Low Enrollment Research Articles

Immunotherapy for inflammatory breast cancer: current evidences and future perspectives.

Inflammatory breast cancer (IBC) is the most fatal type presentation of clinical breast cancer. The immune tumor microenvironment (TME) of IBC is characterized by signals of immune evasion but suggests actionable vulnerability to immune-checkpoint inhibitors (ICIs). In this review, we aimed to summarize the most important preclinical evidences of IBC immune-vulnerability and the first data from clinical trials evaluating ICIs in IBC. IBC is characterized by a preexisting active immune TME suppressed by mechanisms of immune-escape, including inhibitory immune-checkpoints, whose expression is higher than in non-IBC. Clinical trials evaluating ICIs in patients with IBC are burdened by slow accrual and low enrollment. Because of the limited data from clinical trials, no conclusions about the activity of ICIs in IBC can be drawn. Ongoing clinical trials are assessing many promising ICI-based combination approaches. An enhanced multicenter collaboration to evaluate ICIs in patients with this aggressive form of disease and to improve clinical outcomes is required.

Prevalence and correlates of adolescent self-injurious thoughts and behaviors: A population-based study in Burkina Faso.

Self-injurious thoughts and behaviors (SITBs) are a growing concern among youth in sub-Saharan Africa, but their prevalence and correlates in this region are poorly understood. We therefore examined self-reported SITBs in a population-representative sample of youth in rural Burkina Faso. We used interviews from 1,538 adolescents aged 12 to 20 years living in 10 villages and 1 town in northwestern Burkina Faso. Adolescents were asked about their experiences with suicidal and nonsuicidal SITBs, adverse environmental factors, psychiatric symptoms, and interpersonal-social experiences. SITBs included lifetime prevalence of life is not worth living, passive suicide ideation, active suicide ideation, and nonsuicidal self-injury (NSSI). After describing SITB prevalence, we ran logistic and negative binomial regression models to predict SITBs. Weighted lifetime SITB prevalence estimates were: 15.6% (95% confidence interval [CI]: 13.7-18.0) for NSSI; 15.1% (95% CI: [13.2, 17.0]) for life is not worth living; 5.0% (95% CI [3.9, 6.0]) for passive suicide ideation; and 2.3% (95% CI [1.6, 3.0]) for active suicide ideation. Prevalence of life is not worth living increased with age. All four SITBs were significantly positively associated with mental health symptoms (depression symptoms, probable posttraumatic stress disorder) and interpersonal-social experiences (peer and social connectedness, physical assault, sexual assault and unwanted sexual experiences). Females were significantly more likely to report that their life was not worth living compared to males (aOR = 0.68; 95% CI [0.48, 0.96]). There is a high prevalence of SITBs among youth in rural Burkina Faso, most notably NSSI and life is not worth living, with interpersonal-social factors being the strongest predictors. Our results highlight the need for longitudinal SITB assessment to understand how risk for SITBs operates in resource-constrained settings, and to design interventions to mitigate risk. Given low school enrollment in rural Burkina Faso, it will be important to consider youth suicide prevention and mental health initiatives that are not school-based.

Tenecteplase: A Review of Its Pharmacology and Uses.

Tenecteplase: A Review of Its Pharmacology and Uses.

The Good, The Bad, What HBCUs Wish They Had: The Benefit of Data Warehouse Technology

In the middle of a technological revolution, we are working in a global market and organizations are all competing to survive. As these organizations try to develop strategies, many have determined that the solution is data. Planning, development, and implementation of data warehouses will provide the infrastructure for organizations to integrate decision support systems and business tools to generate reporting and data visualizations to assist in decision-making. Many organizations are taking advantage of this technology but many are lagging behind, one example is Historical Black Colleges and Universities (HBCU). HBCUs serve a unique population of students that other institutions may not offer an opportunity to. Due to low enrollment and a harsh economy, many institutions struggle with recruitment and retention, and HBCUs struggle more than others. HBCUs lack the data warehouse and decision support systems as their peers. HBCUs would benefit in the area of retention and recruitment if given data warehouse and decision support system technology.

