Treatment patterns and patient journey in progressive pulmonary fibrosis: a cross-sectional survey.

BACKGROUND: For patients with interstitial lung diseases (ILDs) presenting with a progressive pulmonary fibrosis (PPF) phenotype, current knowledge of disease characteristics at diagnosis, patient journey, and treatment is limited. This study aimed to describe demographics and clinical experiences of patients presenting with PPF in a European real-world setting. METHODS: Data were analysed from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey of pulmonologists and rheumatologists in five European countries (France, Germany, Italy, Spain, United Kingdom) and internal medicine specialists (France) from April to October 2022. Physicians provided data for up to 12 consecutive patients with physician-confirmed ILD with a progressive phenotype other than idiopathic pulmonary fibrosis. Analyses were descriptive. RESULTS: Overall, 265 physicians reported on 1,335 patients. Mean (standard deviation) age at survey date was 60.4 (11.6) years, 91.2% were white, 58.1% female, 44.0% non-smokers. Most patients (63.3%) first consulted a primary care physician. There was a mean delay of 7.8 (22.7) months between first ILD symptom and healthcare professional visit, and another 7.7 (12.8) months to ILD diagnosis. At survey date, 47.7% of patients had physician-reported moderate ILD, 42.3% had mild ILD and 10.0% had severe ILD. Disease progression was reported in the 12 months prior to the survey for 19.5% of patients; of these, progression was based on worsening symptom in 27.3% and lung function decline in 25.8%. For patients experiencing symptoms prior to ILD diagnosis (72.8%), the most common symptoms were dyspnoea on exertion (80.5%) and cough (57.8%). Overall, 17.4% of patients were misdiagnosed prior to ILD diagnosis, with chronic obstructive pulmonary disease suspected in 39.2% of them. The most frequent comorbidities were anxiety (16.9%) and gastroesophageal reflux (15.5%). Although 77.8% of patients were receiving treatment for ILD at survey date, 15.6% of patients had never been prescribed treatment for ILD. CONCLUSIONS: This real-world study expands our understanding of patients, diagnostic delays and treatment gaps experienced by patients diagnosed with PPF in Europe. There was a mean delay of 15.5 months between first ILD symptoms and ILD diagnosis. Given the progressive nature of PPF, diagnostic delay may lead to poor outcomes, including shorter survival. TRIAL REGISTRATION: N/a.

Fetal Mortality: United States, 2022.

Objectives: This report presents 2022 fetal mortality data by maternal race and Hispanic origin, age, tobacco use during pregnancy, and state of residence, as well as by plurality, sex, gestational age, birthweight, and selected causes of death. Trends in fetal mortality are also examined. Methods: Descriptive tabulations of data are presented and interpreted for all fetal deaths reported for the United States for 2022 with a stated or presumed period of gestation of 20 weeks or more. Cause-of-fetal-death data only are restricted to residents of the 43 states and District of Columbia where cause of death was based on the 2003 fetal death report revision and less than 50% of deaths were attributed to Fetal death of unspecified cause (P95). Results: A total of 20,202 fetal deaths at 20 weeks of gestation or more were reported in the United States in 2022. The 2022 U.S. fetal mortality rate was 5.48 fetal deaths at 20 weeks of gestation or more per 1,000 live births and fetal deaths, 4% lower than in 2021 (5.73) and a new historic low for the United States. The fetal mortality rate in 2022 for deaths occurring at 20-27 weeks of gestation was 2.79, a 5% decline from 2021 (2.95). For deaths occurring at 28 weeks of gestation or more, the rate in 2022 was 2.71, a 3% decline from 2021 (2.80). In 2022, the fetal mortality rate was highest for Native Hawaiian or Other Pacific Islander non-Hispanic (10.36) and Black non-Hispanic (10.05) females and lowest for Asian non-Hispanic females (3.70). Fetal mortality rates were highest for women ages 40 and older, for women who smoked during pregnancy, and for women with multiple gestation pregnancies. Five selected causes accounted for 90.0% of fetal deaths in the 43-state and District of Columbia reporting area.

Antiviral Effect of Microalgae Phaeodactylum tricornutum Protein Hydrolysates against Dengue Virus Serotype 2.

