Early focal electroencephalogram and neuroimaging findings predict epilepsy development after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Seizures are a common complication of subarachnoid hemorrhage (SAH) in both acute and late stages: 10-20 % acute symptomatic seizures, 12-25 % epilepsy rate at five years. Our aim was to identify early electroencephalogram (EEG) and computed tomography (CT) findings that could predict long-term epilepsy after SAH. MATERIAL AND METHODS: This is a multicenter, retrospective, longitudinal study of adult patients with aneurysmal SAH admitted to two tertiary care hospitals between January 2011 to December 2022. Routine 30-minute EEG recording was performed in all subjects during admission period. Exclusion criteria were the presence of prior structural brain lesions and/or known epilepsy. We documented the presence of SAH-related cortical involvement in brain CT and focal electrographic abnormalities (epileptiform and non-epileptiform). Post-SAH epilepsy was defined as the occurrence of remote unprovoked seizures ≥ 7 days from the bleeding. RESULTS: We included 278 patients with a median follow-up of 2.4 years. The mean age was 57 (+/-12) years, 188 (68 %) were female and 49 (17.6 %) developed epilepsy with a median latency of 174 days (IQR 49-479). Cortical brain lesions were present in 189 (68 %) and focal EEG abnormalities were detected in 158 patients (39 epileptiform discharges, 119 non-epileptiform abnormalities). The median delay to the first EEG recording was 6 days (IQR 2-12). Multiple Cox regression analysis showed higher risk of long-term epilepsy in those patients with CT cortical involvement (HR 2.6 [1.3-5.2], p 0.009), EEG focal non-epileptiform abnormalities (HR 3.7 [1.6-8.2], p 0.002) and epileptiform discharges (HR 6.7 [2.8-15.8], p < 0.001). Concomitant use of anesthetics and/or antiseizure medication during EEG recording had no influence over its predictive capacity. ROC-curve analysis of the model showed good predictive capability at 5 years (AUC 0.80, 95 %CI 0.74-0.87). CONCLUSIONS: Focal electrographic abnormalities (both epileptiform and non-epileptiform abnormalities) and cortical involvement in neuroimaging predict the development of long-term epilepsy. In-patient EEG and CT findings could allow an early risk stratification and facilitate a personalized follow-up and management of SAH patients.

Experimental Observation of Critical Scaling in Magnetic Dynamic Phase Transitions.

We explore the critical behavior of dynamic phase transitions in ultrathin uniaxial Co films. Our data demonstrate the occurrence of critical fluctuations, which define the critical regime, and in which we conduct a scaling analysis of the dynamic order parameter Q, utilizing a dynamic analog to the Arrott-Noakes equation of state. Our results show dynamic critical exponents that agree with the 2D Ising model as theoretically predicted. However, equilibrium critical exponents of our sample agree with the 3D Ising model. We argue that these differences between dynamic and thermodynamic behavior are due to fundamentally different length scales at which dimensional crossovers occur.

Mammographic features of benign breast lesions and risk of subsequent breast cancer in women attending breast cancer screening.

OBJECTIVES: To evaluate the mammographic features in women with benign breast disease (BBD) and the risk of subsequent breast cancer according to their mammographic findings. METHODS: We analyzed data from a Spanish cohort of women screened from 1995 to 2015 and followed up until December 2017 (median follow-up, 5.9 years). We included 10,650 women who had both histologically confirmed BBD and mammographic findings. We evaluated proliferative and nonproliferative BBD subtypes, and their mammographic features: architectural distortion, asymmetries, calcifications, masses, and multiple findings. The adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for breast cancer were estimated using a Cox proportional hazards model. We plotted the adjusted cumulative incidence curves. RESULTS: Calcifications were more frequent in proliferative disease with atypia (43.9%) than without atypia (36.8%) or nonproliferative disease (22.2%; p value < 0.05). Masses were more frequent in nonproliferative lesions (59.1%) than in proliferative lesions without atypia (35.1%) or with atypia (30.0%; p value < 0.05). Multiple findings and architectural distortion were more likely in proliferative disease (16.1% and 4.7%) than in nonproliferative disease (12.8% and 1.9%). Subsequent breast cancer occurred in 268 (2.5%) women. Compared with women who had masses, the highest risk of subsequent breast cancer was found in those with architectural distortions (aHR, 2.21; 95% CI, 1.16-4.22), followed by those with multiple findings (aHR, 1.89; 95% CI, 1.34-2.66), asymmetries (aHR, 1.66; 95% CI, 0.84-3.28), and calcifications (aHR, 1.60; 95% CI, 1.21-2.12). CONCLUSION: BBD subtypes showed distinct mammographic findings. The risk of subsequent breast cancer was high in those who have shown architectural distortion, multiple findings, asymmetries, and calcifications than in women with masses. KEY POINTS: • The presence of mammographic findings in women attending breast cancer screening helps clinicians to assess women with benign breast disease (BBD). • Calcifications were frequent in BBDs with atypia, which are the ones with a high breast cancer risk, while masses were common in low-risk BBDs. • The excess risk of subsequent breast cancer in women with BBD was higher in those who showed architectural distortion compared to those with masses.

Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

Efficacy of systemic oncological treatments in patients with advanced esophageal or gastric cancers at high risk of dying in the middle and short term: an overview of systematic reviews.

BACKGROUND: Esophageal and gastric cancers are a significant public health problem worldwide, with most patients presenting with advanced-stage disease and, consequently, poor prognosis. Systemic oncological treatments (SOT) have been widely used over more conservative approaches, such as supportive care. Nevertheless, its effectiveness in this scenario is not sufficiently clear. This paper provides an overview of systematic reviews that assessed the effectiveness of SOT compared with the best supportive care (BSC) or placebo in patients with advanced esophageal or gastric cancers in an end-of-life context. METHODS: We searched MEDLINE, EMBASE, The Cochrane Library, Epistemonikos, and PROSPERO for eligible systematic reviews (SRs) published from 2008 onwards. The primary outcomes were overall survival (OS), progression-free survival (PFS), functional status, and toxicity. Two authors assessed eligibility and extracted data independently. We evaluated the methodological quality of included SRs using the AMSTAR-2 tool and the overlap of primary studies (corrected covered area, CCA). Also, we performed a de novo meta-analysis with data reported for each primary study when it was possible. We assessed the certainty of evidence using the GRADE approach. RESULTS: We identified 16 SRs (19 included trials) for inclusion within this overview. Most reviews had a critically low methodological quality, and there was a very high overlap of primary studies. It is uncertain whether SOT improves OS and PFS over more conservative approaches due to the very low certainty of evidence. CONCLUSIONS: The evidence is very uncertain about the effectiveness of SOT for advanced esophageal or gastric cancers. High-quality SRs and further randomized clinical trials that include a thorough assessment of patient-centered outcomes are needed. TRIAL REGISTRATION: Open Science Framework, https://doi.org/10.17605/OSF.IO/7CHX6 .

Status epilepticus without impairment of consciousness: Long-term outcomes according to duration.

OBJECTIVE: The point after which non-convulsive status epilepticus (NCSE) can cause permanent damage remains to be elucidated. The aim of this study was to analyze the association between time to resolution and long-term outcomes in NCSE. METHODS: We performed a retrospective study of all patients with focal NCSE without consciousness impairment at two tertiary care hospitals in Spain. All the data were registered prospectively and the study period was December 2014-May 2018. We collected information on demographics, SE etiology, time to administration of different lines of treatment, time to NCSE resolution, and outcomes at discharge, 1 year, and 4 years. Clinical outcome was prospectively categorized as good (return to baseline function) or poor (new disability and death). RESULTS: Seventy-four patients with a mean (±SD) age of 63.4 ±â€¯17.5 years and a mean follow-up time of 2.4 ±â€¯2.2 years were studied. A poor outcome at discharge was associated with a potentially fatal etiology (p < 0.001), EMSE score (Epidemiology-based Mortality Score in Status Epilepticus) (p = 0.012), lateral periodic discharges on EEG (p = 0.034), and occurrence of major complications during hospitalization (p = 0.007). An SE duration of >100 h was clearly associated with a worse outcome (p < 0.001). In the multiple regression analysis, the only independent predictors of a poor outcome at discharge were an SE duration of >+100 hours (p = 0.001), a potentially fatal etiology (p = 0.001), and complications during hospitalization (p = 0.010). An SE duration of >100 hours retained its value as the optimal cutoff point for predicting poor outcomes at both 1 year (p = 0.037) and 4 years (p = 0.05). Other predictors of poor long-term outcomes were a potentially fatal etiology (p < 0.001) and EMSE score (p = 0.034) at 1 year, and progressive symptomatic etiology at 4 years (p = 0.025). SIGNIFICANCE: In patients with focal NCSE without consciousness impairment, a potentially fatal etiology and an SE duration of >100 h were associated with poor short-term and long-term outcomes.

