ADHERENCE AND PERSISTENCE TO TREATMENT WITH INFLIXIMAB: ANALYSIS OF A PATIENT SUPPORT PROGRAM COHORT IN BRAZIL.

BACKGROUND: Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data have shown low rates of both persistence and adherence to several available biologics. OBJECTIVE: The objective of this study was to describe adherence and persistence rate to IFX treatment and also persistence in the patient support program (PSP), among patients diagnosed with inflammatory bowel diseases (IBD) or rheumatic diseases (RD) enrolled in the program of a large pharmaceutical company in Brazil. METHODS: Retrospective observational analysis using the PSP database. IBD or RD patients using IFX enrolled on the PSP database between September 2015 and August 2019 were retrospectively evaluated to identify the persistence rate and adherence and followed up until March 1, 2020. Patients were excluded if treatment start date was prior to program entry; first infusion prior to September 1st, 2015 or after August 31st, 2019; the patients did not started treatment; and patients with "OTHERS" in "Indication" field. Persistence was assessed considering both persistence in the program ("PSP persistence") and persistence on IFX in the PSP ("IFX persistence in the PSP"). PSP persistence was defined as the proportion of patients remaining in the program at 6, 12, 24, 36 and 48 months after initiating IFX. To determine IFX persistence in the PSP, censoring was defined at the time the patient left the program, died, or was lost to follow-up. Adherence to treatment was measured by medication possession ratio ((MPR) - All days supply / elapsed days from first prescription to last day of medication possession)). Descriptive statistics were initially used. Kaplan-Meier curve, the median time estimated by the survival function, Cox regression model, and restricted mean survival time (RMST) were used to evaluate the treatment persistence time at 24 months and the logistic regression model was performed aiming to identify variables associated with adherence (MPR ≥80%). RESULTS: A total of 10,233 patients were analyzed, 5,826 (56.9%) with the diagnosis of RD and 4,407 (43.1%) of IBD. At the end of the follow-up (median 9.1 months from PSP entry to the last infusion), persistence in the PSP was 65.6%, 48.2%, 31.0%, 20.7% and 13.1% at 6, 12, 24, 36 and 48 months, respectively. Considering persistence on IFX in the PSP, estimates were 93.7%, 87.8%, 77.0%, 62.4% and 53.0% at 6, 12, 24, 36 and 48 months, respectively. Variables associated with the risk of non-persistence were gender, country region and diagnosis of rheumatoid arthritis and ankylosing spondylitis. Median MPR was 94.2%, while the percentage of patients with MPR ≥80% was 91.0%. Variables associated with MPR≥80% were country region and diagnosis of Crohn's disease. CONCLUSION: Many patients leave the program without discontinuing IFX, since the 12-month persistence were very different between program and medication estimates, while high adherence rates were observed among patients enrolled in the PSP. Data highlights the benefits of a PSP.

Malnutrition: muscle wasting, inflammation, RDW, and their relation with adverse outcomes.

OBJECTIVE: The objective of the study was to explore red cell distribution width (RDW) as a surrogate marker of inflammation, alone and in conjunction with muscle wasting to predict malnutrition-related adverse outcomes. METHODS: This was a single-center observational study including adult hospitalized patients. Demographic variables, malnutrition criteria, and RDW were captured within 24 hours of hospital admission. Correlation tests and regression models were performed between these variables (RDW and muscle wasting) and adverse outcomes (in-hospital mortality and unplanned transfer to critical care areas (CCA). RESULTS: Five hundred and forty-five patients were included in the final analysis. Muscle wasting showed an independent association with adverse outcomes in every regression model tested. RDW alone showed fair predictive performance for both outcomes' significance and the adjusted model with muscle wasting showed association only for unplanned transfer to CCA. CONCLUSION: RDW did not improve the prediction of adverse outcomes compared to muscle wasting assessed by physical examination and simple indexes for acute and chronic inflammation. Malnourished patients presented higher RDW values showing a possible metabolic profile (higher inflammation and lower muscle). It is still unknown whether nutrition support can influence RDW value over time as a response marker or if RDW can predict who may benefit the most from nutritional support.

