Trimethoprim-sulfamethoxazole is a commonly used medication. Side effects are numerous and include drug hypersensitivity syndrome. The case of a 24-year-old woman with severe liver failure is presented. Erythema multiforme and thrombocytopenia developed after the acute onset of hepatotoxicity and after all medications had been stopped. Clinical resolution of all features occurred over weeks but laboratory abnormalities persisted up to eight months later. A causal link with sulfamethoxazole was supported by timing, liver biopsy and lymphocyte toxicity test. This case illustrates one presentation and the possible severity of the drug hypersensitivity syndrome associated with trimethoprim-sulfamethoxazole.
The Framingham risk score (FRS) and cardiovascular risk calculator for renal transplant recipients (CRCRTR-MACE) quantify cardiovascular risk in renal transplant recipients (RTR). In contrast to the FRS, the CRCRTR-MACE includes serum creatinine as a variable in the risk prediction equation.To determine the influence of impaired renal function on performances of the two equations.A chart review of 270 RTR transplanted from 1979 to 2012. High risk was defined at scores ≥20%. Standard statistical analyses included multivariate analysis (MVA), stepwise analysis, and odds ratio to estimate contributions of risk factors.Mean transplant duration was 9.51 ± 6.65 yr. Mean eGFR was 59.19 ± 28.26 mL/min/1.73 m(2) . FRS and CRCRTR-MACE scores of least 20% were present in 9.3% and 24.8%, respectively, while 7.2% and 11.2% of RTR with eGFR ≥60 mL/min/1.73 m(2) were high risk, respectively. Mean age, blood pressure, TC:HDL ratio, smoking, and diabetes were evenly distributed in patients with varying eGFR. FRS scores remained similar at wide eGFR range (≤30 mL/min/1.73 m(2) -≥90 mL/min/1.73 m(2) ), while CRCRTR-MACE scores significantly increased as eGFR decreased.CRCRTR-MACE identified more patients at high cardiovascular risk, even in those with more favorable renal function, suggesting a fundamental difference between the two calculators beyond renal function.
Cette etude a eu pour principal objectif de caracteriser les recepteurs α 1 -adrenergiques (RA) exprimes dans les adipocytes bruns des rats adultes. Pour ce faire, on a prepare des fractions de membranes provenant de tissu adipeux brun (TAB) ainsi que d'adipocytes bruns isoles. Ses principaux resultats sont : (i) les membranes de TAB ont ete considerablement enrichies en RA-α 1 (fixation specifique a la [ 3 H]prazosine, B max 79,49 ± 16,77 fmol/mg proteine ; K D 0,24 ± 0,04 nM) ; (ii) dans les cellules du TAB, les adipocytes bruns ont ete enrichis en RA-α 1 ; (iii) >95% des RA-α 1 ont resiste a une inactivation induite par une dose de 20 μM de chloroethylclonidine, qui a inactive facilement et totalement les RA-α 1B dans les membranes de foie de rat ; (iv) les RA-α 1 des membranes de TAB ont montre une haute affinite pour le 5-methyl urapidil (5-MU) (K D 7,23 ± 2,49 nM) et le WB 4101 (K D 0,66 ± 0,30 nM) et une faible affinite pour le BMY 7378 (K D 0,34 ± 0,03 μM) ; les membranes preparees d'adipocytes bruns ont montre des affinites similaires pour ces medicaments ; (v) une analyse EBDA/LIGAND des courbes de competition entre 5-MU, WB 4101 et BMY 7378 a revele la presence d'un seul site de fixation pour ces medicaments. Recemment, une etude a indique que le 5-MU et le WB 4101 interagissent avec une haute affinite avec les RA-α 1A , alors que le BMY 7378 interagit avec une haute affinite avec les RA-α 1D . Collectivement, ces resultats soutiennent l'idee que les RA-α 1 exprimes dans le TAB des rats adultes sont principalement du sous-type α 1A .
Increased plasma total homocysteine is a graded, independent risk factor for the development of atherosclerosis and thrombosis. More than 90% of patients with end-stage renal disease have hyperhomocysteinemia despite vitamin supplementation. It was shown in previous studies that a single intravenous dose of mesna 5 mg/kg caused a drop in plasma total homocysteine that was significantly lower than predialysis levels 2 d after dosing. It was hypothesized 5 mg/kg intravenous mesna administered thrice weekly, before dialysis, for 8 wk would cause a significant decrease in plasma total homocysteine compared with placebo.Patients with end-stage renal disease were randomly assigned to receive either intravenous mesna 5 mg/kg or placebo thrice weekly before dialysis. Predialysis plasma total homocysteine concentrations at weeks 4 and 8 were compared between groups by paired t test.Mean total homocysteine at 8 wk in the placebo group was 24.9 micromol/L compared with 24.3 micromol/L in the mesna group (n = 22 [11 pairs]; mean difference 0.63). Interim analysis at 4 wk also showed no significant difference between mesna and placebo (n = 32 [16 pairs]; placebo 26.3 micromol/L, mesna 24.5 micromol/L; mean difference 1.88). Multivariable adjustments for baseline characteristics did not alter the analysis. Plasma mesna seemed to reach steady-state concentrations by 4 wk.It is concluded that 5 mg/kg mesna does not lower plasma total homocysteine in hemodialysis patients and that larger dosages may be required.
