Patient survival after renal transplantation: IV. Impact of post-transplant diabetes

Patient survival after renal transplantation: IV. Impact of post-transplant diabetes.BackgroundThe development of de novo diabetes mellitus is a serious complication of kidney transplantation. This study examined the cardiovascular risk profile of patients with post-transplant diabetes (PTDM) and assessed the impact of PTDM on patient survival.MethodsThis analysis included 1811 adult, renal allograft recipients, transplanted in a single institution between 1983 and 1998. Patient survival was analyzed by univariable and multivariable Cox regression considering PTDM as a time dependent variable.ResultsAfter a follow-up period of 8.3 ± 4.5 years, 293 patients (20%) developed PTDM, 14% lost their graft, and 20% died. Compared to patients without DM (NoDM, N = 1186) patients with PTDM were significantly older (40 ± 14 vs. 48 ± 12 years, P < 0.001), heavier (76 ± 23 vs. 86 ± 25 kg, P < 0.001), and included more African Americans (18 vs. 28%, P = 0.001). In addition, the incidence of PTDM was significantly higher in patients who were transplanted after 1995 than prior to that year. In contrast, there were no significant differences between PTDM and patients who had DM before the transplant (DM; N = 332). Compared to NoDM, patients with PTDM had significantly higher total serum cholesterol and triglycerides (TG), higher systolic blood pressure and higher pulse pressure throughout the post-transplant period. Of interest, all of these abnormalities preceded the development of PTDM. Hypertriglyceridemia was particularly pronounced in PTDM and elevated TG levels correlated with the subsequent development of PTDM, independent of other risk factors (P = 0.001 by multivariate Cox). Compared to NoDM (16% mortality) a significantly higher percent of DM (31%, P < 0.001) and PTDM (22%, P = 0.005) patients died. By Cox regression, PTDM correlated with reduced patient survival (hazard ratio = 1.80, CI 1.35 to 2.41, P = 0.001), and that relationship was independent of other correlates of reduced survival that included: increasing age; transplant year; reduced serum albumin; and male sex.Conclusions: PTDM is associated with an unfavorable cardiovascular risk profile that precedes the development of hyperglycemia. PTDM is an independent predictor of reduced survival in renal allograft recipients

Distinguishing Increased Adiposity and/or Aerobic Deconditioning as Moderators of Low VO2peak in Obese Men

Peak oxygen uptake (V̇O2peak) in a cardiopulmonary exercise test (CPET) is a strong predictor of morbidity, mortality, and quality of life. V̇O2peak in obese individuals is typically below the lower limit of normal (2 transport and utilization, i.e. aerobic deconditioning; or both. We hypothesized a modified CPET, to measure the fraction of maximum isokinetic power that can be supported by aerobic metabolism, will distinguish between adiposity and deconditioning effects on V̇O2peak. PURPOSE: To compare V̇O2peak and isokinetic neuromuscular performance in obese vs non-obese men. METHODS: A modified CPET with maximal (3 s) isokinetic cycling power at baseline and the limit of ramp-incremental (RI) exercise was used to calculate: A) baseline maximum isokinetic power (Piso); B) tolerance index (TI), % of Piso at V̇O2peak; C) fatigue index (FI), % reduction in Piso per RI-watt at V̇O2peak; D) power reserve (PR), isokinetic power available at V̇O2peak expressed as % RI-wattpeak. The FRIEND nomogram was used to predict V̇O2peak. Data are mean(SD) and were assessed by t-test. RESULTS: Compared to controls (n=24), obese men (n=20) were older (32(5) vs 26(7) yr), had greater BMI (38(6) vs 23(2) kg/m2), but were not different in stature (177(5) vs 180(7) cm) or predicted V̇O2peak (3.49(0.49) vs 3.58(0.36) L/min). Obese men had lower V̇O2peak (2.84(0.42) vs 3.71(0.45) L/min, p2peak (82(15) vs 104(12) %, pIndependent of body mass, obese men had preserved leg strength (normal Piso), but the fraction of maximum isokinetic power supported by aerobic metabolism at RI intolerance was reduced (low TI) with greater fatigability (high FI); each consistent with aerobic deconditioning. A modified CPET with maximal isokinetic power measurements can distinguish the effects of increased adiposity from aerobic deconditioning on V̇O2peak in obese men

Frequency and phenotype associations of rare variants in 5 monogenic cerebral small vessel disease genes in 200,000 UK Biobank participants

BACKGROUND AND OBJECTIVES: Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extracerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of putative pathogenic variants in cSVD genes in the UK Biobank (UKB), a large population-based study. METHODS: We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in CTSA, TREX1, HTRA1, and COL4A1/2. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in the UKB's linked health data from UK hospital admissions, death records, and primary care. Among 199,313 exome-sequenced UKB participants, we assessed the following: the proportion of participants carrying ≥1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach. RESULTS: Among UKB participants, 0.5% had ≥1 variant(s) in studied genes. Using hospital admission and death records, 4%–20% of variant carriers per gene had an associated phenotype. This increased to 7%–55% when including primary care records. Only COL4A1 variant carrier status was significantly associated with having ≥1 phenotype-of-interest and a higher phenotype score (OR = 1.29, p = 0.006). DISCUSSION: While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only approximately half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity, and/or limited statistical power

Racial differences in renal allograft survival: The role of systemic hypertension

