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1.
ACS Appl Mater Interfaces ; 16(20): 26833-26848, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38742590

RESUMO

Optimized extrusion melt-blending of polylactic acid (PLA) polymer with a minor biopolymeric phase, polybutylene adipate terephthalate (PBAT), and compatibilized with random ethylene-methyl acrylate-glycidyl methacrylate terpolymer (EMA-GMA, Trademark: Lotader AX-8900) led to an outstanding improvement in mechanical properties. At the noncompatibilized PLA-PBAT (80-20) blend point, significant enhancement (∼4500%) in toughness and elongation-at-break was already obtained without compromising any elastic properties. The effect of the compatibilizer content on the mechanical properties of the PLA-PBAT (80-20) blend was investigated by an optimal custom response surface methodology. Thus, 2 wt % Lotader content was determined to be optimal by a numerical optimization methodology with a desirability value, D, of 0.882 to maximize toughness and elongation-at-break. The compatibilization and thermal behavior of the Lotader-modified blends were analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Upon adding the compatibilizer, the original phase-separated morphology of the blends changed from PBAT quasi-spherical domains to nearly elongated elliptical ones. It was also found that the interfacial boundary line of the domains faded away, which revealed that interfacial compatibility was achieved. The thermostability of the blends remained largely unaltered following the incorporation of PBAT and Lotader. Moreover, while PBAT exhibited a minor influence on the crystallinity of PLA, Lotader had no discernible impact on crystallinity, as evidenced by the DSC thermograms. Thus, the compatibilizer at the optimal point in the optimized blend ratio led to the formation of a phase-separated morphology that combined internal cavitation, interfacial cavitation, and strong adhesion features at the right proportions in the microstructure which underlies the micromechanisms driving the remarkable enhancement of as much as 7100% in toughness and ductility.

3.
Nat Commun ; 14(1): 5055, 2023 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598213

RESUMO

Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent ("leaky") protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25-0.54]; 0.57 [0.42-0.78]; 0.24 [0.15-0.39]; respectively) and with cellblock exposures (0.61 [0.49-0.75]; 0.69 [0.58-0.83]; 0.41 [0.31-0.55]; respectively) but not with cell exposures (0.89 [0.58-1.35]; 0.96 [0.64-1.46]; 0.80 [0.46-1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.


Assuntos
COVID-19 , Prisioneiros , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Vacinação
4.
Health Justice ; 11(1): 16, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36913159

RESUMO

BACKGROUND: Vaccine hesitancy is common among incarcerated populations and, despite vaccination programs, vaccine acceptance within residents remains low, especially within jails. With the goal of assessing the Connecticut DOC's COVID-19 vaccine program within jails we examined if residents of DOC operated jails were more likely to become vaccinated following incarceration than in the community. Specifically, we conducted a retrospective cohort analysis among people who spent at least one night in a DOC-operated jail between February 2 and November 8, 2021, and were eligible for vaccination at the time of incarceration (intake). We compared the vaccination rates before and after incarceration using an age-adjusted survival analysis with a time-varying exposure of incarceration and an outcome of vaccination. RESULTS: During the study period, 3,716 people spent at least one night in jail and were eligible for vaccination at intake. Of these residents, 136 were vaccinated prior to incarceration, 2,265 had a recorded vaccine offer, and 479 were vaccinated while incarcerated. The age-adjusted hazard of vaccination following incarceration was significantly higher than prior to incarceration (12.5; 95% Confidence Intervals: 10.2-15.3). CONCLUSIONS: We found that residents were more likely to become vaccinated in jail than in the community. Though these findings highlight the utility of vaccination programs within jails, the low level of vaccination in this population speaks to the need for additional program development within jails and the community.

