Prescribing of long-term antibiotics to adolescents in primary care: a retrospective cohort study.

BACKGROUND: Antibiotic overuse is linked to increased risk of antimicrobial resistance. Long-term antibiotics are commonly used for treating acne and prophylaxis of urinary tract infection. Their contribution to the overall burden of antibiotic use is relatively unknown. AIM: To describe the volume of commonly prescribed long-term (≥28 days) antibiotic prescriptions in adolescents and young adults, trends over time, and comparisons with acute prescriptions. DESIGN AND SETTING: A retrospective cohort study using UK electronic primary care records. METHOD: Patients born between 1979 and 1996 and with data in the Care and Health Information Analytics database were included. The main outcome measures were antibiotic prescription rates per 1000 person-years and antibiotic prescription days per person-year between the ages of 11 and 21. RESULTS: In total, 320 722 participants received 710 803 antibiotic prescriptions between the ages of 11 and 21 years from 1998 to 2017. Of these 710 803 prescriptions, 191 443 (26.93%) were for long-term antibiotics (≥28 days and ≤6 months in duration). Long-term antibiotics accounted for more than two-thirds (72.48%) of total antibiotic exposure (days per person-year). Total long-term antibiotic prescribing peaked in 2013 at just under 6 days per person-year and declined to around 4 days in 2017. CONCLUSION: Among adolescents and young adults, exposure to long-term antibiotics (primarily lymecycline used for acne) was much greater than for acute antibiotics and is likely to make an important contribution to antimicrobial resistance. Urgent action is needed to reduce unnecessary exposure to long-term antibiotics in this group. Increasing the use of, and adherence to, effective non-antibiotic treatments for acne is key to achieving this.

A feasibility trial of acupuncture in cancer patients undergoing radiotherapy treatment.

OBJECTIVE: We conducted a feasibility trial of acupuncture in cancer patients undergoing radiotherapy treatment. The trial included training radiographers to deliver acupuncture within patients' routine NHS care. METHODS: Mixed methods pragmatic randomized parallel-group exploratory feasibility trial comparing standard care to standard care plus acupuncture. RESULTS: Most aspects of the research design and acupuncture intervention were acceptable to the 101 participants. Participants' valued the opportunity to receive acupuncture within their NHS care, perceived the treatment as eliciting a number of beneficial effects, and had a positive impact on their NHS cancer treatment. However, quantitative analysis of outcome measure data revealed no consistent significant differences between those receiving standard care and those receiving standard care plus acupuncture. CONCLUSION: It is feasible to implement acupuncture in a busy radiotherapy unit provided by specially trained radiographers. The methodology employed appears acceptable for the evaluation of acupuncture for radiotherapy patients.

Do the effects of acupuncture vary between acupuncturists? Analysis of the Acupuncture Trialists' Collaboration individual patient data meta-analysis.

OBJECTIVES: The degree to which the effects of acupuncture treatment vary between acupuncturists is unknown. We used a large individual patient dataset of trials of acupuncture for chronic pain to assess practitioner heterogeneity. METHODS: Individual patient data linked to identifiable acupuncturists were drawn from a dataset of 39 high-quality trials of acupuncture, where the comparators were either sham acupuncture or non-acupuncture controls, such as standard care or waitlist. Heterogeneity among acupuncturists was assessed by meta-analysis. RESULTS: A total of 1206 acupuncturists in 13 trials were included. Statistically significant heterogeneity was found in trials with sham-control groups (p < 0.0001) and non-acupuncture control groups (p <0.0001). However, the degree of heterogeneity was very small, with the observed distribution of treatment effects virtually overlapping that expected by chance. For instance, for non-acupuncture-controlled trials, the proportion of acupuncturists with effect sizes half a standard deviation greater or less than average was expected to be 34%, but was observed to be 37%. A limitation is that the trials included a relatively limited range of acupuncturists, mainly physician-acupuncturists. DISCUSSION: Although differences in effects between acupuncturists were greater than expected by chance, the degree of variation was small. This suggests that most chronic pain patients in clinical practice would have similar results to those reported in high-quality trials; comparably, we did not find evidence to suggest that greater standardization of acupuncture practice would improve outcomes. Further research needs to be conducted exploring variability using a sample of acupuncturists with a broader range of practice styles, training and experience.

Identifying patients with chronic pain who respond to acupuncture: results from an individual patient data meta-analysis.

