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The profile and trajectory of cognitive impairment in mitochondrial disease are poorly defined. This systematic review sought to evaluate the current literature on cognition in mitochondrial disease, and to determine future research directions. A systematic review was conducted, employing PubMed, Medline, Psycinfo, Embase and Web of Science, and 360‐degree citation methods. English language papers on adult patients were included. The literature search yielded 2421 articles, of which 167 met inclusion criteria. Case reports and reviews of medical reports of patients yielded broad diagnoses of dementia, cognitive impairment and cognitive decline. In contrast, systematic investigations of cognitive functioning using detailed cognitive batteries identified focal cognitive rather than global deficits. Results were variable, but included visuospatial functioning, memory, attention, processing speed and executive functions. Conclusions from studies have been hampered by small sample sizes, variation in genotype and the breadth and depth of assessments undertaken. Comprehensive cognitive research with concurrent functional neuroimaging and physical correlates of mitochondrial disease in larger samples of well‐characterized patients may discern the aetiology and progression of cognitive deficits. These data provide insights into the pattern and trajectory of cognitive impairments, which are invaluable for clinical monitoring, health planning and clinical trial readiness. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane.Methods: Seventy-two male Sprague-Dawley rats weighing 85 to 110 g were divided into two groups and seven subgroups. Group I consisted of rats on iron-deficient chow, and group II consisted of rats on normal chow. Both groups contained dialysis control subgroups (N = 12: IA, IID), dialyzed with Dianeal solution, and tissue control subgroups (N = 6: IE, IIN), in which rats were not dialyzed and catheters were not implanted. Study group I contained the following study subgroups (N = 12): (B) rats dialyzed with Dianeal solution containing 2 mg/L of iron dextran and (C) rats dialyzed with Dianeal solution containing 1 mg/L of iron dextran. Group IID was dialyzed with Dianeal solution containing 2 mg/dL of iron dextran. Study duration was 12 weeks with peritoneal equilibration tests (PETs) performed at baseline, 6 weeks, and 12 weeks. Prior to baseline, rats were placed on iron-deficient chow or normal chow for three weeks. Dialysis was performed with three 25 mL volume exchanges per day. Hematocrit (Hct), serum iron (Fe), and total iron binding capacity (TIBC) were determined for each study interval. After the final PET, the animals were sacrificed, and the peritoneal membrane was evaluated by gross inspection and light microscopy.Results: Rats on an iron-deficient diet developed severe iron-deficiency anemia after three weeks of the diet (Hct 27; Fe 21 to 23; TIBC 799 to 806). After 12 weeks, the rats remained anemic in groups A (Hct 34 +/- 0.9; Fe 16 +/- 2; TIBC 998 +/- 27) and IE (Hct 38 +/- 2.7), whereas the rats corrected anemia in group B (Hct 45.8 +/- 1.8; Fe 115 +/- 15; TIBC 546 +/- 77). The results were not significantly different from those of group IID (Hct 47.1 +/- 1.6; Fe 94 +/- 19; TIBC 516 +/- 46). In group C, Hct (44.8 +/- 2.1) and Fe (94 +/- 19) did not differ significantly from group IID, but TIBC (734 +/- 76) remained significantly higher than that in the group IID. Peritoneal iron deposits were not detected. The morphometric analysis of the submesothelial space did not reveal any difference in thickness between dialysis groups. PETs were not significantly different among groups.Conclusions: Intraperitoneal iron dextran supplementation in concentrations of 2 mg/L of dialysis solution is nontoxic to the peritoneum and effective in correcting iron deficiency in rats maintained on an iron-deficient diet. Iron dextran in concentration of 1 mg/L of dialysis solution may be sufficient for correcting a lesser degree of iron deficiency. [ABSTRACT FROM AUTHOR]

Therapeutic effectiveness is the overall effect of an intervention on clinical and quality-of-life measures. Traditionally, in peripheral arterial disease, this has been evaluated in terms of clinical outcomes only. The lack of correlation between quality-of-life and clinical measures means that these cannot adequately describe overall patient benefit or adverse effects from an intervention. Therefore, patient-based measures such as changes in disease-specific questionnaire scores must be included in the evaluation of therapeutic effectiveness., (Copyright 2001 by W.B. Saunders Company)

