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While many freshwater invaders originate from saline habitats, the physiological mechanisms involved are poorly understood. We investigated the evolution of ion transporter Na+/K+-ATPase (NKA) protein expression between ancestral saline and freshwater invading populations of the copepod Eurytemora carolleae (Atlantic clade of the E. affinis complex). We compared in situ NKA expression between populations under common-garden conditions at three salinities in the maxillary glands. We found the evolution of reduced NKA expression in the freshwater population under freshwater conditions and reduced plasticity (canalization) across salinities, relative to the saline population. Our results support the hypothesis that maxillary glands are involved in ion reabsorption from excretory fluids at low-salinity conditions in the saline population. However, mechanisms of freshwater adaptation, such as increased ion uptake from the environment, might reduce the need for ion reabsorption in the freshwater population. These patterns of ion transporter expression contribute insights into the evolution of ionic regulation during habitat change.
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Background: Rates of alcohol and/or substance use (ASU) among residents of predominantly Black and marginalized communities are similar to ASU rates in White communities. Yet ASU has worse consequences in predominantly Black and marginalized communities (e.g., higher incarceration). Objective: We randomized participants to one of 16 intervention conditions using a 24 full factorial design to optimize a multilevel intervention reducing ASU among 602 formerly incarcerated men with substance-use-disorders (SUD). Candidate intervention components included (1) critical dialogue (CD; six weekly 2-hour-long group sessions vs. no CD sessions), (2) Quality of Life Wheel (QLW; six weekly 1-hour-long group sessions vs. no QLW sessions), (3) capacity building projects (CBP; six weekly 1-hour-long group sessions vs. no CBP sessions), and (4) delivery by a trained peer versus licensed facilitators. Outcome was percentage of days in which participants used alcohol, cocaine, opioid, and/or cannabis in previous 30 days. Results: Intent-to-treat analysis did not meet a priori component selection criteria due to low intervention attendance. After controlling for intervention group attendance (percentage of sessions attended), peer-delivered CD and CBP produced statistically and clinically significant main and interaction effects in ASU over 5 months. Per the multiphase optimization strategy framework, we selected peer-delivered CD and CBP for inclusion as the optimized version of the intervention with a cost of US$1,380 per 10 individuals. No adverse intervention effects occurred. Conclusion: CD and CBP were identified as the only potentially effective intervention components. Future research will examine strategies to improve attendance and test the optimized intervention against standard of care in a randomized-controlled-trial.
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Fortalecimento Institucional , Prisioneiros , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Prisioneiros/psicologia , Pessoa de Meia-Idade , Qualidade de Vida , Alcoolismo/terapia , Alcoolismo/prevenção & controleRESUMO
INTRODUCTION: To understand the experiences of adolescent and adult patients living with alopecia areata (AA) in Australia regarding symptom severity and the impact on psychosocial well-being and work/classroom productivity. MATERIALS AND METHODS: A cross-sectional online patient survey among adolescent and adult patients diagnosed with AA was recruited via the Australia Alopecia Areata Foundation. Patient-reported outcomes were also assessed. RESULTS: A total of 337 patients (49 adolescents; 288 adults), with a mean ± standard deviation age of 14.7 ± 1.55 and 38.9 ± 13.31 years for adolescents and adults, respectively, were included. In the group with extensive hair loss (Scalp Hair Assessment Patient-Reported Outcome, categories 3 + 4, n = 172), we observed higher emotional symptom and activity limitation scores (Alopecia Areata Patient Priority Outcomes, emotional symptoms: adults 2.5 ± 1.03, adolescents 2.2 ± 1.15; activity limitations: adults 1.4 ± 1.15, adolescents 1.2 ± 0.99). Additionally, in adults, the Alopecia Areata Symptom Impact Scale global score was 4.0 ± 2.10 (symptoms subscale score 4.1 ± 1.91; interference subscale scores 3.8 ± 2.73). Hospital Anxiety and Depression Scale scores were high across participants, irrespective of hair loss extent (adults: anxiety 9.2 ± 3.85, depression 6.6 ± 3.95; adolescents: anxiety 9.7 ± 4.65, depression 5.2 ± 3.59). Work and classroom productivity were substantially impaired due to AA, with 70.5% of adults and 57.1% of adolescents reporting activity impairment, and overall work/classroom impairment reported at 39.2% and 44.9%, respectively. CONCLUSIONS: AA impacts the physical, emotional and psychosocial well-being of both adult and adolescent patients. More extensive hair loss more profoundly impacts those living with AA. Patients may benefit from patient-centred care approaches addressing the impact of hair loss on mental and emotional well-being, daily activities and work productivity.
