Functionalization of Alginate Hydrogels with a Multifunctional Peptide Supports Mesenchymal Stem Cell Adhesion and Reduces Bacterial Colonization.

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1-11 region of lactoferrin (LF). The RGD-LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide-functionalized hydrogels was excellent, with values higher than 85 % at day 1, and higher than 95 % after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram-positive and Gram-negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels.

Pediatric Plexiform Fibromyxoma: A Case Report.

The plexiform fibromyxoma is a rare mesenchymal tumor in adults that generally originates in the antrum of stomach, being its occurrence in pediatric patients exceptional. It was classified as a distinct entity by World Health Organization in 2010. No recurrences and metastases have been documented in many of the reported patients to date, being the surgical treatment curative. We report the case of a 3-month-old infant who presented to the emergency department with an episode of intestinal subocclusion requiring an emergent surgery. During the surgical intervention, a mass was identified in the jejunum, causing partial occlusion of its lumen. The surgical pathology report revealed an infiltrative tumor composed of spindle-shaped cells disposed in a stroma with a plexiform pattern alternating myxoid areas. These findings and the immunohistochemical characteristics of the neoplastic cells led to classify the tumor as a plexiform fibromyxoma. A description of the immunophenotype of this tumor is made and differential diagnosis with other gastrointestinal tumors is also discussed.

Exploring the Combined Action of Adding Pertuzumab to Branded Trastuzumab versus Trastuzumab Biosimilars for Treating HER2+ Breast Cancer.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

New Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome cases are caused by the presence of a nonsense variant in compound heterozygosity with the pathogenic repeat expansion in the RFC1 gene.

The biallelic pathogenic repeat (AAGGG)400-2000 intronic expansion in the RFC1 gene has been recently described as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and as a major cause of late-onset ataxia. Since then, many heterozygous carriers have been identified, with an estimated allele frequency of 0.7% to 4% in the healthy population. Here, we describe in two affected CANVAS sisters the presence of the nonsense c.724C > T p.(Arg242*) variant in compound heterozygosity with the pathogenic repeat expansion in the RFC1 gene. Further RNA analysis demonstrated a reduced expression of the p.Arg242* allele in patients confirming an efficient nonsense-mediated mRNA decay. We also highlight the importance of considering the sequencing of the RFC1 gene for the diagnosis, especially in patients with CANVAS diagnosis carriers of the AAGGG repeat expansion.

Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families.

Alazami syndrome is a rare disorder with an autosomal recessive inheritance caused by pathogenic biallelic variants in the LARP7 gene. Clinically, it is mainly characterized by short stature, intellectual disability, and dysmorphic facial features. However, the phenotype is not yet well-defined because less than 50 cases have been described to date. Here, we report three new patients from two unrelated Spanish families who, in addition to the defined features of Alazami syndrome, also exhibit unique features that broaden the phenotypic spectrum of the syndrome. Moreover, we describe the novel frameshift variant c.690_699delins27 in the LARP7 gene, in which loss of function is a known mechanism of Alazami syndrome.

Minors and drug-facilitated sexual assaults: Between submission and chemical vulnerability. / Menores y agresiones sexuales facilitadas por drogas: Entre la sumisión y la vulnerabilidad química.

Drug-facilitated sexual assault (DFSA) is a topic of growing social concern in recent years. Despite this, few empirical studies carried out in Spain have analysed the phenomenon from a preventive approach. The aim of this study, in addition to providing new evidence on DFSA, specifically in minors, was to identify possible associated variables, thus contributing to a better understanding of the problem and to the design of more effective prevention policies. To this end, a survey was carried out among minors in the autonomous community of Galicia. A total of 7,181 students aged 12 to 17 (M = 14.79; SD = 1.57) participated. Data collection was carried out by means of a self-administered questionnaire on paper. Data concerning DFSA were collected by means of specific items, piloted beforehand. Screening instruments for problem drug use (AUDIT, CAST, CRAFFT and EUPI-a) were also used. The results allow us to estimate the rate of victimisation by DFSA in Galician minors at 1.7%, of which only 11.4% would have reported it. Beyond the socio-demographic profile of the victims (females in 2 out of 3 cases), they present different patterns with regard to the pattern of problematic consumption of alcohol and other substances and the pattern of problematic use of the Internet and social networks, with a significantly higher prevalence of online risk behaviours. This suggests that this phenomenon goes far beyond sexual violence, so it is necessary to address it at a preventive level from a comprehensive perspective, including educational and public health perspectives.

Las agresiones sexuales facilitadas por drogas (DFSA) constituyen un tópico que viene suscitando una creciente preocupación social en los últimos años. Pese a ello, son pocos los trabajos empíricos llevados a cabo en España que hayan analizado el fenómeno desde un enfoque preventivo. El objetivo de este trabajo, además de aportar nueva evidencia respecto a las DFSA, concretamente en el ámbito de los menores, ha sido identificar posibles variables asociadas, contribuyendo así a comprender mejor el problema y a diseñar políticas de prevención más eficaces. Para ello se realizó una encuesta entre menores de la comunidad autónoma gallega. Participaron 7.181 estudiantes de 12 a 17 años (M= 14,79; DT=1,57). La recogida de datos se realizó mediante un cuestionario autoadministrado. Los datos referentes a las DFSA fueron recogidos mediante ítems específicos, pilotados previamente. Se utilizaron también instrumentos para el cribado de consumos problemáticos (AUDIT, CAST, CRAFFT y EUPI-a). Los resultados permiten estimar la tasa de victimización por DFSA en menores gallegos en un 1,7%, de los que únicamente habrían denunciado el 11,4%. Más allá del perfil sociodemográfico de las víctimas (mujeres en 2 de cada 3 casos), éstas presentan patrones diferenciados respecto al patrón de consumo problemático de alcohol y otras sustancias y al patrón de uso problemático de Internet y redes sociales, con una prevalencia significativamente mayor de conductas de riesgo online. Ello sugiere que este fenómeno va mucho más allá de la violencia sexual, por lo que es preciso abordarlo a nivel preventivo desde una perspectiva integral, incluyendo la perspectiva educativa y de salud pública.

Experiences and perceptions of care-seeking for febrile illness among caregivers, pregnant women, and health providers in eight districts of Madagascar.

BACKGROUND: Prompt diagnosis and treatment of malaria contributes to reduced morbidity, particularly among children and pregnant women; however, in Madagascar, care-seeking for febrile illness is often delayed. To describe factors influencing decisions for prompt care-seeking among caregivers of children aged < 15 years and pregnant women, a mixed-methods assessment was conducted with providers (HP), community health volunteers (CHV) and community members. METHODS: One health district from each of eight malaria-endemic zones of Madagascar were purposefully selected based on reported higher malaria transmission. Within districts, one urban and one rural community were randomly selected for participation. In-depth interviews (IDI) and focus group discussions (FGD) were conducted with caregivers, pregnant women, CHVs and HPs in these 16 communities to describe practices and, for HPs, system characteristics that support or inhibit care-seeking. Knowledge tests on malaria case management guidelines were administered to HPs, and logistics management systems were reviewed. RESULTS: Participants from eight rural and eight urban communities included 31 HPs from 10 public and 8 private Health Facilities (HF), five CHVs, 102 caregivers and 90 pregnant women. All participants in FGDs and IDIs reported that care-seeking for fever is frequently delayed until the ill person does not respond to home treatment or symptoms become more severe. Key care-seeking determinants for caregivers and pregnant women included cost, travel time and distance, and perception that the quality of care in HFs was poor. HPs felt that lack of commodities and heavy workloads hindered their ability to provide quality malaria care services. Malaria commodities were generally more available in public versus private HFs. CHVs were generally not consulted for malaria care and had limited commodities. CONCLUSIONS: Reducing cost and travel time to care and improving the quality of care may increase prompt care-seeking among vulnerable populations experiencing febrile illness. For patients, perceptions and quality of care could be improved with more reliable supplies, extended HF operating hours and staffing, supportive demeanors of HPs and seeking care with CHVs. For providers, malaria services could be improved by increasing the reliability of supply chains and providing additional staffing. CHVs may be an under-utilized resource for sick children.

Comorbidities increase COVID-19 hospitalization in young people with type 1 diabetes.

OBJECTIVES: We evaluated COVID-19 outcomes in children and young adults with type 1 diabetes (T1D) to determine if those with comorbidities are more likely to experience severe COVID-19 compared to those without. RESEARCH DESIGN AND METHODS: This cross-sectional study included questionnaire data on patients <25 years of age with established T1D and laboratory-confirmed COVID-19 from 52 sites across the US between April 2020 and October 2021. We examined patient factors and COVID-19 outcomes between those with and without comorbidities. Multivariate logistic regression analysis examined the odds of hospitalization among groups, adjusting for age, HbA1c, race and ethnicity, insurance type and duration of diabetes. RESULTS: Six hundred fifty-one individuals with T1D and COVID-19 were analyzed with mean age 15.8 (SD 4.1) years. At least one comorbidity was present in 31%, and more than one in 10%. Obesity and asthma were the most frequently reported comorbidities, present in 19% and 17%, respectively. Hospitalization occurred in 17% of patients and 52% of hospitalized patients required ICU level care. Patients with at least one comorbidity were almost twice as likely to be hospitalized with COVID-19 than patients with no comorbidities (Odds ratio 2.0, 95% CI: 1.3-3.1). This relationship persisted after adjusting for age, HbA1c, race and ethnicity (minority vs nonminority), insurance type (public vs. private), and duration of diabetes. CONCLUSIONS: Our findings show that comorbidities increase the risk for hospitalization with COVID-19 in children and young adults highlighting the need for tailored COVID-19 prevention and treatment strategies in T1D.

Outside the Safe Operating Space of the Planetary Boundary for Novel Entities.

We submit that the safe operating space of the planetary boundary of novel entities is exceeded since annual production and releases are increasing at a pace that outstrips the global capacity for assessment and monitoring. The novel entities boundary in the planetary boundaries framework refers to entities that are novel in a geological sense and that could have large-scale impacts that threaten the integrity of Earth system processes. We review the scientific literature relevant to quantifying the boundary for novel entities and highlight plastic pollution as a particular aspect of high concern. An impact pathway from production of novel entities to impacts on Earth system processes is presented. We define and apply three criteria for assessment of the suitability of control variables for the boundary: feasibility, relevance, and comprehensiveness. We propose several complementary control variables to capture the complexity of this boundary, while acknowledging major data limitations. We conclude that humanity is currently operating outside the planetary boundary based on the weight-of-evidence for several of these control variables. The increasing rate of production and releases of larger volumes and higher numbers of novel entities with diverse risk potentials exceed societies' ability to conduct safety related assessments and monitoring. We recommend taking urgent action to reduce the harm associated with exceeding the boundary by reducing the production and releases of novel entities, noting that even so, the persistence of many novel entities and/or their associated effects will continue to pose a threat.

The silent burden: a landscape analysis of common perinatal mental disorders in low- and middle-income countries.

BACKGROUND: Mental health has long fallen behind physical health in attention, funding, and action-especially in low- and middle-income countries (LMICs). It has been conspicuously absent from global reproductive, maternal, newborn, child, and adolescent health (MNCAH) programming, despite increasing awareness of the intergenerational impact of common perinatal mental disorders (CPMDs). However, the universal health coverage (UHC) movement and COVID-19 have brought mental health to the forefront, and the MNCAH community is looking to understand how to provide women effective, sustainable care at scale. To address this, MOMENTUM Country and Global Leadership (MCGL) commissioned a landscape analysis in December 2020 to assess the state of CPMDs and identify what is being done to address the burden in LMICs. METHODS: The landscape analysis (LA) used a multitiered approach. First, reviewers chose a scoping review methodology to search literature in PubMed, Google Scholar, PsychInfo, and Scopus. Titles and abstracts were reviewed before a multidisciplinary team conducted data extraction and analysis on relevant articles. Second, 44 key informant interviews and two focus group discussions were conducted with mental health, MNCAH, humanitarian, nutrition, gender-based violence (GBV), advocacy, and implementation research experts. Finally, reviewers completed a document analysis of relevant mental health policies from 19 countries. RESULTS: The LA identified risk factors for CPMDs, maternal mental health interventions and implementation strategies, and remaining knowledge gaps. Risk factors included social determinants, such as economic or gender inequality, and individual experiences, such as stillbirth. Core components identified in successful perinatal mental health (PMH) interventions at community level included stepped care, detailed context assessments, task-sharing models, and talk therapy; at health facility level, they included pre-service training on mental health, trained and supervised providers, referral and assessment processes, mental health support for providers, provision of respectful care, and linkages with GBV services. Yet, significant gaps remain in understanding how to address CPMDs. CONCLUSION: These findings illuminate an urgent need to provide CPMD prevention and care to women in LMICs. The time is long overdue to take perinatal mental health seriously. Efforts should strive to generate better evidence while implementing successful approaches to help millions of women "suffering in silence."

First female with Allan-Herndon-Dudley syndrome and partial deletion of X-inactivation center.

Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease. We describe a female with a complete Allan-Herndon-Dudley phenotype, carrying a de novo 543-kb deletion of the X chromosome. The deletion encompasses exon 1 of the SLC16A2 gene and JPX and FTX genes; it is known that the latter two genes participate in the X-inactivation process upregulating XIST gene expression. Subsequent studies in the patient demonstrated the preferential expression of the X chromosome with the JPX and FTX deletion.

Liraglutide hospital discharge trial: A randomized controlled trial comparing the safety and efficacy of liraglutide versus insulin glargine for the management of patients with type 2 diabetes after hospital discharge.

AIM: To compare a glucagon-like peptide-1 receptor agonist with basal insulin at hospital discharge in patients with uncontrolled type 2 diabetes in a randomized clinical trial. METHODS: A total of 273 patients with glycated haemoglobin (HbA1c) 7%-10% (53-86 mol/mol) were randomized to liraglutide (n = 136) or insulin glargine (n = 137) at hospital discharge. The primary endpoint was difference in HbA1c at 12 and 26 weeks. Secondary endpoints included hypoglycaemia, changes in body weight, and achievement of HbA1c <7% (53 mmol/mol) without hypoglycaemia or weight gain. RESULTS: The between-group difference in HbA1c at 12 weeks and 26 weeks was -0.28% (95% CI -0.64, 0.09), and at 26 weeks it was -0.55%, (95% CI -1.01, -0.09) in favour of liraglutide. Liraglutide treatment resulted in a lower frequency of hypoglycaemia <3.9 mmol/L (13% vs 23%; P = 0.04), but there was no difference in the rate of clinically significant hypoglycaemia <3.0 mmol/L. Compared to insulin glargine, liraglutide treatment was associated with greater weight loss at 26 weeks (-4.7 ± 7.7 kg vs -0.6 ± 11.5 kg; P < 0.001), and the proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia was 48% versus 33% (P = 0.05) at 12 weeks and 45% versus 33% (P = 0.14) at 26 weeks in liraglutide versus insulin glargine. The proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia and no weight gain was higher with liraglutide at 12 (41% vs 24%, P = 0.005) and 26 weeks (39% vs 22%; P = 0.014). The incidence of gastrointestinal adverse events was higher with liraglutide than with insulin glargine (P < 0.001). CONCLUSION: Compared to insulin glargine, treatment with liraglutide at hospital discharge resulted in better glycaemic control and greater weight loss, but increased gastrointestinal adverse events.

Factors Associated With Participation in the Chronic Disease Self-Management Program: Findings From the SUCCEED Trial.

BACKGROUND AND PURPOSE: Self-management programs may improve quality of life and self-efficacy for stroke survivors, but participation is low. In a randomized controlled trial of a complex, multidisciplinary, team-based secondary stroke prevention intervention, we offered participants Chronic Disease Self-Management Program (CDSMP) workshops in addition to clinic visits and home visits. To enhance participation, workshops were facilitated by community health workers who were culturally and linguistically concordant with most participants and scheduled CDSMP sessions at convenient venues and times. Over time, we implemented additional strategies such as free transportation and financial incentives. In this study, we aimed to determine factors associated with CDSMP participation and attendance. METHODS: From 2014 to 2018, 18 CDSMP workshop series were offered to 241 English and Spanish-speaking individuals (age ≥40 years) with recent stroke or transient ischemic attack. Zero-inflated Poisson regression was used to identify factors associated with participation and attendance (ie, number of sessions attended) in CDSMP. Missing values were imputed using multiple imputation methods. RESULTS: Nearly one-third (29%) of intervention subjects participated in CDSMP. Moderate disability and more clinic/home visits were associated with participation. Participants with higher numbers of clinic and home visits (incidence rate ratio [IRR], 1.06 [95% CI, 1.01-1.12]), severe (IRR, 2.34 [95% CI, 1.65-3.31]), and moderately severe disability (IRR, 1.55 [95% CI, 1.07-2.23]), and who enrolled later in the study (IRR, 1.12 [95% CI, 1.08-1.16]) attended more sessions. Individuals with higher chaos scores attended fewer sessions (IRR, 0.97 [95% CI, 0.95-0.99]). CONCLUSIONS: Less than one-third of subjects enrolled in the SUCCEED (Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities) intervention participated in CDSMP; however, participation improved as transportation and financial barriers were addressed. Strategies to address social determinants of health contributing to chaos and engage individuals in healthcare may facilitate attendance. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01763203.

Malaria case management and elimination readiness in health facilities of five districts of Madagascar in 2018.

BACKGROUND: Madagascar's Malaria National Strategic Plan 2018-2022 calls for progressive malaria elimination beginning in low-incidence districts (< 1 case/1000 population). Optimizing access to prompt diagnosis and quality treatment and improving outbreak detection and response will be critical to success. A malaria elimination readiness assessment (MERA) was performed in health facilities (HFs) of selected districts targeted for malaria elimination. METHODS: A mixed methods survey was performed in September 2018 in five districts of Madagascar. Randomly selected HFs were assessed for availability of malaria commodities and frequency of training and supervision conducted. Health providers (HPs) and community health volunteers (CHVs) were interviewed, and outpatient consultations at HFs were observed. To evaluate elimination readiness, a composite score ranging from 0 to 100 was designed from all study tools and addressed four domains: (1) resource availability, (2) case management (CM), (3) data management and use, and (4) training, supervision, and technical assistance; scores were calculated for each HF catchment area and district based on survey responses. Stakeholder interviews on malaria elimination planning were conducted at national, regional and district levels. RESULTS: A quarter of the 35 HFs surveyed had no rapid diagnostic tests (RDTs). Of 129 patients with reported or recorded fever among 300 consultations observed, HPs tested 56 (43%) for malaria. Three-quarters of the 35 HF managers reviewed data for trends. Only 68% of 41 HPs reported receiving malaria-specific training. Of 34 CHVs surveyed, 24% reported that treating fever was no longer among their responsibilities. Among treating CHVs, 13 (50%) reported having RDTs, and 11 (42%) had anti-malarials available. The average district elimination readiness score was 52 out of 100, ranging from 48 to 57 across districts. Stakeholders identified several challenges to commodity management, malaria CM, and epidemic response related to lack of training and funding disruptions. CONCLUSION: This evaluation highlighted gaps in malaria CM and elimination readiness in Madagascar to address during elimination planning. Strategies are needed that include training, commodity provision, supervision, and support for CHVs. The MERA can be repeated to assess progress in filling identified gaps and is a feasible tool that could be used to assess elimination targets in other countries.

Marine Organisms from the Yucatan Peninsula (Mexico) as a Potential Natural Source of Antibacterial Compounds.

A total of 51 sponges (Porifera) and 13 ascidians (Chordata) were collected on the coast of the Yucatan Peninsula (Mexico) and extracted with organic solvents. The resulting extracts were screened for antibacterial activity against four multidrug-resistant (MDR) bacterial pathogens: the Gram-negative Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus. The minimum inhibitory concentrations (MICs) of the organic extracts of each marine organism were determined using a broth microdilution assay. Extracts of eight of the species, in particular the Agelas citrina and Haliclona (Rhizoniera) curacaoensis, displayed activity against some of the pathogens tested. Some of the extracts showed similar MIC values to known antibiotics such as penicillins and aminoglycosides. This study is the first to carry out antimicrobial screening of extracts of marine sponges and ascidians collected from the Yucatan Peninsula. Bioassay-guided fractionation of the active extracts from the sponges Amphimedon compressa and A. citrina displayed, as a preliminary result, that an inseparable mixture of halitoxins and amphitoxins and (-)-agelasine B, respectively, are the major compounds responsible for their corresponding antibacterial activities. This is the first report of the antimicrobial activity of halitoxins and amphitoxins against major multidrug-resistant human pathogens. The promising antibacterial activities detected in this study indicate the coast of Yucatan Peninsula as a potential source of a great variety of marine organisms worthy of further research.

Minors and Online Gambling: Prevalence and Related Variables.

Substantial access to the Internet by minors has brought about consequences that are not always positive. The increase of online gambling or betting is one of those. Although in most cases online gambling by minors does not result in a disorder, it does imply a higher probability of developing a gambling disorder in adulthood, and it can cause economic, family, school and social problems. The aim of this study, carried out in the Galician region of Spain with a sample of 3772 students aged between 12 and 17 years, was to estimate the prevalence of online gambling in minors; to characterize the profile of online gamblers; to explore the differences in Internet and smartphone usage habits, online risky practices, problematic Internet use and parental involvement between online gamblers and non-online gamblers; and to analyse the relation between online gambling and academic performance. The results revealed that 6.5% of Galician adolescents are online gamblers, a figure that has more than tripled over seven years. 9 out of 10 online gamblers are male, and their mean age is 15. Online gamblers had significantly higher rates of problematic Internet use, active sexting, cyberbullying, or contacting strangers through the Internet. Furthermore, online gamblers had higher scores on impulsiveness, lower scores on assertiveness, and were lacking parental control. These data show that online gambling is not an isolated problem, so prevention should be understood in a comprehensive manner.

The age of onset for alcohol consumption among adolescents: Implications and related variables. / La edad de inicio en el consumo de alcohol en adolescentes: implicaciones y variables asociadas.

Adolescence is a critical period in the development of addictive behaviors. In particular, the age at which adolescents start drinking is not a trivial matter, given the important consequences that it has. However, relatively little is known about what it is that causes them to start drinking at an ever earlier age. The aim of this paper is to collect new empirical data about the implications of an early age of onset and, at the same time, to identify possible associated variables. Furthermore, the mean age of onset of the different substances is updated by expanding the sample frame of the ESTUDES (14-18 years) to incorporate adolescents aged 12 and 13. The results obtained with a sample of 3,419 adolescents from the Autonomous Community of Galicia (M = 14.57 and SD = 1.76) reveal that at 13.4 years of age, the age at which adolescents tend to start drinking is lower than suggested by ESTUDES 2016-2017. In addition, those who start drinking earlier are more likely to use other substances, their rates of high-risk consumption are 3 times higher and they are more involved in potentially dangerous practices. Finally, variables such as risk perception and expectations of use yield very limited explanatory capacity, especially if they are compared with those related to drinking within the family or peer group. The results reinforce the need to delay the age of alcohol onset as one of the strategic objectives of prevention policies.

La adolescencia constituye un período crítico en el desarrollo de conductas adictivas. En particular, la edad a la que los jóvenes se inician en el consumo de alcohol no es una cuestión banal, habida cuenta de las importantes repercusiones que posee a diferentes niveles. Sin embargo se sabe relativamente poco de por qué cada vez se empieza a consumir de manera más precoz. El objetivo del presente trabajo ha sido recabar nuevos datos empíricos sobre las implicaciones de una edad de inicio temprana e identificar, al mismo tiempo, posibles variables asociadas. Se han actualizado además las edades medias de inicio de consumo de distintas sustancias, ampliando el marco muestral habitual del ESTUDES (14-18 años), incorporando a los adolescentes de 12 y 13 años. Los resultados obtenidos con una muestra de 3419 adolescentes de la comunidad gallega (M = 14,57 y DT = 1,76) permiten constatar que la edad a la que los adolescentes suelen iniciarse en el consumo de alcohol es menor de lo que sugiere el ESTUDES 2016-2017, situándose en 13,4 años. Además quienes se inician antes en su consumo presentan una mayor probabilidad de consumir otras sustancias, tasas de consumo de riesgo 3 veces superiores y se implican más en prácticas potencialmente peligrosas. Por último, variables como la percepción de riesgo o las expectativas presentan una capacidad explicativa escasa, sobre todo si se compara con otras relacionadas con el consumo del entorno familiar o entre iguales. Los resultados refuerzan la necesidad de retrasar la edad de inicio del consumo de alcohol como uno de los objetivos estratégicos de las políticas de prevención.

Empirical validation of the CRAFFT Abuse Screening Test in a Spanish sample. / Validación empírica del CRAFFT Abuse Screening Test en una muestra de adolescentes españoles.

The CRAFFT Substance Abuse Screening Instrument, developed by the Center for Adolescents Substance Abuse Research (CeASAR) (Knight et al., 1999), is a screening tool for high-risk alcohol and drug risk consumption designed for use with adolescents. Since its publication it has been the subject of translations and validations in different countries, populations and contexts that have demonstrated its enormous potential. However, there is still no empirical validation study that would ensure its good psychometric performance in Spain. The aim of this paper is to develop an adapted version of the CRAFFT in Spanish and to analyze its psychometric properties in a sample of Spanish adolescents. For this purpose an individual interview was conducted on 312 adolescents aged between 12 and 18 years of age (M = 15.01; SD = 1.83) from the Galician community. The interview included a part of the Adolescent Diagnostic Interview (ADI) and the Problem Oriented Screening Instrument for Teenagers (POSIT). The results obtained, similar to those found in other countries, allow us to report that the Spanish version of the CRAFFT has a good psychometric behaviorproperties. It was found to have a satisfactory internal consistency with a Cronbach’s alpha value of .74. In terms of sensitivity and specificity, values of 74.4% and 96.4% respectively, were obtained and the area under the ROC curve was .946. The Spanish version of the CRAFFT is made available to researchers and professionals in the field of addictive behaviors, so that it can be used with the necessary psychometric guarantees.

El CRAFFT Abuse Screening Test, desarrollado por el Center for Adolescents Substance Abuse Research (CeASAR) (Knight et al., 1999), es una herramienta de cribado del consumo de riesgo de alcohol y otras sustancias diseñada para su uso con adolescentes. Desde su publicación ha sido objeto de numerosas traducciones y validaciones en diferentes países, poblaciones y contextos que han dado cuenta de su enorme potencial. No obstante, seguimos sin disponer de estudios de validación empírica que garanticen su adecuado comportamiento psicométrico en España. El objetivo del presente trabajo consiste en desarrollar una versión adaptada del CRAFFT en castellano y analizar sus propiedades psicométricas en una muestra de adolescentes españoles. Para ello, se realizó una entrevista individual a 312 adolescentes de entre 12 y 18 años (M = 15,01; DT = 1,83) de la comunidad gallega, que incluyó una parte de la Adolescent Diagnostic Interview (ADI) y del Problem Oriented Screening Instrument for Teenagers (POSIT). Los resultados obtenidos, similares a los encontrados en otros países, permiten informar que la versión española del CRAFFT presenta un buen comportamiento psicométrico. A nivel de consistencia interna se obtuvo un a de Cronbach satisfactorio de ,74. En cuanto a la sensibilidad y especificidad se obtuvieron unos valores del 74,4% y el 96,4% respectivamente, con un área bajo la curva COR de ,946. Por lo tanto, queda a disposición de investigadores y profesionales del ámbito de las conductas adictivas la versión española del CRAFFT, para que pueda ser utilizada en adelante con las garantías psicométricas necesarias.

THE EFFICACY AND SAFETY OF CO-ADMINISTRATION OF SITAGLIPTIN WITH METFORMIN IN PATIENTS WITH TYPE 2 DIABETES AT HOSPITAL DISCHARGE.

OBJECTIVE: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D. METHODS: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53-75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge. RESULTS: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months ( P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups. CONCLUSION: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes.

Screening and management of pre-eclampsia and eclampsia in antenatal and labor and delivery services: findings from cross-sectional observation studies in six sub-Saharan African countries.

BACKGROUND: Preeclampsia and eclampsia (PE/E) are major contributors to maternal and neonatal deaths in developing countries, associated with 10-15% of direct maternal deaths and nearly a quarter of stillbirths and newborn deaths, many of which are preventable with improved care. We present results related to WHO-recommended interventions for screening and management of PE/E during antenatal care (ANC) and labor and delivery (L & D) from a study conducted in six sub-Saharan African countries. METHODS: From 2010 to 2012, cross-sectional studies which directly observed provision of ANC and L & D services in six sub-Saharan African countries were conducted. Results from 643 health facilities of different levels in Ethiopia (n = 19), Kenya (n = 509), Madagascar (n = 36), Mozambique (n = 46), Rwanda (n = 72), and Tanzania (n = 52), were combined for this analysis. While studies were sampled separately in each country, all used standardized observation checklists and inventory assessment tools. RESULTS: 2920 women receiving ANC and 2689 women in L & D were observed. Thirty-nine percent of ANC clients were asked about PE/E danger signs, and 68% had their blood pressure (BP) taken correctly (range 48-96%). Roughly half (46%) underwent testing for proteinuria. Twenty-three percent of women in L & D were asked about PE/E danger signs (range 11-34%); 77% had their BP checked upon admission (range 59-85%); and 6% had testing for proteinuria. Twenty-five cases of severe PE/E were observed: magnesium sulfate (MgSO4) was used in 15, not used in 5, and for 5 use was unknown. The availability of MgSO4 in L & D varied from 16% in Ethiopia to 100% in Mozambique. CONCLUSIONS: Observed ANC consultations and L & D cases showed low use of WHO-recommended practices for PE/E screening and management. Availability of MgSO4 was low in multiple countries, though it was on the essential drug list of all surveyed countries. Country programs are encouraged to address gaps in screening and management of PE/E in ANC and L & D to contribute to lower maternal and perinatal mortality.