Background: The decline of residual renal function (RRF) on dialysis has been reported to be slower in peritoneal dialysis (PD) then hemodialysis (HD). However, some clinicians have questioned whether this reported difference might not be caused by selection bias. In particular, if continuous ambulatory PD (CAPD) delivers only marginally adequate therapy as some clinicians speculate, then perhaps those patients on CAPD with low glomerular filtration rate (GFR) are purposefully switched to HD. If true, transferring CAPD patients with low GFR to HD could create a selection bias that very well may account for the differences in GFR between PD and HD. This is particularly problematic if one then censors patients at the time of transfer from PD to HD from analysis (that is, patients are no longer followed in the study once they have switched treatment modalities). When this occurs, the data are said to be informatively censored, a term used by statisticians to describe any kind of systematic bias associated with censored or incomplete data. In particular, informative censoring occurs when patients who die or transfer to another modality very early have an associated lower starting GFR or higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship differs between PD and HD but is ignored in the analysis, then the results of such analysis may be biased., Methods: This article analyzes the decline in GFR among 141 incident dialysis patients (39 HD and 102 PD) undergoing either HD or PD at the University of Missouri-Columbia. The decline in GFR was modeled as a nonlinear function of time, taking into account the possibility that missing values of GFR may be associated with patient dropout (death, transfer to another modality, or transplantation). To safeguard against this possibility, we utilized a conditional nonlinear mixed-effects model. The model was used to fit and compare each patient's GFR data to time adjusting for the patient's treatment modality (HD vs. PD), cause of dropout (death, transfer, transplant, lost to follow-up/study ended), and time to dropout. The model allowed a comparison of the starting GFR and the rate of decline in GFR between PD and HD adjusting for these three factors., Results and Conclusions: The results of our analysis suggest that such informative censoring is independent of treatment modality and that even after correcting for dropout caused by death or transfer to another modality, patients starting on PD have a lower rate of decline in GFR (that is, better preservation of GFR) than patients starting on HD.

Side holes at the inflow tip are necessary for acute hemodialysis catheters without inflow end-hole. Most catheters for chronic dialysis, both single and dual lumen, are also provided with side holes. There are no data in support of the notion that side holes improve blood flow or prolong the life of chronic catheters. The opposite may be true. Firstly, the side holes are created by drilling and have rough edges as can be seen in scanning electron microscopy. Secondly, many times, while removing chronic catheters, either electively or because of obstruction, a clot is found at the tip of the catheter and anchored in the side hole(s). Such a clot is difficult to strip by a snare in situ. Thirdly, a difficult to remove clot is formed on the outer surface of the catheter and extends to the inside lumen. If so, the holes have no role in extending the life of the catheter. Fourthly, the heparin or other anticoagulant, which is instilled to the catheter lumen at the end of dialysis, may not reach the catheter tip and/or be leached out in the period between dialyses, thus, predisposing to clot formation at the tip of the lumen. Finally, if the inflow bore is occluded and the blood flows through the side holes, it is likely that the vein intima is sucked into the holes, becomes damaged and causes formation of the mural thrombus. In such a case these holes would not be beneficial in prolonging catheter life, but may even preclude the possibility of inserting another catheter into the same vein at a later date.

Objective: To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and advanced glycosylation end-product (AGE) formation in the peritoneal membrane in a diabetic rat model of peritoneal dialysis (PD)., Design: Thirty-three male Sprague-Dawley rats weighing between 275-300 g were divided into five groups: group C (n = 6), control rats implanted with a catheter but not dialyzed; group D (n = 5), diabetic rats implanted with a catheter but not dialyzed; group G (n = 7), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for overnight exchanges; group H (n = 8), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats implanted with a catheter and dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges (25 mL per exchange) were performed three times daily for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics., Results: The level of immunostaining was lowest in group C and highest in group G. Significant differences in immunostaining were seen between group C and group G (p < 0.001), group C and group H (p = 0.001), and group C and group I (p < 0.05). Significant differences were also found between group G and group D (p < 0.05), and between group G and group I (p < 0.05). Over time, the ratio of glucose concentration after 1 hour to glucose concentration at instillation (D/D0) decreased and the dialysate-to-plasma ratio (D/P) of urea increased. Significant differences in D/D0 glucose and D/P urea were found between group C and group H (D/D0: 0.40 +/- 0.01 vs 0.35 +/- 0.01, p < 0.05; D/P urea: 0.87 +/- 0.03 vs 0.97 +/- 0.02, p < 0.05)., Conclusions: These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solution. We conclude that use of icodextrin may help to slow the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Background: Residual renal function (RRF) plays an important role in dialysis patients. Studies in patients on maintenance dialysis suggest that RRF is better preserved in patients receiving peritoneal dialysis (PD) vis-à-vis those receiving hemodialysis (HD). We speculated that regardless of the patient's type of therapy, the estimate obtained for the rate of decline in glomerular filtration rate (GFR) may be biased because of informative censoring associated with patient dropout. Informative censoring occurs when patients who die or transfer to another modality very early have associated with them a lower starting GFR or a higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship is ignored in the analysis, then the estimate obtained of the rate of decline in GFR may be biased., Methods: In an attempt to determine if there is a relationship between patient dropout and the decline in GFR, we reanalyzed the CANUSA data by modeling GFR as a nonlinear function of time with the rate of decline being exponential., Results: This article highlights the significance of "informative censoring" when studying the decline of RRF on dialysis. The results show that for the CANUSA cohort, the mean initial GFR was significantly lower, and the rate of decline was significantly higher for patients who died or transferred to HD than for patients who were randomly censored or received a transplant. It is important to emphasize that the impact of informative censoring on previous analyses of the decline of RRF between PD versus HD is presently unclear. If bias caused by informative censoring is the same regardless of what therapy a patient is on, then conclusions from previous studies comparing the decline in GFR between PD and HD would still be valid. However, if the magnitude of the bias differs according to therapy, then additional adjustments would be needed to fairly compare the decline in GFR between PD and HD. Because this analysis is restricted to patients on PD, it would be scientifically incorrect to interpret previous studies solely on the basis of the results from this analysis., Conclusion: In any longitudinal study designed to estimate trends in an outcome measured over time, it is important that the analysis of the data takes into account any effect patient dropout may have on the estimated trend. This analysis demonstrates that among PD patients, both the starting GFR and the rate of decline in GFR are associated with patient dropout. Consequently, future studies aimed at estimating the rate of decline in GFR among PD patients should also account for any dependencies between dropout and GFR. Similarly, data analyzing for apparent differences in the rate of decline of GFR between PD and HD should also adjust for possible informative censoring.

