Prospective follow-up of primary CMV infections after 6 months of valganciclovir prophylaxis in renal transplant recipients

Background. The occurrence and clinical course of late primaryCMV infections developing after valganciclovir prophylaxis inhigh-risk renal transplant recipients are poorly described. Methods. Helsinki University Hospital district kidney allograftrecipients between January 2004 and March 2007 (N = 175) wereprospectively investigated. Patients with D+/R– CMV serostatusand 1-year follow-up were included (N = 25). After 6 monthsof oral valganciclovir prophylaxis, the patients were monitoredfor CMV-DNAemia with real-time quantitative plasma PCR at 2–6weeks interval and if CMV infection was suspected. Infectionswere treated with i.v. ganciclovir or high-dose valganciclovir,followed by 1–3 months of secondary valganciclovir prophylaxis. Results. CMV infection developed in 12/25 patients a mean of107 days (range 26–330 days) after prophylaxis ended.Two were asymptomatic. In 10 patients symptoms included fever(N = 7), gastrointestinal (N = 5), upper respiratory tract (N= 3) and hepatopathy (N = 2). One patient with infection hadprophylaxis terminated after 5 months (leukopenia). The meanviral load at diagnosis was 49 517 (range 490–325 300),and peak viral load was 84 654 (range 1250–527 400)copies/ml. Five infections were treated with valganciclovirand six with i.v. ganciclovir resulting with negative PCR results.One mild infection with low viral load was treated successfullywith minimization of immunosuppression. Infection relapse developedin three patients a mean of 31 (range 15–61) days afterthe end of the therapy. Relapses were treated with valganciclovir. Conclusions. CMV primary infections were common after 6 monthsof valganciclovir prophylaxis and mostly symptomatic. Relapsescommonly occurred. Primary infections seem to be delayed, butwere not efficiently prevented by 6 months of prophylaxis.     

Access to kidney transplantation in European adults aged 75–84 years and related outcomes: an analysis of the European Renal Association–European Dialysis and Transplant Association Registry

To what extent access to, and allocation of kidney transplants and survival outcomes in patients aged ≥75 years have changed over time in Europe is unclear. We included patients aged ≥75–84 years (termed older adults) receiving renal replacement therapy in thirteen European countries between 2005 and 2014. Country differences and time trends in access to, and allocation of kidney transplants were examined. Survival outcomes were determined by Cox regression analyses. Between 2005 and 2014, 1392 older adult patients received 1406 transplants. Access to kidney transplantation varied from ~0% (Slovenia, Greece and Denmark) to ~4% (Norway and various Spanish regions) of all older adult dialysis patients, and overall increased from 0.3% (2005) to 0.9% (2014). Allocation of kidney transplants to older adults overall increased from 0.8% (2005) to 3.2% (2014). Seven‐year unadjusted patient and graft survival probabilities were 49.1% (95% confidence interval, 95% CI: 43.6; 54.4) and 41.7% (95% CI: 36.5; 46.8), respectively, with a temporal trend towards improved survival outcomes. In conclusion, in the European dialysis population aged ≥75–84 years access to kidney transplantation is low, and allocation of kidney transplants remains a rare event. Though both are increasing with time and vary considerably between countries. The trend towards improved survival outcomes is encouraging. This information can aid informed decision‐making regarding treatment options.     

Patient injury claims involving fractures of the distal radius

Background and purpose — Optimal treatment for distal radius fractures remains controversial, with a significant number of fractures resulting in complications and long-term morbidity. We investigated patient injury claims related to distal radius fractures to detect the critical steps in the treatment leading to avoidable adverse events

Patients and methods — We analyzed all compensated patient injury claims in Finland between 2007 and 2011. Claims were collected from the Patient Insurance Center’s (PIC) nationwide claim register. Patients of all ages were included. Each claim decision, original patient records, and radiographs related to treatment were reviewed.

Results — During the study period, the PIC received 584 claims regarding distal radius fractures, of which 208 (36%) were compensated. Pain and impaired wrist function were the most common subjective reasons to file claims among compensated patients. In 66/208 patients, more than 1 adverse event leading to patient injury was detected. The detected adverse events could be divided into 3 main groups: diagnostic errors (36%, n = 103), decision/planning errors (30%, n = 87), and insufficient technical execution (32%, n = 91). Issues related to malalignment were the main concerns in each group. Diagnostic errors were often related to incorrect assessment of the fracture (re)displacement (75%, n = 78). All of the decision-making errors concerned physicians’ decisions to accept unsatisfactory fracture alignment. The most common technical error was insufficient reduction (29%, n = 26).

Interpretation — We identified avoidable adverse events behind patient injuries related to distal radius fracture treatment. This study will help physicians to recognize the critical steps in the treatment of this common fracture and enhance patient safety.     

N100 Auditory Potential and Electroencephalogram Discriminate Propofol-Induced Sedation Levels

OBJECTIVE: In the present study, we evaluated the electroencephalogram (EEG) and auditory N100 potential (N100) before and during propofol-induced sedation. The aim was to test whether using EEG and N100 the level of sedation may be evaluated. METHODS: Twenty-nine cardiac surgery patients were studied. The EEG signal and the N100 potential were recorded at awake one day before the cardiac operation and two times after the operation, when the clinical level of postoperative propofol sedation was considered deep (Ramsay Score 6) and moderate (Ramsay Score 4). Discriminant analysis was used to select those spectral EEG and/or N100 variables which would predict the correct level of sedation best. The final classification was based on canonical discriminant functions and Mahalanobis' distance. RESULTS: The spectral EEG variables (slow/fast-ratio, delta, and beta2 powers) predicted the correct level of sedation with 81% (canonical discriminant functions) and 80% (Mahalanobis' distance) accuracy. Similarly, the N100 (amplitude, latency, and the first principal component) predicted the correct level of sedation with 91% and 92% accuracy, and the combination of the EEG and N100 with 96% and 93% accuracy. CONCLUSIONS: Our findings suggest that the combined use of EEG and N100 may help to differentiate the propofol-induced sedation levels, and thus be a useful compliment to clinical sedation scales.     

