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1.
Nucleic Acids Res ; 51(2): 574-594, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36537216

RESUMO

The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.


Assuntos
Cromatina , Histona Acetiltransferases , Histonas , Humanos , Cromatina/genética , Ilhas de CpG/genética , DNA , Histona Acetiltransferases/metabolismo , Histonas/metabolismo , Acetilação
2.
Emerg Infect Dis ; 30(6): 1144-1153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781926

RESUMO

Few precise estimates of hospitalization and fatality rates from COVID-19 exist for naive populations, especially within demographic subgroups. We estimated rates among persons with SARS-CoV-2 infection in the United States during May 1-December 1, 2020, before vaccines became available. Both rates generally increased with age; fatality rates were highest for persons >85 years of age (24%) and lowest for children 1-14 years of age (0.01%). Age-adjusted case hospitalization rates were highest for African American or Black, not Hispanic persons (14%), and case-fatality rates were highest for Asian or Pacific Islander, not Hispanic persons (4.4%). Eighteen percent of hospitalized patients and 44.2% of those admitted to an intensive care unit died. Male patients had higher hospitalization (6.2% vs. 5.2%) and fatality rates (1.9% vs. 1.5%) than female patients. These findings highlight the importance of collecting surveillance data to devise appropriate control measures for persons in underserved racial/ethnic groups and older adults.


Assuntos
COVID-19 , Hospitalização , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Adolescente , Idoso , Criança , Pré-Escolar , Pessoa de Meia-Idade , Adulto , Lactente , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Adulto Jovem , Recém-Nascido , Vacinas contra COVID-19/administração & dosagem , Etnicidade/estatística & dados numéricos
3.
Biotechnol Bioeng ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082734

RESUMO

Type 1 diabetes (T1D) prevention is currently limited by the lack of diagnostic tools able to identify disease before autoimmune destruction of the pancreatic ß cells. Autoantibody tests are used to predict risk and, in combination with glucose dysregulation indicative of ß cell loss, to determine administration of immunotherapies. Our objective was to remotely identify immune changes associated with the disease, and we have employed a subcutaneously implanted microporous poly(e-caprolactone) (PCL) scaffold to function as an immunological niche (IN) in two models of T1D. Biopsy and analysis of the IN enables disease monitoring using transcriptomic changes at a distal site from autoimmune destruction of the pancreas, thereby gaining cellular level information about disease without the need for a biopsy of the native organ. Using this approach, we identified gene signatures that stratify healthy and diseased mice in both an adoptive transfer model and a spontaneous onset model of T1D. The gene signatures identified herein demonstrate the ability of the IN to identify immune activation associated with diabetes across models.

4.
Mol Pharm ; 21(1): 53-61, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38029291

RESUMO

Epithelial-mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs, such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumor recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analyzed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance depending on the concentration of its use.


Assuntos
Antineoplásicos , Transição Epitelial-Mesenquimal , Humanos , Docetaxel/farmacologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Células Epiteliais
5.
MMWR Morb Mortal Wkly Rep ; 73(15): 351-357, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38652735

RESUMO

Introduction: Approximately 40,000 U.S. women die from breast cancer each year. Mammography is recommended to screen for breast cancer and reduce breast cancer mortality. Adverse social determinants of heath (SDOH) and health-related social needs (HRSNs) (e.g., lack of transportation and social isolation) can be barriers to getting mammograms. Methods: Data from the 2022 Behavioral Risk Factor Surveillance System were analyzed to estimate the prevalence of mammography use within the previous 2 years among women aged 40-74 years by jurisdiction, age group, and sociodemographic factors. The association between mammography use and measures of SDOH and HRSNs was assessed for jurisdictions that administered the Social Determinants and Health Equity module. Results: Among women aged 50-74 years, state-level mammography use ranged from 64.0% to 85.5%. Having health insurance and a personal health care provider were associated with having had a mammogram within the previous 2 years. Among women aged 50-74 years, mammography prevalence was 83.2% for those with no adverse SDOH and HRSNs and 65.7% for those with three or more adverse SDOH and HRSNs. Life dissatisfaction, feeling socially isolated, experiencing lost or reduced hours of employment, receiving food stamps, lacking reliable transportation, and reporting cost as a barrier for access to care were all strongly associated with not having had a mammogram within the previous 2 years. Conclusions and Implications for Public Health Practice: Identifying specific adverse SDOH and HRSNs that women experience and coordinating activities among health care providers, social services, community organizations, and public health programs to provide services that help address these needs might increase mammography use and ultimately decrease breast cancer deaths.