Objective: To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD)., Study Design: Thirty-three male Sprague-Dawley rats weighing between 275 - 300 g were divided into 5 groups: group C (n = 6), control rats with catheter but not dialyzed; group D (n = 5), diabetic rats with catheter but not dialyzed; group G (n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H (n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics., Results: The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I (p < 0.001, p = 0.001, and p< 0.05 respectively). Significant differences were also found between group G and groups D and I (p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40+/-0.01 vs 0.35+/-0.01, p < 0.05); and between groups C and H for D/P urea (0.87+/-0.03 vs 0.97+/-0.02, p < 0.05)., Conclusions: These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Calcium channel blocker given intraperitoneally (i.p.) in rats was reported to increase urea D/P ratio without protein loss. Chlorpromazine (CP) given i.p. in humans was reported to increase ultrafiltration (UF) and urea clearance. We studied the effects of i.p. Diltiazem (DZ) (15 mg/kg) and i.p. chlorpromazine (0.25 mg/L dialysate)--given alone or in combination--on urea D/P ratio, dialysate protein (Dpro), glucose concentration (Dg), UF, and drainage volume (Vd). Six male Sprague-Dawley rats were studied. The rats underwent 21 consecutive 30-minute exchanges with 15 mL of 1.5% of Dianeal solution (Baxter Healthcare Inc., Deerfield, Illinois, U.S.A.). DZ or CP was added to the dialysis solution during exchanges 4-6 and 10-12. During exchange 16-18 both DZ and CP were added to the dialysis solution. Exchanges 1-3, 7-9, 13-15, and 19-21 were control exchanges performed with 1.5% Dianeal solution alone. The mean weight of the rats was 541.6 +/- 44 g. The animals' blood pressure remained stable during the study period. An increase in D/Purea ratio was observed with DZ, with CP, and with the two drugs in combination, without increase in dialysate protein loss. An increase in UF with a decrease in D/D0 was observed with DZ, with CP, and with the two drugs in combination, suggesting a mechanism other than osmotic gradient--such as increased blood flow or decreased surface tension.

Sexual harassment claims have increased substantially since 1990 and continue to be prominent in the Equal Employment Opportunity Commission's discrimination caseload. The authors surveyed high-level training and human resource practitioners in small, medium, and large health care organizations for suggestions to counter this trend. Three fourths of these professionals suggested that behavior modeling of strong policies combined with effective training helped. The survey results suggest seven preventive medicine strategies for reducing work-related sexual harassment incidents in health care organizations.

Objective: To determine if peritoneal dialysis modality has an impact on protein losses in dialysate., Design: Retrospective, cross-sectional study., Patients: 190 patients who had selected peritoneal dialysis were classified into one of four transport categories (high, high-average, low-average, or low) based on standard peritoneal equilibration test results. Patients were then assigned to continuous ambulatory peritoneal dialysis (CAPD) or nightly intermittent peritoneal dialysis (NIPD) based on membrane transport characteristics and individual preferences., Results: Patients with similar membrane transport characteristics had essentially no differences in dialysate protein and albumin losses whether treated with CAPD or NIPD., Conclusions: Although high transporters may be better managed with short-dwell therapies such as nocturnal intermittent peritoneal dialysis or daily ambulatory peritoneal dialysis, consistent marked decreases in protein losses cannot be cited as a benefit of NIPD over CAPD.