5.
Clin Infect Dis ; 76(3): e327-e335, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35686341

RESUMO

BACKGROUND: The Centers for Disease Control and Prevention recommends serial rapid antigen assay collection within congregate facilities. Although modeling and observational studies from communities and long-term care facilities have shown serial collection provides adequate sensitivity and specificity, the accuracy within correctional facilities remains unknown. METHODS: Using Connecticut Department of Correction data from 21 November 2020 to 15 June 2021, we estimated the accuracy of a rapid assay, BinaxNOW (Abbott), under 3 collection strategies: single test collection and serial collection of 2 and 3 tests separated by 1-4 days. The sensitivity and specificity of the first (including single), second, and third serially collected BinaxNOW tests were estimated relative to RT-PCRs collected ≤1 day of the BinaxNOW test. The accuracy metrics of the testing strategies were then estimated as the sum (sensitivity) and product (specificity) of tests in each strategy. RESULTS: Of the 13 112 residents who contributed ≥1 BinaxNOW test during the study period, 3825 contributed ≥1 RT-PCR paired BinaxNOW test. In relation to RT-PCR, the 3-rapid-antigen-test strategy had a sensitivity of 95.9% (95% CI: 93.6-97.5%) and specificity of 98.3% (95% CI: 96.7-99.1%). The sensitivities of the 2- and 1-rapid-antigen-test strategies were 88.8% and 66.8%, and the specificities were 98.5% and 99.4%, respectively. The sensitivity was higher among symptomatic residents and when RT-PCRs were collected before BinaxNOW tests. CONCLUSIONS: We found serial antigen test collection resulted in high diagnostic accuracy. These findings support serial collection for outbreak investigation, screening, and when rapid detection is required (such as intakes or transfers).


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Teste para COVID-19 , Testes Imunológicos , Sensibilidade e Especificidade , Estabelecimentos Correcionais , Antígenos Virais
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-998859

RESUMO

Introduction@#In the modern era of Medicine, total hip arthroplasty (THA) is found to last longer than ever before due to the fact that there has been improved bearing surfaces and materials available. Despite these modern approaches, failure caused by polyethylene wear, aseptic loosening, instability and mispositioning and even infection could affect THA survival. In the course of addressing anti-wear characteristics of the conventional polyethylene surface various approaches have been made. To date, there are very limited studies done in which polyethylene liner is better.@*General Objective@#To compare the effects of vitamin E diffused highly cross-linked polyethylene liner versus moderately cross-linked polyethylene liner in THA. @*Methodology@#Meta-analysis research design was used in this study. The primary investigators conducted a comprehensive literature search from Medline, Cochrane Library, PubMed, Elsevier, Google Scholar, Embase and ClinicalTrial.gov as electronic database. All randomized controlled trials comparing the effects of vitamin E diffused highly cross-linked polyethylene liner versus moderately cross-linked polyethylene liner in THA were included in the review. @*Conclusions@#The investigation disclosed no statistical significance between moderately cross-linked polyethylene liner and vitamin E diffused highly cross-linked polyethylene liner in terms of migration, head penetration and wear on mediolateral, longitudinal and anteroposterior axes after 2 and 5 years of undergoing THA. Moreover, the data pertaining to patient reported outcomes and clinical outcomes measure also indicated no statistical significance between moderately cross-linked polyethylene liner and vitamin E diffused highly cross-linked polyethylene liner. This indicates that vitamin E diffused highly cross-linked polyethylene liner is comparable with the conventional moderately cross-linked polyethylene liner. Vitamin E-infused highly cross-linked polyethylene ( VEPE) showed an almost similar stability with regard to the wear rates and the component showed similar stability with that of moderately cross-linked polyethylene liner.


Assuntos
Artroplastia de Quadril
7.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-998857