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Alopecia em Áreas , Qualidade de Vida , Humanos , Alopecia em Áreas/psicologia , Adolescente , Masculino , Feminino , Adulto , Estudos Transversais , Austrália , Pessoa de Meia-Idade , Adulto Jovem , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Depressão/psicologia , Depressão/epidemiologia , Ansiedade/psicologia , EficiênciaRESUMO
Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the Dietary Supplement Health and Education Act (DSHEA) of 1994 reduced FDA oversight, these products have become less regulated. Data from 2012 shows 18% of U.S. adults used non-vitamin, non-mineral natural products. Prevalence varies regionally, with higher use in Western states. Among preoperative patients, the most commonly used herbal medications included garlic, ginseng, ginkgo, St. John's wort, and echinacea. However, 50-70% of surgical patients fail to disclose their use of herbal medications to their physicians, and most fail to discontinue them preoperatively. Since herbal medications can interact with anesthetic medications administered during surgery, the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) recommend stopping herbal medications 1-2 weeks before elective surgical procedures. Potential adverse drug effects related to preoperative use of herbal medications involve the coagulation system (e.g., increasing the risk of perioperative bleeding), the cardiovascular system (e.g., arrhythmias, hypotension, hypertension), the central nervous system (e.g., sedation, confusion, seizures), pulmonary (e.g., coughing, bronchospasm), renal (e.g., diuresis) and endocrine-metabolic (e.g., hepatic dysfunction, altered metabolism of anesthetic drugs). During the preoperative evaluation, anesthesiologists should inquire about the use of herbal medications to anticipate potential adverse drug interactions during the perioperative period.
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Interações Ervas-Drogas , Preparações de Plantas , Humanos , Preparações de Plantas/efeitos adversos , Preparações de Plantas/administração & dosagem , Período Perioperatório , Suplementos Nutricionais/efeitos adversos , Assistência Perioperatória/métodos , Anestésicos/efeitos adversos , Anestésicos/administração & dosagem , Fitoterapia/efeitos adversos , Estados Unidos , Interações MedicamentosasRESUMO
Despite tremendous progress in the development of mature heart-on-a-chip models, human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip with circulating immune cells to model severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute myocarditis. We observed hallmarks of coronavirus disease (COVID-19)-induced myocardial inflammation, as the presence of immune cells augmented the secretion of proinflammatory cytokines, triggered progressive impairment of contractile function, and altered intracellular calcium transients. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the heart-on-a-chip and then validated in COVID-19 patients with low left ventricular ejection fraction, demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation-induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2-induced myocardial inflammation, we established that administration of endothelial cell-derived exosomes effectively rescued the contractile deficit, normalized calcium handling, elevated the contraction force, and reduced the ccf-mtDNA and cytokine release via Toll-like receptor-nuclear factor κB signaling axis.
