The Puerto Rico community engagement alliance (PR-CEAL) against COVID-19 disparities: outreach and research engagement efforts in disproportionately affected communities.

In September 2020, the National Institutes of Health acted in response to the COVID-19 pandemic, recognizing the critical need to combat misinformation, particularly in communities disproportionately affected by the crisis. The Community Engagement Alliance (CEAL) emerged as an initiative dedicated to fostering reliable, science-based information, diversity, and inclusion; aiming to implement effective strategies to mitigate the spread of COVID-19 nationwide. One of the teams participating in this initiative is Puerto Rico-CEAL (PR-CEAL). Our whose goal was to raise awareness about the coronavirus disease and advance research, mainly focusing on vulnerable and underserved populations. This concept paper seeks to outline PR-CEAL's infrastructure during its initial two cycles, providing insights into the research and community engagement activities designed to enhance prevention, counter misinformation, and foster awareness and uptake of COVID-19 vaccines. Ultimately, our objective is to reflect on the strengths and challenges encountered thus far as we endeavor to sustain this robust infrastructure, addressing ongoing public health issues with a forward-looking approach.

Trust in information sources during the COVID-19 pandemic and its association with vaccine trust among a sample of Hispanic adults.

BACKGROUND: Public response to the COVID-19 pandemic has underscored the importance of trust, particularly among minority populations. Several factors might affect vaccine safety trust, including source trustworthiness. Using data from the Puerto Rico Community Engagement Alliance, we assessed the association between trust in information sources and the COVID-19 vaccine in a sample of Hispanic adults. METHODS: A cross-sectional survey-based study was conducted from November 2021 to March 2022. Participants were telephone-interviewed to assess sociodemographic, clinical, and COVID-19-related variables. Vaccine trust was assessed by how confident respondents were regarding COVID-19 vaccine safety. Trust in COVID-19 information sources was assessed by asking respondents how much they trusted selected sources of information to provide accurate information about COVID-19, including the US and Puerto Rico governments, Centers for Disease Control and Prevention (CDC), health care professionals, and traditional media (television/radio/newspaper/internet). Logistic regression models estimated the odds ratio (OR, 95% CI) of COVID-19 vaccine trust based on trust in information sources. RESULTS: A total of 200 adults aged ≥21 years completed the telephone interview. While most of the study sample (97.5%) had been inoculated with at least one dose of the COVID-19 vaccine, 86% trusted in the COVID-19 vaccine's safety. After adjusting for age and sex, participants who attested greater trust in their healthcare professionals (OR=1.99, 95% CI=0.71, 5.62), the US government (OR=2.44, 95% CI=0.69, 8.68), and the CDC (OR=8.18, 95% CI=2.97, 22.57) reported increased vaccine trust as compared to those not having great confidence in these entities. CONCLUSION: These findings support that trust in information provided by the CDC is positively associated with COVID-19 vaccine trust. Acknowledging predictors of trust regarding COVID-19 vaccination could help address factors that affect vaccine confidence. In turn, it strengthens COVID-19 prevention efforts, benefiting common welfare, reducing health disparities, and aiding underserved populations.

Real-World Use of Hybrid Closed-Loop Systems during Diabetes Camp: A Preliminary Study for Secure Configuration Strategies in Children and Adolescents.

The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.

Cervical Pap screening among women living with HIV in Puerto Rico and the United States - Medical Monitoring Project, 2018-2021.

Our objective was to determine the prevalence of cervical Pap screening among women living with HIV (WLWH) in Puerto Rico (P.R.) and other selected United States (U.S.) jurisdictions. Additionally, we sought to compare selected characteristics of WLWH who underwent cervical Pap screening between P.R. and the other U.S. jurisdictions. We analyzed data from the 2018-2021 cycles of CDC's Medical Monitoring Project (MMP), a national surveillance system among adults with HIV residing in P.R. (n = 218) and 22 other MMP jurisdictions (n = 3,653). Weighted percentages and 95 % confidence intervals (CIs) for selected characteristics were estimated. Prevalence ratios with predicted marginal means were calculated. An estimated 91.6 % and 84.6 % of WLWH underwent cervical Pap screening in P.R. and the other 22 MMP jurisdictions, respectively (Prevalence Ratio = 1.08, 95% CI = 1.03-1.13). Among WLWH who underwent cervical Pap screening, those in P.R. were more likely to be 50+ years of age, have a household annual income below $20,000, engage in binge drinking, never smoke, and have Medicaid/other public insurance than those in the other 22 MMP jurisdictions (p < 0.05). No differences were found between P.R. and the other 22 MMP jurisdictions in the percentage reporting higher than the median HIV-stigma score, experiencing HIV health care discrimination, and having ≥ 1 sexual partner in the past 12 months. Although cervical Pap screening rates among WLWH were higher in P.R. than in the other 22 MMP jurisdictions, both surpass the Healthy People 2030 target. Future research should assess adherence and compliance with updated cervical cancer screening guidelines.

