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BACKGROUND: Mutations in genes encoding sarcomeric proteins lead to failures in sarcomere assembly, the building blocks of contracting muscles, resulting in cardiomyopathies that are a leading cause of morbidity and mortality worldwide. Splicing variants of sarcomeric proteins are crucial at different stages of myofibrillogenesis, accounting for sarcomeric structural integrity. RBM24 (RNA-binding motif protein 24) is known as a tissue-specific splicing regulator that plays an essential role in cardiogenesis. However, it had been unclear if the developmental stage-specific alternative splicing facilitated by RBM24 contributes to sarcomere assembly and cardiogenesis. Our aim is to study the molecular mechanism by which RBM24 regulates cardiogenesis and sarcomere assembly in a temporal-dependent manner. METHODS: We ablated RBM24 from human embryonic stem cells (hESCs) using CRISPR/Cas9 techniques. RESULTS: Although RBM24-/- hESCs still differentiated into sarcomere-hosting cardiomyocytes, they exhibited disrupted sarcomeric structures with punctate Z-lines due to impaired myosin replacement during early myofibrillogenesis. Transcriptomics revealed >4000 genes regulated by RBM24. Among them, core myofibrillogenesis proteins (eg, ACTN2 [α-actinin 2], TTN [titin], and MYH10 [non-muscle myosin IIB]) were misspliced. Consequently, MYH6 (muscle myosin II) cannot replace nonmuscle myosin MYH10, leading to myofibrillogenesis arrest at the early premyofibril stage and causing disrupted sarcomeres. Intriguingly, we found that the ABD (actin-binding domain; encoded by exon 6) of the Z-line anchor protein ACTN2 is predominantly excluded from early cardiac differentiation, whereas it is consistently included in human adult heart. CRISPR/Cas9-mediated deletion of exon 6 from ACTN2 in hESCs, as well as forced expression of full-length ACTN2 in RBM24-/- hESCs, further corroborated that inclusion of exon 6 is critical for sarcomere assembly. Overall, we have demonstrated that RBM24-facilitated inclusion of exon 6 in ACTN2 at distinct stages of cardiac differentiation is evolutionarily conserved and crucial to sarcomere assembly and integrity. CONCLUSIONS: RBM24 acts as a master regulator to modulate the temporal dynamics of core myofibrillogenesis genes and thereby orchestrates sarcomere organization.
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Processamento Alternativo , Células-Tronco Embrionárias Humanas/metabolismo , Desenvolvimento Muscular , Miócitos Cardíacos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Actinina/genética , Actinina/metabolismo , Diferenciação Celular , Linhagem Celular , Conectina/genética , Conectina/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Humanos , Miócitos Cardíacos/citologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Miosina não Muscular Tipo IIB/genética , Miosina não Muscular Tipo IIB/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
In clinical practice, many patients with heart failure with reduced ejection fraction (HFrEF) are either not prescribed guideline-directed medical therapies for which they are eligible or are prescribed therapies at sub-target doses. The objective of this study was to examine the factors associated with not receiving guideline-directed medical therapies or receiving sub-target doses. We conducted a systematic review of articles published between January 2014 and May 2019 that described dosing patterns and factors associated with non-use and sub-target dosing of HFrEF therapies in clinical practice. Thirty-seven studies were included. The percentages of patients reaching target doses for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists ranged from 4 to 55%, 11 to 87%, 4 to 60%, and 22 to 80%, respectively. Older age and worsening renal function were associated with non-use and sub-target dosing, lower body mass index was commonly associated with non-use, and hyperkalemia and hypotension were commonly associated with sub-target dosing. In conclusion, several common patient characteristics are associated with non-use and sub-target dosing of medical therapy for HFrEF. These high-risk groups are in particular need of further studies to improve implementation of available medications and to define the role of novel therapies.