OBJETIVO: Explorar el ancho de distribución eritrocitaria (ADE) como un marcador subrogado de inflamación, individualmente y en conjunto con el desgaste muscular, para predecir resultados adversos asociados a la desnutrición. MÉTODO: Estudio unicéntrico, observacional, incluyendo pacientes adultos hospitalizados. Se capturaron variables demográficas, criterios de desnutrición y el ADE en las primeras 24 horas de ingreso. Se realizaron pruebas de correlación y modelos de regresión entre dichas variables (ADE y desgaste) y resultados adversos (mortalidad hospitalaria y traslado no planeado a áreas críticas). RESULTADOS: Se incluyeron 545 pacientes. El desgaste muscular mostró asociación independiente con los resultados adversos en cada modelo. El ADE individualmente mostró un desempeño aceptable para la predicción de ambos resultados, y en modelos ajustados con desgaste muscular mostró asociación únicamente con traslado no planeado a áreas críticas. CONCLUSIONES: El ADE no mejoró la predicción de resultados adversos comparado con el desgaste muscular por exploración física e índices simples de inflamación. Los pacientes con desnutrición presentaron mayores valores de ADE, mostrando un posible perfil metabólico (mayor inflamación y menos músculo). Aún se desconoce si el soporte nutricional puede influenciar el ADE como un marcador de respuesta o si puede predecir una respuesta favorable al soporte nutricional.

Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

Dopamine D2 receptor antagonist counteracts hyperglycemia and insulin resistance in diet-induced obese male mice.

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.

Targets and Effects of Common Biocompounds of Hibiscus sabdariffa (Delphinidin-3-Sambubiosid, Quercetin, and Hibiscus Acid) in Different Pathways of Human Cells According to a Bioinformatic Assay.

The utilization of food as a therapeutic measure for various ailments has been a prevalent practice throughout history and across different cultures. This is exemplified in societies where substances like Hibiscus sabdariffa have been employed to manage health conditions like hypertension and elevated blood glucose levels. The inherent bioactive compounds found in this plant, namely, delphinidin-3-sambubioside (DS3), quercetin (QRC), and hibiscus acid (HA), have been linked to various health benefits. Despite receiving individual attention, the specific molecular targets for these compounds remain unclear. In this study, computational analysis was conducted using bioinformatics tools such as Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb to identify the molecular targets, pathways, and hub genes. Supplementary results were obtained through a thorough literature search in PubMed. DS3 analysis revealed potential genetic alterations related to the metabolism of nitrogen and glucose, inflammation, angiogenesis, and cell proliferation, particularly impacting the PI3K-AKT signaling pathway. QRC analysis demonstrated interconnected targets spanning multiple pathways, with some overlap with DS3 analysis and a particular focus on pathways related to cancer. HA analysis revealed distinct targets, especially those associated with pathways related to the nervous system. These findings emphasize the necessity for focused research on the molecular effects of DS3, QRC, and HA, thereby providing valuable insights into potential therapeutic pathways.

Exquisite exposure: Formaldehyde as a metabolic regulator.

Throughout life, whether through external consumption or internal production, we are exposed to different reactive metabolites considered toxic to the body. Pham et al.1 uncover metabolic regulation by one such harmful metabolite: formaldehyde.

Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial.

BACKGROUND/OBJECTIVE: The prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME). PATIENTS/METHODS: Prospective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy. RESULTS: Levosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 µm in CFT (55% vs. 28%), and dropping ≥0.06 mm3 in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected. CONCLUSIONS: Oral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.

Nanosuspensions as carriers of active ingredients: Chemical composition, development methods, and their biological activities.

Nanosuspensions (NSps) are colloidal dispersions of particles that have the potential to solve the delivery problems of active ingredients associated with their low solubility in water or instability due to environmental factors. It is essential to consider their chemical composition and preparation methods because they directly influence drug loading, size, morphology, solubility, and stability; these characteristics of nanosuspensions influence the delivery and bioavailability of active ingredients. NSps provides high loading of drugs, protection against degrading agents, rapid dissolution, high particle stability, and high bioavailability of active ingredients across biological membranes. In addition, they provide lower toxicity compared to other nanocarriers, such as liposomes or polymeric nanoparticles, and can modify the pharmacokinetic profiles, thus improving their safety and efficacy. The present review aims to address all aspects related to the composition of NSps, the different methods for their production, and the main factors affecting their stability. Moreover, recent studies are described as carriers of active ingredients and their biological activities.

Osmotic Stress Responses, Cell Wall Integrity, and Conidiation Are Regulated by a Histidine Kinase Sensor in Trichoderma atroviride.

