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1.
Neurology ; 103(3): e209665, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39008782

RESUMO

BACKGROUND AND OBJECTIVES: Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old. METHODS: This was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors. RESULTS: The sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (ßMMSE = -0.82, 95% CI -1.17 to -0.46; ß3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline. DISCUSSION: Amyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.


Assuntos
Disfunção Cognitiva , Hipocampo , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Substância Branca , Humanos , Feminino , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/metabolismo , Idoso de 80 Anos ou mais , Estudos Longitudinais , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/metabolismo , Cognição/fisiologia , Estudos de Coortes , Tamanho do Órgão , Etilenoglicóis , Compostos de Anilina , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo
2.
Transl Psychiatry ; 14(1): 287, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009577

RESUMO

The causes of depression are complex, and the current diagnosis methods rely solely on psychiatric evaluations with no incorporation of laboratory biomarkers in clinical practices. We investigated the stability of blood DNA methylation depression signatures in six different populations using six public and two domestic cohorts (n = 1942) conducting mega-analysis and meta-analysis of the individual studies. We evaluated 12 machine learning and deep learning strategies for depression classification both in cross-validation (CV) and in hold-out tests using merged data from 8 separate batches, constructing models with both biased and unbiased feature selection. We found 1987 CpG sites related to depression in both mega- and meta-analysis at the nominal level, and the associated genes were nominally related to axon guidance and immune pathways based on enrichment analysis and eQTM data. Random forest classifiers achieved the highest performance (AUC 0.73 and 0.76) in CV and hold-out tests respectively on the batch-level processed data. In contrast, the methylation showed low predictive power (all AUCs < 0.57) for all classifiers in CV and no predictive power in hold-out tests when used with harmonized data. All models achieved significantly better performance (>14% gain in AUCs) with pre-selected features (selection bias), with some of the models (joint autoencoder-classifier) reaching AUCs of up to 0.91 in the final testing regardless of data preparation. Different algorithmic feature selection approaches may outperform limma, however, random forest models perform well regardless of the strategy. The results provide an overview over potential future biomarkers for depression and highlight many important methodological aspects for DNA methylation-based depression profiling including the use of machine learning strategies.


Assuntos
Metilação de DNA , Aprendizado Profundo , Aprendizado de Máquina , Humanos , Estudos de Coortes , Ilhas de CpG , Feminino , Masculino , Depressão/genética , Depressão/sangue , Depressão/diagnóstico , Pessoa de Meia-Idade , Adulto , Biomarcadores/sangue
3.
BMC Palliat Care ; 23(1): 173, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010044

RESUMO

BACKGROUND: Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. METHODS: We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. RESULTS: A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. CONCLUSIONS: Ceiling of care can be predicted with great accuracy from a patient's clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.


Assuntos
COVID-19 , Hospitalização , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hospitalização/estatística & dados numéricos , Espanha/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , SARS-CoV-2 , Comorbidade
4.
Orphanet J Rare Dis ; 19(1): 266, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010060

RESUMO

BACKGROUND: The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. METHODS: We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. RESULTS: IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. CONCLUSIONS: Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Pericardite , Humanos , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Pericardite/tratamento farmacológico , Pericardite/patologia , Pericardite/diagnóstico por imagem , Feminino , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Idoso , Adulto , Arterite/tratamento farmacológico , Arterite/diagnóstico por imagem , Arterite/patologia , Imunoglobulina G , Estudos de Coortes , Glucocorticoides/uso terapêutico
5.
BMC Endocr Disord ; 24(1): 113, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010068

