Use of Tirzepatide in Adults with Type 2 Diabetes Mellitus: Scientific Evidence and Practical Aspects.

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.

Alerta Cannabis: A Tailored-Computer Web-Based Program for the Prevention of Cannabis Use in Adolescents: A Cluster-Randomized Controlled Trial Protocol.

BACKGROUND: The growing use of cannabis in adolescence is a public health problem that must be addressed through prevention. In Spain, the average age of initiation of cannabis use in the adolescent population is 14.8 years. At 14 years, the lifetime prevalence of cannabis use is 11.7%, which increases to 51.,5% at the age of 18; the prevalence of cannabis use in the population aged 14 to 18 years is 28.6%, a figure that must be tried to reduce, that is why this school prevention program is proposed: Alerta Cannabis. METHODS: The Alerta Cannabis research project consists of design, implementation, and evaluation. In the first phase, a computer-tailored eHealth program (Alerta Cannabis) is developed based on the I-Change Model, an integrated model based on three main behavioral change processes: awareness, motivation, and action. This program consists of four 30-minute sessions that will provide culturally adapted and personalized advice to motivate students not to use cannabis through text feedback, animations, and gamification techniques. This phase will also include usability testing. In the implementation phase, secondary school students from Western Andalusia, Spain (Seville, Cádiz, Huelva, and Córdoba) and Eastern Andalusia (Jaén, Málaga, and Granada) will be randomized to an experimental condition (EC) or a control condition (CC) for a cluster randomized clinical trial (CRCT). Each condition will have 35 classes within 8 schools. GI will receive the online intervention Alerta Cannabis. EC and CC will have to fill out a questionnaire at baseline, six months, and twelve months of follow-up. In the last phase, the effect of Alerta Cannabis is evaluated. The primary outcomes are the lifetime prevalence of cannabis use and its use in the last 30 days and at 6 months. At 12 months of follow-up, the prevalence in the last 12 months will also be assessed. The secondary outcome is the intention to use cannabis. DISCUSSION: The study tests the effect of the innovative program specifically aimed to reduce the use of cannabis in the adolescent population through eHealth in Spain. The findings aim to develop and implement evidence-based cannabis prevention interventions, which could support school prevention, for instance, the assistance of school nurses. If the program proves to be effective, it could be useful to prevent cannabis use on a national and international scale. TRIAL REGISTRATION: NCT05849636. Date of registration: March 16, 2023.

Alcohol use among children and adolescents with chronic pain. Scoping review.

AIM: To examine and map alcohol consumption in children and adolescents with chronic pain (CP). METHOD: A scoping review of international databases (CINAHL, WOS, PubMed, PsycINFO, Scopus, Embase, and MEDLINE) and grey literature was conducted between September 2022 and February 2023. Documents addressing the relationship between alcohol consumption and CP in children and adolescents, published in English and Spanish between 2012 and 2023, were included. Those papers with a population suffering from CP derived from neurodegenerative diseases, chronic infectious diseases or cognitive impairment were excluded. We assessed the level of evidence (LE) and the degree of recommendation (DR) of the studies included in accordance with the Scottish Intercollegiate Guidelines Network. Finally, 11 documents were considered out of the 479 reviewed. RESULTS: The relationship between substance consumption and CP in adolescents is a scarcely investigated topic. While there is a trend towards lower rates of alcohol consumption in youth with pain, there is evidence suggesting an association, particularly in cases of intense pain. The use of various substances, both legal and illegal, for pain management underscores the importance of comprehensively addressing this phenomenon in this population. CONCLUSIONS: Further research is needed to assess the relationship between alcohol consumption in children and adolescents with CP.

Evidence that the domesticated fungus Leucoagaricus gongylophorus recycles its cytoplasmic contents as nutritional rewards to feed its leafcutter ant farmers.

