Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 357
Filtrar
1.
Blood Adv ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575558

RESUMO

Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity, mortality, and a disproportionate burden on Black and Hispanic communities. Our objective was to estimate the total healthcare costs and total out-of-pocket costs attributable to SCD among commercially insured individuals over their non-elderly lifetimes (0-64 years of age). We constructed a retrospective cohort of individuals with diagnosed SCD using Truven Health Marketscan commercial claims data from 2007-2018, compared with matched controls from the Medical Expenditure Panel Survey. We estimated Kaplan-Meier sample average costs using previously reported survival curves for SCD and controls. 20,891 individuals with SCD and 33,588 controls were included in our analysis. The SCD sample had a mean age of 25.7 (SD 17.4) years; 58.0% were female. Survival-adjusted costs of SCD peaked at age 13-24 years and declined at older ages. There was no significant difference in total medical costs or OOP costs between the sexes. SCD-attributable costs over 0-64 years of age were estimated to be $1.6 million (95%CI: $1.3M, $1.9M) and $1.7 million (95% CI: $1.4M, $2.1M) for females and males with SCD, respectively. The corresponding OOP estimates were $42,395 (95%CI: $34,756, $50,033) for females and $45,091 (95% CI: $36,491, $53,691) for males. These represent a 907% and 285% increase in total medical and OOP costs over controls, respectively. Although limited to the commercially insured population, these results indicate that the direct economic burden of SCD is substantial and peaks at younger ages, suggesting the need for curative and new medical therapies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35363602

RESUMO

INTRODUCTION: Sickle cell disease (SCD) is a rare genetic disease with limited therapeutic options. Gene-based therapies are being investigated in clinical trials to evaluate their curative potential. The expected life-long benefits of one-time administration of genetically corrected stem cells present uncharted challenges in estimating value of these treatments. Our objective is to conduct a landscape analysis of clinical trials and prompt a discussion estimating the value of gene therapy as a therapeutic option for SCD. AREAS COVERED: We searched Clinicaltrials.gov to identify and characterize clinical trials in gene therapies for SCD. We report available results and discuss current concerns and elements of value necessary to consider as these products come to market. EXPERT OPINION: Gene therapies could represent a major advance in SCD treatment. Although clinical trials are ongoing, reports of serious adverse events have led to pause of these trials, emphasizing the need to prove long-term tolerability. Measured using the methods of health economic evaluation, we anticipate high up-front costs may be offset by potential life-long benefits of these treatments. During development and after treatment approval, attention should be focused on ensuring adequate availability and equitable access to emerging therapies in underserved areas and low-middle-income countries (LMIC).

3.
Metab Brain Dis ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35486209

RESUMO

Japanese Encephalitis Virus (JEV) is a neurotropic virus that invades Central Nervous System (CNS) and causes severe neuroinflammation. Given the abundance and the position of astrocytes in the CNS, we speculate that they might play a critical role in the process of neuroinflammation. Unfortunately, the role of astrocytes in JEV-mediated neuroinflammation has long been understated. In this study, we have attempted to assess the role of astrocyte-mediated neuroinflammation upon JEV infection. Mouse model of JEV infection, generated by intraperitoneal injection, showed severe reactive astrogliosis. To further address our hypothesis, we employed immortalized astrocytic cell line (in vitro) and primary astrocyte-enriched culture (ex vivo) as experimental models. JEV infection in the astrocytes induces proinflammatory cytokines like MCP1/CCL2 and IL6 in both ex vivo and in vitro cultures as observed from the cytometric bead array analysis. A significantly altered cytokine profile was observed using PCR analysis in in vitro and ex vivo models upon infection, with respect to control, validating our previous results. We also show that there exists a major inconsistency in the viral replication kinetics, wherein the cell line showed a robust rate of replication whereas the primary astrocyte-enriched culture showed negligibly low number of plaques, underlining the importance of the selection of appropriate experimental model system. In conclusion, we claim that astrocytes significantly contribute to JEV-mediated neuroinflammation, despite not being a CNS immune cell.