Assuntos
Sistema de Vigilância de Fator de Risco Comportamental , Mamografia , Determinantes Sociais da Saúde , Humanos , Feminino , Pessoa de Meia-Idade , Mamografia/estatística & dados numéricos , Idoso , Estados Unidos/epidemiologia , Adulto , Neoplasias da Mama/epidemiologia , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde
6.
Cancer Causes Control ; 34(8): 657-670, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37126144

RESUMO

PURPOSE: This study is the first to comprehensively describe incidence rates and trends of screening-amenable cancers (colorectal, lung, female breast, and cervical) among non-Hispanic AI/AN (NH-AI/AN) people. METHODS: Using the United States Cancer Statistics AI/AN Incidence Analytic Database, we, calculated incidence rates for colorectal, lung, female breast, and cervical cancers for NH-AI/AN and non-Hispanic White (NHW) people for the years 2014-2018 combined. We calculated age-adjusted incidence rates (per 100,000), total percent change in incidence rates between 1999 and 2018, and trends over this time-period using Joinpoint analysis. Screening prevalence by region was calculated using Behavioral Risk Factor Surveillance System data. RESULTS: Rates of screening-amenable cancers among NH-AI/AN people varied by geographic region and age at diagnosis. Over half of all lung and colorectal cancers in NH-AI/AN people were diagnosed at later stages. Rates of lung and colorectal cancers decreased significantly between 1999-2018 among NH-AI/AN men, but no significant changes were observed in rates of screening-amenable cancers among NH-AI/AN women. CONCLUSION: This study highlights disparities in screening-amenable cancers between NH-AI/AN and NHW people. Culturally informed, community-based interventions that increase access to preventive health services could reduce cancer disparities among AI/AN people.


Assuntos
Indígena Americano ou Nativo do Alasca , Neoplasias Colorretais , Neoplasias Pulmonares , Neoplasias do Colo do Útero , Feminino , Humanos , Masculino , Neoplasias Colorretais/epidemiologia , Incidência , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias Pulmonares/epidemiologia
7.
Transfusion ; 63(4): 737-744, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36789571

RESUMO

BACKGROUND: Computerized physician order entry (CPOE) systems are one way to reinforce evidence-based transfusion indications for blood products. The new CPOE system that was implemented at our institution allowed healthcare providers to select "Other" as an indication and provide reasons for transfusion outside of accepted guidelines. STUDY DESIGN AND METHODS: Transfusion order records for packed red blood cells (RBCs), platelets, and fresh frozen plasma (FFP) from high product-ordering areas of Long Island Jewish Medical Center and Cohen's Children's Medical Center from April 2021, when the new CPOE system was implemented, to November 2021 were reviewed. The percentage of "Other" orders was determined and the reason for each "Other" order was reviewed to identify possible areas for education or valid indications not included in the institutionally recognized indications. RESULTS: 9.7% of RBC orders, 1.9% of platelet orders, and 18.2% of FFP orders were placed with "Other" as the indication for transfusion (χ2 2  = 88.5; p < .001). Reasons for "Other" orders were varied, but notable reasons included indications already institutionally accepted such as, bleeding (15.7% of pediatric "Other" RBC orders), hold for OR (14.3% of pediatric and 15.8% of adult "Other" RBC orders), and novel reasons such as FFP for ACE-inhibitor associated angioedema (84.6% of adult "Other" FFP orders). DISCUSSION: The findings from our study provide examples of potential difficulties hospitals may encounter when they implement a new computerized physician order entry system. Provider education may play an important role to reduce the number of "Other" orders placed for already recognized indications.