Trichoderma atroviride responds to various environmental stressors through the mitogen-activated protein kinase (MAPK) Tmk3 and MAPK-kinase Pbs2 signaling pathways. In fungi, orthologues to Tmk3 are regulated by a histidine kinase (HK) sensor. However, the role of T. atroviride HKs remains unknown. In this regard, the function of the T. atroviride HK Nik1 was analyzed in response to stressors regulated by Tmk3. The growth of the Δnik1 mutant strains was compromised under hyperosmotic stress; mycelia were less resistant to lysing enzymes than the WT strain, while conidia of Δnik1 were more sensitive to Congo red; however, ∆pbs2 and ∆tmk3 strains showed a more drastic defect in cell wall stability. Light-regulated blu1 and grg2 gene expression was induced upon an osmotic shock through Pbs2-Tmk3 but was independent of Nik1. The encoding chitin synthases chs1 and chs2 genes were downregulated after an osmotic shock in the WT, but chs1 and chs3 expression were enhanced in ∆nik1, ∆pbs2, and ∆tmk3. The vegetative growth and conidiation by light decreased in ∆nik1, although Nik1 was unrequired to activate the light-responsive genes by Tmk3. Altogether, Nik1 regulates responses related to the Pbs2-Tmk3 pathway and suggests the participation of additional HKs to respond to stress.

Coat Color in Local Goats: Influence on Environmental Adaptation and Productivity, and Use as a Selection Criterion.

This paper aims to review, systematically synthesize, and analyze fragmented information about the importance of coat color in local goats and its relationship with productivity and other important traits. Topics on current research on color expression are addressed, the relationship that has as a mechanism of environmental adaptation, its relationship with the production of meat, milk, and derivates, and the economic value of this characteristic. The use of this attribute as a tool to establish selection criteria in breeding programs based on results reported in the scientific literature is significant, particularly for low-income production systems, where the implementation of classic genetic improvement schemes is limited due to the lack of productive information, which is distinctive of extensive marginal or low scaled production systems around the world.

Psychopathology, cortisol and testosterone responses to traumatic images: differences between urban and suburban citizens in a middle-income country.

Background: Living in urban places has been associated with a higher risk of psychopathology as well as with altered hypothalamus-pituitary-adrenal (HPA) axis and consequently altered cortisol response, but studies have concentrated mainly in high-income countries population. The role of other hormones such as testosterone, implicated in stress response and with human social behaviors, have not yet been investigated. The aim of this study was to compare symptoms of psychopathology as well as cortisol and testosterone in response to traumatic images between urban and suburban people in a middle-income country. Methods: A sample of 67 women and 55 men (N = 122, 18-45 years) from urban and suburban places of Mexico participated in the study. We quantified salivary cortisol and testosterone in response to images with traumatic and violent content (basal, 15, 30, and 45 min after images). Participants answered a general information questionnaire and the Symptom Checklist-90-R to assess their psychopathological traits. We performed Generalized Estimating Equation Models to analyze hormonal levels and MANOVAs to compare differences in participants' psychopathology symptoms. Area under the curve respect to ground (AUCG) of hormonal levels and sex differences were also compared. Results: Suburban citizens showed no cortisol response, whereas urban people showed a cortisol peak 15 min after the image's exposure; however, suburban people had higher AUCG and basal levels compared to urban ones. Contrastingly, testosterone levels declined in all participants excepting the urban women, who showed no testosterone response. Although similar testosterone profile, AUCG levels were higher in urban than suburban men. Participants living in suburban areas had higher scores of somatizations, obsessive-compulsive, and interpersonal sensitivity, as well as more sleep disorders than participants living in urban areas. Conclusion: This study offers novel evidence about differences in cortisol and testosterone responses to a social stressor and in mental health indicators between a population of urban and suburban citizens, highlighting the impact of urbanization process on physiological and psychological outcomes in a middle-income country.

Apendicitis aguda dentro de una hernia de Spiegel: un caso infrecuente de una patología infrecuente.

INTRODUCTION: Spigelian hernia is a rare entity, with higher improbability of acute appendicitis within it. CASE REPORT: A 75-year-old female with a 30-year evolution hernia, abdominal pain, and fever of 1 week of onset, in whom was found an acute appendicitis within a Spigelian hernia. DISCUSSION: Spigelian hernia comprises 0.12-2% of all abdominal hernias. Presurgical diagnosis is stablished only in 50% of cases, with an hernial ring less than 2 cm and hidden localization. There isn't statistics of this complication because of the lack of case reports.

