A molecular landscape of quiescence and proliferation highlights the role of Pten in mammary gland acinogenesis.

Cell context is key for cell state. Using physiologically relevant models of laminin-rich extracellular matrix (lrECM) induction of mammary epithelial cell quiescence and differentiation, we provide a landscape of the key molecules for the proliferation-quiescence decision, identifying multiple layers of regulation at the mRNA and protein levels. Quiescence occurred despite activity of Fak (also known as PTK2), Src and phosphoinositide 3-kinases (PI3Ks), suggesting the existence of a disconnecting node between upstream and downstream proliferative signalling. Pten, a lipid and protein phosphatase, fulfils this role, because its inhibition increased proliferation and restored signalling via the Akt, mTORC1, mTORC2 and mitogen-activated protein kinase (MAPK) pathways. Pten and laminin levels were positively correlated in developing murine mammary epithelia, and Pten localized apicolaterally in luminal cells in ducts and near the nascent lumen in terminal end buds. Consistently, in three-dimensional acinogenesis models, Pten was required for triggering and sustaining quiescence, polarity and architecture. The multilayered regulatory circuitry that we uncovered provides an explanation for the robustness of quiescence within a growth-suppressive microenvironment, which could nonetheless be disrupted by perturbations in master regulators such as Pten.

Cut-Offs for Disease Activity States in Axial Spondyloarthritis With Ankylosing Spondylitis Disease Activity Score (ASDAS) Based on C-Reactive Protein and ASDAS Based on Erythrocyte Sedimentation Rate: Are They Interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

A Stratified Approach for Managing Patients With Low Back Pain in Primary Care (SPLIT Program): A Before-and-After Study.

PURPOSE: To determine the effects of stratified primary care for low back pain (SPLIT program) in decreasing back-related disability for patients with low back pain (LBP) in primary care. METHODS: We conducted a before-and-after study. We compared health-related outcomes for 2 sequential, independent cohorts of patients with LBP recruited at 7 primary care units in Portugal. The first prospective cohort study characterized usual care (UC) and collected data from February to September 2018. The second was performed when the SPLIT program was implemented and collected data from November 2018 to October 2021. Between cohorts, physical therapists were trained in the implementation of the SPLIT program, which used the STarT Back Screening Tool to categorize patients for matched treatment. We compared back-related disability (Roland-Morris Disability Questionnaire, 0-24 points), pain (Numeric Pain Rating Scale, 0-10 points), perceived effect of treatment (Global Perceived Effect Scale, -5 to +5 points), and health-related quality of life (EuroQoL 5 dimensions 3 levels index, 0-1 points). RESULTS: We enrolled a total of 447 patients: 115 in the UC cohort (mostly treated with pharmacologic treatment) and 332 in the SPLIT cohort (all referred for a physical therapy intervention program). Over the study period of 6 months, patients in the SPLIT program showed significantly greater improvements in back-related disability (ß, -2.94; 95% CI, -3.63 to -2.24; P ≤ .001), pain (ß, -0.88; 95% CI, -1.18 to -0.57; P ≤ .001), perceived effect of treatment (ß, 1.40; 95% CI, 0.97 to 1.82; P ≤ .001), and health-related quality of life (ß, 0.11; 95% CI, 0.08 to 0.14; P ≤ .001) compared with UC. CONCLUSIONS: Patients in the SPLIT program for LBP showed greater benefits regarding health-related outcomes than those receiving UC.

Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation.

OBJECTIVES: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis. METHODS: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student's t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen's d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference. RESULTS: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men's mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented. CONCLUSIONS: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tables.

MyBack - effectiveness and implementation of a behavior change informed exercise programme to prevent low back pain recurrences: a hybrid effectiveness-implementation randomized controlled study protocol.

BACKGROUND: Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context. METHODS: This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence). DISCUSSION: To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system. TRIAL REGISTRATION NUMBER: NCT05841732.

Costs of incident non-hip osteoporosis-related fractures in postmenopausal women from a payer perspective.

