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This perspective article explores how process mining can extract clinical insights from mobile health data and complement data-driven techniques like machine learning. Despite technological advances, challenges such as selection bias and the complex dynamics of health data require advanced approaches. Process mining focuses on analyzing temporal process patterns and provides complementary insights into health condition variability. The article highlights the potential of process mining for analyzing mHealth data and beyond.
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Poor mental health significantly impacts people with HIV (PWH) and those who drink alcohol. Limited data exist on the combined effects of social determinants of health (social vulnerability) on mental health in PWH with unhealthy substance use. We investigated the relationship between social vulnerability and poor mental health in PWH and whether this relationship differed by race/ethnicity. We conducted a cross-sectional analysis using data from the Boston ARCH Cohort among PWH with current or past unhealthy substance use. We created a 23-item social vulnerability index (SVI) using a deficit accumulation approach comprised of social determinants of health indicators. We estimated whether higher SVI score is associated with anxiety and depressive symptoms using logistic regression analysis. Among 251 participants with a mean age of 52 (SD = 10) years, 67.3% were male, 52% Black, 21% Hispanic, 19% White, and 73% unemployed. The SVI had a mean of 9.30 (SD = 3.4) with a 1.5-18 range. Nearly two in five persons reported past month heavy alcohol use and 35% illicit drug use. The prevalence of anxiety and depressive symptoms was 34.4% and 54.2% respectively. Higher SVI score was associated with anxiety symptoms (adjusted odds ratio [aOR] = 2.01, 95% confidence interval [CI] 1.46, 2.76, p ≤ 0.001), and depressive symptoms (aOR = 2.42, 95% CI 1.74, 3.36, p ≤ 0.001). Race/ethnicity did not moderate the relationship between SVI and each mental health outcome. SVI was significantly associated with poor mental health across racial/ethnicity groups in this cohort. Interventions that address social vulnerability may improve well-being and quality of life for PWH.
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BACKGROUND: Unhealthy alcohol use is prevalent among people living with HIV/AIDS (PLWH) and contributes to impaired functioning, diminished quality of life, and poorer HIV outcomes. Common cooccurring conditions such as chronic pain may be associated with negative outcomes both directly and through its influence on unhealthy drinking itself. However, there is relatively little known about how pain influences unhealthy drinking among PLWH over time. The current study examined whether pain was associated with indices of unhealthy alcohol use, namely heavy drinking and alcohol use disorder (AUD) assessed 12 months later. METHODS: The study sample (n = 207) was from the Boston Alcohol Research Collaboration on HIV/AIDS (ARCH) Cohort, a prospective cohort of PLWH with a history of illicit substance or unhealthy alcohol use. We conducted logistic regression analyses to examine the associations between pain and both heavy drinking and AUD status (DSM-5 criteria) (yes/no) over time. In secondary analyses, we examined whether pain was associated with greater AUD severity and whether pain interference was associated with heavy drinking and AUD outcomes. RESULTS: We found that pain at baseline was associated with greater odds of AUD [aOR = 2.29 (95% CI: 1.13, 4.64), p = 0.02] but not heavy drinking [aOR = 0.91 (95% CI: 0.44, 1.88), p = 0.79] at 12 months. Pain was also associated with more severe AUD. Analyses of pain interference showed similar results. CONCLUSIONS: Pain is prospectively associated with higher odds of AUD among PLWH with a substance/unhealthy alcohol use history. Providers should routinely address pain among PLWH to improve AUD outcomes.
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BACKGROUND: Unhealthy alcohol use represents a significant risk for morbidity and mortality among people living with HIV (PLWH), in part through its impact on HIV management. Chronic pain, a common comorbidity, exacerbates suboptimal engagement in the HIV care continuum and has reciprocal detrimental effects on alcohol outcomes. There are no integrated, accessible approaches that address these comorbid conditions among PLWH to date. This paper describes a research study protocol of an integrated telehealth intervention to reduce unhealthy drinking and chronic pain among PLWH (Motivational and Cognitive-Behavioral Management for Alcohol and Pain [INTV]). METHODS: Two-hundred and fifty PLWH with unhealthy drinking and chronic pain will be recruited nationally via online advertisement. Informed consent and baseline assessments occur remotely, followed by 15 days of ecological momentary assessment to assess alcohol use, chronic pain, functioning, and mechanisms of behavior change. Next, participants will be randomized to either the INTV or Control (CTL) condition. Individuals in both conditions will meet with a health counselor through videoconferencing following randomization, and those in the INTV condition will receive 6 additional sessions. At 3- and 6-months post-baseline, participants will complete outcome assessments. It is hypothesized that the INTV condition will result in reduced unhealthy alcohol use and pain ratings compared to the CTL condition. CONCLUSION: This protocol paper describes a randomized controlled trial which tests the efficacy of a novel, integrated telehealth approach to reduce unhealthy alcohol use and chronic pain for PLWH, two common comorbid conditions that influence the HIV treatment cascade. GOV IDENTIFIER: NCT05503173.
