A study protocol for a randomized controlled trial of an anti-inflammatory nutritional intervention in patients with fibromyalgia

BackgroundThis study aims to analyze the effects of a potentially anti-inflammatory nutritional intervention in disease assessment parameters, inflammatory markers, and quality of life of fibromyalgia (FM) patients.MethodsA sample of 100 female patients diagnosed with FM, followed up at Portuguese Institute of Rheumatology (IPR) in Lisbon, is being randomly allocated in two groups. Patients in the intervention group are adopting an anti-inflammatory diet, characterized by the exemption of the intake of foods containing gluten, dairy, sugar, and ultra-processed foods, during 3months. During the first month, a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) diet is implemented, along with the anti-inflammatory diet, followed by the reintroduction of all fruits and vegetables over a consecutive period of 2months. Patients in the control group are adopting a diet based on general recommendations for healthy eating. The outcomes are pain, fatigue, quality of sleep, quality of life, gastrointestinal symptoms, and inflammation. Before and after the 3months intervention, and also 1month after beginning the intervention, the following questionnaires are applied: Revised Fibromyalgia Impact Questionnaire, visual analog pain scale, Brief Pain Inventory,visual analog scale from a list of common gastrointestinal and extraintestinal symptoms in FM, Short Form 36, Fatigue Severity Survey, and Pittsburg Sleep Quality Index. Ultra-sensitive serum C-reactive protein, eritrocyte sedimentation rate, and interleukin-8 are determined. Age, physical activity, anthropometric parameters, and body composition are being collected. Student's t test will assess the association between the disease evaluation parameters, the inflammatory markers, and the dietary interventions.DiscussionThe results of this study are expected to determine whether a change in patient nutrition helps to alleviate symptoms, which would optimize medical intervention.Trial registrationwww.ClinicalTrials.gov NCT04007705. Registered on July 5, 2019

Development and validation of exhaled breath condensate microRNAs to identify and endotype asthma in children

Detection and quantification of microRNAs (miRNAs) in exhaled breath condensate (EBC) has been poorly explored. Therefore we aimed to assess miRNAs in EBC as potential biomarkers to diagnose and endotype asthma in school aged children. In a cross sectional, nested case control study, all the asthmatic children (n = 71) and a random sample of controls (n = 115), aged 7 to 12 years, attending 71 classrooms from 20 local schools were selected and arbitrarily allocated to the development or validation set. Participants underwent skin-prick testing, spirometry with bronchodilation, had exhaled level of nitric oxide determined and EBC collected. Based on previous studies eleven miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. Principal component analysis was applied to identify miRNAs profiles and associations were estimated using regression models. In the development set (n = 89) two clusters of miRNAs were identified. After adjustments, cluster 1 and three of its clustered miRNAs, miR-126-3p, miR-133a-3p and miR-145-5p were positively associated with asthma. Moreover miR-21-5p was negatively associated with symptomatic asthma and positively associated with positive bronchodilation without symptoms. An association was also found between miR-126-3p, cluster 2 and one of its clustered miRNA, miR-146-5p, with higher FEF25-75 reversibility. These findings were confirmed in the validation set (n = 97) where two identical clusters of miRNAs were identified. Additional significant associations were observed between miR-155-5p with symptomatic asthma, negative bronchodilation with symptoms and positive bronchodilation without symptoms. We showed that microRNAs can be measured in EBC of children and may be used as potential biomarkers of asthma, assisting asthma endotype establishment.Authors gratefully acknowledge the funding by Fundação para a Ciência e Tecnologia through the Project NORTE-01-0145-FEDER-000010 - Health, Comfort and Energy in the Built Environment (HEBE), cofinanced by Programa Operacional Regional do Norte (NORTE2020), through Fundo Europeu de Desenvolvimento Regional (FEDER) and EXALAR 21 project financed by FEDER/FNR and by Fundação para a Ciência e Tecnologia (EXALAR 21 02/SAICT/2017 - Project nº 30193). FCM kindly acknowledges the scholarship SFRH/BD/144563/2019 granted by Fundação para a Ciência e Tecnologia, as well as the Fulbright Research Grant 2019/2020 granted by Fulbright Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

An anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols diet improved patient reported outcomes in fibromyalgia: A randomized controlled trial