BACKGROUND: In a recent individual patient data meta-analysis, acupuncture was found to be superior to sham and non-sham controls in patients with chronic pain. It has been suggested that a subgroup of patients has an exceptional response to acupuncture. We hypothesized the presence of exceptional acupuncture responders would lead to a different distribution of pain scores in acupuncture versus control groups, with the former being skewed to the right. METHODS: This individual patient data meta-analysis included 39 high-quality randomized trials of acupuncture for chronic headache, migraine, osteoarthritis, low back pain, neck pain and shoulder pain published before December 2015 (n = 20,827). In all, 25 involved sham acupuncture controls (n = 7097) and 25 non-acupuncture controls (n = 16,041). We analyzed the distribution of change scores and calculated the difference in the skewness statistic-which assesses asymmetry in the data distribution-between acupuncture and either sham or non-acupuncture control groups. We then entered the difference in skewness along with standard error into a meta-analysis. FINDINGS: Control groups were more right-skewed than acupuncture groups, although this difference was very small. The difference in skew was 0.124 for non-acupuncture-controlled trials (p = 0.047) and 0.141 for sham-controlled trials (p = 0.029). In a pre-specified sensitivity analysis excluding three trials with outlying results known a priori, the difference in skew between acupuncture and sham was no longer statistically significant (p = 0.2). CONCLUSION: We did not find evidence to support the notion that there are exceptional acupuncture responders. The challenge remains to identify features of chronic pain patients that can be used to distinguish those that have a good response to acupuncture treatment.

A feasibility study of a psycho-educational support intervention for men with prostate cancer on active surveillance.

BACKGROUND: PROACTIVE is a psycho-educational support intervention for prostate cancer patients managed on Active Surveillance. PROACTIVE is composed of two interdependent components: group workshops and internet-delivered information modules. AIMS: We conducted a feasibility study to determine the practicality of delivering PROACTIVE at two prostate cancer centres. METHODS AND RESULTS: The feasibility study was a mixed-methods randomized parallel-group exploratory trial. Participants were randomised using a ratio of 3:1 PROACTIVE group to treatment as usual. Qualitative semi-structured interviews and quantitative measures were completed at baseline, intervention completion (week 6), and at 6-month follow-up. Interview transcripts were analysed thematically using Framework analysis. Descriptive statistics were used to examine recruitment and retention rates and changing trends in outcome measures. Most aspects of the research design and PROACTIVE intervention were acceptable to those participating in the study. In particular, participants valued the opportunity to share and discuss experiences with other prostate cancer patients on Active Surveillance and receive detailed authoritative information. However, three issues were identified: (a) a low response rate (13 participants recruited, response rate 16%), (b) low utilisation of internet delivered information modules, (c) self-perceived low levels of anxiety amongst participants with the majority perceiving their cancer as not impacting on their day-to-day life or causing anxiety. CONCLUSIONS: Due to these significant research design issues, it is not recommended PROACTIVE be evaluated in a large-scale randomised controlled trial. Further research is required to explore the impact of Active Surveillance on anxiety amongst men with localized prostate cancer managed by Active Surveillance.

Patients' views about screening for atrial fibrillation (AF): a qualitative study in primary care.

OBJECTIVES: There has been increased interest in screening for atrial fibrillation (AF) with commissioned pilot schemes, ongoing large clinical trials and the emergence of inexpensive consumer single-lead ECG devices that can be used to detect AF. This qualitative study aimed to explore patients' views and understanding of AF and AF screening to determine acceptability and inform future recommendations. SETTING: A single primary care practice in Hampshire, UK. PARTICIPANTS: 15 participants (11 female) were interviewed from primary care who had taken part in an AF screening trial. A semistructured interview guide was used flexibly to enable the interviewer to explore any relevant topics raised by the participants. Interviews were recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS: Participants generally had an incomplete understanding of AF and conflated it with other heart problems or with raised blood pressure. With regards to potential drawbacks from screening, some participants considered anxiety and the cost of implementation, but none acknowledged potential harms associated with screening such as side effects of anticoagulation treatment or the risk of further investigations. The screening was generally well accepted, and participants were generally in favour of engaging with prolonged screening. CONCLUSIONS: Our study highlights that there may be poor understanding (of both the nature of AF and potential negatives of screening) among patients who have been screened for AF. Further work is required to determine if resources including decision aids can address this important knowledge gap and improve clinical informed consent for AF screening. TRIAL REGISTRATION NUMBER: ISRCTN 17495003.