4.
Lancet Planet Health ; 6(4): e320-e330, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35397220

RESUMO

BACKGROUND: The US Environmental Protection Agency (EPA) currently sets maximum contaminant levels (MCLs) for ten metals or metalloids in public drinking water systems. Our objective was to estimate metal concentrations in community water systems (CWSs) across the USA, to establish if sociodemographic or regional inequalities in the metal concentrations exist, and to identify patterns of concentrations for these metals as a mixture. METHODS: We evaluated routine compliance monitoring records for antimony, arsenic, barium, beryllium, cadmium, chromium, mercury, selenium, thallium, and uranium, collected from 2006-11 (2000-11 for uranium; timeframe based on compliance monitoring requirements) by the US EPA in support of their second and third Six-Year Reviews for CWSs. Arsenic, barium, chromium, selenium, and uranium (detectable in >10% records) were included in the main analyses (subgroup and metal mixture analyses; arsenic data reported previously). We compared the mean, 75th percentile, and 95th percentile contaminant concentrations and the percentage of CWSs with concentrations exceeding the MCL across subgroups (region, sociodemographic county-cluster, size of population served, source water type, and CWSs exclusively serving correctional facilities). We evaluated patterns in CWS metal concentration estimate profiles via hierarchical cluster analysis. We created an online interactive map and dashboard of estimated CWS metal concentrations for use in future analyses. FINDINGS: Average metal concentrations were available for a total of 37 915 CWSs across the USA. The total number of monitoring records available was approximately 297 000 for arsenic, 165 000 for barium, 167 000 for chromium, 165 000 for selenium, and 128 000 for uranium. The percentage of analysed CWSs with average concentrations exceeding the MCL was 2·6% for arsenic (MCL=10 µg/L; nationwide mean 1·77 µg/L; n=36 798 CWSs), 2·1% for uranium (MCL=30 µg/L; nationwide mean 4·37 µg/L; n=14 503 CWSs), and less than 0·1% for the other metals. The number of records with detections was highest for uranium (63·1%). 75th and 95th percentile concentrations for uranium, chromium, barium, and selenium were highest for CWSs serving Semi-Urban, Hispanic communities, CWSs reliant on groundwater, and CWSs in the Central Midwest. Hierarchical cluster analysis revealed two distinct clusters: an arsenic-uranium-selenium cluster and a barium-chromium cluster. INTERPRETATIONS: Uranium is an under-recognised contaminant in CWSs. Metal concentrations (including uranium) are elevated in CWSs serving Semi-Urban, Hispanic communities independent of location or region, highlighting environmental justice concerns. FUNDING: US National Institutes of Health Office of the Director, US National Institutes for Environmental Health Sciences, and US National Institute of Dental and Craniofacial Research.


Assuntos
Arsênio , Selênio , Urânio , Poluentes Químicos da Água , Arsênio/análise , Bário , Cromo/análise , Estudos Transversais , Urânio/análise , Água , Poluentes Químicos da Água/análise
5.
Pharmacoecon Open ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35471578

RESUMO

BACKGROUND: Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making. OBJECTIVE: We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs. METHODS: We searched MEDLINE and EMBASE (2008-2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle-Ottawa Scale, and costs were adjusted to 2019 US$. RESULTS: Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals (cost difference range: $6636-$63,436 annually). The highest medical cost component for SCD patients was inpatient ($11,978-$59,851 annually), followed by outpatient and then pharmacy. No studies characterized the cost burden throughout the lifetime disease trajectory of an SCD individual, and no studies captured caregiver or productivity costs. CONCLUSION: Our results reveal an incomplete characterization of medical and non-medical costs within SCD. A deeper understanding of the medical and non-medical cost burden requires completion of additional studies that capture the burden across the patient's lifetime, in addition to expression of the impact of existing and emergent health technologies on disease trajectory.