Altered cardiovascular autonomic regulation after salmeterol treatment in asthmatic children

The effects of therapeutic 4 weeks' inhaled salmeterol treatment on the cardiovascular and respiratory autonomic nervous regulation was studied in 11 asthmatic children using inhaled corticosteroid medication. The study followed a randomized, double-blind, placebo-controlled cross-over design. The salmeterol dose was 50 μg twice daily. The 4-week salmeterol treatment increased baseline heart rate, low-frequency/high-frequency (LF/HF) variability ratio of R–R intervals, LF variability of systolic arterial pressure (SAP) and maximum tidal volume during the deep breathing test, as well as morning and evening peak expiratory flow (PEF) values. The 4-week salmeterol treatment decreased baseline HF variability of R–R intervals. As a response to the acute 600 μg of salbutamol, the changes in heart rate, HF variability of R–R intervals and diastolic blood pressure were significantly smaller after 4 weeks' salmeterol treatment. In conclusion, 4 weeks' therapeutic salmeterol treatment decreases basal cardiovagal reactivity, increases sympathetic dominance in the cardiovascular autonomic balance and improves pulmonary function. A tolerance develops in the cardiovascular response but not in the bronchodilatory response.     

Impact of glucose metabolism abnormalities on histopathological changes in kidney transplant protocol biopsies

The impact of post‐transplant diabetes (PTDM) on kidney transplant histopathology has been poorly described. We examined the association of glucose metabolism abnormalities on the progression of histopathological changes in serial protocol biopsies. Helsinki University Hospital kidney transplant recipients during 2004–2006 were followed up. Patients with pre‐existing diabetes or 2‐h oral glucose tolerance test (OGTT) performed at 3 months, and protocol biopsies taken at 0 and 12 months were analyzed (n = 76). Diabetes was defined according to WHO/ADA. Histology was analyzed with chronic allograft damage index (CADI). Altogether 32 patients had pre‐existing diabetes. In OGTT at 3 months, four showed PTDM, eight impaired glucose tolerance (IGT), two impaired fasting glucose, and 30 normal glucose tolerance. Patients with impaired glucose metabolism were older (P = 0.005), received grafts from older donors (P = 0.04), and had reduced renal function at 12 months (P = 0.003). In patients with IGT or PTDM, 2‐h postload glucose values in OGTT correlated with CADI at 12 months (R = 0.84, P = 0.001) and with the change in CADI score between 0 and 12 months (R = 0.67, P = 0.025). Graft survival was reduced in patients with pre‐existing diabetes (P = 0.01). Glucose abnormalities were associated with the progression of histopathological changes, especially in patients with already compromised kidneys, supporting the harmful role of PTDM to the kidney allograft.     

Early initiation of enzyme replacement therapy improves metabolic correction in the brain tissue of aspartylglycosaminuria mice

Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in many somatic tissues, but has only limited efficacy in the brain tissue of the animals. In the current work, ERT of AGU mice was initiated at the age of 1 week with three different dosage schedules of recombinant glycosylasparaginase. The animals received either 3.4 U of AGA/kg every second day for 2 weeks (Group 1), 1.7 U/kg every second day for 9 days followed by an enzyme injection once a week for 4 weeks (Group 2) or 17 U/kg at the age of 7 and 9 days (Group 3). In the Group 1 and Group 3 mice, ERT reduced the amount of aspartylglucosamine by 34 and 41% in the brain tissue, respectively. No therapeutic effect was observed in the brain tissue of Group 2 mice. As in the case of adult AGU mice, the AGA therapy was much more effective in the somatic tissues than in the brain tissue of the newborn AGU mice. The combined evidence demonstrates that a high dose ERT with AGA in newborn AGU mice is up to twofold more effective in reducing the amount of the accumulated storage material from the brain tissue than ERT in adult AGU animals, indicating the importance of early detection and treatment of the disease.     

Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmacokinetics and neonatal exposure

Physiological changes during pregnancy may change pharmacokinetics of compounds. Oxycodone is an increasingly used opioid agonist in acute pain management but its pharmacokinetics in labouring women has not been established. We studied the maternal pharmacokinetics and neonatal exposure of intravenous oxycodone for pain relief in the first stage of labour. The study was prospective, open‐labelled and with a control group. After informed consent, 15 nulliparous parturients and newborns, and newborns in a control group were studied. In the study group, oxycodone boluses of 1 mg i.v., up to a cumulative dose of 5 mg, was administered when labour pain score was 5/10 or higher. As the control group, 30 other newborns after uncomplicated deliveries with no systemic opioids were assessed for the neonatal outcome. In the study group, maternal pharmacokinetics of oxycodone was measured from plasma concentrations during labour, and neonatal exposure was assessed from umbilical plasma samples using population pharmacokinetic methods. Maternal plasma oxycodone concentration decreased with a median half‐life of 2.6 hr (range, 1.8–2.8). Oxycodone concentrations in the umbilical plasma 2.7 μg/l (0.3–14.5) were similar as in maternal plasma 2.4 (0.1–14.8) μg/l at the time of birth. No severe or unexpected adverse effects were noted. To conclude, firstly, maternal elimination half‐life of i.v. oxycodone was significantly shorter than that reported in non‐pregnant women, and secondly, maternal plasma oxycodone at the birth correlated well with neonatal umbilical concentrations and may, thus, be used as an estimate of neonatal exposure.