Placebos in primary care? a nominal group study explicating UK GP and patient views of six theoretically plausible models of placebo practice.

OBJECTIVES: To better understand which theoretically plausible placebogenic techniques might be acceptable in UK primary care. DESIGN: A qualitative study using nominal group technique and thematic analysis. Participants took part in audio-recorded face-to-face nominal groups in which the researcher presented six scenarios describing the application in primary care of theoretically plausible placebogenic techniques: (1) Withholding side effects information, (2) Monitoring, (3) General practitioner (GP) endorsement, (4) Idealised consultation, (5) Deceptive placebo pills and (6) Open-label placebo pills. Participants voted on whether they thought each scenario was acceptable in practice and discussed their reasoning. Votes were tallied and discussions transcribed verbatim. SETTING: Primary care in England. PARTICIPANTS: 21 GPs in four nominal groups and 20 'expert patients' in five nominal groups. RESULTS: Participants found it hard to decide which practices were acceptable and spoke about needing to weigh potential symptomatic benefits against the potential harms of lost trust eroding the therapeutic relationship. Primary care patients and doctors felt it was acceptable to harness placebo effects in practice by patient self-monitoring (scenario 2), by the GP expressing a strongly positive belief in a therapy (scenario 3) and by conducting patient-centred, empathic consultations (scenario 4). Deceptive placebogenic practices (scenarios 1 and 5) were unacceptable to most groups. Patient and GP groups expressed a diverse range of opinions about open-label placebo pills. CONCLUSIONS: Attempts to harness placebo effects in UK primary care are more likely to be accepted and implemented if they focus on enhancing positive patient-centred communication and empathic relationships. Using placebos deceptively is likely to be unacceptable to both GPs and patients. Open-label placebos also do not have clear support; they might be acceptable to some doctors and patients in very limited circumstances-but further evidence, clear information and guidance would be needed.

Machine learning detection of Atrial Fibrillation using wearable technology.

BACKGROUND: Atrial Fibrillation is the most common arrhythmia worldwide with a global age adjusted prevalence of 0.5% in 2010. Anticoagulation treatment using warfarin or direct oral anticoagulants is effective in reducing the risk of AF-related stroke by approximately two-thirds and can provide a 10% reduction in overall mortality. There has been increased interest in detecting AF due to its increased incidence and the possibility to prevent AF-related strokes. Inexpensive consumer devices which measure the ECG may have the potential to accurately detect AF but do not generally incorporate diagnostic algorithms. Machine learning algorithms have the potential to improve patient outcomes particularly where diagnoses are made from large volumes or complex patterns of data such as in AF. METHODS: We designed a novel AF detection algorithm using a de-correlated Lorenz plot of 60 consecutive RR intervals. In order to reduce the volume of data, the resulting images were compressed using a wavelet transformation (JPEG200 algorithm) and the compressed images were used as input data to a Support Vector Machine (SVM) classifier. We used the Massachusetts Institute of Technology (MIT)-Beth Israel Hospital (BIH) Atrial Fibrillation database and the MIT-BIH Arrhythmia database as training data and verified the algorithm performance using RR intervals collected using an inexpensive consumer heart rate monitor device (Polar-H7) in a case-control study. RESULTS: The SVM algorithm yielded excellent discrimination in the training data with a sensitivity of 99.2% and a specificity of 99.5% for AF. In the validation data, the SVM algorithm correctly identified AF in 79/79 cases; sensitivity 100% (95% CI 95.4%-100%) and non-AF in 328/336 cases; specificity 97.6% (95% CI 95.4%-99.0%). CONCLUSIONS: An inexpensive wearable heart rate monitor and machine learning algorithm can be used to detect AF with very high accuracy and has the capability to transmit ECG data which could be used to confirm AF. It could potentially be used for intermittent screening or continuously for prolonged periods to detect paroxysmal AF. Further work could lead to cost-effective and accurate estimation of AF burden and improved risk stratification in AF.

From substance to process: A meta-ethnographic review of how healthcare professionals and patients understand placebos and their effects in primary care.

