A programme to improve quality of care for patients with chronic diseases, Kazakhstan.

OBJECTIVE: To evaluate the effect of a disease management programme in Kazakhstan on quality indicators for patients with hypertension, diabetes and chronic heart failure. METHODS: A supportive, interdisciplinary, quality improvement programme was implemented between November 2014 and November 2015 at seven polyclinics in Pavlodar and Petropavlovsk. Quality improvement teams were established at each clinic and quality improvement tools were introduced, including patient flowsheets, decision support tools, patient registries, a patient recall process, support for patient self-management and patient follow-up with intensity adjusted for level of disease control. Clinic teams met for four 3-day interactive learning sessions within 1 year, with additional coaching visits. Implementation was managed by five local coordinators and consultants trained by international consultants. National and regional steering committees monitored progress. FINDINGS: Between July and October 2015, the proportion of hypertensive patients with the recommended blood pressure increased from 24% (101/424) to 56% (228/409). Among patients with diabetes, the proportion who recently underwent eye examinations increased from 26% (101/391) to 71% (308/433); the proportion who had their low-density lipoprotein cholesterol measured increased from 57% (221/391) to 85% (369/433); and the proportion who had their albumin : creatinine ratio measured increased from 11% (44/391) to 49% (212/433). The proportion of chronic heart failure patients who underwent echocardiography rose from 91% (128/140) to 99% (157/158). All patients set themselves self-management goals. CONCLUSION: This intensive, supportive, multifaceted programme was associated with significant improvements in quality of care for patients with chronic disease. Further investment in coaching capacity is needed to extend the programme nationally.

Promoting the use of self-management in novice chiropractors treating individuals with spine pain: the design of a theory-based knowledge translation intervention.

BACKGROUND: Clinical practice guidelines generally recommend clinicians use self-management support (SMS) when managing patients with spine pain. However, even within the educational setting, the implementation of SMS remains suboptimal. The objectives of this study were to 1) estimate the organizational readiness for change toward using SMS at the Canadian Memorial Chiropractic College (CMCC), Toronto, Ontario from the perspective of directors and deans, 2) estimate the attitudes and self-reported behaviours towards using evidence-based practice (EBP), and beliefs about pain management among supervisory clinicians and chiropractic interns, 3) identify potential barriers and enablers to using SMS, and 4) design a theory-based tailored Knowledge Translation (KT) intervention to increase the use of SMS. METHODS: Mixed method design. We administered three self-administered questionnaires to assess clinicians' and interns' attitudes and behaviours toward EBP, beliefs about pain management, and practice style. In addition, we conducted 3 focus groups with clinicians and interns based on the Theoretical Domain Framework (TDF) to explore their beliefs about using SMS for patients with spine pain. Data were analysed using deductive thematic analysis by 2 independent assessors. A panel of 7 experts mapped behaviour change techniques to key barriers identified informing the design of a KT intervention. RESULTS: Participants showed high level of EBP knowledge, positive attitude of EBP, and moderate frequency of EBP use. A number of barrier factors were identified from clinicians (N = 6) and interns (N = 16) corresponding to 7 TDF domains: Knowledge; Skills; Environmental context and resources; Emotion; Beliefs about Capabilities; Memory, attention & decision making; and Social Influence. To address these barriers, the expert panel proposed a multifaceted KT intervention composed of a webinar and online educational module on a SMS guided by the Brief Action Planning, clinical vignettes, training workshop, and opinion leader support. CONCLUSION: SMS strategies can help maximizing the health care services for patients with spine pain. This may in turn optimize patients' health. The proposed theory-based KT intervention may facilitate the implementation of SMS among clinicians and interns.

Testing the feasibility of training peers with a spinal cord injury to learn and implement brief action planning to promote physical activity to people with spinal cord injury.