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Insuficiência Cardíaca , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Volume SistólicoRESUMO
PURPOSE: Genomics services have the potential to reduce incidence and mortality of diseases by providing individualized, family health history (FHH)-based prevention strategies to clients. These services may benefit from the involvement of community health workers (CHWs) in the provision of FHH-based genomics education and services, as CHWs are frontline public health workers and lay health educators, who share similar ethnicities, languages, socioeconomic statuses, and life experiences with the communities they serve. We developed, implemented, and evaluated the FHH-based genomics training program for CHWs. METHODS: This theory- and evidence-based FHH-focused genomics curriculum was developed by an interdisciplinary team. Full-day workshops in English and Spanish were delivered to 145 Texas CHWs (91.6% were Hispanic/black). Preworkshop, postworkshop, and 3-month follow-up data were collected. RESULTS: CHWs significantly improved their attitudes, intention, self-efficacy, and knowledge regarding adopting FHH-based genomics into their practice after the workshops. At 3-month follow-up, these scores remained higher, and there was a significant increase in CHWs' genomics practices. CONCLUSION: This FHH-based genomics training successfully educated Texas CHWs, and the outcomes were promising. Dissemination of training to CHWs in and outside of Texas is needed to promote better access to and delivery of personalized genomics services for the lay and underserved communities.
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Agentes Comunitários de Saúde/educação , Educação/métodos , Educadores em Saúde/educação , Adulto , Currículo , Feminino , Genômica/educação , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , TexasRESUMO
INTRODUCTION: Treatment adherence and persistence impact the effectiveness of edoxaban for the prevention of thromboembolism in patients with atrial fibrillation (AF). The objective of this analysis was to assess adherence and persistence of edoxaban vs. other non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs). METHODS: Utilizing a German claims database, adults with AF with the first pharmacy claim identified for edoxaban, apixaban, dabigatran, rivaroxaban, or VKAs from January 2013 to December 2017 were included in a propensity score-matched analysis. The first pharmacy claim was the index claim. Adherence (i.e., proportion of days covered [PDC]) and persistence (proportion of patients who continued therapy) were compared between edoxaban and other therapies. Patients receiving once-daily (QD) vs. twice-daily (BID) NOAC were also analyzed. RESULTS: Overall, 21,038 patients were included (1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA). After matching, baseline characteristics were well balanced across cohorts. Adherence was significantly higher for edoxaban vs. apixaban, dabigatran, and VKAs (all P < 0.0001). Significantly more edoxaban patients continued therapy vs. rivaroxaban (P = 0.0153), dabigatran (P < 0.0001), and VKAs (P < 0.0001). Time to discontinuation was significantly longer for edoxaban vs. dabigatran, rivaroxaban, and VKAs (all P < 0.0001). More patients receiving NOACs QD had a PDC ≥ 0.8 compared with those receiving NOACs BID (65.3 vs. 49.6%, respectively; P < 0.05); persistence rates were comparable between QD and BID groups. CONCLUSIONS: Patients with AF receiving edoxaban had significantly higher adherence and persistence compared with those receiving VKAs. This trend was also seen in NOAC QD regimens vs. NOAC BID regimens for adherence. These results provide insight into how adherence and persistence may contribute to the effectiveness of edoxaban for stroke prevention in patients with AF in Germany.
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STUDY OBJECTIVE: To develop, validate, and deploy models for predicting delirium in critically ill adult patients as early as upon intensive care unit (ICU) admission. DESIGN: Retrospective cohort study. SETTING: Single university teaching hospital in Taipei, Taiwan. PATIENTS: 6238 critically ill patients from August 2020 to August 2021. MEASUREMENTS: Data were extracted, pre-processed, and split into training and testing datasets based on the time period. Eligible variables included demographic characteristics, Glasgow Coma Scale, vital signs parameters, treatments, and laboratory data. The predicted outcome was delirium, defined as any positive result (a score ≥ 4) of the Intensive Care Delirium Screening Checklist that was assessed by primary care nurses in each 8-h shift within 48 h after ICU admission. We trained models to predict delirium upon ICU admission (ADM) and at 24 h (24H) after ICU admission by using logistic regression (LR), gradient boosted trees (GBT), and deep learning (DL) algorithms and compared the models' performance. MAIN RESULTS: Eight features were extracted from the eligible features to train the ADM models, including age, body mass index, medical history of dementia, postoperative intensive monitoring, elective surgery, pre-ICU hospital stays, and GCS score and initial respiratory rate upon ICU admission. In the ADM testing dataset, the incidence of ICU delirium occurred within 24 h and 48 h was 32.9% and 36.2%, respectively. The area under the receiver operating characteristic curve (AUROC) (0.858, 95% CI 0.835-0.879) and area under the precision-recall curve (AUPRC) (0.814, 95% CI 0.780-0.844) for the ADM GBT model were the highest. The Brier scores of the ADM LR, GBT, and DL models were 0.149, 0.140, and 0.145, respectively. The AUROC (0.931, 95% CI 0.911-0.949) was the highest for the 24H DL model and the AUPRC (0.842, 95% CI 0.792-0.886) was the highest for the 24H LR model. CONCLUSION: Our early prediction models based on data obtained upon ICU admission could achieve good performance in predicting delirium occurred within 48 h after ICU admission. Our 24-h models can improve delirium prediction for patients discharged >1 day after ICU admission.
