Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study.

OBJECTIVES: To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women. DESIGN: A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation. SETTING: Five inner city UK National Health Service hospitals PARTICIPANTS: Multiethnic pregnant women at 12+0 and 15+6 weeks' gestation with risk factors for gestational diabetes. INTERVENTIONS: 2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, adherence and follow-up. SECONDARY OUTCOME MEASURES: Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs. RESULTS: Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks' and 34% (SD 41) at 36 weeks' gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference -0.6, 95% CI -1.2 to 0.0 and -2.69, 95% CI -5.26 to -0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence. CONCLUSIONS: A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol. TRIAL REGISTRATION NUMBER: ISRCTN48872100.

Physician-Related Variability in the Outcomes of an Invasive Treatment for Neck and Back Pain: A Multi-Level Analysis of Data Gathered in Routine Clinical Practice.

Neuro-reflexotherapy (NRT) is a proven effective, invasive treatment for neck and back pain. To assess physician-related variability in results, data from post-implementation surveillance of 9023 patients treated within the Spanish National Health Service by 12 physicians were analyzed. Separate multi-level logistic regression models were developed for spinal pain (SP), referred pain (RP), and disability. The models included all patient-related variables predicting response to NRT and physician-related variables. The Intraclass Correlation Coefficient (ICC) and the Median Odds Ratio (MOR) were calculated. Adjusted MOR (95% CI) was 1.70 (1.47; 2.09) for SP, 1.60 (1.38; 1.99) for RP, and 1.65 (1.42; 2.03) for disability. Adjusted ICC (95%CI) values were 0.08 (0.05; 0.15) for SP, 0.07 (0.03; 0.14) for RP, and 0.08 (0.04; 0.14) for disability. In the sensitivity analysis, in which the 6920 patients treated during the physicians' training period were excluded, adjusted MOR was 1.38 (1.17; 1.98) for SP, 1.37 (1.12; 2.31) for RP, and 1.25 (1.09; 1.79) for disability, while ICCs were 0.03 (0.01; 0.14) for SP, 0.03 (0.00; 0.19) for RP, and 0.02 (0.00; 0.10) for disability. In conclusion, the variability in results obtained by different NRT-certified specialists is reasonable. This suggests that current training standards are appropriate.

Long-term docosahexaenoic acid (DHA) supplementation in cystic fibrosis patients: a randomized, multi-center, double-blind, placebo-controlled trial.

BACKGROUND: Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1ß, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1ß, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV1, pulmonary exacerbations, antibiotic use, nutritional status and quality of life). RESULTS: Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups. CONCLUSION: In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613).

Predicting the evolution of neck pain episodes in routine clinical practice.

BACKGROUND: The objective of this study was to develop models for predicting the evolution of a neck pain (NP) episode. METHODS: Three thousand two hundred twenty-five acute and chronic patients seeking care for NP, were recruited consecutively in 47 health care centers. Data on 37 variables were gathered, including gender, age, employment status, duration of pain, intensity of NP and pain referred down to the arm (AP), disability, history of neck surgery, diagnostic procedures undertaken, imaging findings, clinical diagnosis, and treatments used. Three separate multivariable logistic regression models were developed for predicting a clinically relevant improvement in NP, AP and disability at 3 months. RESULTS: Three thousand one (93.5%%) patients attended follow-up. For all the models calibration was good. The area under the ROC curve was ≥0.717 for pain and 0.664 for disability. Factors associated with a better prognosis were: a) For all the outcomes: pain being acute (vs. chronic) and having received neuro-reflexotherapy. b) For NP: nonspecific pain (vs. pain caused by disc herniation or spinal stenosis), no signs of disc degeneration on imaging, staying at work, and being female. c) For AP: nonspecific NP and no signs of disc degeneration on imaging. d) For disability: staying at work and no signs of facet joint degeneration on imaging. CONCLUSIONS: A prospective registry can be used for developing valid predictive models to quantify the odds that a given patient with NP will experience a clinically relevant improvement.