Assuntos
Sistemas de Registro de Ordens Médicas , Adulto , Humanos , Criança , Transfusão de Eritrócitos , Transfusão de Sangue , Hemorragia , Plasma
8.
Prev Med ; 175: 107692, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37659614

RESUMO

INTRODUCTION: Acral lentiginous melanoma (ALM) is a rare type of melanoma associated with delayed diagnosis and poor survival rates. This study examines ALM incidence rates in comparison to all other melanoma types. METHODS: We used data from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, which together cover 99% of the US population. We calculated age-adjusted rates and rate ratios for ALM and all other malignant melanomas by sex, race and ethnicity, stage, and year of diagnosis (2010-2019). RESULTS: ALM incidence rates were significantly lower among non-Hispanic Black persons (1.8 per 1,000,000); non-Hispanic Asian/Pacific Islander (API) persons (1.7 per 1,000,000); and Hispanic Black, American Indian/Alaska Native (AI/AN), and API persons (1.5 per 1,000,000) compared to non-Hispanic White persons (2.3 per 1,000,000). Rates were significantly higher among Hispanic White persons (2.8 per 1,000,000) compared to non-Hispanic White persons. For all other melanoma types, incidence rates were significantly higher among non-Hispanic White persons compared to persons in each of the other racial and ethnic categories. The percentage of melanomas that were ALM ranged from 0.8% among non-Hispanic White persons to 19.1% among Hispanic Black, AI/AN, and API persons. CONCLUSION: These findings suggest that awareness of the potential for ALM in patients of all races and ethnicities could be balanced with an understanding of the rarity of the disease and the potential for the development of other melanoma types in racial and ethnic minority groups.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Estados Unidos/epidemiologia , Melanoma/epidemiologia , Etnicidade , Incidência , Grupos Minoritários , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia
9.
Dig Dis Sci ; 68(7): 2908-2920, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36933116

RESUMO

BACKGROUND: Inclusion of evidence-based behavior change techniques (e.g., self-monitoring) in mobile health apps has the potential to promote adherence to inflammatory bowel disease treatment. While inflammatory bowel disease management apps exist, the extent to which they incorporate behavior change techniques remains unknown. AIMS: The present study systematically evaluated the content and quality of free, commercially available inflammatory bowel disease management apps. METHODS: Apps were identified using a systematic search of the Apple App and Google Play stores. Apps were evaluated using Abraham and Michie's taxonomy of 26 behavior change techniques. A literature search was conducted to identify behavior change techniques specific and relevant for people with inflammatory bowel disease. App quality was assessed using the Mobile App Rating Scale with scores ranging from 1 (Inadequate) to 5 (Excellent). RESULTS: A total of 51 inflammatory bowel disease management apps were evaluated. Apps included 0-16 behavior change techniques (Mean = 4.55) and 0-10 inflammatory bowel disease management behavior change techniques (Mean = 3.43). App quality ranged from 2.03 to 4.62 (Mean = 3.39) out of 5.00. Two apps, My IBD Care: Crohn's & Colitis and MyGiHealth GI Symptom Tracker, included the highest number of overall and inflammatory bowel disease management behavior change techniques along with high-quality scores. Bezzy IBD was the only app with a high number of overall and inflammatory bowel disease management behavior change techniques with a primary focus on social support/change. CONCLUSION: Most inflammatory bowel disease management apps reviewed included evidence-based inflammatory bowel disease management behavior change techniques.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Aplicativos Móveis , Telemedicina , Humanos , Terapia Comportamental/métodos , Doenças Inflamatórias Intestinais/terapia
10.
Tob Control ; 32(2): 211-217, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34330882

RESUMO

BACKGROUND: The US Food and Drug Administration requires six text-only warnings for cigar products, including cigarillos. Research has demonstrated the superiority of pictorial over text-only cigarette warnings, yet the relative effectiveness of pictorial warnings for cigarillos has not been examined. We examined the impact of pictorial cigarillo warnings compared with text-only warnings. METHODS: Data were collected from a nationally representative sample of US young adult (18-29) cigarillo users and susceptible non-users. Participants were randomised to one of three experimental conditions: text-only or one of two pictorial conditions (combined for analyses). For each warning, we assessed negative emotional reactions, cognitive elaboration (ie, thinking about cigarillo risks) and perceived message effectiveness (PME). RESULTS: Participants (N=661) were 46.5% female, 64.7% white and 21.9% Hispanic; 34.1% reported past 30-day cigarillo use; 41.4% were lifetime users (excluding past 30-day use); and 24.4% were susceptible non-users. Pictorial warnings elicited more negative emotional reactions and higher PME than text-only warnings (p values<0.01), with interactions showing the largest effects for past 30-day users (emotional reactions: d=0.99, PME: d=0.63). For cognitive elaboration, there was no main effect of warning type, but an interaction revealed effects for past 30-day users (p<0.05, d=0.46). CONCLUSIONS: Pictorial cigarillo warnings elicited greater negative emotional reactions and PME compared with text-only warnings. These effects and the effects on cognitive elaboration were strongest for past 30-day users. Our findings extend research on cigarette warnings to cigarillos, demonstrating that pictorial warnings are superior to text-only warnings for cigarillos in eliciting beneficial responses.


