Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution.

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.

Frequency of gastroschisis and omphalocele and possible influence of maternal folic acid supplementation. A narrative review.

There is an increase in the worldwide prevalence of congenital abdominal wall defects (CAWD), with gastroschisis (GS) and omphalocele (OC) being the most common. It is widely accepted that folic acid supplementation (FAS) in the maternal diet decreases the incidence of anomalies such as neural tube defects, but there is controversy regarding the possible beneficial role for other congenital malformations. Several epidemiological studies raise controversy regarding a possible relationship between vitamin supplementation with the occurrence of abdominal wall malformations. The aim of the present study is to obtain an updated review of the global frequency of CAWD in neonates and the relationship with FAS in the mothers. For this we have carried out a systematic search of epidemiological studies in different article databases between 2011 and 2022. The analysis of 25 studies conducted in different countries where cases of OC and/or GS are registered directly or together with other congenital defects shows that 60% inquire into the relationship of FAS with the incidence of CAWD. Half of them proposes a beneficial effect of FAS and the other half find no association, concluding that there is no unanimous evidence that FAS in the maternal diet decreases the incidence of CAWD. However, it seems that an influential factor to take into account is the nutritional habits of the mothers.

Health equity in urban and rural settings: implementation of the place standard tool in Spain.

The physical, social, and economic characteristics of neighborhoods and municipalities determine the health of their residents, shaping their behaviors and choices regarding health and well-being. Addressing local environmental inequalities requires an intersectoral, participatory, and equity-focused approach. Community participation plays a vital role by providing deeper insights into local contexts, integrating community knowledge and values into processes, and promoting healthier, fairer, and more equitable actions. In recent years, various tools have been developed to assess places and transform them into health-promoting settings. One such tool, the Place Standard Tool (PST), facilitates discussions on Social Determinants of Health grouped into 14 themes, serving as a starting point for local health interventions. In this study, that took place between August 2019 and February 2020, we described the resident's perceptions of two municipalities in the Valencian Community, Spain, using the validated Spanish version of the PST. A mixed-method convergent-parallel design was used to gain a holistic insight into residents' experiences concerning their physical, economic, and social environment. A total of 356 individuals from both municipalities participated in the study through discussion groups, structured interviews, and online survey. Descriptive analysis of the individual questionnaire answers was conducted, and differences between municipalities were explored. Qualitative thematic analysis was conducted on structured interviews and discussion groups. Quantitative and qualitative data were integrated to facilitate their comparison and identify areas of convergence or divergence in the findings. Overall, rural areas received more favorable evaluations compared to urban ones. Public Transport as well as Work and Local Economy were consistently rated the lowest across all groups and contexts, while Identity and Belonging received the highest ratings. In the urban area, additional negative ratings were observed for Traffic and Parking, Housing and Community, and Care and Maintenance. Conversely, Identity and Belonging, Natural Spaces, Streets and Spaces, Social Interaction, and Services emerged as the highest-rated themes overall. In the rural context, positive evaluations were given to Walking or Cycling, Traffic and Parking, Housing and Community, and Influence and Sense of Control. Significant differences (p < 0.01) between urban and rural settings were observed in dimensions related to mobility, spaces, housing, social interaction, and identity and belonging. Our study illustrated the capacity of the PST to identifying aspects within local settings that influence health, revealing both positive and challenging factors. Successful implementation requires appropriate territorial delineation, support from local authorities, and effective management of expectations. Furthermore, the tool facilitated community participation in decision-making about local environments, promoting equity by connecting institutional processes with citizen needs.

Missed opportunities in heart failure diagnosis and management: study of an urban UK population.