RESUMO

Background@#Avascular necrosis (AVN) of the femoral head results from intraosseous pathology causing functional impairment. Early diagnosis allows conservative treatment like core decompression, delaying total hip arthroplasty.@*Objective@#This meta-analysis aims to summarize platelet-rich plasma's (PRP) impact as an adjunct to core decompression (CD) on treatment outcomes and femoral head preservation in hip AVN. @*Methods@#The study conducted a comprehensive literature search using PubMed, Cochrane Library, Science Direct, Google Scholar and Med Line, including randomized controlled trials (RCTs) and previous meta-analyses from various databases. Using a random effects model, it compared PRP+CD with bone grafting to CD with bone grafting alone in AVN patients, evaluating function, pain scores, disease progression and the need for hip surgery.@*Results@#The meta-analysis examined 1041 records and included three studies. The primary outcomes were function and pain scores using Harris Hip Scoring (HHS) and Visual Analog Scale (VAS). Postoperative HHS scores at final follow-up favored the PRP+CD group significantly over CD alone. Postoperative VAS scores showed a trend towards higher scores in the CD alone group. The PRP+CD group demonstrated higher survival from disease progression compared to CD alone. Overall, the study suggests that PRP+CD led to better functional outcomes and disease progression outcomes than CD alone in AVN of the hip.@*Conclusion@#The PRP+CD treatment group showed significant benefits in AVN patients compared to CD alone, including higher HHS scores, improved disease progression survival and reduced need for hip surgery. Although PRP+CD resulted in decreased VAS scores, the difference was not statistically significant.


Assuntos
Osteonecrose , Cabeça do Fêmur , Plasma Rico em Plaquetas , Ensaio Clínico Controlado Aleatório
8.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22275339

RESUMO

ObjectiveTo assess the Connecticut Department of Corrections (DOC) COVID-19 vaccine program within jails. MethodsWe conducted a retrospective cohort analysis among people who were incarcerated in a DOC-operated jail between February 2 and November 8, 2021, and were eligible for vaccination at the time of incarceration (intake). We compared the vaccination rates before and after incarceration using an age-adjusted survival analysis with a time-varying exposure of incarceration and an outcome of vaccination. ResultsDuring the study period, 3,716 people spent [≥]1 night in jail and were eligible for vaccination at intake. Of these residents, 136 were vaccinated prior to incarceration, 2,265 had a recorded vaccine offer, and 476 were vaccinated while incarcerated. The age-adjusted hazard of vaccination following incarceration was significantly higher than prior to incarceration (12.5; 95% CI: 10.2-15.3). ConclusionsWe found that residents were more likely to become vaccinated in jail than the community. Though these findings highlight the utility of vaccination programs within jails, the low level of vaccination in this population speaks to the need for additional program development within jails and the community.

9.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22271803

RESUMO

BackgroundThe CDC recommends serial rapid antigen assay collection within congregate facilities for screening and outbreak testing. Though modeling and observational studies from community and long-term care facilities have shown serial collection provides adequate sensitivity and specificity, the diagnostic accuracy of this testing strategy within correctional facilities remains unknown. MethodsUsing Connecticut Department of Corrections (DOC) data from November 21st 2020 to June 15th 2021, we estimated the accuracy of a rapid assay, BinaxNOW, under three collection strategies, a single test in isolation and two and three serial tests separated by 1-4 day intervals. Diagnostic accuracy metrics were estimated in relation to RT-PCRs collected within one day before the first or after the last included rapid antigen tests in a series. ResultsOf the 17,669 residents who contributed at least one RT-PCR or rapid antigen during the study period, 3,979 contributed [≥]1 paired rapid antigen test series. In relation to RT-PCR, the three-rapid antigen test strategy had a sensitivity of 89.6% (95% confidence intervals: 86.1-92.6%) and specificity of 97.2% (CI: 95.1-98.3%). The sensitivities for two and one-rapid antigen test strategy were 75.2% and 52.8%, respectively, and the specificities were 98.5% and 99.4%, respectively. The sensitivity was higher among symptomatic residents and when the RT-PCR was collected before the rapid antigen tests. ConclusionsWe found the serial collection of an antigen test resulted in high diagnostic accuracy. These findings support serial testing within correctional facilities for outbreak investigation, screening, and when rapid detection is required (such as intakes or transfers).

