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1.
J Biomed Opt ; 29(3): 035001, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38476221

RESUMO

Significance: Endotracheal intubation is a common approach for airway management in critically ill patients. However, the position of the endotracheal tube (ETT) may be altered during the procedure due to head movements. Accidental displacement or dislodge of the ETT may reduce the airflow, leading to moderate to severe complications, and in some cases even fatality. Therefore, timely detection of changes in ETT position in the trachea is critical to ensure immediate and intermediate interventions to maintain the ETT in the proper position. Currently, there are no widely utilized tools for real-time monitoring of ETT positions. Aim: The goal of this study is to develop a cost-effective and easy-to-use near-infrared (NIR) device, named Opt-ETT, capable of continuously monitoring the ETT position in the trachea of a patient. Approach: A side-firing fiber is attached to the side of the ETT to illuminate the trachea tissue with NIR light, and a detector board containing five phototransistors is affixed to the chest skin to measure the intensity of diffusely transmitted light. Displacement of the ETT is estimated using second-order polynomial fitting to the ratios of the phototransistor readings. Monte Carlo simulations, ex vivo experiment on porcine tissue, and in vivo experiments using a swine model have been conducted to assess the feasibility of the device. Results: The design of the Opt-ETT device has been verified by the Monte Carlo simulations and ex vivo experiment. The estimation of displacement from in vivo experiments using the Opt-ETT exhibited a high degree of agreement with that measured by a reference sensor, with a discrepancy between -1.0 to +1.5 mm within a displacement range from -15 to +15 mm. Conclusions: The Opt-ETT device provides a potentially cost-effective solution for real-time and continuous monitoring of ETT position in patient during an intubation procedure.


Assuntos
Intubação Intratraqueal , Traqueia , Humanos , Animais , Suínos , Intubação Intratraqueal/métodos , Raios Infravermelhos , Movimentos da Cabeça
2.
Artigo em Inglês | MEDLINE | ID: mdl-37563906

RESUMO

KEY POINTS: Resumption of continuous positive airway pressure (CPAP) in the immediate postoperative period after endoscopic endonasal approaches (EEA) for pituitary adenomas can be safe.

3.
JCO Oncol Pract ; 19(3): e397-e406, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36480772

RESUMO

PURPOSE: While pain is prevalent among survivors of head and neck cancer (HNC), there is a lack of data on pain management in the community oncology setting. We described sociodemographic correlates and disparities associated with patient-reported pain among patients with HNC. METHODS: We used the 2017-2021 nationwide community oncology data set from Navigating Cancer, which included electronic patient-reported outcomes. We identified a retrospective cohort of patients diagnosed with HNC (N = 25,572), with ≥ 1 patient-reported pain event. We adjusted for demographic (sex, age, smoking history, marital status) and clinical (cancer site) factors associated with pain reporting and pain resolution by new pain prescription on the basis of race (White v non-White patients), using multivariate logistic regression models. RESULTS: Our analytic cohort included 2,331 patients, 90.58% White, 58.62% married, with an average age of 66.47 years. Of these, 857 patients (36.76%) reported ≥ 1 pain event during study period. Mean resolution time (in minutes) for pain incidents was significantly longer for White patients than non-White patients (99.6 ± 3.2 v 74.9 ± 7.2, P < .05). After adjusting for covariates, smoking was associated with a 25% increased odds of reporting pain incidents (adjusted odds ratio [aOR], 1.25; 95% CI, 1.03 to 1.52). There was no statistically significant difference in odds of pain reporting between White versus non-White patients (aOR, 0.97; 95% CI, 0.73 to 1.30). However, White patients were significantly more likely to receive new prescription for pain than non-White patients (aOR, 2.52; 95% CI, 1.09 to 5.86). CONCLUSION: We found racial differences in patient-reported pain management, with White patients significantly more likely to receive new pain prescriptions. As pain management is a mainstay in cancer care, equity in pain management is critical to optimize quality of life for patients with HNC.