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Dor Crônica , Infecções por HIV , Telemedicina , Adulto , Feminino , Humanos , Masculino , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/terapia , Alcoolismo/terapia , Dor Crônica/terapia , Terapia Cognitivo-Comportamental/métodos , Avaliação Momentânea Ecológica , Infecções por HIV/complicações , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The emergence of zoonotic infections that can develop into pathogens of pandemic potential is a major concern for public health. The risks of emergence and transmission relate to multiple factors that range from land use to human-non-human animal contacts. Livestock agriculture plays a potentially significant role in those risks, shaping landscapes and providing hosts that can act as the source or amplifiers of emergent pathogens. The relative risks will be contingent upon the nature of those systems, with comparisons often made between intensive, indoor, biosecure systems and more extensive, outdoor, insecure systems. Microbiological, ecological and veterinary sciences provide useful entry points in specifying and modelling some of the relative risks. Yet, they often do so with little regard for social science inputs and by making assumptions about social and economic conditions. In this article, we respond to recent analyses of relative risks by raising the importance of social and economic drivers of risk. We chart social science insights and research that materially alter the zoonotic risks associated with livestock production. Our purpose is to emphasize the requirement for full appreciation of the social, economic and political components of zoonotic and pandemic risk.
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We present the chromosome-scale genome assembly of the allopolyploid root-knot nematode Meloidogyne javanica. We show that the M. javanica genome is predominantly allotetraploid, comprising two subgenomes, A and B, that most likely originated from hybridisation of two ancestral parental species. The assembly was annotated using full-length non-chimeric transcripts, comparison to reference databases, and ab initio prediction techniques, and the subgenomes were phased using ancestral k-mer spectral analysis. Subgenome B appears to show fission of chromosomal contigs, and while there is substantial synteny between subgenomes, we also identified regions lacking synteny that may have diverged in the ancestral genomes prior to or following hybridisation. This annotated and phased genome assembly forms a significant resource for understanding the origins and genetics of these globally important plant pathogens.
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Genoma Helmíntico , Tylenchoidea , Animais , Tylenchoidea/genética , Raízes de Plantas/parasitologia , Raízes de Plantas/genética , Poliploidia , Cromossomos/genética , Sintenia , Reprodução Assexuada/genética , FilogeniaRESUMO
Background: Clinical trials repurposing pulmonary arterial hypertension (PAH) therapies to patients with lung disease- or hypoxia-pulmonary hypertension (PH) (classified as World Health Organization Group 3 PH) have failed to show a consistent benefit. However, Group 3 PH clinical heterogeneity suggests robust phenotyping may inform detection of treatment-responsive subgroups. We hypothesised that cluster analysis would identify subphenotypes with differential responses to oral PAH therapy. Methods: Two k-means analyses were performed on a national cohort of US veterans with Group 3 PH; an inclusive model (I) of all treated patients (n=196) and a haemodynamic model (H) limited to patients with right heart catheterisations (n=112). The primary outcome was organ failure or all-cause mortality by cluster. An exploratory analysis evaluated within-cluster treatment effects. Results: Three distinct clusters of Group 3 PH patients were identified. In the inclusive model (C1I n=43, 21.9%; C2I n=102, 52.0%; C3I n=51, 26.0%), lung disease and spirometry drove cluster assignment. By contrast, in the haemodynamic model (C1H n=44, 39.3%; C2H n=43, 38.4%; C3H n=25, 22.3%), right heart catheterisation data surpassed the importance of lung disease and spirometry. In the haemodynamic model, compared to C3H, C1H experienced the greatest hazard for respiratory failure or death (HR 6.1, 95% CI 3.2-11.8). In an exploratory analysis, cluster determined treatment response (p=0.006). Conclusions regarding within-cluster treatment responses were limited by significant differences between select variables in the treated and untreated groups. Conclusions: Cluster analysis identifies novel real-world subphenotypes of Group 3 PH patients with distinct clinical trajectories. Future studies may consider this methodological approach to identify subgroups of heterogeneous patients that may be responsive to existing pulmonary vasodilatory therapies.