OBJECTIVE: The present study tested the feasibility of training peers with spinal cord injury (SCI) to learn brief action planning (BAP), an application of motivational interviewing principles, to promote physical activity to mentees with SCI. METHOD: Thirteen peers with SCI attended a half-day BAP workshop. Using a one-arm, pre-, post-test design, feasibility to learn BAP was assessed in terms of peers' (1) BAP and motivational interviewing spirit competence; (2) training satisfaction; and (3) motivations to use BAP as assessed by measures of the theory of planned behavior constructs. Measures were taken at baseline, immediately post-training, and 1 month follow up. RESULTS: Following the training, participants' BAP and motivational interviewing competence significantly increased (P's < 0.05, d's > 2.27). Training satisfaction was very positive with all means falling above the scale midpoint. Participants' perceived behavioral control to use BAP increased from baseline to post (P < 0.05, d = 0.91) but was not maintained at follow up (P > 0.05). CONCLUSION: Training peers with a SCI to learn to use BAP is feasible. PRACTICAL IMPLICATIONS: BAP is a tool that can be feasibly learned by peers to promote physical activity to their mentees.

Racial variation in medical outcomes among living kidney donors.

BACKGROUND: Data regarding health outcomes among living kidney donors are lacking, especially among nonwhite persons. METHODS: We linked identifiers from the Organ Procurement and Transplantation Network (OPTN) with administrative data of a private U.S. health insurer and performed a retrospective study of 4650 persons who had been living kidney donors from October 1987 through July 2007 and who had post-donation nephrectomy benefits with this insurer at some point from 2000 through 2007. We ascertained post-nephrectomy medical diagnoses and conditions requiring medical treatment from billing claims. Cox regression analyses with left and right censoring to account for observed periods of insurance benefits were used to estimate absolute prevalence and prevalence ratios for diagnoses after nephrectomy. We then compared prevalence patterns with those in the 2005-2006 National Health and Nutrition Examination Survey (NHANES) for the general population. RESULTS: Among the donors, 76.3% were white, 13.1% black, 8.2% Hispanic, and 2.4% another race or ethnic group. The median time from donation to the end of insurance benefits was 7.7 years. After kidney donation, black donors, as compared with white donors, had an increased risk of hypertension (adjusted hazard ratio, 1.52; 95% confidence interval [CI], 1.23 to 1.88), diabetes mellitus requiring drug therapy (adjusted hazard ratio, 2.31; 95% CI, 1.33 to 3.98), and chronic kidney disease (adjusted hazard ratio, 2.32; 95% CI, 1.48 to 3.62); findings were similar for Hispanic donors. The absolute prevalence of diabetes among all donors did not exceed that in the general population, but the prevalence of hypertension exceeded NHANES estimates in some subgroups. End-stage renal disease was identified in less than 1% of donors but was more common among black donors than among white donors. CONCLUSIONS: As in the general U.S. population, racial disparities in medical conditions occur among living kidney donors. Increased attention to health outcomes among demographically diverse kidney donors is needed. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

Inhibition of CYP2C19 and CYP3A4 by omeprazole metabolites and their contribution to drug-drug interactions.

The aim of this study was to evaluate the contribution of metabolites to drug-drug interactions (DDI) using the inhibition of CYP2C19 and CYP3A4 by omeprazole and its metabolites as a model. Of the metabolites identified in vivo, 5-hydroxyomeprazole, 5'-O-desmethylomeprazole, omeprazole sulfone, and carboxyomeprazole had a metabolite to parent area under the plasma concentration-time curve (AUC(m)/AUC(p)) ratio ≥ 0.25 when either total or unbound concentrations were measured after a single 20-mg dose of omeprazole in a cocktail. All of the metabolites inhibited CYP2C19 and CYP3A4 reversibly. In addition omeprazole, omeprazole sulfone, and 5'-O-desmethylomeprazole were time dependent inhibitors (TDI) of CYP2C19, whereas omeprazole and 5'-O-desmethylomeprazole were found to be TDIs of CYP3A4. The in vitro inhibition constants and in vivo plasma concentrations were used to evaluate whether characterization of the metabolites affected DDI risk assessment. Identifying omeprazole as a TDI of both CYP2C19 and CYP3A4 was the most important factor in DDI risk assessment. Consideration of reversible inhibition by omeprazole and its metabolites would not identify DDI risk with CYP3A4, and with CYP2C19, reversible inhibition values would only identify DDI risk if the metabolites were included in the assessment. On the basis of inactivation data, CYP2C19 and CYP3A4 inhibition by omeprazole would be sufficient to identify risk, but metabolites were predicted to contribute 30-63% to the in vivo hepatic interactions. Therefore, consideration of metabolites may be important in quantitative predictions of in vivo DDIs. The results of this study show that, although metabolites contribute to in vivo DDIs, their relative abundance in circulation or logP values do not predict their contribution to in vivo DDI risk.