RESUMO

BACKGROUND: Waist circumference (WC), or waist-to-hip ratio (WHR), potentially offers a more accurate reflection of intra-abdominal fat accumulation and could serve as a superior predictor of type 2 diabetes mellitus (T2DM) risk compared to BMI. The current study investigated the relationship between WHR and its influencing factors among diabetes patients enrolled in the Prospective Epidemiological Research Studies in Iran (PERSIAN) Guilan Cohort study (PGCS). METHOD: In this cross-sectional study of 10,520 participants, 2,531 had T2DM. Waist and hip circumference, body mass index (BMI), underlying diseases, and demographical data of participants were recorded. Also, fasting blood sugar (FBS), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed. All data was analyzed using SPSS version 16; the significant level was < 0.05. RESULTS: The mean age of participants was 51.52 ± 8.90 years, and 39.9% had a BMI between 25 and 30 kg/m2. The prevalence of diabetes was 24.1% (n = 2531). About 7628 (72.5%) individuals had abnormal WHR, and 2072 (19.7%) were diabetics. Among patients with diabetes, abnormal WHR was significantly associated with age over 50, female gender, higher BMI, and lower LDL (P < 0.05). CONCLUSION: The study showed a higher prevalence of abnormal WHR in diabetic patients. Abnormal WHR in patients with diabetes was significantly associated with age, gender, and BMI.


Assuntos
Diabetes Mellitus Tipo 2 , Relação Cintura-Quadril , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Irã (Geográfico)/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Índice de Massa Corporal , Estudos Prospectivos , Estudos de Coortes , Fatores de Risco , Circunferência da Cintura , Prevalência , Prognóstico , Seguimentos
6.
Respir Res ; 25(1): 279, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010097

RESUMO

BACKGROUND: We assessed the effect of noninvasive ventilation (NIV) on mortality and length of stay after high flow nasal oxygenation (HFNO) failure among patients with severe hypoxemic COVID-19 pneumonia. METHODS: In this multicenter, retrospective study, we enrolled COVID-19 patients admitted in intensive care unit (ICU) for severe COVID-19 pneumonia with a HFNO failure from December 2020 to January 2022. The primary outcome was to compare the 90-day mortality between patients who required a straight intubation after HFNO failure and patients who received NIV after HFNO failure. Secondary outcomes included ICU and hospital length of stay. A propensity score analysis was performed to control for confounding factors between groups. Exploratory outcomes included a subgroup analysis for 90-day mortality. RESULTS: We included 461 patients with HFNO failure in the analysis, 233 patients in the straight intubation group and 228 in the NIV group. The 90-day mortality did not significantly differ between groups, 58/228 (25.4%) int the NIV group compared with 59/233 (25.3%) in the straight intubation group, with an adjusted hazard ratio (HR) after propensity score weighting of 0.82 [95%CI, 0.50-1.35] (p = 0.434). ICU length of stay was significantly shorter in the NIV group compared to the straight intubation group, 10.0 days [IQR, 7.0-19.8] versus 18.0 days [IQR,11.0-31.0] with a propensity score weighted HR of 1.77 [95%CI, 1.29-2.43] (p < 0.001). A subgroup analysis showed a significant increase in mortality rate for intubated patients in the NIV group with 56/122 (45.9%), compared to 59/233 (25.3%) for patients in the straight intubation group (p < 0.001). CONCLUSIONS: In severely hypoxemic COVID-19 patients, no significant differences were observed on 90-day mortality between patients receiving straight intubation and those receiving NIV after HFNO failure. NIV strategy was associated with a significant reduction in ICU length of stay, despite an increase in mortality in the subgroup of patients finally intubated.


Assuntos
COVID-19 , Ventilação não Invasiva , Oxigenoterapia , Pontuação de Propensão , Humanos , COVID-19/mortalidade , COVID-19/terapia , COVID-19/complicações , Masculino , Feminino , Estudos Retrospectivos , Ventilação não Invasiva/métodos , Idoso , Pessoa de Meia-Idade , França/epidemiologia , Oxigenoterapia/métodos , Resultado do Tratamento , Hipóxia/mortalidade , Hipóxia/terapia , Hipóxia/diagnóstico , Tempo de Internação/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos de Coortes , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais
7.
J Orthop Surg Res ; 19(1): 405, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010095

RESUMO

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.


