Enhancing opportunistic recruitment and retention in primary care trials: lessons learned from a qualitative study embedded in the Cranberry for Urinary Tract Infection (CUTI) feasibility trial.

BACKGROUND: Opportunistic recruitment in primary care is challenging due to the inherent unpredictability of incident conditions, and workload and time pressures. Many clinical trials do not recruit to target, leading to equivocal answers to research questions. Learning from the experiences of patients and recruiters to trials of incident conditions has the potential to improve recruitment and retention to future trials, thereby enhancing the quality and impact of research findings. The aim of this research was to learn from the trial experiences of UTI patients and recruiters to the Cranberry for UTI (CUTI) trial, to help plan an adequately powered trial of similar design. METHODS: One-to-one semi-structured interviews were embedded within the CUTI feasibility trial, an open-label, randomised feasibility trial of cranberry extract for symptoms of acute, uncomplicated Urinary Tract Infection (UTI) in primary care. Interviews were conducted with a sample of: CUTI trial participants; non-CUTI trial UTI patients; and, recruiters to the CUTI trial. Verbatim transcripts were analysed thematically. RESULTS: Twenty-six patients with UTI and eight recruiters (nurses and GPs) to the CUTI trial were interviewed. Three themes were developed around: reasons for participating in research; barriers to opportunistic recruitment; and, UTI patients' experiences of trial procedures. Recruiters found that targeted electronic prompts directed at healthcare practitioners based in clinics where patients with incident conditions were likely to present (e.g. minor illness clinic) were more effective than generic prompts (e.g. desk prompts) at filtering patients from their usual clinical pathway to research clinics. Using a script to explain the delayed antibiotic trial group to patients was found to be helpful, and may have served to boost recruitment. For UTI patients, using an electronic diary to rate their symptoms was considered an acceptable medium, and often preferable to using a paper diary or mobile phone application. CONCLUSIONS: The use of targeted prompts directed at clinicians, a script to explain trial groups that may be deemed less desirable, and an appropriate diary format for patient-reported outcomes, may help to improve trial recruitment and retention.

Non-antibiotic treatment of acute urinary tract infection in primary care: a qualitative study.

BACKGROUND: The views of women with acute, uncomplicated urinary tract infection (auUTI) on the acceptability of non-antibiotic treatment options are poorly understood. AIM: To establish women's thoughts on and experience of non-antibiotic treatment for auUTIs. DESIGN AND SETTING: Qualitative interview study with primary care patients in Oxfordshire, UK, embedded within the Cranberry for Urinary Tract Infection (CUTI) feasibility trial. METHOD: One-to-one, semi-structured interviews were conducted between August 2019 and January 2020 with some CUTI trial participants and some patients who were not part of the CUTI trial who had experienced at least one urinary tract infection (UTI) in the preceding 12 months in Oxfordshire, UK. Interviews were analysed using thematic analysis. RESULTS: In total, 26 interviews were conducted and analysed. Women expected to receive an immediate antibiotic for their UTI but were aware of the potential harms of this approach. They were keen to find a non-antibiotic, 'natural' alternative that could effectively manage their symptoms. In certain situations (early illness, milder illness, and with no important upcoming engagements), women indicated they would be prepared to postpone antibiotic treatment by up to 3 days, especially if offered an interim non-antibiotic option with perceived therapeutic potential. CONCLUSION: Many women with auUTIs are open to trying non-antibiotic treatments first in certain situations. There is scope for more dialogue between primary care clinicians and patients with auUTI around delaying antibiotic treatment and using non-antibiotic options initially, which could reduce antibiotic consumption for this common infection.

Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized clinical trials.

