RESUMEN
A novel microsporidium was observed in wild swamp guppies Micropoecilia picta from Levera Pond within Levera National Park Grenada, West Indies. Initial observations indicated similarity with Pseudoloma neurophilia, an important pathogen in zebrafish Danio rerio. P. neurophilia exhibit broad host specifity, including members of the family Poecillidae, and both parasites infect the central nervous system. However, spore morphology and molecular phylogeny based on rDNA showed that the swamp guppy microsporidium (SGM) is distinct from P. neurophilia and related microsporidia (Microsporidium cerebralis and M. luceopercae). Spores of the SGM were smaller than others in the clade (3.6 µm long). Differences were also noted in histology; the SGM formed large aggregates of spores within neural tissues along with a high incidence of numerous smaller aggregates and single spores within the surface tissue along the ventricular spaces that extended submeninx, whereas P. neurophilia and M. cerebralis infect deep into the neuropile and cause associated lesions. Analysis of small subunit ribosomal DNA sequences showed that the SGM was <93% similar to these related microsporidia. Nevertheless, one of 2 commonly used PCR tests for P. neurophilia cross reacted with tissues infected with SGM. These data suggest that there could be other related microsporidia capable of infecting zebrafish and other laboratory fishes that are not being detected by these highly specific assays. Consequently, exclusive use of these PCR tests may not accurately diagnose other related microsporidia infecting animals in laboratory and ornamental fish facilities.
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Enfermedades de los Peces , Microsporidios , Microsporidiosis , Filogenia , Poecilia , Animales , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/parasitología , Microsporidios/genética , Microsporidios/aislamiento & purificación , Microsporidios/clasificación , Microsporidiosis/veterinaria , Microsporidiosis/microbiología , Grenada/epidemiologíaRESUMEN
The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase ~50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 copy number. Population studies, including USA-based cohorts, showed distinct KIV-2 CN, distributions for European-, African-, and Hispanic-American populations and further underscored the limitations of SNV predictors. We demonstrate that the CN estimates correlate significantly with the available Lp(a) protein levels and that phasing is highly important.
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Disclosure of suicidal ideation and behaviours, defined as thoughts, plans, or attempts, to other people provides opportunity for intervention and prevention. This study is the first to meta-analyze all available studies to estimate the prevalence of disclosure, to whom people disclose, and examine factors that influence disclosure. Databases were searched for studies reporting samples of people who had experienced suicidal ideation or behaviours (including those who had died by suicide) and whether they had disclosed this. Almost 100 studies (k = 94, N participants = 1,044,629) were included in the overall prevalance analysis. The results showed less than half of people disclosed suicidal ideation or behaviour: 45.9% (95%CI 41.9-49.9%, PI 12.3-81.8%; k = 94). High heterogeneity, common to prevalence studies, was found (Q[93] = 130,584, p < .001; I2 = 99.9%). No publication bias was detected. Removing outliers did not change the prevalence estimate, but provided tighter prediction intervals: 45.6% (95%CI 43.4-47.9%, PI 35.8-55.7%; k = 33). Disclosure was related to higher prevalence of psychiatric disorders, female gender, and a longer timeframe of suicidal ideation or behaviour. Prevalence of disclosure was lower among people who died by suicide, relative to community samples, and lower when reported verbally rather than written online. Disclosure, and proportions of disclosures, to family members, was numerically higher than to friends or professionals, but could not be directly compared. In conclusion, between 50 and 60% of people do not disclose their suicidal ideation and behaviours to other people, and therefore remain unidentified and potentially untreated.