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Delírio , Adulto , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Estado Terminal , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Marsh's internal/external (I/E) frame of reference model depicts the relationship between achievement and self-concept in specific academic domains. Few efforts have been made to examine concurrent relationships among cognitive ability, achievement, and academic self-concept (ASC) within an I/E model framework. AIM: To simultaneously examine the influences of domain-specific cognitive ability and grades on domain self-concept in an extended I/E model, including the indirect effect of domain-specific cognitive ability on domain self-concept via grades. SAMPLE: Tenth grade respondents (628 male, 452 female) to a national adolescent survey conducted in Taiwan. METHOD: Respondents completed surveys designed to measure maths and verbal aptitudes. Data on Maths and Chinese class grades and self-concepts were also collected. RESULTS: Statistically significant and positive path coefficients were found between cognitive ability and self-concept in the same domain (direct effect) and between these two constructs via grades (indirect effect). The cross-domain effects of either ability or grades on ASC were negatively significant. CONCLUSIONS: Taiwanese 10th graders tend to evaluate their ASCs based on a mix of ability and achievement, with achievement as a mediator exceeding ability as a predictor. In addition, the cross-domain effects suggest that Taiwanese students are likely to view Maths and verbal abilities and achievements as distinctly different.
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Logro , Aptidão , Cognição , Controle Interno-Externo , Autoimagem , Adolescente , Coleta de Dados , Feminino , Humanos , Masculino , TaiwanRESUMO
The current protocol aims to showcase the technology integration, providing a detailed description of adopting the HealthCloud app, developed by the Healthy Landscape and Healthy People Lab, National Taiwan University (HLHP-NTU), on smartphones and smartwatches to collect data on users' real-time psychological and physiological responses and environmental information. A flexible and integrated research method was proposed because it can be difficult to measure multi-dimensional aspects of personal data in on-site studies in landscape and outdoor recreation research. An on-site study conducted in 2020 at the National Taiwan University campus was used as an application example. A dataset of 385 participants was used after excluding invalid samples. During the experiment, participants were asked to walk around campus for 30 min when their heart rate and psychological-scale items were measured, together with several environmental metrics. This work aimed to provide a possible solution to help on-site studies track real-time human responses that match ambient factors. Due to the app's flexibility, its use on wearable devices shows excellent potential for multidisciplinary research studies.
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Aplicativos Móveis , Dispositivos Eletrônicos Vestíveis , Nível de Saúde , Humanos , Monitorização Fisiológica , SmartphoneRESUMO
Breast cancer cells release a large quantity of biocargo-bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV-bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and ß1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular-body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early-stage patients. With a magnetic bead-based flow cytometry assay, we confirmed that integrins αv and ß1 are enriched in the CD63+ subsets of EVs from both human and mouse highly metastatic cells. By analysing the level of integrin αv on circulating EVs, this assay could predict the metastatic potential of a xenografted mouse model. To explore the export mechanism of integrins into EVs, we performed immunoprecipitation mass spectrometry and identified members of the galectin family as potential shuttlers of integrin αvß1 into EVs. In particular, knockdown of galectin-3, but not galectin-1, causes a reduction in the levels of cell surface integrins ß1 and αv, and decreases the colocalization of these integrins with CD63. Importantly, knockdown of galectin-3 leads to a decrease of integrin αvß1 export into the EVs concomitant with a decrease in the metastatic potential of breast cancer cells. Moreover, inhibition of the integrin αvß1 complex leads to a reduction in the binding of EVs to fibronectin, suggesting that integrin αvß1 is important for EV retention in the extracellular matrix. EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV-bound integrin αvß1 with breast cancer metastasis and provide additional insights into the export of integrin αvß1 into EVs in the context of metastasis.