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 µg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.

Evidence from recent clinical trials in fibrotic interstitial lung diseases.

PURPOSE OF REVIEW: Idiopathic pulmonary fibrosis (IPF) is the prototype of fibrosing interstitial lung diseases. It is mirrored by progressive pulmonary fibrosis (PPF), an umbrella term which characterizes disease behavior of various fibrotic interstitial lung diseases with irreversible progression, accounting for loss of lung function, exercise intolerance and respiratory failure leading to early mortality. Pirfenidone and nintedanib halve the decline in lung function but do not halt disease progression. RECENT FINDINGS: Since the publication in 2014 of pivotal pirfenidone and nintedanib studies, a number of clinical trials were conducted, many of them did not reach their primary endpoints. In IPF, promising phase 2 trials were followed by large phase 3 trials that did not confirm a favorable efficacy to tolerability favorable profile, including those with ziritaxestat, an autotaxin-1 inhibitor, zinpentraxin-alpha (human recombinant pentraxin-2), and the monoclonal antibody pamrevlumab targeting connective tissue growth factor. Nevertheless, newer compounds that hold promise are currently being evaluated in phase 3 or phase 2b randomized controlled trials, including: nerandomilast, a preferential phosphodiesterase 4B inhibitor; admilparant, a lysophosphatidic acid receptor antagonist; inhaled treprostinil, a prostacyclin agonist; and bexotegrast, a dual-selective inhibitor of αvß6 and αvß1 integrins. Nerandomilast, admilparant, inhaled treprostinil, and inhaled AP01 (pirfenidone), are currently studied in patients with PPF. SUMMARY: Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF.

[Influence of Clinical Practice Guidelines on the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis. Data from the Registry of the Spanish Society of Pulmonology and Thoracic Surgery]. / Influencia de las guías de práctica clínica en el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Datos del Registro de la Sociedad Española de Neumología y Cirugía Torácica.

Objective: The objective of the study was to analyze the diagnostic process and the time until the start of treatment of patients with idiopathic pulmonary fibrosis in relation to the publication of successive clinical practice guide. Material and methods: Multicenter, observational, ambispective study, in which patients includes in the idiopathic pulmonary fibrosis registry of the Spanish Society of Pulmonologist and Thoracic Surgery were analyzed. An electronic data collection notebook was enabled on the society's website. Sociodemographic and clinical variables were collected at diagnosis and follow-up of the patients. Results: From January 2012 to december 2019, 1064 patients were included in the registry, with 929 finally analyzed. The diagnosis process varied depending on the year in which it was performed, and the radiological pattern observed in the high-resolution computed tomography. Up to 26.3% of the cases (244) were diagnosed with chest high-resolution computed tomography and clinical evaluation. Surgical biopsy was used up to 50.2% of cases diagnosed before 2011, while it has been used in 14.2% since 2018. The median time from the onset of symptoms to diagnosis was 360 days (IQR 120-720), taking more than 2 years in the 21.0% of patients. A percentage of 79.4 of patients received antifibrotic treatment. The average time from diagnosis to the antifibrotic treatment has been 309 ± 596.5 days, with a median of 49 (IQR 0-307). Conclusions: The diagnostic process, including the time until diagnosis and the type of test used, has changed from 2011 to 2019, probably due to advances in clinical research and the publication of diagnostic-therapeutic consensus guidelines.

Chromosomal instability in a patient with ring chromosome 14 syndrome: a case report.

BACKGROUND: Ring chromosome 14 syndrome is a rare disorder primarily marked by early-onset epilepsy, microcephaly, distinctive craniofacial features, hypotonia, intellectual disability, and delay in both development and language acquisition. CASE PRESENTATION: A 21-year-old woman with a history of epileptic seizures since the age of 1.5 years presented with distinctive craniofacial features, including a prominent and narrow forehead, sparse and short eyebrows, palpebral ptosis, horizontal palpebral fissures, a broad nasal bridge, a prominent nasal tip, a flat philtrum, hypertelorism, midfacial hypoplasia, horizontal labial fissures, a thin upper lip, crowded teeth, an ogival palate, retrognathia, and a wide neck. Additional physical abnormalities included kyphosis, lumbar scoliosis, pectus carinatum, cubitus valgus, thenar and hypothenar hypoplasia, bilateral hallux valgus, shortening of the Achilles tendon on the left foot, and hypoplasia of the labia minora. Chromosomal analysis identified a ring 14 chromosome with breakpoints in p11 and q32.33. An aCGH study revealed a ~ 1.7 Mb deletion on chromosome 14qter, encompassing 23 genes. Genomic instability was evidenced by the presence of micronuclei and aneuploidies involving the ring and other chromosomes. CONCLUSION: The clinical features of our patient closely resembled those observed in other individuals with ring chromosome 14 syndrome. The most important point was that we were able to verify an instability of the r(14) chromosome, mainly involving anaphasic lags and its exclusion from the nucleus in the form of a micronucleus.