Effectiveness and acceptability of myo-inositol nutritional supplement in the prevention of gestational diabetes (EMmY): a protocol for a randomised, placebo-controlled, double-blind pilot trial.

INTRODUCTION: Gestational diabetes increases maternal and offspring complications in pregnancy and cardiovascular complications in the long term. The nutritional supplement myo-inositol may prevent gestational diabetes; however, further evaluation is required, especially in multiethnic high-risk mothers. Our pilot trial on myo-inositol to prevent gestational diabetes will evaluate trial processes, assess acceptability to mothers and obtain preliminary estimates of effect and cost data prior to a large full-scale trial. METHODS AND ANALYSIS: EMmY is a multicentre, placebo-controlled, double-blind, pilot, randomised trial, with qualitative evaluation. We will recruit pregnant women at 12-15+6 weeks' gestation, with gestational diabetes risk factors, from five maternity units in England between 2018 and 2019. We will randomise 200 women to take either 2 g of myo-inositol powder (intervention) or placebo, twice daily until delivery. We will assess rates of recruitment, randomisation, adherence to intervention and follow-up. Gestational diabetes will be diagnosed at 24-28 weeks as per the National Institute for Health and Care Excellence (NICE) criteria (fasting plasma glucose: ≥5.6 mmol/L and 2-hour plasma glucose: ≥7.8 mmol/L). We will assess the effects of myo-inositol on glycaemic indices at 28 weeks and on other maternal, fetal and neonatal outcomes at postnatal discharge. Qualitative evaluation will explore the acceptability of the trial and the intervention among women and healthcare professionals. Cost data and health-related quality of life measures will be captured. We will summarise feasibility outcomes using standard methods for proportions and other descriptive statistics, and where appropriate, report point estimates of effect sizes (eg, mean differences and relative risks) and associated 95% CIs. ETHICS AND DISSEMINATION: Ethical approval was obtained through the London Queen Square Research Ethics Committee (17/LO/1741). Study findings will be submitted for publication in peer-reviewed journals. Newsletters will be made available to participants, healthcare professionals and members of Katie's Team (a patient and public advisory group) to disseminate. TRIAL REGISTRATION NUMBER: ISRCTN48872100. PROTOCOL VERSION AND DATE: Version 4.0, 15 January 2018.

Postpartum care of women with gestational diabetes: survey of healthcare professionals.

OBJECTIVE: To assess the knowledge and practices of healthcare professionals on the postpartum care of women with gestational diabetes. STUDY DESIGN: We surveyed 106 healthcare professionals including obstetricians, diabetologists, general practitioners and midwives in East London and West Midlands in England (September 2014). The questionnaire assessed postpartum screening practices, care provision, future risk and strategies to prevent diabetes in women with gestational diabetes. RESULTS: The response rate was 87% (92/106). Nearly all respondents offered advice on diet (99%; CI 95%, 100%) and exercise (92%; CI 85%, 97%) postnatally in women with diagnosis of gestational diabetes. The preferred screening time for diabetes was 6 weeks to 3 months postpartum (76%; CI 66%, 85%). Overall, oral glucose tolerance test was the preferred test (57%; CI 46%, 67%), although general practitioners preferred fasting glucose (50%; CI 33%, 67%) and glycated hemoglobin (47%; CI 30%, 64%). Most midwives (81%, 17/21) and obstetricians (52%, 11/21) either underestimated or were unsure of the future risk of diabetes. There was lack of consensus on responsibility for immediate postpartum screening. CONCLUSION: The survey highlights the need for improved awareness of future risk of diabetes in women with gestational diabetes, consensus on optimal postpartum screening and identification of the main healthcare provider responsible for further management. This is particularly important for areas of social deprivation.

The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients.