AIMS: This study aimed to examine the diagnostic pathways and outcomes of patients with heart failure (HF), stratified by left ventricular ejection fraction (EF), and to highlight deficiencies in real-world HF diagnosis and management. METHODS AND RESULTS: We conducted a retrospective cohort study in Salford, United Kingdom, utilizing linked primary and secondary care data for HF patients diagnosed between January 2010 and November 2019. We evaluated characteristics, diagnostic patterns, healthcare resource utilization, and outcomes. Patients were categorized according to baseline (the latest measure prior to or within 90 days post-diagnosis) as having HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF), or preserved EF (HFpEF). The data encompassed a 2 year period before diagnosis and up to 5 years post-diagnosis. A total of 3227 patients were diagnosed with HF between January 2010 and November 2019. The mean follow-up time was 2.6 [±1.9 standard deviation (SD)] years. The mean age at diagnosis was 74.8 (±12.7 SD) years, and 1469 (45.5%) were female. HFpEF was the largest cohort (46.6%, npEF = 1505), HFmrEF constituted 16.1% (nmrEF = 520), and HFrEF 18.5% (nrEF = 596) of the population, while 18.8% (nu = 606) of patients remained unassigned due to insufficient evidence to support categorization. At baseline, measurement of natriuretic peptide (NP; brain NP and N-terminal pro-B-type NP) and echocardiographic report data were available for 592 (18.3%) and 2621 (81.2%) patients, respectively. A total of 2099 (65.0%) of the HF cohort had access to a cardiology-led outpatient clinic prior to the HF diagnosis, and 602 (18.7%) attended cardiac rehabilitation post-diagnosis. The 5 year crude survival rate was 37.8% [95% confidence interval (CI) (35.2-40.7%)], 42.3% [95% CI (38.0-47.2%)], and 45.5% [95% CI (41.0-50.4%)] for HFpEF, HFrEF, and HFmrEF, respectively. CONCLUSIONS: Low survival rates were observed across all HF groups, along with suboptimal rates of NP testing and specialist assessments. These findings suggest missed opportunities for timely and accurate HF diagnosis, a pivotal first step in improving outcomes for HF patients. Addressing these gaps in diagnosis and management is urgently needed.

Impact of initiation of SGLT2 inhibitor treatment on the development of arrhythmias in patients with implantable cardiac devices.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have been associated with improved prognosis in patients with heart failure, but their impact on atrial arrhythmic (AA) and ventricular arrhythmic (VA) events is not fully understood. METHODS: This multicenter retrospective study included patients with implantable cardioverter-defibrillators who initiated treatment with SGLT2i. AA and VA events were compared in 2 time periods for each patient: 1 year before and 1 year after starting SGLT2i. RESULTS: The study included 195 patients (66.8 [61.3-73.1] years, 18.5% women). In the post-SGLT2i period, there was a reduction in the percentage of patients with any VA (pre: 52.3% vs post: 30.3%; P<.001) and clinically relevant VA (excluding nonsustained ventricular tachycardia) (pre: 21.5% vs post: 8.7%; P<.001). There was also a decrease in the number of episodes per patient/y of nonsustained ventricular tachycardia (pre: 2 (1-5) vs post: 1 (0-2); P<.001) and sustained ventricular tachycardia (pre: 1 (1-3) vs post: 0 (0-2); P=0.046). However, no differences were observed in the prevalence of AA (24.7% vs 18.8%; P=.117) or the burden of atrial fibrillation (pre: 0% (0-0.1) vs post: 0% (0-0); P=.097). CONCLUSIONS: Initiation of SGLT2i treatment was associated with a decrease in the percentage of patients with relevant VA but this effect was not observed for AA.

Extended-spectrum ß-lactamase-producing Enterobacterales in diverse foodstuffs: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The involvement of non-human-to-human transmission of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread. Aim: We aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city. Methods: Chicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing. Results: Among 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species. Escherichia coli and Serratia fonticola were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (p < 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with E. coli as predominant (17.6%). ESBL-producing Enterobacter cloacae was detected among different greens. Yet, ESBL-producing Klebsiella pneumoniae was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (p < 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-E. coli (33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (p = 0.122). Instead, differences were observed between regions of food production and countries (p < 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (p = 0.107). Conclusion: Our findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially E. coli, while greens are more prone to carry ESBL-K. pneumoniae and E. cloacae. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species.

Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients.

Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records. In this investigation, 76 ESBL-K. pneumoniae species complex and 284 ESBL-E. coli isolates were recovered from 19 and 61 patients. Strain persistence was detected in all patients colonized with ESBL-K. pneumoniae species complex, and 83.6% of patients colonized with ESBL-E. coli. We frequently observed isolates of the same strain recovered from different body sites associated with either colonization or infection. Antimicrobial resistance genes, plasmid replicons, and whole ESBL-plasmids were shared between isolates regardless of chromosomal relatedness. Our study suggests that patients colonized with ESBL-producers may act as durable reservoirs for ongoing transmission of ESBLs, and that they are at prolonged risk of recurrent infection with colonizing strains.

Spatiotemporal dissemination of ESBL-producing Enterobacterales in municipal sewer systems: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The contribution of community and hospital sources to the transmission of extended-spectrum ß-lactamase producing Enterobacterales (ESBL-PE) remains elusive. Aim: To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel. Methods: Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites, n = 17) or community and hospital wastewater (mixed sites, n = 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification. Results: Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates, Escherichia coli (85%, 1,140/1,334) and Klebsiella pneumoniae (11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with E. coli consistently predominating. The proportion of K. pneumoniae isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of E. coli was higher in samples from urban sites (p = 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 102 vs. 1.6 × 102 CFU/mL). E. coli-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21). Conclusion: ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent.

Investigación en fisuras faciales: quo vadis España? / Investigation in facial fissures: quo vadis Spain?

Las fisuras orofaciales representan un grupo heterogéneo de malformaciones congénitas que afectan a distintas estructuras de la cavidad oral y de la cara. Globalmente, los bebés con estos trastornos presentan una mayor morbilidad y mortalidad a lo largo de su vida en comparación con individuos no afectados. Por ello, los avances en la investigación biomédica resultan ineludibles. Así, el objetivo general de este trabajo fue llevar a cabo una revisión bibliográfica para analizar narrativamente los 10 principales estudios primarios sobre fisuras orofaciales llevados a cabo en España, publicados del 2018 hasta la actualidad. Según esto, a nivel institucional, destaca la Universidad Complutense de Madrid (UCM) con cuatro artículos publicados por el grupo de investigación UCM 920202. También sobresale la Universidad Rey Juan Carlos de Madrid, con tres artículos relacionados con diferentes aspectos de la personalidad y la calidad de vida de los pacientes fisurados, así como otras muchas variables cognitivo-emocionales. En relación con la Universidad de Valencia, encontramos dos artículos llevados a cabo en amplias muestras de pacientes con fisuras. Por último, en Barcelona resulta destacable un estudio observacional sobre problemas otorrinolaringológicos en pacientes operados de fisura palatina. En conclusión, si bien en los últimos años se han publicado varios artículos sobre distintos aspectos relacionados con las fisuras, aún queda mucho trabajo por hacer. España debería seguir potenciando proyectos con líneas de trabajo centradas en estas alteraciones del desarrollo craneofacial. Se necesitan estudios amplios, multicéntricos y colaborativos, para ahondar en los mecanismos etiológicos y, en última instancia, en las posibles herramientas para su prevención. Del mismo modo, se necesitan ayudas para dilucidar mejor las cuestiones relacionadas con los tratamientos en todas las dimensiones de la salud, preferentemente a partir de ensayos clínicos controlados aleatorizados, que faciliten la traslación de conocimientos y su accesibilidad universal dentro del sistema sanitario público español.

SUMMARY: Orofacial clefts represent a heterogeneous group of congenital malformations affecting different structures of the oral cavity and face. Overall, infants with these disorders have a higher lifetime morbidity and mortality compared to unaffected individuals. Therefore, advances in biomedical research are unavoidable. Thus, the overall objective of this work was to conduct a literature review to narratively analyse the 10 main primary studies on orofacial clefts carried out in Spain, published from 2018 to date. According to this review, at an institutional level, the Complutense University of Madrid (UCM) is notable with 4 articles published by the UCM 920202 research group. The Rey Juan Carlos University of Madrid also stands out, with three papers related to different aspects of the personality and quality of life of cleft patients, as well as many other cognitive-emotional variables. In relation to the University of Valencia, we found two studies carried out on large samples of cleft patients. Finally, in Barcelona, an observational study on otorhinolaryngological problems in cleft palate patients is noteworthy. In conclusion, although several studies have been published in recent years on different aspects related to clefts, there is still much work to be done. Spain should craniofacial development. Large, multicenter and collaborative studies are needed to delve deeper into the aetiological mechanisms and, ultimately, into the possible tools for their prevention. Similarly, support is needed to better elucidate questions related to treatments in all dimensions of health, preferably randomised controlled clinical trials, which facilitate the transfer of knowledge and its universal accessibility within the Spanish public health system.

Prevalence of retromolar foramen in nineteenth century Spanish population.

Among the non-metrical variants of the mandible that have been proven to be a key issue for dental practitioners, the retromolar foramen constitutes one of the most controversial details regarding its prevalence and associated variables. Thus, this study evaluated the prevalence of the retromolar foramen and the variables associated with its presence in a large Spanish collection of human dry mandibles from the nineteenth century. Six hundred Spanish human dry mandibles (1200 sides) belonging to an osteology collection were examined. The presence of teeth, the presence or absence of retromolar foramen, as well as its side, diameter, number, and location were evaluated. Descriptive analysis and analysis of the associations between the variables were performed. The retromolar foramen was observed in 184 mandibles (31%) and was predominantly present unilaterally (60.8%). Most mandibles (54.9%) had a single foramen. The most common location was the retromolar trigone region (84%). On analysis of the association of variables, it was observed a strong association (p < 0.001) between the presence or absence of the foramen and the presence of teeth. Moreover, a significant association was also found between sex vs. presence of teeth (p = 0.033), sex vs. presentation side of the foramen (p = 0.028), sex vs. number of foramina found (p = 0.004), and diameter vs. number of foramina found (p < 0.001). This study reveals that the retromolar foramen showed a high prevalence of 31% in nineteenth century Spaniards and was located primarily in the retromolar trigone, suggesting that dentists should be aware of and consider the relevant findings of this study.

Study of the functional relationships between the buccinator muscle and the connective tissue of the cheek in humans.

BACKGROUND: The buccinator muscle derives from the mesenchyme of the second pharyngeal arch. In adults, it has a quadrilateral shape, occupying the deepest part of the cheek region. Its function is complex, being active during swallowing, chewing, and sucking. To our knowledge, there are no studies that have specifically analyzed the relationship of the buccinator muscle fibers and neighboring connective tissue of the cheek in humans, neither during development nor in adults. Such relationships are fundamental to understand its function. Thus, in this study the relations of the buccinator muscle with associated connective tissue were investigated. METHODS: The buccinator muscle region was investigated bilaterally in 41 human specimens of 8-17 weeks of development. Moreover, four complete adult tissue blocks from human cadavers (including mucosa and skin) were obtained from the cheek region (between the anterior border of the masseter muscle and the nasolabial fold). All samples were processed with standard histological techniques. In addition, subsets of sections were stained with picrosirius red (PSR). Furthermore, immunoreactivity against type I and III collagen was also studied in adult tissues. RESULTS: The buccinator muscle showed direct relationships with its connective tissue from 8 to 17 weeks of development. Collagen fibers were arranged in septa from the submucosa to the skin through the muscle. These septa were positive for type I collagen and presented elastic fibers. Fibrous septa that were positive for type III collagen were arranged from the lateral side of the muscle to the skin. CONCLUSIONS: The intimate relationship between buccinator muscle fibers and cheek connective tissue may explain the complex functions of this muscle.

Mast cells impair melanoma cell homing and metastasis by inhibiting HMGA1 secretion.

Metastatic disease is the major cause of death from cancer. From the primary tumour, cells remotely prepare the environment of the future metastatic sites by secreted factors and extracellular vesicles. During this process, known as pre-metastatic niche formation, immune cells play a crucial role. Mast cells are haematopoietic bone marrow-derived innate immune cells whose function in lung immune response to invading tumours remains to be defined. We found reduced melanoma lung metastasis in mast cell-deficient mouse models (Wsh and MCTP5-Cre-RDTR), supporting a pro-metastatic role for mast cells in vivo. However, due to evidence pointing to their antitumorigenic role, we studied the impact of mast cells in melanoma cell function in vitro. Surprisingly, in vitro co-culture of bone-marrow-derived mast cells with melanoma cells showed that they have an intrinsic anti-metastatic activity. Mass spectrometry analysis of melanoma-mast cell co-cultures secretome showed that HMGA1 secretion by melanoma cells was significantly impaired. Consistently, HMGA1 knockdown in B16-F10 cells reduced their metastatic capacity in vivo. Importantly, analysis of HMGA1 expression in human melanoma tumours showed that metastatic tumours with high HMGA1 expression are associated with reduced overall and disease-free survival. Moreover, we show that HMGA1 is reduced in the nuclei and enriched in the cytoplasm of melanoma metastatic lesions when compared to primary tumours. These data suggest that high HMGA1 expression and secretion from melanoma cells promote metastatic behaviour. Targeting HMGA1 expression intrinsically or extrinsically by mast cells actions reduce melanoma metastasis. Our results pave the way to the use of HMGA1 as anti-metastatic target in melanoma as previously suggested in other cancer types.

Herramienta Entornos de Vida: innovación en el análisis participativo de salud con enfoque de equidad / Entornos de Vida tool: innovation in participatory health analysis with an equity approach

Los gobiernos municipales tienen capacidad para abordar los determinantes sociales de la salud que actúan sobre sus territorios. La estrategia de acción local en red de la Comunitat Valenciana promueve un abordaje intersectorial, participativo y con enfoque de equidad de las desigualdades en salud resultantes de la distribución de estos determinantes en los barrios y municipios. Para orientar la acción local en salud se requieren metodologías que recojan los conocimientos y las experiencias de la comunidad, y que favorezcan su participación en todas las etapas de la acción. Esta nota metodológica expone cómo llevar a cabo el proceso de evaluación de un territorio aplicando la herramienta Entornos de Vida. Este instrumento permite analizar los barrios y municipios identificando de forma específica y operativa cómo sus características impactan en la salud y en el bienestar de las personas que los habitan.(AU)

Municipal governments have the capacity to tackle the social determinants of health that play a role in their territories. The Valencian Community's local health action strategy promotes an intersectoral, participatory and equity-oriented approach to health inequalities affecting neighborhoods and municipalities across the region. To guide local health action, there is a need to adopt methodologies that capture community-based knowledge and experiences, encouraging community engagement at all stages. This article presents a methodology to carry out a local health needs assessment applying the Entornos de Vida tool. This tool enables the analysis of neighborhoods and municipalities through identifying how their characteristics have an impact on the health and well-being of their inhabitants. (AU)

Craniofacial and three-dimensional palatal analysis in cleft lip and palate patients treated in Spain.

Growth alterations have been described in patients operated on for oral clefts. The purpose of this work was to analyze the craniofacial and palate morphology and dimensions of young adults operated on for oral clefts in early childhood in Spain. Eighty-three patients from eight different hospitals were divided into four groups based on their type of cleft: cleft lip (CL, n = 6), unilateral cleft lip and palate (UCLP, n = 37), bilateral cleft lip and palate (BCLP, n = 16), and cleft palate only (CPO, n = 24). A control group was formed of 71 individuals. Three-dimensional (3D) digital models were obtained from all groups with an intraoral scanner, together with cephalometries and frontal, lateral, and submental facial photographs. Measurements were obtained and analyzed statistically. Our results showed craniofacial alterations in the BCLP, UCLP, and CPO groups with an influence on the palate, maxilla, and mandible and a direct impact on facial appearance. This effect was more severe in the BCLP group. Measurements in the CL group were similar to those in the control group. Cleft characteristics and cleft type seem to be the main determining factors of long-term craniofacial growth alterations in these patients. Prospective research is needed to clearly delineate the effects of different treatments on the craniofacial appearance of adult cleft patients.

Persistence with daily growth hormone among children and adolescents with growth hormone deficiency in the UK.

Background: Children with growth hormone deficiency (GHD) are treated with daily somatropin injections; however, poor treatment persistence and adherence have been recognized previously and have been shown to negatively impact growth outcomes. A recent real-world study of a US pediatric GHD population found that a substantial proportion of children discontinued somatropin therapy, but similar data for a real-world UK population are lacking. Objectives: To describe the discontinuation of, and persistence with, daily somatropin treatment among children with GHD in the UK. Methods: This was a retrospective cohort study of children (≥3 and <16 years old) with ≥1 medication prescription for daily injectable somatropin from 1 July 2000 to 31 December 2020 in the IQVIA Medical Research DATA (IMRD) database. Early persistence was defined as the proportion of children prescribed ≥1 somatropin refill (≥2 prescriptions). Discontinuation was defined as the first date at which a medication gap for somatropin (of >60 or >90 days between prescriptions) occurred. Kaplan-Meier methods were used to evaluate persistence (non-discontinuation) over time to assess time to first discontinuation event. Cox proportional hazards models were used to evaluate the relationship between patient characteristics and time to medication discontinuation. Results: Among the cohort identified in this study (n = 117), the majority (n = 84, 71.8%) had 48 months of available follow-up; 56.4% were boys and the mean (median) age was 8.6 (8.0) years. About 98% exhibited early persistence, but persistence over the follow-up period decreased with follow-up duration. Using the conservative 90-day gap definition of persistence, an estimated 72.4%, 52.8%, and 43.3% were persistent at 12, 36, and 48 months. Lower persistence rates were observed using the 60-day definition. No significant patient predictors of time to discontinuation were identified. Conclusions: Despite high early persistence with somatropin, a high percentage of children with GHD were increasingly non-persistent over time. More than 1 in 4 were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months of follow-up. These results suggest that strategies to support improved medication-taking behavior among children with GHD in the UK are warranted.

[Entornos de Vida tool: innovation in participatory health analysis with an equity approach]. / Herramienta Entornos de Vida: innovación en el análisis participativo de salud con enfoque de equidad.

Municipal governments have the capacity to tackle the social determinants of health that play a role in their territories. The Valencian Community's local health action strategy promotes an intersectoral, participatory and equity-oriented approach to health inequalities affecting neighborhoods and municipalities across the region. To guide local health action, there is a need to adopt methodologies that capture community-based knowledge and experiences, encouraging community engagement at all stages. This article presents a methodology to carry out a local health needs assessment applying the Entornos de Vida tool. This tool enables the analysis of neighborhoods and municipalities through identifying how their characteristics have an impact on the health and well-being of their inhabitants.

Pharmaceutical care at discharge for patients with feeding tubes.

Introduction: Objective: to assess and analyse a medication adaptation pathway for feeding tube administration followed by clinical pharmacists for patients at discharge, and to analyse the level of physician acceptance of the recommendations issued by pharmacists in pharmaceutical care reports to improve patient therapy. Methods: a multidisciplinary protocol for treatment adaptation to feeding tube administration at discharge was implemented in a 350-bed hospital during 2019, in which pharmacists prepared feeding tube medication-adaptation reports during pharmaceutical care visits. The number of recommendations related to adaptation of a drug to route of administration was recorded and classified as need for change of active substance or change of pharmaceutical form. Physician acceptance of pharmacist recommendations was analysed in a one-year retrospective observational study. Results: a total of 66 pharmaceutical care visits were recorded for 57 patients (1.2 visits per patient). In 47 of these 66 visits (71.2 %), at least one drug modification was required in a patient prescription, and the median number of drugs per patient needing to be modified was 2. Overall, 93 of the 489 prescribed drugs (19.0 %) required some changes to be suitable for administration via feeding tube: change of active substance in 52.7 % (49/93) of cases, and change of pharmaceutical form in 47.3 % (44/93) of cases. The physicians' level of acceptance of recommendations was 43.0 % (40/93), and change of pharmaceutical form was less accepted than change of active substance. Conclusion: the inclusion of clinical pharmacists in multidisciplinary teams leads to an improvement in adapting medication to feeding tube administration, but also shows a lack of communication or understanding of pharmacist recommendations by physicians resulting in a low rate of prescription changes.