How soon should urgent EEG be performed following a first epileptic seizure?

PURPOSE: Patients with a first unprovoked epileptic seizure are often seen in emergency services. Electroencephalography (EEG) is indicated for diagnosing epilepsy, but the optimal time to perform this test has not been defined. This study aimed to determine the time interval following a seizure within which EEG has the greatest diagnostic yield. METHODS: We conducted a retrospective study of all adult patients with a first unprovoked seizure who had undergone emergency EEG (July 2014-December 2019). Data collection included demographics, seizure type, time interval to EEG study, EEG pattern identified, and the prescription after emergency assessment. An optimal cut-off point for time to EEG was obtained, and an adjusted regression model was performed to establish associations with the presence of epileptiform abnormalities. RESULTS: A total of 170 patients were included (mean age: 50.7 years, 40.6% women). Epileptiform discharges were identified in 34.1% of recordings, nonepileptiform abnormalities in 46.5%, and normal findings in 19.4%. A lower latency from seizure to EEG was associated with a higher probability of finding epileptiform discharges (median: 12.7 in the epileptiform EEGs vs. 20 h in the nonepileptiform EEGs, p < 0.001). The time interval associated with the highest probability of detecting an epileptiform EEG pattern was within the first 16 h after seizure onset: 52.1% of recordings performed before the 16-h cut-off showed these abnormal patterns compared with 20.2% performed after (p < 0.001). These findings were not related to the presence of an epileptogenic lesion in neuroimaging or to other clinical variables. The finding of epileptiform abnormalities was followed by a greater prescription of antiseizure drugs (96.4% vs. 66% in nonepileptiform patterns, p < 0.001). CONCLUSION: The diagnostic yield of EEG following a first unprovoked epileptic seizure is highest when this test is performed within the first 16 h after onset of the event.

Cancer-related fatigue and its determinants in a cohort of women with breast cancer: the DAMA Cohort.

Cancer-related fatigue (CRF) is one of the most prolonged discomforts suffered by people who have had cancer. Seventy-eight to ninety-six percent of cancer patients experience fatigue, especially while undergoing treatment. CRF is related to insomnia, anxiety, depression, and also varies depending on age. However, little is known about the factors contributing to CRF and better understanding of determinants of CRF makes it easier to identify early patients at risk and in designing intervention planning. The aim of this study was to assess the influence of precipitating factors (diagnosis of breast cancer and other clinical aspects) and perpetuating factors (social network, quality of life, mental disorders) on the presence of chronic fatigue in women from our cultural context, by social class each other determinants. METHODS: It was carried out a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were data from the Brief Fatigue Inventory questionnaire and hospital medical records. The dependent variable was fatigue and the independent variables were age, social class, time since diagnoses, cohabitation, comorbidity, relapse, body mass index, mental health (anxiety and depression), social network, social support, and quality of life. RESULTS: Seventy-two percent of the women in the DAMA cohort reported moderate to severe fatigue. Risk of suffering from severe fatigue was greatest among individuals with low social class, those aged under 50 years, those with chronic disorders who had relapsed, and those with symptoms of anxiety and depression. In our study, CRF did not appear to be related to the stage of the cancer at diagnosis, or to the time since diagnosis. CONCLUSIONS: CRF is an element that the professionals responsible for the control and monitoring of women should take into account as another element to be taken into consideration.

A survey to assess awareness and opinion of initiatives and recommendations on low-value diagnostic practices.