INTRODUCCIÓN: La hernia de Spiegel es una afección infrecuente, con una improbabilidad aún mayor de apendicitis aguda en su interior. CASO CLÍNICO: Mujer de 75 años que acude con una hernia de 30 años, dolor abdominal y fiebre de 1 semana de inicio, en quien se encontró apendicitis aguda dentro de una hernia de Spiegel. DISCUSIÓN: La hernia de Spiegel comprende el 0.12-2% de las hernias abdominales. El diagnóstico prequirúrgico se ha logra en el 50% de los casos, con defecto menor de 2 cm y de localización oculta. No existe estadística de esta complicación debido a la escasez de casos reportados.

Measles and Rubella Seroprevalence Among Children and Adolescents of Córdoba, Argentina: A Cross-Section Study in the Context of the Elimination Program.

We determined anti-rubella and anti-measles immunoglobulin G (IgG) in 7- to 19-year-old children and adolescents with vaccine only-induced immunity of Córdoba, Argentina, during a 6-month period over 2021-2022. Of the 180 individuals studied, 92.2% and 88.3% were positive for anti-measles and anti-rubella IgG, respectively. No significant differences were found comparing anti-rubella IgG concentrations (p = 0.144) and anti-measles IgG concentrations (p = 0.105) of individuals classified by age, but anti-measles IgG and anti-rubella IgG levels were significantly higher among female individuals compared with males (p = 0.031 and p = 0.036, respectively). Female subjects in the younger age group had higher concentrations of anti-rubella IgG as well (p = 0.020), even when anti-measles IgG concentrations did not differ among female age-subgroups (p = 0.187). In contrast, age subgroups of male individuals did not have significantly different IgG concentrations for rubella (p = 0.745) or measles (p = 0.124). Among samples with discordant results (22/180, 12.6%), 9.1% were negative for rubella but positive for measles; 13.6% were equivocal for rubella and positive for measles; 22.7% were equivocal for rubella and negative for measles, while 54.5% were positive for rubella but negative for measles. The findings indicate a seroprevalence below recommended for preventing measles in the population studied, while they evidence the need for standardization of serological tests for rubella IgG.

Variables predictoras de la satisfacción vital: Comparaciones entre estudiantes universitarios de minorías sexuales en Chile / Predictors of life satisfaction: Comparisons between university students from sexual minorities in Chile

Resumen En tiempos recientes, la literatura en psicología sobre orientación sexual ha pasado de centrarse en aspectos negativos experimentados por personas no heterosexuales a examinar factores que potencien el bienestar de estas. Estos estudios se han enfocado mayoritariamente en lesbianas y hombres gay (orientación hacia un único género o monosexual), mientras la inclusión de otras orientaciones, como bisexual y pansexual (orientaciones hacia más de un género o plurisexual) es un interés emergente. En Latinoamérica, un tema poco explorado en este sentido es la satisfacción vital y las variables asociadas, como el apoyo social y el revelar la orientación sexual, y cómo estas pueden variar entre personas de distintas orientaciones no heterosexuales. Por ello, el objetivo general de este estudio fue comparar el grado de revelación de la orientación sexual, el apoyo social percibido, la conexión con la comunidad LGBTIQ+ (sigla que incluye a lesbianas, gay, bisexual, transgénero, transexual, travesti, intersexual y queer) y la satisfacción vital entre estudiantes universitarios lesbianas y gays (LG), y bisexuales y pansexuales (BP). La muestra fue tomada entre 82 estudiantes universitarios LGBP, quienes respondieron un cuestionario en línea que incluía datos sociodemográficos y escalas destinadas a evaluar las variables en estudio. Los resultados mostraron que estudiantes universitarios LG revelan más su orientación sexual que estudiantes BP. Igualmente, se destaca la asociación positiva entre el apoyo social percibido y satisfacción vital, y entre la conexión con la comunidad LGBTIQ+ y la revelación de la orientación sexual. Este estudio contribuye al conocimiento sobre variables asociadas a la satisfacción vital según la orientación sexual, diferenciando entre estudiantes universitarios lesbianas y gays y estudiantes bisexuales y pansexuales.