Introducción: Objetivo: evaluar y analizar un circuito de adaptación de la medicación para la administración por sonda de alimentación llevado a cabo por farmacéuticos clínicos para pacientes al alta, y analizar el nivel de aceptación por parte de los médicos de las recomendaciones emitidas por los farmacéuticos en los informes de atención farmacéutica para mejorar la terapia de los pacientes. Métodos: durante el año 2019 se implementó en un hospital de 350 camas un protocolo multidisciplinario de adaptación del tratamiento para la administración por sonda de alimentación al alta, en el cual los farmacéuticos elaboraron informes de adaptación de la medicación por sonda de alimentación durante las visitas de atención farmacéutica. Se registró el número de recomendaciones relacionadas con la adecuación del fármaco a la vía de administración y se clasificaron como necesidad de cambio de principio activo o cambio de forma farmacéutica. La aceptación de las recomendaciones de los farmacéuticos por parte de los médicos se analizó en un estudio observacional retrospectivo de un año. Resultados: se registraron un total de 66 visitas de atención farmacéutica para 57 pacientes (1,2 visitas por paciente). En 47 de estas 66 visitas (71,2 %) se requirió al menos una modificación de medicamentos en la prescripción de los pacientes, y la mediana de medicamentos por paciente que necesitaban modificarse fue de 2. En total, 93 de los 489 medicamentos prescritos (19,0 %) requirió algunos cambios para ser aptos para la administración por sonda: cambio de principio activo en el 52,7 % (49/93) de los casos y cambio de forma farmacéutica en el 47,3 % (44/93) de los casos. El nivel de aceptación de las recomendaciones por parte de los médicos fue del 43,0 % (40/93), siendo menos aceptado el cambio de forma farmacéutica que el cambio de principio activo. Conclusión: la inclusión de farmacéuticos clínicos en equipos multidisciplinarios conduce a una mejora en la adaptación de la medicación a la administración por sonda de alimentación, pero también muestra que existe una falta de comunicación o comprensión de las recomendaciones de los farmacéuticos por parte de los médicos, lo que resulta en una baja tasa de cambios en la prescripción.

Quality of life and satisfaction of patients two years after endodontic and dental implant treatments performed by experienced practitioners.

OBJECTIVES: To compare oral health related quality of life (OHRQoL) and patients´ satisfaction with root canal treatment (RCT) and dental implant (DI) therapy performed by experienced practitioners. METHODS: Patients with both an RCT and a DI performed respectively by an endodontist and an oral surgeon with more than 15 years of experience two years prior to the study were included. The survival and satisfactory outcome of both treatments were verified with clinical and radiographic data. Participants completed two constructed questionnaire (one for each treatment). OHRQoL assessment included 24 items (OHIP-14 plus other relevant 10 items from the original OHIP-49 questionnaire). Satisfaction regarding duration, cost and pain (both during and after treatment) of treatment was assessed with a 0-10 scale and perceptions with true/false questions. Weighted sums for each dimension, total OHIP scores, prevalence of impact and general satisfaction of patients were then calculated for DI and RCT and compared using the Wilcoxon test for related samples. Patients´ perceptions were compared with Chi-square test. RESULTS: Total OHIP scores were low for both treatments (8.82 and 7.87, respectively for RCT and DI). No significant differences were detected in OHIP total score or any dimension, except for physical pain (significantly higher for RCT than DI (p=0.044)). All patients were satisfied with both treatments; however, patients recalled that pain during treatment was significantly worse for RCT than DI (p=0.003). CONCLUSIONS: High long-term OHRQoL and satisfaction is expected with either DI or RCT performed by experienced practitioners; however, physical pain dimension is higher for RCT. CLINICAL SIGNIFICANCE: This study demonstrated a high satisfaction and long-term quality of life of patients undergoing both DI and RCT if treatments provide a functional balance and are performed by experienced practitioners. Very importantly, all participants had received both treatment modalities and being their own control eliminates individual variability.