BACKGROUND: The need to reduce healthcare practices that provide no value has led to the development of initiatives that generate and publish recommendations to improve the appropriateness of clinical practice by identifying potentially inappropriate services, making recommendations, and proposing improvements. DianaHealth (www.dianahealth.com) identifies, classifies, and publishes recommendations from numerous scientific societies. The purpose of this study was to determine the awareness and perceived usefulness and applicability of published recommendations on low-value diagnostic measures, as judged by physicians who are recognised clinical leaders in their respective centres. METHODS: We designed a questionnaire on the diagnostic recommendations considered relevant for each medical specialty and made it available, until September 2016, on DianaHealth. The survey was administered online to clinical leaders from 25 Spanish healthcare centres (hospitals and primary care centres). RESULTS: A total of 413 (40.0%) physicians from 34 different specialties participated. The participation rate varied between centres (range 21.1%-100.0%) and specialties (range 12.5%-78.9%). Do Not Do (57.1%) was the most widely-known initiative. Most participants (82.6%; IQR 77.9%-94.9%) stated that they knew at least one of the 12 initiatives that identify non-recommended practices, and on average they were aware of four initiatives (range 1-12). The initiatives were perceived useful by 82.4% (IQR 73.3%-90.4%), and perceived applicable by 75.6% (IQR 67.4%-86.8%). A total of 531 recommendations were assessed. Sixty-three percent (IQR 53.6%-77.5%) of participants reported they were aware of the recommendations for their corresponding specialty. A total of 84.5% (IQR 75.0%-90.0%) stated they agreed with the recommendations and 84.5% (IQR 75.0%-90.0%) considered them useful. Among those who agreed with their respective recommendations, a median of 51.5% (IQR 41.4%-60.9%) perceived the guidelines as being fully implemented, 40.1% (IQR 31.9%-46.8%) considered them partially implemented, and 7.1% (IQR 3.7%-12.9%), not implemented. CONCLUSIONS: Clinical leaders' awareness of initiatives that generate and publish recommendations to improve clinical appropriateness remains low, although they did consider them useful. In general, participants were familiar with their speciality-specific diagnostic recommendations, agreed with them, and perceived them as useful and implemented in their centres. More needs to be done to raise awareness among professionals who do not know of or apply these recommendations.

Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy? / ¿Existe transmisión materno-fetal del SARS-CoV-2 durante la gestación?

BACKGROUND AND OBJECTIVE: On January 7th, 2020, a new coronavirus, SARS-CoV-2, was identified, as responsible for a new human disease: COVID-19. Given its recent appearance, our current knowledge about the possible influence that this disease can exert on pregnancy is very limited. One of the unknowns to be solved is whether there is a vertical transmission of the infection during pregnancy. PATIENTS AND METHODS: Using the Real-time Polymerase Chain Reaction techniques for SARS-CoV-2 nucleic acids, the possible presence of this germ in vaginal discharge and amniotic fluid was investigated in four pregnant Caucasian patients affected by mild acute symptoms of COVID-19 during the second trimester of pregnancy. RESULTS: There is no laboratory evidence to suggest a possible passage of SARS-CoV-2 from the infected mother to the amniotic fluid. CONCLUSIONS: It is necessary to expand the investigation of COVID-19 cases diagnosed during pregnancy to clarify the real influence that SARS-CoV-2 has on pregnant women and their offspring, as well as those factors that modulate the disease.

Bayesian model of disease progression in GNE myopathy.

One Sentence Summary: A Bayesian repeated measures model based on quantitative muscle strength data from a prospective Natural History Study was developed to determine disease progression and design clinical trials for GNE myopathy, a rare and slowly progressive muscle disease. GNE myopathy is a rare muscle disease characterized by slowly progressive weakness and atrophy of skeletal muscles. To address the significant challenges of defining the natural history and designing clinical trials for GNE myopathy, we developed a Bayesian latent variable repeated measures model to determine disease progression. The model is based on longitudinal quantitative muscle strength data collected as part of a prospective Natural History Study. The GNE Myopathy Progression Model provides an understanding of disease progression that would have otherwise required a natural history of unfeasible duration. "Disease age," the model-generated measure of disease progression, highly correlates with a variety of clinical, functional and patient-reported outcomes. With the incorporation of a treatment effect parameter to the GNE Disease Progression Model, we describe a novel GNE Myopathy Disease Modification Analysis that significantly increases power and reduces the number of subjects required to test the effectiveness of novel therapies when compared to more traditional analysis methods. The GNE Myopathy Disease Progression Model and Disease Modification Analysis can be applied to muscle diseases with prospectively collected muscle strength data, and a variety of rare and slowly progressive diseases.