OBJECTIVES: The stability of the reservoir of latently infected memory CD4 T-cells may be associated with continuous replenishment from residual HIV-1, not completely eliminated by otherwise successful antiretroviral therapy (ART). Treatment intensification could help to control residual virus and to modify the latent reservoir. The objective of this work is to assess the effect of intensifying therapy with raltegravir on the HIV-1 cell reservoir. DESIGN: A pilot open-label phase-II clinical trial was performed to analyze ART intensification with raltegravir after 48 weeks in chronically HIV-1-infected patients on stable ART. METHODS: We measured the number of latently infected memory CD4 T cells, residual viremia, 2-long terminal repeat circles, CD4/CD8 T-cell activation, lymphocyte subpopulations, gut homing receptor, and bacterial translocation. RESULTS: A significant decay of HIV-1 latent reservoir was observed after intensification in the nine patients included (P = 0.021). No variation was found in either residual viremia or 2-long terminal repeat circles, whereas CD8 T-cell activation decreased at week 36 (P = 0.028). No differences were found in naive T-cell or effector memory cell counts, and the frequencies of gut homing receptor on activated or effector memory CD8 T cells. Bacterial translocation was stable, with the exception of a late decrease in lipopolysaccharide levels. CONCLUSIONS: In this pilot noncomparative trial, treatment intensification with raltegravir significantly decreased the latent cellular HIV-1 reservoir and CD8 T-cell activation. Despite the limitations inherent to trial design, our results suggest that ART intensification should be considered as an adjuvant strategy to eradicate HIV-1 infection.

Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis.

OBJECTIVE: To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were "birth attend*", "traditional midwife", "lay birth attendant", "dais", and "comadronas". Review methods We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. RESULTS: We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). CONCLUSION: Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants.

Abdominal palpation to determine fetal position at labor onset: a test accuracy study.

OBJECTIVE: To examine the accuracy of abdominal palpation for identifying left-occipito-anterior (LOA) fetal position using abdominal ultrasound as the reference standard. DESIGN: Classical test accuracy study undertaken in 2005-2007. SETTING: Birmingham Women's Foundation NHS Trust serving a large, socio-economically and ethnically varied population. SAMPLE: All nulliparous women with spontaneous or induced labor before established labor (cervix <4cm dilated), with a singleton live pregnancy of over 37 completed gestational weeks without known fetal abnormalities. METHODS. Accuracy of abdominal palpation (index test) in identifying LOA fetal position, with abdominal ultrasound as reference. Trained observers blind to the index test results performed the ultrasound independently. MAIN OUTCOME MEASURES: Accuracy of palpation in determining LOA position. RESULTS: Midwives' abdominal palpation and ultrasound data were obtained from 629 women. There were 61 (9%) fetuses in LOA position that were verified by ultrasound. The sensitivity and specificity of palpation to detect LOA position were 34% (95%CI 23-46) and 71% (67-74), respectively. Midwives with experience >5 years achieved higher sensitivity compared to those with ≤5 years (odds ratio 4.02; 1.26-12.9; p=0.019). Sensitivity was higher for community compared with hospital midwives (OR 6.59; 1.11-39.11; p=0.038). CONCLUSIONS: Abdominal palpation to determine LOA position at the onset of labor had poor accuracy in nulliparous women on arrival at the maternity unit with a cervix dilation of <4cm. If future research demonstrates that an optimal fetal position at labor onset exists, ultrasound scan to confirm fetal position on arrival for birth may improve midwives' ability to prognosticate.

Neuro-reflexotherapy for the management of myofascial temporomandibular joint pain: a double-blind, placebo-controlled, randomized clinical trial.

