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Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration. 纤毛症基因 CFAP410 的编码和非编码变异导致早发性非综合症视网膜变性。
Research Square Pub Date : 2024-02-09 DOI: 10.21203/rs.3.rs-3871956/v1
K. Bujakowska, Riccardo Sangermano, Priya Gupta, Cherrell Price, Jinu Han, Julien Navarro, C. Condroyer, Emily Place, A. Antonio, Shizuo Mukai, Xavier Zanlonghi, J. Sahel, Jacque Duncan, Eric A. Pierce, Christina Zeitz, I. Audo, Rachel Huckfeldt
{"title":"Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration.","authors":"K. Bujakowska, Riccardo Sangermano, Priya Gupta, Cherrell Price, Jinu Han, Julien Navarro, C. Condroyer, Emily Place, A. Antonio, Shizuo Mukai, Xavier Zanlonghi, J. Sahel, Jacque Duncan, Eric A. Pierce, Christina Zeitz, I. Audo, Rachel Huckfeldt","doi":"10.21203/rs.3.rs-3871956/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3871956/v1","url":null,"abstract":"Abstract Inherited retinal degenerations are blinding genetic disorders characterized by high genetic and phenotypic heterogeneity. The implementation of next-generation sequencing in routine diagnostics, together with advanced clinical phenotyping including multimodal retinal imaging, have contributed to the increase of reports describing novel genotype-phenotype associations and phenotypic expansions. In this study, we describe sixteen families with early-onset non-syndromic retinal degenerations in which affected probands carried rare bi-allelic variants in CFAP410, a ciliary gene previously associated with syndromic recessive Jeune syndrome. The most common retinal phenotypes were cone-rod and rod-cone dystrophies, but the clinical presentations were unified by their early onset as well as the severe impact on central visual function. Twelve variants were detected (three pathogenic, seven likely pathogenic, two of uncertain significance), eight of which were novel. One deep intronic change, c.373+91A>G, led to the creation of a cryptic splice acceptor site in intron four, followed by the inclusion of a 200-base pair pseudoexon and subsequent premature stop codon formation. To our knowledge this is the first likely pathogenic deep-intronic variant identified in this gene. Meta-analysis of all published and novel CFAP410 variants revealed no clear correlation between the severity of the CFAP410-associated phenotypes and the identified causal variants. This is supported by the fact that the frequently encountered missense variant p.(Arg73Pro), often found in syndromic cases, was also associated with non-syndromic retinal degeneration. This study expands the current knowledge of CFAP410-associated ciliopathy by enriching its mutational landscape and supports its association with non-syndromic retinal degeneration.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunogenicity and efficacy of XBB.1.5 rS vaccine against EG.5.1 variant of SARS-CoV-2 in Syrian hamsters XBB.1.5 rS 疫苗对叙利亚仓鼠 SARS-CoV-2 EG.5.1 变异株的免疫原性和有效性
Research Square Pub Date : 2024-02-09 DOI: 10.21203/rs.3.rs-3873514/v1
Jacco Boon, Nadia Soudani, T. Bricker, T. Darling, K. Seehra, Nita Patel, M. Guebre‐Xabier, Gale Smith, M. Suthar, Ali Ellebedy, Meredith E. Davis-Gardner
{"title":"Immunogenicity and efficacy of XBB.1.5 rS vaccine against EG.5.1 variant of SARS-CoV-2 in Syrian hamsters","authors":"Jacco Boon, Nadia Soudani, T. Bricker, T. Darling, K. Seehra, Nita Patel, M. Guebre‐Xabier, Gale Smith, M. Suthar, Ali Ellebedy, Meredith E. Davis-Gardner","doi":"10.21203/rs.3.rs-3873514/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3873514/v1","url":null,"abstract":"Abstract The continued emergence of SARS-CoV-2 variants necessitates updating COVID-19 vaccines to match circulating strains. The immunogenicity and efficacy of these vaccines must be tested in pre-clinical animal models. In Syrian hamsters, we measured the humoral and cellular immune response after immunization with the nanoparticle recombinant Spike (S) protein-based COVID-19 vaccine (Novavax, Inc.). We also compared the efficacy of the updated monovalent XBB.1.5 variant vaccine to previous COVID-19 vaccines for the induction of XBB.1.5 and EG.5.1 neutralizing antibodies and protection against a challenge with the EG.5.1 variant of SARS-CoV-2. Immunization induced high levels of spike-specific serum IgG and IgA antibodies, S-specific IgG and IgA antibody secreting