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BACKGROUND: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. METHODS: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. RESULTS: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%]; p = 0.007). CONCLUSIONS: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.
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COVID-19 , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Metilprednisolona , SARS-CoV-2 , Dexametasona , Resultado do TratamentoRESUMO
OBJECTIVES: Spanish population lifespan is one of the longest in the world. Moreover, it is known that elderly people have less chronic illnesses associated with aging. Our aims were to determine how Clinical Risk Group (CRG) predicts future use of healthcare resources in extremely elderly people without diabetes (T2DM) and to explore CRG correlation with health conditions. DESIGN: Prospective cross-sectional study. SETTING: Rio Hortega University Hospital. PARTICIPANTS: Hospitalized patients >80 years old without T2DM, during 2017. MAIN OUTCOME MEASURES: Mental status was evaluated using Pfeiffer test (SPMQS), Basic Activities of Daily Living (BADLs) and Instrumental Activities of Daily Living (IADLs) were estimated using the Older Americans Resources and Services questionnaire. Comorbidity was evaluated using Charlson index (CI) and health-related quality of life (HRQoL) with EuroQoL (EQ5D3L). CRG classification system was obtained from electronic clinical records. Data were analyzed using SPSS v.15.0. RESULTS: In total, 305 patients were identified (59% women), mean age 88 ± 5 and 38% were aged >90. Estimated HRQoL was 0.43 ± 0.33 for EQ5D3L-index-value. Mean dependence level was 6.2 ± 5 for BADLs and 9.2 ± 5 for IADLs. In total, 31.6% of patients had severe cognitive impairment with a mean score of 5.4 ± 3.6 in SPMQS. In total, 30.2% of patients were categorized as G3, and presented high comorbidity more frequently than the rest. Corrected CI mean score was 6.2 ± 1.7. Significant relationship was founded in survival time, number of admissions and CI score. CONCLUSIONS: Using predictive risk models like CRG is supposed to assess the complexity of morbidity but in our extremely elderly population partially fail in stratify and predict health resource consumption.
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Atividades Cotidianas , Multimorbidade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Recursos em Saúde , Humanos , Masculino , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection was highest among older adults early in the COVID-19 pandemic; however, this pattern was later reversed with young adults showing the highest incidence. The aim of this study was to identify risk factors in healthcare workers (HCWs) associated with this evolution. METHODS: We conducted a survey nested within a prospective cohort study of 680 HCWs from a tertiary referral public hospital who received 2 doses of SARS-CoV2 vaccine in January and February 2021 (VACCICO-VAO cohort). In October 2022 all participants were invited to participate in a survey. Risk factors were tested for association with COVID-19 ever, the number of COVID-19 episodes, and the time to the first episode. RESULTS: Among 350 respondents (51% response rate, 90% female, mean age 48.1 years), 323 COVID-19 episodes were diagnosed during the study period. Multivariable analysis revealed that age <â¯35 years vs. >â¯50 years (odds ratio, OR 2.12, 95% confidence interval, CI 1.27-3.51; Pâ¯= 0.004) and not maintaining social distance at social events (OR: 1.82, 95% CI: 1.16-3.19; Pâ¯= 0.011) were associated with a higher risk of COVID-19. Age <â¯35 years (hazard ratio, HR 1.70, 95% CI 1.14-2.54; Pâ¯= 0.010), and not maintaining social distance (HR 1.34, 95% CI 1.05-1.72; Pâ¯= 0.020) were also associated with the time to the first episode. CONCLUSIONS: The youngest HCWs had the highest incidence rate of COVID-19, which was not explained by occupational risk factors or health conditions. The increase in nonoccupational exposure since the end of the lockdowns in summer 2020 could by a key factor.