Assuntos
Neoplasias de Cabeça e Pescoço , Manejo da Dor , Humanos , Idoso , Estudos Retrospectivos , Qualidade de Vida , Dor , Medidas de Resultados Relatados pelo Paciente
4.
Hum Vaccin Immunother ; 18(7): 2148825, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36484115

RESUMO

It is unclear how the COVID-19 pandemic impacted human papillomavirus (HPV) vaccine uptake and which sociodemographic groups may have been most impacted. We aimed to assess differences in HPV vaccine uptake (initiation and completion) before and during the pandemic in the United States. We conducted a cross-sectional study using data from the 2019 to 2020 National Immunization Surveys - Teen (NIS-Teen), comparing vaccine initiation and completion rates in 2019 vs. 2020, based on confirmed reports by a healthcare provider. Weighted logistic regression analysis estimated odds of vaccine initiation and completion for both adolescent and parental characteristics. There were 18,788 adolescents in 2019 and 20,162 in 2020. There was 3.6% increase in HPV vaccine initiation (71.5% vs. 75.1%) and a 4.4% in completion (54.2% vs. 58.6%) rates from 2019 to 2020. In 2020, Non-Hispanic White teens were significantly less likely to initiate (aOR = 0.62, 95% CI: 0.49, 0.79) and complete (aOR = 0.71, 95% CI: 0.58, 0.86) vaccine uptake compared with non-Hispanic Black teens. Additionally, teens who lived above the poverty line were also less likely to initiate HPV vaccination (aOR = 0.63, 95% CI: 0.49, 0.80) or complete them (aOR = 0.73, 95% CI: 0.60, 0.90), compared to those who lived below the poverty line. During the COVID-19 pandemic in 2020, some historically advantaged socioeconomic groups such as those living above the poverty line were less likely to receive HPV vaccine. The impact of the pandemic on HPV vaccine uptake may transcend traditional access to care factors.


Assuntos
COVID-19 , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Estados Unidos/epidemiologia , Humanos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Pandemias , Papillomavirus Humano , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação
5.
Hum Vaccin Immunother ; 18(6): 2109892, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36070503

RESUMO

On the basis of their training, medical students are considered "the best case scenario" among university students in knowledge of the human papillomavirus (HPV). We evaluated differences in knowledge of HPV, HPV vaccine, and head and neck cancer (HNC) among medical students. A previously validated questionnaire was completed by 247 medical students at a Midwestern university. Outcomes of interest were knowledge score for HPV and HPV vaccine, and HNC, derived from combining questionnaire items to form HPV knowledge and HNC scores, and analyzed using multivariate linear regression. Mean scores for HPV knowledge were 19.4 out of 26, and 7.2 out of 12 for HNC knowledge. In the final multivariate linear regression model, sex, race, and year of study were independently associated with HPV and HPV vaccine knowledge. Males had significantly lower HPV vaccine knowledge than females (ß = -1.53; 95% CI: -2.53, -0.52), as did nonwhite students (ß = -1.05; 95% CI: -2.07, -0.03). There was a gradient in HPV vaccine knowledge based on the year of study, highest among fourth year students (ß = 6.75; 95% CI: 5.17, 8.33). Results were similar for factors associated with HNC knowledge, except for sex. HNC knowledge similarly increased based on year of study, highest for fourth year students (ß = 2.50; 95% CI: 1.72, 3.29). Among medical students, gaps remain in knowledge of HPV, HPV vaccine, and HPV-linked HNC. Male medical students have significantly lower knowledge of HPV. This highlights the need to increase medical student knowledge of HPV and HPV-linked HNC.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Estudantes de Medicina , Feminino , Masculino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Papillomavirus Humano , Neoplasias de Cabeça e Pescoço/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários
6.
Am J Otolaryngol ; 43(5): 103529, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35700606

