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Background: Elderly patients with advanced chronic kidney disease require accurate outcome descriptions to make treatment decisions. Methods: The PSPA [Parcours de soins des personnes âgées (Treatment pathways for elderly patients)] prospective multicentre cohort study included 573 such patients with a median age of 82 [interquartile range (IQR) 79-86] years and a median estimated glomerular filtration rate of 14 (IQR 11-17) mL/min/1.73 m2 and studied their 5-year outcomes according to the dialysis component of their treatment plans. Results: Mean follow-up for the overall cohort was 34.5 ± 21 months and the 5-year survival rate was 27%. During follow-up, 288 (50%) patients started dialysis and 237 (42%) died before dialysis. At baseline, the four possible dialysis plans were dialysis when needed (38%), stable without mention of a dialysis plan (40%) and dialysis specifically excluded by the patient's (9%) or nephrologist's decision (12%). These baseline plans were associated with death and dialysis start. Follow-up plans were those decided during the study period: dialysis when needed for 47%, stable without mention of a dialysis plan for 20% and dialysis excluded at any time for 32%. For the subgroup of patients who started dialysis, those whose follow-up plan was dialysis started under better conditions than those who had stable or no dialysis follow-up plans before starting. However, survival afterwards did not differ significantly. Conclusions: These findings indicate that nephrology care should accommodate changes over time in older patients' treatment preferences and plans concerning dialysis. These changes are associated with whether, when and how these patients initiate dialysis but are not necessarily associated with post-dialysis survival.
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Tratamento Conservador/métodos , Taxa de Filtração Glomerular/fisiologia , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
CONTEXT: Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS). OBJECTIVE: This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS. METHODS: A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11). RESULTS: In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P < .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P < .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P < .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients. CONCLUSION: Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.
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Insuficiência Adrenal , Síndrome de Cushing , Humanos , Síndrome de Cushing/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Hormônio Adrenocorticotrópico , Hidrocortisona/uso terapêuticoRESUMO
OBJECTIVE: Pneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not. METHODS: This was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP. RESULTS: Twenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424±1.102nmol/L and urinary free cortisol>10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667±541nmol/L at the onset of PcP (P<0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP. CONCLUSION: High mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.
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Síndrome de Cushing , Pneumonia por Pneumocystis , Humanos , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/diagnóstico , Estudos Retrospectivos , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/epidemiologia , Hidrocortisona , Metirapona/uso terapêuticoRESUMO
BACKGROUND: Witholding treatment in asymptomatic/pauci-symptomatic high-grade central vein stenosis (CVS), i.e. those not causing debilitating painful extremity oedema, the benefits of which have been shown in only one study in grafts, is debatable. The aim of our study was to assess the short- and long-term benefits of such a strategy in mainly autogenous fistulas. METHODS: We retrospectively compared the outcomes of 53 untreated asymptomatic/pauci-symptomatic and 50 symptomatic high-grade CVS treated by dilation with or without stenting between January 1998 and August 2010 at a single center. Central vein and access patency was estimated by Kaplan-Meier analysis. RESULTS: Mean age, central catheter use and location of stenosis (brachiocephalic vein) in asymptomatic/pauci-symptomatic and symptomatic CVS were significantly different at 69 versus 75 years, 28 versus 48% and 74 versus 56%, respectively. Ninety percent of the cases had an autogenous fistula. The mean degree of stenosis was >80%. Fourty percent of asymptomatic/pauci-symptomatic CVS became severely symptomatic after 4 years. Primary central vein patency at 3, 12, 24 and 36 months in asymptomatic/pauci-symptomatic and symptomatic CVS were 87±5 versus 82±6, 77±6 versus 55±9, 71±7 versus 35±9 and 67±7 versus 18±9%, respectively (P=0.002). Primary access circuit patency rate was not significantly different between the two groups with 66±5 versus 50±4% at 1 year. Secondary central vein and access circuit patency rates at 1 and 3 years were 100 and 93±7 versus 89±5 and 84±7% (P=0.014). CONCLUSIONS: Withholding treatment in asymptomatic/pauci-symptomatic CVS in dialysis fistulas yielded significantly better short- and long-term central vein patency than treatment of symptomatic cases without detrimental effects on overall dialysis circuit.