Abstract In recent years, there has been a growing shift in research on sexual orientation. This focus has moved from centering on negative experiences, related to psychopathology and stigmatization, to examining subjective well-being factors in individuals belonging to these populations. In Latin American countries such as Chile, a scarcely explored link in this regard is satisfaction with life -the cognitive component of subjective well-being- and associated variables. The minority stress model indicates that individuals who belong to minority groups are exposed to additional stressors to which the general population is not exposed. These specific stressors are related to the marginalization, prejudice and exclusion suffered by the minority group of belonging. Researchers have shown that these stressors and their consequences may result in lower life satisfaction in non-heterosexual people compared to their heterosexual peers. Furthermore, different non-heterosexual orientations face specific forms of prejudice and, therefore, could experience a different impact on their life satisfaction. In this paper, the distinction is made between individuals with a monosexual orientation (towards one gender) and those with a plurisexual orientation, (towards more than one gender or independently of gender); namely, lesbians and gay men (LG) on the one hand, and bisexuals and pansexuals (BP) on the other. Research indicates that BP people experience lower levels of well-being than LG individuals. Compared to the latter, BP individuals tend to disclose their sexual orientation to a lesser extent, perceive less social support, and experience greater exclusion from community spaces destined to the general community of lesbian, gay, bisexual, transgender, intersex, and other queer identities (LGBTIQ+). Moreover, these differences between non-heterosexual orientations in terms of life satisfaction have been little explored in Latin American university students. To fill this gap in the literature, the general objective of this study was to compare the levels of disclosure of sexual orientation, perceived social support, connectedness with the LGBTIQ+ community, and life satisfaction among lesbian, gay, bisexual, and pansexual university students. Four hypotheses were proposed that addressed the comparisons between LG and BP participants for these variables. A non-probability sample of 82 LGBP university students was recruited to answer an online questionnaire. Of the sample, 32.9 % were lesbian or gay, and 67.1 % were bisexual or pansexual. Most participants were women (67.1 %), compared to 29.3 % men and 3.7 % of another gender. The questionnaire consisted of a section of sociodemographic data, a sexual orientation disclosure scale, the Multidimensional Scale of Perceived Social Support, the LGBTIQ + Community Connectedness Scale, and the Life Satisfaction Scale. Analyses included comparisons of means between groups. A confirmatory factor analysis (CFA) was conducted for the Connectedness Scale to test its validity. Results showed that LG and BP students reported similar levels of perceived social support, community connectedness, and life satisfaction, while LG students tended to disclose their sexual orientation to more people than BP students. A positive association was also found between perceived social support and life satisfaction, and between connectedness and disclosure of sexual orientation. The CFA showed that the Connectedness Scale is valid for its use in university samples in Chile and other Latin American populations. Limitations regarding sample size and recommendations for future research are discussed. This study contributes to the knowledge about variables associated with life satisfaction in non-heterosexual university students, highlighting the differential needs for support of those with a monosexual orientation (lesbians and gays) and those with a plurisexual orientation (bisexual and pansexual).

Elexacaftor/tezacaftor/ivacaftor projected survival and long-term health outcomes in people with cystic fibrosis homozygous for F508del.

BACKGROUND: A series of phase 3 clinical trials have demonstrated that elexacaftor plus tezacaftor plus ivacaftor (ELX/TEZ/IVA) is safe and efficacious in people with cystic fibrosis (pwCF) aged ≥12 years with ≥1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The impact of this treatment on lifetime clinical outcomes and survival, however, has yet to be assessed. METHODS: We used a person-level microsimulation model to estimate the survival and lifetime clinical benefits of ELX/TEZ/IVA treatment versus other CFTR modulator combinations (tezacaftor plus ivacaftor [TEZ/IVA] or lumacaftor plus ivacaftor [LUM/IVA]) or best supportive care (BSC) alone in pwCF aged ≥12 years who are homozygous for F508del-CFTR. Disease progression inputs were derived from published literature; clinical efficacy inputs were derived from an indirect treatment comparison conducted using relevant phase 3 clinical trial data and extrapolations of clinical data. RESULTS: The median projected survival for pwCF homozygous for F508del-CFTR treated with ELX/TEZ/IVA was 71.6 years. This was an increase of 23.2 years versus TEZ/IVA, 26.2 years versus LUM/IVA, and 33.5 years versus BSC alone. Treatment with ELX/TEZ/IVA also reduced disease severity as well as the number of pulmonary exacerbations and lung transplants. In a scenario analysis, the median projected survival for pwCF initiating ELX/TEZ/IVA between the ages of 12 and 17 years was 82.5 years, an increase of 45.4 years compared with BSC alone. CONCLUSIONS: The results from our model suggest ELX/TEZ/IVA treatment may substantially increase survival for pwCF, with early initiation potentially allowing pwCF to achieve near-normal life expectancy.