AIM: To critically appraise and evaluate the evidence for effectiveness of curcuminoids in the treatment of osteoarthritis (OA) in adults. METHODS: We conducted electronic searches in Medline, Embase, AMED, Cinahl and the Cochrane library. We included randomized controlled trials (RCTs) that investigated the effectiveness of orally-administered curcuminoids in OA in adults, and assessed risk of bias using the Cochrane risk of bias criteria. We used a random-effect model for meta-analysis. RESULTS: We included seven studies with a total of 797 participants with primarily knee OA. All studies were conducted in Asia. The overall risk of bias was moderate. Compared with placebo, curcuminoids significantly reduced knee pain (visual analogue scale): (standardized mean difference: -3.45; 95% CI: -5.52 to -1.38; I2  = 95% P = 0.001), and improved quality of life (Lequesne pain-function index): (mean difference: -2.69; 95% CI: -3.48 to -1.90; I2  = 0% P < 0.00001). There were significantly fewer effects on pain relief, knee stiffness and physical function with curcuminoids compared with ibuprofen. Significant improvements in Western Ontario and McMaster Universities Arthritis Index total scores, with significant reductions in the use of rescue medication were also observed with curcuminoids. No serious adverse events were reported. CONCLUSIONS: Curcuminoids may have some beneficial effects on knee pain and quality of life in patients with knee OA. However, they are less effective at relieving pain compared with ibuprofen. Curcuminoids appear safe on the short-term, and may reduce the need for rescue medication. Published RCTs vary in reporting quality, are characterized by small sample sizes, and have all been conducted in Asia. Further clinical trials are therefore warranted.

The efficacy of supplementation with the novel medical food, Souvenaid, in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND RATIONALE: Certain nutritional supplements are being marketed for the management of Alzheimer's disease (AD), but the evidence for their effectiveness is not established. The objective of this review was to evaluate the evidence from randomized clinical trial (RCTs) examining the effect of Souvenaid in patients with AD. METHODS: We conducted electronic searches in Medline, Embase, PsychINFO, CINAHL, and The Cochrane Library. The reporting quality of the included studies was determined using the Cochrane collaboration tool for assessing the risk of bias. Two reviewers independently determined eligibility, assessed the reporting quality of included studies and extracted data. RESULTS: Three studies with a total of 1011 participants were included. All were of good reporting quality. Meta-analyses revealed non-significant differences in cognition (ADAS-cog scores MD: 0.08, 95% CI: -0.71 to 0.88) and function (ADCS-ADL scores MD: 0.36, 95% CI: -0.54 to 1.25) between Souvenaid and placebo. One study showed significant increase in neuropsychological test battery composite z-score with Souvenaid compared with placebo, and another reported significant improvement in delayed verbal recall for a subgroup of patients with very mild AD. There was no significant effect on global clinical function. No serious adverse events were observed. CONCLUSIONS: The evidence from published clinical trials does not show that supplementation with Souvenaid has beneficial effects on functional ability, behaviour, or global clinical change. Souvenaid may cause improvements in verbal recall in patients at early stages of AD. Few RCTs examining the effect of Souvenaid have been conducted, and they are all funded by same manufacturer. Future research should include using unified tools to measure cognition, function, and behaviour in AD.

The effect of cactus pear (Opuntia ficus-indica) on body weight and cardiovascular risk factors: a systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Hundreds of dietary supplements are currently marketed as weight loss supplements. However, the advertised health claims of effectiveness for most of these have not been proven. The aim of this study was to critically appraise and evaluate the evidence for effectiveness of cactus pear, Opuntia ficus-indica (OFI), using data from published randomized clinical trials. METHODS: We conducted electronic searches in Medline, Embase, Amed, Cinahl, and the Cochrane Library. No restrictions on age, time, or language were imposed. The risk for bias in the studies included was assessed using the Cochrane Collaboration criteria. Two reviewers independently determined the eligibility of included studies, assessed reporting quality, and extracted data. RESULTS: We identified seven eligible studies, of which five were included. The studies varied in design and reporting quality. Meta-analysis revealed a nonsignificant difference in body weight between OFI and controls (mean difference = -0.83 kg; 95% confidence interval, -2.49 to 0.83; I(2) = 93%). Significant reductions in body mass index, percentage body fat, systolic and diastolic blood pressures, and total cholesterol were observed. Adverse events included gastric intolerance and flu symptoms. CONCLUSION: The evidence from randomized clinical trials does not indicate that supplementation with OFI generates statistically significant effects on body weight. Consumption of OFI can cause significant reductions in percentage body fat, blood pressure, and total cholesterol. Few clinical trials evaluating the effects of OFI have been published. They vary in design and methodology, and are characterized by inconsistent quality of reporting. Further clinical trials evaluating the effects of OFI on body composition and metabolic parameters are warranted.