Osteoporosis-related fractures lead to high morbidity, mortality, and healthcare costs among post-menopausal women. This study showed that incident non-hip osteoporosis-related fractures are frequent among women aged 50 + in Portugal, leading to excessive healthcare costs of €74 million per year, in a conservative scenario. PURPOSE: This study aimed to estimate the costs of incident non-hip osteoporosis-related fractures among postmenopausal women living in Portugal from a payer perspective. METHODS: The study includes women ≥ 50 years old who participated in the baseline assessment (2011-2013) and the first follow-up wave (2013-2015) of the Epidemiology of Chronic Diseases cohort, a Portuguese community-based longitudinal prospective study (n = 2,762). Incident non-hip osteoporosis-related fractures were defined as any self-reported low impact non-hip fractures since baseline. Healthcare resource utilization during the year following fracture was obtained from an informal panel of experts. The amounts of resources used were multiplied by the national tariffs practiced in the National Health Service (NHS) to obtain the cost per patient in the year following a wrist, vertebral, or other site fracture, which was subsequently multiplied by the estimated annual number of incident fractures to obtain the total annual cost of incident non-hip osteoporosis-related fractures among postmenopausal women. RESULTS: Each year approximately 5,000 wrist, 3,500 vertebral, and 39,000 other-site osteoporosis-related fractures occur in women aged 50 + in Portugal. Healthcare costs per patient in the year following fracture vary from €2,709.52 for vertebral fractures to €3,096.35 for other fractures. Non-hip incident osteoporosis-related fractures among 50 + women cost approximately €74 million per year. Among all healthcare services, physiotherapy represents the bulk of costs. CONCLUSIONS: This study pinpoints the relevance of preventing non-hip osteoporosis-related fractures, as these cost about €74 million per year in direct healthcare costs, a substantial impact on the budget of the Portuguese NHS.

Decreased plasma levels and dietary intake of minerals in women with migraine.

It has been suggested that an imbalance in mineral levels is involved in the pathophysiology of migraine. However, only a few studies have investigated the circulating levels of mineral in patients with migraine during the pain-free period (i.e. interictal). This study aimed to investigate whether the interictal plasma levels of minerals of women with migraine differ from those of women without migraine (controls). This is a cross-sectional study involving 67 women, of which 38 were diagnosed with migraine and 29 were controls. The groups were similar in age and body mass index. Plasma levels of magnesium (Mg), copper (Cu), calcium (Ca), zinc (Zn), iron (Fe), and selenium (Se) were measured. Dietary intake was assessed using a 24-hour food recall, and migraine impact was evaluated using the Headache Impact Test, version 6 (HIT-6). The association between migraine disability, and plasma levels and dietary intake of minerals was assessed through correlation and logistic regression analyses. Women with migraine had significantly lower plasma levels of Mg, Ca, Cu, and Zn than controls. In parallel, dietary intake of Mg, Cu, and Fe was significantly lower in patients with migraine. Migraine impact was not associated with plasma levels or dietary intake of minerals. The results suggest that patients with migraine have lower plasma levels of minerals, and dietary intervention to ensure adequate mineral intake should be considered as a therapeutic strategy for migraine.

Health-related quality of life among spondyloarthritis and chronic low back pain patients: results from a nationwide population-based survey.