Treatment Patterns, Survival, Quality of Life, and Healthcare Resource Use Among Patients With Triple-Class Refractory Multiple Myeloma in US Clinical Practice: Findings From the Connect MM Disease Registry.

BACKGROUND: Adults with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognosis, but the burden of TCR MM has not been well characterized. This study evaluated treatment patterns, overall survival (OS), health-related quality of life (HRQoL), and healthcare resource use (HCRU) among patients with TCR MM in US clinical practice. PATIENTS AND METHODS: Patients with TCR MM in the Connect MM Registry (NCT01081028; a large, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM) were included. Patient characteristics, treatment patterns, HRQoL, and HCRU were analyzed using descriptive statistics. OS was calculated using Kaplan-Meier methodology for the overall cohort and for patients with/without ≥1 post-TCR line of therapy (LOT). RESULTS: A total of 232 patients with TCR MM were included; 155 (67%) had ≥1 post-TCR LOT (post-TCR-Treated subgroup; median 9.9 months of follow-up). Most common post-TCR treatments were carfilzomib (47%), pomalidomide (40%), and daratumumab (26%); median treatment duration was 3.3 months. Median OS was 9.9 months in the overall population, 10.8 months in post-TCR-Treated patients, and 2.6 months for those with no new post-TCR LOT. HRQoL deteriorated and pain increased over 1 year of follow-up, with clinically meaningfully changes in EQ-5D (mean, -0.06 points) and FACT-G (mean, -9.9 points). 124 (53%) patients had ≥1 all-cause hospitalization and 58 (25%) had ≥1 MM-related hospitalization; median annualized length of stay was 35.3 and 42.9 days, respectively. CONCLUSION: The burden of TCR MM is substantial, emphasizing the need for more effective treatment options in the TCR setting.

Manejo estomatológico de mínima intervención en paciente pediátrico con tetralogía de Fallot: Reporte de caso / Gestão estomatológica com intervenção mínima em paciente pediátrico com tetralogia de Fallot: relatório de caso / Minimal intervention dentistry in a pediatric patient with tetralogy of Fallot: case report

La tetralogía de Fallot es la cardiopatía congénita cianótica más frecuente, su prevalencia es del 0,08% afectando aproximadamente a 1 de cada 8.500 nacidos vivos. El manejo de pacientes con cardiopatía congénita representa un desafío para el odontopediatra, ya que requiere conocimientos y habilidades específicas. La odontología de mínima intervención permite ofrecer a los pacientes un tratamiento gentil, mejorando el abordaje conductual ayudando a la adaptación del paciente al tratamiento dental. El objetivo de este reporte consiste describir el manejo estomatológico con odontología de mínima intervención en una paciente femenina de 5 años de edad con diagnóstico de tetralogía de Fallot. Conclusión: la odontología de mínima intervención fue eficaz para el tratamiento de paciente con cardiopatía congénita aportando herramientas significativas destinadas a mejorar la conducta, brindando tratamientos sencillos, rápidos y conservadores. Dando la posibilidad de este tipo de tratamientos en cualquier otro paciente con compromiso médico

A tetralogia de Fallot é a cardiopatia congênita cianótica mais comum, com uma prevalência de 0,08%, afetando aproximadamente 1 em 8.500 nascidos vivos. O tratamento de pacientes com cardiopatias congênitas representa um desafio para os dentistas pediátricos, pois requer conhecimentos e habilidades específicas. A odontologia de intervenção mínima permite oferecer aos pacientes um tratamento gentio, melhorando a abordagem comportamental e ajudando na adaptação do paciente ao tratamento odontológico. O objetivo deste relatório é descrever o tratamento estomatológico com intervenção odontológica mínima em um paciente de 5 anos diagnosticado com tetralogia de Fallot. Conclusão: A odontologia com intervenção mínima foi eficaz no tratamento de pacientes com doenças cardíacas congênitas, fornecendo ferramentas significativas destinadas a melhorar o comportamento, oferecendo tratamentos simples, rápidos e conservadores. Ela oferece a possibilidade deste tipo de tratamento em qualquer outro paciente com comprometimento médico