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Ideación Suicida , Suicidio , Humanos , Femenino , Intento de Suicidio/psicología , Revelación , PrevalenciaRESUMEN
BACKGROUND: Insufficient cost data and limited capacity constrains the understanding of the actual resources required for effective TB control. This study used process maps and time-driven activity-based costing to document TB service delivery processes. The analysis identified the resources required to sustain TB services in Zimbabwe, as well as several opportunities for more effective and efficient use of available resources. METHODS: A multi-disciplinary team applied time-driven activity-based costing (TDABC) to develop process maps and measure the cost of clinical pathways used for Drug Susceptible TB (DS-TB) at urban polyclinics, rural district and provincial hospitals, and community based targeted screening for TB (Tas4TB). The team performed interviews and observations to collect data on the time taken by health care worker-patient pairs at every stage of the treatment pathway. The personnel's practical capacity and capacity cost rates were calculated on five cost domains. An MS Excel model calculated diagnostic and treatment costs. FINDINGS: Twenty-five stages were identified in the TB care pathway across all health facilities except for community targeted screening for TB. Considerable variations were observed among the facilities in how health care professionals performed client registration, taking of vital signs, treatment follow-up, dispensing medicines and processing samples. The average cost per patient for the entire DS-TB care was USD324 with diagnosis costing USD69 and treatment costing USD255. The average cost for diagnosis and treatment was higher in clinics than in hospitals (USD392 versus USD256). Nurses in clinics were 1.6 time more expensive than in hospitals. The main cost components were personnel (USD130) and laboratory (USD119). Diagnostic cost in Tas4TB was twice that of health facility setting (USD153 vs USD69), with major cost drivers being demand creation (USD89) and sputum specimen transportation (USD5 vs USD3). CONCLUSION: TDABC is a feasible and effective costing and management tool in low-resource settings. The TDABC process maps and treatment costs revealed several opportunities for innovative improvements in the NTP under public health programme settings. Re-engineering laboratory testing processes and synchronising TB treatment follow-up with antiretroviral treatments could produce better and more uniform TB treatments at significantly lower cost in Zimbabwe.
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Costos de la Atención en Salud , Hospitales , Estudios de Factibilidad , Humanos , Factores de Tiempo , Zimbabwe/epidemiologíaRESUMEN
BACKGROUND: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS). PATIENTS AND METHODS: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance). Due to an enforced redesign of the trial in September 2011, the primary endpoint became PFS between arms A and C which we have previously published, and the overall survival (OS) was defined as a secondary endpoint, which is reported here. RESULTS: After a median follow-up of 25.6 months, strong evidence of an effect of concurrent plus maintenance cediranib on PFS was observed [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.72, P < 0.0001]. In this final update of the survival analysis, 90% of patients have died. There was a 7.4-month difference in median survival and an HR of 0.86 (95% CI: 0.67-1.11, P = 0.24) in favour of arm C. There was strong evidence of a departure from the assumption of non-proportionality using the Grambsch-Therneau test (P = 0.0031), making the HR difficult to interpret. Consequently, the restricted mean survival time (RMST) was used and the estimated difference over 6 years by the RMST was 4.8 months (95% CI: -0.09 to 9.74 months). CONCLUSIONS: Although a statistically significant difference in time to progression was seen, the enforced curtailment in recruitment meant that the secondary analysis of OS was underpowered. The relative reduction in the risk of death of 14% risk of death was not conventionally statistically significant, but this improvement and the increase in the mean survival time in this analysis suggest that cediranib may have worthwhile activity in the treatment of recurrent ovarian cancer and that further research should be undertaken.
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Neoplasias Ováricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Quinazolinas/uso terapéuticoRESUMEN
BACKGROUND: More than 100 US physicians have died from COVID-19. I considered the number of US physician deaths in comparison to the expected COVID death rate in the general population. AIMS: To estimate the whether US physicians are at increased risk of death from COVID-19 due to occupational exposures. METHODS: COVID-related physician deaths were identified through searches using Medscape In Memoriam, and multiple internet searches using Google and Facebook. An obituary or death notice was obtained in all but one case. Death rates among physicians were compared to the expected rate based on COVID deaths in the US population. RESULTS: Up to 7 October 2020, there were 108 deaths among US physicians. Physicians make up about 0.33% of the US population. By 1 October 2020, there were 210 000 COVID deaths in the US population with 693 expected physician deaths. Observed deaths were 16% of expected. Seventy-five per cent of the deaths occurred among physicians older than age 60 and about half appeared to be among those retired from clinical practice. CONCLUSIONS: Observed physician deaths were significantly below expected based on deaths the general population. Prudent use of personal protective equipment may explain the lower-than-expected death rates.