Non-monetary incentives to increase enrollment in payments for environmental services

Abstract Payments for Environmental Services (PESs) are increasingly used to foster farmers’ adoption of greener practices, but their effectiveness is often undermined by low enrollment. In a large randomized field experiment (N = 20,000), we test several non-monetary incentives to increase enrollment into the French implementation of the Agri-Environmental Schemes program of the European Union. We find that sending 10,000 information letters triggers the enrollment of 75 ± 52 farmers at a cost of 102 $\pm\ $71 Euros/new enrollee. Pre-stamped reply forms increase contacts with caseworkers but fail to raise enrollment. Testimonies by other farmers seem to decrease the effectiveness of the letters. Diffusion effects could increase the impact of our non-monetary incentives by 40% to 50% and decrease the cost of an additional enrollee by around 30%.

Faith-based communities’ preferred interventions to improve the participation of black/African-American persons in medical research and clinical trials: A focus group study.

e18648 Background: A variety of interventions within faith-based and medically underserved communities have been utilized to increase racial/ethnic minorities’ participation in health programming and clinical trials. However, the literature lacks studies on which interventions are preferred by church members and leaders to address disparities in clinical trials. Methods: The study utilized focus groups to understand participants’ knowledge and attitudes about medical research/clinical trials and to develop and appraise interventions for and in collaboration with members and leaders of predominately Black/African American faith-based organizations. Participants were recruited by convenience and snowball sampling from organizations involved in the Cleveland Clinic Taussig Cancer Center Community Outreach program’s faith based model called, Stopping Cancer In Its Tracks (SCIIT). Study personnel conducted 6 focus groups at 6 different churches from June through August 2022. Results: 30 participants joined the study. Conversations lasted 90-120 minutes and covered a range of topics. Each group included deep, cathartic sharing about disparities in accessing medical/cancer care and racism, particularly within medicine. Participants explained that low enrollment among Black/African-Americans in clinical trials is a result of everyday and structural racism. Also disparities are linked to the compounded, long-term lack of beneficence or human rights within research and health care for their communities. Accordingly, diversity in clinical trials may improve by creating interventions that address distrust, communication, and information and access gaps, and are tailored to each church. Preferred interventions should: 1) Embody a deep, long-term, relationship-building process. 2) Focus on creating trust by sharing in church services/activities/meals/two-way conversations/cancer screenings. 3) Leverage testimonials from cancer survivors who have participated in clinical trials. The focus groups themselves were felt by participants to be an example of the trust building and knowledge sharing necessary to address disparities. Participants expressed interest to develop interventions in partnership with the study personnel of health care workers. Conclusions: The study fills a gap in the literature by analyzing and amplifying the ideas of Black/African-American church members and leaders from medically underserved communities who generally have been excluded from research. Participants preferred interventions that feature long-term relationship building and engagement. Future research should implement and test the effectiveness of these interventions.

Evolution of Government-funded health insurance for universal health coverage in India.

India has run multiple Government-Funded Health Insurance schemes (GFHIS) over the past decades to ensure affordable healthcare. We assessed GFHIS evolution with a special focus on two national schemes - Rashtriya Swasthya Bima Yojana (RSBY) and Pradhan Mantri Jan Arogya Yojana (PMJAY). RSBY suffered from a static financial coverage cap, low enrollment, inequitable service supply, utilization, etc. PMJAY expanded coverage and mitigated some of RSBY's drawbacks. Investigating equity in PMJAY's supply and utilization across geography, sex, age, social groups, and healthcare sectors depicts several systemic skews. Kerala and Himachal Pradesh with low poverty and disease burden use more services. Males are more likely to seek care under PMJAY than females. Mid-age population (19-50 years) is a common group availing services. Scheduled Caste and Scheduled Tribe people have low service utilization. Most hospitals providing services are private. Such inequities can lead the most vulnerable populations further into deprivation due to healthcare inaccessibility.

Utilizing vancomycin as secondary prophylaxis for the prevention of recurrent Clostridioides difficile infection

Background: Recurrent Clostridioides difficile infection (CDI) is associated with significant morbidity, mortality, and healthcare-related costs. Although data are minimal, agents including oral vancomycin have been used as secondary prophylaxis to prevent recurrent CDI. Methods: We conducted a randomized, double-blind, placebo-controlled trial to determine the effectiveness of vancomycin at preventing CDI from October 2019 to September 2022. Eligible patients had a history of at least 1 episode of CDI and were receiving systemic antibiotics for another condition. Participants were randomized 1:1 to oral vancomycin 125 mg by mouth twice daily and were interviewed at 1, 2, and 3 months thereafter to assess recurrence. We enrolled 26 patients: 15 completed the 1-month interview, 12 completed the 2-month interview, and 11 completed the full study. Those 15 participants who did not complete the 3-month interview were considered dropouts. The final sample for this study included those 11 participants who completed all interviews. Demographics and outcomes are shown in Table 1. Results: One case of recurrent CDI was reported at the 1-month interview and a second was reported at 3 months; both cases had received the placebo. The study was terminated early due to low enrollment. Conclusions: Although our results did not reach statistical significance and this study was limited in small sample size, our findings suggest that secondary prophylaxis with oral vancomycin may be beneficial in patients who are actively receiving antibiotics, which is consistent with prior retrospective studies. Future studies with larger sample sizes are still needed to examine this important question of whether secondary prophylaxis is useful for preventing recurrent CDI.Disclosure: None

