To evaluate the long-term reproducibility of diurnal intraocular pressure (IOP) patterns in patients with primary open-angle glaucoma (POAG).
Database study.
Ninety-two patients with POAG.
We ...reviewed the records of patients with POAG who underwent 4 diurnal IOP curve measurements 6 months apart with Goldmann applanation tonometry recorded in the sitting position at 9 am, 10 am, 11 am, noon, 2 pm, 3 pm, 4 pm, and 5 pm.
Intervisit agreement of IOP by time point and of diurnal IOP curve parameters (mean, standard deviation, range, maximum, maximum hour, minimum, and minimum hour) was assessed using intraclass correlation coefficients (ICCs). Analyses were performed in all eyes and separately in eyes with and without hypotensive medications, and in eyes naïve and non-naïve of filtering surgery.
Between-visit agreement of IOP values at each time point was generally poor, with ICCs ranging from 0.26 to 0.77 in all patients (1 of 8 time points with ICC >0.75), from -0.07 to 0.60 in patients without hypotensive medications (zero time points with ICC >0.75), from 0.29 to 0.80 in patients with hypotensive medications (3 time points with ICCs >0.75), from 0.21 to 0.68 in filtering surgery-naïve patients (zero time points with ICC >0.75), and from 0.21 to 0.87 in patients with previous filtering surgeries (5 time points with ICCs >0.75). The predictive value of the first diurnal IOP curve to estimate the risk of IOP fluctuations during the 3 subsequent curves was limited (only 6.4% of the patients with an IOP range ≥30% of the mean IOP on the first curve presented similar fluctuations on the 3 subsequent curves; 77.1% of the patients who did not have an IOP range ≥30% of the mean IOP on the first curve had an IOP range ≥30% of the mean IOP on at least 1 of the 3 subsequent curves).
Patients with POAG do not manifest a reproducible diurnal IOP pattern from month to month. A single diurnal IOP curve in patients with POAG poorly characterizes IOP fluctuations and has limited value in clinical practice.
Strong geographic variations in the incidence of end-stage renal disease (ESRD) are observed in developed countries. The reasons for these variations are unknown. They may reflect regional ...inequalities in the population's sociodemographic characteristics, related diseases, or medical practice patterns. In France, at the district level, the highest incidence rates have been found in the Nord-Pas-de-Calais region. This area, with a high population density and homogeneous healthcare provision, represents a geographic situation which is quite suitable for the study, over small areas, of spatial disparities in the incidence of ESRD, together with their correlation with a deprivation index and other risk factors. The Renal Epidemiology and Information Network is a national registry, which lists all ESRD patients in France. All cases included in the Nord-Pas-de-Calais registry between 2005 and 2011 were extracted. Adjusted and smoothed standardized incidence ratio (SIR) was calculated for each of the 170 cantons, thanks to a hierarchical Bayesian model. The correlation between ESRD incidence and deprivation was assessed using the quintiles of Townsend index. Relative risk (RR) and credible intervals (CI) were estimated for each quintile. Significant spatial disparities in ESRD incidence were found within the Nord-Pas-de-Calais region. The sex- and age-adjusted, smoothed SIRs varied from 0.66 to 1.64. Although no correlation is found with diabetic or vascular nephropathy, the smoothed SIRs are correlated with the Townsend index (RR: 1.18, 95% CI 1.00-1.34 for Q2; 1.28, 95% CI 1.11-1.47 for Q3; 1.30, 95% CI 1.14-1.51 for Q4; 1.44, 95% CI 1.32-1.74 for Q5). For the first time at this aggregation level in France, this study reveals significant geographic differences in ESRD incidence. Unlike the time of renal replacement care, deprivation is certainly a determinant in this phenomenon. This association is probably independent of the patients' financial ability to gain access to healthcare.
Background
Despite long‐term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long‐term outcome after early CNI ...withdrawal.
Methods
This intention‐to‐treat study assessed the 10‐year outcome of 108 patients randomly converted from a cyclosporine (CsA)—mycophenolate mofetil (MMF)—prednisone regimen to a dual therapy (CsA‐prednisone or MMF‐prednisone) at 3 months postgraft.
Results
At 10 years, 3.7% in the CsA group and 35.2% in the MMF group remained on the protocol regimen (P<.001). eGFR was higher in the MMF group (64.4±21 vs 49.7±14.7 mL/min/1.73 m², P<.001), although acute rejection (12 vs 4 in the CsA group, P=.03) and Class II DSA incidences were increased. CNI‐related toxicity (P=.019) and moderate‐to‐severe IF/TA (P=.004) were higher in the CsA group. Ten‐year graft and patient survivals were not different. In multivariate analysis, acute rejection remained the strongest predictor of graft loss (HR=11.64, 95% CI 5.05‐26.79, P<.0001).