[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.

Anal cancer risk and HPV infection knowledge and awareness among Hispanic persons living with HIV in Puerto Rico.

Background: Persons living with HIV (PLWH) have a higher risk of persistent infection with human papillomavirus (HPV) and anal cancer. We evaluated knowledge and awareness of HPV infection and risk factors for anal cancer among PLWH in Puerto Rico (PR). Methods: Data from a cross-sectional study (2020-2021) were analyzed (n=212). Inclusion criteria included PLWH, aged ≥ 26 years, and living in PR. Telephone interviews collected information on sociodemographic, lifestyle and clinical characteristics. Two 13-item scales were used to assess knowledge of HPV and anal cancer risk factors; adequate knowledge for both scales were defined as scoring >70%. Logistic regression models using generalized linear models were used to determine the association between 1) HPV infection awareness, 2) HPV infection knowledge, and 3) Anal cancer risk factors knowledge. Results: The median age was 54 years (IQR: 46,58), 67.5% were male, 71.7% reported having an income <$20,000, and 54.3% had an education level of more than high school. HPV awareness was high (82.1%), but only 40.2% and 3.8% had adequate knowledge of HPV and anal cancer risk factors, respectively. In adjusted logistic regression models, men who have sex with men (OR: 1.26, 95%CI: 1.07-1.47) and women (OR: 1.35, 95%CI: 1.15-1.59) aged ≥50 years had higher odds of HPV awareness than heterosexual men in that age group. Moreover, those with history of anal Pap test aged <50 years had more HPV awareness (OR 1.34, 95%CI: 1.08-1.66) than their counterparts. Adequate HPV knowledge was higher among participants with an education level of more than high-school (OR:1.28, 95%CI: 1.10-1.50) and with a history of HPV diagnosis (OR:1.33, 95%CI: 1.08-1.65) than their counterparts. In addition, people with good/very good/excellent health perception had higher odds of HPV knowledge (OR:1.23, 95%CI: 1.03-1.47) than those who reported poor/regular health perception. For anal cancer risk factors, PLWH for ≥15 years had increased odds of having adequate knowledge (OR:1.07, 95%CI: 1.02-1.14) than their counterparts. Conclusions: Despite high awareness of HPV, limited knowledge about HPV and anal cancer risk factors was observed among PLWH. Results from our study highlight the need for educational efforts within this population as an anal cancer prevention strategy.

Association of body mass index with anal human papillomavirus infection and histologically confirmed high-grade squamous intraepithelial lesions in people who receive services at the Anal Neoplasia Clinic in Puerto Rico.

Objective: This study aimed to assess the association of body mass index (BMI) with anal high-risk human papillomavirus (HR-HPV) and biopsy-confirmed histologic anal high-grade squamous intraepithelial lesions (HSIL) among a clinic-based sample of Hispanics in Puerto Rico. Methods: This cross-sectional study evaluated medical records of adults who received services at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center between October 2014 and December 2022. The study included 543 records with complete clinical information regarding anal HR-HPV and anal HSIL status. Chi-square and logistic regression analyses were performed. Results: Mean age of participants was 44.10 ± 13.24 years, 65.2% were men, 71.7% were HIV-infected, 74.4% had anal HR-HPV infection, and 37.9% had biopsy-confirmed HSIL. Regarding BMI, 2.4% were underweight, 31.9% normal weight, and 39.0 % overweight; while 17.3 % had class I, 5.2% class II, and 4.2% class III obesity. No significant association was observed between BMI and anal HR-HPV infection in adjusted analyses. Lower odds of anal HSIL were observed among overweight individuals (OR: 0.63, 95% CI: 0.41 - 0.99) and those with class II/III obesity (OR: 0.48, 95% CI: 0.22 - 1.01) compared to adults with underweight/normal BMI, after adjusting for potential confounders. No significant association was observed for class I obesity. Conclusion: BMI was not associated with anal HR-HPV infection. Overweight and obese individuals had lower odds of having anal HSIL than adults with underweight/normal BMI. This finding could suggest underdiagnosis of HSIL among overweight/obese individuals, or reduced risk in this group.

Cell type specific roles of FOXP1 during early neocortical murine development.