Assuntos
Rotulagem de Produtos , Produtos do Tabaco , Humanos , Feminino , Adulto Jovem , Masculino , Prevenção do Hábito de Fumar , Produtos do Tabaco/efeitos adversos , Emoções/fisiologia
11.
BMC Health Serv Res ; 23(1): 190, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823637

RESUMO

BACKGROUND: Poor quality of care, including overprovision (unnecessary care) is a global health concern. Greater provider effort has been shown to increase the likelihood of correct treatment, but its relationship with overprovision is less clear. Providers who make more effort may give more treatment overall, both correct and unnecessary, or may have lower rates of overprovision; we test which is true in the Tanzanian private health sector. METHODS: Standardised patients visited 227 private-for-profit and faith-based facilities in Tanzania, presenting with symptoms of asthma and TB. They recorded history questions asked and physical examinations carried out by the provider, as well as laboratory tests ordered, treatments prescribed, and fees paid. A measure of provider effort was constructed on the basis of a checklist of recommended history taking questions and physical exams. RESULTS: 15% of SPs received the correct care for their condition and 74% received unnecessary care. Increased provider effort was associated with increased likelihood of correct care, and decreased likelihood of giving unnecessary care. Providers who made more effort charged higher fees, through the mechanism of higher consultation fees, rather than increased fees for lab tests and drugs. CONCLUSION: Providers who made more effort were more likely to treat patients correctly. A novel finding of this study is that they were also less likely to provide unnecessary care, suggesting it is not simply a case of some providers doing "more of everything", but that those who do more in the consultation give more targeted care.


Assuntos
Honorários e Preços , Setor Privado , Humanos , Instituições Privadas de Saúde , Encaminhamento e Consulta , Qualidade da Assistência à Saúde
12.
Health Commun ; 38(6): 1201-1212, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-34781799

RESUMO

Many adolescents and young adults hold erroneous beliefs that cigarillos and waterpipe tobacco (WT) are safer than cigarettes, contributing to use. Communication campaigns can correct misperceptions and increase risk beliefs. We tested point-of-sale (POS) communication campaigns focused on chemical exposure for cigarillos and WT. We conducted two cluster randomized trials at 20 gas stations with convenience stores (10 stores for cigarillos, 10 for WT) in North Carolina between June and November 2017. Within each trial, stores were randomly assigned to either the intervention (campaign messages displayed) or a no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 adolescents and young adults (ages 16-25) per store, at baseline and follow-up. There were 978 participants (mean age = 20.9 years) in the cigarillo trial, and 998 participants (mean age = 21.0 years) in the WT trial. Rates of campaign exposure were low (26% for cigarillos; 24.3% for WT). The cigarillo campaign increased knowledge that ammonia is in cigarillo smoke (p < .01). There were also significant increases in knowledge about ammonia and cyanide in cigarillo smoke and arsenic in WT smoke (p < .05) in the sub-sample who reported exposure to the campaign. No differences were found in outcome expectancies, product attitudes, worry about chemical exposure, or behavioral intentions in either campaign. Garnering attention for communication campaigns in saturated POS environments, often dominated by tobacco advertising, is challenging. Our study demonstrates the feasibility of anti-tobacco campaigns at the POS and points to several lessons learned for future POS campaigns.


