The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction ...of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study.
Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised.
Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs.
Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of ...patients with ANCA associated vasculitis treated with current regimens is uncertain.
To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease.
Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models.
The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival.
Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
Granulomatosis with polyangiitis and microscopic polyangiitis are ANCA-associated vasculitides (AAVs). The Vasculitis Damage Index (VDI) quantifies damage. This study aims to determine the factors ...associated with long-term damage in the AAVs.
Data from 535 patients from four European Vasculitis Study Group trials were studied. A long-term follow-up (LTFU) questionnaire at 7 years post-diagnosis was completed. The associations between baseline (age, creatinine and BVAS score) and cumulative (number of relapses and duration of glucocorticoid use) factors and damage accrued (total VDI scores and individual treatment-related damage items) during follow-up were explored. Multiple regressions identified independent associations between baseline measures, cumulative factors and VDI scores at LTFU.
Two hundred and ninety-six patients had glucocorticoid use and VDI data available at LTFU, with the mean length of glucocorticoid use being 40.4 months (S.D. 16.7). High levels of damage were independently associated with older age at baseline (P = 0.051), lower glomerular filtration rate (P = 0.041), higher BVAS scores (P = 0.046), increased cumulative glucocorticoid use (P = 0.016) and increasing number of relapses. Patients with longer duration of glucocorticoid treatment were more likely to have a total VDI score ≥5 odds ratio 1.26 per 12 months of glucocorticoid use (95% CI 1.03, 1.53), P = 0.022. The main limitation is that approximately half of the patients enrolled had no LTFU data available; these patients were older with more severe initial disease.
Long-term damage in the AAVs may be associated with severity of initial disease, age, number of relapses and duration of glucocorticoid use.
Recipient age and donor age are well-known prognostic factors in adult heart transplantation. However, the association between donor age and recipient age and their interaction and short- and ...long-term mortality is unknown.
We studied 64,354 heart transplants to adult recipients between 1988 and 2013 in the ISHLT Registry. Donor age and recipient age were analyzed as continuous and categorical variables and restricted cubic spline functions to assess non-linear associations and interactions. The end-point was all-cause mortality.
In the multivariable analysis, the odds ratio for 30-day mortality per 10-year increase in recipient age was 1.05 (95% confidence interval CI 1.01 to 1.08, p = 0.009) compared with 1.19 (95% CI 1.15 to 1.22, p < 0.001) for donor age. In the first year, the hazard ratio for mortality was 1.05 (95% CI 1.02 to 1.07, p < 0.001) for a 10-year increase in recipient age and 1.16 (1.14 to 1.18, p < 0.001) for donor age. In Years 1 to 3, 3 to 5, and 5 to 10 post-transplant, the hazard ratio was 0.89 (95% CI 0.86 to 0.92, p < 0.001), 0.98 (95% CI 0.94 to 1.02, p = 0.266), and 1.14 (95% CI 1.11 to 1.17, p < 0.001) for recipient age, and 1.12 (95% CI 1.08 to 1.14, p < 0.001), 1.07 (95% CI 1.03 to 1.10, p < 0.001), and 1.07 (95% CI 1.05 to 1.10, p < 0.001) for donor age, respectively. There was no interaction of recipient age and donor age with survival at any follow-up time-point.
At 30 days, both higher donor age and recipient age were associated with higher mortality. At 1 to 10 years, older donor age was associated with higher mortality at all follow-up time-points, but the hazard was greater in the short term, and recipient age was associated only with longer term mortality. The risk from donor age appears equal across recipient age groups.
Purpose
To examine the impact of systematic medication reconciliations upon hospital admission and of a medication review while in hospital on the number of inappropriate medications and unscheduled ...drug-related hospital revisits in elderly patients.
Methods
This was a prospective, controlled study in 210 patients, aged 65 years or older, who were admitted to one of three internal medicine wards at a University Hospital in Sweden. Intervention patients received the complete Lund Integrated Medicines Management model (medication reconciliation upon admission and discharge, and medication review and monitoring) provided by a multi-professional team, including a clinical pharmacist. Control patients received standard care and medication reconciliation upon discharge. Blinded reviewers evaluated the appropriateness of the prescribing (using the Medication Appropriateness Index) on admission and discharge, and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within 3 months of discharge (using World Health Organisation causality criteria).
Results
There was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population {51% 95% confidence interval (CI) 43–58% vs. 39% (95% CI 30–48%);
p
= 0.0446} and the per-protocol population 60% (95% CI 51–67%) vs. 44% (95% CI 34–52%);
p
= 0.0106). There were six revisits to hospital in the intervention group which were judged as ‘possibly, probably or certainly drug-related’, compared with 12 in the control group (
p
= 0.0469).
Conclusions
In this study, medication reconciliation and review provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits among elderly patients.