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COVID-19 , Pessoal de Saúde , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Pessoal de Saúde/estatística & dados numéricos , Adulto , Estudos Prospectivos , Fatores Etários , Incidência , SARS-CoV-2 , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Estudos de Coortes , Pandemias , Áustria/epidemiologia , Vacinas contra COVID-19/administração & dosagemRESUMO
The most widely accepted etiopathogenesis hypothesis of the origin of osteoporosis and its complications is that they are a consequence of bone aging and other environmental factors, together with a genetic predisposition. Evidence suggests that oxidative stress is crucial in bone pathologies associated with aging. The aim of this study was to determine whether genetic variants in oxidative stress-related genes modified the risk of osteoporotic fracture. We analysed 221 patients and 354 controls from the HORTEGA sample after 12-14 years of follow up. We studied the genotypic and allelic distribution of 53 SNPs in 24 genes involved in oxidative stress. The results showed that being a carrier of the variant allele of the SNP rs4077561 within TXNRD1 was the principal genetic risk factor associated with osteoporotic fracture and that variant allele of the rs1805754 M6PR, rs4964779 TXNRD1, rs406113 GPX6, rs2281082 TXN2 and rs974334 GPX6 polymorphisms are important genetic risk factors for fracture. This study provides information on the genetic factors associated with oxidative stress which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications.
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Fraturas por Osteoporose/genética , Estresse Oxidativo/genética , Polimorfismo de Nucleotídeo Único , Idoso , Densidade Óssea/genética , Estudos Transversais , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Glutationa Peroxidase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Receptor IGF Tipo 2/genética , Espanha , Tiorredoxina Redutase 1/genética , Tiorredoxinas/genéticaRESUMO
BACKGROUND: Osteoporosis and obesity are major public health problems that are closely correlated, as they share various features, including a genetic predisposition. A genetic correlation between obesity and osteoporosis due to the biological common pathways of bone and fat metabolism, which implies pleiotropic genes regulating has been described. The objective of our study was to analyse whether polymorphisms in obesity-related genes modify the risk of osteoporotic bone fracture. METHODS: We studied 575 subjects from the Hortega Study. The subjects were followed-up for 12-14 years. 202 subjects were overweight, 143 obese and 221 had bone fractures. The distribution of 39 genetic variants in 22 obesity-related genes were studied. RESULTS: The results showed a relationship between polymorphisms in the FTO and NEGR1 genes and the susceptibility to osteoporotic fracture. The variant genotype of the rs2568958 NEGR1 polymorphism and the rs6499649, rs3751812, and rs8044769 genetic variants in FTO were associated with susceptibility to bone fracture. In the best of our knowledge, this is the first time that these variants in NEGR1 and FTO genes have been associated with the susceptibility to osteoporotic bone fracture, supporting the hypothesis that the NEGR1 and FTO genes might be candidates for osteoporosis and bone fracture. CONCLUSIONS: In conclusion, this study associates obesity-related polymorphisms in the NEGR1 and FTO genes with osteoporotic bone fracture, reinforcing the hypothesis that obesity and bone metabolism are closely correlated genetically.
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Fraturas por Osteoporose , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Seguimentos , Predisposição Genética para Doença , Humanos , Obesidade/complicações , Obesidade/genética , Fraturas por Osteoporose/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Smoking can play a key role in SARS-CoV-2 infection and in the course of the disease. Previous studies have conflicting or inconclusive results on the prevalence of smoking and the severity of the coronavirus disease (COVID-19). METHODS: Observational, multicenter, retrospective cohort study of 14,260 patients admitted for COVID-19 in Spanish hospitals between February and September 2020. Their clinical characteristics were recorded and the patients were classified into a smoking group (active or former smokers) or a non-smoking group (never smokers). The patients were followed up to one month after discharge. Differences between groups were analyzed. A multivariate logistic regression and Kapplan Meier curves analyzed the relationship between smoking and in-hospital mortality. RESULTS: The median age was 68.6 (55.8-79.1) years, with 57.7% of males. Smoking patients were older (69.9 [59.6-78.0 years]), more frequently male (80.3%) and with higher Charlson index (4 [2-6]) than non-smoking patients. Smoking patients presented a worse evolution, with a higher rate of admission to the intensive care unit (ICU) (10.4 vs 8.1%), higher in-hospital mortality (22.5 vs. 16.4%) and readmission at one month (5.8 vs. 4.0%) than in non-smoking patients. After multivariate analysis, smoking remained associated with these events. CONCLUSIONS: Active or past smoking is an independent predictor of poor prognosis in patients with COVID-19. It is associated with higher ICU admissions and in-hospital mortality.