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Neoplasias da Mama , Vesículas Extracelulares , Animais , Neoplasias da Mama/metabolismo , Vesículas Extracelulares/metabolismo , Feminino , Galectina 3 , Humanos , Integrina alfaV , Melanoma , Camundongos , Receptores de Vitronectina/metabolismo , Neoplasias Cutâneas , Microambiente Tumoral , Melanoma Maligno CutâneoRESUMO
OBJECTIVE: To analyze the differences between ondansetron and palonosetron in healthcare resource use (i.e., inpatient/ outpatient encounters) among patients receiving intraperitoneal cisplatin. METHOD: A medical record review was performed. Intraperitoneal cisplatin administrations for gynecological cancers from January through June 2006 and from October 2007 through June 2008 were divided into two groups based on the serotonin-receptor antagonist used. The occurrence of chemotherapy-induced nausea and vomiting (CINV)-related hospital readmissions, emergency department visits, and outpatient encounters occurring within 7 days after cisplatin administration was compared. CINV-related resource use was defined as events associated with dehydration, hypovolemia, nausea/vomiting, hypokalemia, constipation, shortness of breath, or syncope/collapse. RESULTS: Ondansetron or palonosetron was used in 39 and 89 cisplatin administrations, respectively. The baseline characteristics were similar between the groups with mean age of 59 years and ovarian cancer being the most common cancer. Length of stay was approximately 2 days. Palonosetron was always administered as a single-day therapy while one- or multi-day ondansetron therapy was administered in 27% and 73% of cycles, respectively. A trend towards more CINV-related hospitalizations with ondansetron versus palonosetron was observed (5.1% vs. 0%, p = 0.09) with no significant difference in other CINV-related encounters. CONCLUSION: Palonosetron was associated with a trend to a lower risk of CINV-related hospital readmission than ondansetron in patients receiving intraperitoneal cisplatin for gynecological cancers, although not statistically significant. The duration of ondansetron therapy might be suboptimal with 27% of patients receiving only 1 day of therapy during hospital stay. These findings need to be confirmed in future studies.
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Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Recursos em Saúde/estatística & dados numéricos , Isoquinolinas/administração & dosagem , Náusea/prevenção & controle , Ondansetron/administração & dosagem , Pré-Medicação , Quinuclidinas/administração & dosagem , Antagonistas da Serotonina/administração & dosagem , Vômito/prevenção & controle , Adulto , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Antieméticos/efeitos adversos , Antineoplásicos/administração & dosagem , Boston , Cisplatino/administração & dosagem , Esquema de Medicação , Substituição de Medicamentos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Neoplasias das Tubas Uterinas/tratamento farmacológico , Feminino , Humanos , Isoquinolinas/efeitos adversos , Tempo de Internação , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Ondansetron/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Palonossetrom , Readmissão do Paciente , Quinuclidinas/efeitos adversos , Medição de Risco , Fatores de Risco , Antagonistas da Serotonina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
OBJECTIVE: To examine pregabalin dose titration and its impact on treatment adherence and duration in patients with neuropathic pain (NeP). METHODS: MarketScan database (2009-2014) was used to extract a cohort of incident adult pregabalin users with NeP who had at least 12 months of follow-up data. Any dose augmentation within 45 days following the first pregabalin claim was defined as dose titration. Adherence (measured by medication possession ratio/MPR) and persistence (measured as the duration of continuous treatment) were compared between the cohorts with and without dose titration. Logistic regressions and Cox proportional hazards models were used to identify the factors associated with adherence (MPR ≥ 0.8) and predictors of time to discontinuation. RESULTS: Among the 5,186 patients in the analysis, only 18% of patients had dose titration. Patients who had dose titration were approximately 2.6 times as likely to be adherent (MPR ≥ 0.8) (odds ratio = 2.59, P < 0.001) than those who did not have dose titration. Kaplan-Meier analysis shows that the time to discontinuation or switch was significantly longer among patients who had dose titration (4.99 vs. 4.04 months, P = 0.009). CONCLUSIONS: Dose titration was associated with improved treatment adherence and persistence among NeP patients receiving pregabalin. The findings will provide valuable evidence to increase physician awareness of dose recommendations in the prescribing information and to educate patients on the importance of titration and adherence.