RESUMO

PURPOSE: Pott's puffy tumor (PPT) is a rare clinical entity characterized by osteomyelitis of the frontal bone with subperiosteal abscess collection. The frequency of reported cases of PPT in the literature has increased in recent years. Previous reviews of PPT exist primarily in the form of small, retrospective case series and anecdotal case reports. Therefore, the aim of this study is to provide the literature's largest comprehensive, up-to-date review of the essential clinical findings, diagnostic modalities, microbiologic considerations, and treatment approaches utilized in the management of PPT, both in pediatric and adult populations. MATERIALS AND METHODS: We searched MEDLINE, PubMed, and Embase databases for English-language studies published from January 1950 through January 30, 2022. The authors reviewed all cases of PPT, focusing specifically on those describing therapeutic management of PPT. A total of 321 patients were included, consisting of 318 patients (from 216 articles) and an additional 3 adult cases from our institution. RESULTS: PPT most often results from untreated rhinosinusitis, as well as direct head trauma, substance use, and odontogenic disease. Infections are classically polymicrobial with an anaerobe-predominant microbiome. Both CT and MRI imaging modalities are commonly obtained for presurgical assessment of sinusitis and intracranial extension. The core of treatment is an early and aggressive approach to prevent long-term complications. A significant association exists between surgical management and clinical outcomes for patients with PPT. Recent literature suggests endoscopic sinus surgery is essential for successful disease resolution. CONCLUSIONS: PPT is an important and relatively morbid disease process that is often underrecognized and misdiagnosed at presentation due to its variable clinical presentation. Management of PPT includes both antimicrobial therapy and surgical intervention. Determination of the optimal approach depends on patient clinical features including age, history of prior endoscopic sinus surgery, and presence of intracranial involvement on presentation. An individualized, targeted, and interdisciplinary approach to the treatment of PPT is critical for successful disease resolution.


Assuntos
Tumor de Pott , Sinusite , Abscesso/diagnóstico , Abscesso/etiologia , Abscesso/terapia , Adulto , Criança , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Tumor de Pott/complicações , Tumor de Pott/diagnóstico , Tumor de Pott/terapia , Estudos Retrospectivos , Sinusite/complicações
7.
Cureus ; 14(3): e22857, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35399399

RESUMO

Objective Management of patients with post-tonsillectomy hemorrhage (PTH) is not well defined but may include observation, topical bedside treatments, or return to the operating room. Data on the use and efficacy of silver nitrate as a topical bedside agent for the management of PTH remain unexplored. Our primary objective was to assess the efficacy of silver nitrate in reducing the need for operative control of PTH. Methods Single-institution retrospective chart review included patients aged 5-18 years who presented with tonsillar bleeding within 30 days of tonsillectomy. Patients undergoing observation or bedside silver nitrate cautery were compared based on clinical characteristics and experience of the physician performing the procedure. The outcome of interest was rebleeding requiring operative control. Sample characteristics according to treatment modality were described using Fisher's exact tests and ANOVA. Results Of the patients eligible for inclusion, 29 (20%) were observed and 70 (48.3%) were treated with topical silver nitrate. Age was the only statistically significant clinical difference among treatment groups. The silver nitrate group had more patients who underwent operative control of PTH compared to the observation group (p = 0.004). When comparing the need for operative control between the observation group and patients who had initial success with silver nitrate, there was no difference (p = 0.29). No differences were found in the rate of bleeding requiring operative control when comparing experience of the physician performing the procedure (p = 0.20). Conclusion More patients who underwent silver nitrate cautery required PTH control in the operating room compared to the observation group. This may be due to patient selection as our results also suggest that there is no statistical difference in rates of operative control of PTH when comparing initial successful treatment with topical silver nitrate to observation. Age is likely a factor that was used by physicians in this study to decide the initial management of PTH. Provider experience does not appear to affect rebleeding rates. Future studies are necessary to evaluate the clinical impact of silver nitrate in the context of PTH and will benefit from more robust sample sizes and enhanced diversity in the sample group.

8.
Anat Rec (Hoboken) ; 305(8): 2065-2074, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35388627

RESUMO

The nasopharynx is an integral component of the upper aerodigestive tract, whose morphologic features share an intimate relationship with a vast array of clinical, functional, and quality of life conditions related to contemporary humans. Its composite architecture and central location amidst the nasal cavity, pharyngotympanic tube, palate, and skull base bears implications for basic physiologic functions including breathing, vocalization, and alimentation. Over the course of evolution, morphological modifications of nasopharyngeal anatomy have occurred in genus Homo which serve to distinguish the human upper aerodigestive tract from that of other mammals. Understanding of these adaptive changes from both a comparative anatomy and clinical perspective offers insight into the unique blueprint which underpins many clinical pathologies currently encountered by anthropologists, scientists, and otorhinolaryngologists alike. This discussion intends to familiarize readers with the fundamental role that nasopharyngeal morphology plays in upper aerodigestive tract conditions, with consideration of its newfound clinical relevance in the era of the COVID-19 pandemic.