6.
PLoS One ; 17(4): e0267448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35482721

RESUMO

BACKGROUND: Sickle cell disease (SCD) is a clinically heterogeneous disease with many acute and chronic complications driven by ongoing vaso-occlusion and hemolysis. It causes a disproportionate burden on Black and Hispanic communities. Our objective was to follow the SMDM/ISPOR Task Force recommendations for good practices and create a conceptual model of the progression of SCD under current clinical practice to inform cost-effectiveness analyses (CEA) of promising curative therapies in the pipeline over a lifetime horizon. METHODS: We used consultations with experts, providers, and patients to identify acute events and chronic conditions in the conceptual model. We compared our model structure to previous CEA models of interventions for SCD, assessed the prevalence of the identified disease attributes in Medicaid and Medicare claims databases, and identified relevant outcomes following the 2nd Panel in CEA. We determined an appropriate modeling technique and relevant data sources for parameterizing the model. RESULTS: The conceptual model structure included four dimensions of disease: chronic pain, acute events, chronic conditions, and treatment complications, spanning 26 disease attributes with significant impacts on health-related quality of life and resource. We modeled chronic pain separately to reflect its importance to patients and interaction with all other disease attributes. We identified additional data sources for health state utilities and non-medical costs and benefits of SCD. We will use a microsimulation model with age- and sex-specific transitions between health states predicted by patient demographic characteristics and disease history. CONCLUSION: Developing the model structure through an explicit process of model conceptualization can increase the transparency and accuracy of results. We will populate the conceptual model with the data sources described and evaluate the cost-effectiveness of curative therapies.


Assuntos
Anemia Falciforme , Dor Crônica , Idoso , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Feminino , Humanos , Masculino , Medicare , Modelos Teóricos , Qualidade de Vida , Estados Unidos
7.
Surg Obes Relat Dis ; 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397945

RESUMO

BACKGROUND: Comparative evidence is needed when deciding which bariatric operation to undergo for long-term cardiovascular risk reduction. OBJECTIVES: The Effectiveness of Gastric Bypass vs. Gastric Sleeve for Cardiovascular Disease (ENGAGE CVD) study compared the effectiveness of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations for reduction of the American College of Cardiology and the American Heart Association-predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk 5 years after surgery. SETTING: Data for this study came from a large integrated healthcare system in the Southern California region of the United States. This is one of the most ethnically diverse (64% non-White) bariatric populations in the literature. METHODS: The ENGAGE CVD cohort consisted of 22,095 patients who underwent VSG or RYGB from 2009-2016. The VSG and RYGB were compared using a local instrumental variable approach to address observed and unobserved confounding, as well as to conduct heterogeneity of treatment effects for patients of different age groups, baseline-predicted 10-year CVD risk using the ASCVD risk score, and those who had type 2 diabetes (T2D) at the time of surgery. RESULTS: Patients (2771 RYGB and 6256 VVSG) were primarily women (80.6%), Hispanic or non-Hispanic Black (63.7%), and 46 ± 10 years of age, with a body mass index of 43.40 ± 6.5 kg/m2. The predicted 10-year ASCVD risk at surgery was 4.1% for VSG and 5.1% for RYGB, decreasing to 2.6% for VSG and 2.8% for RYGB 1 year postoperatively. By 5 years after surgery, patients remained with relatively low risk levels (3.0% for VSG and 3.3% for RYGB) and there were no significant differences in predicted 10-year ASCVD risk between VSG and RYGB at any time. CONCLUSION: Predicted 10-year ASCVD risk was low in this population and remained low up to 5 years for those with diabetes, Black and Hispanic patients, and older adults. Literature reporting significant differences between VSG and RYGB in 10-year ASCVD risk may be a result of residual confounding.

8.
Health Serv Res ; 57(3): 603-613, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35235203

RESUMO

OBJECTIVE: To assess the effects of a program mandating the statewide adoption of an Emergency Department Information Exchange (EDIE) on health care utilization and spending among Medicaid enrollees in Washington state. DATA SOURCE: Medicaid claims and managed care encounters from the Washington Health Care Authority. STUDY DESIGN: A difference-in-differences analysis with trends was used to compare changes in ED visits, inpatient admissions, primary care visits, and expenditures among frequent ED users (≥5 ED visits in past year) to those of infrequent users through the second year Washington's program. DATA EXTRACTION: The study population included adult Medicaid enrollees with ED visits between January 2010 and October 2014. PRINCIPAL FINDINGS: There were 505,667 ED visits among 153,543 unique enrollees included in the analysis. Washington's program was associated with a small, but statistically significant differential change of -0.70 ED visits per enrollee per year (95% CI: -1.24, -0.16) in the first year after EDIE was mandated, or 8.2% of the baseline ED visit rate among frequent users. However, by the second year of implementation, these effects on ED use were no longer significant, nor were there any measurable effects on inpatient admissions, primary care use, or expenditures in any period. CONCLUSIONS: Statewide implementation of EDIE was associated with a small reduction in ED use among frequent users in the first year of the program but did not change overall spending or other utilization outcomes.