cells, and antigen specific CD4 + T-cells. The XBB.1.5 and XBB.1.16 vaccines, but not the Prototype vaccine, induced high levels of neutralizing antibodies against XBB.1.5 and EG.5.1 variants of SARS-CoV-2. Upon challenge with the Omicron EG.5.1 variant, the XBB.1.5 and XBB.1.16 vaccines reduced the virus load in the lungs, nasal turbinates, trachea and nasal washes. The bivalent vaccine continued to offer protection in the trachea and lungs, but protection was reduced in the upper airways. In contrast, the monovalent Prototype vaccine no longer offered good protection, and breakthrough infections were observed in all animals and tissues. Thus, the protein-based XBB.1.5 vaccine is immunogenic and can protect against the Omicron EG.5.1 variant in the Syrian hamster model.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139964719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identifying the Heterogeneity in the Association between Workforce Diversity and Retention in Opioid Treatment among Black clients 确定黑人客户中劳动力多样性与阿片类药物治疗保留率之间的异质性关系
Research Square Pub Date : 2024-02-08 DOI: 10.21203/rs.3.rs-3932153/v1
Yinfei Kong, Erick G. Guerrero, J. Frimpong, Tenie Khachikian, Suojin Wang, Thomas A. D’Aunno, Daniel Howard
{"title":"Identifying the Heterogeneity in the Association between Workforce Diversity and Retention in Opioid Treatment among Black clients","authors":"Yinfei Kong, Erick G. Guerrero, J. Frimpong, Tenie Khachikian, Suojin Wang, Thomas A. D’Aunno, Daniel Howard","doi":"10.21203/rs.3.rs-3932153/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3932153/v1","url":null,"abstract":"Abstract Background This study investigates the impact of workforce diversity, specifically staff identified as Black/African American, on retention in opioid use disorder (OUD) treatment, aiming to enhance patient outcomes. Employing a novel machine learning technique known as 'causal forest,' we explore heterogeneous treatment effects on retention. Methods We relied on four waves of the National Drug Abuse Treatment System Survey (NDATSS), a nationally representative longitudinal dataset of treatment programs. We analyzed OUD program data from the years 2000, 2005, 2014 and 2017 (n = 627). Employing the 'causal forest' method, we analyzed the heterogeneity in the relationship between workforce diversity and retention in OUD treatment. Interviews with program directors and clinical supervisors provided the data for this study. Results The results reveal diversity-related variations in the association with retention across 61 out of 627 OUD treatment programs (less than 10%). These programs, associated with positive impacts of workforce diversity, were more likely private-for-profit, newer, had lower percentages of Black and Latino clients, lower staff-to-client ratios, higher proportions of staff with graduate degrees, and lower percentages of unemployed clients. Conclusions While workforce diversity is crucial, our findings underscore that it alone is insufficient for improving retention in addiction health services research. Programs with characteristics typically linked to positive outcomes are better positioned to maximize the benefits of a diverse workforce in client retention. This research has implications for policy and program design, guiding decisions on resource allocation and workforce diversity to enhance retention rates among Black clients with OUDs.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deciphering the tissue-specific functional effect of Alzheimer risk SNPs with deep genome annotation 利用深度基因组注释解密阿尔茨海默氏症风险 SNPs 的组织特异性功能效应
Research Square Pub Date : 2024-02-08 DOI: 10.21203/rs.3.rs-3871665/v1
Pradeep Varathan Pugalenthi, Bing He, Linhui Xie, K. Nho, A. Saykin, Jingwen Yan
