Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children

The incidence of recurrence of nephrotic syndrome/focal segmental glomerulosclerosis (NS/FSGS) is variable (~30%). The incidence of recurrence is less in African-Americans than in whites and Hispanics. Graft survival rates are decreased in recipients with FSGS, especially if remission of the NS is not achieved in those with recurrence. Although controversial, the use of living donor (LD) transplants are not contraindicated; however, obligatory heterozygote parental grafts with a podocin mutation should be used with caution. Optimal treatment to induce a remission post-transplant has not been delineated. Pre-transplant and/or prophylactic post-transplant pre-operative plasmapheresis (PP) for high-risk patients—especially those with recurrence in a previous graft—may be promising. An international multicenter controlled study is required to delineate the optimal approach to prevent and/or treat the recurrence of NS/FSGS

Growth following solid organ transplantation in childhood

One of the ultimate goals of successful solid organ transplantation in pediatric recipients is attaining an optimal final adult height. This manuscript will discuss growth following transplantation in pediatric recipients of kidney, liver, heart, lung or small bowel transplants. Remarkably similar factors impact growth in all of these recipients. Age is a primary factor, with younger recipients exhibiting the greatest immediate catch-up growth. Graft function is a significant contributing factor, with a reduced glomerular filtration rate correlating with poor growth in kidney recipients and the need for re-transplantation with impaired growth in liver recipients. The known adverse impact of steroids on growth has led to modification of the steroid dose and even steroid withdrawal and avoidance. In kidney and liver recipients, this strategy has been associated with the development of acute rejection. In infant heart transplantation, avoiding maintenance corticosteroid immunosuppression is associated with normal growth velocity in the majority of patients. With marked improvements in patient and graft survival rates in pediatric organ recipients, quality of life issues, such as normal adult height, should now receive paramount attention. In general, normal growth following solid organ transplantation should be an achievable goal that results in normal adult height

Diamonds are Forever

We defend the thesis that every necessarily true proposition is always true. Since not every proposition that is always true is necessarily true, our thesis is at odds with theories of modality and time, such as those of Kit Fine and David Kaplan, which posit a fundamental symmetry between modal and tense operators. According to such theories, just as it is a contingent matter what is true at a given time, it is likewise a temporary matter what is true at a given possible world; so a proposition that is now true at all worlds, and thus necessarily true, may yet at some past or future time be false in the actual world, and thus not always true. We reconstruct and criticize several lines of argument in favor of this picture, and then argue against the picture on the grounds that it is inconsistent with certain sorts of contingency in the structure of time

Steady improvement in renal allograft survival among North American children: A five year appraisal by the North American Pediatric Renal Transplant Cooperative Study

Steady improvement in renal allograft survival among North American children. From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we have analyzed one and two year graft survival by annual cohorts for the years 1987 through 1991. For the 1987 cohort one and two year graft survival was 72% and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively. Using a proportional hazards model, and comparing the 1987 cohort to the 1991 cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of practice patterns revealed the following changes which may have been associated with this improved graft survival: (1) use of T cell induction antibody, 38% in 1987 and 67% in 1991 (P ≤ 0.001); (2) the increased use of cyclosporine (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to 97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12 months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991 (P = 0.03); (4) the decreased use of random transfusions, 54% receiving >5 transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use of younger cadaver donors between 1987 and 1991 (P < 0.001)

Growth hormone prevents steroid-induced growth depression in health and uremia

Growth hormone prevents steroid-induced growth depression in health and uremia. Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normallized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed and ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed

Are we under-utilizing the talents of primary care personnel? A job analytic examination

BACKGROUND: Primary care staffing decisions are often made unsystematically, potentially leading to increased costs, dissatisfaction, turnover, and reduced quality of care. This article aims to (1) catalogue the domain of primary care tasks, (2) explore the complexity associated with these tasks, and (3) examine how tasks performed by different job titles differ in function and complexity, using Functional Job Analysis to develop a new tool for making evidence-based staffing decisions. METHODS: Seventy-seven primary care personnel from six US Department of Veterans Affairs (VA) Medical Centers, representing six job titles, participated in two-day focus groups to generate 243 unique task statements describing the content of VA primary care. Certified job analysts rated tasks on ten dimensions representing task complexity, skills, autonomy, and error consequence. Two hundred and twenty-four primary care personnel from the same clinics then completed a survey indicating whether they performed each task. Tasks were catalogued using an adaptation of an existing classification scheme; complexity differences were tested via analysis of variance. RESULTS: Objective one: Task statements were categorized into four functions: service delivery (65%), administrative duties (15%), logistic support (9%), and workforce management (11%). Objective two: Consistent with expectations, 80% of tasks received ratings at or below the mid-scale value on all ten scales. Objective three: Service delivery and workforce management tasks received higher ratings on eight of ten scales (multiple functional complexity dimensions, autonomy, human error consequence) than administrative and logistic support tasks. Similarly, tasks performed by more highly trained job titles received higher ratings on six of ten scales than tasks performed by lower trained job titles. Contrary to expectations, the distribution of tasks across functions did not significantly vary by job title. CONCLUSION: Primary care personnel are not being utilized to the extent of their training; most personnel perform many tasks that could reasonably be performed by personnel with less training. Primary care clinics should use evidence-based information to optimize job-person fit, adjusting clinic staff mix and allocation of work across staff to enhance efficiency and effectiveness

Competing risks survival analysis applied to data from the Australian Orthopaedic Association National Joint Replacement Registry

BACKGROUND AND PURPOSE: The Kaplan-Meier (KM) method is often used in the analysis of arthroplasty registry data to estimate the probability of revision after a primary procedure. In the presence of a competing risk such as death, KM is known to overestimate the probability of revision. We investigated the degree to which the risk of revision is overestimated in registry data. PATIENTS AND METHODS: We compared KM estimates of risk of revision with the cumulative incidence function (CIF), which takes account of death as a competing risk. We considered revision by (1) prosthesis type in subjects aged 75–84 years with fractured neck of femur (FNOF), (2) cement use in monoblock prostheses for FNOF, and (3) age group in patients undergoing total hip arthroplasty (THA) for osteoarthritis (OA). RESULTS: In 5,802 subjects aged 75–84 years with a monoblock prosthesis for FNOF, the estimated risk of revision at 5 years was 6.3% by KM and 4.3% by CIF, a relative difference (RD) of 46%. In 9,821 subjects of all ages receiving an Austin Moore (non-cemented) prosthesis for FNOF, the RD at 5 years was 52% and for 3,116 subjects with a Thompson (cemented) prosthesis, the RD was 79%. In 44,365 subjects with a THA for OA who were less than 70 years old, the RD was just 1.4%; for 47,430 subjects > 70 years of age, the RD was 4.6% at 5 years. INTERPRETATION: The Kaplan-Meier method substantially overestimated the risk of revision compared to estimates using competing risk methods when the risk of death was high. The bias increased with time as the incidence of the competing risk of death increased. Registries should adopt methods of analysis appropriate to the nature of their data.Marianne H. Gillam, Philip Ryan, Stephen E. Graves, Lisa N. Miller, Richard N. de Steiger and Amy Salte