Effect of the novel functional fibre, polyglycoplex (PGX), on body weight and metabolic parameters: A systematic review of randomized clinical trials.

BACKGROUND & AIMS: Hundreds of dietary supplements are marketed as weight loss pills, but the evidence for effectiveness for most is unproven. The objective of this review was to critically appraise and evaluate the evidence from published randomized clinical trials (RCTs) examining the effectiveness of polyglycoplex (PGX), a novel functional fibre, on body weight and metabolic parameters. METHODS: We conducted electronic searches in Medline, Embase, Amed, Cinahl and The Cochrane Library. Only double-blinded RCTs were considered for inclusion. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined eligibility, assessed the quality of reporting, and extracted the data. RESULTS: We included four RCTs with a total of 217 participants. The RCTs varied in the quality of their reporting. The evidence from the RCTs suggested that PGX has no significant effects on body weight; however, significant reductions were noted for total and LDL cholesterol. Adverse events reported included diarrhea and abdominal bloating. CONCLUSION: The evidence from available RCTs does not indicate that PGX intake causes reductions in body weight. PGX may cause reductions in total and LDL cholesterol. Few trials examining the effects of PGX have been conducted; they are characterized by small sample sizes, deficiencies in reporting quality, and are funded by a single manufacturer. Future clinical trials evaluating its effect should be adequately powered and better reported.

Effect of the natural sweetener, steviol glycoside, on cardiovascular risk factors: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular risk factors, using data from randomised clinical trials (RCTs). METHODS: Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also searched Google Scholar, and hand searched the bibliography of retrieved full texts. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined the eligibility, assessed the reporting quality, and extracted the data. RESULTS: Nine studies with a total of 756 participants were included. There was a variation in the reporting quality of included studies. Meta-analysis revealed a non-significant difference in systolic blood pressure between steviol glycoside and placebo, mean difference (MD): -2.98 mm Hg (-6.23 to 0.27). Significant reductions in diastolic blood pressure and fasting blood glucose were observed. There was no significant effect on blood lipid profile. Heterogeneity was significant. Adverse events included abdominal fullness, epigastric pain, and dizziness. CONCLUSION: The evidence from published RCTs suggests that stevioside may generate reductions in blood pressure and fasting blood glucose. The sizes of the effects are small, and the substantial heterogeneity limits the robustness of any conclusions. Rebaudioside A does not appear to have any significant effects on blood pressure or cardiovascular risk factors. Available clinical trials vary in design and reporting quality, and some are characterised by inadequate sample sizes. In addition, the participants in most of the trials have high cardiovascular risk. Further clinical trials and regulatory assessments are warranted.

Vitamin K for improved anticoagulation control in patients receiving warfarin.