Tetralogy of Fallot is the most common cyanotic congenital heart disease, with a prevalence of 0,08%, affecting approximately 1 in every 8,500 live births. Treatment patients with congenital heart disease represents a challenge for pediatric dentists, it requires specific knowledge and skills. Minimal intervention dentistry allows offering patients a gentle treatment, improving the behavioral approach and helping the patient's adaptation to dental treatment. The aim of this report is to describe the management with minimal intervention dentistry in a 5-year-old female patient with a diagnosis of tetralogy of Fallot. Conclusion: Minimal intervention dentistry was effective in the treatment of patients with congenital heart disease, providing significant tools aimed at improving behavior, offering simple, fast and conservative treatments. It gives the possibility of this type of treatment in any other patient with medical compromise.

Fatty-Acid-Rich Agave angustifolia Fraction Shows Antiarthritic and Immunomodulatory Effect.

Agave angustifolia is a xerophytic species widely used in Mexico as an ingredient in sweet food and fermented beverages; it is also used in traditional medicine to treat wound pain and rheumatic damage, and as a remedy for psoriasis. Among the various A. angustifolia extracts and extract fractions that have been evaluated for their anti-inflammatory effects, the acetonic extract (AaAc) and its acetonic (F-Ac) and methanolic (F-MeOH) fractions were the most active in a xylene-induced ear edema model in mice, when orally administered. Four fractions resulting from chemically resolving F-Ac (F1-F4) were locally applied to mice with phorbol 12-myristate 13-acetate (TPA)-induced ear inflammation; F1 inhibited inflammation by 70% and was further evaluated in a carrageenan-induced mono-arthritis model. When administered at doses of 12.5, 25, and 50 mg/kg, F1 reduced articular edema and the spleen index. In addition, it modulated spleen and joint cytokine levels and decreased pain. According to a GC-MS analysis, the main components of F1 are fatty-acid derivatives: palmitic acid methyl ester, palmitic acid ethyl ester, octadecenoic acid methyl ester, linoleic acid ethyl ester, and oleic acid ethyl ester.

Human parvovirus B19 infection in a pregnant patient resulting in severe hydrops, foetal death and persistent infection.

Human parvovirus B19 (B19V) is the aetiological agent of erythema infectiosum. Primary infection during pregnancy can be transmitted to the foetus and cause foetal abnormalities related to depletion of erythrocyte progenitor cells, including congenital anaemia, hydrops, and foetal death. In this paper we report the detection of B19V infection in a pregnant patient, which onset occurred without appreciable signs and symptoms until she developed inappropriate contractions for gestational age and fluid loss. B19V infection resulted in severe hydrops fetalis with a fatal course for the foetus, while persisted in the mother at least 12 months after foetal death. The objective of this report is to highlight the importance of optimizing B19V diagnosis through early suspicion and testing during pregnancy. Knowing the mother's immune status before or at the beginning of gestation can contribute, together with early diagnosis, to improve the management of patients at risk.

The beneficial metabolic actions of prolactin.

The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of its actions. In contrast with the negative outcomes associated with very high (>100 µg/L) and very low (<7 µg/L) PRL levels, moderately high PRL levels, both within but also above the classically considered physiological range are beneficial for metabolism and have been defined as HomeoFIT-PRL. In animal models, HomeoFIT-PRL levels counteract insulin resistance, glucose intolerance, adipose tissue hypertrophy and fatty liver; and in humans associate with reduced prevalence of insulin resistance, fatty liver, glucose intolerance, metabolic syndrome, reduced adipocyte hypertrophy, and protection from type 2 diabetes development. The beneficial actions of PRL can be explained by its positive effects on main metabolic organs including the pancreas, liver, adipose tissue, and hypothalamus. Here, we briefly review work supporting PRL as a promoter of metabolic homeostasis in rodents and humans, the PRL levels associated with metabolic protection, and the proposed mechanisms involved. Finally, we discuss the possibility of using drugs elevating PRL for the treatment of metabolic diseases.