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Malaria transmission is influenced by climate and land use/land cover change (LULC). This study examines the impact of climate and LULC on malaria risk in the Ecuadorian Amazon. Weekly malaria surveillance data between 2008 and 2019 from Ecuador's Ministry of Public Health were combined with hydrometeorological and LULC data. Cross-correlation analyses identified time lags. Bayesian spatiotemporal models estimated annual LULC rates of change (ARC) by census area and assessed the effects on Plasmodium vivax and Plasmodium falciparum incidence. ARC for the five land cover classes (forest, agriculture, urban, shrub vegetation, water) ranged from -1 to 4% with agriculture increasing across areas. Forest and shrub vegetation ARC were significantly associated with both Plasmodium vivax and Plasmodium falciparum. Temperature and terrestrial water content showed consistent negative relationships with both species. Precipitation had varying effects on Plasmodium vivax (null) and Plasmodium falciparum (increase) incidence. Shrubs and forest expansion, increased temperature, and terrestrial water content reduced malaria incidence, while increased precipitation had varying effects. Relationships between malaria, LULC, and climate are complex, influencing risk profiles. These findings aid decision-making and guide further research in the region.
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INTRODUCTION: Understanding human mobility's role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. METHODS: We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses will be ranked and the 2-3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country's malaria surveillance system to test the effects of mobility on disease risk. ETHICS AND DISSEMINATION: This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.
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Redes Comunitárias , Malária , Humanos , Peru/epidemiologia , Equador/epidemiologia , Brasil/epidemiologia , Malária/epidemiologia , Malária/prevenção & controleRESUMO
Objectives: Understanding human mobility's role on malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. Design: A community-level network survey. Setting: We collect data on community connectivity along three river systems in the Amazon basin: the Pastaza river corridor spanning the Ecuador-Peru border; and the Amazon and Javari river corridors spanning the Brazil-Peru border. Participants: We interviewed key informants in Brazil, Ecuador, and Peru, including from indigenous communities: Shuar, Achuar, Shiwiar, Kichwa, Ticuna, and Yagua. Key informants are at least 18 years of age and are considered community leaders. Primary outcome: Weekly, community-level malaria incidence during the study period. Methods: We measure community connectivity across the study area using a respondent driven sampling design. Forty-five communities were initially selected: 10 in Brazil, 10 in Ecuador, and 25 in Peru. Participants were recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses were ranked and the 2-3 most connected communities were then selected and surveyed. This process was repeated for a third round of data collection. Community network matrices will be linked with eadch country's malaria surveillance system to test the effects of mobility on disease risk. Findings: To date, 586 key informants were surveyed from 126 communities along the Pastaza river corridor. Data collection along the Amazon and Javari river corridors is ongoing. Initial results indicate that network sampling is a superior method to delineate migration flows between communities. Conclusions: Our study provides measures of mobility and connectivity in rural settings where traditional approaches are insufficient, and will allow us to understand mobility's effect on malaria transmission.
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[This corrects the article DOI: 10.3389/fpubh.2022.913096.].
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OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Estudos de Coortes , Estudos Prospectivos , HospitaisRESUMO
Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumour types, including melanoma, glioma, leukaemia and cardiac angiosarcoma. We sequenced all coding exons of the POT1 gene in 2928 European-descent melanoma cases and 3298 controls, identifying 43 protein-changing genetic variants. We performed POT1-telomere binding assays for all missense and stop-gained variants, finding nine variants that impair or disrupt protein-telomere complex formation, and we further define the role of variants in the regulation of telomere length and complex formation through molecular dynamics simulations. We determine that POT1 coding variants are a minor contributor to melanoma burden in the general population, with only about 0.5% of melanoma cases carrying germline pathogenic variants in this gene, but should be screened in individuals with a strong family history of melanoma and/or multiple malignancies.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Complexo Shelterina , Proteínas de Ligação a Telômeros/genética , Telômero/metabolismo , Estudos de Casos e Controles , Melanoma Maligno CutâneoAssuntos
Hipertensão , Pressão Sanguínea , Humanos , Hipertensão/terapia , Estudos Longitudinais , Pediatras , Atenção Primária à SaúdeRESUMO
Genome-wide association studies (GWAS) have been very successful at identifying genetic variants influencing a large number of traits. Although the great majority of these studies have been performed in European-descent individuals, it has been recognised that including populations with differing ancestries enhances the potential for identifying causal SNPs due to their differing patterns of linkage disequilibrium. However, when individuals from distinct ethnicities are included in a GWAS, it is necessary to implement a number of control steps to ensure that the identified associations are real genotype-phenotype relationships. In this Review, we discuss the analyses that are required when performing multi-ethnic studies, including methods for determining ancestry at the global and local level for sample exclusion, controlling for ancestry in association testing, and post-GWAS interrogation methods such as genomic control and meta-analysis. We hope that this overview provides a primer for those researchers interested in including distinct populations in their studies.