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Objectives: Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. Methods: This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included change from baseline in FVC, quantitative lung fibrosis (QLF) extent (%), and changes from baseline in fibrosis-related biomarkers. Measurements and Main Results: Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (62/89 [69.7%] and 21/31 [67.7%], respectively). Diarrhea was the most common TEAE; most participants with diarrhea also received nintedanib. Participants who were treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those who received placebo, with or without background therapy. A dose-dependent antifibrotic effect of bexotegrast was observed with QLF imaging, and a decrease in fibrosis-associated biomarkers was observed with bexotegrast versus placebo. Conclusions: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses suggest an antifibrotic effect according to FVC, QLF imaging, and circulating levels of fibrosis biomarkers. Clinical trial registered with www.clinicaltrials.gov (NCT04396756).

A Study on the Psychological Profile and Coping With the Disease in Patients With Lymphangioleiomyomatosis.

Introduction: Lymphangioleiomyomatosis (LAM) is a rare disease that affects women almost exclusively. We aimed to determine the psychological profile in patients with LAM, and their potential association with sociodemographic and clinical features, and to know their role in coping with the disease. Material and methods: Cross-sectional and descriptive study in collaboration with the Spanish Association of LAM (AELAM). The variables measured were: socio-demographic, psychological (anxiety, depression, demoralization, spirituality, resilience, social support), clinical (treatment) and health-related quality of life. Results: We studied 87 LAM patients, with a mean (SD) age of 47.7 (7.7) years, and time since diagnose was 10.1 (5.4) years. 75.9% of patients were receiving sirolimus or everolimus, and oxygen therapy was required in 34.5% of patients. Anxiety was found in 46% of patients, depression in 55%, while only 2% presented demoralization and 14% deficit in spirituality. Social support and resilience were adequate. The "non-severe" group (without oxygen therapy) presented worse results in anxiety. A structural equation model to explore association between variables, showed very adequate fit indices: χ2(14) = 29.743 (p = .074); CFI = .983; TLI = .967; SRMR = .058; RMSEA = .075[.000-.128]. The model identifies resilience, spirituality and social support as "protective factors" from anxiety, depression, and demoralization. Conclusions: This study performed on a large series of women with LAM describes their psychological profile, in addition to showing how they cope with the disease. We have found that other psychological constructs, such as perceived social support and resilience, are protective factors. Early psychological evaluation and intervention is necessary to reduce comorbidities and prevent mental health problems in women with LAM.