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Redução da Medicação/métodos , Adesão à Medicação/psicologia , Pregabalina/uso terapêutico , Adulto , Estudos de Coortes , Bases de Dados Factuais , Redução da Medicação/tendências , Duração da Terapia , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Pregabalina/administração & dosagem , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Children's food approach and food avoidance are appetitive traits with genetic or biological bases. Nonetheless, parents play a critical role in children's dietary intake through parenting and feeding practices. The present study tested parents' controlling feeding practices (i.e., restriction and pressure to eat) as mediating mechanisms between child appetitive traits and child BMI in an economically and ethnically diverse sample. Participants were 139 children aged 4 to 6 years (51.8% males, M = 4.77 years, SD = 0.84) and their parents. Results showed that restriction and pressure to eat mediated the relation between child food approach or food avoidance and child BMI. Mediation effects did not differ across poverty status or racial/ethnic groups. Also, the type of controlling feeding that parents exert related to children's weight status in diametrically different or opposite ways. Thus, food-related parenting appears to be a promising point of entry for childhood obesity prevention programs. Findings are consistent with a biopsychosocial model of the development of eating and weight in childhood which takes into account both parent and child behavior and characteristics and links child biology and behavior with psychosocial processes and environment.
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Peso Corporal/fisiologia , Comportamento Infantil/psicologia , Comportamento Alimentar/psicologia , Relações Pais-Filho , Poder Familiar/psicologia , Personalidade/fisiologia , Adulto , Índice de Massa Corporal , Criança , Comportamento Infantil/etnologia , Pré-Escolar , Comportamento Alimentar/etnologia , Feminino , Humanos , Masculino , Relações Pais-Filho/etnologia , Poder Familiar/etnologiaRESUMO
INTRODUCTION: The physical, social, psychological, and economic burden of opioid use disorder (OUD) is substantial. As of the year 2019, the predominant focus of OUD research was outcomes such as retention and abstinence. We report herein the effects of extended-release buprenorphine (BUP-XR), the first FDA-approved subcutaneously injected, monthly treatment for OUD, on patient-centered outcomes. MATERIALS AND METHODS: Patient-centered outcomes were collected during an open-label safety study of participants with OUD (NCT# 02510014) evaluating BUP-XR. Measures collected during the study included the EQ-5D-5L, SF-36v2, Treatment Effectiveness Assessment (TEA), Addiction Severity Index-Lite (ASI-Lite), employment/insurance status questionnaire, and Medication Satisfaction Questionnaire (MSQ). Changes from baseline to end of study week 49 were analyzed using mixed models for repeated measures. "Baseline" was defined as the value collected prior to the first BUP-XR injection. Results presented are for those participants who initiated treatment on BUP-XR during the open-label study and were eligible to receive up to 12 injections. RESULTS: Four hundred twelve participants were included in analyses; 206 participants discontinued BUP-XR prematurely. Mean EQ-5D-5L scores remained stable from baseline to end of study. Statistically significant improvements from baseline to end of study were noted for the SF-36v2 mental component summary score (difference = 5.0, 95%CI: 3.5-6.5) and 7 of 8 domain scores (P < .05 for all comparisons); the SF-36v2 physical component summary remained stable from baseline to end of study. The TEA total score (difference = 9.3 points, 95%CI: 8.0-10.5) and 4 of 4 domain scores (difference = 2-3 points per domain) significantly improved from baseline to end of study. Significant improvements (P < .05 for all comparisons) on the ASI-Lite were seen for all problem areas except alcohol use from baseline to end of study. Employment rate increased 7% whereas health insurance status remained stable from baseline to end of study. Medication satisfaction measured using the MSQ was >88% at end of study. CONCLUSIONS: Treatment with BUP-XR monthly injections for up to 12 months in this cohort of treatment-seeking individuals with OUD led to positive PCOs and high treatment satisfaction, which correspond to personal recovery.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Buprenorfina/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Emprego , Humanos , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Assistência Centrada no PacienteRESUMO
Chemokine receptor CXCR4 is a major drug target for numerous diseases because of its involvement in the regulation of cell migration and the developmental process. In this study, atomic-level molecular dynamics simulations were used to determine the activation mechanism and internal water formation of CXCR4 in complex with chemokine CXCL12 and Gi-protein. The results indicated that CXCL12-bound CXCR4 underwent transmembrane 6 (TM6) outward movement and a decrease in tyrosine toggle switch by eliciting the breakage of hydrophobic layer to form a continuous internal water channel. In the GDP-bound Gαi-protein state, the rotation and translation of the α5-helix of Gαi-protein toward the cytoplasmic pocket of CXCR4 induced an increase in interdomain distance for GDP leaving. Finally, an internal water channel formation model was proposed based on our simulations for CXCL12-bound CXCR4 in complex with Gαi-protein upon activation for downstream signaling. This model could be useful in anticancer drug development.