BACKGROUND: Effective use of warfarin involves keeping the international normalised ratio (INR) within a relatively narrow therapeutic range. However, patients respond widely to their dose of warfarin. Overcoagulation can lead to an increased risk of excessive bleeding, while undercoagulation can lead to increased clot formation. There is some evidence that patients with a variable response to warfarin may benefit from a concomitant low dose of vitamin K. OBJECTIVES: To assess the effects of concomitant supplementation of low-dose oral vitamin K for anticoagulation control in patients being initiated on or taking a maintenance dose of warfarin. SEARCH METHODS: To identify previous reviews, we searched the Database of Abstracts of Reviews of Effects (DARE via The Cochrane Library, Wiley) (Issue 2, 2011). To identify primary studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL via The Cochrane Library, Wiley) (Issue 2, 2014), Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations database and Ovid MEDLINE (R) (OvidSP) (1946 to 25 February 2014), Embase (OvidSP) (1974 to week 8 of 2014), Science Citation Index Expanded™ & Conference Proceedings Citation Index - Science (Web of Science™) (1945 to 27 February 2014), and the NHS Economics Evaluations Database (NHS EED) (via The Cochrane Library, Wiley) (Issue 2, 2014). We did not apply any language or date restrictions. We used additional methods to identify grey literature and ongoing studies. SELECTION CRITERIA: Randomised controlled trials comparing the addition of vitamin K versus placebo in patients initiating warfarin or already taking warfarin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and extracted data from included studies. When disagreement arose, a third author helped reached a consensus. We also assessed risk of bias. MAIN RESULTS: We identified two studies with a total of 100 participants for inclusion in the review. We found the overall risk of bias to be unclear in a number of domains. Neither study reported the time taken to the first INR in range. Only one study (70 participants) reported the mean time in therapeutic range as a percentage. This study found that in the group of participants deemed to have poor INR control, the addition of 150 micrograms (mcg) oral vitamin K significantly improved anticoagulation control in those with unexplained instability of response to warfarin. The second study (30 participants) reported the effect of 175 mcg oral vitamin K versus placebo on participants with high variability in their INR levels. The study concluded that vitamin K supplementation did not significantly improve the stability of anticoagulation for participants on chronic anticoagulation therapy. However, the study was only available in abstract form, and communication with the lead author confirmed that there were no further publications. Therefore, we interpreted this conclusion with caution. Neither study reported any thromboembolic events, haemorrhage, or death from the addition of vitamin K supplementation. AUTHORS' CONCLUSIONS: Two included studies in this review compared whether the addition of a low dose (150 to 175 mcg) of vitamin K given to participants with a high-variability response to warfarin improved their INR control. One study demonstrated a significant improvement, while another smaller study (published in abstract only) suggested no overall benefit. Currently, there are insufficient data to suggest an overall benefit. Larger, higher quality trials are needed to examine if low-dose vitamin K improves INR control in those starting or already taking warfarin.

Device-guided breathing exercises in the control of human blood pressure: systematic review and meta-analysis.

OBJECTIVE: To evaluate whether device-guided breathing (DGB) lowers blood pressure (BP) in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched Medline (1950-2010), Embase (1980-2010), the Cochrane Library including the Cochrane Central register of Controlled Trials (CENTRAL), AMED (1985-2010), CINAHL (1980-2010) and the Current Controlled Trials registry (as of October 2010). OUTCOME MEASURES: Primary outcomes included the mean change in SBP and DBP. Secondary outcomes included change in heart rate, quality of life, compliance with the device and any side effects of the device. RESULTS: We included eight trials of the Resperate device (InterCure Ltd, Lod, Israel), consisting of 494 adult patients. Use of this device resulted in significantly reduced SBP by 3.67 mmHg [95% confidence interval (CI) = -5.99 to -1.39; P = 0.002] and decreased DBP by 2.51 mmHg (95% CI = -4.15 to -0.87; P = 0.003). However, sensitivity analysis was carried out excluding the five trials sponsored by or involving the manufacturers of the device, which revealed no overall effect on BP using the device. The maximum trial duration was 9 weeks and no overall effect was seen on heart rate or quality of life using the device. CONCLUSION: There is evidence that short-term use of DGB may reduce both DBP and DBP. However, five of the eight trials were sponsored by or involved the manufactures of the device. When these trials were excluded we found no overall effect. We conclude that longer term, independent trials are required to validate this intervention.