Conclusions
MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.
Strong geographic variations in the incidence of end-stage renal disease (ESRD) are observed in developed countries. The reasons for these variations are unknown. They may reflect regional ...inequalities in the population's sociodemographic characteristics, related diseases, or medical practice patterns. In France, at the district level, the highest incidence rates have been found in the Nord-Pas-de-Calais region. This area, with a high population density and homogeneous healthcare provision, represents a geographic situation which is quite suitable for the study, over small areas, of spatial disparities in the incidence of ESRD, together with their correlation with a deprivation index and other risk factors.
The Renal Epidemiology and Information Network is a national registry, which lists all ESRD patients in France. All cases included in the Nord-Pas-de-Calais registry between 2005 and 2011 were extracted. Adjusted and smoothed standardized incidence ratio (SIR) was calculated for each of the 170 cantons, thanks to a hierarchical Bayesian model. The correlation between ESRD incidence and deprivation was assessed using the quintiles of Townsend index. Relative risk (RR) and credible intervals (CI) were estimated for each quintile.
Significant spatial disparities in ESRD incidence were found within the Nord-Pas-de-Calais region. The sex- and age-adjusted, smoothed SIRs varied from 0.66 to 1.64. Although no correlation is found with diabetic or vascular nephropathy, the smoothed SIRs are correlated with the Townsend index (RR: 1.18, 95% CI 1.00-1.34 for Q2; 1.28, 95% CI 1.11-1.47 for Q3; 1.30, 95% CI 1.14-1.51 for Q4; 1.44, 95% CI 1.32-1.74 for Q5).
For the first time at this aggregation level in France, this study reveals significant geographic differences in ESRD incidence. Unlike the time of renal replacement care, deprivation is certainly a determinant in this phenomenon. This association is probably independent of the patients' financial ability to gain access to healthcare.
Le patient greffé rénal est exposé à un risque accru de iatrogénie médicamenteuse (IM). Le but de l’étude est de mesurer l’impact des interventions du pharmacien clinicien sur l’IM évitable.
Les cas ...d’IM ont été recueillis sur 3 périodes : sans intervention, avec conciliation médicamenteuse (CM) d’entrée, et avec une CM d’entrée et entretien pharmaceutique de sortie. Les cas d’IM ont été classés selon leur nature, leur gravité et leur évitabilité.
Les patients inclus étaient majoritairement des hommes, d’environ 55 ans, en stade 3 d’IRC, greffés depuis moins de 3 mois ou depuis plus d’un an, avec des facteurs de risque cardiovasculaire, une néphropathie polykystique et en moyenne 9 médicaments/jour. Vingt pour cent des cas d’IM étaient évitables et majoritairement graves. À la période 1, 27,7 % des patients présentaient au moins un cas d’IM, 21,3 % à la période 2, et 17,4 % à la période 3 (p=0,03). Cent dix patients ont eu une CM à l’entrée avec en moyenne 0,6 divergence non intentionnelle/patient. Elle portait surtout sur des oublis de médicament (81 %) et concernait des médicaments des voies digestives et métaboliques (24,5 %), du système cardiovasculaire (23 %) et du système nerveux (23 %). Soixante-huit entretiens pharmaceutiques de sortie ont été réalisés, révélant des pratiques d’automédication.
Notre étude montre qu’une CM d’entrée associée à un entretien pharmaceutique de sortie pourrait être bénéfique pour réduire l’IM chez le patient greffé rénal. Il serait licite d’envisager une étude spécifique pour conforter ces résultats.
Drug related problems (DRP) can lead to severe consequences in kidney recipients. The aim of the study was to assess the impact of the clinical pharmacist interventions on the incidence of DRP.
The number of DRP were evaluated according to 3periods: Without intervention, with medication reconciliation at admission, and with medication reconciliation at admission associated with an interview with the clinical pharmacist at discharge.
Patients concerned were mainly men, 55years old (median age), stage3 of CKD, transplanted for less than 3months or more than 1year, with cardiovascular risk factors and receiving an average of 9drugs/day. Among the DRP, 20% were avoidable and severe in most cases. In period1, 27.7% patients had at least 1DRP, in period2, 21.3% patients had at least 1DRP, and in period3, 17.4% of patients had at least 1DRP (P=0.03). One hundred and ten patients had medication reconciliation at admission with a mean of 0.6unintentional discrepancies per patient (omission in 81% of cases). The main drugs involved concerned the digestive-metabolic (24.5%), cardiovascular (23%), and nervous (23%) system. Sixty-eight interviews at discharge were realized and revealed self-medication habits.