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Border regions have been implicated as important hot spots of malaria transmission, particularly in Latin America, where free movement rights mean that residents can cross borders using just a national ID. Additionally, rural livelihoods largely depend on short-term migrants traveling across borders via the Amazon's river networks to work in extractive industries, such as logging. As a result, there is likely considerable spillover across country borders, particularly along the border between Peru and Ecuador. This border region exhibits a steep gradient of transmission intensity, with Peru having a much higher incidence of malaria than Ecuador. In this paper, we integrate 13 years of weekly malaria surveillance data collected at the district level in Peru and the canton level in Ecuador, and leverage hierarchical Bayesian spatiotemporal regression models to identify the degree to which malaria transmission in Ecuador is influenced by transmission in Peru. We find that increased case incidence in Peruvian districts that border the Ecuadorian Amazon is associated with increased incidence in Ecuador. Our results highlight the importance of coordinated malaria control across borders.
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Malária/transmissão , Teorema de Bayes , Equador/epidemiologia , Humanos , Malária/epidemiologia , Peru/epidemiologia , Análise Espaço-TemporalRESUMO
OBJECTIVE: To estimate the prevalence of metabolic syndrome (MetS) and examine its association with chronic kidney disease progression in children enrolled in the Chronic Kidney Disease in Children study. STUDY DESIGN: MetS was defined as being overweight or obese and having ≥2 cardiometabolic risk factors (CMRFs). Incidence and prevalence of MetS were assessed using pairs of visits approximately 2 years apart. RESULTS: A total of 799 pairs of person-visits (contributed by 472 children) were included in the final analysis. Of these, 70% had a normal body mass index (BMI), 14% were overweight, and 16% were obese. At the first visit, the prevalence of MetS in the overweight group was 40% and in the obese group was 60%. In adjusted models, annual percent estimated glomerular filtration rate decline in those who had normal BMI and incident or persistent multiple CMRFs or those with persistent MetS was -6.33%, -6.46%, and -6.08% (respectively) compared with children who never had multiple CMRFs (-3.38%, P = .048, .045, and .036, respectively). Children with normal BMI and incident multiple CMRFs and those with persistent MetS had approximately twice the odds of fast estimated glomerular filtration rate decline (>10% per year) compared with those without multiple CMRFs and normal BMI. CONCLUSION: Children with chronic kidney disease have a high prevalence of MetS. These children as well as those with normal BMI but multiple CMRFs experience a faster decline in kidney function.
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Doenças Cardiovasculares/epidemiologia , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fatores Etários , Índice de Massa Corporal , Doenças Cardiovasculares/fisiopatologia , Criança , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Síndrome Metabólica/fisiopatologia , Obesidade/fisiopatologia , Prevalência , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Medição de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS: The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Hexanonas/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Intervalo Livre de Progressão , Gencitabina , Neoplasias PancreáticasRESUMO
Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by venous malformations and a predisposition to pulmonary embolism. We reviewed the imaging findings of 7 adult patients with KTS who underwent thoracic CT. While the superficial manifestations of KTS predominantly affect the extremities, patients frequently develop abnormalities of the pulmonary arterial system, particularly chronic thromboembolic pulmonary hypertension. Additionally, some patients are seen to develop pulmonary arteriolar aneurysms; the physiologic significance of this finding is unknown at this time. Radiologists should be aware of these potential findings and have a high index of suspicion for chronic PE in patients with KTS.
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Aneurisma/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Hipertrofia Ventricular Direita/diagnóstico por imagem , Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Aneurisma/complicações , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertrofia Ventricular Direita/complicações , Síndrome de Klippel-Trenaunay-Weber/complicações , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Radiografia Torácica/métodos , Estudos RetrospectivosRESUMO
CONTEXT: With increasing utilization of computed tomography pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE), many patients undergo repeat CTs. OBJECTIVE: The aim of this study is to identify the rate of positive subsequent CTPAs after an initial negative CTPA and whether there is a risk-free period after a negative CTPA. METHODS: We evaluated 318 patients with at least 1 subsequent CTPA after an initial negative CTPA, with 786 total CTPAs. We also evaluated a control group of 200 unselected CTPAs. RESULTS: The positive rate in the repeat group was 7% at the first repeat CTPA and 10% per-patient within 1000 days. The positive rate in the control group was 9% (P= not significant). No risk-free period was seen, with a positive rate of 5% within 2 weeks after a negative CTPA. The number of prior negative CTPAs showed a trend towards decreasing rate of the subsequent CTPA being positive, but this did not meet statistical significance. DISCUSSION: There is no risk-free period after an initial negative CTPA, and therefore, patients with clinical suspicion of PE should be rescanned even after a recent negative study. Even patients with multiple negative prior CTPAs have a measurable risk of subsequent PE. Established clinical prediction scoring systems must be used to triage the patients who need CTPAs.