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The study of complex process models often encounters challenges in terms of comprehensibility. This paper explores using modularization as a strategy to mitigate such challenges, notably the reduction in complexity. Previous research has delved into the comprehensibility of modularized process models, yet an unresolved question about the cognitive factors at play during their comprehension still needs to be answered. Addressing the latter, the paper presents findings from an innovative study combining eye-tracking and concurrent think-aloud techniques involving 25 participants. The study aimed to comprehend how individuals comprehend process models when presented in three different modular formats: flattened process models, models with grouped elements, and models with subprocesses. The results shed light on varying comprehension strategies employed by participants when navigating through these modularized process models. The paper concludes by suggesting avenues for future research guided by these insights.
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Individual-level assessment of health and well-being permits analysis of community well-being and health risk evaluations across several dimensions of health. It also enables comparison and rankings of reported health and well-being for large geographical areas such as states, metropolitan areas, and counties. However, there is large variation in reported well-being within such large spatial units underscoring the importance of analyzing well-being at more granular levels, such as ZIP codes. In this paper, we address this problem by modeling well-being data to generate ZIP code tabulation area (ZCTA)-level rankings through spatially informed statistical modeling. We build regression models for individual-level overall well-being index and scores from five subscales (Physical, Financial, Social, Community, Purpose) using individual-level demographic characteristics as predictors while including a ZCTA-level spatial effect. The ZCTA neighborhood information is incorporated by using a graph Laplacian matrix; this enables estimation of the effect of a ZCTA on well-being using individual-level data from that ZCTA as well as by borrowing information from neighboring ZCTAs. We deploy our model on well-being data for the U.S. states of Massachusetts and Georgia. We find that our model can capture the effects of demographic features while also offering spatial effect estimates for all ZCTAs, including ones with no observations, under certain conditions. These spatial effect estimates provide community health and well-being rankings of ZCTAs, and our method can be deployed more generally to model other outcomes that are spatially dependent as well as data from other states or groups of states.
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Características de Residência , Humanos , Masculino , Feminino , Características da Vizinhança , Adulto , Pessoa de Meia-Idade , Nível de Saúde , Modelos Estatísticos , IdosoRESUMO
The European Society of Toxicologic Pathology (ESTP) organized a panel of 24 international experts from many fields of toxicologic clinical pathology (e.g., industry, academia, and regulatory) that came together in 2021 to align the use of terminology to convey the importance of clinical pathology findings in preclinical toxicity studies. An additional goal consisted of how to identify important findings in standard and nonstandard clinical pathology associated endpoints. This manuscript summarizes the information and opinions discussed and shared at the ninth ESTP International Expert Workshop, April 5 to 6, 2022. In addition to terminology usage, the workshop considered topics related to the identification and conveyance of the importance of test item-related findings. These topics included sources of variability, comparators, statistics, reporting, correlations to other study data, nonstandard biomarkers, indirect/secondary findings, and an overall weight-of-evidence approach.
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Patologia Clínica , Testes de Toxicidade , Toxicologia , Animais , Toxicologia/normas , Toxicologia/métodos , Testes de Toxicidade/métodos , Patologia Clínica/normas , Avaliação Pré-Clínica de Medicamentos , Humanos , Terminologia como AssuntoRESUMO
Alcohol contributes to higher fall risk in people living with HIV (PLWH), yet fall prevention trials for PWH with alcohol use are lacking. To assess the feasibility of conducting a randomized controlled trial of a 10-week online fall prevention intervention tailored for PLWH with alcohol use. The intervention consisted of weekly virtual group discussions, individual phone check-ins, and home exercises. Of those eligible, 53.5% (23/43) enrolled (12 to the intervention and 11 to control). Mean age was 58 years; 82.6% had a past 6-month fall; 65.2% had alcohol use disorder; and 95.7% completed postintervention assessments. The intervention was highly rated (Client Satisfaction Questionnaire-8 score M = 30.4, SD = 1.6) with a wide range of group and individual phone session attendance. Preliminary analyses suggest the intervention may reduce the odds of falling and alcohol use frequency. Findings support the feasibility of a larger randomized trial. ClinicalTrials.gov Identifier: NCT04804579.