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COVID-19 , Idoso , COVID-19/epidemiologia , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2RESUMO
Introduction: Smoking can play a key role in SARS-CoV-2 infection and in the course of the disease. Previous studies have conflicting or inconclusive results on the prevalence of smoking and the severity of the coronavirus disease (COVID-19). Methods: Observational, multicenter, retrospective cohort study of 14,260 patients admitted for COVID-19 in Spanish hospitals between February and September 2020. Their clinical characteristics were recorded and the patients were classified into a smoking group (active or former smokers) or a non-smoking group (never smokers). The patients were followed up to one month after discharge. Differences between groups were analysed. A multivariate logistic regression and Kapplan Meier curves analysed the relationship between smoking and in-hospital mortality. Results: The median age was 68.6 (55.8-79.1) years, with 57.7% of males. Smoking patients were older (69.9 (59.6-78.0 years)), more frequently male (80.3%) and with higher Charlson index (4 (2-6)) than non-smoking patients. Smoking patients presented a worse evolution, with a higher rate of admission to the intensive care unit (ICU) (10.4 vs. 8.1%), higher in-hospital mortality (22.5 vs. 16.4%) and readmission at one month (5.8 vs. 4.0%) than in non-smoking patients. After multivariate analysis, smoking remained associated with these events. Conclusions: Active or past smoking is an independent predictor of poor prognosis in patients with COVID-19. It is associated with higher ICU admissions and in-hospital mortality.
Introducción: El tabaquismo puede tener un papel importante en la infección por SARS-CoV-2 y en el curso de la enfermedad. Los estudios previos muestran resultados contradictorios o no concluyentes sobre la prevalencia de fumar y la severidad en la enfermedad por coronavirus (COVID-19). Material y métodos: Estudio de cohortes observacional, multicéntrico y retrospectivo de 14.260 pacientes que ingresaron por COVID-19 en hospitales españoles desde febrero a septiembre de 2020. Se registraron sus características clínicas y se clasificaron en el grupo con tabaquismo si tabaquismo activo o previo o en el grupo sin tabaquismo si nunca habían fumado. Se realizó un seguimiento hasta un mes después del alta. Se analizaron las diferencias entre grupos. La relación entre tabaquismo y mortalidad intrahospitalaria se valoró mediante una regresión logística multivariante y curvas de Kapplan Meier. Resultados: La mediana de edad fue 68,6 (55,879,1) años, con un 57,7% de varones. El grupo con tabaquismo presentó mayor edad (69,9 (59,678,0 años)), predominio masculino (80,3%) y mayor índice de Charlson (4 (2−6)). La evolución fue peor en estos pacientes, con una mayor tasa de ingreso en UCI (10,4 vs 8,1%), mayor mortalidad intrahospitalaria (22,5 vs 16,4%) y reingreso al mes (5,8 vs 4,0%) que el grupo sin tabaquismo. Tras el análisis multivariante, el tabaquismo permanecía asociado a estos eventos. Conclusiones: El tabaquismo de forma activa o pasada es un factor predictor independiente de mal pronóstico en los pacientes con COVID-19, estando asociada a mayor probabilidad de ingreso en UCI y a mayor mortalidad intrahospitalaria.
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OBJECTIVES: To evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards. METHODS: The presence of N-antigenemia was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis. RESULTS: Prevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09-3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26-0.85). DISCUSSION: The presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.
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COVID-19 , Anticorpos Antivirais , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Estudos Prospectivos , SARS-CoV-2RESUMO
PURPOSE: To determine whether a 6-day course of methylprednisolone (MP) improves outcome in patients with severe SARS-CoV2 (Corona Virus Disease 2019 [COVID-19]). METHODS: The study was a multicentric open-label trial of COVID-19 patients who were aged ≥â¯18 years, receiving oxygen without mechanical ventilation, and with evidence of systemic inflammatory response who were assigned to standard of care (SOC) or SOC plus intravenous MP (40â¯mg bid for 3 days followed by 20â¯mg bid for 3 days). The primary outcome was a composite of death, admission to the intensive care unit, or requirement for noninvasive ventilation. Both intention-to-treat (ITT) and per protocol (PP) analyses were performed. RESULTS: A total of 91 patients were screened, and 64 were randomized (mean age70⯱ 12 years). In the ITT analysis, 14 of 29 patients (48%) in the SOC group and 14 of 35 (40%) in the MP group suffered the composite endpoint (40% versus 20% in patients under 72 years and 67% versus 48% in those over 72 years; pâ¯= 0.25). In the PP analysis, patients on MP had a significantly lower risk of experiencing the composite endpoint (age-adjusted risk ratio 0.42; 95% confidence interval, CI 0.20-0.89; pâ¯= 0.043). CONCLUSION: The planned sample size was not achieved, and our results should therefore be interpreted with caution. The use of MP had no significant effect on the primary endpoint in ITT analysis; however, the PP analysis showed a beneficial effect due to MP, which consistent with other published trials support the use of glucocorticoids in severe cases of COVID-19.