The ADAN scale: a proposed scale for pre-hospital use to identify status epilepticus.

BACKGROUND AND PURPOSE: The prognosis of status epilepticus (SE) depends on the time between onset and the diagnosis and start of treatment. Our aim was to design a scale with predictive value for pre-hospital diagnosis of SE. METHODS: This was a retrospective study of 292 patients who attended the emergency department for an epileptic seizure. A total of 49 patients fulfilled the criteria for SE. We recorded the patients' history and clinical features. Variables independently associated with SE were combined to design a clinical scale. The performance of the scale was evaluated in a validation dataset of 197 patients. RESULTS: A total of 50.3% of the patients were male and the mean age was 55.9 years. The following features were more prevalent in patients with SE: abnormal speech (79.6% vs. 18.9%, P < 0.001), eye deviation (69.4% vs. 14.0%, P < 0.001), automatism (22.4% vs. 6.3%, P < 0.001), hemiparesis (24.5% vs. 10.9%, P = 0.011), state of stupor/coma (46.9% vs. 4.2%, P < 0.001) and number of pre-hospital seizures, i.e. two (34.7% vs. 4.5%, P < 0.001) or more than two (51.0% vs. 0.4%, P < 0.001). Based on these findings, we designed a scale that scored 1 point each for presence of abnormal speech, eye deviation, automatism and two seizures, and 2 points for more than two seizures. The predictive capacity of the scale for identifying SE in the validation dataset was 98.7% (95% confidence interval, 97.3%-100%) and 85.4% of patients with a score >1 had SE. CONCLUSIONS: A score >1 on the ADAN scale is a robust predictor of the diagnosis of SE in patients who experience an epileptic seizure. This scale may be a useful tool for clinical use and warrants further investigation.

Outcome of cancer-related seizures in patients treated with lacosamide.

OBJECTIVES: Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients. MATERIALS AND METHODS: Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy. RESULTS: Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug-resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio-/chemotherapy. Lacosamide-related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug-related adverse events. CONCLUSION: Lacosamide is an AED to consider in cases of cancer-related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio-/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus.

MRI features of the placenta in fetuses with and without CNS abnormalities.

AIM: To investigate if magnetic resonance imaging (MRI) features of the placenta are different in fetuses with and without central nervous system (CNS) abnormalities. MATERIAL AND METHODS: Institutional research ethics board approval was obtained. Fetal MRI of 97 singleton pregnancies were analysed retrospectively (19-25 weeks gestation), 65 with CNS morphological abnormalities and 32 controls. Placental T2 signal intensity, placental and fetal volumes, placental-to-fetal volume ratio, and placental apparent diffusion coefficient (ADC) values were assessed. Measurements were compared with the presence or absence of CNS fetal abnormalities using the Mann-Whitney test. Separate slopes models and intercept models were used to check for significant differences in the slopes and intercepts, respectively, among the groups. RESULTS: Placental ADC values were significantly lower in placentas of fetuses with CNS abnormalities compared to controls (p=0.04). Placental T2 signal intensity, fetal and placental volumes did not differ between the two groups. The rate of increase in fetal-to-placental volume ratio with gestational age (GA) was greater among the controls. CONCLUSION: The presence of fetal CNS abnormalities is associated with reduced ADC values of the placenta. Moreover, placentas of fetuses with CNS abnormalities show a less rapid increase in fetal to placental volume ratio with GA. Therefore, ADC mapping, as well as different growth kinetics of the placenta relative to the fetus, may potentially serve as early markers of pathological neurodevelopment.

Temporal distribution of, and effect of anthropic modifications on, phlebotomine populations in the Chaco Bioregion, Argentina.