Safety of checkpoint inhibitors in older patients with genitourinary cancers.

12059 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients with genitourinary (GU) cancers however many of the clinical trials that have led to the approval of ICIs in GU cancers often have low enrollments of older patients aged 65 and above for which safety data in this cohort is limited. Methods: A retrospective study was performed that included all patients aged 65 and older with kidney, bladder, and upper tract urothelial carcinoma (UTUC), who were treated at the University of Florida Health Cancer Center between January 2018 and September 2022, and received at least one dose of ICI (pembrolizumab, nivolumab, ipilimumab with nivolumab, avelumab, or atezolizumab). Data was collected on all documented immune related adverse events (irAEs) that were deemed attributable to the checkpoint inhibitor by the treating provider. The grading of toxicities was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: We identified a total of 139 patients who met the inclusion criteria of our study. The ages of patients ranged from 65 to 93 and the median age was 74. Females accounted for 31 patients (22%) while 108 patients (78%) were male. There were 56 patients (40%) with bladder cancer, 58 patients (42%) with kidney cancer, and 25 patients (18%) with UTUC. An irAE was documented in 76 patients (55%) while 63 patients (45%) had no documented irAE. Patients were categorized by the highest grade of toxicity experienced. A Grade 1 toxicity was found in 15 patients (11%), while a grade 2 toxicity was found in 41 patients (29%), with 18 patients (13%) having a grade 3 toxicity, and 2 patients (1%) experiencing a grade 4 toxicity. There were no documented grade 5 toxicities, i.e. no deaths were directly attributed to treatment. We found that 27 patients (19%) required either oral or intravenous steroids to manage their irAE. Discontinuation of treatment due to an irAE was observed in 16 patients (12%). Inpatient hospitalization due to an irAE occurred in 12 patients (9%). Conclusions: Our study demonstrates that the majority of patients aged 65 and older either have no irAEs or developed mild irAEs when treated with ICIs. Severe and life-threatening adverse events are uncommon, rarely require hospital admission, and did not lead to any deaths. This study should help to provide valuable information on the safety of checkpoint inhibitors in older patients with GU cancers and assist in the shared decision-making process for cancer treatment. [Table: see text]

Estimated Costs of Intervening in Health-Related Social Needs Detected in Primary Care

Health-related social needs are increasingly being screened for in primary care practices, but it remains unclear how much additional financing is required to address those needs to improve health outcomes. To estimate the cost of implementing evidence-based interventions to address social needs identified in primary care practices. A decision analytical microsimulation of patients seen in primary care practices, using data on social needs from the National Center for Health Statistics from 2015 through 2018 (N = 19 225) was conducted. Primary care practices were categorized as federally qualified health centers (FQHCs), non-FQHC urban practices in high-poverty areas, non-FQHC rural practices in high-poverty areas, and practices in lower-poverty areas. Data analysis was performed from March 3 to December 16, 2022. Simulated evidence-based interventions of primary care-based screening and referral protocols, food assistance, housing programs, nonemergency medical transportation, and community-based care coordination. The primary outcome was per-person per-month cost of interventions. Intervention costs that have existing federally funded financing mechanisms (eg, the Supplemental Nutrition Assistance Program) and costs without such an existing mechanism were tabulated. Of the population included in the analysis, the mean (SD) age was 34.4 (25.9) years, and 54.3% were female. Among people with food and housing needs, most were program eligible for federally funded programs, but had low enrollment (eg, due to inadequate program capacity), with 78.0% of people with housing needs being program eligible vs 24.0% enrolled, and 95.6% of people with food needs being program eligible vs 70.2% enrolled. Among those with transportation insecurity and care coordination needs, eligibility criteria limited enrollment (26.3% of those in need being program eligible for transportation programs, and 5.7% of those in need being program eligible for care coordination programs). The cost of providing evidence-based interventions for these 4 domains averaged $60 (95% CI, $55-$65) per member per month (including approximately $5 for screening and referral management in clinics), of which $27 (95% CI, $24-$31) (45.8%) was federally funded. While disproportionate funding was available to populations seen at FQHCs, populations seen at non-FQHC practices in high-poverty areas had larger funding gaps (intervention costs not borne by existing federal funding mechanisms). In this decision analytical microsimulation study, food and housing interventions were limited by low enrollment among eligible people, whereas transportation and care coordination interventions were more limited by narrow eligibility criteria. Screening and referral management in primary care was a small expenditure relative to the cost of interventions to address social needs, and just under half of the costs of interventions were covered by existing federal funding mechanisms. These findings suggest that many resources are necessary to address social needs that fall largely outside of existing federal financing mechanisms.