Background: Fibromyalgia (FM) has been associated with dysbiosis and low-grade inflammation. Studies have reported that diet influences clinical features in FM. Objective: To evaluate the effect of an anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols (FODMAP) diet on clinical outcomes of patients with FM. Methods: This two arms Randomized Controlled Trial (NCT04007705) included 46 female patients with FM. The intervention group (n = 22) adopted an anti-inflammatory diet for 3 months, excluding gluten, dairy, added sugar, and ultra-processed foods, along with a low FODMAPs diet in the first month. The control group (n = 24) followed general healthy eating recommendations. Both diets were applied by a certified dietitian. Before and after the intervention, participants were assessed regarding pain, fatigue, gastrointestinal symptoms, quality of sleep, and quality of life, through the Revised Fibromyalgia Impact Questionnaire (FIQR), Visual Analogue Pain Scale (VAS), Visual Analog Scale from gastrointestinal symptoms (VAS GI), Brief Pain Inventory (BPI), Pittsburg Sleep Quality Index (PSQI), Fatigue Severity Survey (FSS), and The Short Form Health Survey (SF-36). A blood sample was collected and high-sensitive C-Reactive Protein and Erythrocyte Sedimentation Rate were quantified. Paired Samples t-test/Wilcoxon and independent samples t-test/Mann-Whitney were used to compare variables between groups. Results: After intervention, there was an improvement in intervention group scores of FIQR (p = 0.001), VAS (p = 0.002), BPI (p = 0.011), FSS (p = 0.042), VAS_GI (p = 0.002), PSQI (p = 0.048), and SF36 (p = 0.045) compared to control group. Inflammatory biomarkers (hs-CRP, ESR) did not change in both groups. The intervention was beneficial in the intervention group, regardless of age, disease duration, body mass index variation, and body fat change between baseline and post-intervention. Conclusion: An anti-inflammatory and low-FODMAP diet improved clinical features in patients with FM and may be useful as a complement to pharmacological therapy

Qual o Papel dos Bloqueadores-Beta numa Coorte de Tratamento Contemporânea de Doentes com Síndrome Coronária Aguda? Análise de Emparelhamento de Score de Propensão

INTRODUCTION: The evidence for beta-blocker use in patients after acute coronary syndrome (ACS), particularly in those with left ventricular (LV) dysfunction, dates from the late 1990s. We aimed to assess the role of beta-blockers in a contemporary population of patients with ACS. METHODS: Propensity-score matching (1:2) was performed for the use of beta-blockers in a population of consecutive patients admitted to our department with ACS. After matching, 1520 patients were analyzed. Cox regression analysis was used to assess the impact of beta-blocker use on the primary outcome (one-year all-cause mortality). RESULTS: Patients who did not receive beta-blockers were less aggressively treated with other pharmacological and invasive interventions and had higher one-year mortality (20.3% vs. 7.5%). Beta-blocker use was an independent predictor of mortality, with a significant relative risk reduction of 56%. The other independent predictors were age, diabetes, LV dysfunction, heart rate, systolic blood pressure and creatinine on admission. The impact of beta-blockers was significant for all classes of LV function, including patients with normal or mildly reduced ejection fraction. CONCLUSIONS: In a contemporary ACS population, we confirmed the benefits of beta-blocker use after ACS, including in patients with normal or mildly to moderately impaired LV function.info:eu-repo/semantics/publishedVersio

Motivational interviewing for the prevention of alcohol misuse in young adults

Background Alcohol use and misuse in young people is a major risk behaviour for mortality and morbidity. Motivational interviewing (MI) is a popular technique for addressing excessive drinking in young adults. Objectives To assess the effects of motivational interviewing (MI) interventions for preventing alcohol misuse and alcohol‐related problems in young adults. Search methods We identified relevant evidence from the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 12), MEDLINE (January 1966 to July 2015), EMBASE (January 1988 to July 2015), and PsycINFO (1985 to July 2015). We also searched clinical trial registers and handsearched references of topic‐related systematic reviews and the included studies. Selection criteria We included randomised controlled trials in young adults up to the age of 25 years comparing MIs for prevention of alcohol misuse and alcohol‐related problems with no intervention, assessment only or alternative interventions for preventing alcohol misuse and alcohol‐related problems. Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results We included a total of 84 trials (22,872 participants), with 70/84 studies reporting interventions in higher risk individuals or settings. Studies with follow‐up periods of at least four months were of more interest in assessing the sustainability of intervention effects and were also less susceptible to short‐term reporting or publication bias. Overall, the risk of bias assessment showed that these studies provided moderate or low quality evidence. At four or more months follow‐up, we found effects in favour of MI for the quantity of alcohol consumed (standardised mean difference (SMD) −0.11, 95% confidence interval (CI) −0.15 to −0.06 or a reduction from 13.7 drinks/week to 12.5 drinks/week; moderate quality evidence); frequency of alcohol consumption (SMD −0.14, 95% CI −0.21 to −0.07 or a reduction in the number of days/week alcohol was consumed from 2.74 days to 2.52 days; moderate quality evidence); and peak blood alcohol concentration, or BAC (SMD −0.12, 95% CI −0.20 to 0.05, or a reduction from 0.144% to 0.131%; moderate quality evidence). We found a marginal effect in favour of MI for alcohol problems (SMD −0.08, 95% CI −0.17 to 0.00 or a reduction in an alcohol problems scale score from 8.91 to 8.18; low quality evidence) and no effects for binge drinking (SMD −0.04, 95% CI −0.09 to 0.02, moderate quality evidence) or for average BAC (SMD −0.05, 95% CI −0.18 to 0.08; moderate quality evidence). We also considered other alcohol‐related behavioural outcomes, and at four or more months follow‐up, we found no effects on drink‐driving (SMD −0.13, 95% CI −0.36 to 0.10; moderate quality of evidence) or other alcohol‐related risky behaviour (SMD −0.15, 95% CI −0.31 to 0.01; moderate quality evidence). Further analyses showed that there was no clear relationship between the duration of the MI intervention (in minutes) and effect size. Subgroup analyses revealed no clear subgroup effects for longer‐term outcomes (four or more months) for assessment only versus alternative intervention controls; for university/college vs other settings; or for higher risk vs all/low risk participants. None of the studies reported harms related to MI. Authors' conclusions The results of this review indicate that there are no substantive, meaningful benefits of MI interventions for preventing alcohol use, misuse or alcohol‐related problems. Although we found some statistically significant effects, the effect sizes were too small, given the measurement scales used in the included studies, to be of relevance to policy or practice. Moreover, the statistically significant effects are not consistent for all misuse measures, and the quality of evidence is not strong, implying that any effects could be inflated by risk of bias.info:eu-repo/semantics/publishedVersio

Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus.