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COVID-19 , Infecciones por Coronavirus , Coronavirus , Médicos , Humanos , Persona de Mediana Edad , SARS-CoV-2RESUMEN
AIMS: To determine whether loss of muscle mass (approximated using fat free mass [FFM]) is associated with risk for type 2 diabetes mellitus (T2DM) in Hispanic/Latino adults in the United States. METHODS: Participants were Hispanic/Latino adults (18-74-year-olds) who completed Visit 2 of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; multi-site, prospective cohort study; 6.1-year follow-up) and did not have T2DM at baseline (n = 6264). At baseline and Visit 2, FFM was measured using bioelectrical impedance analysis and fasting glucose, HbA1c, and fasting insulin were measured by examiners. Diabetes was defined according to American Diabetes Association criteria. Survey-weighted Poisson regression models examined the association of percent change in relative FFM (%ΔFFM) with incident prediabetes and T2DM. Survey-weighted multivariable regression models examined associations of %ΔFFM with changes in glucose and insulin measures. RESULTS: Relative FFM declined by 2.1% between visits. %ΔFFM was inversely associated with incident prediabetes (p-for-trend = 0.001) and with changes in glucose and insulin measures (p-for-trend <0.0001). Findings were null, except for HOMA-IR, after adjustment for changes in adiposity measures. Associations were generally stronger for individuals with baseline overweight/obesity. CONCLUSIONS: Reducing loss of FFM during adulthood may reduce prediabetes risk (primarily insulin resistance), particularly among individuals with overweight/obesity.
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Diabetes Mellitus Tipo 2/etiología , Fuerza Muscular/fisiología , Salud Pública/métodos , Adolescente , Adulto , Anciano , Diabetes Mellitus Tipo 2/patología , Femenino , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Estados Unidos , Adulto JovenRESUMEN
Anthelmintic resistance in equine cyathostomins is both widespread and highly prevalent in the benzimidazole and tetrahydropyrimidine classes; however, reports of resistance to macrocyclic lactone (ML) drugs are sparse and sporadic. This study reports a case of clear ML resistance in a group of Thoroughbred yearlings imported from Ireland to the US in 2019. Fecal egg count reduction (FECR) following ivermectin administered in February 2020 demonstrated 100% reduction in the US bred yearlings, but 93.5%, 70.5%, and 74.5% reduction in three groups of the imported yearlings. The two former groups were then retreated with ivermectin, yielding FECRs of 33.8% and 23.5%, respectively. Horses from these two groups were then assigned randomly to two possible treatments; moxidectin or a triple combination of moxidectin, oxibendazole, and pyrantel pamoate. The groups treated with moxidectin had FECRs of 90.2%, 57.3%, and 50.0%, while the triple combination had a 100% FECR in all treated groups. Subsequently, the efficacy of ivermectin was reassessed in June 2020 yielding FECRs of 99.8%, 87.7%, and 62.0% in the three imported groups. The FECRs of the US bred yearlings all remained in the 99-100% range. This is the first study to clearly demonstrate ML resistance in cyathostomins and to confirm the suspicion through reassessment. These data demonstrate that ML-resistant cyathostomins were imported from Ireland and serve to illustrate that the global movement of horses has the potential to quickly spread ML-resistant parasite isolates around the world. The equine industry is strongly encouraged to routinely monitor anthelmintic efficacy, so occurrence of ML resistant cyathostomins can be detected and appropriate interventions implemented as early as possible.
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Antihelmínticos , Enfermedades de los Caballos , Lactonas , Animales , Antihelmínticos/farmacología , Resistencia a Medicamentos , Granjas , Heces , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/parasitología , Caballos , Humanos , Irlanda , Ivermectina/uso terapéutico , Recuento de Huevos de ParásitosRESUMEN
BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals' cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH's cost savings. RESULTS: After removing non-transferable sources of efficiency, NH's residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH's high annual CABG volume facilitates such supervised work "downshifting." The study is subject to limitations inherent in case studies, does not account for the younger age of NH's patients, or capture savings attributable to NH's negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital's cost advantage would require more flexible American states' hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.
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Puente de Arteria Coronaria/economía , Enfermedad de la Arteria Coronaria/cirugía , Procedimientos Quirúrgicos Electivos/economía , Costos de Hospital , Medicare/economía , Transferencia de Pacientes/economía , Enfermedad de la Arteria Coronaria/economía , Femenino , Humanos , India , Masculino , Estados UnidosRESUMEN
OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.