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OBJECTIVE: To summarize the evidence on pharmacologic options in preventing postoperative ileus (POI). DATA SOURCES: The Cochrane Database of Reviews and OVID databases and Food and Drug Administration (FDA) Web site were searched (1950-April 2009) using the term postoperative ileus. STUDY SELECTION AND DATA EXTRACTION: Meta-analyses and randomized controlled trials were included for review. The FDA Web site was searched for clinical reviews and label information for drugs indicated for the prevention of POI. DATA SYNTHESIS: Three meta-analyses, 2 on gum-chewing and 1 on alvimopan, and 18 clinical trials were identified. Only gum chewing and alvimopan were effective in preventing POI. Gum chewing reduced the time to first flatus and bowel movement (weighted mean difference 21h; p = 0.0006 and 33h; p = 0.0002, respectively). In one meta-analysis, gum chewing significantly reduced length of stay (LOS) by 2.4 days (p < 0.00001) but this was not replicated in the second meta-analysis. Alvimopan shortened the time to reach a composite endpoint of solid food intake, plus/minus flatus, and bowel movement (93 vs 105 h; p < 0.001). A higher incidence of myocardial infarction was observed in a 12-month study of alvimopan for the treatment of opioid-induced bowel dysfunction, but not in studies in patients undergoing bowel resection. Alvimopan decreased the time to written hospital discharge order (hazard ratio 1.35; p < 0.01), while the significance of a reduction in LOS (0.2-1.3 days) was not reported. CONCLUSIONS: Gum chewing and alvimopan are effective in preventing POI, but given safety concerns and higher cost with alvimopan, gum chewing may be preferred.
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Goma de Mascar , Íleus/prevenção & controle , Piperidinas/uso terapêutico , Ensaios Clínicos como Assunto , Custos de Medicamentos , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/economia , Fármacos Gastrointestinais/uso terapêutico , Humanos , Íleus/etiologia , Piperidinas/efeitos adversos , Piperidinas/economia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/prevenção & controleRESUMO
We conducted the first needs assessment study by examining the information needs in genetic testing for autism spectrum disorders among parents of children with autism spectrum disorders in Taiwan. Parents of children with autism spectrum disorders in 236 public elementary schools with special education services were invited to complete a survey. About two-thirds of participants (65.7%) had never heard about genetic testing for autism spectrum disorders. Yet, the majority (71.4%) expressed an interest in learning about this testing. The top three topics participants identified to assist them in making informed decisions before undergoing genetic testing (for themselves, their affected children, or other family members) were testing accuracy (79.7%), genetic causes of autism spectrum disorders (79.4%), and the link between testing and treatment (79.4%). A health education brochure (47.2%) was the most desired educational approach. Our results can be utilized to develop information and counseling materials for genetic testing for autism spectrum disorders in Taiwan as well as to address the needs of parents of children with autism spectrum disorders, particularly in informed decisions-making. Moreover, to promote better communication between the providers and parents, when discussing genetic testing for autism spectrum disorders with Taiwanese parents of children with autism spectrum disorders, healthcare professionals' priorities should be in line with the preferred topics identified in this study.
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Transtorno do Espectro Autista/genética , Aconselhamento Genético , Testes Genéticos , Avaliação das Necessidades , Pais , Acesso à Informação , Adulto , Criança , Tomada de Decisões , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Inquéritos e Questionários , TaiwanRESUMO
Background: Guidelines recommend selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) as first-line treatments for major depressive disorder (MDD) and emphasize the importance of early pharmacological treatment as key factors to treatment success.Objectives: To compare the MDD-related healthcare resource utilization (HCRU) and cost among patients (1) with early vs late pharmacological treatment initiation and (2) achieving minimum therapeutic dose (MTD) early vs late.Methods: The MarketScan database (2010-2015) was used. Adults who were newly-treated with SSRI/SNRI within 12 months after the initial MDD diagnosis (index) were included. Patients who initiated SSRI/SNRI within 2 weeks of the index date were defined as early initiators; those who reached MTD within 4 weeks of index date were defined as early MTD achievers. MDD-related HCRU and costs per year after the index date were compared between early and late initiators and between early and late achievers using propensity score matching and generalized linear models.Results: Of the 55,539 patients, 60% were early initiators and 61% were early MTD achievers. The mean number of MDD-related outpatient visits per year were significantly higher for late initiator (6.7 vs 4.2, p < .001) and late MTD achievers (6.5 vs 4.5, p < .001) vs their early counterparts. Mean annual MDD-related outpatient, drug, and total cost were significantly higher for late initiators and MTD achievers vs the early groups.Conclusions: There is an opportunity to improve outcomes by treating MDD patients with SSRI/SNRI within 2 weeks and at or above the MTD within 4 weeks of diagnosis or less.