Leafcutter ants farm a fungal cultivar (Leucoagaricus gongylophorus) that converts inedible vegetation into food that sustains colonies with up to millions of workers. Analogous to edible fruits of crops domesticated by humans, L. gongylophorus has evolved specialized nutritional rewards-swollen hyphal cells called gongylidia that package metabolites and are consumed by ant farmers. Yet, little is known about how gongylidia form, and thus how fungal physiology and ant provisioning collectively govern farming performance. We explored the process of gongylidium formation using advanced microscopy to image the cultivar at scales of nanometers, and both in vitro experiments and in silico analyses to examine the mechanisms of gongylidia formation when isolated from ant farmers. We first used transmission electron, fluorescence, and confocal microscopy imaging to see inside hyphal cells. This imaging showed that the cultivar uses a process called autophagy to recycle its own cellular material (e.g. cytosol, mitochondria) and then shuttles the resulting metabolites into a vacuole whose continual expansion displaces other organelles and causes the gongylidium cell's bulging bulb-like appearance. We next used scanning electron microscopy and light microscopy to link this intracellular rearrangement to the external branching patterns of gongylidium cells as they clump together into edible bundles called staphyla. We next confirmed that autophagy plays a critical role in gongylidium formation both: (1) in vitro as gongylidium suppression occurred when isolated fungal cultures were grown on media with autophagy inhibitors, and (2) in silico as differential transcript expression (RNA-seq) analyses showed upregulation of multiple autophagy gene isoforms in gongylidia relative to undifferentiated hyphae. While autophagy is a ubiquitous and often highly derived process across the tree of life, our study reveals a new role for autophagy as a mechanism of functional integration between ant farmers and their fungal crop, and potentially as a signifier of higher-level homeostasis between uniquely life-time committed ectosymbionts.

Adolescents and youths' opinions about the factors associated with cannabis use: a qualitative study based on the I-Change model.

BACKGROUND: To learn about the experiences and opinions of adolescent non-consumers and regular cannabis users about cannabis use and the factors that determine its use, using the I-Change explanatory model as a basis. METHODS: Qualitative methodology with a content analysis was used. Focus groups were conducted with adolescents who were non-regular cannabis users (those who had not tried cannabis or had only experimented with it before) and semi-structured interviews were conducted with adolescent and young adult in recovery who were in a detoxification program. A deductive analysis of the audio-recorded and transcribed interviews was performed, using the domains of the I-Change Model as a reference. RESULTS: Personal problems, social problems or family problems can lead to cannabis use. There was a lack of knowledge and low risk perception about consumption of this drug. There are other factors that influence consumption, the perception of advantages, such as the feeling of freedom and the influence of the peer group. The consumption of this substance in girls is changing, becoming more and more equal to that of boys. The family has an important role to play in preventing drug use. CONCLUSION: Knowledge of these factors is of vital importance as a prior step to the development of efficient intervention measures adjusted to the needs identified and the characteristics of the population.

Evaluating the influence of sleep quality and quantity on glycemic control in adults with type 1 diabetes.

Background: Sleep quality disturbances are frequent in adults with type 1 diabetes. However, the possible influence of sleep problems on glycemic variability has yet to be studied in depth. This study aims to assess the influence of sleep quality on glycemic control. Materials and methods: An observational study of 25 adults with type 1 diabetes, with simultaneous recording, for 14 days, of continuous glucose monitoring (Abbott FreeStyle Libre system) and a sleep study by wrist actigraphy (Fitbit Ionic device). The study analyzes, using artificial intelligence techniques, the relationship between the quality and structure of sleep with time in normo-, hypo-, and hyperglycemia ranges and with glycemic variability. The patients were also studied as a group, comparing patients with good and poor sleep quality. Results: A total of 243 days/nights were analyzed, of which 77% (n = 189) were categorized as poor quality and 33% (n = 54) as good quality. Linear regression methods were used to find a correlation (r =0.8) between the variability of sleep efficiency and the variability of mean blood glucose. With clustering techniques, patients were grouped according to their sleep structure (characterizing this structure by the number of transitions between the different sleep phases). These clusters showed a relationship between time in range and sleep structure. Conclusions: This study suggests that poor sleep quality is associated with lower time in range and greater glycemic variability, so improving sleep quality in patients with type 1 diabetes could improve their glycemic control.

Accelerated Synthesis of Bicyclo[1.1.1]pentylamines: A High-Throughput Approach.

Strained bicyclic substructures such as bicyclo[1.1.1]pentylamines (BCPAs) are increasingly targeted in medicinal chemistry as arylamine bioisosteres. Here, we leverage high-throughput automated synthesis to rapidly develop library-amenable reaction conditions and maximize design space to expand access to BCPAs. This new protocol relies on a copper-mediated C-N coupling approach and uses accessible and bench-stable iodo-BCP building blocks. Its applicability has been exemplified by incorporating BCPs in drug-like compounds, providing straightforward access to a library of valuable aniline-like isosteres.