Assuntos
Neoplasias Ósseas , Denosumab , Tumor de Células Gigantes do Osso , Microambiente Tumoral , Humanos , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/patologia , Microambiente Tumoral/imunologia , Feminino , Masculino , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/imunologia , Pessoa de Meia-Idade , Estudos de Coortes , Adulto Jovem , Resultado do Tratamento , Prognóstico , Conservadores da Densidade Óssea/uso terapêutico , Adolescente
8.
Nutr J ; 23(1): 77, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010085

RESUMO

BACKGROUND & AIMS: Obesity has been linked to various detrimental health consequences. While there is established evidence of a negative correlation between seafood consumption and obesity in adults, the current research on the association between seafood intake in childhood/adolescence and the risk of obesity is lacking. Our aim was to evaluate the association between seafood intake in childhood/adolescence and the risk of obesity in a Chinese nationwide cohort. METHODS: We utilized data from the China Health and Nutrition Survey (CHNS) from the year of 1997 to 2015. Seafood consumption was evaluated through 3-day 24-hour recalls. In our study, overweight/obesity status was determined based on the Chinese Criteria of Overweight and Obesity in School-age Children and Adolescents (WS/T 586-2018), while abdominal obesity status was determined according to the Chinese Criteria of Waist Circumference Screening Threshold among Children and Adolescents (WS/T 611-2018). RESULTS: During an average follow-up of 7.9 years, 404 cases developed overweight/obesity among 2206 participants in the seafood-overweight/obesity analysis, while 381 cases developed abdominal obesity among 2256 participants in the seafood-abdominal-obesity analysis. The high-consumer group was associated with 35% lower risk of overweight/obesity risk and 26% lower risk of abdominal obesity after fully adjusting for sociodemographic and lifestyle factors, compared with the non-consumer group. Considering different cooking methods, boiled seafood consumption was associated with 43% lower risk of overweight/obesity and 23% lower risk of abdominal obesity in the fully adjusted model, while stir-fried seafood did not demonstrate a statistical significance. CONCLUSION: Higher intake of seafood in childhood/adolescents, particularly in a boiled way, was associated with lower obesity risk.


Assuntos
Inquéritos Nutricionais , Alimentos Marinhos , Humanos , Criança , Feminino , Adolescente , Masculino , Alimentos Marinhos/estatística & dados numéricos , China/epidemiologia , Estudos de Coortes , Inquéritos Nutricionais/estatística & dados numéricos , Inquéritos Nutricionais/métodos , Fatores de Risco , Obesidade Infantil/epidemiologia , Dieta/estatística & dados numéricos , Dieta/métodos , Dieta/efeitos adversos , Obesidade Abdominal/epidemiologia , Sobrepeso/epidemiologia
9.
Isr J Health Policy Res ; 13(1): 26, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010194

RESUMO

BACKGROUND: Frailty, a significant risk factor for adverse outcomes and mortality, poses an emerging challenge with profound implications for public health and clinical practice. The measurement of frailty offers potential enhancements in healthcare services for older adults. The prevalence of frailty and its association with long-term mortality in a nationwide, unselected population of community-dwelling older adults, particularly those aged 75 and over, has not been previously studied on a large scale in Israel. METHODS: A retrospective cohort study was conducted at Meuhedet Health Maintenance Organization, Israel's third largest healthcare service provider, serving 1,276,000 people (13.8% of Israelis). The prevalence of frailty and its association with all-cause mortality were studied among older adults aged 75 years and over who were followed for 2-8 years. Frailty, defined by the cumulative deficit method, utilized clinical data from the preceding 10-year period, comprising 28 chronic diseases and age-related health deficits. RESULTS: The cohort included 43,737 older adults, with a median age of 77 years (IQR 75-82 years); among them, 19,300 (44.1%) were males. Overall, 19,396 (44.3%) older adults were frail: 12,260 (28.0%) mildly frail, 5,533 (12.7%) moderately frail and 1,603 (3.7%) severely frail. During the follow-up period 15,064 (34.4%) older adults died: 4,782 (39.0%) mildly frail, 3,016 (54.5%) moderately frail and 1,080 (67.4%) severely frail. Cox regression analysis demonstrated that mortality was associated with severe frailty (HR 2.63, 95%CI 2.45-2.80), moderate frailty (HR 2.05, 95%CI 1.96-2.14), and mild frailty (HR 1.45, 95%CI 1.39-1.51), independent of age, gender, and population sector. Among patients aged 90 years and over, no significant differences in cumulative survival were found between those with moderate and severe frailty (p = 0.408). CONCLUSIONS: Frailty is prevalent among community-dwelling Israeli older adults aged 75 years and over, and it is associated with long-term mortality. Considering its association with long-term mortality across frailty levels until the age of 90, early identification and intervention for frailty are recommended within this population. Policymakers should consider the use of the cumulative deficit method for evaluating frailty at both the population health and clinical levels.