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Transtorno Depressivo Maior/tratamento farmacológico , Intervenção Médica Precoce , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Análise Custo-Benefício , Transtorno Depressivo Maior/economia , Transtorno Depressivo Maior/epidemiologia , Intervenção Médica Precoce/economia , Intervenção Médica Precoce/normas , Feminino , Alocação de Recursos para a Atenção à Saúde/métodos , Humanos , Masculino , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVE: Teriflunomide is a once-daily oral immunomodulatory agent approved in 80 countries for the treatment of patients with relapsing multiple sclerosis (RMS). The study objective was to estimate the cost effectiveness of teriflunomide (14 mg tablet, daily) versus interferon beta-1b (250 mcg subcutaneous injection, every other day) among RMS patients from the Chinese healthcare system perspective. METHODS: A Markov model with annual cycles and a lifetime horizon was utilized to assess cost-effectiveness of teriflunomide in comparison with interferon beta-1b in RMS patients. Treatment effects, including 3-month confirmed disability worsening and annualized relapse rate, were derived from a network meta-analysis. Cost inputs included costs related to treatment acquisition, administration, monitoring, natural disease management through Expanded Disability Status Scale states, relapse treatment, and adverse event management. These costs were calculated as the product between unit costs from published sources and healthcare resource utilization patterns identified in a survey conducted among 11 neurologists across different areas in China. Health effects were expressed as quality-adjusted life years (QALYs) with costs in local currency (¥) and US dollars (US$), 2018. RESULTS: Teriflunomide dominated interferon beta-1b and was associated with lower total costs (teriflunomide ¥1,887,144 vs interferon beta-1b ¥2,061,393) and higher QALYs (teriflunomide 9.60 QALYs vs interferon beta-1b 8.88 QALYs). In probabilistic sensitivity analysis, teriflunomide was dominant in 62.2% of model runs. CONCLUSION: Teriflunomide is a cost-effective therapy over a lifetime time horizon compared to interferon beta-1b in the treatment of RMS patients in China. Results should be interpreted with caution as head-to-head comparisons are not available.
Assuntos
Crotonatos/administração & dosagem , Fatores Imunológicos/administração & dosagem , Interferon beta-1b/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Toluidinas/administração & dosagem , Adulto , China , Análise Custo-Benefício , Crotonatos/economia , Feminino , Humanos , Hidroxibutiratos , Fatores Imunológicos/economia , Injeções Subcutâneas , Interferon beta-1b/economia , Masculino , Esclerose Múltipla Recidivante-Remitente/economia , Nitrilas , Anos de Vida Ajustados por Qualidade de Vida , Recidiva , Toluidinas/economiaRESUMO
OBJECTIVE: Opioid use disorder (OUD) is associated with physical, social, psychological, and economic burden. This analysis assessed the effects of RBP-6000, referred to as BUP-XR (extended-release buprenorphine), a subcutaneously injected, monthly buprenorphine treatment for OUD compared with placebo on patient-centered outcomes measuring meaningful life changes. METHODS: Patient-centered outcomes were collected in a 24-week, phase 3, placebo-controlled study assessing the efficacy, safety, and tolerability of BUP-XR 300/300âmg (6â×â300âmg) and 300/100âmg (2â×â300âmg followed by 4â×â100âmg) injections in treatment-seeking participants with moderate-to-severe OUD. Measures included the EQ-5D-5L, SF-36v2, Medication Satisfaction Questionnaire, employment/insurance status, and healthcare resource utilization (HCRU). Changes from baseline to end of study were compared across treatment arms, using mixed models for repeated measures. RESULTS: Participants receiving BUP-XR (nâ=â389) versus placebo (nâ=â98) had significantly greater changes from baseline on the EQ-5D-5L index (300/300âmg: differenceâ=â0.0636, Pâ=â0.003), EQ-5D-5L visual analog scale (300/300âmg: differenceâ=â5.9, Pâ=â0.017; 300/100âmg: differenceâ=â7.7, Pâ=â0.002), and SF-36v2 physical component summary score (300/300âmg: differenceâ=â3.8, Pâ<â0.001; 300/100âmg: differenceâ=â3.2, Pâ=â0.002). Satisfaction was significantly higher for participants receiving BUP-XR 300/300âmg (88%, Pâ<â0.001) and 300/100âmg (88%, Pâ<â0.001) than placebo (46%). Employment and percentage of insured participants increased by 10.8% and 4.1% with BUP-XR 300/300âmg and 10.0% and 4.7% with 300/100âmg but decreased by 12.6% and 8.4% with placebo. Participants receiving BUP-XR compared with placebo had significantly fewer hospital days per person-year observed. CONCLUSIONS: These results show the feasibility of measuring patient-centered life changes in substance use disorder clinical studies. Participants receiving up to 6 monthly injections of BUP-XR, compared with placebo, reported better health, increased medication satisfaction, increased employment, and decreased healthcare utilization.