11.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867356

RESUMO

One of the leading trends in the modern tissue engineering is the development of new effective methods of decellularization aimed at the removal of cellular components from a donor tissue, reducing its immunogenicity and the risk of rejection. Supercritical CO2 (scCO2)-assisted processing has been proposed to improve the outcome of decellularization, reduce contamination and time costs. The resulting products can serve as personalized tools for tissue-engineering therapy of various somatic pathologies. However, the decellularization of heterogeneous 3D structures, such as the aortic root, requires optimization of the parameters, including preconditioning medium composition, the type of co-solvent, values of pressure and temperature inside the scCO2 reactor, etc. In our work, using an ovine aortic root model, we performed a comparative analysis of the effectiveness of decellularization approaches based on various combinations of these parameters. The protocols were based on the combinations of treatments in alkaline, ethanol or detergent solutions with scCO2-assisted processing at different modes. Histological analysis demonstrated favorable effects of the preconditioning in a detergent solution. Following processing in scCO2 medium provided a high decellularization degree, reduced cytotoxicity, and increased ultimate tensile strength and Young's modulus of the aortic valve leaflets, while the integrity of the extracellular matrix was preserved.


Assuntos
Valva Aórtica/ultraestrutura , Estruturas Celulares , Engenharia Tecidual/métodos , Animais , Dióxido de Carbono , Células Cultivadas , Módulo de Elasticidade , Matriz Extracelular , Humanos , Células-Tronco Mesenquimais , Ovinos , Resistência à Tração
12.
Artigo em Inglês | MEDLINE | ID: mdl-32923912

RESUMO

PURPOSE: Radiotherapy for childhood cancer is associated with elevated subsequent neoplasm (SN) risk, but the contribution of rare variants in DNA damage response and radiation sensitivity genes to SN risk is unknown. PATIENTS AND METHODS: We conducted whole-exome sequencing in a cohort of childhood cancer survivors originally diagnosed during 1970 to 1986 (mean follow-up, 32.7 years), with reconstruction of doses to body regions from radiotherapy records. We identified patients who developed SN types previously reported to be related to radiotherapy (RT-SNs; eg, basal cell carcinoma [BCC], breast cancer, meningioma, thyroid cancer, sarcoma) and matched controls (sex, childhood cancer type/diagnosis, age, SN location, radiation dose, survival). Conditional logistic regression assessed SN risk associated with potentially protein-damaging rare variants (SnpEff, ClinVar) in 476 DNA damage response or radiation sensitivity genes with exact permutation-based P values using a Bonferroni-corrected significance threshold of P < 8.06 × 10-5. RESULTS: Among 5,105 childhood cancer survivors of European descent, 1,108 (21.7%) developed at least 1 RT-SN. Out-of-field RT-SN risk, excluding BCC, was associated with homologous recombination repair (HRR) gene variants (patient cases, 23.2%; controls, 10.8%; odds ratio [OR], 2.6; 95% CI, 1.7 to 3.9; P = 4.79 × 10-5), most notably but nonsignificantly for FANCM (patient cases, 4.0%; matched controls, 0.6%; P = 9.64 × 10-5). HRR variants were not associated with likely in/near-field RT-SNs, excluding BCC (patient cases, 12.7%; matched controls, 12.9%; P = .92). Irrespective of radiation dose, risk for RT-SNs was also associated with EXO1 variants (patient cases, 1.8%; controls, 0.4%; P = 3.31 × 10-5), another gene implicated in DNA double-strand break repair. CONCLUSION: In this large-scale discovery study, we identified novel associations between RT-SN risk after childhood cancer and potentially protein-damaging rare variants in genes involved in DNA double-strand break repair, particularly HRR. With replication, these results could affect screening recommendations for childhood cancer survivors and risk-benefit assessments of treatment approaches.