Assuntos
Idoso Fragilizado , Fragilidade , Vida Independente , Humanos , Idoso , Masculino , Feminino , Israel/epidemiologia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/mortalidade , Fragilidade/epidemiologia , Vida Independente/estatística & dados numéricos , Prevalência , Mortalidade/tendências , Fatores de Risco , Estudos de Coortes , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos
10.
Elife ; 132024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012339

RESUMO

Background: Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. Methods: The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. Conclusions: PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. Funding: This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).


Assuntos
COVID-19 , Influenza Humana , Pneumonia , Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Influenza Humana/tratamento farmacológico , Masculino , Feminino , COVID-19/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Pneumonia/epidemiologia , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , SARS-CoV-2 , Adulto , Reino Unido/epidemiologia , Suscetibilidade a Doenças , Modelos de Riscos Proporcionais
12.
PLoS One ; 19(7): e0304822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39012863

RESUMO

BACKGROUND: To describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes. METHODS: This observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts. RESULTS: We included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001). CONCLUSIONS: There was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.


Assuntos
Anticorpos Monoclonais Humanizados , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Registros Eletrônicos de Saúde , Hospitalização , Humanos , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Retrospectivos , Antivirais/uso terapêutico , Estados Unidos/epidemiologia , SARS-CoV-2/isolamento & purificação , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estudos de Coortes , Anticorpos Neutralizantes
13.
Neurology ; 103(3): e209656, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39013126

RESUMO

BACKGROUND AND OBJECTIVES: The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. METHODS: Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. RESULTS: CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. DISCUSSION: A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.


Assuntos
Doença por Corpos de Lewy , alfa-Sinucleína , Humanos , Doença por Corpos de Lewy/líquido cefalorraquidiano , Doença por Corpos de Lewy/diagnóstico , Feminino , Idoso , Masculino , alfa-Sinucleína/líquido cefalorraquidiano , Pessoa de Meia-Idade , Estudos Transversais , Estudos Longitudinais , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Idoso de 80 Anos ou mais
15.
Rev Colomb Obstet Ginecol ; 75(1)2024 03 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39013201

RESUMO

Objectives: To determine if there is an association between the neutrophil to lymphocyte ratio (NLR) and prognosis in patients with epithelial ovarian cancer (EOC) diagnosed and treated in a Spanish population. Material and methods: Retrospective cohort of patients with epithelial ovarian cancer who had neutrophil and lymphocyte values in complete blood count before the histopathological diagnosis and survival of at least three months, in an intermediate complexity hospital. Convenience sampling. Measured variables included age, menopausal stage, parity, International Federation of Gynecology and Obstetrics (FIGO) stage, treatment type, residual tumor, lymph node involvement, presence of ascites, cytology, histologic type, differentiation grade, and CA-125 values. Additionally, outcomes, overall survival, disease/progression-free survival were also measured. Bivariate inferential and Cox regression analyses were performed. Results: Out of 78 candidates, 60 women with EOC were included. Of them, 24 (40%) had a low NLR (≤ 2,9) while 36 (60%) had a high NLR (> 2,9). An association was found between high NLR levels and suboptimal cytoreductive surgery. High NLR ratios were associated with lower overall survival (Hazard ratio (HR): 4.1; 95% CI: 1.4-11.8) and lower 5-year disease-free survival (HR: 2.6; 95% CI: 1.2-5.7). Conclusions: A plasma neutrophil to lymphocyte ratio of more than 2.9 was associated with poor prognosis in patients with epithelial ovarian cancer in our setting. There is a need to establish the optimal cut-off point and conduct prospective studies with larger patient numbers in order to support this information.