Cortical development is a tightly controlled process and any deviation during development may increase the susceptibility to neurodevelopmental disorders, such as autism spectrum disorders (ASD). Numerous studies identified mutations in FOXP1, a transcription factor enriched in the neocortex, as causal for ASD and FOXP1 syndrome. Our group has shown that Foxp1 deletion in the mouse cortex leads to overall reduced cortex thickness, alterations in cortical lamination, and changes in the relative thickness of cortical layers. However, the developmental and cell type-specific mechanisms underlying these changes remained unclear. This work characterizes the developmental requirement of neocortical Foxp1 at key embryonic and perinatal ages using a conditional knock-out of Foxp1. We find that Foxp1 deletion results in accelerated pseudo-age during early neurogenesis, increased cell cycle exit during late neurogenesis, altered gene expression and chromatin accessibility, and selective migration deficits in a subset of upper-layer neurons. These data explain the postnatal differences observed in cortical layers and relative cortical thickness. We also highlight genes regulated by FOXP1 and their enrichment with high-confidence ASD or synaptic genes. Together, these results underscore a network of neurodevelopmental disorder-related genes that may serve as potential modulatory targets for postnatal modification relevant to ASD and FOXP1 syndrome.

Exercise in cancer patients: assistance levels and referral pathways-a position statement from the Spanish Society of Medical Oncology.

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients.

Presymptomatic Testing for Huntington's Disease in Mexico: 28 Years of Experience.

INTRODUCTION: Huntington's disease (HD) is a genetic neurodegenerative disorder with dominant inheritance. Our center in Mexico City has offered presymptomatic testing (PT) since 1995. OBJECTIVE: To describe the main clinical and demographic characteristics of at-risk HD individuals who applied to the PT program, the reasons for seeking it, and the molecular results. METHODS: A cross-sectional study was conducted with sociodemographic and clinical data of all PT applicants from 1995-2023. Reasons for seeking PT were assessed using a modified questionnaire. In addition, anxiety, and depressive symptoms before and after PT were evaluated with Beck's instruments; cognitive impairment (CI) was assessed with the Mini-Mental State Examination (MMSE) and molecular results. RESULTS: 214 people applied for PT (2.1% of the at-risk population identified in our center); 63% were women (mean age of 37.11 years). 204 (95.3%) were accepted and 190 received results. 70% indicated that the main reason for applying for PT was to inform their offspring about the risk of inheriting HD. Significant differences were observed in the reasons for seeking PT by age group. Although some subjects received treatment, Beck's instrument scores did not indicate special attention or pharmacological treatment. The MMSE showed probable CI in 20 subjects. Of those who received results, 37% were carriers of a full penetrance allele. CONCLUSION: Our center has the only formal PT program for HD in Mexico. The reasons for seeking PT are varied and age-related. Although PT is offered to all subjects at risk for HD, uptake remains low.

Protecting Caribbean patients diagnosed with cancer from compounding disasters.

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions.

Treatment Interruptions and Mortality among Puerto Rican Women with Gynecologic Cancers in Puerto Rico after Hurricanes Irma and María: A Retrospective Cohort Study.

OBJECTIVE: Cancer patients are among the most vulnerable populations during and after a disaster. We evaluated the impact of treatment interruption on the survival of women with gynecologic cancer in Puerto Rico following hurricanes Irma and María. METHODS: Retrospective cohort study among a clinic-based sample of women diagnosed between January 2016-September 2017 (n=112). Women were followed up from their diagnosis until December 2019, to assess vital status. Kaplan-Meier survival curves and Cox proportional hazards models were performed. RESULTS: Mean age was 56 (±12.3) years; corpus uteri (58.9%) was the most common gynecologic cancer. Predominant treatments were surgery (91.1%) and chemotherapy (44.6%). Overall, 75.9% were receiving treatment before the hurricanes, 16.1% experienced treatment interruptions and 8.9% died during the follow-up period. Factors associated with treatment interruption in bivariate analysis included younger age (≤55 years), having regional/distant disease, and receiving >1 cancer treatment (p<0.05). Crude analysis revealed an increased risk of death among women with treatment interruption (HR: 3.88, 95% CI=1.09-13.77), persisting after adjusting for age and cancer stage (HR: 2.49, 95% CI= 0.69-9.01). CONCLUSIONS: Findings underscore the detrimental impact of treatment interruption on cancer survival in the aftermath of hurricanes, emphasizing the need for emergency response plans for this vulnerable population.

Shared Decision-making in Breast Cancer Reconstructive Surgery: Experience in a Leading Hospital.