{"title":"Deciphering the tissue-specific functional effect of Alzheimer risk SNPs with deep genome annotation","authors":"Pradeep Varathan Pugalenthi, Bing He, Linhui Xie, K. Nho, A. Saykin, Jingwen Yan","doi":"10.21203/rs.3.rs-3871665/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3871665/v1","url":null,"abstract":"Abstract Alzheimer’s disease (AD) is a highly heritable brain dementia, along with substantial failure of cognitive function. Large-scale genome-wide association studies (GWASs) have led to a significant set of SNPs associated with AD and related traits. GWAS hits usually emerge as clusters where a lead SNP with the highest significance is surrounded by other less significant neighboring SNPs. Although functionality is not guaranteed even with the strongest associations in GWASs, lead SNPs have historically been the focus of the field, with the remaining associations inferred to be redundant. Recent deep genome annotation tools enable the prediction of function from a segment of a DNA sequence with significantly improved precision, which allows in-silico mutagenesis to interrogate the functional effect of SNP alleles. In this project, we explored the impact of top AD GWAS hits on chromatin functions and whether it will be altered by the genetic context (i.e., alleles of neighboring SNPs). Our results showed that highly correlated SNPs in the same LD block could have distinct impacts on downstream functions. Although some GWAS lead SNPs showed dominant functional effects regardless of the neighborhood SNP alleles, several other SNPs did exhibit enhanced loss or gain of function under certain genetic contexts, suggesting potential additional information hidden in the LD blocks and the need for reanalysis of GWAS findings as clusters.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multilevel and multicomponent intervention to promote colorectal cancer screening among underserved Vietnamese Americans: A cluster randomized trial 多层次、多成分干预措施,促进服务不足的越南裔美国人接受大肠癌筛查:分组随机试验
Research Square Pub Date : 2024-02-08 DOI: 10.21203/rs.3.rs-3934937/v1
Grace X. Ma, Lin Zhu, Yin Tan, Phuong Do, Guercie Guerrier, Min Qi Wang, Minhhuyen Nguyen, Tam Tran, Philip Pham
{"title":"Multilevel and multicomponent intervention to promote colorectal cancer screening among underserved Vietnamese Americans: A cluster randomized trial","authors":"Grace X. Ma, Lin Zhu, Yin Tan, Phuong Do, Guercie Guerrier, Min Qi Wang, Minhhuyen Nguyen, Tam Tran, Philip Pham","doi":"10.21203/rs.3.rs-3934937/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3934937/v1","url":null,"abstract":"Abstract Purpose The fecal immunochemical test (FIT) is a non-invasive method for colorectal cancer (CRC) screening, particularly effective in underserved Vietnamese American communities with low screening rates. This study reports on a culturally tailored multilevel intervention, incorporating FIT, aimed at increasing CRC screening among these populations aged 50 or above in the Greater Philadelphia metropolitan area. Methods From 2017 to 2020, we conducted a two-arm cluster randomized controlled trial to test the efficacy of a culturally tailored, multicomponent multilevel intervention aimed at increasing CRC screening uptake via enhanced self-awareness and self-efficacy, improved access to care, and changes in social norms and removal of stigma. The intervention group received multicomponent, multilevel CRC intervention including provision of a FIT self-sampling kit, with intervention approaches informed by the Centers for Disease Control's Clinical Preventive Services (CPS) Guidelines for adults 50+. The control group received only the CPS education. Results The study sample consisted of 746 eligible Vietnamese American participants recruited from 20 community-based organizations, with 95% having limited English proficiency. At 12-month follow-up, the intervention group showed substantially higher rates of FIT completion (89.56% vs. 7.59%, p < .001) and any CRC testing (91.48% vs. 42.41%, p < .001) compared to the control group. Conclusion The results suggest that the community-based, culturally-tailored multilevel intervention, which incorporates with FIT self-testing, effectively enhances CRC screening among low-income Vietnamese Americans. Additionally, these results underscore the significance of community-oriented strategies, like collaborating with relevant community-based organizations, in achieving CRC screening targets.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Practices and attitudes of herbalists regarding informed consent in Uganda: A qualitative study 乌干达草药医生对知情同意的做法和态度:定性研究
Research Square Pub Date : 2024-02-08 DOI: 10.21203/rs.3.rs-3911823/v1
Sumayiya Nalubega, P. Kutyabami, Adeline Twimukye, D. Mafigiri, Nelson K. Sewankambo