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COVID-19 , Metilprednisolona , Adulto , Idoso , Humanos , Respiração Artificial , SARS-CoV-2 , Resultado do TratamentoRESUMO
(1) Background: The inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. (2) Methods: Retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. (3) Results: A total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. (4) Conclusion: The present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters.
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Osteoporosis is the most common bone disorder worldwide and is associated with a reduced quality of life with important clinical and economic consequences. The most widely accepted etiopathogenic hypothesis on the origin of osteoporosis and its complications is that they are a consequence of the synergic action of environmental and genetic factors. Bone is constantly being remodelled through anabolic and catabolic pathways in which inflammation, the NF-kB pathway and the renin-angiotensin-aldosterone system (RAAS) are crucial. The aim of our study was to determine whether polymorphisms in genes implicated in inflammation, the NF-kB pathway and RAAS modified the risk of osteoporotic fracture. We analysed 221 patients with osteoporotic fracture and 354 controls without fracture from the HORTEGA sample after 12-14â¯years of follow up. In addition, we studied the genotypic distribution of 230 single nucleotide polymorphisms (SNPs) in genes involved in inflammation, NF-kB pathway and RAAS. Our results showed that be carrier of the C allele of the rs2228145 IL6R polymorphism was the principal genetic risk factor associated with osteoporotic fracture. The results also showed that variant genotypes of the rs4762 AGT, rs4073 IL8, rs2070699 END1 and rs4291 ACE polymorphisms were important genetic risk factors for fracture. The study provides information about the genetic factors associated with inflammation, the NF-kB pathway and RAAS, which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications.
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Fraturas por Osteoporose , Sistema Renina-Angiotensina , Seguimentos , Humanos , Inflamação/genética , NF-kappa B/genética , Fraturas por Osteoporose/genética , Qualidade de Vida , Sistema Renina-Angiotensina/genéticaRESUMO
OBJECTIVE: To assess the relationship between the FRAX index and the Barthel index/MiniMental State Examination in older people. PATIENTS AND METHODS: Observational descriptive study. Demographic data, comorbidity, dependency and cognitive state, and risk of osteoporotic fracture were collected. RESULTS: A total of 375 patients were included (60% female) Patients with a low-risk FRAX for hip fractures had a higher Mini-mental (25, 95% CI = 24-27 vs. 22, 95% = 21 to 23, p = .0001), a higher Barthel index (88, 95% CI = 84-93 vs 72, 69 to 76, p = .0001) without differences in the Charlson index. Bivariate analysis showed an inverse association between FRAX and scales but logistic regression showed only female sex (OR 4.4, 95% CI = 2.6-7.6) and the non-dependent Barthel index (OR = 0.104, 95% CI = 0.014-0.792) remained significant and. Barthel index/Mini-mental constructed a significant model capable of predicting a risk of hip fracture of >3% measured by the FRAX index, with an area under the curve of 0.76 (95% CI = 0.7-0.81). CONCLUSIONS: The FRAX index is related to other markers of geriatric assessment and the association between these variables can predict a risk of hip fracture of >3% measured by the FRAX index. Key messages Geriatric assessment indexes may be as important as the FRAX index, which is based on clinical risk factors, in predicting the fracture risk in older patient.
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Densidade Óssea/fisiologia , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Avaliação Geriátrica/métodos , Osteoporose/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/fisiopatologia , Feminino , Avaliação Geriátrica/estatística & dados numéricos , Fraturas do Quadril/etiologia , Fraturas do Quadril/fisiopatologia , Fraturas do Quadril/prevenção & controle , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Osteoporose/complicações , Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/prevenção & controle , Medição de Risco/métodos , Fatores de RiscoRESUMO
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