Objetivos: evaluar si hay asociación entre los valores del cociente plasmático neutrófilos/ linfocitos (NLR) y el pronóstico en pacientes con cáncer epitelial de ovario (CEO) diagnosticadas y tratadas en una población española. Materiales y métodos: cohorte retrospectiva de pacientes con cáncer epitelial de ovario que tuvieran un recuento de neutrófilos y linfocitos en hemograma previo al diagnóstico histopatológico en un hospital de nivel medio de complejidad y posterior sobrevida de, al menos, 3 meses. Muestreo por conveniencia. Se midieron: edad, estado menopáusico, paridad, estadio Federación International de Ginecología y Obstetricia (FIGO), tipo de tratamiento, tumor residual, afectación ganglionar, presencia de ascitis, citología, tipo histológico, grado de diferenciación y cifras de CA-125; como desenlaces, sobrevida global y sobrevida libre de enfermedad o progresión. Análisis inferencial bivariado y por regresión de Cox. Resultados: de 78 candidatas, ingresaron 60 mujeres con CEO. De ellas, 24 (40%) presentaron un NLR bajo (≤ 2,9) y 36 (60 %) elevado (> 2,9). Se encontró asociación entre los niveles altos de NLR y cirugía citoreductora subóptima. Los niveles altos de NLR se asociaron a menor sobrevida global (Hazard ratio (HR): 4,1; IC 95%: 1,4-11,8) y menor sobrevida libre de enfermedad a los 5 años (HR:2,6; IC 95 %: 1,2-5,7). Conclusiones: un cociente plasmático neutrófilos/linfocitos mayor de 2,9 se asoció a un mal pronóstico en pacientes con cáncer epitelial de ovario en nuestro medio. Se necesita determinar el punto de corte óptimo y realizar estudios prospectivos con mayor número de pacientes que avalen esta información.


Assuntos
Carcinoma Epitelial do Ovário , Linfócitos , Neutrófilos , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Prognóstico , Pessoa de Meia-Idade , Linfócitos/patologia , Idoso , Adulto , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução , Espanha/epidemiologia , Intervalo Livre de Doença , Contagem de Linfócitos , Taxa de Sobrevida , Período Pré-Operatório , Contagem de Leucócitos
16.
Isr J Health Policy Res ; 13(1): 30, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004759

RESUMO

BACKGROUND: In Israel, coverage of health needs is delivered by four health maintenance organizations (HMOs), which are budgeted by the government according to the recommendations of the National Drug Formulary (NDF) Committee. For medications not listed in the NDF, individuals may request to cover the costs by the HMO Exemptions Committee (DEC). The objectives of the current study, a first of its kind, are to document the DEC decision process, to identify its components and to determine the decisions' clinical outcome. METHODS: This retrospective cohort study included all members (≥ age 18) of the Maccabi Healthcare Service (MHS) who submitted a request to the DEC between June 2017 and December 2018. Collected data include patient demographics, clinical information and components of the decision process. Decision success (i.e., clinical outcome correlated with DEC decision) was determined by clinical outcome over at least one-year follow-up. RESULTS: A total of 335 requests were included. Strong evidence and rare disease were positively associated with approvals, while the availability of alternative treatments and costs were negatively associated. The majority of decisions (75%) met predicted clinical outcomes. Only estimated costs were found to be associated with decision success. CONCLUSIONS: Factors that reduce the potential costs of a requested drug are significantly associated with higher odds for drug approval, but only when the evidence supports potential benefit.


Assuntos
Sistemas Pré-Pagos de Saúde , Humanos , Estudos Retrospectivos , Sistemas Pré-Pagos de Saúde/estatística & dados numéricos , Masculino , Israel , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Tomada de Decisões , Formulários Farmacêuticos como Assunto , Estudos de Coortes , Cobertura do Seguro/estatística & dados numéricos
17.
J Orthop Trauma ; 38(8): 452-458, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39007663

