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1.
PLoS One ; 16(8): e0255510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34351970

RESUMO

BACKGROUND: Novel virus outbreaks, such as the COVID-19 pandemic, may increase psychological distress among frontline workers. Psychological distress may lead to reduced performance, reduced employability or even burnout. In the present study, we assessed experienced psychological distress during the COVID-19 pandemic from a self-determination theory perspective. METHODS: This mixed-methods study, with repeated measures, used surveys (quantitative data) combined with audio diaries (qualitative data) to assess work-related COVID-19 experiences, psychological need satisfaction and frustration, and psychological distress over time. Forty-six participants (nurses, junior doctors, and consultants) completed 259 surveys and shared 60 audio diaries. Surveys and audio diaries were analysed separately. RESULTS: Quantitative results indicated that perceived psychological distress during COVID-19 was higher than pre-COVID-19 and fluctuated over time. Need frustration, specifically autonomy and competence, was positively associated with psychological distress, while need satisfaction, especially relatedness, was negatively associated with psychological distress. In the qualitative, thematic analysis, we observed that especially organisational logistics (rostering, work-life balance, and internal communication) frustrated autonomy, and unfamiliarity with COVID-19 frustrated competence. Despite many need frustrating experiences, a strong connection with colleagues and patients were important sources of relatedness support (i.e. need satisfaction) that seemed to mitigate psychological distress. CONCLUSION: The COVID-19 pandemic resulted in an increase of psychological distress among frontline workers. Both need frustration and need satisfaction explained unique variance of psychological distress, but seemed to originate from different sources. Challenging times require healthcare organisations to better support their professionals by tailored formal and informal support. We propose to address both indirect (e.g. organisation) and direct (e.g. colleagues) elements of the clinical and social environment in order to reduce need frustration and enhance need satisfaction.


Assuntos
COVID-19/psicologia , Pessoal de Saúde/psicologia , Angústia Psicológica , Adulto , Ansiedade/psicologia , Esgotamento Profissional/psicologia , Depressão/psicologia , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Pandemias , Satisfação Pessoal , SARS-CoV-2/patogenicidade , Inquéritos e Questionários
2.
Br J Cancer ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400802

RESUMO

Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.

3.
Transplantation ; 105(5): 1106-1115, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32639409

RESUMO

BACKGROUND: Galectin-3 may play a causal role in kidney inflammation and fibrosis, which may also be involved in the development of kidney graft failure. With novel galectin-3-targeted pharmacological therapies increasingly coming available, we aimed to investigate whether galectin-3 is associated with risk of late graft failure in kidney transplant recipients (KTR). METHODS: We studied adult KTR who participated in TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study, recruited in a university setting (2001-2003). Follow-up was performed for a median of 9.5 (interquartile range, 6.2-10.2) years. Overall and stratified (Pinteraction < 0.05) multivariable-adjusted Cox proportional-hazards regression analyses were performed to study the association of galectin-3 with risk of graft failure (restart of dialysis or retransplantation). RESULTS: Among 561 KTR (age 52 ± 12 y; 54% males), baseline median galectin-3 was 21.1 (interquartile range, 17.0-27.2) ng/mL. During follow-up, 72 KTR developed graft failure (13, 18, and 44 events over increasing tertiles of galectin-3). Independent of adjustment for donor, recipient, and transplant characteristics, galectin-3-associated with increased risk of graft failure (hazard ratios [HR] per 1 SD change, 2.12; 95% confidence interval [CI], 1.63-2.75; P < 0.001), particularly among KTR with systolic blood pressure ≥140 mmHg (HR, 2.29; 95% CI, 1.80-2.92; P < 0.001; Pinteraction = 0.01) or smoking history (HR, 2.56; 95% CI, 1.95-3.37; P < 0.001; Pinteraction = 0.03). Similarly, patients in the highest tertile of galectin-3 were consistently at increased risk of graft failure. CONCLUSIONS: Serum galectin-3 levels are elevated in KTR, and independently associated with increased risk of late graft failure. Whether galectin-3-targeted therapies may represent novel opportunities to decrease the long-standing high burden of late graft failure in stable KTR warrants further studies.

