapeutic alliance over task (ηp2=0.10, 95% CI 0.07 to 0.14) and practitioner-rated outcome expectancies (ηp2=0.08, 95% CI 0.05 to 0.11) demonstrated the largest effect sizes. Patients' self-efficacy, LBP perceptions and psychosocial distress partially mediated these relationships. There were no interactions with treatment approach. CONCLUSIONS: Enhancing contextual components in musculoskeletal healthcare could improve patient outcomes. Interventions should focus on helping practitioners and patients forge effective therapeutic alliances with strong affective bonds and agreement on treatment goals and how to achieve them.

Pelargonium sidoides root extract for the treatment of acute cough due to lower respiratory tract infection in adults: a feasibility double-blind, placebo-controlled randomised trial.

BACKGROUND: Pelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or "Kaloba®", is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries. STUDY DESIGN: Feasibility double-blind randomised placebo-controlled clinical trial. METHODS: We aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2-4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial. RESULTS: Of 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18-21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex. CONCLUSIONS: It was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition. TRIAL REGISTRATION: HATRIC was registered on the ISRCTN registry ( ISRCTN17672884 ) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884 .

The RUTI trial: A feasibility study exploring Chinese herbal medicine for the treatment of recurrent urinary tract infections.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is a widely used traditional intervention that may have a role to play in addressing the global problem of antimicrobial resistance in conditions such as recurrent urinary tract infections (RUTIs). AIM OF THE STUDY: To evaluate the feasibility of administering standardised and individualised formulations of CHM for RUTIs as a Clinical Trial of an Investigational Medicinal Product (CTIMP) within primary care of the UKs National Health Service (NHS). MATERIALS AND METHODS: Regulatory approval was applied for a placebo controlled, double blinded randomised controlled feasibility trial comparing a) standardised CHM vs placebo administered via General practitioners, and b) individualised CHM vs placebo administered by an experienced CHM practitioner. Primary feasibility outcomes included: gaining regulatory approval, recruitment, randomisation, retention, safety and the relevance of outcomes measures. RESULTS: Regulatory approval for testing CHM as a CTIMP was successfully obtained. Recruitment to the trial was slow and non-NHS self help networks were required to find participants for the individualised arm (n = 31). Retention and data collection in the standardised arm (n-30) were problematic, but these were acceptable in the individualised arm. The use of a daily symptom diary was not a suitable outcome measure for women with continuous infection. Other measures showed promising preliminary data for the individualised arm on improvement in symptoms, and reduction in antibiotic use during and after the trial. CONCLUSION: CHM can fulfil the demanding requirements of a CTIMP study but it may not be feasible at this point in time to recruit and treat via NHS primary care. However acceptable rates of recruitment and retention via self-help groups and promising preliminary results in the individualised arm suggest it would be worth testing this approach in a full trial.

Managing Antidepressant Discontinuation: A Systematic Review.

PURPOSE: We aimed to determine the effectiveness of interventions to manage antidepressant discontinuation, and the outcomes for patients. METHODS: We conducted a systematic review with narrative synthesis and meta-analysis of studies published to March 2017. Studies were eligible for inclusion if they were randomized controlled trials, quasi-experimental studies, or observational studies assessing interventions to facilitate discontinuation of antidepressants for depression in adults. Our primary outcomes were antidepressant discontinuation and discontinuation symptoms. Secondary outcomes were relapse/recurrence; quality of life; antidepressant reduction; and sexual, social, and occupational function. RESULTS: Of 15 included studies, 12 studies (8 randomized controlled trials, 2 single-arm trials, 2 retrospective cohort studies) were included in the synthesis. None were rated as having high risk for selection or detection bias. Two studies prompting primary care clinician discontinuation with antidepressant tapering guidance found 6% and 7% of patients discontinued, vs 8% for usual care. Six studies of psychological or psychiatric treatment plus tapering reported cessation rates of 40% to 95%. Two studies reported a higher risk of discontinuation symptoms with abrupt termination. At 2 years, risk of relapse/recurrence was lower with cognitive behavioral therapy plus taper vs clinical management plus taper (15% to 25% vs 35% to 80%: risk ratio = 0.34; 95% CI, 0.18-0.67; 2 studies). Relapse/recurrence rates were similar for mindfulness-based cognitive therapy with tapering and maintenance antidepressants (44% to 48% vs 47% to 60%; 2 studies). CONCLUSIONS: Cognitive behavioral therapy or mindfulness-based cognitive therapy can help patients discontinue antidepressants without increasing the risk of relapse/recurrence, but are resource intensive. More scalable interventions incorporating psychological support are needed.

Andrographis paniculata (Chuan Xin 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, Chuan Xin 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.

Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study.