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Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Constrição Patológica , Oclusão de Enxerto Vascular/terapia , Diálise Renal/efeitos adversos , Extremidade Superior/irrigação sanguínea , Grau de Desobstrução Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Chronic kidney disease (CKD) is a disease which is spreading worldwide, especially among older patients. Several prognostic scores have been developed to predict death in older CKD patients, but they have not been validated. We aimed to evaluate the existing risk scores for predicting death before dialysis start, identified via an in-depth review, in a cohort of elderly patients with advanced CKD. METHODS: We performed a review to identify scores predicting death, developed in and applicable to CKD patients. Each score was evaluated with an absolute risk calculation from the patients' baseline characteristics. We used a French prospective multicentre cohort of elderly patients (> 75 years) with advanced CKD [estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2], recruited from nephrological centres, with a 5-year follow-up. The outcome considered was death before initiating dialysis. Discrimination [area under curve (AUC)], calibration and Brier score were calculated for each score at its time frame. RESULTS: Our review found 6 equations predicting death before dialysis in CKD patients. Four of these (GOLDFARB, BANSAL, GRAMS 2 and 4 years) were evaluated. The validation cohort (Parcours de Soins des Personnes Âgées Parcours de Soins des Personnes Âgées, PSPA) included 573 patients, with a median age of 82 years and a median eGFR of 13 mL/min/1.73 m2. At the end of follow-up, 287 (50%) patients had started dialysis and 238 (41%) patients had died before dialysis. The four equations evaluated showed average discrimination (AUC 0.61-0.70) and, concerning calibration, a global overestimation of the risk of death. DISCUSSION: The available scores predicting death before dialysis showed low performance among older patients with advanced CKD in a French multicentre cohort, indicating the need to upgrade them or develop new scores for this population.
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Diálise Renal , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Prognóstico , Estudos Prospectivos , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Fatores de RiscoRESUMO
French health insurance data showed that the incidence of type 1 diabetes mellitus (T1DM) in children increased over the years to 2015. The objective of our study was to assess the evolution of the number of incident cases of paediatric and adult type 1 diabetes in our institution, and to describe their clinical presentation and its evolution. All patients with T1DM managed at diagnosis at Reims University Hospital between 1997 and 2019 were included. The clinical and biological data were extracted from the Champagne-Ardenne Diabetes Network database. Included were 847 patients with a median age of 10.3 years. Diagnosis was established in 71% of cases before 15 years, 7.4% after 35 years. The number of newly diagnosed cases was 3.6-times higher in 2019 compared to 1997. Ketoacidosis, the frequency of which decreased with age (P < 0.0001), revealed diabetes in a total of 32% of cases and in 46% of children under 5 years. It was more severe in children than in adults (P = 0.03), and its frequency increased over the study period. Hypotrophy was found in 23% of children under 15 years of age, and was more pronounced before 5 years of age, with no improvement over time. We saw an increase in the frequency of obesity or overweight among adults. Our study showed an increase in incident cases of diabetes in our hospital that continued over time for both children and adults. Clinical features at diagnosis deteriorated during this period for those under 15 years of age with an increase in ketoacidosis frequency.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Cetose , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/etiologia , Hospitais , Humanos , Incidência , Estudos RetrospectivosRESUMO