Cost-effectiveness and cost-utility analyses of a web-based computer-tailored intervention for prevention of binge drinking among Spanish adolescents.

BACKGROUND: Binge drinking (BD) among adolescents is a public health concern worldwide. This study assessed the cost-effectiveness and cost-utility of a web-based computer-tailored intervention to prevent BD in adolescence. METHODS: The sample was drawn from a study evaluating the Alerta Alcohol program. The population consisted of adolescents 15 to 19 years of age. Data were recorded at baseline (January to February 2016) and after 4 months (May to June 2017) and were used to estimate costs and health outcomes, as measured by the number of BD occasions and quality-adjusted life years (QALYs). Incremental cost-effectiveness and cost-utility ratios were calculated from National Health Service (NHS) and societal perspectives and for a time horizon of 4 months. A multivariate deterministic sensitivity analysis of best/worst scenarios by subgroups was used to account for uncertainty. RESULTS: The cost of reducing BD occasions by one per month was €16.63 from the NHS perspective, which from the societal perspective resulted in savings of €7986.37. From the societal perspective, the intervention resulted in an incremental cost of €71.05 per QALY gained from the NHS perspective and this was dominant, resulting in savings of €34,126.64 per QALY gained in comparison with the control group. Subgroup analyses showed that the intervention was dominant for girls from both the perspectives and for individuals 17 years or older from the NHS perspective. CONCLUSIONS: Computer-tailored feedback is a cost-effective way to reduce BD and increase QALYs among adolescents. However, long-term follow-up is needed to evaluate more fully changes in both BD and health-related quality of life.

Impact of the first wave of the COVID-19 pandemic on non-COVID inpatient care in southern Spain.

We assessed the impact of the first wave of COVID-19 pandemic on non-COVID hospital admissions, non-COVID mortality, factors associated with non-COVID mortality, and changes in the profile of non-COVID patients admitted to hospital. We used the Spanish Minimum Basic Data Set with diagnosis grouped according to the Diagnostic Related Groups. A total of 10,594 patients (3% COVID-19; 97% non-COVID) hospitalised during the first wave in 2020 (27-February/07-June) were compared with those hospitalised within the same dates of 2017-2019 (average annual admissions: 14,037). We found a decrease in non-COVID medical (22%) and surgical (33%) hospitalisations and a 25.7% increase in hospital mortality among non-COVID patients during the first pandemic wave compared to pre-pandemic years. During the officially declared sub-period of excess mortality in the area (17-March/20-April, in-hospital non-COVID mortality was even higher (58.7% higher than the pre-pandemic years). Non-COVID patients hospitalised during the first pandemic wave (compared to pre-pandemic years) were older, more frequently men, with longer hospital stay and increased disease severity. Hospitalisation during the first pandemic wave in 2020, compared to hospitalisation during the pre-pandemic years, was an independent risk factor for non-COVID mortality (HR 1.30, 95% CI 1.07-1.57, p = 0.008), reflecting the negative impact of the pandemic on hospitalised patients.

Which factors are associated with cannabis use among adolescents in Andalusia? An application of the I-Change model.

BACKGROUND: Cannabis use is increasing among Andalusian adolescents, causing health, social and financial problems. School nurses visit schools and provide health promotion to adolescents in Andalusia. In order to better tailor health promotion programs, it is important to understand the sociodemographic and motivational factors related to cannabis use in Andalusian adolescents. DESIGN/METHODS: In this cross-sectional study, 369 students (aged 15-18 years) from secondary schools in Andalusia were involved. An anonymous questionnaire based on the I-Change Model was self-administered during school hours. Cannabis users were compared with non-cannabis users regarding sociodemographic and motivational factors. Contingency tables, mean comparison tests, and logistic regression analyses were conducted. RESULTS: The prevalence of cannabis use in the last year was 21.6%. Non-cannabis users had a few positive beliefs toward cannabis use (e.g. the ability to relax or medical benefits), as well as users. Users recognized some disadvantages of cannabis use but played down their importance and mentioned more advantages. Moreover, social influence, especially from peers, plays a critical role in cannabis use. Specific social situations and moods seemed to be special risk factors for cannabis use, such as being at a celebration or feeling good. Results of regression analysis showed that cannabis use is mainly associated with age, low family function, low family affluence, high pocket money, perceiving few disadvantages of cannabis use, much social modeling of cannabis use, social norm and pressure favoring cannabis, low self-efficacy to resist using cannabis and positive intentions to use cannabis. CONCLUSIONS: Based on our results, prevention programmes lead by nurses can be tailored to the factors important to prevent cannabis use, focusing on outlining the disadvantages of cannabis use, alternatives for using cannabis when feeling good, increasing salience of healthy social influences and reinforcing self-efficacy to resist temptations to use cannabis are recommended. CLINICAL RELEVANCE: Nurses need to know the sociodemographic factors and motivations associated with the use of cannabis in adolescents in order to establish effective preventive interventions at school.