4.
Am J Transplant ; 21(4): 1535-1544, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32946659

RESUMO

Urinary liver-type fatty acid-binding protein (uL-FABP) is a biomarker of kidney hypoxia and ischemia, and thus offers a novel approach to identify early kidney insults associated with increased risk of graft failure in outpatient kidney transplant recipients (KTR). We investigated whether uL-FABP is associated with graft failure and whether it improves risk prediction. We studied a cohort of 638 outpatient KTR with a functional graft ≥1-year. During a median follow-up of 5.3 years, 80 KTR developed graft failure. uL-FABP (median 2.11, interquartile range 0.93-7.37 µg/24"/>h) was prospectively associated with the risk of graft failure (hazard ratio 1.75; 95% confidence interval 1.27-2.41 per 1-SD increment; P = .001), independent of potential confounders including estimated glomerular filtration rate and proteinuria. uL-FABP showed excellent discrimination ability for graft failure (c-statistic of 0.83) and its addition to a prediction model composed by established clinical predictors of graft failure significantly improved the c-statistic to 0.89 (P for F-test <.001). These results were robust to several sensitivity analyses. Further validation studies are warranted to evaluate the potential use of a risk-prediction model including uL-FABP to improve identification of outpatient KTR at high risk of graft failure in clinical care.


Assuntos
Transplante de Rim , Proteínas de Ligação a Ácido Graxo , Humanos , Transplante de Rim/efeitos adversos , Fígado , Pacientes Ambulatoriais , Transplantados
5.
BMC Med ; 18(1): 307, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33032595

RESUMO

BACKGROUND: There is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome. METHODS: The main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity. RESULTS: The final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1-201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations < 140 pmol/l were associated with a small increase in all-cause (hazard ratio, HR 1.39, 95% CI 1.08-1.78, p = 0.011) and cardiovascular (HR 1.64, 95% CI 1.08-2.47, p = 0.020) mortality. Similarly, high serum B12 concentrations > 700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01-2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity. CONCLUSIONS: In the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe.


Assuntos
Vitamina B 12/sangue , Adolescente , Adulto , Estudos Transversais , Suplementos Nutricionais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Inquéritos Nutricionais , Prognóstico , Análise de Sobrevida , Vitamina B 12/administração & dosagem , Adulto Jovem
6.
PLoS Med ; 17(6): e1003140, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32542023

RESUMO

BACKGROUND: Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. METHODS AND FINDINGS: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. CONCLUSIONS: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.


Assuntos
Transplante de Rim/mortalidade , Inibidores da Bomba de Prótons/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco
7.
Nephrol Dial Transplant ; 35(3): 512-519, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32133530

RESUMO

BACKGROUND: In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs. METHODS: The plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers. RESULTS: Median circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31-6.45] µmol/L. During a follow-up period of 6.4 (IQR 5.6-6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03-1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30-2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45-3.00) per 1-SD increment]. CONCLUSIONS: Circulating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Nefropatias/mortalidade , Transplante de Rim/mortalidade , Malondialdeído/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Transplantados
8.
Ther Adv Endocrinol Metab ; 11: 2042018820908456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32166012

RESUMO

Background: Serum calcification propensity can be monitored using the maturation time of calciprotein particles in serum (T50 test). A shorter T50 indicates greater propensity to calcify; this is an independent determinant of cardiovascular disease. As the intraperitoneal (IP) route of insulin administration mimics the physiology more than the subcutaneous (SC) route in persons with type 1 diabetes (T1DM), we hypothesized that IP insulin influences determinants of calcium propensity and therefore result in a longer T50 than SC insulin administration. Methods: Prospective, observational case-control study. Measurements were performed at baseline and at 26 weeks in age and gender matched persons with T1DM. Results: A total of 181 persons, 39 (21.5%) of which used IP and 142 (78.5%) SC insulin were analysed. Baseline T50 was 356 (45) minutes. The geometric mean T50 significantly differed between both treatment groups: 367 [95% confidence interval (CI) 357, 376] for the IP group and 352 (95% CI 347, 357) for the SC group with a difference of -15 (95% CI -25, -4) minutes, in favour of IP treatment. In multivariable analyses, the IP route of insulin administration had a positive relation on T50 concentrations while higher age, triglycerides and phosphate concentrations had an inverse relation. Conclusion: Among persons with T1DM, IP insulin administration results in a more favourable calcification propensity time then SC insulin. It has yet to be shown if this observation translates into improved cardiovascular outcomes.