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COVID-19 , Exossomos , Miocardite , Humanos , DNA Mitocondrial/genética , Volume Sistólico , Cálcio , Função Ventricular Esquerda , Inflamação , SARS-CoV-2 , CitocinasRESUMO
BACKGROUND: The United States envisions a 90% reduction in HIV infections by 2030. However, the COVID-19 pandemic disrupted the HIV continuum and disproportionately affected access to social and health services for people at the highest vulnerability. This study shows how stakeholders in the State of Michigan handled disruptions and their key recommendations. As a case study, this study adds to the literature about preparedness for future pandemics. METHODS: We interviewed 33 statewide Michigan HIV/AIDS Council members-practitioners, researchers, and community representatives, guiding service planning, improvement, and resource allocations, measuring group cohesiveness using a tested scale. We measured group cohesiveness as a proxy for how individual opinions reflected those of the Council as a group. We used qualitative questions to assess: (1) how the COVID-19 pandemic disrupted HIV prevention; (2) how disruptions were handled; and (3) recommendation to help address disruptions now and in the future. Using thematic analysis, we coded the interviews. RESULTS: We found a high degree of cohesiveness. Participants agreed that the pandemic disrupted HIV prevention services (e.g., HIV testing, PrEP education, referrals to primary care, etcetera) offered by community organizations, hospital clinics, and health departments across the state. In response, they developed online and curbside services to maintain HIV services, abate social isolation, and address structural issues like lack of food and public transportation. We organized results in four categories: (1) HIV service disruptions (e.g., "Housing for women and children who are fleeing a legal situation"); (2) Responses to disruptions (e.g., "Some of them, we would say, hey, weather permitting, we'll come out to your car"); (3) Minoritized groups disproportionately affected (e.g., "Especially in my community, to get people if there's ever a vaccine, Black people are going to be the last people to take it"); and (4) Recommendations (below). CONCLUSIONS: The pandemic unsettled and further exacerbated every aspect of HIV service provision. The main recommendation was to overhaul communication systems between government and organizations offering HIV services to mitigate disruptions and improve the chances of achieving a 90% reduction.
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Síndrome da Imunodeficiência Adquirida , COVID-19 , Infecções por HIV , Criança , Feminino , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Pandemias/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , Diretivas AntecipadasRESUMO
T-cell-engaging bispecific antibody (T-BsAb, also known as BiTE) therapy has emerged as a powerful therapeutic modality against multiple myeloma. Given that T-BsAb therapy redirects endogenous T cells to eliminate tumor cells, reinvigorating dysfunctional T cells may be a potential approach to improve the efficacy of T-BsAb. While various immunostimulatory cytokines can potentiate effector T-cell functions, the optimal cytokine treatment for T-BsAb therapy is yet to be established, partly due to a concern of cytokine release syndrome driven by aberrant interferon (IFN)-γ production. Here, we functionally screen immunostimulatory cytokines to determine an ideal combination partner for T-BsAb therapy. This approach reveals interleukin (IL)-21 as a potential immunostimulatory cytokine with the ability to augment T-BsAb-mediated release of granzyme B and perforin, without increasing IFN-γ release. Transcriptome profiling and functional characterization strongly support that IL-21 selectively targets the cytotoxic granule exocytosis pathway, but not pro-inflammatory responses. Notably, IL-21 modulates multiple steps of cytotoxic effector functions including upregulation of co-activating CD226 receptor, increasing cytotoxic granules, and promoting cytotoxic granule delivery at the immunological synapse. Indeed, T-BsAb-mediated myeloma killing is cytotoxic granule-dependent, and IL-21 priming significantly augments cytotoxic activities. Furthermore, in vivo IL-21 treatment induces cytotoxic effector reprogramming in bone marrow T cells, showing synergistic anti-myeloma effects in combination with T-BsAb therapy. Together, harnessing the cytotoxic granule exocytosis pathway by IL-21 may be a potential approach to achieve better responses by T-BsAb therapy.
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Anticorpos Biespecíficos , Exocitose , Mieloma Múltiplo , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Humanos , Camundongos , Animais , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Mieloma Múltiplo/patologia , Citotoxicidade Imunológica , Interleucinas/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Granzimas/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/efeitos dos fármacosRESUMO
PURPOSE: Necrotizing enterocolitis (NEC) is a severe intestinal disease primarily affecting premature infants, marked by impaired epithelial regeneration. Breastfed infants are less susceptible to NEC than formula-fed ones, and human milk oligosaccharides (HMO) found in breast milk have prebiotic properties that can protect against NEC. However, it is unclear how HMOs influence intestinal epithelium regeneration in relation to the gut microbiota. METHODS: Broad-spectrum antibiotics were administered to pregnant dams to reduce the microbiota in offspring. NEC was induced through administration of hyperosmolar formula, lipopolysaccharide, and hypoxia from postnatal days (p) 5-9. Intestinal epithelial organoids were derived from p9 mice. HMOs were isolated from human donor breast milk and then solubilized in the formula for each feed or culture media for organoids. RESULTS: HMOs did not alter the microbiota profile in the presence of a normal or reduced microbiota. In the reduced microbiota, HMO treatment decreased NEC intestinal injury, and increased proliferation and stem cell activity. Additionally, in the complete absence of the microbiota, HMOs stimulated intestinal organoid growth. CONCLUSION: This study demonstrates that HMOs promoted intestinal epithelial regeneration independent of the gut microbiota. These findings provide further insight into the various benefits HMOs may have in the protection against NEC.