INTRODUCTION: Type 1 diabetes is associated with an increased risk of vascular complications. We aimed to investigate the association between serum and tissue advanced glycation end-products (AGEs) and micro- and macrovascular complications in type 1 diabetes (T1D). METHODS: We conducted a cross-sectional study on 196 adults with T1D (mean age 44.53 ± 16, mean duration of diabetes 22 ± 12 years, mean HbA1c 8 ± 1.2%). AGEs were measured in blood serum (i.e., carboxymethyllysine (CML), methylglyoxal-hydroimidazolone-1 (MGH1), and pentosidine) and by measurement of skin autofluorescence (SAF). Associations between AGEs levels and vascular complications were analyzed using binary logistic regression. Correlations between AGEs and pulse wave velocity (PWV) were also assessed by linear regressions. Significant differences were set for p values less than 0.05. RESULTS: We found positive associations between different AGEs and vascular complications. SAF was associated with both microangiopathy (retinopathy: OR = 1.92, p = 0.011; neuropathy: OR = 2.02, p = 0.04; any microangiopathy: OR = 2.83, p < 0.0001) and macroangiopathy (coronaropathy: OR = 3.11, p = 0.009; any macroangiopathy: OR = 2.78, p = 0.003). For circulating AGEs, pentosidine was significantly associated with coronaropathy (OR = 1.61, p = 0.01) and any macroangiopathy (OR = 1.52, p = 0.005) while MGH1 was associated with nephropathy (OR 1.72, p = 0.03). Furthermore, a significant linear correlation was found between PWV and SAF (r = 0.43, p < 0.001), pentosidine (r = 0.28, p < 0.001), and MGH1 (r = 0.16, p = 0.031), but not for CML (r = 0.03, p = 0.598). CONCLUSIONS: Skin autofluorescence appears to be a useful marker for investigating both micro- and macrovascular complications in T1D. In this study, pentosidine was associated with macroangiopathy and MGH1 with nephropathy among the circulating AGEs. Furthermore, the correlations between PWV and AGEs may suggest their value in early prediction of vascular complications in T1D.
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INTRODUCTION: The pathophysiology of Charcot neuroarthropathy (CN) remains unclear. There are a number of hypotheses but these are not exclusive. In its clinical presentation, this complication intersects with the semiology of diabetic-induced neuropathy, such as peripheral hypervascularization and the appearance of arteriovenous shunt. The EPICHAR study is as yet an unpublished cohort of people living with diabetes complicated by CN (in active or chronic phase). Based on the findings of the EPICHAR study, this study aimed to investigate whether a reduction in the rate of hyperglycemia accompanies the onset of an active phase of CN. RESEARCH DESIGN AND METHODS: Hemoglobin A1c (HbA1c) levels were assessed 3 months (M3) and 6 months (M6) before the diagnosis of active CN (M0). RESULTS: 103 patients living with diabetes and presenting active CN were included between January and December 2019 from the 31 centers participating in this study (30 in France and 1 in Belgium). The mean age of the participants was 60.2±12.2 years; the vast majority were men (71.8%) living with type 2 diabetes (75.5%). Mean HbA1c levels significantly declined between M6 (median 7.70; Q1, Q3: 7.00, 8.55) and M3 (median 7.65; Q1, Q3: 6.90, 8.50) (p=0.012), as well as between M6 and M0 (median 7.40; Q1, Q3: 6.50, 8.50) (p=0.014). No significant difference was found between M3 and M0 (p=0.072). CONCLUSIONS: A significant reduction in HbA1c levels seems to accompany the onset of the active phase of CN. TRIAL REGISTRATION NUMBER: NCM03744039.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Hiperglicemia , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Feminino , Hemoglobinas Glicadas , Humanos , Hiperglicemia/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Clinical decision-making about care plans can be difficult for very elderly people with advanced chronic kidney disease (CKD). Current guidelines propose the use of prognostic tools predicting end stage renal disease (ESRD) to assist in a patient-centered shared decision-making approach. Our objective was to evaluate the existing risk model scores predicting ESRD, from data collected for a French prospective multicenter cohort of mainly octogenarians with advanced CKD. METHODS: We performed a rapid review to identify the risk model scores predicting ESRD developed from CKD patient cohorts and evaluated them with data from a prospective multicenter French cohort of elderly (> 75 years) patients with advanced CKD (estimated glomerular filtration rate [eGFR] < 20 mL/min/1.75m2), followed up for 5 years. We evaluated these scores (in absolute risk) for discrimination, calibration and the Brier score. For scores using the same time frame, we made a joint calibration curve and compared areas under the curve (AUCs). RESULTS: The PSPA cohort included 573 patients; their mean age was 83 years and their median eGFR was 13 mL/min/1.73 m2. At the end of follow-up, 414 had died and 287 had started renal replacement therapy (RRT). Our rapid review found 12 scores that predicted renal replacement therapy. Five were evaluated: the TANGRI 4-variable, DRAWZ, MARKS, GRAMS, and LANDRAY scores. No score performed well in the PSPA cohort: AUCs ranged from 0.57 to 0.65, and Briers scores from 0.18 to 0.25. CONCLUSIONS: The low predictiveness for ESRD of the scores tested in a cohort of octogenarian patients with advanced CKD underlines the need to develop new tools for this population.