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Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Infecciones por VIH/complicaciones , Sobrevivientes de VIH a Largo Plazo/estadística & datos numéricos , Adulto , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Recuento de Linfocito CD4 , Calcio/metabolismo , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/etiología , Enfermedades de las Arterias Carótidas/inmunología , Grosor Intima-Media Carotídeo , Estudios de Cohortes , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Humanos , Receptores de Lipopolisacáridos/sangre , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Receptores de Superficie Celular/sangre , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Impairments in the specificity of autobiographical memory (AM) and future thinking are associated with a range of affective and psychopathological states, however, whether these deficits also occur in the context of state anxiety is not well known. We examined the effects of increasing state anxiety on the specificity of AM and future thoughts, as well as whether changes in rumination and executive functioning mediate any observed effects. METHODS: Sixty-four participants (M ageâ¯=â¯29.1, SDâ¯=â¯11.5) were randomized to either an anxiety or neutral mood induction and completed pre and post-measures of the constructs of interest. RESULTS: There were significant decreases observed in AM specificity in the anxiety induction group, relative to the neutral group. No changes were observed for future thinking specificity. Rumination was increased as a result of the anxiety induction, but only a non-significant trend was observed with respect to its association with changes in AM and future thinking specificity. Verbal fluency and working memory were not affected by the induction. LIMITATIONS: Physiological measures of anxiety were not used. State anxiety, although increased, was not high in severity. Future research might use a clinical sample to assess generalizability of these findings. CONCLUSIONS: Although preliminary, these findings provide first evidence of the causal impact of an anxiety induction on the ability to retrieve specific AM.
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Ansiedad/fisiopatología , Función Ejecutiva/fisiología , Memoria Episódica , Recuerdo Mental/fisiología , Rumiación Cognitiva/fisiología , Pensamiento/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Experts recommend a change in the control of equine parasites across the world in order to adopt a surveillance-based approach utilizing parasite faecal egg counts (FEC). Several European countries have implemented prescription-only restrictions of anthelmintic usage by law, which is in stark contrast to US, where all anthelmintic products continue to be available over the counter. This study aimed to describe and compare equine parasite control strategies employed in Germany, Austria, the Netherlands, US, and Denmark. An invitation to participate in an online questionnaire survey was published on a large equine news website in each of the participating countries. The main focus of the study was on usage of FEC and anthelmintic treatment intensity in three different equine age groups; foals, 1-3 year-olds and >3 years old. A total of 3092 respondents participated in the study. Danish respondents used significantly more faecal analyses in their parasite control strategies than participants from the other four countries (pâ¯<â¯0.0001). Similarly, Danish participants administered significantly fewer anthelmintic treatments per horse per year (pâ¯<â¯0.0001) independent of the age of the horse, and had been using a selective treatment strategy for a significantly longer time period than their counterparts in other countries (pâ¯<â¯0.0001). Only minor differences were found between respondents from the other four countries. This is remarkable as both Austria and Germany have had prescription-only restrictions for 3-4 decades. Yet, their parasite control strategies were more similar to those employed by American respondents. The Netherlands had only recently introduced prescription-only restrictions by the time this survey was conducted which can explain why Dutch respondents were also similar to their American counterparts. Taken together, this study illustrates substantially different worm control strategies practiced in Denmark, and this difference cannot be explained by legislation alone.
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Antihelmínticos/provisión & distribución , Control de Enfermedades Transmisibles/legislación & jurisprudencia , Enfermedades de los Caballos/prevención & control , Recuento de Huevos de Parásitos/veterinaria , Infecciones Equinas por Strongyloidea/prevención & control , Factores de Edad , Crianza de Animales Domésticos/legislación & jurisprudencia , Crianza de Animales Domésticos/estadística & datos numéricos , Animales , Antihelmínticos/uso terapéutico , Austria/epidemiología , Control de Enfermedades Transmisibles/métodos , Dinamarca/epidemiología , Europa (Continente)/epidemiología , Heces/parasitología , Alemania/epidemiología , Enfermedades de los Caballos/epidemiología , Caballos/parasitología , Países Bajos/epidemiología , Recuento de Huevos de Parásitos/métodos , Infecciones Equinas por Strongyloidea/tratamiento farmacológico , Infecciones Equinas por Strongyloidea/epidemiología , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND AIMS: Existing literature in individuals without diabetes has not demonstrated a relationship between IR and incident AF; however, data are limited and only fasting glucose measures of IR were assessed. We evaluated the relationship of both fasting and post-glucose load IR measures with the development of atrial fibrillation in nondiabetic older adults. METHODS AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), those without prevalent AF or diabetes and with IR measures at baseline were followed for the development of AF, identified by follow-up visit electrocardiograms, hospital discharge diagnosis coding, or Medicare claims data, through 2014. Fasting IR was determined by the homeostatic model of insulin resistance (HOMA-IR) and post-glucose load IR was determined by the Gutt index. Cox proportional hazards models were used to determine the association of IR with risk of AF. Analyses included 3601 participants (41% men) with a mean age of 73 years. Over a median follow-up of 12.3 years, 1443 (40%) developed AF. After multivariate adjustment, neither HOMA-IR nor the Gutt index was associated with risk of developing AF [hazard ratios (95% confidence intervals): 0.96 (0.90, 1.03) for 1-SD increase in HOMA-IR and 1.03 (0.97, 1.10) for 1-SD decrease in the Gutt index]. CONCLUSIONS: We found no evidence of an association between either fasting or post-glucose load IR measures and incident AF.