RESUMO

OBJECTIVES: To determine (1) the rate of positive cultures in presumed aseptic nonunions, (2) the rate and microbial spectrum of positive cultures that represented occult infection, and (3) rates of nonunion healing. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS SELECTION CRITERIA: Adult patients with a presumed aseptic nonunion treated with single-stage revision between 2002 and 2022. OUTCOME MEASURES AND COMPARISONS: The rate of positive cultures compared for 2 protocols: old: 1-2 samples cultured 7 days versus new: 5 samples cultured 14 days. The rate of positive cultures meeting occult infection criteria with the new protocol (≥2 samples with phenotypically indistinguishable microorganisms, or ≥1 sample with a high virulent microorganism). Nonunion healing rates between protocols and between groups based on culture results with the new protocol. RESULTS: One hundred seventy-nine patients were included. The rate of positive cultures was 14% (n = 15/105) with the old protocol and 51% (n = 38/74) with the new protocol (P < 0.001). With the new protocol, the rate of positive cultures meeting occult infection criteria was 19% (n = 14/74), and coagulase-negative staphylococci (48%) and Cutibacterium acnes (38%) were the most common microorganisms. Nonunion healing rates after the primary revision did not differ between protocols (old: 82% vs. new: 86%, P = 0.41) and groups based on culture result (sterile: 86% vs. occultly infected: 93%, P = 0.66). The final overall nonunion healing rate was 97%. CONCLUSIONS: Occult infections were identified in 1 in 5 presumed aseptic nonunions using a standardized protocol with 5 intraoperative samples cultured 14 days and were predominantly caused by slow growing, gram-positive microorganisms. The local spectrum and antimicrobial sensitivity of occult infections should be considered when developing empiric antimicrobial protocols. Patients with presumed aseptic nonunions can expect high healing rates, regardless of the culture result. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas não Consolidadas , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Fraturas não Consolidadas/microbiologia , Fraturas não Consolidadas/cirurgia , Adulto , Idoso , Consolidação da Fratura , Estudos de Coortes , Resultado do Tratamento , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/diagnóstico , Reoperação , Fixação Interna de Fraturas
18.
PLoS One ; 19(7): e0305537, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008450

RESUMO

OBJECTIVE: Endodontic microbiota appears to undergo evolutionary changes during disease progression from inflammation to necrosis and post-treatment. The aim of this study was to compare microbiome composition and diversity in primary and post-treatment endodontic infections from a cohort of patients from the UAE. DESIGN: Intracanal samples were collected from primarily infected (n = 10) and post-treatment infected (n = 10) root canals of human teeth using sterile paper points. Bacterial DNA was amplified from seven hypervariable regions (V2-V4 and V6-V9) of the 16S rRNA gene, then sequenced using next-generation sequencing technology. The data was analyzed using appropriate bioinformatic tools. RESULTS: Analyses of all the samples revealed eight major bacterial phyla, 112 genera and 260 species. Firmicutes was the most representative phylum in both groups and was significantly more abundant in the post-treatment (54.4%) than in primary (32.2%) infections (p>0.05). A total of 260 operational taxonomic units (OTUs) were identified, of which 126 (48.5%) were shared between the groups, while 83 (31.9%) and 51 (19.6%) disparate species were isolated from primary and post-treatment infections, respectively. A significant difference in beta, but not alpha diversity was noted using several different indices (p< 0.05). Differential abundance analysis indicated that, Prevotella maculosa, Streptococcus constellatus, Novosphigobium sediminicola and Anaerococcus octavius were more abundant in primary infections while Enterrococcus faecalis, Bifidobacterium dentium, Olsenella profusa and Actinomyces dentalis were more abundant in post-treatment infections (p <0.05). CONCLUSION: Significant differences in the microbiome composition and diversity in primary and post-treatment endodontic infections were noted in our UAE cohort. Such compositional differences of microbiota at various stages of infection could be due to both intrinsic and extrinsic factors impacting the root canal ecosystem during disease progression, as well as during their therapeutic management. Identification of the key microbiota in primarily and secondarily infected root canals can guide in the management of these infections.