Introducción: La linfangioleiomiomatosis (LAM) es una enfermedad rara que afecta casi exclusivamente a las mujeres. Nuestro objetivo fue determinar el perfil psicológico en los pacientes con LAM, y su potencial asociación con características sociodemográficas y clínicas, y conocer su papel en el afrontamiento de la enfermedad. Material y métodos: Estudio transversal y descriptivo en colaboración con la Asociación Española de LAM (AELAM). Las variables medidas fueron: sociodemográficas, psicológicas (ansiedad, depresión, desmoralización, espiritualidad, resiliencia, apoyo social), clínicas (tratamiento) y calidad de vida relacionada con la salud. Resultados: Se estudiaron 87 pacientes con LAM, con una edad media (DE) de 47,7 ± 7,7 años y un tiempo desde el diagnóstico de 10,1 ± 5,4 años. El 75,9% de los pacientes estaban recibiendo sirolimus o everolimus, y el 34,5% de los pacientes requirió oxigenoterapia. La ansiedad se encontró en el 46% de los pacientes, la depresión en el 55%, mientras que solo el 2% presentó desmoralización y el 14% déficit en la espiritualidad. El apoyo social y la resiliencia fueron adecuados. El grupo «no grave¼ (sin oxigenoterapia) presentó peores resultados en ansiedad. Un modelo de ecuaciones estructurales para explorar asociación entre variables, mostró índices de ajuste muy adecuados: χ2(14) = 29,743 (p = 0,074); CFI = 0,983; TLI = 0,967; SRMR = 0,058; RMSEA = 0,075 (0,000-0,128). El modelo identifica la resiliencia, la espiritualidad y el apoyo social como «factores protectores¼ contra la ansiedad, la depresión y la desmoralización. Conclusiones: Este estudio realizado en una amplia serie de mujeres con LAM describe su perfil psicológico, además de mostrar cómo afrontan la enfermedad. Hemos descubierto que otros constructos psicológicos, como el apoyo social percibido y la resiliencia, son factores protectores. La evaluación e intervención psicológica temprana es necesaria para reducir las comorbilidades y prevenir problemas de salud mental en mujeres con LAM.

Association between lipid profile and clinical outcomes in COVID-19 patients.

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.

Births: Final Data for 2022.

Objectives- This report presents 2022 data on U.S. births by selected characteristics. Trends in fertility patterns and maternal and infant characteristics are described. Methods-Descriptive tabulations based on birth certificates of the 3.67 million births registered in 2022 are shown by maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates also are shown. Trends for 2010 to 2022 are presented for selected items, and by race and Hispanic origin for 2016-2022. Results-A total of 3,667,758 births occurred in the United States in 2022, essentially unchanged from 2021. The general fertility rate declined 1% from 2021 to 56.0 births per 1,000 females ages 15-44 in 2022. The birth rate for females ages 15-19 declined 2% from 2021 to 2022; birth rates fell 7% for women ages 20-24, rose 1% to 5% for women ages 25-29 and 35-44, and rose 12% for women ages 45-49 (the first increase since 2016). The total fertility rate declined less than 1% to 1,656.5 births per 1,000 women in 2022. Birth rates declined for unmarried women but increased for married women from 2021 to 2022. Prenatal care beginning in the first trimester declined to 77.0% in 2022; the percentage of women who smoked during pregnancy declined to 3.7%. The cesarean delivery rate was unchanged in 2022 (32.1%); Medicaid was the source of payment for 41.3% of births. The preterm birth rate declined 1% to 10.38%; the low birthweight rate rose 1% to 8.60%. The twin birth rate was unchanged in 2022 (31.2 per 1,000 births); the 2% decrease in the triplet and higher-order multiple birth rate.

Psychometric Validation of the Patient-Reported Experience Measure (PREM) Questionnaire "HowRwe" in Patients With Respiratory Disease Receiving Home Respiratory Therapies.

Introduction: The patient experience is defined as all the interactions that occur between patients and the healthcare system. The experience of patients with respiratory disease with home respiratory treatments (HRT) is not captured in currently available Patient-Reported Outcome Measures (PROM). We present the psychometric validation of the Patient-Reported Experience Measure (PREM) 'HowRwe' in Spanish and for respiratory patients with HRT. Methods: After translation following ISPOR guidelines (International Society for Pharmacoeconomics and Outcomes Research), the questionnaire was administered to adult respiratory patients who were receiving treatment at Hospital Universitario de La Princesa. The administration was done in two stages with 6 months of difference between the pre- and post-test. Results: We studied 228 respiratory patients, with a mean (SD) age of 64.1 (13.2) years, 52.2% were men, 68.0% were married or coupled, and 56.6% were retired. Reliability coefficients of the scale were adequate, with α = .921 and Ω = .929 for pre-test, and α = .940 and Ω = .958 for post. The confirmatory factor analysis tested for pre- and post-intervention, showed an excellent overall fit: χ2(2) = 49.380 (p < .001), CFI = .941 and SRMR = .072; and χ2(2) = 37.579 (p < .001), CFI = .982 and SRMR = .046, respectively. No statistically significant associations were observed for neither age, adherence nor quality of life, except between HowRwe post-test and quality of life pre-test (r = .14 [.01,.26]; p = .035). No significant differences were found in sociodemographic variables. No differences in pre-test or post-test were found in effect of HRT. 85.6% of patients found the content of HowRwe "Useful", and the preferred channel to respond it were paper, app and email. Conclusions: The Spanish version of the 'HowRwe' questionnaire to measure the experience in respiratory patients with home respiratory treatments (HRT), has adequate psychometric properties and conceptual and semantic equivalence with the original English version.