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Fibrilación Atrial/epidemiología , Glucemia/metabolismo , Ayuno/sangre , Trastornos del Metabolismo de la Glucosa/sangre , Trastornos del Metabolismo de la Glucosa/epidemiología , Resistencia a la Insulina , Anciano , Fibrilación Atrial/diagnóstico , Biomarcadores/sangre , Electrocardiografía , Femenino , Trastornos del Metabolismo de la Glucosa/diagnóstico , Trastornos del Metabolismo de la Glucosa/fisiopatología , Prueba de Tolerancia a la Glucosa , Humanos , Incidencia , Estudios Longitudinales , Masculino , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.
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Electrocardiografía/efectos de los fármacos , Etnicidad/genética , Compuestos de Sulfonilurea/efectos adversos , Anciano , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/genética , Citocromo P-450 CYP2C9/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Femenino , Variación Genética/efectos de los fármacos , Variación Genética/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética/métodos , Pruebas de Farmacogenómica/métodos , Compuestos de Sulfonilurea/uso terapéuticoRESUMEN
Background: We sought to determine the survival benefits that patients judged sufficient to warrant adjuvant therapy with sorafenib for 1 year, or for 3 years after resection of renal cell carcinoma in the SORCE trial. Methods: SORCE participants from all sites in Australia and New Zealand, and selected sites in the UK, completed a validated preferences questionnaire at months 0, 3, 15, and 42 to elicit the minimum survival benefits they judged sufficient to warrant adjuvant sorafenib for 1 year (versus observation), or for 3 years (versus 1 year). The questionnaires used reference survival times of 5 and 15 years; and reference survival rates at 5 years of 65% and 85%. Results: The 233 participants had a median age of 57 years (range 29-78) and 71% were male. For 1 year of sorafenib versus no adjuvant therapy, the median benefits in survival times judged sufficient to warrant treatment were an extra 9 months beyond 5 years and an extra 1 year beyond 15 years; the median benefit in survival rates were an extra 4% beyond 65% and an extra 3% beyond 85% at 5 years. For 3 years of sorafenib versus 1 year of sorafenib, the median benefit in survival time judged sufficient to warrant extended treatment was an extra 1 year beyond both 5 and 15 years. Participants randomly allocated to treatment with sorafenib judged larger benefits necessary than those allocated to placebo. Participants' preferences were not associated with their baseline characteristics or the interval from randomisation. Conclusion: Most participants judged an extra year of survival necessary to warrant 1 year of adjuvant sorafenib worthwhile, and an additional year of survival to warrant extending the duration of sorafenib from 1 to 3 years. Patients' preferences are important in shared decision making. SORCE trial clinical trials number: NCT00492258.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Prioridad del Paciente , Sorafenib/uso terapéutico , Adulto , Anciano , Carcinoma de Células Renales/mortalidad , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/mortalidad , Femenino , Humanos , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
This corrects the article DOI: 10.1038/jhh.2016.98.