Assuntos
COVID-19 , Hominidae , Animais , Humanos , Mamíferos , Nasofaringe/anatomia & histologia , Nasofaringe/fisiologia , Pandemias , Qualidade de Vida
9.
Pediatr Res ; 92(2): 563-571, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34645953

RESUMO

BACKGROUND: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.


Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Adiponectina/genética , Adolescente , Biomarcadores , Doenças Cardiovasculares/genética , Grelina/genética , Hispânico ou Latino/genética , Humanos , Insulina , Resistência à Insulina/genética , Leptina , Estudos Longitudinais , Orexinas
10.
Cancer Control ; 28: 10732748211041894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34696619

RESUMO

OBJECTIVES: Human papillomavirus (HPV)-associated cancers account for about 9% of the cancer mortality burden in the United States; however, survival differs among sociodemographic factors. We determine sociodemographic and clinical variables associated with HPV-associated cancer survival. METHODS: Data derived from the Surveillance, Epidemiology, and End Results 18 cancer registry were analyzed for a cohort of adult patients diagnosed with a first primary HPV-associated cancer (anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers), between 2007 and 2015. Multivariable Fine and Gray proportional hazards regression models stratified by anatomic site estimated the association of sociodemographic and clinical variables and cancer-specific survival. RESULTS: A total of 77 774 adults were included (11 216 anal, 27 098 cervical, 30 451 oropharyngeal, 2221 penile, 1176 vaginal, 5612 vulvar; average age = 57.2 years). The most common HPV-associated cancer was cervical carcinoma (58%) for females and oropharyngeal (81%) for male. Among patients diagnosed with anal/rectal squamous cell carcinoma (SCC), males had a higher risk of death than females. NonHispanic (NH) blacks had a higher risk of death from anal/rectal SCC, oropharyngeal SCC, and cervical carcinoma; and Hispanics had a higher risk of death from oropharyngeal SCC than NH whites. Marital status was associated with risk of death for all anatomic sites except vulvar. Compared to nonMedicaid insurance, patients with Medicaid and uninsured had higher risk of death from anal/rectal SCC, oropharyngeal SCC, and cervical carcinoma. CONCLUSIONS: There exists gender (anal) and racial and insurance (anal, cervical, and oropharyngeal) disparities in relative survival. Concerted efforts are needed to increase and sustain progress made in HPV vaccine uptake among these specific patient subgroups, to reduce cancer incidence.


Assuntos
Neoplasias/epidemiologia , Neoplasias/etiologia , Infecções por Papillomavirus/complicações , Fatores Sociodemográficos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/virologia , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Programa de SEER , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
12.
Nat Genet ; 53(6): 840-860, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34059833

RESUMO

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.


Assuntos
Glicemia/genética , Característica Quantitativa Herdável , População Branca/genética , Alelos , Epigênese Genética , Perfilação da Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Hemoglobinas Glicadas/metabolismo , Humanos , Herança Multifatorial/genética , Mapeamento Físico do Cromossomo , Locos de Características Quantitativas/genética
13.
Head Neck ; 43(7): 2136-2147, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33780066

RESUMO

PURPOSE: Privately insured patients with head and neck cancer (HNC) typically have better outcomes; however, differential outcome among Medicaid versus the uninsured is unclear. We aimed to describe outcome disparities among HNC patients uninsured versus on Medicaid. METHODS: A cohort of 18-64-year-old adults (n = 57 920) with index HNC from the Surveillance, Epidemiology, and End Results 18 database (2007-2015) was analyzed using Fine and Gray multivariable competing risks proportional hazards models for HNC-specific mortality. RESULTS: Medicaid (sdHR = 1.65, 95% CI 1.58, 1.72) and uninsured patients (sdHR = 1.55, 95% CI 1.46, 1.65) had significantly greater mortality hazard than non-Medicaid patients. Medicaid patients had increased HNC mortality hazard than those uninsured. CONCLUSION: Compared with those uninsured, HNC patients on Medicaid did not have superior survival, suggesting that there may be underlying mechanisms/factors inherent in this patient population that could undermine access to care benefits from being on Medicaid.


Assuntos
Neoplasias de Cabeça e Pescoço , Medicaid , Adolescente , Adulto , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Cobertura do Seguro , Seguro Saúde , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
14.
Am J Hum Genet ; 108(4): 564-582, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33713608

RESUMO

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.