9.
Nephrol Dial Transplant ; 35(2): 357-365, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165500

RESUMO

BACKGROUND: It currently remains understudied whether low consumption of fruits and vegetables after kidney transplantation may be a modifiable cardiovascular risk factor. We aimed to investigate the associations between consumption of fruits and vegetables and cardiovascular mortality in renal transplant recipients (RTRs). METHODS: Consumption of fruits and vegetables was assessed in an extensively phenotyping cohort of RTRs. Multivariable-adjusted Cox proportional hazards regression analyses were performed to assess the risk of cardiovascular mortality. RESULTS: We included 400 RTRs (age 52 ± 12 years, 54% males). At a median follow-up of 7.2 years, 23% of RTRs died (53% were due to cardiovascular causes). Overall, fruit consumption was not associated with cardiovascular mortality {hazard ratio [HR] 0.82 [95% confidence interval (CI) 0.60-1.14]; P = 0.24}, whereas vegetable consumption was inversely associated with cardiovascular mortality [HR 0.49 (95% CI 0.34-0.71); P < 0.001]. This association remained independent of adjustment for several potential confounders. The association of fruit consumption with cardiovascular mortality was significantly modified by estimated glomerular filtration rate (eGFR; Pinteraction = 0.01) and proteinuria (Pinteraction = 0.01), with significant inverse associations in patients with eGFR > 45 mL/min/1.73 m2 [HR 0.56 (95% CI 0.35-0.92); P = 0.02] or the absence of proteinuria [HR 0.62 (95% CI 0.41-0.92); P = 0.02]. CONCLUSIONS: In RTRs, a relatively higher vegetable consumption is independently and strongly associated with lower cardiovascular mortality. A relatively higher fruit consumption is also associated with lower cardiovascular mortality, although particularly in RTRs with eGFR > 45 mL/min/1.73 m2 or an absence of proteinuria. Further studies seem warranted to investigate whether increasing consumption of fruits and vegetables may open opportunities for potential interventional pathways to decrease the burden of cardiovascular mortality in RTRs.


Assuntos
Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/mortalidade , Frutas , Nefropatias/mortalidade , Transplante de Rim/mortalidade , Transplantados/estatística & dados numéricos , Verduras , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Feminino , Humanos , Nefropatias/complicações , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
10.
J Clin Med ; 8(12)2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771233

RESUMO

There is a changing trend in mortality causes in kidney transplant recipients (KTR), with a decline in deaths due to cardiovascular causes along with a relative increase in cancer mortality rates. Vitamin C, a well-known antioxidant with anti-inflammatory and immune system enhancement properties, could offer protection against cancer. We aimed to investigate the association of plasma vitamin C with long-term cancer mortality in a cohort of stable outpatient KTR without history of malignancies other than cured skin cancer. Primary and secondary endpoints were cancer and cardiovascular mortality, respectively. We included 598 KTR (mean age 51 ± 12 years old, 55% male). Mean (SD) plasma vitamin C was 44 ± 20 µmol/L. At a median follow-up of 7.0 (IQR, 6.2-7.5) years, 131 patients died, of which 24% deaths were due to cancer. In Cox proportional hazards regression analyses, vitamin C was inversely associated with cancer mortality (HR 0.50; 95%CI 0.34-0.74; P < 0.001), independent of potential confounders, including age, smoking status and immunosuppressive therapy. In secondary analyses, vitamin C was not associated with cardiovascular mortality (HR 1.16; 95%CI 0.83-1.62; P = 0.40). In conclusion, plasma vitamin C is inversely associated with cancer mortality risk in KTR. These findings underscore that relatively low circulating plasma vitamin C may be a meaningful as yet overlooked modifiable risk factor of cancer mortality in KTR.

11.
J Clin Med ; 8(10)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614925

RESUMO

Graft failure (GF) remains a significant limitation to improve long-term outcomes in renal transplant recipients (RTR). Urinary epidermal growth factor (uEGF) is involved in kidney tissue integrity, with a reduction of its urinary excretion being associated with fibrotic processes and a wide range of renal pathologies. We aimed to investigate whether, in RTR, uEGF is prospectively associated with GF. In this prospective cohort study, RTR with a functioning allograft ≥1-year were recruited and followed-up for three years. uEGF was measured in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of GF was assessed by Cox-regression analyses and its predictive ability by C-statistic. In 706 patients, uEGF/Cr at enrollment was 6.43 [IQR 4.07-10.77] ng/mg. During follow-up, 41(6%) RTR developed GF. uEGF/Cr was inversely associated with the risk of GF (HR 0.68 [95% CI 0.59-0.78]; P < 0.001), which remained significant after adjustment for immunosuppressive therapy, estimated Glomerular Filtration Rate, and proteinuria. C-statistic of uEGF/Cr for GF was 0.81 (P < 0.001). We concluded that uEGF/Cr is independently and inversely associated with the risk of GF and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising marker for use in clinical practice.

12.
Clin J Am Soc Nephrol ; 14(10): 1512-1520, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31530552

RESUMO

BACKGROUND AND OBJECTIVES: In kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., Nε -[Carboxymethyl]lysine (CML) and Nε -[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes's procedure. RESULTS: We included 555 kidney transplant recipients (age 51±12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P<0.001; and hazard ratio, 1.53; 95% confidence interval 1.18 to 1.98; P=0.002), independent of age, diabetes, smoking status, body mass index, eGFR and proteinuria. Further adjustments, including cardiovascular history, did not materially change these findings. In mediation analyses, free thiol groups and soluble vascular cell adhesion molecule-1 consistently explained approximately 35% of the association of CML and CEL with cardiovascular mortality. CONCLUSIONS: In stable kidney transplant recipients, circulating levels of AGEs are independently associated with long-term risk of cardiovascular mortality. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_17_CJN00540119.mp3.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Produtos Finais de Glicação Avançada/sangue , Transplante de Rim , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/cirurgia , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Medição de Risco , Fatores de Tempo
13.
J Clin Med ; 8(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987358

RESUMO

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92-3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6-6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36-0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.

14.
J Clin Med ; 8(2)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717286

RESUMO

BACKGROUND: Low circulating magnesium (Mg) is associated with an increased risk of developing type 2 diabetes mellitus (T2DM). We aimed to study the performance of a nuclear magnetic resonance (NMR)-based assay that quantifies ionized Mg in EDTA plasma samples and prospectively investigate the association of Mg with the risk of T2DM. METHODS: The analytic performance of an NMR-based assay for measuring plasma Mg was evaluated. We studied 5747 subjects free of T2DM at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. RESULTS: Passing⁻Bablok regression analysis, comparing NMR-measured ionized Mg with total Mg measured by the Roche colorimetric assay, produced a correlation of r = 0.90, with a slope of 1.08 (95% CI: 1.00⁻1.13) and an intercept of 0.02 (95% CI: -0.02⁻0.08). During a median follow-up period of 11.2 (IQR: 7.7⁻12.0) years, 289 (5.0%) participants developed T2DM. The association of NMR-measured ionized Mg with T2DM risk was modified by sex (Pinteraction = 0.007). In women, we found an inverse association between Mg and the risk of developing T2DM, independent of adjustment for potential confounders (HR: 1.80; 95% CI: 1.20⁻2.70). In men, we found no association between Mg and the risk of developing T2DM (HR: 0.90; 95%: 0.67⁻1.21). CONCLUSION: Lower NMR-measured plasma ionized Mg was independently associated with a higher risk of developing T2DM in women, but not in men.

15.
Ned Tijdschr Geneeskd ; 1622018 12 05.
Artigo em Holandês | MEDLINE | ID: mdl-30570928

RESUMO

Errors in the diagnostic process contribute substantially to medical errors and adverse events in the health care system. Research into ways to reduce diagnostic errors is still in its infancy. In this article, it is argued that checklists and time-outs for a brief moment of diagnostic reflection may be advisable.


Assuntos
Lista de Checagem , Erros de Diagnóstico/prevenção & controle , Humanos , Segurança do Paciente
16.
Nutrients ; 10(10)2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30282924

RESUMO

Marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely associated with cardiovascular and all-cause mortality in renal transplant recipients (RTRs). Recommendations to increase marine-derived n-3 PUFAs by increasing fish intake may have a drawback in concomitant stimulation of mercury intake, which could lead to higher circulating mercury concentrations and mitigation of otherwise beneficial effects of n-3 PUFAs. We aimed to monitor circulating mercury concentrations, and to prospectively evaluate whether it counteracts the potential association between fish intake and cardiovascular and all-cause mortality in a cohort of RTRs (n = 604, 53 ± 13 years-old, 57% men) with long-term follow-up (median of 5.4 years; 121 deaths). Circulating mercury concentration (median 0.30 (IQR 0.14⁻0.63) µg/L) positively associated with fish intake (std. ß = 0.21, p < 0.001). Multivariable-adjusted Cox-proportional hazards regression analyses showed that prior to, and after additional adjustment for circulating mercury concentrations, fish intake was inversely associated with both cardiovascular (HR 0.75, 95% CI 0.58⁻0.96; and, HR 0.75, 95% CI 0.58⁻0.97, respectively) and all-cause mortality (HR 0.84, 95% CI 0.72⁻0.97; and, HR 0.86, 95% CI 0.74⁻0.99, respectively). Secondary analyses accounting for marine-derived n-3 PUFAs intake revealed associations of similar magnitude. In conclusion, we found no evidence of a counteracting effect conferred by circulating mercury concentrations on the associations between fish and marine-derived n-3 PUFAs intake and the risks of cardiovascular and all-cause mortality in RTRs.


Assuntos
Dieta , Transplante de Rim/mortalidade , Mercúrio/sangue , Alimentos Marinhos , Adulto , Idoso , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Peixes , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
17.
Am J Transplant ; 18(10): 2523-2533, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29464830

RESUMO

Renal transplant recipients (RTR) are at risk of decline of graft function and premature mortality, with high blood pressure as an important risk factor for both. To study the association of the Dietary Approach to Stop Hypertension (DASH) diet with these adverse events, we conducted a prospective cohort study of adult RTR. Dietary data were collected using a validated 177-item food frequency questionnaire and an overall DASH-score was obtained. We included 632 stable RTR (mean ± standard deviation age 53.0 ± 12.7 years, 57% men). Mean DASH score was 23.8 ± 4.7. During median follow-up of 5.3 (interquartile range, 4.1-6.0) years, 119 (18.8%) RTR had renal function decline, defined as a combined endpoint of doubling of serum creatinine and death-censored graft failure, and 128 (20.3%) died. In Cox-regression analyses, RTR in the highest tertile of the DASH score had lower risk of both renal function decline (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33-0.96, P = .03) and all-cause mortality (HR = 0.52; 95%CI, 0.32-0.83, P = .006) compared to the lowest tertile, independent of potential confounders. Adherence to a DASH-style diet is associated with lower risk of both renal function decline and all-cause mortality. These results suggest that a healthful diet might benefit long-term outcome in RTR.