PURPOSE: To assess the efficacy of neuro-reflexotherapy intervention (NRT) for treating temporomandibular joint dysfunction attributed to myofascial pain. Neuro-reflexotherapy intervention consists of the temporary implantation of epidermal devices in trigger points in the back and ear. It has shown efficacy, effectiveness, and cost-effectiveness in treating subacute and chronic common back pain. No study, however, has explored its efficacy in treating myofascial temporomandibular joint pain (MF/TMJP). PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled trial. Patients with MF/TMJP for more than 3 months in spite of conservative treatment, and with no evidence of major structural damage in the joint, were recruited at the Maxillofacial Department of the Hospital Clínico Universitario, a teaching hospital in Madrid, Spain. Patients were randomly assigned to an intervention group and to a control group. Patients in the treated group underwent 2 NRTs, immediately after baseline assessment and 45 days later. Sham interventions in the control group consisted of placement of the same number of epidermal devices within a 5-cm radius of the target zones. In both groups, conservative treatment during follow-up was allowed and recorded. Patients underwent clinical evaluations on 4 occasions: 5 minutes before intervention, 5 minutes after intervention, and 45 and 90 days later. The preintervention assessment was performed by the physician at the hospital service who included the patient in the study. The 3 follow-up assessments were performed independently by 1 of 2 physicians who had no connection with the research team, and who were blinded to patients' assignments. The primary outcome variable was level of pain severity during jaw movements at the last assessment (90 days), and the key comparison of interest was change in pain over time (pain levels at baseline and at 90 days). Level of pain was measured using a visual analog scale (VAS). RESULTS: Fifty-one patients with MF/TMJP were recruited into the study. Random assignment allocated 27 patients to the intervention group, and 24 to the control group. Differences in pain severity in favor of the intervention group appeared immediately after the intervention, persisted for 45 days, and increased after the second intervention. Differences at last follow-up were highly clinically and statistically significant (4 to 5 points on the VAS, P = .000), allowing for patients in the intervention group to cease drug treatment (P = .005). There were no differences in the evolution of crepitus or clicking in the joint. There were no clinically relevant side effects associated with the intervention. CONCLUSIONS: For patients in whom conservative treatment has failed, NRT improves the chronic pain associated with MF/TMJP syndrome.

Prognostic factors for neuroreflexotherapy in the treatment of subacute and chronic neck and back pain: a study of predictors of clinical outcome in routine practice of the Spanish National Health Service.

STUDY DESIGN: Prospective cohort follow-up study. OBJECTIVES: To refine the indication criteria for neuroreflexotherapy (NRT) in the treatment of subacute and chronic neck (NP), thoracic (TP) and low back pain (LBP) in the Spanish National Health Service (SNHS), by identifying prognostic factors for clinical outcome. SUMMARY OF BACKGROUND DATA: NRT consists of the temporary subcutaneous implantation of surgical devices in trigger points. Previous randomized controlled trials have shown its efficacy, effectiveness, and cost-effectiveness for treating subacute and chronic LBP. Clinical audits in routine practice have shown similar results in NP, TP, and LBP patients. PATIENTS AND METHODS: All 1514 patients from the SNHS in the Balearic Islands in which a NRT intervention was performed and who were discharged between January 1, 2004, and December 31, 2005, were included in this study. Treatment failure was defined as a baseline score equivalent to or lower than the corresponding one at discharge for local pain, referred pain, or LBP-related disability. Multivariate logistic regression models were developed for each of those variables. Maximal models included reason for referral (NP, TP, or LBP), age, sex, baseline values for each variable, number of days in which the surgical devices used in NRT were left implanted, duration of the current episode, time elapsed since the first episode, and previous failed surgery for the current episode. Calibration of the models was assessed through the Hosmer-Lemeshow test, while discrimination was assessed through the area under the ROC curve and the Nagelkerke R test. RESULTS: When referred to NRT, patients' median (IQR) duration of the episode was 210 (90, 730) days. Failure rates ranged between 9.9% for local pain and 14.5% for disability. Variables associated with a worst prognosis for local pain, referred pain, and disability were surgical devices remaining implanted for a shorter duration and, especially, a longer pain duration. Patients referred for NP were more likely to improve than those referred for TP or LBP. Regarding the evolution of local and referred pain, lesser improvement was observed in the least severe complaint at baseline. Models showed a good calibration. The area under the ROC curve ranged between 0.719 and 0.804, and R ranged between 0.101 and 0.255. CONCLUSION: A longer duration of the current episode is the worst detected prognostic factor for response to NRT, but prognostic models are inaccurate for predicting the clinical outcome of a given patient. In order to improve the success rate of this technology, these results only support earlier referral for patients complying with current indication criteria.