A subset of neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating depth and frequency of breathing in response to changes in tissue CO2/H+. The activity of chemosensitive RTN neurons is also subject to modulation by CO2/H+-dependent purinergic signaling. However, mechanisms contributing to purinergic regulation of RTN chemoreceptors are not entirely clear. Recent evidence suggests adenosine inhibits RTN chemoreception in vivo by activation of A1 receptors. The goal of this study was to characterize effects of adenosine on chemosensitive RTN neurons and identify intrinsic and synaptic mechanisms underlying this response. Cell-attached recordings from RTN chemoreceptors in slices from rat or wild-type mouse pups (mixed sex) show that exposure to adenosine (1 µM) inhibits chemoreceptor activity by an A1 receptor-dependent mechanism. However, exposure to a selective A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, DPCPX; 30 nM) alone did not potentiate CO2/H+-stimulated activity, suggesting activation of A1 receptors does not limit chemoreceptor activity under these reduced conditions. Whole-cell voltage-clamp from chemosensitive RTN neurons shows that exposure to adenosine activated an inward rectifying K+ conductance, and at the network level, adenosine preferentially decreased frequency of EPSCs but not IPSCs. These results show that adenosine activation of A1 receptors inhibits chemosensitive RTN neurons by direct activation of a G-protein-regulated inward-rectifier K+ (GIRK)-like conductance, and presynaptically, by suppression of excitatory synaptic input to chemoreceptors

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged tau and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.Supported by Portuguese grants from FCT (POCI/SAU-FCF/60803/2004 and POCI/SAU-MMO/61547/2004) through Cardiovascular R&D Unit (FCT No. 51/94)

Global effect of the COVID-19 pandemic on paediatric cancer care: a cross-sectional study

BACKGROUND: Although mortality due to COVID-19 has been reportedly low among children with cancer, changes in health-care services due to the pandemic have affected cancer care delivery. This study aimed to assess the effect of the COVID-19 pandemic on childhood cancer care worldwide. METHODS: A cross-sectional survey was distributed to paediatric oncology providers worldwide from June 22 to Aug 21, 2020, through the St Jude Global Alliance and International Society for Paediatric Oncology listservs and regional networks. The survey included 60 questions to assess institution characteristics, the number of patients diagnosed with COVID-19, disruptions to cancer care (eg, service closures and treatment abandonment), adaptations to care, and resources (including availability of clinical staff and personal protective equipment). Surveys were included for analysis if respondents answered at least two thirds of the items, and the responses were analysed at the institutional level. FINDINGS: Responses from 311 health-care professionals at 213 institutions in 79 countries from all WHO regions were included in the analysis. 187 (88%) of 213 centres had the capacity to test for SARS-CoV-2 and a median of two (range 0-350) infections per institutution were reported in children with cancer. 15 (7%) centres reported complete closure of paediatric haematology-oncology services (median 10 days, range 1-75 days). Overall, 2% (5 of 213) of centres were no longer evaluating new cases of suspected cancer, while 43% (90 of 208) of the remaining centers described a decrease in newly diagnosed paediatric cancer cases. 73 (34%) centres reported increased treatment abandonment (ie, failure to initiate cancer therapy or a delay in care of 4 weeks or longer). Changes to cancer care delivery included: reduced surgical care (153 [72%]), blood product shortages (127 [60%]), chemotherapy modifications (121 [57%]), and interruptions to radiotherapy (43 [28%] of 155 institutions that provided radiotherapy before the pandemic). The decreased number of new cancer diagnoses did not vary based on country income status (p=0·14). However, unavailability of chemotherapy agents (p=0·022), treatment abandonment (p<0·0001), and interruptions in radiotherapy (p<0·0001) were more frequent in low-income and middle-income countries than in high-income countries. These findings did not vary based on institutional or national numbers of COVID-19 cases. Hospitals reported using new or adapted checklists (146 [69%] of 213), processes for communication with patients and families (134 [63%]), and guidelines for essential services (119 [56%]) as a result of the pandemic. INTERPRETATION: The COVID-19 pandemic has considerably affected paediatric oncology services worldwide, posing substantial disruptions to cancer diagnosis and management, particularly in low-income and middle-income countries. This study emphasises the urgency of an equitably distributed robust global response to support paediatric oncology care during this pandemic and future public health emergencies. FUNDING: American Lebanese Syrian Associated Charities. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section