10.
Alzheimers Dement ; 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35293675

RESUMO

INTRODUCTION: We estimate the spending attributable to Alzheimer's disease and related dementias (ADRD) to the United States government for the first 5 years post-diagnosis. METHODS: Using data from the Health and Retirement Study matched to Medicare and Medicaid claims, we identify a retrospective cohort of adults with a claims-based ADRD diagnosis along with matched controls. RESULTS: The costs attributable to ADRD are $15,632 for traditional Medicare and $8833 for Medicaid per dementia case over the first 5 years after diagnosis. Seventy percent of Medicare costs occur in the first 2 years; Medicaid costs are concentrated among the longer-lived beneficiaries who are more likely to need long-term care and become Medicaid eligible. DISCUSSION: Because the distribution of the incremental costs varies over time and between insurance programs, when interventions occur and the effect on the disease course will have implications for how much and which program reaps the benefits.

11.
BMC Health Serv Res ; 22(1): 80, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034656

RESUMO

BACKGROUND: Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. METHODS: This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. RESULTS: There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. CONCLUSIONS: All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Atenção à Saúde , Infecções por HIV/tratamento farmacológico , Haiti , Humanos , Análise de Regressão
12.
BMC Psychiatry ; 22(1): 32, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012512

RESUMO

BACKGROUND: Long-acting injectable antipsychotics (LAIs) are an essential maintenance treatment option for individuals with schizophrenia or bipolar I disorder (BP-I). This report summarizes a roundtable discussion on the impact of COVID-19 on the mental healthcare landscape and use of LAIs for individuals with schizophrenia or BP-I. METHODS: Ten experts and stakeholders from diverse fields of healthcare participated in a roundtable discussion on the impact of the COVID-19 pandemic, treatment challenges, and gaps in healthcare for individuals with schizophrenia or BP-I, informed by a literature search. RESULTS: Individuals with schizophrenia or BP-I are at increased risk of COVID-19 infection and increased risk of mortality after COVID-19 diagnosis. LAI prescriptions decreased early on in the pandemic, driven by a decrease in face-to-face consultations. Mental healthcare services are adapting with increased use of telehealth and home-based treatment. Clinical workflows to provide consistent, in-person LAI services include screening for COVID-19 exposure and infection, minimizing contact, and ensuring mask-wearing by individuals and staff. The importance of continued in-person visits for LAIs needs to be discussed so that staff can share that information with patients, their caregivers, and families. A fully integrated, collaborative-care model is the most important aspect of care for individuals with schizophrenia or BP-I during and after the COVID-19 pandemic. CONCLUSIONS: The COVID-19 pandemic has highlighted the importance of a fully integrated collaborative-care model to ensure regular, routine healthcare contact and access to prescribed treatments and services for individuals with schizophrenia and BP-I.


Assuntos
Antipsicóticos , Transtorno Bipolar , COVID-19 , Esquizofrenia , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Teste para COVID-19 , Preparações de Ação Retardada/uso terapêutico , Humanos , Adesão à Medicação , Pandemias , SARS-CoV-2 , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia
15.
Value Health ; 25(2): 276-287, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35094801

RESUMO

OBJECTIVES: Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies emerge, comprehensive cost-effectiveness models will inform their value. These models will require descriptions of health states and their corresponding utility values that accurately reflect health-related quality of life over the disease trajectory. The objectives of this systematic review were to develop a catalog of health state utility (HSU) values for SCD, identify research gaps, and provide future directions for preference elicitation. METHODS: Records were identified through searches of PubMed and Embase, Tufts Medical Center Cost-Effectiveness Analysis Registry, reference lists of relevant articles, and consultation with SCD experts (2008-2020). We removed duplicate records and excluded ineligible studies. For included studies, we summarized the study characteristics, methods used for eliciting HSUs, and HSU values. RESULTS: Five studies empirically elicited utilities using indirect methods (EQ-5D) (n = 3) and Short Form-6 Dimension (n = 2); these represent health states associated with general SCD (n = 1), SCD complications (n = 2), and SCD treatments (n = 3). Additionally, we extracted HSUs from 7 quality-adjusted life-years-based outcome research studies. The HSU among patients with general SCD without specifying complications ranged from 0.64 to 0.887. Only 36% of the HSUs used in the quality-adjusted life-year-based outcomes research studies were derived from individuals with SCD. No study estimated HSUs in caregivers. CONCLUSIONS: There is a dearth of literature of HSUs for use in SCD models. Future empirical studies should elicit a comprehensive set of HSUs from individuals with SCD and their caregivers.