{"title":"Practices and attitudes of herbalists regarding informed consent in Uganda: A qualitative study","authors":"Sumayiya Nalubega, P. Kutyabami, Adeline Twimukye, D. Mafigiri, Nelson K. Sewankambo","doi":"10.21203/rs.3.rs-3911823/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3911823/v1","url":null,"abstract":"Abstract Background Informed consent (IC) is a fundamental principle in medical ethics that upholds respect for patient autonomy. Although widely applied in healthcare, its feasibility and implementation in herbal medicine have been underexplored. This study therefore aimed to explore the practices and attitudes of herbalists regarding informed consent. Methods To achieve these objectives, a qualitative cross-sectional study was conducted from June to December 2020. Twenty-one in-depth interviews with herbalists and four key informant interviews with leaders of the different traditional medicine organizations were also conducted. The data were analyzed thematically using NVivo version 12 software. Results Sixteen of the twenty-one participants acquired oral herbal medicine knowledge from their relatives. Although a positive inclination toward obtaining IC was evident, the focus was on disclosing basic information. Discussions of alternative treatments and herbal specifics less frequent. Disease management decisions often involve shared responsibility within families or societies. Documented IC procedures are rare among herbalists, who deem consent forms unnecessary, although they recognize the potential benefits of IC in fostering trust and professionalism. Challenges hindering IC implementation included regulatory gaps, inadequate skills, and the absence of mechanisms to protect the intellectual property rights of herbal medicine. Conclusion This study illuminates how educational, cultural, familial, and regulatory factors influence herbalists' practices and attitudes toward informed consent.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Putting measurement-based care into action: A mixed methods study of the benefits of integrating routine client feedback in coordinated specialty care programs for early psychosis 将基于测量的护理付诸行动:一项混合方法研究,探讨将常规客户反馈纳入早期精神病专科协调护理计划的益处
Research Square Pub Date : 2024-02-08 DOI: 10.21203/rs.3.rs-3918063/v1
P. Meyer-Kalos, Grace Owens, Melissa Fisher, Lionel Wininger, Anne Williams-Wengerd, Kimberleigh Breen, Josephine Abate, Ariel Currie, Nathan Olinger, Sophia Vinogradov
{"title":"Putting measurement-based care into action: A mixed methods study of the benefits of integrating routine client feedback in coordinated specialty care programs for early psychosis","authors":"P. Meyer-Kalos, Grace Owens, Melissa Fisher, Lionel Wininger, Anne Williams-Wengerd, Kimberleigh Breen, Josephine Abate, Ariel Currie, Nathan Olinger, Sophia Vinogradov","doi":"10.21203/rs.3.rs-3918063/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3918063/v1","url":null,"abstract":"Abstract Background: Measurement-based care (MBC) is an effective tool in the delivery of evidence-based practices (EBPs). MBC utilizes feedback loops to share information and drive changes throughout a learning healthcare system. Few studies have demonstrated this practice in team-based care for people with early psychosis. This paper describes the development of a personalized feedback report derived from routine assessments that is shared with clients and clinicians as part of a MBC process. Methods: We used a quasi pre-post comparison design with mixed methods to evaluate the implementation of a personalized feedback report at 5 early psychosis coordinated specialty care programs (CSC). We compared clients enrolled in CSC who did and did not receive a feedback report over the first 6 months of treatment. The sample included 204 clients: 146 who did not receive the feedback report and were enrolled over 2 years, and 58 who received the feedback report. A subset of 67 clients completed measures at both intake and 6-month follow-up, including 42 who received the report and 25 who did not. We compared the two groups with regard to self-reported symptoms, likelihood of completing treatment, and perception of shared decision making. . We conducted qualitative interviews with 5 clients and 5 clinicians to identify the benefits and challenges associated with the personalized feedback report. Results: People who received a personalized feedback report reported significant improvements in shared decision-making and had greater improvements over time in their intent to attend future treatment