Assuntos
Comunicação em Saúde , Produtos do Tabaco , Tabaco para Cachimbos de Água , Adolescente , Adulto Jovem , Humanos , Adulto , Amônia , Estudos Transversais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fumaça
13.
Health Commun ; : 1-12, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37937858

RESUMO

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1). Based on survey findings, we selected a message focused on nicotine and brain development for the point-of-sale trial (Phase 2). We then conducted a cluster-randomized trial at six gas stations with convenience stores, randomly assigned to the intervention (messages displayed) or no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 participants (ages 16-25) per store, at baseline and a four-week follow-up. Phase 1 included 1,636 participants in the online study. Intervention messages were rated as more attention grabbing than plain text messages (p < .05), though were rated similarly on other outcomes. Exposure to intervention messages resulted in larger changes from pre- to posttest for beliefs about addiction and relative harms versus cigarettes (p < .05). Phase 2 included 586 participants in the point-of-sale study. Real-world campaign exposure was low (31.8%), and no differences were found between conditions. E-cigarette prevention messages focused on nicotine's impact on brain development show promise. However, garnering attention for communication campaigns in saturated point-of-sale environments, often dominated by tobacco advertising, is challenging. Future efforts should utilize additional communication channels to directly target adolescents and young adults.

14.
J Am Chem Soc ; 144(31): 14112-14120, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35901278

RESUMO

Non-viral delivery is an important strategy for selective and efficient gene therapy, immunization, and RNA interference, which overcomes problems of genotoxicity and inherent immunogenicity associated with viral vectors. Liposomes and polymers are compelling candidates as carriers for intracellular, non-viral delivery, but maximal efficiencies of around 1% have been reported for the most advanced non-viral carriers. Here, we develop a library of dendronized bottlebrush polymers with controlled defects, displaying a level of precision surpassed only by biological molecules like DNA, RNA, and proteins. We test concurrent and competitive delivery of DNA and show for the first time that, while intracellular communication is thought to be an exclusively biomolecular phenomenon, such communication between synthetic macromolecular complexes can also take place. Our findings challenge the assumption that delivery agents behave as bystanders that enable transfection by passive intracellular release of genetic cargo and improve upon coarse strategies in intracellular carrier design lacking control over polymer sequence, architecture, and composition, leading to a hit-or-miss outcome. Understanding the communication that takes place between macromolecules will help improve the design of non-viral delivery agents and facilitate translation of genome engineering, vaccines, and nucleic acid-based therapies.


Assuntos
Lipossomos , Polímeros , Comunicação Celular , DNA/metabolismo , Técnicas de Transferência de Genes , Lipossomos/metabolismo , Transfecção
15.
Epilepsia ; 63(8): 1889-1898, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35582761

RESUMO

Many brain insults and injuries are "epileptogenic": they increase the risk of developing epilepsy. It is desirable to identify treatments that are "antiepileptogenic": treatments that prevent the development of epilepsy, if administered after the occurrence of an epileptogenic insult. Current antiepileptic drugs are not antiepileptogenic, but evidence of antiepileptogenic efficacy is accumulating for a growing number of other compounds. From among these candidate compounds, statins are deserving of particular attention because statins are reported to be antiepileptogenic in more published studies and in a wider range of brain insults than any other individual or class of compounds. Although many studies report the antiepileptogenic effect of statins, it is unclear how many studies provide evidence that statins exhibit the following two essential features of a clinically viable antiepileptogenic drug: the drug must exert an antiepileptogenic effect even if it is initiated after the epileptogenic brain insult has already occurred, and the antiepileptogenic effect must endure even after the drug has been discontinued. In the current work, we interrogate published preclinical and clinical studies, to determine if statins fulfill these essential requirements. There are eight different statins in clinical use. To enable the clinical use of one of these statins for antiepileptogenesis, its antiepileptogenic effect will have to be established through future time- and resource-intensive clinical trials. Therefore, it is desirable to review the published literature to determine which of the statins emerges as the most promising candidate for antiepileptogenic therapy. Hence, in the current work, we also collate and analyze published data-clinical and pre-clinical, direct and indirect-that help to answer the question: Which statin is the most promising candidate to take forward into an antiepileptogenesis clinical trial?