Research suggests that a 'placebo' can improve conditions common in primary care including pain, depression and irritable bowel syndrome. However, disagreement persists over the definition and clinical relevance of placebo treatments. We conducted a meta-ethnographic, mixed-research systematic review to explore how healthcare professionals and patients understand placebos and their effects in primary care. We conducted systematic literature searches of five databases - augmented by reference chaining, key author searches and expert opinion - related to views on placebos, placebo effects and placebo use in primary care. From a total of 34 eligible quantitative, qualitative and mixed-methods articles reporting findings from 28 studies, 21 were related to healthcare professionals' views, 11 were related to patients' views and two were related to both groups. In the studies under review, healthcare professionals reported using placebos at markedly different frequencies. This was highly influenced by how placebos were defined in the studies. Both healthcare professionals and patients predominantly defined placebos as material substances such as 'inert' pills, despite this definition being inconsistent with current scientific thinking. However, healthcare professionals also, but less prevalently, defined placebos in a different way: as contextual processes. This better concurs with modern placebo definitions, which focus on context, ritual, meaning and enactivism. However, given the enduring ubiquity of substance definitions, for both healthcare professionals and patients, we question the practical, clinical validity of stretching the term 'placebo' towards its modern iteration. To produce 'placebo effects', therefore, primary healthcare professionals may be better off abandoning placebo terminology altogether.

Assessment of the quality of reporting in studies of acupuncture for patients with cancer using the STRICTA guidelines.

INTRODUCTION: There has been a burgeoning of research evaluating acupuncture for various symptoms of cancer and the side-effects associated with its treatment. A systematic review was conducted to examine the quality of reporting in published studies of acupuncture in cancer according to the STRICTA (STandards for Reporting Interventions in Clinical Trials of Acupuncture) guidelines. METHODS: Systematic review of published research of acupuncture for symptoms of cancer and the side-effects associated with its treatment. Databases searched were: Medline, CINAHL, Cochrane (all databases), Scopus, and PubMed from their inception to December 2014. Clinical trials, pilot/feasibility studies, observational studies, and case studies were included. Only full journal papers published in English were included. The quality of reporting was evaluated using STRICTA guidelines. Each included paper was assessed by two independent reviewers, with disagreements adjudicated by a third reviewer. RESULTS: 88 papers were identified which met the inclusion criteria. The median number of STRICTA items reported in trials with a control or comparator arm (n=47) was 14 out of 17 (range 8 to 17, IQR 4). For studies without a control or comparator arm the median was 11 out of a possible 15 (range 5 to 15, IQR 3). Key weaknesses in reporting included details of other components of treatments, and details of the acupuncturist administering treatments. CONCLUSIONS: Despite the widespread use of the STRICTA guidelines in acupuncture research, adherence remains poor for a few specific items. Further research is required to explore the reasons why authors fail to report those items, and to develop strategies to improve the adherence to the guidelines.

Supporting informed choice in acupuncture: effects of a new person-, evidence- and theory-based website for patients with back pain.

OBJECTIVES: To test whether a newly developed person-, theory- and evidence-based website about acupuncture helps patients make informed decisions about whether or not to use acupuncture for back pain. METHODS: A randomised online study compared a newly developed 'enhanced website' to a 'standard website'. The enhanced website provided evidence-based information in a person-based manner and targeted psychological constructs. The standard website was based on a widely used patient information leaflet. In total, 350 adults with recent self-reported back pain were recruited from general practices in South West England. The two primary outcomes were knowledge change and making an informed choice about using acupuncture. Secondary outcomes were beliefs about and willingness to have acupuncture. RESULTS: Participants who viewed the enhanced acupuncture website had a significantly greater increase in knowledge about acupuncture (M = 1.1, standard deviation (SD) = 1.7) than participants who viewed the standard website (M = 0.2, SD = 1.1; F(1, 315) = 37.93, p < 0.001, η2 = .107). Participants who viewed the enhanced acupuncture website were also 3.3 times more likely to make an informed choice about using acupuncture than those who viewed the standard website (χ2(1) = 23.46, p < 0.001). There were no significant effects on treatment beliefs or willingness to have acupuncture. CONCLUSION: The enhanced website improved patients' knowledge and ability to make an informed choice about acupuncture, but did not optimise treatment beliefs or change willingness to have acupuncture. The enhanced website could be used to support informed decision-making among primary care patients and members of the general public considering using acupuncture for back pain.

The Effect of Patient Characteristics on Acupuncture Treatment Outcomes: An Individual Patient Data Meta-Analysis of 20,827 Chronic Pain Patients in Randomized Controlled Trials.