Objectives: To better define the targets for initiation of chronic dialysis, we compared the relationship between the normalized protein equivalent of nitrogen appearance (nPNA, g/kg standard weight/day) and weekly urea clearance (Kt) normalized to total body water (V) in predialysis chronic renal failure (CRF) patients and in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). We also studied the relationships of other nutritional parameters to weekly Kt/Vurea in CRF patients., Design: This cross-sectional study was a prospective observational design meant to study each patient once., Setting: The University Hospital and Clinics and Harry S. Truman VA Medical Center, Columbia, Missouri., Patients: Forty-five consecutive predialysis CRF patients were enrolled and the results compared with patients on CAPD and HD., Results: In CRF, the nPNA calculated from urea appearance correlated with the weekly Kt/Vurea (r = 0.57, p < 0.0001) and, using exponential best-fit, nPNA = 1.217 x (1-e-0.769Kt/V). This exponential relationship was similar to that for CAPD and both were different from that in patients on HD. Likewise, nPNAs, calculated from Kjeldahl nitrogen output, and weekly Kt/Vurea were correlated (r = 0.37, p = 0.014) and, using exponential best-fit, nPNA = 1.102(1-e-0.867Kt/V), similar to the relationship in patients on CAPD. Evidence is presented that these relationships are not explained only by mathematical coupling. There was a significant correlation between the weekly Kt/Vurea and 24-hour urinary creatinine excretion., Conclusions: The findings suggest that in CRF, as in CAPD, a weekly Kt/Vurea less than 2.0 is likely to be associated with a nPNA less than 0.9 g/kg standard weight. In CRF patients, initiation of chronic dialysis should be considered if weekly renal Kt/Vurea falls below 2.0 and a nPNA greater than 0.8 is desired.

Objectives: Since the introduction of the peritoneal equilibration test (PET), the 4-hour dialysate/plasma creatinine (D/P Cr) has been used by several authors for determining continuous ambulatory peritoneal dialysis (CAPD) prescriptions. However, the results have been unsatisfactory because the 4-hr D/P Cr does not accurately reflect the D/P Cr in 24-hr collections. The PET and the 24-hr dialysate collections differ in the duration of dwell and the tonicity and volume of dialysate, all of which influence the equilibrated D/P Cr. It can be assumed that the D/P Cr in 24-hr collections in these patients is closer to a 6-hr D/P Cr. Because a 6-hr PET is inconvenient, we developed a mathematical model to calculate the 5- and 6-hr D/P using the results of a standard PET., Design: In a retrospective analysis, D/P Cr ratios in 24-hr collections and D/P Cr ratios calculated from a mathematical formula were correlated. Using a mathematical model, the data collected fit an exponential relation of the type D/P = a(1-e-t/tau). The values of a and tau are unique for a given patient and were determined using a nonlinear regression technique. The formula performed well on our published data-the true and predicted 6-hr D/P Cr being 0.696 and 0.71, respectively., Setting: The University Hospital and Clinics, Dalton Cardiovascular Research Center and Dialysis Clinic, Inc., Columbia, Missouri., Patients: All CAPD patients on four 2-L exchanges/day at the time of the 24-hr collections were included., Interventions: None., Main Outcome Measures: Closeness of 4-hr and 6-hr D/P Cr values to those of 24-hr ratios., Results: The study group comprised 74 patients (age, mean +/- SEM: 56.4 +/- 1.8 yr) with 80 PETs and 145 (24-hr) collections. The interval between the two tests was 8.3 +/- 0.9 months (0-48.7 months). The median 24-hr D/P Cr of 0.760 did not differ significantly from the predicted median 6-hr D/P Cr of 0.755. A subgroup analysis, based on transport type, showed that this relationship was most precise in the high-average transporters. The predicted 6-hr D/P Cr was within 10% of the 24-hr D/P Cr in 48% of patients and within 20% in 77% of patients. The margin of error was greatest in the low transporters., Conclusions: To conclude, the 4-hr D/P Cr from a PET cannot be used interchangeably with the D/P Cr in the 24-hr dialysate collections, hence, the clearances calculated thereof will be inaccurate. Using the proposed model, it is feasible to use the 4-hr PET results to obtain 5- and 6-hr D/P Cr values. In our study, using this model, the extrapolated 6-hr D/P Cr is similar to the D/P Cr in 24-hr dialysate collections only in the high-average transporters. Hence, the best way to determine clearances in peritoneal dialysis patients is still by collecting 24-hr dialysates.