Assuntos
População Negra/genética , Estatura/genética , Estudo de Associação Genômica Ampla , África/etnologia , Negro ou Afro-Americano/genética , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
16.
J Matern Fetal Neonatal Med ; 33(22): 3809-3815, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30810416

RESUMO

Background: For women who suffer from abruption in the first pregnancy, the extent to which birth spacing has an impact on maternal and fetal outcomes in a second pregnancy remains unclear.Objectives: To examine the effect of interpregnancy interval (IPI) after a first pregnancy complicated by placental abruption, on adverse maternal and fetal outcomes in a subsequent pregnancy.Study design: This was a population-based retrospective cohort study using maternally-linked Missouri birth registry from 1989 to 2005 (n = 2069). Exposure of interest was IPI and outcomes were placental abruption, preeclampsia, preterm birth, small for gestational age, cesarean delivery, and neonatal plus fetal deaths (neofetal death) in a second pregnancy. Logistic regressions were used to assess the association between IPI and the outcomes.Results: Compared with women with an IPI of 1-2 years, those with short IPI (<1 year) were more likely to experience preterm birth (aOR 3.01, 95% CI 1.71-5.28) and neonatal death (aOR 3.52, 95% CI 1.24-10.02) in their subsequent pregnancy. No significant associations between IPI and recurrent placental abruption or preeclampsia were detected.Conclusions: Women who become pregnant in less than a year's time of an initial placental abruption are at increased risk for preterm birth and neofetal death in a subsequent pregnancy. Other ischemic placental disease conditions are also shown to have serious health implications for a woman's next pregnancy.


Assuntos
Descolamento Prematuro da Placenta , Nascimento Prematuro , Descolamento Prematuro da Placenta/epidemiologia , Intervalo entre Nascimentos , Feminino , Número de Gestações , Humanos , Recém-Nascido , Missouri/epidemiologia , Placenta , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Fatores de Risco
17.
Nat Commun ; 10(1): 4957, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673082

RESUMO

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.


Assuntos
Tamanho Corporal/genética , Cognição , Consanguinidade , Fertilidade/genética , Nível de Saúde , Depressão por Endogamia/genética , Assunção de Riscos , Alelos , Haplótipos , Homozigoto , Humanos
18.
BMJ ; 366: l4292, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345923

RESUMO

OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Adulto , Alelos , Diabetes Mellitus Tipo 2/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
19.
Biol Psychiatry ; 85(11): 946-955, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30679032

RESUMO

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Exoma , Variação Genética/fisiologia , Fumar/fisiopatologia , Consumo de Bebidas Alcoólicas/genética , Bases de Dados Genéticas , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Genótipo , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fumar/genética
20.
Sci Rep ; 9(1): 297, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670748

RESUMO

This study assessed if race and gender predict known sexual risk factors associated with HPV. Data (n = 301) were from a cross-sectional study conducted at a drag racing event on September 12-13, 2015 in Madison, Illinois. Both multivariable logistic and linear regression models estimated the association between race, gender, and sexual risk factors. About 63% of participants were males, and 65% identified as Blacks. Compared to females, males were more likely to have a higher number of oral sexual partners (OR = 2.10; 95% CI: 1.23, 3.57). Males were also more likely to have earlier oral sexual (b = -2.10; 95% CI: -3.60, -0.60) and vaginal sexual (b = -1.10; 95% CI: -1.69, -0.31) debuts compared to females. Blacks were more likely to have higher number of vaginal sexual partners (OR = 3.38; 95% CI: 1.81, 6.31) and earlier vaginal sex (b = -1.09; 95% CI: -1.78, -0.41) but less likely to have earlier oral sexual debuts compared with Whites (b = 2.67; 95% CI: 1.21, -4.13). Because HPV is associated with several cancers, our findings provide impetus for the development of targeted educational interventions aimed at improving the knowledge of these sexual risk factors, especially among men and across race groups.


Assuntos
Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/etiologia , Comportamento Sexual , Adulto , População Negra , Estudos Transversais , Feminino , Humanos , Illinois , Masculino , Pessoa de Meia-Idade , Fatores Raciais , Fatores de Risco , Fatores Sexuais , Parceiros Sexuais , População Branca
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