Introducción: La experiencia del paciente se define como todas las interacciones que ocurren entre los pacientes y el sistema de salud. La experiencia de los pacientes con enfermedades respiratorias con terapias respiratorias domiciliarios (TRD) no se refleja en las Medidas de resultados informados por el paciente (PROM) disponibles actualmente. Presentamos la validación psicométrica de la Medida de Experiencia Reportada por el Paciente (PREM por sus siglas en inglés) 'HowRwe' en español y para pacientes respiratorios con TRD. Métodos: Después de la traducción siguiendo las pautas de ISPOR (Sociedad Internacional de Farmacoeconomía e Investigación de Resultados), el cuestionario se administró a pacientes respiratorios adultos que estaban recibiendo tratamiento en el Hospital Universitario de La Princesa. La administración se realizó en dos etapas con 6 meses de diferencia entre el pre y post test. Resultados: Se estudiaron 228 pacientes respiratorios, con una edad media (DE) de 64,1 ± 13,2 años, el 52,2% eran hombres, el 68,0% estaban casados o en pareja y el 56,6% eran jubilados. Los coeficientes de confiabilidad de la escala fueron adecuados, con α = .921 y Ω = .929 para el pretest, y α = .940 y Ω = .958 para el post. El análisis factorial confirmatorio testado para pre y postintervención, mostró un ajuste global excelente: χ2(2) = 49.380 (p < .001), CFI = .941 y SRMR = .072; y χ2(2) = 37,579 (p < .001), CFI = .982 y SRMR = .046, respectivamente. No se observaron asociaciones estadísticamente significativas ni para la edad, la adherencia ni para la calidad de vida, excepto entre HowRwe postest y calidad de vida pretest (r = .14 [.01,.26];p = .035). No se encontraron diferencias significativas en las variables sociodemográficas. No se encontraron diferencias en el efecto de la TRH en el pretest o postest. El 85,6% de los pacientes encontró "útil" el contenido de HowRwe y el canal preferido para responder fue el papel, la aplicación y el correo electrónico. Conclusiones: La versión española del cuestionario 'HowRwe' para medir la experiencia en pacientes respiratorios con tratamientos respiratorios domiciliarios (TRH), tiene adecuadas propiedades psicométricas y equivalencia conceptual y semántica con la versión original en inglés.

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.

Perinatal Mortality in the United States, 2020-2021.

Perinatal mortality(late fetal deaths at 28 completed weeks of gestation or more and early neonatal deaths younger than age 7 days) can be an indicator of the quality of health care before, during, and after delivery, and of the health status of the nation (1,2). The U.S. perinatal mortality rate declined 30% from 1990 through 2011, was stable from 2011 through 2016, and declined 4% from 2017 through 2019 (1,3-5). This report describes changes in perinatal mortality, as well as its components, late fetal and early neonatal mortality, from 2020 to 2021, during the COVID-19 pandemic. Also shown are perinatal mortality rates by mother's age, the three largest race and Hispanic-origin groups, and state for 2021 compared with 2020.

Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.

The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.

Scientific facts improve cannabis perception and public opinion: results from Sinaloa, México.