Tacrolimus placental transfer at delivery and neonatal exposure through breast milk.

AIM(S): The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. METHODS: Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. RESULTS: Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml(-1)) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml(-1)). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml(-1)) and unbound drug concentrations (0.003 ± 0.001 ng ml(-1)) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. CONCLUSIONS: Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.

Urine IL-18, NGAL, IL-8 and serum IL-8 are biomarkers of acute kidney injury following liver transplantation.

BACKGROUND: AKI is common following liver transplantation and is associated with significant morbidity and mortality. Biomarkers of AKI have not been well established in this setting but are needed to help guide patient care and facilitate development of novel therapeutics. METHODS: Serum creatinine, cystatin C, IL-6, and IL-8 and urine IL-18, NGAL, IL-6, and IL-8 were measured before and within 24 hours after liver transplantation in 40 patients. AKI was defined as a ≥50% sustained increase in creatinine above pre-operative values occurring within 24 hours of transplantation and persisting for at least 24 hours. RESULTS: Seven patients met criteria for AKI (17.5%), with mean creatinines of 0.81 mg/dL pre-operatively and 1.75 mg/dL post-operatively. While pre-operative biomarker levels in patients with AKI were similar to those in patients without AKI, differences were seen between the groups with regard to median post-operative serum IL-8 (pg/mL) (242.48 vs. 82.37, p = 0.0463) and urine NGAL (ng/mL) (386.86 vs. 24.31, p = 0.0039), IL-6 (pg/mL) (52 vs. 7.29, p=0.0532), IL-8 (pg/mL) (14.3 vs. 0, p = 0.0224), and IL-18 (pg/mL) (883.09 vs. 0, p = 0.0449). The areas under receiver operating characteristic (ROC) curves were 0.749 for urine IL-18, 0.833 for urine NGAL, 0.745 for urine IL-6, 0.682 for serum IL-6, 0.773 for urine IL-8, and 0.742 for serum IL-8. Post-operative cystatin C was not significantly different between AKI and no AKI groups. CONCLUSION: Serum IL-8 and urine IL-18, NGAL, IL-6, and IL-8 are elevated in AKI within the first 24 hours following liver transplantation.

An inducible cytochrome P450 3A4-dependent vitamin D catabolic pathway.

Vitamin D(3) is critical for the regulation of calcium and phosphate homeostasis. In some individuals, mineral homeostasis can be disrupted by long-term therapy with certain antiepileptic drugs and the antimicrobial agent rifampin, resulting in drug-induced osteomalacia, which is attributed to vitamin D deficiency. We now report a novel CYP3A4-dependent pathway, the 4-hydroxylation of 25-hydroxyvitamin D(3) (25OHD(3)), the induction of which may contribute to drug-induced vitamin D deficiency. The metabolism of 25OHD(3) was fully characterized in vitro. CYP3A4 was the predominant source of 25OHD(3) hydroxylation by human liver microsomes, with the formation of 4ß,25-dihydroxyvitamin D(3) [4ß,25(OH)(2)D(3)] dominating (V(max)/K(m) = 0.85 ml · min(-1) · nmol enzyme(-1)). 4ß,25(OH)(2)D(3) was found in human plasma at concentrations comparable to that of 1α,25-dihydroxyvitamin D(3), and its formation rate in a panel of human liver microsomes was strongly correlated with CYP3A4 content and midazolam hydroxylation activity. Formation of 4ß,25(OH)(2)D(3) in primary human hepatocytes was induced by rifampin and inhibited by CYP3A4-specific inhibitors. Short-term treatment of healthy volunteers (n = 6) with rifampin selectively induced CYP3A4-dependent 4ß,25(OH)(2)D(3), but not CYP24A1-dependent 24R,25-dihydroxyvitamin D(3) formation, and altered systemic mineral homeostasis. Our results suggest that CYP3A4-dependent 25OHD(3) metabolism may play an important role in the regulation of vitamin D(3) in vivo and in the etiology of drug-induced osteomalacia.

Pharmacokinetics of tacrolimus during pregnancy.