sessions. They engaged in more sessions for Supported Employment and Education (SEE), case management, and peer support, and fewer medication visits over the first 6 months of treatment. Both groups showed significant improvement in symptoms and functioning. Results from the qualitative analysis indicated that the experience of receiving the reports was valuable and validating for both patients and clinicians. Conclusions: A personalized feedback report was integrated into standard of care for early psychosis programs. This process may improve shared decision-making, strengthen the likelihood to stay in treatment, and increase engagement in psychosocial interventions. We posit that this process facilitates strengths-focused discussions, enhances intrinsic motivation, and strengthens the therapeutic alliance.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of Infectious Complications with BCMA-directed Therapies in Multiple Myeloma 多发性骨髓瘤中 BCMA 导向疗法的感染并发症比较
Research Square Pub Date : 2024-02-07 DOI: 10.21203/rs.3.rs-3911922/v1
A. Lesokhin, Karthik Nath, Tala Shekarkhand, D. Nemirovsky, Andriy Derkach, B. Costa, Noriko Nishimura, Tasmin Farzana, Colin Rueda, David Chung, Heather Landau, O. Lahoud, M. Scordo, G. Shah, H. Hassoun, K. Maclachlan, N. Korde, Urvi A Shah, Carlyn Rose Tan, M. Hultcrantz, S. Giralt, Saad Z Usmani, Zainab Shahid, S. Mailankody
{"title":"Comparison of Infectious Complications with BCMA-directed Therapies in Multiple Myeloma","authors":"A. Lesokhin, Karthik Nath, Tala Shekarkhand, D. Nemirovsky, Andriy Derkach, B. Costa, Noriko Nishimura, Tasmin Farzana, Colin Rueda, David Chung, Heather Landau, O. Lahoud, M. Scordo, G. Shah, H. Hassoun, K. Maclachlan, N. Korde, Urvi A Shah, Carlyn Rose Tan, M. Hultcrantz, S. Giralt, Saad Z Usmani, Zainab Shahid, S. Mailankody","doi":"10.21203/rs.3.rs-3911922/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3911922/v1","url":null,"abstract":"Abstract B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥ 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25–0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31–3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05–3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21–0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17–0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Behavioral Economic and Wellness-based Approaches for Reducing Alcohol Use and Consequences Among Diverse Non-Student Emerging Adults: Study Protocol for Project BLUE, a Randomized Controlled Trial 以行为经济学和健康为基础的方法减少不同非学生新成人的酒精使用和后果:随机对照试验 BLUE 项目的研究方案
Research Square Pub Date : 2024-02-07 DOI: 10.21203/rs.3.rs-3732598/v1
James G. Murphy, Ashley A Dennhardt, Jacob Tempchin, Hannah E. Colgonis, Meghan McDevitt-Murphy, Brian Borsari, Kristoffer S. Berlin
{"title":"Behavioral Economic and Wellness-based Approaches for Reducing Alcohol Use and Consequences Among Diverse Non-Student Emerging Adults: Study Protocol for Project BLUE, a Randomized Controlled Trial","authors":"James G. Murphy, Ashley A Dennhardt, Jacob Tempchin, Hannah E. Colgonis, Meghan McDevitt-Murphy, Brian Borsari, Kristoffer S. Berlin","doi":"10.21203/rs.3.rs-3732598/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3732598/v1","url":null,"abstract":"Abstract Background: Emerging adults (EAs) who are not 4-year college students nor graduates are at elevated risk for lifetime alcohol use disorder, comorbid drug use, and mental health symptoms, compared to college graduates. There is a need for tailored brief alcohol intervention (BAI) approaches to reduce alcohol risk and to facilitate healthy development in this high-risk population. Most BAIs include a single session focused on discussing risks associated with drinking and correcting normative beliefs about drinking rates. EAs may benefit from additional elements that enhance general wellness. The Substance-Free Activity Session (SFAS) aims to clarify life goals and values and increase goal-directed activities that provide alternatives to alcohol use, and the Relaxation Training (RT) session teaches relaxation and stress reduction skills. Methods: The present study is a randomized 3-group (BAI+SFAS vs. RT+SFAS vs. education control) trial with 525 EAs (175 per group; estimated 50% women & 50% African American) who report recent risky drinking and who are not students or graduates of 4-year