Assuntos
Dieta , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Hipertensão/mortalidade , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/dietoterapia , Rejeição de Enxerto/etiologia , Humanos , Hipertensão/dietoterapia , Hipertensão/etiologia , Falência Renal Crônica/cirurgia , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Transplantados
18.
Eur J Clin Invest ; 48(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29171874

RESUMO

BACKGROUND: Low-normal thyroid function within the euthyroid range has been suggested to enhance atherosclerosis susceptibility. Paraoxonase-1 (PON-1) may protect against atherosclerotic cardiovascular disease development by attenuating oxidative stress. We evaluated relationships of PON-1 with thyroid stimulating hormone (TSH), free T4 , free T3 , lipids and apolipoprotein (apo)A-I in euthyroid subjects, and assessed whether such relationships are modified in the context of the metabolic syndrome (MetS). MATERIALS AND METHODS: Serum PON-1 activity (arylesterase activity), TSH, free T4 , free T3 , lipids and apoA-I was measured in 2206 euthyroid subjects (aged 28-75 years; 1138 men (age 49 ± 13 years) and 1068 women (age 46 ± 12 years), recruited from the general population (PREVEND cohort). RESULTS: In age- and sex-adjusted analysis, PON-1 activity (divided into tertiles) was positively related to TSH (ß = -0.045, P = .036) and inversely to free T4 (ß = -0.042, P = .050) but not to free T3 (ß = -0.027, P = .20). PON-1 activity was positively related to total cholesterol, non-HDL cholesterol and triglycerides, as well as to HDL cholesterol and apoA-I (P < .01 to <.001). The inverse relationship of PON-1 activity with free T4 remained present after adjustment for lipids and other potential confounders (ß = -0.066, P = .002), but the positive relationship with TSH lost significance (ß = 0.034, P = .11). The inverse relationship of PON-1 activity with free T4 was not different in subjects with vs without MetS (P = .94), nor modified by the presence of its individual components (P ≥ .22 for each). CONCLUSIONS: Serum PON-1 activity is inversely associated with free T4 in euthyroid subjects, suggesting that low-normal thyroid function may affect PON-1 regulation.


Assuntos
Arildialquilfosfatase/metabolismo , Glândula Tireoide/enzimologia , Tiroxina/metabolismo , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tireotropina/metabolismo
19.
Drug Saf ; 41(4): 415-427, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29230691

RESUMO

INTRODUCTION: The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. OBJECTIVE: The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring. METHODS: A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. RESULTS: The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3-11.0). CONCLUSION: Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Antagonistas Adrenérgicos beta/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Complicações na Gravidez/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Estudos de Casos e Controles , Anormalidades Congênitas/etiologia , Feminino , Cardiopatias Congênitas/induzido quimicamente , Humanos , Razão de Chances , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Prevalência , Sistema de Registros , Fatores de Risco , Adulto Jovem
20.
Nutrients ; 9(6)2017 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-28574431

RESUMO

Vitamin C may reduce inflammation and is inversely associated with mortality in the general population. We investigated the association of plasma vitamin C with all-cause mortality in renal transplant recipients (RTR); and whether this association would be mediated by inflammatory biomarkers. Vitamin C, high sensitive C-reactive protein (hs-CRP), soluble intercellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured in a cohort of 598 RTR. Cox regression analyses were used to analyze the association between vitamin C depletion (≤28 µmol/L; 22% of RTR) and mortality. Mediation analyses were performed according to Preacher and Hayes's procedure. At a median follow-up of 7.0 (6.2-7.5) years, 131 (21%) patients died. Vitamin C depletion was univariately associated with almost two-fold higher risk of mortality (Hazard ratio (HR) 1.95; 95% confidence interval (95%CI) 1.35-2.81, p < 0.001). This association remained independent of potential confounders (HR 1.74; 95%CI 1.18-2.57, p = 0.005). Hs-CRP, sICAM-1, sVCAM-1 and a composite score of inflammatory biomarkers mediated 16, 17, 15, and 32% of the association, respectively. Vitamin C depletion is frequent and independently associated with almost two-fold higher risk of mortality in RTR. It may be hypothesized that the beneficial effect of vitamin C at least partly occurs through decreasing inflammation.


Assuntos
Deficiência de Ácido Ascórbico/complicações , Ácido Ascórbico/sangue , Nefropatias/mortalidade , Transplante de Rim , Adulto , Biomarcadores/sangue , Composição Corporal , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Creatinina/sangue , Suplementos Nutricionais , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/complicações , Molécula 1 de Adesão Intercelular/sangue , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/diagnóstico , Molécula 1 de Adesão de Célula Vascular/sangue
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