A fall prevention feasibility trial for people with HIV and alcohol useAlcohol contributes to higher fall risk in people living with HIV (PLWH), yet fall prevention studies for PLWH with alcohol use are lacking. We conducted a 10-week online fall prevention intervention for PLWH (n = 23) with recent alcohol use to assess if the intervention was feasible and acceptable for PLWH. The intervention consisted of weekly virtual group discussions and individual phone check-ins with an occupational therapist and a customized home exercise program. The mean age was 58 years. Almost all fell in the past 6 months (82.6%), had impaired physical functioning (91.3%), and had alcohol use disorder (65.2%). Participants reported high intervention satisfaction. Preliminary analyses suggest that the intervention may reduce the odds of falling and alcohol use frequency. Findings support the feasibility of an online fall prevention intervention study for PLWH.
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BACKGROUND: To estimate the effects on pain of two medications (low-dose naltrexone and gabapentin) compared to placebo among people with HIV (PWH) with heavy alcohol use and chronic pain. METHODS: We conducted a pilot, randomized, double-blinded, 3-arm study of PWH with chronic pain and past-year heavy alcohol use in 2021. Participants were recruited in St. Petersburg, Russia, and randomized to receive daily low-dose naltrexone (4.5mg), gabapentin (up to 1800mg), or placebo. The two primary outcomes were change in self-reported pain severity and pain interference measured with the Brief Pain Inventory from baseline to 8 weeks. RESULTS: Participants (N = 45, 15 in each arm) had the following baseline characteristics: 64% male; age 41 years (SD±7); mean 2 (SD±4) heavy drinking days in the past month and mean pain severity and interference were 3.2 (SD±1) and 3.0 (SD±2), respectively. Pain severity decreased for all three arms. Mean differences in change in pain severity for gabapentin vs. placebo, and naltrexone vs. placebo were -0.27 (95% confidence interval [CI] -1.76, 1.23; p = 0.73) and 0.88 (95% CI -0.7, 2.46; p = 0.55), respectively. Pain interference decreased for all three arms. Mean differences in change in pain interference for gabapentin vs. placebo, and naltrexone vs. placebo was 0.16 (95% CI -1.38, 1.71; p = 0.83) and 0.40 (95% CI -1.18, 1.99; p = 0.83), respectively. CONCLUSION: Neither gabapentin nor low-dose naltrexone appeared to improve pain more than placebo among PWH with chronic pain and past-year heavy alcohol use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT4052139).
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Transtornos Relacionados ao Uso de Álcool , Dor Crônica , Infecções por HIV , Adulto , Feminino , Humanos , Masculino , Dor Crônica/complicações , Dor Crônica/tratamento farmacológico , Método Duplo-Cego , Gabapentina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Naltrexona/uso terapêutico , Manejo da Dor , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
There is a limited literature regarding factors associated with self-medication of pain and discomfort using alcohol, non-prescription substances or overuse of prescription medications among people living with Human Immunodeficiency Virus (HIV). This cross-sectional analysis used data from the Boston ARCH Cohort among participants with HIV infection and a history of alcohol or other substance use. Among 248 participants, 37% were female, 50% Black, 25% Latinx; 36% reported fair to poor health and 89% had CD4 cell counts >200/mm3. Half reported self-medication and of those, 8.8% reported doing so only with alcohol, 48.8% only with other substances and 42.4% with both alcohol and other substances. Those reporting self-medication were significantly (p < .05) younger (mean 47 vs 50 years), less employed (11% vs 21%), and less likely to have HIV viral suppression (60% vs. 80%). Depression, anxiety, and HIV symptoms were associated with significantly greater odds of self-medicating, as were substance dependence, recent injection substance use, heavy alcohol use, cocaine use, opioid use, sedative use, and cannabis use. Self-medication, highly prevalent and associated with worse mental health symptoms, greater substance use, and lesser HIV disease control, should be explored by HIV clinicians caring for people who use substances.