13.
J Clin Oncol ; 37(35): 3436-3445, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31622129

RESUMO

PURPOSE: Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors. PATIENTS AND METHODS: In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses. We conducted analyses separately for bone and soft-tissue sarcomas occurring in the head and neck (in/near the radiotherapy field) versus body and extremities (out of field). RESULTS: Of 105 bone and 124 soft-tissue sarcomas, more than one half occurred in the head and neck (bone, 53.3%; soft tissue, 51.6%), one quarter in the body and extremities (bone, 29.5%; soft tissue, 25.0%), and approximately one fifth in unknown/unspecified locations (bone, 17.1%; soft tissue, 23.4%). We noted substantially higher risks compared with the general population for head and neck versus body and extremity tumors for both bone (SIR, 2,213; 95% CI, 1,671 to 2,873 v SIR, 169; 95% CI, 115 to 239) and soft-tissue sarcomas (SIR, 542; 95% CI, 418 to 692 v SIR, 45.7; 95% CI, 31.1 to 64.9). Head and neck bone and soft-tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood, reaching a 60-year cumulative incidence of 6.8% (95% CI, 5.0% to 8.7%) and 9.3% (95% CI, 7.0% to 11.7%), respectively. In contrast, body and extremity bone sarcoma incidence flattened after adolescence (3.5%; 95% CI, 2.3% to 4.8%), whereas body and extremity soft-tissue sarcoma incidence was rare until age 30, when incidence rose steeply (60-year cumulative incidence, 6.6%; 95% CI, 4.1% to 9.2%), particularly for females (9.4%; 95% CI, 5.1% to 13.8%). CONCLUSION: Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.


Assuntos
Neoplasias Ósseas/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Radioterapia/efeitos adversos , Retinoblastoma/radioterapia , Sarcoma/epidemiologia , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Neoplasias Ósseas/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Prognóstico , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Neoplasias da Retina/radioterapia , Retinoblastoma/genética , Retinoblastoma/patologia , Medição de Risco , Fatores de Risco , Sarcoma/etiologia , Taxa de Sobrevida , Adulto Jovem
15.
J Natl Cancer Inst ; 111(9): 961-969, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698734

RESUMO

BACKGROUND: Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood. METHODS: Among 2053 retinoblastoma patients diagnosed during 1914-2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population. RESULTS: Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15-29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER<15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients. CONCLUSION: Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Retinoblastoma/mortalidade , Fatores Etários , Causas de Morte , Pré-Escolar , Feminino , História do Século XX , História do Século XXI , Humanos , Lactente , Masculino , Vigilância da População , Prevalência , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiologia , Retinoblastoma/etiologia , Estados Unidos/epidemiologia
16.
JAMA Oncol ; 5(3): 318-325, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30570657

RESUMO

Importance: Therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML) is a rare, usually fatal complication of chemotherapy, including certain alkylating agents, topoisomerase II inhibitors, and platinum compounds. With the introduction of new chemotherapeutic agents, expanded indications for established agents, and increased neoadjuvant and adjuvant chemotherapy, tMDS/AML risks in the modern age are poorly understood. Objectives: To quantify tMDS/AML risk after chemotherapy for solid cancer among United States adults since 2000 and correlate tMDS/AML risk patterns with chemotherapy treatment practices. Design, Setting, and Participants: A population-based cohort study was conducted using cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims. Risk analyses included 1619 tMDS/AML cases among 700 612 adults (age, 20-84 years) who were diagnosed with first primary solid cancer during 2000 to 2013 (followed up through 2014), received initial chemotherapy, and survived 1 year or longer, as reported to SEER. Descriptive analyses were conducted of SEER records linked with Medicare claims for chemotherapy in 165 820 older adults (age, 66-84 years) receiving initial chemotherapy for a first primary solid cancer in 2000-2013. Data analysis was conducted from October 2017 to April 2018. Exposures: Receipt of initial chemotherapy for solid cancer. Main Outcomes and Measures: Second primary tMDS/AML. Results: Based on 1619 tMDS/AML cases in the SEER database (mean [SD] age, 64.3 [12.2] years; 1148 [70.9%] female), tMDS/AML risks were statistically significantly elevated after chemotherapy for 22 of 23 solid cancers (all except colon). Relative risks ranged from 1.5 to greater than 10 and excess absolute risks from 1.4 to greater than 15 cases per 10 000 person-years compared with the general population. Overall survival following tMDS/AML diagnosis was poor (1270 of 1619 patients [78.4%] died; median overall survival, 7 months). For patients treated with chemotherapy at the present time, approximately three-quarters of tMDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy. In the SEER-Medicare database, use of known leukemogenic agents, particularly platinum compounds, in initial chemotherapy increased substantially since 2000, most notably for gastrointestinal tract cancers (esophagus, stomach, colon, and rectum; 10% in 2000-2001 to 81% during 2012-2013). Conclusions and Relevance: Large-scale, United States population-based data demonstrate excess tMDS/AML risks following chemotherapy for nearly all solid tumor types, consistent with expanded use of known leukemogenic agents in the 21st century. Continued efforts to reduce treatment-related adverse events, particularly for solid cancer patients with favorable prognosis, are needed.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Leucemia Mieloide Aguda/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/prevenção & controle , Masculino , Medicare , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/prevenção & controle , Medição de Risco , Fatores de Risco , Programa de SEER , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
17.
J Pharm Sci ; 106(4): 982-993, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27988163