Assuntos
Epilepsia , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticonvulsivantes/uso terapêutico , Encéfalo , Epilepsia/etiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
16.
J Theor Biol ; 540: 111063, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35189135

RESUMO

Individual variation in susceptibility and exposure is subject to selection by natural infection, accelerating the acquisition of immunity, and reducing herd immunity thresholds and epidemic final sizes. This is a manifestation of a wider population phenomenon known as "frailty variation". Despite theoretical understanding, public health policies continue to be guided by mathematical models that leave out considerable variation and as a result inflate projected disease burdens and overestimate the impact of interventions. Here we focus on trajectories of the coronavirus disease (COVID-19) pandemic in England and Scotland until November 2021. We fit models to series of daily deaths and infer relevant epidemiological parameters, including coefficients of variation and effects of non-pharmaceutical interventions which we find in agreement with independent empirical estimates based on contact surveys. Our estimates are robust to whether the analysed data series encompass one or two pandemic waves and enable projections compatible with subsequent dynamics. We conclude that vaccination programmes may have contributed modestly to the acquisition of herd immunity in populations with high levels of pre-existing naturally acquired immunity, while being crucial to protect vulnerable individuals from severe outcomes as the virus becomes endemic.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Imunidade Coletiva , Pandemias/prevenção & controle , Vacinação
17.
BMC Pregnancy Childbirth ; 22(1): 952, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539750

RESUMO

BACKGROUND: The provision of quality obstetric care in health facilities is central to reducing maternal mortality, but simply increasing childbirth in facilities not enough, with evidence that many facilities in sub-Saharan Africa do not fulfil even basic requirements for safe childbirth care. There is ongoing debate on whether to recommend a policy of birth in hospitals, where staffing and capacity may be better, over lower level facilities, which are closer to women's homes and more accessible. Little is known about the quality of childbirth care in Liberia, where facility births have increased in recent decades, but maternal mortality remains among the highest in the world. We will analyse quality in terms of readiness for emergency care and referral, staffing, and volume of births. METHODS: We assessed the readiness of the Liberian health system to provide safe care during childbirth use using three data sources: Demographic and Health Surveys (DHS), Service Availability and Readiness Assessments (SARA), and the Health Management Information System (HMIS). We estimated trends in the percentage of births by location and population caesarean-section coverage from 3 DHS surveys (2007, 2013 and 2019-20). We examined readiness for safe childbirth care among all Liberian health facilities by analysing reported emergency obstetric and neonatal care signal functions (EmONC) and staffing from SARA 2018, and linking with volume of births reported in HMIS 2019. RESULTS: The percentage of births in facilities increased from 37 to 80% between 2004 and 2017, while the caesarean section rate increased from 3.3 to 5.0%. 18% of facilities could carry out basic EmONC signal functions, and 8% could provide blood transfusion and caesarean section. Overall, 63% of facility births were in places without full basic emergency readiness. 60% of facilities could not make emergency referrals, and 54% had fewer than one birth every two days. CONCLUSIONS: The increase in proportions of facility births over time occurred because women gave birth in lower-level facilities. However, most facilities are very low volume, and cannot provide safe EmONC, even at the basic level. This presents the health system with a serious challenge for assuring safe, good-quality childbirth services.


Assuntos
Cesárea , Serviços de Saúde Materna , Recém-Nascido , Gravidez , Feminino , Humanos , Estudos Transversais , Libéria , Declaração de Nascimento , Censos , Parto Obstétrico , Parto , Instalações de Saúde , Acessibilidade aos Serviços de Saúde
18.
BMC Health Serv Res ; 22(1): 1165, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114536

RESUMO

BACKGROUND: The vast majority of refugees are hosted in low and middle income countries (LMICs), which are already struggling to finance and achieve universal health coverage for their own populations. While there is mounting evidence of barriers to health care access facing refugees, there is more limited evidence on equity in access to and affordability of care across refugee and host populations. The objective of this study was to examine equity in terms of health needs, service utilisation, and health care payments both within and between South Sudanese refugees and hosts communities (Ugandan nationals), in two districts of Uganda. METHODS: Participants were recruited from host and refugee villages from Arua and Kiryandongo districts. Twenty host villages and 20 refugee villages were randomly selected from each district, and 30 households were sampled from each village, with a target sample size of 2400 households. The survey measured condition incidence, health care seeking and health care expenditure outcomes related to acute and chronic illness and maternal care. Equity was assessed descriptively in relation to household consumption expenditure quintiles, and using concentration indices and Kakwani indices (for expenditure outcomes). We also measured the incidence of catastrophic health expenditure- payments for healthcare and impoverishment effects of expenditure across wealth quintiles. RESULTS: There was higher health need for acute and chronic conditions in wealthier groups, while maternal care need was greater among poorer groups for refugees and hosts. Service coverage for acute, chronic and antenatal care was similar among hosts and refugee communities. However, lower levels of delivery care access for hosts remain. Although maternal care services are now largely affordable in Uganda among the studied communities, and service access is generally pro-poor, the costs of acute and chronic care can be substantial and regressive and are largely responsible for catastrophic expenditures, with service access benefiting wealthier groups. CONCLUSIONS: Efforts are needed to enhance access among the poorest for acute and chronic care and reduce associated out-of-pocket payments and their impoverishing effects. Further research examining cost drivers and potential financing arrangements to offset these will be important.