Assuntos
Buprenorfina/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Satisfação do Paciente/estatística & dados numéricos , Qualidade de Vida , Adulto , Analgésicos Opioides/sangue , Analgésicos Opioides/urina , Buprenorfina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Emprego , Feminino , Humanos , Injeções Subcutâneas , Seguro Saúde/economia , Modelos Logísticos , Masculino , Antagonistas de Entorpecentes/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde , Cooperação do Paciente , Assistência Centrada no Paciente , Estados UnidosRESUMO
BACKGROUND: Over 10 million Chinese are affected by schizophrenia. The annual cost of schizophrenia in China was estimated at US$2586 per patient. AIMS: The study has two aims: (1) to conduct a targeted literature review of the economic literature on oral ziprasidone in China, and (2) to develop an inpatient economic model that compared the cost of intramuscular ziprasidone with other regimens including electroconvulsive therapy (ECT) for the management of acute agitation in patients with schizophrenia from a hospital's perspective in China. METHODS: A targeted literature review was conducted using PubMed and the Chinese literature databases for studies published between January 2007 and December 2017. Studies that assessed costs associated with oral ziprasidone treatment for schizophrenia in China were summarised. In the inpatient economic model, cost measures included hospital room and board, antipsychotics, ECT and medications for the management of extrapyramidal symptoms (EPS). Input for standard antipsychotic regimens and unit cost were obtained from the literature. Hospital length of stay (LOS), utilisation of ECT and incidence of EPS were derived from the literature and supplemented/validated with a survey of psychiatrists in China. Cost was presented in 2017 Chinese yuan. RESULTS: The average estimated LOS was 29 days with ziprasidone, 33 days with risperidone+benzodiazepine, 32 days with olanzapine, 35 days with haloperidol and 29 days with ECT. The cost of antipsychotics was ¥1260 with ziprasidone, ¥137 with risperidone+benzodiazepine, ¥913 with olanzapine and ¥210 with haloperidol; ECT treatment cost ¥785. The base-case analysis suggested that higher antipsychotic cost with ziprasidone was offset by savings with shorter LOS. Using intramuscular ziprasidone for acute management was associated with a total cost of ¥11 157, the lowest among all antipsychotic regimens (¥11 424 with risperidone+benzodiazepine, ¥11 711 with olanzapine and ¥11 912 with haloperidol) and slightly higher than ECT (¥10 606). The cost of antipsychotics and ECT accounted for 1 %-11 % of the total cost. Varying LOS between the lower and upper bounds of the 95% CI, the total cost was comparable between these regimens. CONCLUSIONS: Overall, the cost for the management of acute agitation was similar between intramuscular ziprasidone and other antipsychotics. Compared with other antipsychotics, the higher medication cost of intramuscular ziprasidone can be offset by savings with shorter hospital stay. The results from this economic analysis were complementary to the findings in the published literature assessing the economic outcomes of oral ziprasidone.
RESUMO
When analyzing complex longitudinal data, especially data from different educational settings, researchers generally focus only on the mean part (i.e., the regression coefficients), ignoring the equally important random part (i.e., the random effect variances) of the model. By using Project English Language and Literacy Acquisition (ELLA) data, we demonstrated the importance of taking the complex data structure into account by carefully specifying the random part of the model, showing that not only can it affect the variance estimates, the standard errors, and the tests of significance of the regression coefficients, it also can offer different perspectives of the data, such as information related to the developmental process. We used xxM (Mehta, 2013), which can flexibly estimate different grade-level variances separately and the potential carryover effect from each grade factor to the later time measures. Implications of the findings and limitations of the study are discussed.