Impact of the human papillomavirus vaccine in low-resource settings

Impact of the human papillomavirus vaccine in low-resource settings

Current state of clinical trials on xenograft.

Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone marrow, aortic valve and kidney xenografts, leading to a clear sorting of efforts made in this field. In December 2022, we searched clinicaltrial.gov for interventional clinical trials related to xenograft of skin, pancreas, bone marrow, aortic valve and kidney. A total of 14 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus. Content of trials was reviewed and summarized. Only 14 clinical trials met our study's criteria. The majority were completed, and most of the trials' enrolment was between 11 and 50 participants. Nine trials used a xenograft of porcine origin. Six trials targeted skin xenotransplantation, four targeted β-cells, two targeted bone marrow and one trial targeted each of the kidney and aortic valve. The average length of trials was 3.38 years. Four trials were conducted in the United States and two trials in each of Brazil, Argentina and Sweden. Of all the included trials, none had any results provided and only three had published work. Phases I, III, and IV had only one trial each. A total of 501 participants were enrolled in these trials. This study sheds the light on the current state of clinical trials on xenograft. Characteristically, trials on this field are of low number, low enrolment, short duration, few related publications and no published results. Porcine organs are the most used in these trials, and skin is the most studied organ. An extension of the literature is highly needed due to the variety of conflicts mentioned. Overall, this study sheds the light on the necessity of managing research efforts, leading to the initiation of more trials targeting the field of xenotransplantation.

WASTAGE AND STAGNATION OF GOVERNMENT PRIMARY SCHOOLS IN MANIPUR: A CRITICAL ANALYSIS

Wastage and stagnation in government primary schools have been persistent concerns in the educational landscape of Manipur. This critical analysis aims to examine the causes and consequences of wastage and stagnation in government primary schools, shedding light on the complex factors that contribute to these issues. Through a comprehensive review of relevant literature and analysis of available data, this study explores the underlying causes of wastage and stagnation in government primary schools in Manipur. Factors such as low enrolment rates, high dropout rates, inadequate infrastructure, teacher shortages, and socio-economic disparities are identified as key contributors to the problem. Additionally, cultural and linguistic factors, lack of parental involvement, and ineffective pedagogical practices are also examined. The consequences of wastage and stagnation in government primary schools are multifaceted and far-reaching. Students who drop out or repeat grades are at a disadvantage in terms of their educational attainment and future prospects. The educational system as a whole suffers from inefficiencies and a lack of skilled human capital. The long-term socio-economic development of Manipur is hindered by the perpetuation of an undereducated workforce. To address these issues, a comprehensive approach is necessary. Strategies such as improving access to quality education, enhancing teacher training and support, strengthening community engagement, and addressing socio-economic disparities are crucial. Furthermore, the development and implementation of evidence-based policies and interventions tailored to the specific needs of Manipur's government primary schools are essential. This critical analysis emphasizes the urgency of addressing wastage and stagnation in government primary schools in Manipur. It highlights the need for collaborative efforts among government bodies, educational institutions, communities, and stakeholders to tackle this complex issue. By investing in the improvement of primary education, Manipur can nurture a generation of well-educated individuals equipped with the skills necessary for their personal growth and the overall development of the state. Further research should focus on evaluating the effectiveness of specific interventions aimed at reducing wastage and stagnation in government primary schools. Longitudinal studies tracking the educational trajectories of students and examining the long-term outcomes of interventions would provide valuable insights into the effectiveness of various strategies.