RESUMO

The chemical degradation of farglitazar (1) was investigated using a series of controlled stress testing experiments. Farglitazar drug substance was stressed under acidic, natural pH, basic, and oxidative conditions in solution. In the solid state, the drug substance was stressed with heat, high humidity, and light. Farglitazar was found to be most labile toward oxidative stress. A series of mechanistic experiments are described in which the use of 18O-labelled oxygen demonstrated that oxidative degradation of farglitazar is caused primarily by singlet oxygen formed under thermal conditions. Major degradation products were isolated and fully characterized. Mechanisms for the formation of degradation products are proposed. Drug product tablets were also stressed in the solid state with heat, high humidity, and light. Stressed tablets afforded many of the same degradation products observed during drug substance stress testing, with oxidation again being the predominant degradation pathway. Evidence for the activity of singlet oxygen, formed during thermal stress testing of the solid oral dosage form, is presented. The degradation pathways observed during stress testing matched those observed during long-term stability trials of the drug product.


Assuntos
Química Farmacêutica/métodos , Oxazóis/análise , Oxazóis/metabolismo , Processos Fotoquímicos , Tirosina/análogos & derivados , Temperatura Alta/efeitos adversos , Umidade/efeitos adversos , Hidrólise , Luz/efeitos adversos , Oxazóis/química , Oxirredução , Tirosina/análise , Tirosina/química , Tirosina/metabolismo
18.
Ethn Dis ; 26(1): 91-8, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26843801

RESUMO

BACKGROUND: While routine HIV testing in the general population is a national recommendation, actual practice may vary. PURPOSE: To determine risk factors associated with HIV testing after the adoption of a New York State law in 2010 mandating that health care providers offer HIV testing in all clinical settings. METHODS: Survey data from Monroe County, New York, were collected in 2012 for adults aged 18-64 years and analyzed in 2014. Logistic regression was used to identify risk factors independently associated with HIV testing and high-risk behavior. RESULTS: Among adults aged 18-34, fewer Whites were offered HIV testing in the past year by their doctors compared with Blacks (34% vs 64%) despite having similar rates of any HIV high-risk behavior (20% overall). For adults aged 35-64 years, fewer Whites than Blacks were ever tested for HIV (42% vs 71%), offered HIV testing in past year (17% vs 40%), and reported any HIV high-risk behavior (3% vs 13%). Latinos showed intermediate levels. With logistic regression analysis, ever tested for HIV was independently associated with only race/ethnicity; offered HIV testing in the past year was associated with females, Blacks and Latinos, aged 18-34 years, and having a routine health checkup in past year; any HIV high-risk behavior was associated with only younger age. CONCLUSIONS: To improve HIV testing rates as well as compliance with state laws and national guidelines, targeted efforts should be considered that improve perceptions of risk and emphasize the value of routine HIV screening, including those directed at White adults and their health care providers.