Introduction Non-adherence after kidney transplantation contributes to increased rejections, hospitalisations and healthcare expenditures. Although effective adherence interventions are sorely needed, increasing education and support to transplant recipients demands greater use of care providers’ time and resources in a healthcare system that is stretched. The objective of this clinical trial is to determine the effectiveness of an electronically delivered video series and adherence behaviour contract on improving medication adherence to immunosuppressant medications. Methods and analysis A multicentre, parallel arm, randomised controlled trial will be conducted with four sites across North America (Saskatoon, Calgary, Halifax, Chicago). Adult patients will be randomised (1:1) to either the intervention (ie, home-based video education +behaviour contract plus usual care) or usual care alone. De novo transplant recipients will be enrolled prior to their hospital discharge and will be provided with electronic access to the video intervention (immediately) and adherence contract (1 month post-transplant). Follow-up electronic surveys will be provided at 3 and 12 months postenrolment. The primary outcome will be adherence at 12 months post-transplant, as measured by self-report Basel Assessment of Adherence to Immunosuppressive medications and immunosuppressant levels. Secondary outcomes include the difference in knowledge score between the intervention and control in groups (measured by the Kidney Transplant Understanding Tool); differences in self-efficacy (Generalised Self-efficacy Scale), Beliefs of Medicine Questionnaire (BMQ), quality of life (Short Form-12), patient satisfaction and cost utilisation. The study aims to recruit at least 200 participants across participating sites. Ethics and dissemination Ethical approval was obtained from the University of Saskatchewan Behavioural Ethics Committee (Beh 18–63), and all patients provide informed consent prior to participating. This educational intervention aims to improve information retention and self-efficacy, leading to improved medication adherence after kidney transplantation, at low cost, with little impact to existing healthcare personnel. If proven beneficial, delivery can be easily implemented into standard of care. Trial registration number NCT03540121 ; Pre-results.
Sub-optimal adherence to immunosuppressant medications reduces graft survival for kidney transplant recipients and adherence-enhancing interventions are resource and time intensive. We performed a multi-center randomized controlled trial to investigate the impact of an electronically delivered intervention on adherence. Of 203 adult kidney transplant recipients who received a de novo kidney transplant n = 173 agreed to participate (intent-to-treat population) and were randomized to the intervention (video education plus behavior contract n = 91) or the control (standard education, n = 82). No significant differences were found between the groups for medication adherence measured by the Basel Assessment of Adherence to Immunosuppressive Medications Scale, intrapatient variability in tacrolimus levels, time in therapeutic range for any immunosuppressant, knowledge, self-efficacy, QOL, or hospitalizations. Among a subgroup of 64 participants randomized to the intervention group who completed a post-intervention questionnaire, two-thirds (67%, n = 43) reported watching at least 80% of the videos and 58% (n = 37) completed the electronic goal setting exercise and adherence contract. An autonomous goal setting exercise and electronic behavioural contract added to standard of care did not improve any outcomes. Our findings reiterate that nonadherence in transplantation is a difficult multifactorial problem that simple solutions will not solve. Trial registration number NCT03540121.
SUMMARY: Background: N‐acetylcysteine (NAC) is commonly administered to high‐risk individuals to attenuate the risk of contrast‐induced nephropathy in spite of the debate regarding its efficacy. In several studies serum creatinine decreased after exposure to NAC and contrast dye. The mechanism by which NAC attenuates the decline in renal function is not known. Studies in subjects with normal renal function suggest NAC may have an effect on tubular secretion. Aim: The aim of this study was to determine the effect of NAC on renal function, measured by serum creatinine and Cystatin C, in patients with stage 3 chronic kidney disease. Method: Serum creatinine and Cystatin C were measured prior to, 4, 24 and 48 h after the administration of 600 mg oral NAC in 30 patients. The protocol was repeated with the addition of 1200 mg oral cimetidine administered 3 h before NAC. Results: Serum creatinine was not significantly different from baseline (186 ± 65 μmol/L) to 4 h (185 ± 62 μmol/L), 24 h (187 ± 64 μmol/L) or 48 h (184 ± 61 μmol/L) post NAC, nor were Cystatin C levels. Co‐administration of cimetidine resulted in a significant rise in serum creatinine with no change in Cystatin C levels. Conclusion: This study failed to detect a change in serum creatinine or Cystatin C after a single dose of NAC in participants with stage 3 chronic kidney disease. Further randomized trials of multiple doses and longer follow up are needed to confirm these results.
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