PURPOSE: Both spondyloarthritis and chronic low back pain (CLBP) significantly impact health-related quality of life (HRQoL). It is important to clarify whether these disorders have different impacts on the several domains of HRQoL as different mechanisms may necessitate different treatment interventions. Moreover, the factors associated with HRQoL can inform more targeted group interventions to promote HRQoL. METHODS: We used data from EpiReumaPt, a population-based survey conducted from September 2011 to December 2013. HRQoL was assessed with EuroQoL-5-Dimensions (EQ-5D). Spondyloarthritis was diagnosed by expert opinion (rheumatologist) and predefined criteria. CLBP was diagnosed if low back pain was present on the day of the interview and persisted for > 90 days. Univariable and multivariable linear regression analyses compared HRQoL among subjects with spondyloarthritis, CLBP, and no rheumatic diseases. Multivariable linear regression analyses evaluated HRQoL factors in spondyloarthritis and CLBP subjects. RESULTS: We included 92 spondyloarthritis patients, 1376 CLBP patients, and 679 subjects without rheumatic diseases. HRQoL was similarly affected in spondyloarthritis and CLBP (ß = - 0.03, 95% CI [- 0.08; 0.03]) in all EQ5D dimensions. A much lower HRQoL was found in spondyloarthritis and CLBP patients compared with subjects without rheumatic diseases (ß = - 0.14, 95% CI [- 0.19; - 0.10]; ß = - 0.12, 95% CI [- 0.14; - 0.09], respectively). In spondyloarthritis subjects, multimorbidity and active disease were associated with worse HRQoL (ß = - 0.18; 95% CI [- 0.24; 0.03]; ß = - 0.13; 95% CI [- 0.29; - 0.05], respectively), and regular physical exercise was associated with better HRQoL (ß = 0.18; 95% CI [0.10; 0.30]). In CLBP subjects, multimorbidity (ß = - 0.11; 95% CI [- 0.14; - 0.08]), obesity (ß = - 0.04; 95% CI [- 0.08; - 0.01]), and low back pain intensity (ß = - 0.02; 95% CI [- 0.03; - 0.02]) were associated with worse HRQoL, and regular physical exercise (ß = 0.08; 95% CI [0.05; 0.11]) was significantly associated with better HRQoL. CONCLUSION: Spondyloarthritis and CLBP subjects reported similar levels of impairment in the mental, physical, and social domains of HRQoL. Future health plans should address modifiable factors associated with HRQoL in these conditions to achieve better outcomes.

Zgli: A Pipeline for Clustering by Compression with Application to Patient Stratification in Spondyloarthritis.

The normalized compression distance (NCD) is a similarity measure between a pair of finite objects based on compression. Clustering methods usually use distances (e.g., Euclidean distance, Manhattan distance) to measure the similarity between objects. The NCD is yet another distance with particular characteristics that can be used to build the starting distance matrix for methods such as hierarchical clustering or K-medoids. In this work, we propose Zgli, a novel Python module that enables the user to compute the NCD between files inside a given folder. Inspired by the CompLearn Linux command line tool, this module iterates on it by providing new text file compressors, a new compression-by-column option for tabular data, such as CSV files, and an encoder for small files made up of categorical data. Our results demonstrate that compression by column can yield better results than previous methods in the literature when clustering tabular data. Additionally, the categorical encoder shows that it can augment categorical data, allowing the use of the NCD for new data types. One of the advantages is that using this new feature does not require knowledge or context of the data. Furthermore, the fact that the new proposed module is written in Python, one of the most popular programming languages for machine learning, potentiates its use by developers to tackle problems with a new approach based on compression. This pipeline was tested in clinical data and proved a promising computational strategy by providing patient stratification via clusters aiding in precision medicine.

Using Patient-Reported Outcome Measures to Evaluate Care for Patients With Inflammatory Chronic Rheumatic Disease.

OBJECTIVES: Few countries integrate patient-reported outcome measures (PROMs) in routine performance assessment and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modeling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and rheumatology center primarily responsible for their care. METHODS: Using data from the Portuguese Register of Rheumatic Diseases, we assess health status using the Health Assessment Questionnaire-Disability Index for rheumatic patients receiving biological drugs between 2000 and 2017. We specify a fixed-effects model using the least squares dummy variables estimator. RESULTS: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 rheumatology centers report higher health status than those at other centers. CONCLUSIONS: PROMs can be used for those with chronic conditions to provide the patient's perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organizations monitor PROMs and engage in performance assessment initiatives on a routine basis.

The quality and inflammatory index of the diet of patients with migraine.

BACKGROUND: The association between diet and migraine has been reported in the literature, but only a few studies have evaluated whether the diet consumed by patients with migraine differs from individuals without migraine. OBJECTIVE: Herein, we aimed to investigate whether the quality and the Dietary Inflammatory Index (DII) of diet consumed by migraine patients differ from that consumed by healthy controls. We also evaluated whether the severity of migraine and headache frequency were associated with these parameters. METHODS: Patients of both sexes, aged between 18 and 65, with episodic migraine and healthy controls were enrolled in this cross-sectional study. Disability and impact caused by migraine and depressive symptoms were evaluated. Dietary intake was assessed using a 24-hour dietary recall and a three-day non-consecutive food record. The quality of the diet was calculated using the Healthy Eating Index (HEI)-2015 adapted to the Brazilian population, and DII was calculated based on the method developed by Shivappa et al. (2014). RESULTS: Ninety patients with migraine and 62 individuals without migraine were included in this study. The groups did not differ regarding age, sex, marital status, years of schooling, anthropometric characteristics, and depressive symptoms. Patients with migraine had lower HEI total score than controls, indicating that these patients have a lower quality of the diet. Patients with migraine also had higher DII than controls. Nevertheless, HEI and DII scores did not correlate with migraine frequency and severity. CONCLUSION: This study corroborates the view that the characteristics of the diet might be involved in migraine pathophysiology.