Our study shows that medication reconciliation at admission associated with an interview with the clinical pharmacist at discharge can help to reduce DRP in kidney recipients. Further studies are needed to confirm our results.
Nous rapportons un cas d’intoxication à la vancomycine chez un patient âgé de 43 ans. Le patient reçoit accidentellement 25g de vancomycine à la première injection. Une insuffisance rénale aiguë ...anurique survient rapidement. La vancomycinémie est mesurée à 360mg/L au moment de la prise en charge (norme 15–35mg/L). Nous débutons en urgence un traitement par hémodialyse intermittente (HDI) à visée toxicologique. Après huit séances d’hémodialyse quotidiennes (en dehors du jour de fermeture du centre d’hémodialyse), la vancomycinémie est à nouveau en zone thérapeutique. Trois séances supplémentaires sont nécessaires en raison d’une insuffisance rénale oligurique persistante. Trois semaines après la sortie de l’hospitalisation, la fonction rénale est à nouveau normale (créatininémie à 80micromol/L). À notre connaissance, il s’agit du premier succès décrit d’une technique d’HDI chez l’adulte dans le cadre d’une intoxication à la vancomycine compliquée d’insuffisance rénale aiguë anurique.
We report a case of a 43 years old man who was intoxicated by a 25g vancomycin overload. An anuric acute renal failure rapidly occured. The vancomycinemia was measured as high as 360mg/L (normal range: 15–35mg/L). We started an intermittent hemodialysis program to clear out the vancomycin. The vancomycinemia decreased below the treshold of our laboratory after the eighth session. Three supplementary sessions were needed because of a persistant oliguria. The kidney function slowly improved and was back to normal (seric creatinin: 80micromol/L) 3 weeks after the patient had gone home. To our knowledge, it is the first success of this technic concerning vancomycin poisoning in adults with anuric kidney failure.
En transplantation rénale, plusieurs scores ont été récemment développés afin d’aider la prise de décision en pratique clinique. L’objectif de cette mise au point est de mettre l’accent sur ces ...nouveaux scores qui permettent de mieux évaluer la qualité du greffon rénal, d’affiner la politique d’attribution, de guider l’inscription sur liste des receveurs âgés, ou encore d’estimer le risque de développer une insuffisance rénale terminale pour les donneurs vivants.
In renal transplant medicine, several scores have been recently developed in order to help decision-making in clinical practice. The aim of this update is to focus on these new scores that allow to better estimate the quality of the renal transplant, to refine the allocation policy, to help registration of old recipients on the waiting list, or to evaluate the risk to develop end-stage renal failure after living donation.
Abstract
The rabbit antithymocyte globulin
T
hymoglobulin first became available over 25 yr ago and is the most widely used lymphocyte‐depleting preparation in solid organ transplantation. ...Thymoglobulin targets a wide range of
T
‐cell surface antigens as well as natural killer‐cell antigens,
B
‐cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors, resulting in profound, long‐lasting
T
‐cell depletion. Randomized studies have established the anti‐rejection efficacy of
T
hymoglobulin in kidney transplantation. Experimental and clinical data suggest that
T
hymoglobulin administration may ameliorate ischemia reperfusion injury, thus reducing the incidence of delayed graft function (
DGF
). Studies have demonstrated the benefit of using
T
hymoglobulin to facilitate immunosuppression minimization, both for corticosteroid and calcineurin inhibitor (
CNI
) withdrawal or avoidance, with potential improvement in cardiovascular and renal outcomes. The optimal cumulative dose for
T
hymoglobulin induction is 6–7.5 mg/kg, with vigilant short‐ and long‐term monitoring of hematological status. Induction with
T
hymoglobulin is now indicated in immunologically high‐risk patients, in those at increased risk of
DGF
and to maintain efficacy in low‐risk transplant recipients receiving steroid or
CNI
minimization or avoidance regimens. We suggest that in future trials
T
hymoglobulin be tested with costimulation signal blockers and other immunosuppressants with the objective of establishing operational tolerance.
Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that ...tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients.
We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 transplant recipients who maintained good allograft function without immunosuppression for at least 1 year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.
We identified rare variants of
(3/36, FDR 0.0387),
(5/36, FDR 0.0362), and
(3/36, FDR 0.102) in 10 tolerant patients
. 0 controls. One patient carried a variant in both
and
. Furthermore, the three genes showed an identical variant in two patients each. The three genes are expressed at the primary cilium, a key structure in immune responses.
Rare protein coding variants are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.ClinicalTrials.gov, identifier: NCT05124444.
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