Racial differences in renal allograft survival: The role of systemic hypertension. The rate of decline in the number of functioning renal allografts beyond the first year after transplantation has changed little in the last 25 years, and during long-term follow-up most allografts are lost due to chronic transplant rejection or patient death. The recipient race correlates with allograft survival, and African American recipients have a lower allograft survival than Caucasians. The goal of the present study was to identify clinical variables present during the first six months after transplantation that predict the loss of renal allografts beyond six months after transplantation, and in particular to determine the role of systemic hypertension on renal allograft survival in black and white recipients. This study includes 547 recipients of first cadaveric renal allografts performed at The Ohio State University. All patients were treated with a uniform immunosuppressive protocol and had a follow-up of at least three years. By multivariate analysis the following variables correlate with poor allograft survival: an elevated serum creatinine concentration measured six months after transplantation (SCr6mo) (P < 0.0001); black race (P < 0.0001); increasing numbers of acute rejection episodes (ATR) (P = 0.002); and young recipients (P = 0.026). Allograft survival is significantly worse in black (mean allograft half-life of 7.7 ± 1.3 years) than in white recipients (24 ± 3 years) (P < 0.0001). Black recipients also have a significantly higher six month average mean arterial blood pressure (MAP) (105 ± 8 mm Hg) than white recipients (102 ± 7 mm Hg) (P = 0.002). However, the prevalence of hypertension is not significantly different in black (33%) than in white recipients (26%). Furthermore, increasing MAP levels correlate with a shorter allograft half-life in black recipients (P = 0.0002), but not in white recipients (P = 0.84). Allograft survival was eight times shorter in hypertensive black (3.1 ± 0.7 years) than in hypertensive white recipients (24.6 ± 7 years). In contrast, allograft survival was not statistically different between normotensive black and white patients. In conclusion, the presence of poorly controlled systemic hypertension, early after renal transplantation, correlates with poor allograft survival in black recipients. Thus, systemic hypertension may explain, in part, differences in renal allograft survival between black and white patients

The Opacity of Nearby Galaxies from Colors and Counts of Background Galaxies: I. The Synthetic Field Method and its Application to NGC 4536 and NGC 3664

We describe a new, direct method for determining the opacity of foreground galaxies which does not require any a priori assumptions about the spatial distribution or the reddening law of the obscuring material. The method is to measure the colors and counts of background galaxies which can be identified through the foreground system. The method is calibrated, and the effects of confusion and obscuration are decoupled by adding various versions of a suitable deep reference frame containing only field galaxies with known properties into the image of the foreground galaxy, and analyzing these ``synthetic field'' images in the same way as the real images. We test the method on HST WFPC2 archived images of two galaxies which are quite different: NGC 4536 is a large Sc spiral, and NGC 3664 is a small Magellanic irregular. The reference frames are taken from the Hubble Deep Field. From the background galaxy counts, NGC 4536 shows an extinction A_I ~ 1 mag in the northwestern arm region, and lower than 0.5 mag in the corresponding interarm region (no correction for inclination has been attempted). However, from the galaxy colors, the same reddening of E(V - I) ~ 0.2 is observed in both the arm and the interarm regions. In the interarm region, the combination of extinction and reddening can be explained by a diffuse component with a Galactic reddening law (R_V ~ 3). In the spiral arm, however, the same diffuse, low opacity component seems to coexist with regions of much higher opacity. Since the exposures are shorter the results for NGC 3664 are less clear, but also appear to be consistent with a two component distribution.Comment: 42 pages, 18 figures; accepted for publication in The Astrophysical Journal, Vol. 506, October 10, 199

The Empirical Foundations of Telemedicine Interventions for Chronic Disease Management

The telemedicine intervention in chronic disease management promises to involve patients in their own care, provides continuous monitoring by their healthcare providers, identifies early symptoms, and responds promptly to exacerbations in their illnesses. This review set out to establish the evidence from the available literature on the impact of telemedicine for the management of three chronic diseases: congestive heart failure, stroke, and chronic obstructive pulmonary disease. By design, the review focuses on a limited set of representative chronic diseases because of their current and increasing importance relative to their prevalence, associated morbidity, mortality, and cost. Furthermore, these three diseases are amenable to timely interventions and secondary prevention through telemonitoring. The preponderance of evidence from studies using rigorous research methods points to beneficial results from telemonitoring in its various manifestations, albeit with a few exceptions. Generally, the benefits include reductions in use of service: hospital admissions/re-admissions, length of hospital stay, and emergency department visits typically declined. It is important that there often were reductions in mortality. Few studies reported neutral or mixed findings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140284/1/tmj.2014.9981.pd

Physicians’ Perspectives on the Diagnosis and Treatment of Chronic Nonbacterial Osteomyelitis

Background/Purpose. Understanding the practices of pediatric rheumatologists in diagnosing and treating chronic nonbacterial osteomyelitis (CNO) can provide important information to guide the development of consensus treatment plans. The objectives of this study were to determine physicians’ approaches to (1) diagnosing and monitoring CNO, (2) ordering a bone biopsy, and (3) making treatment decisions. Methods. A survey was distributed among members of the Childhood Arthritis and Rheumatology Research Alliance using a web-based questionnaire. Results. 121 of 277 (41%) attending physician members completed the survey. Plain radiographs (89%) were most commonly used followed by regional MRI (78%), bone scintigraphy (43%), and whole-body MRI (36%). The top three reasons for performing a biopsy were constitutional findings (66%), unifocal bone lesions (64%), and nocturnal bone pain (45%). Nearly all responders (95%) prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) as initial therapy. For patients who failed NSAID treatment, methotrexate (67%), tumor necrosis factor inhibitors (65%), and bisphosphonates (46%) were the next most commonly used treatments. The presence of a spinal lesion increased the use of bisphosphonate treatment. Conclusion. The diagnostic approach and disease activity monitoring for CNO varied among surveyed physicians. Our survey findings provided important background for the development of consensus treatment plans for CNO

Predictors of contemporary coronary artery bypass grafting outcomes

n/

National Telemedicine Initiatives: Essential to Healthcare Reform

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78116/1/tmj.2009.9960.pd