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Falência Renal Crônica , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Prognóstico , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Fatores de RiscoRESUMO
Respect of patient's autonomy is essential. So that patients are able to write their advance directives in case of a situation where they are unable to make decisions for themselves. Currently, few people have written advance directives. We studied the feasibility of a systematic implementation of advance directives in haemodialysis patients. This prospective, single-center study was conducted in an ambulatory hemodialysis center. There were 4 steps: caregivers survey about advance directives; selection of patients and information about advance directives; writing advance directives with the interested patients; and finally, non-participation causes assessment of the other informed patients. Caregivers are not comfortable with advance directives, and have reluctances: the patient's lack of medical knowledge; the anxiety generated by end-of-life talk. Fifty-six patients (51.6%) were included and received the information. Nine of them wanted to write their advance directives on a suitable form. Eight finalised them (7.4% of the initial population). The majority wanted a therapeutic limitation. Twenty-nine patients, who have received the information about advance directives, didn't want to write them, the main reason was that they felt healthy or that they thought that their relatives would take the right decisions. Eighteen patients left the centre during the study. The development of advance directives requires information and training of caregivers and patient support. Few patients went to the end of the process. The limit of the patient's ability to decide for himself is difficult to define. The role of the doctor is central to accompany the patient during this process.
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Diretivas Antecipadas , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Interconnections between major cardiovascular events (MCVEs) and renal events are recognized in diabetes, however, the specific impact of atrial fibrillation (AF), heart failure (HF) and acute coronary syndrome (ACS) on the risk of end-stage renal disease (ESRD) on top of established renal risk factors is unclear in type 2 diabetes mellitus. METHODS: We conducted a retrospective study in 861 consecutive patients followed in a nephrology setting during the 2000-13 period. RESULTS: The mean age was 70 ± 10 years, 65.1% were men and the estimated glomerular filtration rate (eGFR) was 42.4 ± 21.0 mL/min/1.73 m2. During follow-up (median 59 months), 194 patients reached ESRD. A history of AF, HF or ACS was associated with an increased risk of reduced baseline eGFR. In turn, reduced baseline eGFR resulted in a greater risk of new MCVE (especially HF) during follow-up. Finally, all new MCVEs were risk factors for subsequent acute kidney injury (AKI) {HF: hazard ratio [HR] 8.99 [95% confidence interval (CI) 7.06-11.4]; AF: HR 5.42 (3.91-7.52); ACS: HR 8.82 (6.24-12.5); all P < 0.0001} and ESRD [HF: HR 5.52 (95% CI 4.01-7.60), P < 0.0001; AF: HR 3.48 (2.30-5.21), P < 0.0001; ACS: HR 2.31 (1.43-3.73), P = 0.0006]. The AF- and HF-associated risks of ESRD were significant after adjustments on all renal risks of ESRD (gender, blood pressure, eGFR, albuminuria, renin-angiotensin blockers, retinopathy and AKI), but the association was less strong for ACS. Importantly, no association was noted between other major events such as stroke or infections and the risk of ESRD. CONCLUSIONS: Past and new cardiovascular events (more HF and AF than ACS) have a strong, independent impact on the development of ESRD above and beyond established risk factors in diabetes.