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Enterocolite Necrosante , Doenças do Recém-Nascido , Microbiota , Lactente , Feminino , Gravidez , Recém-Nascido , Animais , Humanos , Camundongos , Leite Humano , Enterocolite Necrosante/prevenção & controle , Mucosa Intestinal , Oligossacarídeos/farmacologia , RegeneraçãoRESUMO
OBJECTIVES: Vaccinations are an important preventative measure in reducing the spread of infectious diseases worldwide. However, concerns of undervaccination during childhood have become increasingly common. The current study aims to investigate changes in attitudes towards childhood vaccinations prior to the COVID-19 pandemic using a national sample from New Zealand. DESIGN: Age-based, period-based, and cohort-based changes were assessed using cohort-sequential latent growth modelling in 11 overlapping birth cohorts, which spanned the ages of 23-79 years. SETTING AND PARTICIPANTS: Data were taken from the New Zealand Attitudes and Values Study where 58 654 adults completed at least one wave across a 7-year period (2013 and 2015-2019). RESULTS: The period-based and cohort-based models fit the data equally well (χ2(282)=8547.93, p<0.001, comparative fit index, CFI=0.894, root mean square error of approximation, (RMSEA)=0.074, standardised root mean square residual, SRMR=0.105; χ2(273)=8514.87, p<0.001, CFI=0.894, RMSEA=0.075, SRMR=0.105, respectively) suggesting societal factors contribute to childhood vaccination attitudes. Additionally, the findings suggest attitudes towards childhood vaccinations were becoming increasingly more positive in all birth cohorts (ps<0.001), with younger and older birth cohorts exhibiting even positive attitudes compared with middle-aged cohorts. CONCLUSION: Overall, both the cohort-based and period-based models reveal changes in vaccination attitudes suggesting that even prior to the COVID-19 pandemic, societal influences had an impact on attitudes towards childhood vaccination.
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COVID-19 , Pandemias , Adulto , Pessoa de Meia-Idade , Humanos , Adulto Jovem , Idoso , Nova Zelândia/epidemiologia , Efeito de Coortes , Inquéritos e Questionários , Vacinação , COVID-19/epidemiologia , COVID-19/prevenção & controle , AtitudeRESUMO
T-cell-engaging bispecific antibodies (T-BsAb) have produced impressive clinical responses in patients with relapsed/refractory B-cell malignancies, although treatment failure remains a major clinical challenge. Growing evidence suggests that a complex interplay between immune cells and tumor cells is implicated in the mechanism of action and therefore, understanding immune regulatory mechanisms might provide a clue for how to improve the efficacy of T-BsAb therapy. Here, we investigated the functional impact of regulatory T (Treg) cells on anti-tumor immunity elicited by T-BsAb therapy. In a preclinical model of myeloma, the activation and expansion of Treg cells in the bone marrow were observed in response to anti-B-cell maturation antigen (BCMA) T-BsAb therapy. T-BsAb triggered the generation of induced Treg cells from human conventional CD4 cells after co-culture with tumor cells. Moreover, T-BsAb directly activated freshly isolated circulating Treg cells, leading to the production of interleukin-10 and inhibition of T-BsAb-mediated CD8 T-cell responses. The activation of Treg cells was also seen in bone marrow samples from myeloma patients after ex vivo treatment with T-BsAb, further supporting that T-BsAb have an impact on Treg homeostasis. Importantly, transient ablation of Treg cells in combination with T-BsAb therapy dramatically improved effector lymphocyte activities and disease control in the preclinical myeloma model, leading to prolonged survival. Together, this information suggests that therapy-induced activation of Treg cells critically regulates anti-tumor immunity elicited by T-BsAb therapy, with important implications for improving the efficacy of such treatment.
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Anticorpos Biespecíficos , Mieloma Múltiplo , Humanos , Linfócitos T Reguladores , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Linfócitos T CD4-Positivos , Linfócitos T CD8-PositivosRESUMO
PURPOSE: Neonatal sepsis is a systemic inflammatory infection common in premature infants and a leading cause of mortality. Argon is an emerging interest in the field of noble gas therapy. Neonates with severe sepsis are frequently mechanically ventilated creating an opportunity for inhalation therapy. We aimed to investigate argon inhalation as a novel experimental therapy in neonatal sepsis. METHODS: Sepsis was established in C57BL/6 neonatal mice by a lipopolysaccharide intraperitoneal injection on postnatal day 9. Septic pup mice were exposed to room air as well as non-septic controls. In the argon group, septic pup mice were exposed to argon (70% Ar, 30% O2) for 6 h in a temperature-controlled environment. RESULTS: At 6 h, survival was significantly enhanced when septic mice received argon compared to septic controls. Serum profiles of cytokine release were significantly attenuated as well as lung architecture restored. CONCLUSIONS: Our findings suggest that argon inhalation as a novel treatment for neonatal sepsis, reducing mortality and counteracting the acute systemic inflammatory response in the blood and preserving the architecture of the lung. This research can contribute to a paradigm shift in the treatment and outcome of neonates with sepsis.
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Sepse Neonatal , Sepse , Humanos , Lactente , Animais , Camundongos , Camundongos Endogâmicos C57BL , Argônio/uso terapêutico , Sepse/terapia , InflamaçãoRESUMO
Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases. When fine-scale population structure was explored using NETVIEW, cases were distributed throughout an extended pedigree. When genotyped cases (n = 49) and dogs from the control group (n = 281) were compared in a genome-wide association analysis of lymphoma risk, the most prominent associated regions were detected on CFA13 and CFA33. The top SNPs in a 5.4 Mb region on CFA13 were significant at a chromosome-wide level, and the region was fine-mapped to ~1.2 Mb (CFA13: 25.2-26.4 Mb; CanFam3.1) with four potential functional candidates, including the MYC proto-oncogene bHLH transcription factor (MYC) and a region syntenic with the human and mouse lncRNA Pvt1 oncogene (PVT1). A 380 Kb associated region at CFA33: 7.7-8.1 Mb contained the coding sequence for SUMO specific peptidase7 (SENP7) and NFK inhibitor zeta (NFKBIZ) genes. These genes have annotations related to cancer, amongst others, and both have functional links to MYC regulation. Genomic signatures identified in lymphoma cases suggest that increased risk contributed by the regions identified by GWAS may complement a complex predisposing genetic background.
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Community-based research has found racial differences in suicide attempts for Black and White men and in how men are treated after a suicide attempt; however, prison-based research has largely not explored such differences. This study examined racial differences in the circumstances of incarcerated men's suicide attempts and investigated health care disparities in staff responses to these suicide attempts. With administrative data from three state prisons over a 5-year period, we conducted a latent class analysis to explore patterns of suicide attempts for 207 incarcerated men. We examined race as a predictor of class membership. Black men were more likely than White men to use a method of hanging/suffocation for attempting suicide, and they were also commonly subjected to segregation when they attempted suicide. Black men were less likely to receive health care post-attempt than White men. Given the findings of this study, several key researches, practices, and policy directions are needed to prevent suicide and promote the health and well-being of incarcerated men, particularly incarcerated Black men.
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The outpatient dialysis setting presents unique challenges in the medication process. Dialysis staff conduct all steps in the medication process, including transcribing and verifying orders, preparing and administering medications, and monitoring for therapeutic and adverse effects. When addressing best medication practices, consideration should be given to education and resources provided to staff. This article explores the multiple strategies taken by a national dialysis network to support clinical staff and improve patient safety.
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Erros de Medicação , Diálise Renal , Humanos , Erros de Medicação/prevenção & controle , Segurança do PacienteRESUMO
With climate change, habitat salinity is shifting rapidly throughout the globe. In addition, many destructive freshwater invaders are recent immigrants from saline habitats. Recently, populations of the copepod Eurytemora affinis species complex have invaded freshwater habitats multiple times independently from saline estuaries on three continents. This review discusses features of this species complex that could enhance their evolutionary potential during rapid environmental change. Remarkably, across independent freshwater invasions, natural selection has repeatedly favored the same alleles far more than expected. This high degree of parallelism is surprising, given the expectation of nonparallel evolution for polygenic adaptation. Factors such as population structure and the genome architecture underlying critical traits under selection might help drive rapid adaptation and parallel evolution. Given the preponderance of saline-to-freshwater invasions and climate-induced salinity change, the principles found here could provide invaluable insights into mechanisms operating in other systems and the potential for adaptation in a changing planet.
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Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.
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BACKGROUND: The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10 cm without vascular invasion and metastasis. METHODS: From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10 cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored. RESULTS: The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS. CONCLUSIONS: HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Infusões Intra-Arteriais , Resultado do TratamentoRESUMO
AIM: To identify key predictors of general practitioner (GP) satisfaction and increase insight into the mechanisms behind ethnic health inequities in New Zealand. METHOD: Regression analyses were conducted using data from the 2019 New Zealand Attitudes and Values Study (n=38,465). RESULTS: Initially, Maori and Asian peoples showed lower, and Pasifika peoples showed no significant difference in GP satisfaction level relative to New Zealand (NZ) Europeans. However, after accounting for differences in patient-perceived GP cultural respect and GP ethnic similarity, Maori and Pasifika peoples showed higher and Asian peoples showed no difference in GP satisfaction level relative to NZ Europeans. These effects continued to hold when adjusting for a range of demographic factors. Subsequent regression analyses were conducted to investigate the impact of GP perceptions, GP satisfaction and demographic factors on healthcare access satisfaction and health status across ethnic groups. For all ethnic groups, GP satisfaction was the strongest predictor of satisfaction with access to healthcare. Higher GP satisfaction was also a significant predictor of higher self-rated health and lower psychological distress. CONCLUSION: Lack of GP cultural respect is a key contributor to lower GP satisfaction among ethnic minorities, which can further exacerbate inequities in healthcare access and health outcomes. Interventions to enhance GPs' provision of culturally respectful and safe healthcare services may help reduce ethnic health inequities and improve population health.
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Etnicidade , Clínicos Gerais , Humanos , Nova Zelândia/epidemiologia , Satisfação do Paciente , Povo MaoriRESUMO
BACKGROUND: Adaptive interventions are often used in individualized health care to meet the unique needs of clients. Recently, more researchers have adopted the Sequential Multiple Assignment Randomized Trial (SMART), a type of research design, to build optimal adaptive interventions. SMART requires research participants to be randomized multiple times over time, depending upon their response to earlier interventions. Despite the increasing popularity of SMART designs, conducting a successful SMART study poses unique technological and logistical challenges (e.g., effectively concealing and masking allocation sequence to investigators, involved health care providers, and subjects) in addition to other challenges common to all study designs (e.g., study invitations, eligibility screening, consenting procedures, and data confidentiality protocols). Research Electronic Data Capture (REDCap) is a secure, browser-based web application widely used by researchers for data collection. REDCap offers unique features that support researchers' ability to conduct rigorous SMARTs. This manuscript provides an effective strategy for performing automatic double randomization for SMARTs using REDCap. METHODS: Between January and March 2022, we conducted a SMART using a sample of adult (age 18 and older) New Jersey residents to optimize an adaptive intervention to increase COVID-19 testing uptake. In the current report, we discuss how we used REDCap for our SMART, which required double randomization. Further, we share our REDCap project XML file for future investigators to use when designing and conducting SMARTs. RESULTS: We report on the randomization feature that REDCap offers and describe how the study team automated an additional randomization that was required for our SMART. An application programming interface was used to automate the double randomizations in conjunction with the randomization feature provided by REDCap. CONCLUSIONS: REDCap offers powerful tools to facilitate the implementation of longitudinal data collection and SMARTs. Investigators can make use of this electronic data capturing system to reduce errors and bias in the implementation of their SMARTs by automating double randomization. TRIAL REGISTRATION: The SMART study was prospectively registered at Clinicaltrials.gov; registration number: NCT04757298, date of registration: 17/02/2021.