Spanish teachers’ perceptions about their positive impact on their students to maintain their interest

The shortage of foreign language speakers in the United States has reached alarming levels. While Spanish is the most widely spoken and studied foreign language, it has also been experiencing low enrollments and discontinuation after a short term of study, leading to lack of acquisition of communicative competence, which is essential for fluency in the language. To that end, this mixed-method study, which forms part of a large-scale study on foreign language teachers’ perceptions, investigated Spanish teachers’ perceptions about how they determine if they successfully impact their students to maintain their interest in the language and study it long enough to acquire communicative competence. Findings revealed that the teachers believe that the factors that indicate to them that they have a positive impact on their students to maintain their interest in the language are the students’ interest in their classes and the language, their motivation toward the language, the feedback they provide, teacher–student relationships, and the students’ engagement in classroom activities and academic success. Recommended follow-up studies include an investigation of students’ perceptions to ascertain where the teachers’ and the students’ perceptions coincide and where they differ in order to ensure the successful maintenance of students’ interest in the language.

A Study on the Operation of College Liberal Arts Education for the Improvement of Quantitative Reasoning Competency as Data Literacy

The goal of this study is to suggest the potential and significance of quantitative reasoning education as a college liberal arts program and to come up with methods to improve it. To do so, this study analyzed the case of <Quantitative Reasoning and Computational Thinking> at S National University, presenting its achievements, weaknesses, and improvement plans. From the first semester in 2020, <Quantitative Reasoning and Computational Thinking> at S National University has been offered as a semi-compulsory subject with the purpose of cultivating quantitative reasoning based on quantitative relationships and computational thinking for everyday algorithms. In the class, instructors refrain from using mere problem solving using mathematical and/or scientific formulas, and instead an activity-oriented learning approach is emphasized. This allows for the students to interpret quantitative data based on logical algorithms. According to a survey about this subject, most students were satisfied with its contents and reported that it had helped them solve problems creatively based on quantitative and computational thinking. Nevertheless, various problematic issues such as the low enrollment of students in the humanities and social sciences, the dualization of subject operation between classes, and the difficulty in securing lecturers, were raised. To address these issues, it is necessary for us to expand awareness among students that <Quantitative Reasoning and Computational Thinking> aims to promote thinking ability through the understanding and interpretation of quantitative data. Also, it is important that we have faculties that operate on a consistent basis, so that the courses offered are able to meet the goals of the subject. By applying these improvements, the effort to develop liberal arts subjects that enhance students’ data-driven scientific thinking should be continued.

Exploring implementation outcomes in the clinical trial context: a qualitative study of physician trial stakeholders

IntroductionCancer clinical trials can be considered evidence-based interventions with substantial benefits, but suffer from poor implementation leading to low enrollment and frequent failure. Applying implementation science approaches such as outcomes frameworks to the trial context could aid in contextualizing and evaluating trial improvement strategies. However, the acceptability and appropriateness of these adapted outcomes to trial stakeholders are unclear. For these reasons, we interviewed cancer clinical trial physician stakeholders to explore how they perceive and address clinical trial implementation outcomes.MethodsWe purposively selected 15 cancer clinical trial physician stakeholders from our institution representing different specialties, trial roles, and trial sponsor types. We performed semi-structured interviews to explore a previous adaptation of Proctor’s Implementation Outcomes Framework to the clinical trial context. Emergent themes from each outcome were developed.ResultsThe implementation outcomes were well understood and applicable (i.e., appropriate and acceptable) to clinical trial stakeholders. We describe cancer clinical trial physician stakeholder understanding of these outcomes and current application of these concepts. Trial feasibility and implementation cost were felt to be most critical to trial design and implementation. Trial penetration was most difficult to measure, primarily due to eligible patient identification. In general, we found that formal methods for trial improvement and trial implementation evaluation were poorly developed. Cancer clinical trial physician stakeholders referred to some design and implementation techniques used to improve trials, but these were infrequently formally evaluated or theory-based.ConclusionImplementation outcomes adapted to the trial context were acceptable and appropriate to cancer clinical trial physician stakeholders. Use of these outcomes could facilitate the evaluation and design of clinical trial improvement interventions. Additionally, these outcomes highlight potential areas for the development of new tools, for example informatics solutions, to improve the evaluation and implementation of clinical trials.