BACKGROUND: Information on the pharmacokinetics of tacrolimus during pregnancy is limited to case reports despite the increasing number of pregnant women being prescribed tacrolimus for immunosuppression. METHODS: Blood, plasma, and urine samples were collected over 1 steady-state dosing interval from women treated with oral tacrolimus during early to late pregnancy (n = 10) and postpartum (n = 5). Total and unbound tacrolimus as well as metabolite concentrations in blood and plasma were assayed by a validated liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method. A mixed-effect linear model was used for comparison across gestational age and using postpartum as the reference group. RESULTS: The mean oral clearance (CL/F) based on whole-blood tacrolimus concentration was 39% higher during mid-pregnancy and late pregnancy compared with postpartum (47.4 ± 12.6 vs. 34.2 ± 14.8 L/h, P < 0.03). Tacrolimus-free fraction increased by 91% in plasma (f(P)) and by 100% in blood (f(B)) during pregnancy (P = 0.0007 and 0.002, respectively). Increased fP was inversely associated with serum albumin concentration (r = -0.7, P = 0.003), which decreased by 27% during pregnancy. Pregnancy-related changes in f(P) and f(B) contributed significantly to the observed gestational increase in tacrolimus whole-blood CL/F (r² = 0.36 and 0.47, respectively, P < 0.01). In addition, tacrolimus whole-blood CL/F was inversely correlated with both hematocrit and red blood cell counts, suggesting that binding of tacrolimus to erythrocytes restricts its availability for metabolism. Treating physicians increased tacrolimus dosages in study participants during pregnancy by an average of 45% to maintain tacrolimus whole-blood trough concentrations in the therapeutic range. This led to striking increases in unbound tacrolimus trough concentrations and unbound area under the concentration-time curve, by 112% and 173%, respectively, during pregnancy (P = 0.02 and 0.03, respectively). CONCLUSIONS: Tacrolimus pharmacokinetics are altered during pregnancy. Dose adjustment to maintain whole-blood tacrolimus concentration in the usual therapeutic range during pregnancy increases circulating free drug concentrations, which may impact clinical outcomes.

Hepatorenal syndrome: the 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.

INTRODUCTION: Renal dysfunction is a common complication in patients with end-stage cirrhosis. Since the original publication of the definition and diagnostic criteria for the hepatorenal syndrome (HRS), there have been major advances in our understanding of its pathogenesis. The prognosis of patients with cirrhosis who develop HRS remains poor, with a median survival without liver transplantation of less than six months. However, a number of pharmacological and other therapeutic strategies have now become available which offer the ability to prevent or treat renal dysfunction more effectively in this setting. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. METHODS: We undertook a systematic review of the literature using Medline, PubMed and Web of Science, data provided by the Scientific Registry of Transplant Recipients and the bibliographies of key reviews. We determined a list of key questions and convened a two-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. RESULTS: Of the 30 questions considered, we found inadequate evidence for the majority of questions and our recommendations were mainly based on expert opinion. There was insufficient evidence to grade three questions, but we were able to develop a consensus definition for acute kidney injury in patients with cirrhosis and provide consensus recommendations for future investigations to address key areas of uncertainty. CONCLUSIONS: Despite a paucity of sufficiently powered prospectively randomized trials, we were able to establish an evidence-based appraisal of this field and develop a set of consensus recommendations to standardize care and direct further research for patients with cirrhosis and renal dysfunction.

The impact of current immunosuppression strategies in renal transplantation on the field of reconstructive transplantation.

Composite tissue allograft (CTA) transplantation, such as the clinical face and hand transplants, has now been performed in multiple centers across the world. The transplants have successfully treated complex injuries that have either failed conventional approaches or where autologous reconstruction could not restore both form and function. CTA transplantation has the potential to improve outcomes over traditional techniques. However, the widespread application of CTA transplantation continues to be limited by the need for chronic immunosuppression. Due to the small numbers of CTA transplants performed, any modification in the immunosuppression used will likely be based from the solid organ literature. The renal transplantation literature has served as the basis for the current selection of CTA drug regimens and in this article we review the evidence in the renal transplant literature for the selection of immunosuppressive regimens. The study then compares the regimens used in both the face and hand transplantation with those regimens currently used for renal transplantation.

Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations.

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.

Simultaneous measurement of plasma vitamin D(3) metabolites, including 4ß,25-dihydroxyvitamin D(3), using liquid chromatography-tandem mass spectrometry.