Assuntos
Anemia Falciforme/economia , Anemia Falciforme/terapia , Qualidade de Vida , Adulto , Anemia Falciforme/epidemiologia , Antidrepanocíticos/uso terapêutico , Transfusão de Sangue/métodos , Criança , Comorbidade , Análise Custo-Benefício , Feminino , Indicadores Básicos de Saúde , Humanos , Hidroxiureia/uso terapêutico , Masculino , Avaliação de Resultados em Cuidados de Saúde , Dor/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários
16.
Value Health ; 25(1): 59-68, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35031100

RESUMO

OBJECTIVES: We investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field. METHODS: We reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center's CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios. RESULTS: Fourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization. CONCLUSIONS: The omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug's cost-effectiveness.


Assuntos
Custos de Medicamentos , Medicamentos Genéricos/economia , Avaliação da Tecnologia Biomédica/normas , Análise Custo-Benefício , Humanos , Anos de Vida Ajustados por Qualidade de Vida
17.
Med Decis Making ; 42(4): 474-486, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34747265

RESUMO

BACKGROUND: Patient surveillance using repeated biomarker measurements presents an opportunity to detect and treat disease progression early. Frequent surveillance testing using biomarkers is recommended and routinely conducted in several diseases, including cancer and diabetes. However, frequent testing involves tradeoffs. Although surveillance tests provide information about current disease status, the complications and costs of frequent tests may not be justified for patients who are at low risk of progression. Predictions based on patients' earlier biomarker values may be used to inform decision making; however, predictions are uncertain, leading to decision uncertainty. METHODS: We propose the Personalized Risk-Adaptive Surveillance (PRAISE) framework, a novel method for embedding predictions into a value-of-information (VOI) framework to account for the cost of uncertainty over time and determine the time point at which collection of biomarker data would be most valuable. The proposed sequential decision-making framework is innovative in that it leverages the patient's longitudinal history, considers individual benefits and harms, and allows for dynamic tailoring of surveillance intervals by considering the uncertainty in current information and estimating the probability that new information may change treatment decisions, as well as the impact of this change on patient outcomes. RESULTS: When applied to data from cystic fibrosis patients, PRAISE lowers costs by allowing some patients to skip a visit, compared to an "always test" strategy. It does so without compromising expected survival, by recommending less frequent testing among those who are unlikely to be treated at the skipped time point. CONCLUSIONS: A VOI-based approach to patient monitoring is feasible and could be applied to several diseases to develop more cost-effective and personalized strategies for ongoing patient care. HIGHLIGHTS: In many patient-monitoring settings, the complications and costs of frequent tests are not justified for patients who are at low risk of disease progression. Predictions based on patient history may be used to individualize the timing of patient visits based on evolving risk.We propose Personalized Risk-Adaptive Surveillance (PRAISE), a novel method for personalizing the timing of surveillance testing, where prediction modeling projects the disease trajectory and a value-of-information (VOI)-based pragmatic decision-theoretic framework quantifies patient- and time-specific benefit-harm tradeoffs.A VOI-based approach to patient monitoring could be applied to several diseases to develop more personalized and cost-effective strategies for ongoing patient care.


Assuntos
Neoplasias , Biomarcadores , Análise Custo-Benefício , Progressão da Doença , Humanos , Incerteza
18.
Diabetes Care ; 45(1): 92-99, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34518376

RESUMO

OBJECTIVE: There are few studies testing the amount of weight loss necessary to achieve initial remission of type 2 diabetes mellitus (T2DM) following bariatric surgery and no published studies with use of weight loss to predict initial T2DM remission in sleeve gastrectomy (SG) patients. RESEARCH DESIGN AND METHODS: With Cox proportional hazards models we examined the relationship between initial T2DM remission and percent total weight loss (%TWL) after bariatric surgery. Categories of %TWL were included in the model as time-varying covariates. RESULTS: Of patients (N = 5,928), 73% were female; mean age was 49.8 ± 10.3 years and BMI 43.8 ± 6.92 kg/m2, and 57% had Roux-en-Y gastric bypass (RYGB). Over an average follow-up of 5.9 years, 71% of patients experienced initial remission of T2DM (mean time to remission 1.0 year). With 0-5% TWL used as the reference group in Cox proportional hazards models, patients were more likely to remit with each 5% increase in TWL until 20% TWL (hazard ratio range 1.97-2.92). When categories >25% TWL were examined, all patients had a likelihood of initial remission similar to that of 20-25% TWL. Patients who achieved >20% TWL were more likely to achieve initial T2DM remission than patients with 0-5% TWL, even if they were using insulin at the time of surgery. CONCLUSIONS: Weight loss after bariatric surgery is strongly associated with initial T2DM remission; however, above a threshold of 20% TWL, rates of initial T2DM remission did not increase substantially. Achieving this threshold is also associated with initial remission even in patients who traditionally experience lower rates of remission, such as patients taking insulin.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Gastrectomia , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Perda de Peso
19.
J Med Virol ; 94(2): 480-490, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-31017674

RESUMO

Chandipura virus (CHPV) is a neurotropic virus, known to cause encephalitis in humans. The microRNAs (miRNA/miR) play an important role in the pathogenesis of viral infection. The present study is focused on the role of miRNAs during CHPV (strain 1653514) infection in human microglial cells. The deep sequencing of CHPV-infected human microglial cells identified a total of 12 differentially expressed miRNA (DEMs). To elucidate the role of DEMs, the target gene prediction, Gene Ontology term (GO Term), pathway enrichment analysis, and miRNA-messenger RNA (mRNA) interaction network analysis was performed. The GO terms and pathway enrichment analysis provided 146 enriched genes; which were involved in interferon response, cytokine and chemokine signaling. Further, the WGCNA (weighted gene coexpression network analysis) of the enriched genes were discretely categorized into three modules (blue, brown, and turquoise). The hub genes in the blue module may correlate to CHPV induced neuroinflammation. Altogether, the miRNA-mRNA interaction network and WGCNA study revealed the following pairs, hsa-miR-542-3p and FAF1, hsa-miR-92a-1-5p and MYD88, and hsa-miR-3187-3p and TNFRSF21, which may contribute to neuroinflammation during CHPV infection in human microglial cells.


Assuntos
Redes Reguladoras de Genes/genética , MicroRNAs/genética , Microglia/metabolismo , Vesiculovirus/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Humanos , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/genética , /virologia , Receptores do Fator de Necrose Tumoral/genética , Infecções por Rhabdoviridae/genética , Infecções por Rhabdoviridae/virologia
20.
J Neurochem ; 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34967002

RESUMO

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in humans is characterized by a plethora of symptoms varying in intensity, such as non-specific febrile illness, dry cough, dyspnea, hypoxemia to severe lung damage, and even death. In addition to pulmonary complications associated with coronavirus disease-19 (COVID-19), perturbations in the physiology of multiple other organ systems have been reported, resulting in multiorgan failure (MoF) that is frequently observed in severe COVID-19 cases. Central nervous system (CNS) infection by SARS-CoV-2 is characterized by neurological impairments in patients with COVID-19, with the development of encephalopathy at the severe end of the spectrum. While mechanistic investigations of SARS-CoV-2-related encephalitis may reveal promising therapeutic candidates for reducing COVID-19-associated disease morbidity, the discovery of biomarkers capable of diagnosing and predicting prognosis in patients with encephalitis upon SARS-CoV-2 infection will afford significant value for the rapid detection of encephalitis and predicting disease outcomes. This will ultimately enable appropriate modifications of therapeutic regimens aimed at reducing disease morbidity and mortality. In this editorial, we highlight a study by Le Guennec and colleagues, entitled "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis", reporting the association of increased serum angiopoietin-like 4 (ANGPTL4) abundance with COVID-19-related encephalitis. The study highlights ANGPTL4 as a potential molecular marker for this disease. These novel findings may catalyze developments in the field of COVID-19-associated encephalitis by facilitating accurate and rapid diagnosis of encephalitis and timely treatment initiation, thus improving patient outcomes by ameliorating disease burden.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...