A moderated mediation analysis of the low enrollment intention at international higher education in Indonesia

PurposeThis paper aims to analyze the relationship between the brand awareness of an international university operating in Indonesia and enrollment intention serially mediated by brand congruity and brand attitude and moderated by brand experience.Design/methodology/approachA moderated serial mediation model was developed and was tested using the partial least squares structural equation modeling (PLS-SEM) to examine the proposed relationship. There were 132 prospective students involved as respondents.Findings(1) brand awareness may not always directly affect purchase intention; (2) brand congruity and brand attitude serially mediate the relationship between brand awareness and enrollment intention; (3) brand experience may not always moderate the relationship between brand awareness and consumer behavior.Research limitations/implicationsThis paper considers generalizability as its limitation with suggestions to undertake future studies in other settings and the longitudinal and broader scope. Future research could examine other variables to enhance the model.Practical implicationsThis paper also proposes theoretical and managerial implications in higher education branding and marketing.Originality/valueThis study closed the gap in the unsuccessful relationship between brand awareness and behavioral intention that the mediating variables of brand congruity and brand attitude must be serially present. This study also confirmed that brand experience is not empirically suitable as a moderator.

Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis.

Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar® Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials. In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis. Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified. RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis. ClinicalTrials.gov identifier: NCT03320070.

Intramuscular Polydeoxyribonucleotides in Fibrotic and Atrophic Localized Scleroderma: An Explorative Prospective Cohort Study

Effective options in the quiescent, scantily inflammatory phase of localized scleroderma (morphea) are lacking. A cohort study in patients with histologically confirmed fibroatrophic morphea explored the therapeutic value of the anti-dystrophic A2A adenosine agonist polydeoxyribonucleotide (PDRN, one daily 5.625 mg/3 mL ampoule for 90 days with a three-month follow-up). Primary efficacy endpoints: Localized Scleroderma Cutaneous Assessment Tool mLoSSI and mLoSDI subscores for disease activity and damage in eighteen areas; Physicians Global Assessment for Activity (PGA-A) and Damage (PGA-D) VAS scores; skin echography. Secondary efficacy endpoints: mLoSSI, mLoSDI, PGA-A, PGA-D, and morphea areas (photographs) over time; Dermatology Life Quality Index (DLQI); skin biopsy scores and induration over time. Twenty-five patients enrolled; 20 completed the follow-up period. Highly significant improvements at the end of the 3-month treatment period: mLoSSI–73.7%, mLoSDI–43.9%, PGA-A–60.4%, PGA-D–40.3%, with further improvements at follow-up visit for all disease activity and damage indexes. Overall, the outcomes suggest that a daily PDRN ampoule intramuscularly for 90 days reduces disease activity and damage rapidly and significantly in quiescent, modestly inflammatory morphea with few currently therapeutic options. The COVID-19 pandemic and lockdowns caused difficulties in enrollment, and some patients were lost to follow-up. Due to low final enrollment, the study outcomes may have only an exploratory value, yet they appear impressive. The anti-dystrophic potential of the PDRN A2A adenosine agonist deserves further in-depth exploration.

Factors associated with low antiretroviral therapy enrollment of children in the Simiyu region: A cross-sectional Creswell mixed-methods sequential explanatory design.

Despite substantial antiretroviral therapy (ART) coverage in other groups with the human immunodeficiency virus (HIV) in Tanzania, there is a progressive decline in ART enrollment among HIV-infected children. This study aimed to determine the factors affecting the enrollment of children with HIV in ART and to identify an effective, sustainable intervention to address children's ART care enrollment. To achieve this, we conducted a cross-sectional study using a mixed-method sequential explanatory design, including children with HIV aged 2 to 14 years in the Simiyu region. Stata™ and NVIVO™ software were used to perform quantitative and qualitative data analyses, respectively. In the quantitative analyses, we considered 427 children, with a mean age of 8.54 ± 3.54 years and a median age of 3 years (interquartile range: 1-6 years). The mean length of ART initiation delay was 3.71 ± 3.21 years. Additionally, independent child enrollment predictors included distance to the facility (adjusted odds ratio [AOR]: 3.31; 95% confidence interval [CI]:1.14-9.58), caregivers' income (AOR: 0.17; 95% CI: 0.07-0.43), and fear of stigma (AOR: 3.43; 95% CI: 1.14-10.35). In qualitative analyses, 36 respondents reported that stigma, distance, and lack of HIV-positive status disclosure to their fathers were causes for low enrollment in ART. Overall, this study demonstrated that a caregiver's income, distance to obtain HIV care services, HIV-positive status non-disclosure to the father, and fear of stigma played a significant role in children's enrollment in HIV care. As such, HIV/acquired immunodeficiency syndrome programs would benefit from having intensive interventions to address distance, such as scaling up care and treatment centers, as well as techniques to reduce stigma in the population.