Simultaneous and accurate measurement of circulating vitamin D metabolites is critical to studies of the metabolic regulation of vitamin D and its impact on health and disease. To that end, we have developed a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that permits the quantification of major circulating vitamin D(3) metabolites in human plasma. Plasma samples were subjected to a protein precipitation, liquid-liquid extraction, and Diels-Alder derivatization procedure prior to LC-MS/MS analysis. Importantly, in all human plasma samples tested, we identified a significant dihydroxyvitamin D(3) peak that could potentially interfere with the determination of 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] concentrations. This interfering metabolite has been identified as 4ß,25-dihydroxyvitamin D(3) [4ß,25(OH)(2)D(3)] and was found at concentrations comparable to 1α,25(OH)(2)D(3). Quantification of 1α,25(OH)(2)D(3) in plasma required complete chromatographic separation of 1α,25(OH)(2)D(3) from 4ß,25(OH)(2)D(3). An assay incorporating this feature was used to simultaneously determine the plasma concentrations of 25OHD(3), 24R,25(OH)(2)D(3), 1α,25(OH)(2)D(3), and 4ß,25(OH)(2)D(3) in healthy individuals. The LC-MS/MS method developed and described here could result in considerable improvement in quantifying 1α,25(OH)(2)D(3) as well as monitoring the newly identified circulating metabolite, 4ß,25(OH)(2)D(3).

How to increase living donation.

Living donation is the key to increasing access to successful solid organ transplantation worldwide. However, the means to expanding the number of living donors on a global scale are not known. Although there have been many suggestions for the best approach, cultural issues may limit the effectiveness of some strategies. Only a few ideas have been studied, and one in particular- outright payment to donors - may raise ethical issues that are difficult to surmount and might negatively alter altruistic behavior. With respect to the present environment, this article will describe some of the approaches that are being discussed to increase the number of living donors, with a particular focus on kidney transplantation.

Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation.

The impact of subclinical viral infection on chronic allograft injury in the pediatric renal transplant population is not well defined. We prospectively assessed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia by monthly PCR in 55 pediatric renal transplant recipients for the first 2 years after transplantation. Subclinical CMV and EBV infection occurred in 22 and 36%, respectively. Multivariable linear regression analysis suggested that both subclinical CMV and EBV infection independently associate with significant declines in GFR during the first 2 years after transplantation. CMV seronegativity associated with a significantly greater decline in GFR than seropositivity (P < 0.01). Subclinical CMV infection and subclinical EBV infection each associated with approximately fourfold greater odds of histologic evidence of chronic allograft injury (odds ratio 4.61 [95% confidence interval 1.18 to 18.07] and odds ratio 4.33 [95% confidence interval 1.34 to 14.00], respectively). An increase in viral load of CMV or EBV also associated with increased risk for moderate to severe chronic allograft injury. Taken together, these results demonstrate an association between subclinical CMV and EBV infections, which occur despite standard antiviral prophylaxis, and chronic allograft injury in pediatric renal transplant recipients.

A qualitative assessment of personal and social responsibility for kidney disease: the Increasing Kidney Disease Awareness Network Transplant Project.

INTRODUCTION: Limited qualitative research has explored opinions of kidney disease health care providers regarding racial and ethnic disparities in access to and receipt of kidney transplantation. METHODS: Key informant interviews were conducted among transplant nephrologists, nephrologists, transplant social workers, and transplant coordinators to determine barriers to transplantation among African Americans compared to whites with end-stage renal disease (ESRD). ANALYSIS: Thirty-eight interviews were audio recorded and transcribed to hardcopy for content analysis. Grounded theory was used to determine dominant themes within the interviews. Reliability and validity were ensured by several coinvestigators independently sorting verbatim responses used for generating themes and subsequent explanations. RESULTS: Several major categories arose from analysis of the transcripts. Under the category of personal and social responsibility for kidney transplantation, interviews revealed 4 major themes: negative personal behaviors, acquisition of and lack of self-treatment of comorbid conditions, lack of individual responsibility, and the need for more social responsibility. Many providers perceived patients as being largely responsible for the development of ESRD, while some providers expressed the idea that more social responsibility was needed to improve poor health status and disparities in kidney transplantation rates. CONCLUSION: Kidney disease health providers seemed torn between notions of patients' accountability and social responsibility for racial disparities in chronic kidney disease and ESRD. Further research is needed to clarify which aspects contribute most to disparities in access to transplantation.