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INTRODUCTION: The offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. Orthèse diabète is a new customized removable knee-high offloading device immobilizing foot and ankle joints, with some specific and innovative features that may improve offloading. We aimed to evaluate the efficiency of this device in DFU healing. RESEARCH, DESIGN AND METHODS: The evaluation of Offloading using a new removable ORTHOsis in DIABetic foot study is a French multicenter (13 centers) randomized controlled trial with blinded end points evaluation. Adults with neuropathic DFU were randomly assigned to either Orthèse Diabète (experimental device), or any type of conventional (usually used in France) removable offloading devices (control group). The primary outcome was the 3-month proportion of patients with fully healed DFU. RESULTS: Among 112 randomized patients (men 78%, age 62±10 years), the primary outcome occurred in 19 (33%) participants using conventional device vs 19 (35%) Orthèse Diabète users (p=0.79). Study groups were also comparable in terms of prespecified secondary end points including occurrence of new DFU (25% vs 27% in conventional and experimental groups), ipsilateral lower-limb amputation (4% vs 10%) or infectious complications (14% vs 13%) (p>0.05 for all). Adverse events were comparable between groups, including 4 deaths unrelated to study allocation (1 sudden death, 2 ventricular arrhythmias and 1 pancreatic cancer). Adverse events believed to be related to the device were higher in the Orthèse Diabète group than in the control group (15% vs 4%). Orthèse Diabète was less frequently worn than conventional devices (46% vs 66%, p=0.04). CONCLUSIONS: Orthèse Diabète, a new removable offloading orthosis immobilizing foot and ankle joints did not show superiority compared with conventional removable devices in neuropathic DFU healing and cannot be recommended to heal DFU. TRIAL REGISTRATION NUMBER: NCT01956162.
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Diabetes Mellitus , Pé Diabético , Adulto , Idoso , Amputação Cirúrgica , Pé Diabético/terapia , Humanos , Masculino , Pessoa de Meia-Idade , CicatrizaçãoRESUMO
French recommendations for the screening of hepatitis B virus (HBV) infection were updated in 2019 with the association of three markers: HBs Ag, anti-HBs Ab and anti-HBc Ab. These three markers allow identification of infected patients, vaccinated patients and patients who have been in contact with HBV. A positive HBs Ag is usually associated with HBV infection but this interpretation must take into account the clinical context. In particular, the absence of anti-HBc Ab, normal ALAT levels and the absence of jaundice can be associated with recent HBV vaccination or false-positive HBs Ag. Recent HBV vaccination can usually be confirmed by patient questioning, while confirmatory tests are useful to detect false positive HBs Ag. If necessary, a second sample can be requested to confirm the interpretation.
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Erros de Diagnóstico , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/diagnóstico , Idoso de 80 Anos ou mais , Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , VacinaçãoAssuntos
Anticorpos Monoclonais Murinos/farmacocinética , Antineoplásicos/farmacocinética , Crioglobulinemia/prevenção & controle , Linfoma não Hodgkin/tratamento farmacológico , Troca Plasmática , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/sangue , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Simulação por Computador , Crioglobulinemia/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma não Hodgkin/sangue , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , RituximabRESUMO
AIMS: To determine the relationship between early markers of diabetes control and diabetic retinopathy (DR) in type 1 diabetes. METHODS: A historic cohort study was conducted on 712 patients from the CARéDIAB database. HbA1c and usual metabolic parameters were measured one year after diagnosis of diabetes. First occurrences of severe hypoglycemia and ketoacidosis during follow-up were selected as time-dependent markers of diabetes control. Data were analyzed in a Cox model using SPSS software to predict DR with significance level at p-value <0.05. RESULTS: In multivariate regression, any diabetic retinopathy was predicted by HbA1c (HRâ¯=â¯1.38; CIâ¯=â¯1.25-1.52; pâ¯<â¯0.0001), severe hypoglycemia (HRâ¯=â¯3; CIâ¯=â¯1.99-4.52; pâ¯<â¯0.0001), ketoacidosis (HRâ¯=â¯1.96; CIâ¯=â¯1.17-3.22; pâ¯=â¯0.009), and age at diagnosis (HRâ¯=â¯1.016; CIâ¯=â¯1.002-1.031; pâ¯=â¯0.02). Proliferative DR was predicted by HbA1c (HRâ¯=â¯1.67; CIâ¯=â¯1.51-1.79; pâ¯<â¯0.0001), severe hypoglycemia (HRâ¯=â¯3.67; CIâ¯=â¯2.74-5.25; pâ¯<â¯0.0001), and ketoacidosis (HRâ¯=â¯2.37; CIâ¯=â¯1.56-3.18; pâ¯<â¯0.0001). CONCLUSION: This study shows that the failure to achieve diabetes control after the first year of diagnosis as well as early episodes of acute diabetes complications may contribute to the occurrence of diabetic retinopathy in type 1 diabetes patients.