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Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Masculino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Transversais , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/psicologia , Dor/tratamento farmacológico , Dor/complicações , Etanol/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/complicaçõesRESUMO
BACKGROUND: Given alcohol and/or other drug (AOD) use occurs among people with HIV (PWH), we examined its association with falls and fall-related outcomes and whether frailty moderates the association. SETTING: Northeastern US city. METHODS: We analyzed an observational cohort of PWH with current or past AOD use. Alcohol measures were any past 14-day heavy use, average alcohol/day, and days with heavy use. Drug use measures were past 30-day illicit use of cocaine, opioids, and sedatives. Repeated cross-sectional associations were estimated with separate multivariable generalized estimating equation regression models for each fall-related outcome. RESULTS: Among PWH (n = 251; mean age 52 [SD = 10]), 35% reported heavy alcohol use, 24% cocaine, 16% illicit opioids, 13% illicit sedatives, and 35% any fall; 27% were frail. Heavy alcohol use was associated with a fall (AOR = 1.49, 95% CI: 1.08 to 2.07), multiple falls (AOR = 1.55 95% CI: 1.10 to 2.19), and fall/fracture-related emergency department visit or hospitalization (AOR = 1.81, 95% CI: 1.10 to 2.97). Higher average alcohol/day and more heavy drinking days were associated with multiple falls. Illicit sedative use was associated with a fall, multiple falls, and emergency department visit/hospitalization and opioid use with fracture. Frailty moderated the association of heavy alcohol use and a fall (AOR = 2.26, 95% CI: 1.28 to 4.01 in those frail) but not in those not frail. CONCLUSION: The effect of AOD use on falls and fall-related outcomes was most pronounced with alcohol, particularly among frail PWH. Heavy alcohol, illicit sedative, and illicit opioid use are high-priority targets for preventing falls and fall-related consequences for PWH.
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Consumo de Bebidas Alcoólicas , Fraturas Ósseas , Infecções por HIV , Drogas Ilícitas , Humanos , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Analgésicos Opioides , Cocaína , Estudos Transversais , Fraturas Ósseas/epidemiologia , Fragilidade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Opioides , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Immune-modifying medications are widely available and recognized as valuable by most gastroenterologists. However, approximately 40% of patients with Crohn's disease (CD) do not comply with regimens using these medications, resulting in complications, hospitalization, and surgeries. We sought to identify factors that motivate adherence or nonadherence with medication recommendations for CD. METHODS: We conducted qualitative interviews with patients living with CD who were identified as adherent or nonadherent to immune-modifying medication recommendations by their treating gastroenterologist. Semistructured interview guides were developed based on an established framework for understanding health behaviors. We conducted content analysis of the resulting qualitative data using an inductive-deductive approach to identify emergent themes that influence medication decision-making. RESULTS: Twenty-five patients with CD completed interviews for this study. Interviews were independently coded and analyzed for thematic content. Two broad domains emerged comprising (1) themes reflected in the Theoretical Domains Framework and (2) novel themes specific to medication decision-making in CD. Adherent patients conveyed a sense of trust in science and healthcare provider expertise, while nonadherent patients were more likely to express beliefs in their ability to self-manage CD, concern about risks associated with medication, and a general ambivalence to treatment. CONCLUSIONS: There are clear cognitive, behavioral, and relational factors that guide patients' medication-related decision-making. Several of the factors share features of other behavioral change and decision-making processes, while others are specific to the experience of patients with CD. A fuller understanding of these factors is essential to developing effective behavioral interventions to improve adherence to evidence-based treatment recommendations.
This study identified the determinants of medication adherence in a sample of patients receiving treatment for Crohn's disease. A total of 13 determinants across 2 domains were identified as contributing to patient decisions regarding the use of immune-modifying medications.
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Importance: Despite the benefits of goals-of-care (GOC) communication, many hospitalized individuals never communicate their goals or preferences to clinicians. Objective: To assess whether a GOC video intervention delivered by palliative care educators (PCEs) increased the rate of GOC documentation. Design, Setting, and Participants: This pragmatic, stepped-wedge cluster randomized clinical trial included patients aged 65 years or older admitted to 1 of 14 units at 2 urban hospitals in New York and Boston from July 1, 2021, to October 31, 2022. Intervention: The intervention involved PCEs (social workers and nurses trained in GOC communication) facilitating GOC conversations with patients and/or their decision-makers using a library of brief, certified video decision aids available in 29 languages. Patients in the control period received usual care. Main Outcome and Measures: The primary outcome was GOC documentation, which included any documentation of a goals conversation, limitation of life-sustaining treatment, palliative care, hospice, or time-limited trials and was obtained by natural language processing. Results: A total of 10â¯802 patients (mean [SD] age, 78 [8] years; 51.6% male) were admitted to 1 of 14 hospital units. Goals-of-care documentation during the intervention phase occurred among 3744 of 6023 patients (62.2%) compared with 2396 of 4779 patients (50.1%) in the usual care phase (P < .001). Proportions of documented GOC discussions for Black or African American individuals (865 of 1376 [62.9%] vs 596 of 1125 [53.0%]), Hispanic or Latino individuals (311 of 548 [56.8%] vs 218 of 451 [48.3%]), non-English speakers (586 of 1059 [55.3%] vs 405 of 863 [46.9%]), and people living with Alzheimer disease and related dementias (520 of 681 [76.4%] vs 355 of 570 [62.3%]) were greater during the intervention phase compared with the usual care phase. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of older adults, a GOC video intervention delivered by PCEs resulted in higher rates of GOC documentation compared with usual care, including among Black or African American individuals, Hispanic or Latino individuals, non-English speakers, and people living with Alzheimer disease and related dementias. The findings suggest that this form of patient-centered care delivery may be a beneficial decision support tool. Trial Registration: ClinicalTrials.gov Identifier: NCT04857060.