Animal foods and mobility limitations in community-dwelling young-old adults: longitudinal analysis of the EpiDoC cohort.

BACKGROUND: Nutrition and particularly protein play a role in optimally stimulating muscle protein synthesis and maintaining function. Animal foods are excellent sources of high-quality protein. Therefore, we aimed to determine the association between the consumption of animal foods and mobility limitations in young-old adults. METHODS: The analytic sample was composed of 2860 community-dwelling adults aged 50 and over from a nationally representative longitudinal cohort of Portuguese adults who were followed up to 2.7 years. An animal food intake score was derived from the frequency of consumption of meat, fish, and dairy products. Mobility limitations were defined as the difficulty standing up from a chair, walking, and climbing stairs. To determine the association between animal food intake and mobility limitations mixed effects logistic models were fitted. RESULTS: Associations between quartiles of animal food intake and mobility limitations (for example, for walking outdoors Quartile 4 v Q1: OR: 0.29; 95%CI: 0.15, 0.56) in unadjusted models were present, but there was no difference in the rate of change of mobility limitations over time in unadjusted models. These associations were no longer present when models were adjusted for sociodemographic, lifestyle and health variables. For example, participants in Q4 of animal food intake were not more or less likely to have difficulty climbing stairs than those in Q1 (OR: 0.95; 95%CI: 0.65, 1.38) nor have a different rate of change over time (OR: 0.86; 95%CI: 0.54, 1.37). CONCLUSIONS: No convincing evidence was found to support an effect of animal foods intake measured at baseline on self-reported mobility limitations over a short period of time.

Obesity- attributable costs of absenteeism among working adults in Portugal.

BACKGROUND: Obesity leads to poor health outcomes and may adversely affect work productivity. This study, aimed to investigate the obesity- attributable costs of absenteeism among working adults in Portugal. METHODS: The study population included individuals actively working at baseline from the Epidemiology of Chronic Diseases Cohort (EpiDoC), a large Portuguese population-based prospective study. Body mass index was measured at baseline and in two follow-up interviews. Absenteeism in each wave of the EpiDoC was assessed by the question "Did you have a sick leave in the previous 12 months? yes/no", followed by "How many days did you miss work due to sickness in the previous twelve months?". Body mass index (BMI) was classified into underweight, normal weight, overweight, and obese, based on the standard World Health Organization definition. Association between obesity and absenteeism was estimated with the negative binomial regression model adjusted for BMI, chronic diseases, and lifestyle. Obesity- attributable costs were calculated using lost gross income during the time absent from work, through the human-capital approach. RESULTS: The EpiDoC included 4338 working adults at baseline. Of these, 15.2% were obese at the beginning of the study and 22.7% of the population had been absent from work in the last 12 months. Participants with obesity missed 66% more days at work (IRR: 1.66; CI 95%:1.13-2.44; (p = 0.009.) than those with normal weight. The odds of having been absent from work were 1.4 times higher in obese compared to non-obese individuals (CI 95%: 1.18-1.67; p < 0.01) adjusted to sex and type of work. Obese individuals missed 3.8 more days per year than those with normal weight (95%CI: 3.1-4.5). Extrapolating to the entire Portuguese working population, absenteeism due to obesity incurred an additional cost of €238 million per year. CONCLUSION: Obesity imposes a financial burden due to absenteeism in Portugal. Employers and national health regulators should seek effective ways to reduce these costs.

Transcontinental Dissemination of the L2b/D-Da Recombinant Chlamydia trachomatis Lymphogranuloma venereum (LGV) Strain: Need of Broad Multi-Country Molecular Surveillance.

Previously, we identified a Chlamydia trachomatis lymphogranuloma venereum (LGV) recombinant strain possessing a non-LGV ompA genotype. Here, culture-independent genome sequencing confirms its circulation in Europe, Middle East, and North America, and unveils emergence of antibiotic resistance. Broad surveillance is needed.

A Home-Based eHealth Intervention for an Older Adult Population With Food Insecurity: Feasibility and Acceptability Study.

BACKGROUND: Food insecurity is a global public health challenge, affecting predominately the most vulnerable people in society, including older adults. For this population, eHealth interventions represent an opportunity for promoting healthy lifestyle habits, thus mitigating the consequences of food insecurity. However, before their widespread dissemination, it is essential to evaluate the feasibility and acceptability of these interventions among end users. OBJECTIVE: This study aims to explore the feasibility and acceptability of a home-based eHealth intervention focused on improving dietary and physical activity through an interactive television (TV) app among older adults with food insecurity. METHODS: A pilot noncontrolled quasi-experimental study was designed with baseline and 3-month follow-up assessments. Older adult participants with food insecurity were recruited from 17 primary health care centers in Portugal. A home-based intervention program using an interactive TV app aimed at promoting healthy lifestyle behaviors was implemented over 12 weeks. Primary outcomes were feasibility (self-reported use and interest in eHealth) and acceptability (affective attitude, burden, ethicality, perceived effectiveness, and self-efficacy), which were evaluated using a structured questionnaire with a 7-point Likert scale. Secondary outcomes were changes in food insecurity (Household Food Insecurity Scale), quality of life (European Quality of Life Questionnaire with five dimensions and three levels and Functional Assessment of Chronic Illness Therapy-Fatigue), physical function (Health Assessment Questionnaire, Elderly Mobility Scale, grip strength, and regularity of exercise), and nutritional status (adherence to the Mediterranean diet). RESULTS: A sample of 31 older adult individuals with food insecurity was enrolled in the 12-week intervention program with no dropouts. A total of 10 participants self-reported low use of the TV app. After the intervention, participants were significantly more interested in using eHealth to improve food insecurity (baseline median 1.0, IQR 3.0; 3-month median 5.0, IQR 5.0; P=.01) and for other purposes (baseline median 1.0, IQR 2.0; 3-month median 6.0, IQR 2.0; P=.03). High levels of acceptability were found both before and after (median range 7.0-7.0, IQR 2.0-0.0 and 5.0-7.0, IQR 2.0-2.0, respectively) the intervention, with no significant changes for most constructs. Clinically, there was a reduction of 40% in food insecurity (P=.001), decreased fatigue (mean -3.82, SD 8.27; P=.02), and improved physical function (Health Assessment Questionnaire: mean -0.22, SD 0.38; P=.01; Elderly Mobility Scale: mean -1.50, SD 1.08; P=.01; regularity of exercise: baseline 10/31, 32%; 3 months 18/31, 58%; P=.02). No differences were found for the European Quality of Life Questionnaire with five dimensions and three levels, grip strength, or adherence to the Mediterranean diet. CONCLUSIONS: The home-based eHealth intervention was feasible and highly acceptable by participants, thus supporting a future full-scale trial. The intervention program not only reduced the proportion of older adults with food insecurity but also improved participants' fatigue and physical function. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.6626.

Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine.

BACKGROUND: Previous studies have shown an analgesic effect of ginger in the acute treatment of migraine, and there is anecdotal evidence of its efficacy in migraine prophylaxis. OBJECTIVE: This study aimed to evaluate the potential of ginger to prevent migraine attacks. METHODS: This double-blind, placebo-controlled randomized clinical trial took place at the Headache Clinic, Universidade Federal de Minas Gerais (Belo Horizonte, Minas Gerais, Brazil), involving 107 patients. Only subjects diagnosed with episodic migraine, aged between 18 and 60 years old, and who were not taking any prophylactic medication, were enrolled in the study. After one month of observation, subjects selected for the study were randomized 1:1 into placebo and treatment groups. Patients received capsules three times per day of 200 mg of dry extract of ginger (5% active ingredient) or placebo (cellulose) for three months. Visits were performed monthly and the patients were asked to fill in a migraine diary. The adherence to treatment was evaluated by counting capsules. RESULTS: The percentage of patients who responded to treatment (i.e. a reduction of 50% in the number of migraine attacks at the end of treatment) did not differ between the groups. There was a decrease in the number of days with severe pain, analgesic use for acute migraine and duration of migraine attacks in both groups, without significant difference between ginger and placebo groups. CONCLUSIONS: Ginger provides no greater benefit in the prophylactic treatment of migraine when compared to placebo. This trial is registered at ClinicalTrials.gov (NCT02570633).

Altered Serum Levels of Renin-Angiotensin System Markers in Migraine.

OBJECTIVE: To compare the serum levels of renin-angiotensin system (RAS) components between patients with migraine and healthy controls, and to evaluate whether these levels are associated with migraine severity. We hypothesized that migraine would be associated with the activation of the inflammatory arm of the RAS, possibly leading to increased levels of angiotensin (Ang) II. BACKGROUND: Recent studies have proposed the use of drugs that interfere with RAS, a hormonal system primarily implicated in blood pressure regulation, as a prophylactic strategy for migraine. However, no previous studies have directly assessed RAS components in migraine. METHODS: This was a cross-sectional study involving 30 patients with episodic migraine who were in the interictal period and 20 healthy controls. This study was conducted at Hospital das Clínicas (Universidade Federal de Minas Gerais, Belo Horizonte, Brazil) outpatient clinic. Headache severity was evaluated using the Headache Impact Test, version 6 (HIT-6) and the Migraine Disability Test (MIDAS) questionnaires. Given that migraine is comorbid with mood disorders, depressive and anxious symptoms were evaluated using the Beck Anxiety and Depression Inventories (BDI and BAI), respectively. Clinical and demographic data were also collected. Serum levels of angiotensin-converting enzyme (ACE), ACE2, Ang II, and Ang (1-7) were measured by enzyme-linked immunosorbent assay. RESULTS: Patients with migraine and controls were comparable in age, body mass index, blood pressure, and depressive and anxious symptoms. Patients with migraine showed lower levels of ACE [85.2 (66.8, 101.2) vs 65.5 (54.2, 77.5); P = .005] and lower ACE/ACE2 ratio [4.3 (3.4, 5.2) vs 3.5 (2.9, 4.1); P = .032] than controls. Conversely, patients with migraine had higher levels of Ang II [309.7 ± 147.4 vs 605.4 ± 200.4; difference: -287.1 (95% CI: -391.4--182.8), P < .001] and Ang (1-7) [214.4 ± 155.8 vs 397.9 ± 217.9; difference: -184.6 (95% CI: -296.7--72.6), P = .001] than controls. There were no correlations between RAS serum markers and migraine severity scores (HIT and MIDAS) or depressive and anxious symptoms (BDI and BAI) (P > .05). CONCLUSIONS: Altogether, our results suggest the participation of RAS in migraine pathophysiology, but not in its severity.

Double-blind placebo-controlled randomized clinical trial of ginger ( Zingiber officinale Rosc.) addition in migraine acute treatment.

BACKGROUND: Previous studies have demonstrated the analgesic effects of ginger in different conditions, but evidence about its efficacy in migraine treatment is scarce. OBJECTIVE: This study aimed to evaluate the potential of ginger to improve acute migraine as an add-on strategy to standard treatment. METHODS: A double-blind placebo-controlled randomized clinical trial in the emergency room of a general hospital was conducted. Patients who sought medical care at the time of migraine attack were enrolled in this study. Only adults with episodic migraine (one to six migraine attacks per month) with or without aura were included. Sixty participants were randomized into two groups in which they received 400 mg of ginger extract (5% active ingredient) or placebo (cellulose), in addition to an intravenous drug (100 mg of ketoprofen) to treat the migraine attack. Patients filled a headache diary before, 0.5 h, 1 h, 1.5 h and 2 h after the medication. Pain severity, functional status, migraine symptoms and treatment satisfaction were also recorded. RESULTS: Patients treated with ginger showed significantly better clinical response after 1 h ( p = 0.04), 1.5 h ( p = 0.01) and 2 h ( p = 0.04). Furthermore, ginger treatment promoted reduction in pain and improvement on functional status at all times assessed. CONCLUSIONS: The addition of ginger to non-steroidal anti-inflammatory drugs may contribute to the treatment of migraine attack. This trial is registered at ClinicalTrials.gov (NCT02568644).

Peer Adoption and Development of Health Innovations by Patients: National Representative Study of 6204 Citizens.

BACKGROUND: There is growing evidence that many patients and caregivers innovate by developing new solutions to cope with their health disorders. Given the easy access to vast internet resources and peers globally, it is increasingly important to understand what may influence user innovation and its adoption in health for improving individual well-being and ensuring their safety, in particular, how interactions with peers and physicians or search behavior, along with sociodemographics, may influence the decision to develop a solution or adopt one developed by a peer. OBJECTIVE: The aim of this paper was to study the development and peer-to-peer adoption of user innovations in health care and identify individual-level factors associated with these processes. METHODS: Data were collected via computer-assisted phone survey from a large, random, and representative sample of adult residents in Portugal (N=6204). User innovation questions were added to 1 wave of an ongoing observational, longitudinal, population-based epidemiological study. By asking about individual innovation activity, the sample was split into 3 groups: (1) the developers of health-related solutions for own use (developers), (2) the adopters of solutions developed by other patients or caregivers (peer-to-peer adopters), and (3) the rest of the population. Within the last group, intention to adopt was measured and used as a proxy of future behavior. Regression analysis is used to test the associations. RESULTS: In the population considered in this paper, an estimated 1.3% (75/6008) reported having developed a solution for own use and 3.3% reported to have adopted a solution developed by peers. The 3 groups (developers, adopters, and remaining population) have distinctive characteristics. Gender plays an important role in the solution development, as women are less likely to develop one (odds ratio [OR] 0.4, 95% CI 0.20-0.81; P<.05). Education is positively associated with the development activity (OR 1.13, 95% CI 1.03-1.24; P<.05) but also with the intentions to adopt a peer-developed solution. Search for health-related information is positively associated with the development, adoption, and the intentions to adopt a solution. Interactions with peers over the internet are rare, but in-person interactions are frequent and have a positive association with the dependent variables in all 3 groups. The results also suggest that trust in doctors represents an important dimension that shapes the attitudes of the population toward peer-developed solutions. CONCLUSIONS: This paper demonstrates the importance of the peer community, doctor-patient relationship, citizen's search for information on innovation, and individual attitudes toward peer-to-peer adoption in health care. It stresses the need for a reliable Web-based health-related information and the necessity to deeper understand complex relationships between the need to improve health and fulfill the need and the perception of the health care system.

Sagittal abdominal diameter resembles waist circumference as a surrogate marker of insulin resistance in adolescents-Brazilian Metabolic Syndrome Study.

OBJECTIVE: To evaluate the association of the sagittal abdominal diameter (SAD) with insulin resistance (IR) and metabolic syndrome (MetS) components, and to compare SAD with waist circumference (WC). SUBJECTS/METHODS: This was a multicenter, cross-sectional study of 520 adolescents (10- to 18-years old). IR was assessed using the homeostasis model assessment of IR (HOMA-IR) and the hyperglycaemic clamp (n = 76). RESULTS: SAD and WC were positively correlated with HOMA-IR (r = 0.637 and r = 0.653) and inversely correlated with the clamp-derived insulin sensitivity index (ISI) (r = -0.734 and r = -0.731); P < .001. In the multivariable linear regression analysis, SAD was positively associated with HOMA-IR (B = 0.046 ± 0.003) and inversely associated with the clamp-derived ISI (B = -0.084 ± 0.009) after adjusting for sex, age, and Tanner's stages (P < .001). When WC replaced the SAD, it was positively associated with HOMA-IR (B = 0.011 ± 0.001) and inversely associated with the clamp-derived ISI (B = -0.018 ± 0.002); P < .001. The values of the areas under the curves (AUC) were 0.823 and 0.813 for SAD and WC, respectively. In Bland-Altman analysis, there were agreement between both, SAD and WC, with the clamp-derived ISI (mean = 0.00; P > .05). The SAD and WC were positively associated with blood pressure, triglycerides, and uric acid, and inversely associated with high-density lipoprotein (HDL)-cholesterol after adjusting for sex, age, and Tanner's stages. CONCLUSION: The SAD was associated with IR and MetS components, with a good discriminatory power for detecting IR. When compared to WC, SAD showed equivalent results.