Assuntos
Infecções por HIV/diagnóstico , Programas Obrigatórios , Programas de Rastreamento/legislação & jurisprudência , Padrões de Prática Médica , Adolescente , Adulto , Etnicidade/estatística & dados numéricos , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , New York , Grupos Raciais , Racismo , Fatores de Risco , Inquéritos e Questionários , População Branca/estatística & dados numéricos , Adulto Jovem
19.
Public Health Rep ; 130(3): 245-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25931628

RESUMO

OBJECTIVES: Smartphone applications (apps) are increasingly used to facilitate casual sexual relationships, increasing the risk of sexually transmitted diseases (STDs). In STD investigations, traditional contact elicitation methods can be enhanced with smartphone technology during field interviews. METHODS: In 2013, the Monroe County Department of Public Health conducted a large, multi-infection STD investigation among men who have sex with men (MSM) using both index case and cluster interviews. When patients indicated meeting sexual partners online, disease intervention specialists (DISs) had access to smartphone apps and were able to elicit partners through access to inboxes and profiles where traditional contact information was lacking. Social network mapping was used to display the extent of the investigation and the impact of access to smartphones on the investigation. RESULTS: A total of 14 index patient interviews and two cluster interviews were conducted; 97 individuals were identified among 117 sexual dyads. On average, eight partners were elicited per interview (range: 1-31). The seven individuals who used apps to find partners had an average of three Internet partners (range: 1-5). Thirty-six individuals either had a new STD (n=7) or were previously known to be HIV-positive (n=29). Of the 117 sexual dyads, 21 (18%) originated either online (n=8) or with a smartphone app (n=13). Of those originating online or with a smartphone app, six (29%) partners were located using the smartphone and two (10%) were notified of their exposure via a website. Three of the new STD/HIV cases were among partners who met online. CONCLUSION: Smartphone technology used by DISs in the field improved contact elicitation and resulted in successful partner notification and case finding.


Assuntos
Busca de Comunicante/métodos , Homossexualidade Masculina , Aplicativos Móveis , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/transmissão , Adolescente , Adulto , Humanos , Internet , Masculino , Grupos Raciais , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Adulto Jovem
20.
Am J Prev Med ; 46(3): 259-64, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24512864

RESUMO

BACKGROUND: Early childhood lead exposure is associated with numerous adverse health effects. Eliminating blood lead poisoning is a national health objective for 2020. OBJECTIVE: To assess temporal trends in childhood elevated blood lead level (EBLL) rates. METHODS: Laboratory surveillance data were collected from 1997 to 2011 and analyzed in 2013 using linear regression to assess trends in confirmed EBLL rates among children aged <6 years in the U.S., New York State ([NYS], excluding New York City), and Monroe County NY. Monroe County was also examined as a case study of local public health efforts to reduce childhood lead exposures. Blood lead screening and home lead hazard inspection data were collected from 1990 to 2012 and analyzed in 2013. RESULTS: The prevalence of EBLL≥10 µg/dL per 100 tested children decreased from 13.4 to 1.1 in Monroe County, 6.3 to 1.0 in NYS, and 7.6 to 0.6 in the U.S. between 1997 and 2011. The absolute yearly rate of decline in Monroe County (slope=-0.0083, p<0.001) occurred 2.4-fold faster than that in NYS (slope=-0.0034, p<0.001) and 1.8-fold faster than that in the U.S. (slope=-0.0046, p<0.001). The childhood blood lead testing rate was consistently higher in Monroe County than in NYS and the U.S.; however, testing increased for all three areas (all slopes>0, p<0.05), with greater improvements observed for U.S. children overall (slope=0.0075, p<0.001). CONCLUSIONS: In addition to national and statewide policies, local efforts may be important drivers of population-based declines in childhood EBLL rates.


Assuntos
Intoxicação por Chumbo/epidemiologia , Chumbo/sangue , Programas de Rastreamento/métodos , Saúde Pública , Pré-Escolar , Feminino , Humanos , Modelos Lineares , Masculino , New York/epidemiologia , Prevalência , Fatores de Tempo , Estados Unidos/epidemiologia
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