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Embolia Pulmonar/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Surgical management of snoring and obstructive sleep apnea is indicated when a surgically correctable abnormality is believed to be the source of the problem. Many patients opt for surgical treatment after noninvasive forms of treatment have been proven ineffective or difficult to tolerate. With increasing frequency, functional rhinoplasty, septoplasty, turbinoplasty, palatal surgery, and orthognathic surgery are being used in the management of snoring and obstructive sleep apnea. Plastic surgeons' experience with aesthetic nasal surgery, nasal reconstruction, palatal surgery, and craniofacial surgery puts them at the forefront of performing surgery for snoring and sleep apnea. The role of functional septorhinoplasty, turbinoplasty, palatal surgery, genioglossal advancement, and orthognathic surgery is indispensable in the surgical management of obstructive sleep apnea. Multidisciplinary management of these patients is critical, and plastic surgeons are encouraged to work collaboratively with sleep medicine clinicians and centers.
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Procedimentos Cirúrgicos Ortognáticos/métodos , Rinoplastia/métodos , Apneia Obstrutiva do Sono/cirurgia , Humanos , Anamnese , Exame Físico , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Resultado do TratamentoRESUMO
The purpose of this study was to compare computed tomography density (ρCT ) obtained using typical clinical computed tomography scan parameters to ash density (ρash ), for the prediction of densities of femoral head trabecular bone from hip fracture patients. An experimental study was conducted to investigate the relationships between ρash and ρCT and between each of these densities and ρbulk and ρdry . Seven human femoral heads from hip fracture patients were computed tomography-scanned ex vivo, and 76 cylindrical trabecular bone specimens were collected. Computed tomography density was computed from computed tomography images by using a calibration Hounsfield units-based equation, whereas ρbulk, ρdry and ρash were determined experimentally. A large variation was found in the mean Hounsfield units of the bone cores (HUcore) with a constant bias from ρCT to ρash of 42.5 mg/cm3. Computed tomography and ash densities were linearly correlated (R 2 = 0.55, p < 0.001). It was demonstrated that ρash provided a good estimate of ρbulk (R 2 = 0.78, p < 0.001) and is a strong predictor of ρdry (R 2 = 0.99, p < 0.001). In addition, the ρCT was linearly related to ρbulk (R 2 = 0.43, p < 0.001) and ρdry (R 2 = 0.56, p < 0.001). In conclusion, mineral density was an appropriate predictor of ρbulk and ρdry , and ρCT was not a surrogate for ρash . There were linear relationships between ρCT and physical densities; however, following the experimental protocols of this study to determine ρCT , considerable scatter was present in the ρCT relationships.
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BACKGROUND: Malaria caused by Plasmodium falciparum infects roughly 30,000 individuals in Haiti each year. Haiti has used chloroquine (CQ) as a first-line treatment for malaria for many years and as a result there are concerns that malaria parasites may develop resistance to CQ over time. Therefore it is important to prepare for alternative malaria treatment options should CQ resistance develop. In many other malaria-endemic regions, antifolates, particularly pyrimethamine (PYR) and sulphadoxine (SDX) treatment combination (SP), have been used as an alternative when CQ resistance has developed. This study evaluated mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes that confer PYR and SDX resistance, respectively, in P. falciparum to provide baseline data in Haiti. This study is the first comprehensive study to examine PYR and SDX resistance genotypes in P. falciparum in Haiti. METHODS: DNA was extracted from dried blood spots and genotyped for PYR and SDX resistance mutations in P. falciparum using PCR and DNA sequencing methods. Sixty-one samples were genotyped for PYR resistance in codons 51, 59, 108 and 164 of the dhfr gene and 58 samples were genotyped for SDX resistance codons 436, 437, 540 of the dhps gene in P. falciparum. RESULTS: Thirty-three percent (20/61) of the samples carried a mutation at codon 108 (S108N) of the dhfr gene. No mutations in dhfr at codons 51, 59, 164 were observed in any of the samples. In addition, no mutations were observed in dhps at the three codons (436, 437, 540) examined. No significant difference was observed between samples collected in urban vs rural sites (Welch's T-test p-value = 0.53 and permutations p-value = 0.59). CONCLUSION: This study has shown the presence of the S108N mutation in P. falciparum that confers low-level PYR resistance in Haiti. However, the absence of SDX resistance mutations suggests that SP resistance may not be present in Haiti. These results have important implications for ongoing discussions on alternative malaria treatment options in Haiti.