OBJECTIVES: To optimally select chronic pain patients for different treatments, as it is of interest to identify patient characteristics that might moderate treatment effect. Our aim was to evaluate the impact of possible moderators on the effect of acupuncture treatment using a large data set. METHODS: We used data from an individual patient data meta-analysis of high-quality randomized trials of acupuncture for chronic headache and migraine, osteoarthritis, and back, neck, and shoulder pain. Using meta-analytic trial-level and patient-level regression analyses, we explored the impact of 5 documented patient characteristics (patients' age at baseline, sex, pain duration, baseline pain severity and baseline psychological distress) on the effect of acupuncture. RESULTS: A total of 39 trials met the inclusion criteria: 25 use sham-acupuncture controls (n = 7097) and 25 non-acupuncture controls (n = 16,041). Of the 5 patient characteristics analyzed, only baseline pain severity was found to potentially moderate the treatment effect of acupuncture, with patients reporting more severe pain at baseline experiencing more benefit from acupuncture compared to either sham-control or non-acupuncture control. Baseline psychological distress showed small treatment moderating effects, and results for sex were inconsistent. There was no strong evidence that age or duration of pain influenced the response to acupuncture. DISCUSSION: Of 5 patient characteristics tested, we found only baseline severity of pain to potentially moderate the effect of acupuncture treatment. For clinical practice, the evidence from this analysis does not justify stratifying chronic pain patients into subgroups that should or should not receive acupuncture on the basis of these 5 characteristics. Future acupuncture trials should assess other potentially important effect moderators.

Informing Adults With Back Pain About Placebo Effects: Randomized Controlled Evaluation of a New Website With Potential to Improve Informed Consent in Clinical Research.

BACKGROUND: Placebo effects and their underpinning mechanisms are increasingly well understood. However, this is poorly communicated to participants in placebo-controlled trials. For valid informed consent, participants should be informed about the potential benefits and risks of participating in placebo-controlled trials. Existing information leaflets often fail to describe the potential benefits and adverse effects associated with placebo allocation. This study tested the effects of a new website designed to inform patients about placebo effects (The Power of Placebos, PoP). PoP was designed using qualitative methods in combination with theory- and evidence-based approaches to ensure it was engaging, informative, and addressed patients' concerns. OBJECTIVE: This study aimed to test the effects of PoP, compared with a control website, on people's knowledge about placebo and the ability to make an informed choice about taking part in a placebo-controlled trial. METHODS: A total of 350 adults with back pain recruited from 26 general practices in Southern England participated in this Web-based study. Participants were randomly assigned to PoP (which presented scientifically accurate information about placebo effects in an engaging way) or a control website (based on existing information leaflets from UK trials). Participants self-completed Web-based pre- and postintervention questionnaire measures of knowledge about placebo effects and preintervention questionnaire measures of attitudes toward and intentions to participate in a placebo-controlled trial. The 2 primary outcomes were (1) knowledge and (2) informed choice to take part in a placebo-controlled trial (computed from knowledge, attitudes, and intentions). RESULTS: After viewing PoP, participants had significantly greater knowledge about placebos (mean 8.28 [SD 1.76]; n=158) than participants who viewed the control (mean 5.60 [SD 2.24]; n=174; F1,329=173.821; P<.001; η2=.346). Participants who viewed PoP were 3.16 times more likely than those who viewed the control to make an informed choice about placebos (χ21=36.5; P<.001). CONCLUSIONS: In a sample of adults with back pain, PoP increased knowledge and rates of informed choice about placebos compared with a control website. PoP could be used to improve knowledge about placebo effects in back pain. After essential further development and testing in clinical trial settings, it could support informed consent in placebo-controlled trials.

Chiropractors' views on the use of patient-reported outcome measures in clinical practice: a qualitative study.