RESUMEN
BACKGROUND: Level of alcohol consumption is associated with differential risk of atherosclerosis, but little research has investigated this association among HIV+ persons. We evaluated the association between long-term alcohol use and incident atherosclerosis among HIV+ persons. METHODS: We utilized data from HIV+ participants of the Women's Interagency HIV Study (n=483) and the Multicenter AIDS Cohort Study (n=305) without history of cardiovascular disease. Atherosclerosis was assessed two times by B-mode carotid artery ultrasound imaging from 2004 to 2013. Presence of plaque was defined as focal carotid intima-media thickness over 1.5mm. Those with no plaque at baseline and plaque at follow-up were considered incident cases of atherosclerosis. Group-based trajectory models were used to categorize participants into 10-year drinking patterns representing heavy, moderate, or abstinent-low. Multivariable logistic regressions were conducted to assess the association of long-term moderate and heavy use on atherosclerosis, compared to abstinent-low. RESULTS: Heavy alcohol consumption was not statistically significantly associated with risk for incident atherosclerosis in women (AOR 1.10, CI 0.40-3.02) or men (AOR 1.31, CI 0.43-4.00), compared to abstinence-low. Moderate consumption was associated with 54% lower odds for incident disease in men (AOR 0.46, CI 0.21-1.00), but not in women (AOR 1.08, CI 0.58-2.00). In cohort-combined analyses, alcohol consumption was not statistically significantly association with incident atherosclerosis (moderate AOR 0.78, CI 0.48-1.27; heavy AOR 1.33, CI 0.66-2.69). CONCLUSION: Moderate alcohol consumption was associated with a significant protective effect on incident atherosclerosis in men only. No other levels of alcohol consumption significantly predicted atherosclerosis in men and women compared to abstinent-low.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Aterosclerosis/virología , Infecciones por VIH/complicaciones , Adulto , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Grosor Intima-Media Carotídeo , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores Protectores , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Measurement error in assessment of sodium and potassium intake obscures associations with health outcomes. The level of this error in a diverse US Hispanic/Latino population is unknown. We investigated the measurement error in self-reported dietary intake of sodium and potassium and examined differences by background (Central American, Cuban, Dominican, Mexican, Puerto Rican and South American). In 2010-2012, we studied 447 participants aged 18-74 years from four communities (Miami, Bronx, Chicago and San Diego), obtaining objective 24-h urinary sodium and potassium excretion measures. Self-report was captured from two interviewer-administered 24-h dietary recalls. Twenty percent of the sample repeated the study. We examined bias in self-reported sodium and potassium from diet and the association of mismeasurement with participant characteristics. Linear regression relating self-report with objective measures was used to develop calibration equations. Self-report underestimated sodium intake by 19.8% and 20.8% and potassium intake by 1.3% and 4.6% in men and women, respectively. Sodium intake underestimation varied by Hispanic/Latino background (P<0.05) and was associated with higher body mass index (BMI). Potassium intake underestimation was associated with higher BMI, lower restaurant score (indicating lower consumption of foods prepared away from home and/or eaten outside the home) and supplement use. The R2 was 19.7% and 25.0% for the sodium and potassium calibration models, respectively, increasing to 59.5 and 61.7% after adjusting for within-person variability in each biomarker. These calibration equations, corrected for subject-specific reporting error, have the potential to reduce bias in diet-disease associations within this largest cohort of Hispanics in the United States.
Asunto(s)
Potasio en la Dieta/orina , Autoinforme , Sodio en la Dieta/orina , Adulto , Anciano , Biomarcadores/orina , Calibración , Estudios de Cohortes , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
SETTING: Cape Town, South Africa. OBJECTIVE: To evaluate anti-tuberculosis treatment outcomes and rate of antiretroviral therapy (ART) initiation using weekly community-based adherence support compared to daily directly observed therapy (DOT). METHODS: This was a retrospective analysis comparing two cohorts treated for tuberculosis (TB) in 70 TB clinics during 6-month periods before and after the introduction of a new adherence model comprising treatment literacy sessions during 2 weeks of DOT, followed by weekly home visits by community care workers to eligible patients managing their own treatment. Odds ratios (ORs) of treatment success and ART initiation were calculated using multivariable random effects logistic regression models. Hazard ratios (HRs) of default and death were calculated using multivariable random effects Cox regression models. RESULTS: The pre-intervention cohort comprised 11 896 patients with TB and the post-intervention cohort 11 314. There was no difference in pre- and post-intervention anti-tuberculosis treatment success rates (respectively 82.8% and 82.5%, adjusted OR [aOR] 1.02, 95%CI 0.89-1.17, P = 0.76) nor an increased hazard of death (adjusted HR [aHR] 0.98, 95%CI 0.80-1.21, P = 0.87) or default (aHR 0.97, 95%CI 0.81-1.15, P = 0.69). The ART initiation rate increased from 67% to 74% (aOR 1.43; 95%CI 1.01-1.85, P < 0.01). CONCLUSION: Weekly community-based adherence support was a viable alternative to daily DOT, with no deterioration in anti-tuberculosis treatment outcomes and an increase in ART initiation.