Migonemyia migonei is the predominant species in the dry ecoregion and Nyssomyia neivai in the humid region, although co-dominance in humid highly modified areas could be observed. Vector abundance seems to be modulated by environmental anthropization, as the abundance and predominance of Ny. neiviai and Mg. migonei increased in highly modified areas. In Humid Chaco, the risk of human-vector contact would be present throughout the year, being particularly high in spring/summer, and in Dry Chaco, the risk would be restricted to temperate and humid months.

Effectiveness of an educational group intervention in primary healthcare for continued exclusive breast-feeding: PROLACT study.

BACKGROUND: The World Health Organization leads a global strategy to promote the initiation and maintenance of breast-feeding. Existing literature shows that education and supportive interventions, both for breast-feeding mothers as well as for healthcare professionals, can increase the proportion of women that use exclusive breast-feeding, however, more evidence is needed on the effectiveness of group interventions. METHODS: This study involves a community-based cluster randomised trial conducted at Primary Healthcare Centres in the Community of Madrid (Spain). The project aims to evaluate the effectiveness of an educational group intervention performed by primary healthcare professionals in increasing the proportion of mother-infant pairs using exclusive breastfeeding at six months compared to routine practice. The number of patients required will be 432 (216 in each arm). All mother-infant pairs using exclusive breastfeeding that seek care or information at healthcare centres will be included, as long as the infant is not older than four weeks, and the mother has used exclusive breastfeeding in the last 24 h and who gives consent to participate. The main response variable is mother-infant pairs using exclusive breast-feeding at six months. Main effectiveness will be analysed by comparing the proportion of mother-infant pairs using exclusive breast-feeding at six months between the intervention group and the control group. All statistical tests will be performed with intention-to-treat. The estimation will be adjusted using an explanatory logistic regression model. A survival analysis will be used to compare the two groups using the log-rank test to assess the effect of the intervention on the duration of breastfeeding. The control of potential confounding variables will be performed through the construction of Cox regression models. DISCUSSION: We must implement strategies with scientific evidence to improve the percentage of exclusive breast-feeding at six months in our environment as established by the WHO. Group education is an instrument used by professionals in Primary Care that favours the acquisition of skills and modification of already-acquired behaviour, all making it a potential method of choice to improve rates of exclusive breast-feeding in this period. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov under code number NCT01869920 (Date of registration: June 3, 2013).

Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening.

BACKGROUND: Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer. METHODS: The cohort included 42 928 women first screened at the age of 50-51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams. RESULTS: The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively. CONCLUSIONS: Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.

Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions.

BACKGROUND: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. RESULTS: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/µl with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. CONCLUSIONS: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

When does chronic migraine strike? A clinical comparison of migraine according to the headache days suffered per month.

Introduction According to the IHCD-3ß classification, chronic migraine (CM) is headache occurring on 15 or more days/month. Episodic migraine (EM) can be divided into low frequency (LFEM) and high frequency (HFEM) depending on the headache days suffered per month. Methods We performed a clinical comparison of migraine characteristics according to monthly headache days suffered. Patients were divided into three groups: LFEM (1-9 headache days/month), HFEM (10-14 headache days/month) and CM (≥15 headache days/month). Results The analysis included 1109 patients. Previously reported differences between EM and CM were replicated. However, there were three times more clinical differences between LFEM and HFEM than between HFEM and CM (15 vs. 6). A new model that takes 10 headache days as a cut-off value for CM would have a minimally higher predictive capacity (72.8%) and no statistical differences (71.8%) when comparing it to the current classification. Conclusions HFEM patients have few clinical differences compared with CM patients. This includes the poor outcomes regarding headache-related disability and impact on daily life. According to these findings, neurologists and headache specialists should consider that the emotional and functional impact in HFEM patients could be as disabling as in those with CM.

Description of Pintomyia salomoni sp. n., a new phlebotomine species from northwest Argentina.

A new species of phlebotomine sandfly is described and illustrated using male and female specimens collected in the provinces of Jujuy and Tucumán, Argentina. Both male and female morphological characters allow the inclusion of the new species within the Pintomyia genus, Pifanomyia subgenus, serrana series (Diptera: Psychodidae). The species was denominated as Pintomyia salomoni n. sp., and is closely related to Pintomyia (Pifanomyia) torresi and Pintomyia (Piffanomyia) boliviana.