Abstract Background There is little consensus on a standard approach to analysing bone scan images. The Bone Scan Index (BSI) is predictive of survival in patients with progressive prostate cancer ...(PCa), but the popularity of this metric is hampered by the tedium of the manual calculation. Objective Develop a fully automated method of quantifying the BSI and determining the clinical value of automated BSI measurements beyond conventional clinical and pathologic features. Design, setting, and participants We conditioned a computer-assisted diagnosis system identifying metastatic lesions on a bone scan to automatically compute BSI measurements. A training group of 795 bone scans was used in the conditioning process. Independent validation of the method used bone scans obtained ≤3 mo from diagnosis of 384 PCa cases in two large population-based cohorts. An experienced analyser (blinded to case identity, prior BSI, and outcome) scored the BSI measurements twice. We measured prediction of outcome using pretreatment Gleason score, clinical stage, and prostate-specific antigen with models that also incorporated either manual or automated BSI measurements. Measurements The agreement between methods was evaluated using Pearson’s correlation coefficient. Discrimination between prognostic models was assessed using the concordance index (C-index). Results and limitations Manual and automated BSI measurements were strongly correlated (ρ = 0.80), correlated more closely (ρ = 0.93) when excluding cases with BSI scores ≥10 (1.8%), and were independently associated with PCa death ( p < 0.0001 for each) when added to the prediction model. Predictive accuracy of the base model (C-index: 0.768; 95% confidence interval CI, 0.702–0.837) increased to 0.794 (95% CI, 0.727–0.860) by adding manual BSI scoring, and increased to 0.825 (95% CI, 0.754–0.881) by adding automated BSI scoring to the base model. Conclusions Automated BSI scoring, with its 100% reproducibility, reduces turnaround time, eliminates operator-dependent subjectivity, and provides important clinical information comparable to that of manual BSI scoring.
Sarcopenia and poor physical function are common in patients with chronic kidney disease (CKD). Our aim was to investigate the relationships between muscle mass and measured glomerular filtration ...rate (GFR) and between muscle mass and strength and balance, respectively, in patients with CKD stages 3-5.
This is a baseline data analysis of a randomized controlled clinical trial. A total of 148 adult patients with an estimated GFR <30 mL/min/1.72 m2, not on renal replacement therapy, irrespective of the number of comorbidities were included from the Department of Nephrology, Skåne University Hospital, Lund, from 2011 to 2016. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). GFR was measured by iohexol clearance. Balance was measured by functional reach and the Berg balance test and strength by handgrip strength and isometric quadriceps strength.
Measured GFR ranged from 8 to 55 mL/min/1.73 m2. Lean mass (P < 0.05), fat mass (P < 0.05), appendicular skeletal muscle (P < 0.001) and appendicular skeletal muscle index (P < 0.05) were associated with GFR. Functional reach was associated with leg lean mass (P < 0.05) and the Berg balance test score was associated with trunk lean mass (P < 0.05). Handgrip strength was associated with arm lean mass (P < 0.001). Isometric quadriceps strength was associated with leg lean mass (P < 0.001). More men (44%) suffered from low muscle mass than women (22%), whereas more women (36%) suffered from low muscle strength than men (26%). However, when combining both, men (16%) suffered from sarcopenia to a greater extent than women (8%).
Among patients with CKD stages 3-5, loss of lean body mass, especially appendicular skeletal muscle, was significantly related to GFR decline. Two important markers of physical function, balance and strength, were significantly related to muscle mass. Moreover, men were more prone to sarcopenia than women during kidney function decline.
Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients ...undergoing long-term follow-up who were randomly allocated to azathioprine after 3-6 months or after 12 months of cyclophosphamide treatment.
Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3-6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up.
Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio sHR for relapse was 1.63 (95% confidence interval 95% CI, 0.99 to 2.71), the composite of relapse or death hazard ratio HR was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79).
It remains uncertain whether converting to azathioprine after 3-6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy.
Objectives
The objectives were to survey MR safety incidents in Sweden during a 12-month period, to assess severity scores, and to evaluate the confidence of MR personnel in incident-reporting ...mechanisms.
Method
Data were collected within a web-based questionnaire on safety in clinical MR environments with CT for comparison. Data reported MR and CT safety incidents (human injury, material damage, and close calls), incident severity, and confidence of participants in incident-reporting systems.
Results
The study population consisted of 529 eligible participants. Participants reported 200 MR and 156 CT safety incidents. Among MR incidents, 16% were given the highest potential severity score. More MR workers (73%) than CT workers (50%) were confident in being aware of any incident occurring at their workplace. However, 69% MR workers (83% for CT) were not aware of reported incidents at their hospitals.
Conclusion
Safety incidents resulting in human injury, material damage, and close calls in clinical MR environments do occur. According to national risk assessment recommendations, risk level is high. Results indicated that MR personnel tend to a false sense of security, as a high proportion of staff members were sure that they would have been aware of any incident occurring in their own department, while in reality, incidents did occur without their knowledge. We conclude that false sense of security exists for MR.
Key Points
• Safety incidents in clinical MR environments still result in human injury and material damage.
• Severity level of MR incidents—assessed using Swedish national risk assessment recommendations—is high.
• Confidence of MR personnel in incident-reporting mechanisms is high, but reflects a false sense of security, as a high proportion of staff is unaware of reported incidents in the same workplace.
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