The influence of peer's social networks on adolescent's cannabis use: a systematic review of longitudinal studies.

Aim: A systematic review was performed to summarize the key findings of the peer influence on cannabis use through Social Network Analysis (SNA) studies and identify limitations and gaps with the purpose of informing future research and practice. Longitudinal studies were included since they provide robust information about social relationships change over time. Background: Adolescents' cannabis use is a global problem, which has awakened an interest in its determinants such as social influences. Research has shown the importance of these influences on cannabis uptake and use. SNA is an useful relational approach to examine socialization mechanisms related to the onset of cannabis use in adolescents. Method: A search was conducted in PyscINFO, PubMed, Scopus and Web of Science for longitudinal articles published until February 2023, to examine cannabis use and peer's social networks. We focus on peers' influence of peers on cannabis use. Additionally, information about effect of cannabis use for peer selection was collected. Results: The results of the included studies (n = 8) showed that friends' cannabis use was most often/strongly associated with cannabis use. There was also an increase of cannabis use when the adolescent did not feel close to the school's peers, had a higher proportion of friendships relative to the total number of ties in the neighborhood, had a central position, did not belong to any group but had ties to members of two or more groups, had cannabis user friends (especially in early ages), and lived in a neighborhood where cannabis was used. Conclusion: Cannabis use is mainly related to friends' use. Yet, future studies are warranted to control for relevant selection effects to further knowledge on network effects on cannabis use, improving the design, and improving the modeling of the network. This systematic review may inform about the critical aspects of preventing cannabis use among adolescents, taking into consideration their complex social environment.

Effects of repeated-sprint hypoxic training on physical fitness ofactive adults / Efectos del entrenamiento de esprints repetidos en hipoxia sobrela condición física de adultos activos

Due to the time is, commonly, a barrier to exercise, the scientific community has paid attention to a new model of training. Repeated-sprint hypoxic training is now considered an effective time-efficient method for improving physical performance in different sport modalities. However, few researchers have studied the effect of this strategy in healthy untrained or moderately trained individuals. Depending of the prior fitness status, different findings may be obtained. Therefore, this study determined the effects of 4 weeks of repeated-sprint in hypoxia on cardiorespiratory fitness and anaerobic capacity in healthy men. Twenty-four physically active males (were randomly assigned to repeated-sprint in normoxia (n=8; 0.20 FiO2 ), in hypoxia (n=8; 0.14 FiO2 ) or a control group (n=8). Participants of both exercise groups developed eight training sessions consisted of 2 sets of 5 all-out cycling sprints of 10 s with a recovery of 20 s between sprints and 10 min between sets. Repeated sprint ability, vertical jump performance and estimated maximal oxygen consumption were tested at baseline, 7 days and 2 weeks after the last session. Seven days after the last sessions, significant differences (p<0.05) between normoxia (+7.8%; p<0.001; ES=1.66) and hypoxia groups (+9.9%; p=0.000; ES=1.42) compared with control group were found in estimated maximal oxygen consumption. In the hypoxia group, the number of sprints to exhaustion (7 days Post +55.6%; ES=1.40; 2 weeks Post +10.0%; ES=1.80) improved with a large effect size at 7 days and 2 weeks after the last sessions compared with baseline. Eight sessions of repeated-sprint training in hypoxia conditions could produce improvements and delayed effects on anaerobic capacity.(AU)

La comunidad científica ha prestado atención en los últimos años a un nuevo modelo de entrenamiento, debido a que la falta de tiempo es comúnmente la principal barrera para la práctica deportiva. En este contexto, el entrenamiento de esprint repetidos en hipoxia es considerado como una prometedora estrategia para mejorar el rendimiento físico en diferentes modalidades deportivas. Sin embargo, existen pocos estudios que investiguen los efectos sobre población moderadamente entrenada o sedentaria. Así, este estudio determina los efectos de un entrenamiento de esprint repetidos en hipoxia sobre la condición física de hombres sanos. Veinticuatro hombres fueron asignados aleatoriamente a un grupo normoxia (n=8; 0.20 FiO2 ), hipoxia (n=8; 0.14 FiO2 ) o control (n=8). Después de ocho sesiones de esprint repetido en cicloergómetros de 10s, la habilidad de esprint repetido, el rendimiento en el salto vertical, así como el consumo de oxígeno fueron evaluados en la línea base y a los días y 2 semanas de la última sesión de entrenamiento. A los 7 días, se observaron diferencias significativas entre normoxia (+7,8%; p<0.001; ES=1,66) e hipoxia (+9,9%; p=0,000; ES=1,42) comparado con el grupo control en el consumo máximo de oxígeno estimado. En hipoxia, el número de esprint hasta la extenuación (7 días Post +55,6%; ES=1,40; 2 semanas Post +10,0%; ES=1,80) también mejoró con tamaño del efecto elevado a los 7 días y 2 semanas de la última sesión comparado con la línea base. El protocolo de 8 sesiones de esprines repetido en hipoxia podría producir mejoras y retrasar los efectos sobre el rendimiento anaeróbico de hombres sanos. (AU)

Risk Factors for Infection, Predictors of Severe Disease, and Antibody Response to COVID-19 in Patients With Inflammatory Rheumatic Diseases in Portugal-A Multicenter, Nationwide Study.

Objective: To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients. Methods: Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls. Results: 162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099-0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053-0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21-81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03-1.05; P = 0.057). Conclusions: TNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.

Factors Associated with Quality of Life in Relatives of Adults with Serious Mental Illness: A Systematic Review.

Caring for a family member with a serious mental illness often has an impact on the quality of life (QoL) of caregivers. This could have negative repercussions on their caring skills and thus affect the care provided to that individual. The aim of this paper is to identify current evidence on QoL factors affecting relatives of individuals suffering from serious mental illness. A systematic review related to the research question was conducted in six databases by two independent reviewers. The QoL factors of relatives include sociodemographic, contextual, psychological, physical, and patient factors. The findings are consistent with the results of previous research. Mental health professionals may support a family with a member diagnosed with a serious mental illness by enhancing their education about QoL factors, which would trigger and promote protective factors so that family members could assess and act on them on an ongoing basis.

Longitudinal SARS-CoV-2 seroprevalence in Portugal and antibody maintenance 12 months after infection.

During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, 6 months after the initial moderate wave. Here, we show the seroprevalence changes 6 months later, up to the second week of March 2021, shortly following the third wave, which was one of the most severe in the world, and 2 months following the start of the vaccination campaign. A longitudinal epidemiological study was conducted, with a stratified quota sample of the Portuguese population. Serological testing was performed, including ELISA determination of antibody class and titers. The proportion of seropositives, which was 2.2% in September 2020, rose sharply to 17.3% (95% CI: 15.8-18.8%) in March 2021. Importantly, circulating IgG and IgA antibody levels were very stable 6 months after the initial determination and up to a year after initial infection, indicating long-lasting infection immunity against SARS-CoV-2. Moreover, vaccinated people had higher IgG levels from 3 weeks post-vaccination when compared with previously infected people at the same time post-infection.

Family and Social Variables Associated with Family Health.

The current study examined the interrelationships among potentially relevant family and social factors associated with family health. A cross-sectional study was conducted by collecting demographic information from 432 families, including family typology, family life cycle (FLC), and social status as well as social support and stressful life events (SLEs), with self-perception of family health being measured as a dependent variable. Descriptive analysis of the sample and univariate and multivariate linear regression analyses were performed. Multivariate analyses showed that the FLC stage of families as launching centers, lower educational level of household heads, and impact of SLEs were negatively associated with family health, whereas adequate perceived social support and the number of close friends and relatives were positively associated with family health. Therefore, these factors must be considered by family nurses to promote family health and prevent family dysfunction.