Background: Patient-reported outcome measures (PROMs) are widely available for use in musculoskeletal care. However, there is little research exploring the implementation of PROMs in clinical practice. This qualitative study explored chiropractors' views on PROMs to identify any barriers and facilitators to implementing PROMs in chiropractic care and the training needs of chiropractors regarding the use of PROMs. Methods: A qualitative study of chiropractors' views on PROMs was undertaken as part of a larger project to address the feasibility of conducting a randomised controlled trial of PROM use in chiropractic clinics for patients with low back pain. Contact was made with chiropractors working in chiropractic companies with multiple clinic sites. Semi-structured interviews were conducted with eight chiropractors, either face-to-face at their place of work or over the telephone. The interviews were transcribed verbatim and analysed using thematic analysis. The data were coded inductively by two authors. Results: Chiropractors discussed their knowledge and engagement with PROMs in clinical practice, identifying reasons for their use, such as understanding clinic performance, clinical practice, and research. They also discussed how they used PROMs within their clinical practice and the benefits of using them with individual patients, for example during the consultation, identifying yellow flags, and tracking patient progress. Chiropractors voiced concerns about patient engagement with PROMs, questioning if patients find them burdensome, and the appropriate PROMs to use with patients with pain. Finally, chiropractors acknowledged the organisational barriers and facilitators to using PROMs within their practice, such as busy practices, electronic systems, and use of reception staff. Conclusions: Using participating chiropractors' views of PROMs, the study identified barriers and facilitators to implementing PROMs in chiropractic care, such as clinician knowledge, engagement, and organisational concerns and identified the potential training needs of chiropractors regarding PROMs. The results from the study suggested chiropractors use PROMs with their individual patients, but PROMs should be meaningful to patients and chiropractors to improve engagement.

Correction: Andrographis paniculata (Chuan Xin Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0181780.].

Screening for Atrial Fibrillation Using Economical and Accurate Technology (From the SAFETY Study).

The prevalence of atrial fibrillation (AF) is estimated at more than 3% in the adult population and there has been increased interest in screening for AF. In the SAFETY trial we chose to evaluate if inexpensive, wearable, consumer electrocardiography (ECG) sensing devices (Polar-H7 [PH7] and Firstbeat Bodyguard 2 [BG2]), could be used to detect AF accurately. We undertook a case-control study of 418 participants aged >65 (82 with AF and/or flutter at the study visit and 336 without) attending 3 general practice surgeries in Hampshire, UK for a single screening visit. The PH7 and BG2 devices were tested alongside 2 established AF detection devices (AliveCor and WatchBP) in random order and the diagnosis of AF was confirmed by 12-Lead ECG interpreted by a panel of cardiologists. The sensitivity (95% confidence interval [CI] range), specificity (95% CI range), and overall accuracy (95% CI range) of the 4 devices were: AliveCor: 87.8% (78.7% to 94.0%), 98.8% (97.0% to 99.7%), 96.7% (94.4% to 98.2%); WatchBP: 96.3% (89.7% to 99.2%), 93.5% (90.3% to 95.9%), 94.0% (91.3% to 96.1%): PH7: 96.3% (89.7% to 99.2%), 98.2% (96.2% to 99.3%), 97.9% (96.0% to 99.0%). BG2: 96.3% (89.7% to 99.2%), 98.5% (96.6% to 99.5%), 98.1% (96.3% to 99.2%). The PH7 and BG2 devices were highly reliable (the devices acquired sufficient data and obtained a diagnostic result in all but 1 participant on the first attempt). In conclusion, inexpensive, consumer heart rate monitoring devices (PH7 and BG2) can be used to detect AF accurately with sensitivity and specificity >95%. The consumer devices performed as well or better than WatchBP and AliveCor and have the capability to store or transmit ECG data which could be used to confirm AF.

Influence of delayed sample processing on blood immune cell phenotypes, immune cell responses and serum anti-influenza vaccine antibody titres.

Provision of blood from distant research partners to a central laboratory can result in delayed blood processing prior to assessment of immune parameters. It is important to evaluate the effect of such delays on immune parameters. This study investigated the effect of storage of blood at room temperature for up to 72 h prior to processing and analysis on a range of immune parameters. Blood was collected from 10 healthy participants and analysed immediately (day 0) or after storage at room temperature for 24, 48 or 72 h (days 1, 2 and 3). A full blood count, immune cell phenotypes (flow cytometry), plasma cytokines, chemokines and soluble receptors (multiplex immunoassay), neutrophil and monocyte phagocytosis (flow cytometry), whole blood cytokine responses to stimulation and antibody titres to the seasonal influenza vaccine were assessed. The full blood count, most immune cell phenotypes, monocyte phagocytosis and anti-influenza vaccine antibody titres were little affected by blood storage of ≤72 h prior to processing. Plasma cytokine concentrations increased with blood storage time while whole blood responses to stimulation with lipopolysaccharide or phytohaemagglutinin decreased with blood storage time. In conclusion, while fresh blood is optimal for analysing human immune parameters, it is possible to store blood for up to 72 h at room temperature and obtain reliable measures of several immune markers. However, plasma cytokines and related mediators as well as whole blood cultures should be analysed using freshly isolated blood. Storage of blood for longer than one day may result in the unreliable assessment of these outcomes.