Background: The paradigm of healthcare has evolved toward patient-centered approaches, where shared decision-making (SDM) plays a pivotal role. This study aimed to explore the implementation of SDM during breast cancer reconstruction consultations and assess its impact on patient satisfaction and the decision-making process as a whole. Methods: A total of 102 female patients undergoing breast reconstruction were included in a multidisciplinary breast pathology unit. A streamlined SDM model involving choice introduction, option description, and preference exploration was implemented. A validated Spanish version of the nine-item Shared Decision Making Questionnaire was used alongside a complementary questionnaire. Data analysis was carried out using electronic data capture software. Results: The nine-item Shared Decision Making Questionnaire results indicate strong agreement in presenting various options and explaining their advantages and disadvantages. Patients were less confident about their participation in decision-making. The Complementary Shared Decision Making Questionnaire highlighted high satisfaction with interview times and language clarity but areas for improvement in consultation space and therapeutic choice participation. Conclusions: Integrating SDM into breast reconstruction consultations empowers patients in the decision-making process and enhances satisfaction. Decision aids prove effective in this context, facilitating patients' comprehension and reducing decisional conflict. There are areas for improvement within the SDM strategy, and they are detectable through scales. Although challenges in information transmission and patient involvement persist, adopting an SDM model has potential benefits that warrant further investigation.

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.

Increased blood draws for ultrasensitive ctDNA and CTCs detection in early breast cancer patients.

Early breast cancer patients often experience relapse due to residual disease after treatment. Liquid biopsy is a methodology capable of detecting tumor components in blood, but low concentrations at early stages pose challenges. To detect them, next-generation sequencing has promise but entails complex processes. Exploring larger blood volumes could overcome detection limitations. Herein, a total of 282 high-volume plasma and blood-cell samples were collected for dual ctDNA/CTCs detection using a single droplet-digital PCR assay per patient. ctDNA and/or CTCs were detected in 100% of pre-treatment samples. On the other hand, post-treatment positive samples exhibited a minimum variant allele frequency of 0.003% for ctDNA and minimum cell number of 0.069 CTCs/mL of blood, surpassing previous investigations. Accurate prediction of residual disease before surgery was achieved in patients without a complete pathological response. A model utilizing ctDNA dynamics achieved an area under the ROC curve of 0.92 for predicting response. We detected disease recurrence in blood in the three patients who experienced a relapse, anticipating clinical relapse by 34.61, 9.10, and 7.59 months. This methodology provides an easily implemented alternative for ultrasensitive residual disease detection in early breast cancer patients.

Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial.

BACKGROUND: Maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib's efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination-deficient tumors. METHODS: OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator's discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator's discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination-deficient. The primary endpoint is the pre-interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1. DISCUSSION: OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination-deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.

Antifibrotic treatment adherence, efficacy and outcomes for patients with idiopathic pulmonary fibrosis in Spain: a real-world evidence study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood. METHODS: An observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected. RESULTS: 232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity. CONCLUSIONS: in this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.

Screening for Delirium During Pediatric Brain Injury Rehabilitation.

OBJECTIVE: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: 144 children (median 10.8 years) with ABI (N=144). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percent compliance with twice daily delirium screening; prevalence of positive delirium screens; trajectories in CAPD scores and their relation with FIM for Children (WeeFIM) scores. RESULTS: Screening was feasible (mean 75% compliance for each of 144 children). Of 16,136 delirium screens, 29% were positive. 62% of children had ≥1 positive screen. Four primary patterns of CAPD trajectories were identified: Static Encephalopathy (10%), Episodic Delirium (10%), Improving (32%), and No Delirium (48%). Validity of these trajectories was demonstrated through association with WeeFIM and CALS outcomes. Younger age at admission was associated with positive delirium screens, and rehabilitation length of stay was significantly longer for the Improving group. CONCLUSIONS: Delirium occurs frequently in children with ABI during inpatient rehabilitation. Routine delirium screening provides clinically relevant information including the potential to facilitate early detection and intervention for medical complications. Longitudinal ratings of delirium symptoms may also have a role in developing a standardized definition for Post Traumatic Confusional State (PTCS) stage of recovery in children.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Ecological and Syntaxonomic Analysis of the Communities of Glebionis coronaria and G. discolor (Malvion neglectae) in the European Mediterranean Area.

Nitrophilous communities dominated by Glebionis coronaria and Glebionis discolor in the European Mediterranean area were studied. The nomenclature was corrected according to the current taxonomy, following the International Code of Phytosociological Nomenclature (ICPN). The statistical analysis revealed six new associations and one subassociation, with four in Spain, one in Greece, and one in Italy. Additionally, a subassociation of high relevance due to its endemic character was identified. These grasslands exhibit requirements for organic matter and other edaphic nutrients that are closer to those of Malva neglecta communities than to those of Hordeum murinum subsp. leporinum. We confirmed the published syntaxon with the rank of Resedo albae-Glebionenion coronariae suballiance and its subordination to the Malvion neglectae alliance, and we established the type association for this suballiance. Sisimbrietalia officinalis J. Tüxen in Lohmeyer et al. 1962 em. Rivas-Martínez, Báscones, T. E. Díaz, Fernández-González & Loidi 1991. Stellarietea mediae Tüxen, Lohmeyer & Preising ex von Rochow 1951.