colleges. Participants will have the option of completing the intervention sessions in person or via a secure video teleconference. Levels of drinking and alcohol-related problems will be evaluated at baseline and 1, 3, 6, and 12-months post-intervention. The primary hypothesis is that both BAI+SFAS and RT+SFAS participants will report significantly greater reductions in alcohol use and problems relative to education control participants, with no differences in outcomes between the two active treatment conditions. Discussion: The results of this study will inform alcohol prevention efforts for high-risk community dwelling emerging adults. ClinicalTrials.gov Identifier: NCT04776278","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Experiences and perceptions of conditional cash incentive provision and cessation among people with HIV for care engagement: A qualitative study 艾滋病病毒感染者对有条件现金奖励的提供和停止参与护理的体验和看法:定性研究
Research Square Pub Date : 2024-02-07 DOI: 10.21203/rs.3.rs-3905074/v1
Julia Giordano, J. Lewis-Kulzer, Lina Montoya, E. Akama, H. Adhiambo, Everlyne Nyadieka, Sarah Iguna, Elizabeth A. Bukusi, T. Odeny, Carol S. Camlin, Harsha Thirumurthy, Maya Petersen, Elvin Geng
{"title":"Experiences and perceptions of conditional cash incentive provision and cessation among people with HIV for care engagement: A qualitative study","authors":"Julia Giordano, J. Lewis-Kulzer, Lina Montoya, E. Akama, H. Adhiambo, Everlyne Nyadieka, Sarah Iguna, Elizabeth A. Bukusi, T. Odeny, Carol S. Camlin, Harsha Thirumurthy, Maya Petersen, Elvin Geng","doi":"10.21203/rs.3.rs-3905074/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3905074/v1","url":null,"abstract":"Abstract Background Consistent engagement in HIV treatment is needed for healthy outcomes, yet substantial loss-to-follow up persists, leading to increased morbidity, mortality and onward transmission risk. Although conditional cash transfers (CCTs) address structural barriers, recent findings suggest that incentive effects are time-limited, with cessation resulting in HIV care engagement deterioration. We explored incentive experiences, perceptions, and effects after cessation to investigate potential mechanisms of this observation. Methods This qualitative study was nested within a larger trial, AdaPT-R (NCT02338739), focused on HIV care engagement in western Kenya. A subset of participants were purposively sampled from AdaPT-R participants: adults with HIV who had recently started ART, received CCTs for one year, completed one year of follow-up without missing a clinic visit, and were randomized to either continue or discontinue CCTs for one more year of follow-up. In-depth interviews were conducted by an experienced qualitative researcher using a semi-structed guide within a month of randomization. Interviews were conducted in the participants’ preferred language (Dholuo, Kiswahili, English). Data on patient characteristics, randomization dates, and clinic visit dates to determine care lapses were extracted from the AdaPT-R database. A codebook was developed deductively based on the guide and inductively refined based on initial transcripts. Transcripts were coded using Dedoose software, and thematic saturation was identified. Results Of 38 participants, 15 (39%) continued receiving incentives, while 23 (61%) were discontinued from receiving incentives. Half were female (N = 19), median age was 30 years (range: 19–48), and about three-quarters were married or living with partners. Both groups expressed high intrinsic motivation to engage in care, prioritized clinic attendance regardless of CCTs and felt the incentives expanded their decision-making options. Despite high motivation, some participants reported that cessation of the CCTs affected their ability to access care, especially those with constrained financial situations. Participants also expressed concerns that incentives might foster dependency. Conclusions This study helps us better understand the durability of financial incentives for HIV care engagement, including when incentives end. Together with the quantitative findings in the parent AdaPT-R study, these results support the idea that careful consideration be exercised when implementing incentives for sustainable engagement effects.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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