Assuntos
Refugiados , Estudos Transversais , Feminino , Gastos em Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Gravidez , Uganda/epidemiologia
19.
J Cancer Educ ; 37(3): 770-778, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-32968953

RESUMO

When detected early, melanoma is highly treatable and rarely fatal. Self-skin checks can identify changes in moles that could be an indicator of melanoma. Cancer risk perceptions may influence the uptake of important preventive health behaviors such as self-skin checks. The purpose of this study is to examine cancer risk perception factors associated with those who have checked their skin for signs of skin cancer using the 2017 HINTS data. Retrospective cross-sectional analysis of a nationally representative sample of U.S. adults using the Health Information National Trends Survey (HINTS). Logistic regressions were performed to identify associations between having checked skin for signs of skin cancer, risk perceptions, and demographic variables. White women over the age of 45 with a college degree and annual incomes greater than $75,000 were more likely to check their skin for signs of skin cancer. More than a third reported they would rather not know if they had cancer and more than 60% had some level of worry about having cancer. Those with a personal or family history of cancer were more likely to check. HINTS is a cross-sectional survey which provides only a glimpse of behavioral predictors. Self-skin checks are simple and cost-effective to detect melanoma early and improve outcomes. Fear and worry about cancer were significant factors in the likelihood of checking skin for signs of skin cancer. Population-based strategies could be developed to reduce concerns about early detection.


Assuntos
Melanoma , Neoplasias Cutâneas , Adulto , Estudos Transversais , Feminino , Humanos , Melanoma/diagnóstico , Melanoma/prevenção & controle , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/prevenção & controle , Inquéritos e Questionários
20.
Prev Med ; 153: 106760, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34352307

RESUMO

Cigarette smoking is disproportionately high among sexual minority populations, but it is unclear whether these disparities exist among race/ethnicity subgroups. This study examined trends in sexual orientation disparities in cigarette smoking by race/ethnicity. Data are from the 2014-2019 Behavioral Risk Factor Surveillance System (N = 1,194,768). Trend analyses compared cigarette smoking by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic other) and sexual orientation (straight, lesbian or gay, bisexual, something else/don't know/refused). Multivariable analyses examined associations between sexual orientation and cigarette use for each race/ethnicity, controlling for other sociodemographic characteristics. Between 2014 and 2019, lesbian or gay, and bisexual populations consistently had higher smoking rates than straight populations, which held across race/ethnicity. Among non-Hispanic White adults, lesbians (OR = 1.51, 95% CI = 1.29, 1.76), bisexual females (OR = 1.56, 95% CI = 1.39, 1.75), gay (OR = 1.38, 95% CI = 1.22, 1.55), and bisexual males (OR = 1.22, 95% CI = 1.04, 1.43) had higher odds of smoking compared those self-identifying as straight. Among non-Hispanic Black adults, lesbians (OR = 1.90, 95% CI =1.33, 2.73) and bisexual females (OR = 1.85, 95% CI =1.42, 2.41) were more likely to currently smoke. Among Hispanic adults, those self-identifying as lesbian or gay (OR = 1.58, 95% CI = 1.19, 2.09) or bisexual (OR = 2.40, 95% CI = 1.88, 3.07) were more likely to currently smoke, though the associations were not significant in Hispanic males. Disparities in cigarette smoking by race/ethnicity and sexual orientation suggest that aggregating these groups mask important differences and limit efforts to target those most at risk.


Assuntos
Fumar Cigarros , Minorias Sexuais e de Gênero , Adulto , Bissexualidade , Fumar Cigarros/epidemiologia , Etnicidade , Feminino , Humanos , Masculino , Comportamento Sexual
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