BACKGROUND: High sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut. METHODS: A double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19-59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose) versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract. RESULTS: Thirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC) (glucose (mmol / L x h)) for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316), -14.0% (-26.0%, -2.0%; p = 0.022) and -22.0% (-33.9%, -10.0%; p<0.001) respectively. The difference in the pIAUC (insulin (mIU / L x h)) for half, normal and double dose ME compared with placebo was -9.7% (-25.8%, 6.3%; p = 0.234), -23.8% (-39.9%, -7.8%; p = 0.004) and -24.7% (-40.8%, -8.6%; p = 0.003) respectively. There were no statistically significant differences between any of the 4 groups in the odds of experiencing one or more gastrointestinal symptoms (nausea, abdominal cramping, distension or flatulence). CONCLUSIONS: Mulberry leaf extract significantly reduces total blood glucose rise after ingestion of maltodextrin over 120 minutes. The pattern of effect demonstrates a classical dose response curve with significant effects over placebo. Importantly, total insulin rises were also significantly suppressed over the same time-period. There were no statistically significant differences between any of the treatment groups (including placebo) in the odds of experiencing one or more gastrointestinal symptoms. Mulberry extract may have multiple modes of action and further studies are necessary to evaluate ME as a potential target for the prevention of type 2 diabetes and the regulation of dysglycaemia.

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.

Standardised Chinese herbal treatment delivered by GPs compared with individualised treatment administered by practitioners of Chinese herbal medicine for women with recurrent urinary tract infections (RUTI): study protocol for a randomised controlled trial.

BACKGROUND: In the UK, urinary tract infections (UTIs) are the most common bacterial infection presented by women in primary care. Recurrent urinary tract infections (RUTIs) are defined as three episodes of UTI in the last 12 months, or two episodes in the last 6 months. Between 20 and 30 % of women who have had one episode of UTI will have an RUTI, and approximately 25 % of these will develop subsequent recurrent episodes. RUTIs can have a significant negative effect on the quality of life, and have a high impact on health care costs as a result of outpatient visits, diagnostic tests and prescriptions. Chinese herbal medicine (CHM) has a recorded history of treatments for the symptoms of UTIs for more than 2000 years. More recent clinical research in China has provided some preliminary evidence that CHM can alleviate the symptoms of UTIs and reduce the rate of recurrence, but more rigorous investigation is required. METHODS/DESIGN: The RUTI trial is a double-blind, randomised, placebo-controlled, feasibility trial. A total of 80 women will be randomised to 'individualised' herbs prescribed by a Chinese herbal practitioner or to 'standardised' herbs provided by primary care clinicians. Both arms will have herbs for prevention of UTIs and treatment of acute episodes. Treatment duration is for 16 weeks. The primary outcomes are the number of episodes of recurrent UTIs during the trial period and in the 6 months of follow-up, and the number of days of symptoms rated moderately bad or worse based on patient diaries. Secondary outcomes will assess participant expectations and beliefs, adherence to the treatment, adverse events and health economics and provide quantitative and qualitative assessments of the impact of recurrent infections on the lives of women. DISCUSSION: The RUTI trial is the first instance of CHM delivered as a clinical trial of an investigatory medicinal product in the UK. This study provides important information regarding the feasibility and acceptability of researching and using CHM in Primary care. Once completed, it will provide provisional estimates of the variance of change in continuous outcomes to inform a power calculation for a larger, more definitive trial. TRIAL REGISTRATION: EudraCT, 2013-004657-24 . Registered on 5 September 2014.

Mulberry extract to modULate Blood glucosE Responses in noRmoglYcaemic adults (MULBERRY): study protocol for a randomised controlled trial.

BACKGROUND: Worldwide sugar consumption has tripled during the last fifty years. High sugar intake is associated with weight gain and increased incidence of diabetes and has been linked with increased cardiovascular mortality. Reducing the health impact of dietary sugar and poor quality carbohydrate intake is a public health priority. IminoNorm®, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary sugar and carbohydrate intake by reducing absorption of glucose from the gut. Previous research has shown that ME can reduce blood glucose and improve insulin responses in healthy subjects and also in subjects with raised fasting blood glucose levels. Mulberry leaf has an excellent safety profile. This pilot study will test a novel, safe, water soluble product in normoglycaemic adults in the UK to determine if it can reduce glucose absorption without increasing plasma insulin concentration. METHODS/DESIGN: The trial will be a double-blind, individually randomised, four-arm single-dose crossover design to test the effect of three doses of ME in order to determine efficacy, dose response relationship and gastrointestinal side effects with respect to placebo. A total of 40 subjects will participate in this study and attend for four visits receiving each of the four interventions in random order. DISCUSSION: We aim to test the evidence that mulberry leaf extract can reduce blood glucose without a disproportionate increase in blood insulin responses in healthy individuals in a high-quality research study based in the UK. It is hoped that this will lead to further randomised controlled trials and an effective dietary supplement to lower blood glucose concentrations. ISRCTN: ISRCTN14597438 (21 April 2015).