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Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Retinopatia Diabética/diagnóstico , Adolescente , Adulto , Glicemia/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Retinopatia Diabética/epidemiologia , Progressão da Doença , Diagnóstico Precoce , Feminino , Seguimentos , França/epidemiologia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/complicações , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Renal patients with diabetes mellitus are at very high risk of death before and after chronic dialysis initiation. Risk factors for death in this population are not clearly identified. METHODS: We performed a retrospective survival analysis in 861 patients with diabetes mellitus consecutively followed up in the 2000-13 period in a nephrology setting. RESULTS: The mean age was 70 ± 10 years [men 65.2%; diabetes duration 13.7 ± 10.3 years; mean estimated glomerular filtration rate (eGFR) 42.4 ± 21.0 mL/min/1.73 m2). During follow-up (median 60 months; up 15 years), 263 patients died (184 before and 79 after dialysis initiation) and 183 started chronic dialysis. In multivariate analyses, age, elevated systolic and low diastolic arterial pressures, peripheral artery disease, cancer, loop diuretic use and atrial fibrillation at baseline and acute kidney injury (AKI), heart failure (HF) and amputation during follow-up were identified as risk factors for death. After adjustments on these parameters, eGFRs at the time of the first outpatient visit-eGFR <45 mL/min/1.73 m2 {hazard ratio [HR] 1.58 [95% confidence interval (CI) 1.15-2.17]}, P = 0.005 and eGFR <30 [HR 1.53 (1.05-2.05)], P = 0.004, but not eGFR <60-were powerful risk factors for death. When initiation of dialysis was entered into the multivariate models, it was not associated with a risk of premature death [HR 1.19 (95% CI 0.91-1.55), P = 0.2069], even in patients >80 years of age [HR 1.08 (95% CI 0.64-1.81), P = 0.7793]. CONCLUSIONS: In patients with diabetes mellitus, high systolic and low diastolic arterial pressure, peripheral artery disease and development of AKI and HF are significant risk factors for death. In addition to these parameters, eGFR <45 mL/min/1.73 m2 at the time of referral is also a powerful risk factor for death.
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BACKGROUND: Vancomycin is usually administered after the dialysis sessions to patients undergoing hemodialysis. Administration of vancomycin during (as opposed to after) sessions would save time, and would be more acceptable to patients and staff, but may lead to vancomycin underexposure. The aim of this study was to propose a new dosing regimen of vancomycin taking into account the dialysis-related losses of vancomycin when administered during dialysis. METHODS: In this monocentric prospective study, vancomycin was infused to dialyzed patients during the last hour of the dialysis session at increased doses. Monitoring of vancomycin was performed using repeated blood samples by pharmacokinetics modeling. Patients were treated according to our protocol and guidelines. RESULTS: Twenty patients were included. Vancomycin protocol was efficient: 17 of 20 (85%) patients were cured, 1 needed additional vancomycin treatment, and 2 died (sepsis n = 1, multiple organ failure n = 1). Median pre-dialysis concentration was adequate (16.2 [10.2-24.4] µg/mL), and there was no emergence of resistant bacteria. Infusion of vancomycin during dialysis therefore decreased the exposure to vancomycin by 25% compared to infusion of vancomycin after dialysis. For a typical patient, the dose of vancomycin to be administered during dialysis would be 1.4 g. CONCLUSION: Administration of vancomycin during the last hour of dialysis session is safe, efficacious with regards to infection control, achieved recommended vancomycin concentrations despite the use of high-flux membranes, and improved patients' quality of life.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Diálise Renal/métodos , Vancomicina/administração & dosagem , Vancomicina/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Infecções Relacionadas a Cateter/tratamento farmacológico , Simulação por Computador , Esquema de Medicação , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/sangueRESUMO
Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy.