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The promise of drug repurposing is to accelerate the translation of knowledge to treatment of human disease, bypassing common challenges associated with drug development to be more time- and cost-efficient. Repurposing has an increased chance of success due to the previous validation of drug safety and allows for the incorporation of omics. Hypothesis-generating omics processes inform drug repurposing decision-making methods on drug efficacy and toxicity. This review summarizes drug repurposing strategies and methodologies in the context of the following omics fields: genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, phenomics, pregomics, and personomics. While each omics field has specific strengths and limitations, incorporating omics into the drug repurposing landscape is integral to its success.
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Reposicionamiento de Medicamentos/métodos , Preparaciones Farmacéuticas/administración & dosificación , Animales , Toma de Decisiones , Desarrollo de Medicamentos/economía , Desarrollo de Medicamentos/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , HumanosRESUMEN
INTRODUCTION: Despite the public health system's critical role in non-communicable disease (NCD) surveillance in Vietnam, limited evidence exists on the implementation of NCD surveillance activities within these systems and the need for capacity building across different system levels to meet expected NCD surveillance goals. This study aimed to evaluate the status of and describe factors affecting the implementation of NCD surveillance activities and to identify the NCD surveillance capacity building needs of the public health system in Vietnam. METHODS: We used a mixed-methods approach in four provinces, conducting self-completed surveys of staff from six Preventive Medicine Institutes (PHI), 53 Centres for Disease Control (CDC) and 148 commune health stations (CHS), as well as 14 in-depth interviews and 22 focus group discussions at four PHI, four CDC, and eight district health centres and CHS. RESULTS: Study findings highlighted that although Vietnam has a well-functioning NCD surveillance system, a number of quality issues related to NCD surveillance data were salient. Multifactorial reasons were identified for incomplete, unconfirmed, and inaccurate mortality data and current disease surveillance data. Data on NCD management and treatment were reported to be of better quality than data for screening, targeted treatment, and counselling communication. Main factors affected the effective implementation of NCD surveillance, namely lack of complete and specific guidelines for NCD surveillance, limitations in human resource capacity within NCD departments, and shortage of funding for NCD surveillance activities. CONCLUSION: Study findings provide practical strategies for strengthening health system capacity for NCD surveillance through developing policies, guidelines, and standardised tools to guide NCD surveillance and a road map for integrated NCD surveillance, developing training packages and manuals for all levels of the health system, and conducting utilisation-focused surveillance training programs.
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Enfermedades no Transmisibles , Salud Pública , Humanos , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/prevención & control , Vietnam/epidemiología , Recursos Humanos , Encuestas y CuestionariosRESUMEN
Malnutrition is a threat to optimal child development, with its occurrence during foetal and infancy stages associated with poor cognitive, motor and socio-emotional skills. However, information on the effects of various types of malnutrition on early childhood development (ECD) is limited in Nepal. To assess the association of stunting, wasting and underweight (three prominent forms of malnutrition) with the four domains of the ECD index (literacy-numeracy, physical, social-emotional and learning development) among children 36-59 months of age, we conducted an adjusted logistic regression using Nepal's national household Multiple Indicator Cluster Survey (MICS) 2019 data set. The study sample consisted of children aged 36-59 months (n = 2871). Children were considered developmentally on track if they met criteria in each of the four ECD domains. Regarding ECD status of children 36-59 months old, 35% of children were not developmentally on track for the ECD index. The adjusted odds ratio indicated that stunting was associated with lower odds of not being developmentally on track according to the ECD index as well as the literacy-numeracy, physical and learning domains of the ECD index. Likewise, underweight was associated with lower odds of not being developmentally on track according to the ECD index, primarily for ECD domains of literacy-numeracy, physical and learning. Notably, no association between wasting and ECD indicators was observed. Children's nutrition status impacts child development outcomes. Adding ECD interventions, such as responsive and stimulating caregiving, within nutrition programmes among children who are stunted and underweight could improve child development outcomes.
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Trastornos de la Nutrición del Niño , Desnutrición , Niño , Desarrollo Infantil , Trastornos de la Nutrición del Niño/epidemiología , Preescolar , Estudios Transversales , Femenino , Trastornos del Crecimiento/epidemiología , Humanos , Lactante , Desnutrición/epidemiología , Nepal/epidemiología , Prevalencia , Delgadez/epidemiologíaRESUMEN
Hemoglobin H (Hb H) disease is the most significant health problem of the α-thalassemia syndromes. The Hb disease patients are categorized based on their genotype to deletional and nondeletional, with the latter genotype presents the more severe clinical symptoms. Since telomere length is an indicator of biological aging and health, we hypothesized that telomere length could reflect Hb H disease's severity. In this study, we recruited 48 deletional and 47 nondeletional Hb H disease patients, along with 109 normal controls, for telomere length assessment. The leukocyte telomere length was assessed by monochromatic multiplex real-time PCR and reported as the telomere to single-copy gene (T/S) ratio. When telomere length was adjusted for age, the analysis of covariance between the control and the two Hb H disease groups revealed no significant difference. However, the telomere shortening rate was more rapid in the nondeletional Hb H disease group than those of the control and deletional Hb H disease groups. Gender analysis found that male patients have a significantly lower T/S ratio than females in the nondeletional group but not in the control and deletional groups. In the two disease groups, the T/S ratio was not influenced by ferritin level or transfusion burden but was positively correlated with the absolute reticulocyte count.
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Hemoglobina H/genética , Acortamiento del Telómero , Talasemia alfa/genética , Globinas beta/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea , Niño , Femenino , Ferritinas/sangre , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto Joven , Talasemia alfa/sangre , Talasemia alfa/diagnóstico , Talasemia alfa/terapiaRESUMEN
To contribute to tuberculosis (TB) elimination, TB preventive treatment (TPT) should integrate innovative approaches including tele-contact investigation (TCI), mathematical modelling, and participatory governance. Aligning with the World Health Organisation's primary health care framework, supply is provided by the provincial health system, demand is cultivated by the community, while governance is represented by the governor, who oversees the health leadership structure, local policies, and allocation of resources. A healthy dynamic between these three components is required to achieve universal health coverage (UHC). Because of their potential to integrate health systems and engage communities, primary health care principles underpin an effective approach to TB prevention. First, the provincial health system should connect with the community through TCI to transform the status quo of passive service delivery. Second, community participation should strengthen the linkage between the health system and governance, which ensures that community action plans are aligned with provincial TPT targets. Third, governance should leverage mathematical modelling to allocate resources to those with greatest need. Central to this is a reliable TB information system that should validate a robust mathematical model to measure cost-effectiveness of the intervention. Collectively, this holistic approach to TB prevention could provide a proof-of-concept that investing in primary health care is the key to UHC.
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Currently, Cambodia uses performance-based financing (PBF) and a national quality enhancement monitoring system as key components of its strategy to achieve universal health coverage and the health-related Sustainable Development Goals. PBF is one among many strategies to improve the quality of healthcare services and its effects and limitations have been widely documented. We share lessons learnt from the use of quality improvement collaboratives, a facility-based quality improvement strategy, to amplify and complement PBF to address specific service delivery gaps, improve provider competency, and increase patient trust and satisfaction in the health system, a driver of healthcare utilisation.
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Mejoramiento de la Calidad , Cobertura Universal del Seguro de Salud , Cambodia , Atención a la Salud , Servicios de Salud , HumanosRESUMEN
As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants' next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones' altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.
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Actitud , Muerte , Familia , Infecciones por VIH , Cuidado Terminal/psicología , California , Femenino , Grupos Focales , Humanos , Masculino , Investigación CualitativaRESUMEN
A growing body of research is beginning to elucidate reasons people living with HIV (PLWHIV) might prefer oral daily antiretroviral treatment (ART) compared with emerging long-acting ART (LA-ART) or HIV remission strategies under investigation. Our objective is to provide qualitative insights into the reasons why PLWHIV might prefer one of these HIV control therapies over others. From May to August 2018, we implemented a semistructured cross-sectional survey of PLWHIV in the United States to better understand patient preferences around various HIV treatment and remission options. Using free text, respondents were asked to explain why they preferred one HIV control option over the other two. We analyzed responses to the open-ended survey questions on reasons for preferring oral daily ART versus LA-ART versus HIV remission strategies using conventional content analysis. The results showed that PLWHIV preferred oral daily ART because of its familiarity and known safety and efficacy profile, whereas those who preferred LA-ART would value the convenience it offers. Finally, HIV remission strategies would be preferred to avoid taking ART altogether. The qualitative results provide insights into reasons why PLWHIV in the United States might prefer oral daily ART versus novel therapies. More importantly, they provide information to better align HIV virological control strategies with end-user perspectives. To make informed choices around evolving HIV therapeutics, PLWHIV and HIV care providers would benefit from decision tools to better assess options and trade-offs. More research is needed on how best to effectively support PLWHIV and HIV care providers in shared decision-making.
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Infecciones por VIH , Antirretrovirales/uso terapéutico , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Humanos , Investigadores , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Little is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members' perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research. METHODS: Two focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years. RESULTS: Qualitative focus group data revealed five major themes underlying study staff members' multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants' altruism, fulfillment, and control at the end of life, 2) perceptions of staff members' close involvement in the Last Gift study, with sub-themes related to staff members' cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites. DISCUSSION: Understanding staff members' nuanced emotional and procedural experiences is crucial to the Last Gift study's sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study's potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV.
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Investigadores/psicología , Cuidado Terminal/psicología , Adulto , Altruismo , Autopsia , Muerte , Femenino , Grupos Focales/métodos , VIH/patogenicidad , Infecciones por VIH/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Participación del Paciente/psicología , Investigación Cualitativa , Conducta SocialRESUMEN
A growing number of people living with HIV/AIDS are participating in HIV cure-related research at the end of life (EOL). Due to the novelty of EOL HIV cure-related research, there is a need to understand how their next-of-kin (NOK) perceive such research. We conducted in-depth interviews with NOK of the Last Gift study participants at the University of California, San Diego. The Last Gift study occurs in the context of the EOL and involves a full body donation. NOK completed two interviews: (1) shortly after the participants' enrollment in the study and (2) following death. We applied thematic analysis to analyze qualitative data. NOK included seven individuals (five males and two females), including two spouses, one ex-partner, one sister, a grandmother/grandfather, and a close friend. Thematic analysis revealed five key themes: (1) NOK viewed the Last Gift program in a positive light and had an accurate overall understanding of the study; (2) NOK identified factors that motivated participants to donate their body to science; (3) NOK identified benefits of the Last Gift program for both the donors and themselves; (4) NOK did not perceive any physical risks or decisional regrets of study but wanted to minimize psychosocial impacts and ensure the dignity of participants at all times; and (5) NOK noted elements that remained essential to the successful implementation of EOL HIV cure-related research, such as early involvement and clear communication. Our study uniquely contributes to increased understanding and knowledge of what is important from the point of view of supportive NOK to ensure successful implementation of EOL HIV cure-related research. More research will be needed to understand perspectives of less supportive NOK.
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Autopsia , Familia , Infecciones por VIH , Muerte , Femenino , Humanos , Masculino , Percepción , Investigación CualitativaRESUMEN
End-of-life (EOL) HIV cure-related research provides a novel approach to studying HIV reservoirs. The Last Gift is a rapid autopsy research study at the University of California San Diego that enrolls terminally ill people living with HIV (PLWHIV) with a desire to contribute to HIV cure-related research. We conducted in-depth baseline and follow-up interviews with Last Gift study participants. We analyzed interview data applying conventional content analysis. Since summer 2017, 13 participants have been enrolled (n = 11 males and 2 females; aged 45-89 years) and 8 participants interviewed. Terminal illnesses included cancers, heart diseases, and neurodegenerative illnesses. Our analysis revealed five key themes: (1) The Last Gift study has tremendous meaning for participants at the end of their life. (2) HIV-specific altruism was a primary motivator to join the Last Gift study, nested within the context of community, scientific advancement, and moral obligation. (3) Participants did not expect physical benefits yet they perceived emotional/psychological, financial, and societal/scientific benefits. (4) There were minimal participant-perceived risks and concerns. (5) Last Gift participants expressed immense gratitude toward study staff. The Last Gift study provides a framework for ethical HIV cure-related research at EOL and highlighted participants' perspectives, motivations, and experiences. Knowing how PLWHIV understand and experience such studies will remain critical to designing ethical, fully informed HIV cure research protocols that are acceptable to PLWHIV.
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Infecciones por VIH , Autopsia , Cognición , Muerte , Femenino , Humanos , Masculino , RiesgoRESUMEN
INTRODUCTION: The question of what motivates people to participate in research is particularly salient in the HIV field. While participation in HIV research was driven by survival in the 1980's and early 1990's, access to novel therapies became the primary motivator with the advent of combination antiretroviral therapy (cART) in the late 1990s. In the HIV cure-related research context, the concept of altruism has remained insufficiently studied. METHODS: We conducted a scoping review to better contextualize and understand how altruism is or could be operationalized in HIV cure-related research. We drew from the fields of altruism in general, clinical research, cancer, and HIV clinical research-including the HIV prevention, treatment, and cure-related research fields. DISCUSSION: Altruism as a key motivating factor for participation in clinical research has often been intertwined with the desire for personal benefit. The cancer field informs us that reasons for participation usually are multi-faceted and complex. The HIV prevention field offers ways to organize altruism-either by the types of benefits achieved (e.g., societal versus personal), or the origin of the values that motivate research participation. The HIV treatment literature reveals the critical role of clinical interactions in fostering altruism. There remains a dearth of in-depth knowledge regarding reasons surrounding research participation and the types of altruism displayed in HIV cure-related clinical research. CONCLUSION: Lessons learned from various research fields can guide questions which will inform the assessment of altruism in future HIV cure-related research.
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For over a decade, the binary concepts of 'sterilizing' versus 'functional' cure have provided an organizing framework for the field of HIV cure-related research. In this article, we examine how the expression 'functional cure' is employed within the field, published literature, and community understanding of HIV cure research. In our synthesis of the different meanings attributed to 'functional cure' within contemporary biomedical discourse, we argue that employing the 'functional cure' terminology poses a series of problems. The expression itself is contradictory and inconsistently used across a wide array of HIV cure research initiatives. Further, the meaning and acceptability of 'functional cure' within communities of people living with and affected by HIV is highly variable. After drawing lessons from other fields, such as cancer and infectious hepatitis cure research, we summarize our considerations and propose alternative language that may more aptly describe the scientific objectives in question. We call for closer attention to language used to describe HIV cure-related research, and for continued, significant, and strategic engagement to ensure acceptable and more precise terminology.
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Competencia Cultural , Atención a la Salud/métodos , Salud Global , Humanos , Tailandia , Estados UnidosRESUMEN
Nucleotide excision repair (NER) is essential for removing many types of DNA lesions from the genome, yet the mechanisms of NER in humans remain poorly understood. This review summarizes our current understanding of the structure, biochemistry, interaction partners, mechanisms, and disease-associated mutations of one of the critical NER proteins, XPA.