Effects of empathic and positive communication in healthcare consultations: a systematic review and meta-analysis.

Background Practitioners who enhance how they express empathy and create positive expectations of benefit could improve patient outcomes. However, the evidence in this area has not been recently synthesised. Objective To estimate the effects of empathy and expectations interventions for any clinical condition. Design Systematic review and meta-analysis of randomised trials. Data sources Six databases from inception to August 2017. Study selection Randomised trials of empathy or expectations interventions in any clinical setting with patients aged 12 years or older. Review methods Two reviewers independently screened citations, extracted data, assessed risk of bias and graded quality of evidence using GRADE. Random effects model was used for meta-analysis. Results We identified 28 eligible (n = 6017). In seven trials, empathic consultations improved pain, anxiety and satisfaction by a small amount (standardised mean difference -0.18 [95% confidence interval -0.32 to -0.03]). Twenty-two trials tested the effects of positive expectations. Eighteen of these (n = 2014) reported psychological outcomes (mostly pain) and showed a modest benefit (standardised mean difference -0.43 [95% confidence interval -0.65 to -0.21]); 11 (n = 1790) reported physical outcomes (including bronchial function/ length of hospital stay) and showed a small benefit (standardised mean difference -0.18 [95% confidence interval -0.32 to -0.05]). Within 11 trials (n = 2706) assessing harms, there was no evidence of adverse effects (odds ratio 1.04; 95% confidence interval 0.67 to 1.63). The risk of bias was low. The main limitations were difficulties in blinding and high heterogeneity for some comparisons. Conclusions Greater practitioner empathy or communication of positive messages can have small patient benefits for a range of clinical conditions, especially pain. Protocol registration Cochrane Database of Systematic Reviews (protocol) DOI: 10.1002/14651858.CD011934.pub2.

Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis.

Despite wide use in clinical practice, acupuncture remains a controversial treatment for chronic pain. Our objective was to update an individual patient data meta-analysis to determine the effect size of acupuncture for 4 chronic pain conditions. We searched MEDLINE and the Cochrane Central Registry of Controlled Trials randomized trials published up until December 31, 2015. We included randomized trials of acupuncture needling versus either sham acupuncture or no acupuncture control for nonspecific musculoskeletal pain, osteoarthritis, chronic headache, or shoulder pain. Trials were only included if allocation concealment was unambiguously determined to be adequate. Raw data were obtained from study authors and entered into an individual patient data meta-analysis. The main outcome measures were pain and function. An additional 13 trials were identified, with data received for a total of 20,827 patients from 39 trials. Acupuncture was superior to sham as well as no acupuncture control for each pain condition (all P < .001) with differences between groups close to .5 SDs compared with no acupuncture control and close to .2 SDs compared with sham. We also found clear evidence that the effects of acupuncture persist over time with only a small decrease, approximately 15%, in treatment effect at 1 year. In secondary analyses, we found no obvious association between trial outcome and characteristics of acupuncture treatment, but effect sizes of acupuncture were associated with the type of control group, with smaller effects sizes for sham controlled trials that used a penetrating needle for sham, and for trials that had high intensity of intervention in the control arm. We conclude that acupuncture is effective for the treatment of chronic pain, with treatment effects persisting over time. Although factors in addition to the specific effects of needling at correct acupuncture point locations are important contributors to the treatment effect, decreases in pain after acupuncture cannot be explained solely in terms of placebo effects. Variations in the effect size of acupuncture in different trials are driven predominantly by differences in treatments received by the control group rather than by differences in the characteristics of acupuncture treatment. PERSPECTIVE: Acupuncture is effective for the treatment of chronic musculoskeletal, headache, and osteoarthritis pain. Treatment effects of acupuncture persist over time and cannot be explained solely in terms of placebo effects. Referral for a course of acupuncture treatment is a reasonable option for a patient with chronic pain.

Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial.

BACKGROUND: Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. METHODS/DESIGN: Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below: Group 1 - Uva-ursi + advice to take ibuprofen Group 2 - Placebo + advice to take ibuprofen Group 3 - Uva-ursi + no advice to take ibuprofen Group 4 - Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2-4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. DISCUSSION: The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN43397016 . Registered on 11 February 2015.