Assuntos
Bactérias , Microbiota , RNA Ribossômico 16S , Humanos , Emirados Árabes Unidos/epidemiologia , Masculino , Feminino , RNA Ribossômico 16S/genética , Adulto , Microbiota/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Cavidade Pulpar/microbiologia , Pessoa de Meia-Idade , Estudos de Coortes , DNA Bacteriano/genética , Adulto Jovem , Filogenia , Biodiversidade
19.
PLoS One ; 19(7): e0307120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008468

RESUMO

AIM: Sleep duration has been suggested to be associated with hypertension (HTN). However, evidence of the nature of the relationship and its direction has been inconsistent. Therefore, we performed a meta-analysis to assess the relationship between sleep duration and risk of HTN incidence, and to distinguish more susceptible populations. METHODS: PubMed, Embase, Scopus, Web of Science, and ProQuest were searched from January 2000 to May 2023 for cohort studies comparing short and long sleep durations with 7-8 hours of sleep for the risk of HTN incidence. Random-effect model (the DerSimonian-Laird method) was applied to pool risk ratios (RR) and 95% confidence interval (CI). RESULTS: We included sixteen studies ranging from 2.4 to 18 years of follow-up duration evaluating HTN incidence in 1,044,035 people. Short sleep duration was significantly associated with a higher risk of developing HTN (HR: 1.07, 95% CI: 1.06-1.09). The association was stronger when the sleep duration was less than 5 hours (HR: 1.11, 95% CI: 1.08-1.14). In contrast to males, females (HR: 1.07, 95% CI: 1.04-1.09) were more vulnerable to developing HTN due to short sleep duration. No significant difference between different follow-up durations and age subgroups was observed. Long sleep duration was not associated with an increased incidence of HTN. CONCLUSION: Short sleep duration was associated with higher risk of HTN incidence, however, there was no association between long sleep duration and incidence of HTN. These findings highlight the importance of implementing target-specific preventive and interventional strategies for vulnerable populations with short sleep duration to reduce the risk of HTN.


Assuntos
Hipertensão , Sono , Humanos , Hipertensão/epidemiologia , Sono/fisiologia , Incidência , Masculino , Estudos de Coortes , Feminino , Fatores de Risco , Fatores de Tempo , Duração do Sono
20.
PLoS One ; 19(7): e0307264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008514

RESUMO

BACKGROUND: Understanding the prognostic impact of percutaneous coronary intervention (PCI) in chronic total occlusion (CTO) is crucial for patient management. Previous studies have primarily been studying prognostic impact of successful versus unsuccessful CTO PCI. This study investigated the prognostic impact of successful and unsuccessful percutaneous coronary intervention (PCI) of chronic total occluded coronary arteries (CTO) with non-CTO PCI as reference. METHODS: Patients treated with PCI from 2009 to 2019 in the Central Region of Denmark were included in a population-based cohort study. We compared successful and unsuccessful CTO PCI with non-CTO PCI. Exclusion criteria was myocardial infarction within 30 days. Primary outcome was difference in a composite major adverse cardio- and cerebrovascular events (MACCE) encompassing all-cause death, any myocardial infarction, stroke, hospitalization for heart failure or revascularization tracked via nationwide registries. RESULTS: Of 21,141 screened patients, 10,638 were enrolled: 9,065 underwent non-CTO PCI, 1,300 had successful CTO PCI, and 273 had unsuccessful CTO PCI. Median follow-up time was 5.9 [3.5;9.0] years and 4,750 MACCEs were recorded. Compared to non-CTO PCI, the adjusted MACCE rate for successful CTO PCI was equivalent (Hazard Ratio (HR): 0.98, 95% Confidence Interval (CI): 0.90-1.07, p = 0.71). In contrast, unsuccessful CTO PCI was associated with a higher MACCE rate (HR: 1.22, 95% CI: 1.04-1.43, p<0.01). HR was adjusted for age, body-mass index, previous revascularization, smoking, kidney disease, two or three-vessel disease, left ventricular ejection fraction, diabetes and comorbidities. CONCLUSIONS: The pre-specified hypothesis was accepted. Successful CTO PCI was associated with equivalent long-term outcomes as non-CTO PCI, and unsuccessful CTO PCI was identified as a high-risk group associated to worse outcomes.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Oclusão Coronária/cirurgia , Dinamarca/epidemiologia , Resultado do Tratamento , Estudos de Coortes , Doença Crônica , Prognóstico , Sistema de Registros , Fatores de Risco , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/cirurgia
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