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Doença de Alzheimer , Humanos , Masculino , Idoso , Feminino , Objetivos , Comunicação , Documentação , Cuidados PaliativosRESUMO
Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans1,2, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-CreERT2::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-CreERT2::CFTRL/L). By comparing these models with cystic fibrosis ferrets3,4, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-CreERT2::CFTRL/L ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl- and HCO3-. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.
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Fibrose Cística , Modelos Animais de Doenças , Furões , Pulmão , Transgenes , Animais , Humanos , Animais Geneticamente Modificados , Linhagem da Célula , Fibrose Cística/genética , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Furões/genética , Furões/fisiologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Pulmão/patologia , Traqueia/citologia , Transgenes/genéticaRESUMO
Few studies have been conducted on the relationship between "outside-residing" resilience characteristics and the risk of developing drug use disorder later in life. These characteristics include responsive and caring parenting, household routines involving regular family meals and bedtime routines, social support from peers, participation in organized activities, and religious service attendance. We quantified the association between these resilience promotion factors during childhood and the risk of developing criteria for drug use disorder during adulthood using data from a retrospective cohort study of 618 adults born in Massachusetts during 1969-1983, including those with adverse childhood experiences (ACEs). Self-administered questionnaires gathered information on criteria for drug use disorder, ACEs, and family and community resilience promotion factors. Compared to individuals with "low" numbers of resilience promotion factors, 30% (95% CI: 0.5-0.9) and 50% reductions (95% CI: 0.4-0.8) in the risk of developing one or more criteria for drug use disorder were observed among those with "moderate" and "high" numbers of resilience factors, respectively (p value for trend=0.003). Overall, family factors were associated with greater risk reductions than comparable numbers of community factors. Among individuals with ACEs, a "high" number of family factors but not community factors were associated with a reduction in risk (RR:0.6, 95% CI:0.4-1.0 for family factors, RR:1.0, 95% CI:0.5-1.8 for community factors). These results suggest that the risk of developing criteria for drug use disorder decreases in a dose-response fashion according to the number of "outside-residing" resilience promotion factors during childhood, and that family factors are associated with greater risk reductions than community factors, particularly among individuals with ACEs. Coordinated prevention efforts at the family and community level are recommended to reduce the risk of this important societal problem.
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The proliferation of online eHealth has made it much easier for users to access healthcare services and interventions from the comfort of their own homes. This study looks at how well one such platform-eSano-performs in terms of user experience when delivering mindfulness interventions. In order to assess usability and user experience, several tools such as eye-tracking technology, think-aloud sessions, a system usability scale questionnaire, an application questionnaire, and post-experiment interviews were employed. Participants were evaluated while they accessed the first module of the mindfulness intervention provided by eSano to measure their interaction with the app, and their level of engagement, and to obtain feedback on both the intervention and its overall usability. The results revealed that although users generally rated their experience with the app positively in terms of overall satisfaction, according to data collected through the system usability scale questionnaire, participants rated the first module of the mindfulness intervention as below average. Additionally, eye-tracking data showed that some users skipped long text blocks in favor of answering questions quickly while others spent more than half their time reading them. Henceforth, recommendations were put forward to improve both the usability and persuasiveness of the app-such as incorporating shorter text blocks and more engaging interactive elements-in order to raise adherence rates. Overall findings from this study provide valuable insights into how users interact with the eSano's participant app which can be used as guidelines for the future development of more effective and user-friendly platforms. Moreover, considering these potential improvements will help foster more positive experiences that promote regular engagement with these types of apps; taking into account emotional states and needs that vary across different age groups and abilities. Supplementary Information: The online version contains supplementary material available at 10.1007/s12652-023-04635-4.