Preemptive transplantation and the transplant first initiative.

PURPOSE OF REVIEW: Preemptive kidney transplant (PKT) is the focus of a new initiative, 'Transplant First'. This initiative focuses on increasing patient transition to transplantation prior to the need for dialysis. This review will evaluate the benefits of PKT and means to accomplish this goal. RECENT FINDINGS: Outcomes data show PKT significantly improves long-term survival for the recipient and the allograft. In addition quality of life is improved. This also holds true for children and particularly for adolescents. In 2008, 5.7% of incident patients with end-stage renal disease were placed on the waiting list before beginning dialysis and 0.8% underwent preemptive living donor transplant before wait listing. If patients are evaluated before starting dialysis and are acceptable candidates, up to 40% will receive a preemptive transplant. Recent articles stress that patients want information from their physician; important impediments to PKT remain provider and patient education, insurance coverage and patient reluctance to ask for living donation. SUMMARY: Preemptive transplant saves lives. Increased education focused on providers, patients and entire communities is key, as is an increase in living donation. Furthermore, to maximize the impact of transplant first, increased living donor protections and immunosuppression coverage for the life of the allograft are essential.

Twelve evidence-based principles for implementing self-management support in primary care.

BACKGROUND: Recommendations to improve self-management support and health outcomes for people with chronic conditions in primary care settings are provided on the basis of expert opinion supported by evidence for practices and processes. Practices and processes that could improve self-management support in primary care were identified through a nominal group process. In a targeted search strategy, reviews and meta-analyses were then identifed using terms from a wide range of chronic conditions and behavioral risk factors in combination with Self-Care, Self-Management, and Primary Care. On the basis of these reviews, evidence-based principles for self-management support were developed. FINDINGS: The evidence is organized within the framework of the Chronic Care Model. Evidence-based principles in 12 areas were associated with improved patient self-management and/or health outcomes: (1) brief targeted assessment, (2) evidence-based information to guide shared decision-making, (3) use of a nonjudgmental approach, (4) collaborative priority and goal setting, (5) collaborative problem solving, (6) self-management support by diverse providers, (7) self-management interventions delivered by diverse formats, (8) patient self-efficacy, (9) active followup, (10) guideline-based case management for selected patients, (11) linkages to evidence-based community programs, and (12) multifaceted interventions. A framework is provided for implementing these principles in three phases of the primary care visit: enhanced previsit assessment, a focused clinical encounter, and expanded postvisit options. CONCLUSIONS: There is a growing evidence base for how self-management support for chronic conditions can be integrated into routine health care.

Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

The contribution of podocytes to chronic allograft nephropathy.

BACKGROUND: Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. However, the causes are not fully elucidated. Podocytes function to prevent proteinuria; injury to this glomerular cell leads to glomerulosclerosis. The potential role of podocytes in the failing transplanted kidney is unknown. A rat model of kidney transplantation, characterized by proteinuria and glomerulosclerosis, was utilized to examine the potential role of podocytes. METHODS: Archival tissue was examined from allografts (Dark Agouti kidneys transplanted into operationally tolerant Albino Surgery rats), isografts (Dark Agouti) and controls (Dark Agouti: age-matched or after unilateral nephrectomy). The number of podocytes (by WT-1 staining) as well as the podocyte proteins podocin, nephrin and synaptopodin (by immunostaining) were measured at days 0, 2, 6 and at 6 months after transplantation. Changes in these parameters were compared between groups and correlated with urinary protein excretion. RESULTS: At 6 months, podocyte number was reduced in allografted kidneys, accompanied by a decrease in nephrin and synaptopodin, but not podocin staining. Remnant kidneys in the uninephrectomized rats also showed a decreased podocyte number but no change in podocyte protein staining. Podocyte loss in allografts was established on day 6, whereas a decrease in nephrin and synaptopodin was not evident until 6 months. In contrast, podocyte number and protein staining was decreased but not significantly so in remnant and isografted kidneys. CONCLUSION: A decrease in the slit diaphragm proteins, nephrin and synaptopodin, is a component of chronic allograft pathology.