Cannabis, the most prevalent drug in Latin America, has long been associated with the state of Sinaloa, Mexico, known for its cultivation and distribution. Despite increasing global acceptance, cannabis use remains stigmatized in Mexican society, driven by perceptions of it as a highly psychoactive and addictive substance lacking medicinal or industrial value. This study investigates the impact of scientific information on societal perceptions of cannabis in Sinaloa. A large convenience sample of 3162 individuals from Sinaloa participated in this research, responding to a questionnaire on cannabis consumption and attitudes. Participants were then subjected to an intervention consisting of an informative briefing based on the documents "Using Evidence to Talk About Cannabis" and "State of the Evidence: cannabis use and regulation" by the International Centre for Science in Drug Policy. After the intervention, participants' attitudes were immediately reevaluated through the same questionnaire, allowing for a comparison of pre- and post-intervention responses. The results indicate that the intervention (providing scientific information) significantly influenced attitudes toward cannabis, with education and age playing prominent roles in its effectiveness. Notably, the intervention fostered more positive or more neutral attitudes, potentially reducing stigma and promoting a better-informed perspective on cannabis. This study highlights the pivotal role of evidence in shaping informed citizens' views, while underscoring the importance of countering misinformation for societal progress. These findings have significant implications for forthcoming cannabis policy modifications in Mexico, emphasizing the necessity of engaging knowledgeable individuals in policy decisions to address the violence and inequalities associated with the illicit drug trade, particularly in Sinaloa.

Clinical Predictors of Monkeypox Diagnosis: A Case-Control Study in a Nonendemic Region during the 2022 Outbreak.

Monkeypox (Mpox) is an emerging zoonotic disease with the potential for severe complications. Early identification and diagnosis are essential to prompt treatment, control its spread, and reduce the risk of human-to-human transmission. This study aimed to develop a clinical diagnostic tool and describe the clinical and sociodemographic features of 19 PCR-confirmed Mpox cases during an outbreak in a nonendemic region of northwestern Mexico. The median age of patients was 35 years, and most were male. Mpox-positive patients commonly reported symptoms such as fever, lumbago, and asthenia, in addition to experiencing painful ulcers and a high frequency of HIV infection among people living with HIV (PLWH). Two diagnostic models using logistic regression were devised, with the best model exhibiting a prediction accuracy of 0.92 (95% CI: 0.8-1), a sensitivity of 0.86, and a specificity of 0.93. The high predictive values and accuracy of the top-performing model highlight its potential to significantly improve early Mpox diagnosis and treatment in clinical settings, aiding in the control of future outbreaks.

Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with progressive pulmonary fibrosis (FIBRONEER-ILD).

INTRODUCTION: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD). METHODS AND ANALYSIS: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, stratified by background nintedanib use. Patients must be diagnosed with pulmonary fibrosis other than IPF that is progressive, based on predefined criteria. Patients must have forced vital capacity (FVC) ≥45% predicted and haemoglobin-corrected diffusing capacity of the lung for carbon monoxide ≥25% predicted. Patients must be receiving nintedanib for at least 12 weeks, or not receiving nintedanib for at least 8 weeks, prior to screening. Patients on stable treatment with permitted immunosuppressives (eg, methotrexate, azathioprine) may continue their treatment throughout the trial. Patients with clinically significant airway obstruction or other pulmonary abnormalities, and those using immunosuppressives that may confound FVC results (cyclophosphamide, tocilizumab, mycophenolate, rituximab) or high-dose steroids will be excluded. The primary endpoint is absolute change from baseline in FVC (mL) at week 52. The key secondary endpoint is time to the first occurrence of any acute ILD exacerbation, hospitalisation for respiratory cause or death, over the duration of the trial. ETHICS AND DISSEMINATION: The trial is being carried out in accordance with the ethical principles of the Declaration of Helsinki, the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The study results will be disseminated at scientific congresses and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05321082.

Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF).

IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in a phase II study in patients with IPF. This study design describes the subsequent pivotal phase III study of BI 1015550 in patients with IPF (FIBRONEER-IPF). METHODS AND ANALYSIS: In this placebo-controlled, double-blind, phase III trial, patients are being randomised in a 1:1:1 ratio to receive 9 mg or 18 mg of BI 1015550 or placebo two times per day over at least 52 weeks, stratified by use of background antifibrotics (nintedanib/pirfenidone vs neither). The primary endpoint is the absolute change in FVC at week 52. The key secondary endpoint is a composite of time to first acute IPF exacerbation, hospitalisation due to respiratory cause or death over the duration of the trial. ETHICS AND DISSEMINATION: The trial is being carried out in compliance with the ethical principles of the Declaration of Helsinki, in accordance with the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The results of the study will be disseminated at scientific congresses and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05321069.