High urine amylase level and the risk of enteric conversion in solitary pancreas transplant recipients.

INTRODUCTION: Compared with enteric drainage, bladder-drained solitary pancreas transplants can be monitored for rejection by measuring urine amylase levels. However, bladder drainage is associated with a higher risk of infection and metabolic complications, necessitating enteric conversion in about one third of patients. We hypothesized that hypersecreting pancreata with high urine amylase levels have a higher propensity for enteric conversion from an antecedent elevated enzymatic effect on the urinary tract and increased fluid losses. PATIENTS AND METHODS: We analyzed the risk for enteric conversion in 312 bladder-drained solitary pancreas transplant recipients. Urine amylase levels at 30 days were used to identify those at risk for enteric conversion. Time-to-event analysis was used to evaluate the risk of enteric conversion at 10 years, adjusting for urine amylase level and other confounding factors. Confounding risk factors statistically related to enteric conversion were incorporated into the multivariable analysis by using Cox proportional hazards regression at 3 years' posttransplant. RESULTS: During the median follow-up of 184.6 months, 31% of recipients underwent duct conversion. A majority of recipients (84.5%) who required duct conversion were primary transplants. The 30-day median urine amylase level was 1749 IU/h (quartile 1, <777 IU/h; quartile 3, ≥3272 IU/h). Using receiver operating characteristic analysis, it was determined that urine amylase levels >3272 IU/h had the greatest specificity for predicting risk of enteric conversion. In the multivariate analysis, high urine amylase levels increased the risk of enteric conversion only in repeated pancreas transplants. CONCLUSIONS: Primary transplants are more likely to undergo enteric conversion than retransplants. High urine amylase levels increase the risk of enteric conversion in retransplants only, and therefore this enzyme alone cannot serve as the sole predictor for conversion in primary transplants. Other factors, such as fluid and bicarbonate losses, increased bladder pressure, and a pre-existing lower urinary tract pathologic condition may be also responsible for the development of complications; these factors warrant additional study.

Comprehensive health assessment and five-yr follow-up of allogeneic islet transplant recipients.

In patients with type 1 diabetes mellitus (T1DM) complicated by severe hypoglycemic episodes, fear of hypoglycemia can significantly impact daily life. We evaluated whether restoration of glycemic awareness and prevention of hypoglycemia by islet allotransplant could reduce fear and improve health status. We conducted a comprehensive evaluation of patient-based outcomes in 48 T1DM subjects screened for allogeneic islet transplant alone (ITA) and 27 subjects who received an ITA. A battery of generic health status and diabetes-specific measures were used to assess ITA at evaluation, six months, and then annually after ITA. Allogeneic islet transplant was associated with a reduction in behaviors adopted in avoiding hypoglycemia (p Value < 0.001) and attenuation in concerns about hypoglycemic episodes (p Value < 0.001). Changes in hypoglycemia fear tracked most closely with insulin use. While there was a trend toward global improvement in health as measured by the EQ-5D (p Value = 0.002) and in depression symptoms as measured by the Beck (p Value = 0.003), physical health remained unchanged following ITA. Our findings support the socioemotional benefits of ITA during the five years after ITA, which to some extent remains dependent on preservation of islet graft function.

Proposed thresholds for pancreatic tissue volume for safe intraportal islet autotransplantation after total pancreatectomy.

The simple question of how much tissue volume (TV) is really safe to infuse in total pancreatectomy-islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) precipitated this analysis. We examined a large cohort of CP patients (n = 233) to determine major risk factors for elevated portal pressure (PP) during islet infusion, using bivariate and multivariate regression modeling. Rates of bleeding requiring operative intervention and portal venous thrombosis (PVT) were evaluated. The total TV per kilogram body weight infused intraportally was the best independent predictor of change in PP (ΔPP) (p < 0.0001; R(2) = 0.566). Rates of bleeding and PVT were 7.73% and 3.43%, respectively. Both TV/kg and ΔPP are associated with increased complication rates, although ΔPP appears to be more directly relevant. Receiver operating characteristic analysis identified an increased risk of PVT above a suggested cut-point of 26 cmH2O (area under the curve = 0.759), which was also dependent on age. This ΔPP threshold was more likely to be exceeded in cases where the total TV was >0.25 cm(3)/kg. Based on this analysis, we have recommended targeting a TV of <0.25 cm(3)/kg during islet manufacturing and to halt intraportal infusion, at least temporarily, if the ΔPP exceeds 25 cmH2O. These models can be used to guide islet manufacturing and clinical decision making to minimize risks in TP-IAT recipients.

Metabolic assessment prior to total pancreatectomy and islet autotransplant: utility, limitations and potential.

Islet autotransplant (IAT) may ameliorate postsurgical diabetes following total pancreatectomy (TP), but outcomes are dependent upon islet mass, which is unknown prior to pancreatectomy. We evaluated whether preoperative metabolic testing could predict islet isolation outcomes and thus improve assessment of TPIAT candidates. We examined the relationship between measures from frequent sample IV glucose tolerance tests (FSIVGTT) and mixed meal tolerance tests (MMTT) and islet mass in 60 adult patients, with multivariate logistic regression modeling to identify predictors of islet mass ≥2500 IEQ/kg. The acute C-peptide response to glucose (ACRglu) and disposition index from FSIVGTT correlated modestly with the islet equivalents per kilogram body weight (IEQ/kg). Fasting and MMTT glucose levels and HbA1c correlated inversely with IEQ/kg (r values -0.33 to -0.40, p ≤ 0.05). In multivariate logistic regression modeling, normal fasting glucose (<100 mg/dL) and stimulated C-peptide on MMTT ≥4 ng/mL were associated with greater odds of receiving an islet mass ≥2500 IEQ/kg (OR 0.93 for fasting glucose, CI 0.87-1.0; OR 7.9 for C-peptide, CI 1.75-35.6). In conclusion, parameters obtained from FSIVGTT correlate modestly with islet isolation outcomes. Stimulated C-peptide ≥4 ng/mL on MMTT conveyed eight times the odds of receiving ≥2500 IEQ/kg, a threshold associated with reasonable metabolic control postoperatively.

A composite risk model for predicting technical failure in pancreas transplantation.

Technical failure (TF) continues to have a significant impact on the success of pancreas transplantation. We assessed risk factors for TF in 1115 pancreas transplants performed at a single center between 1998 and 2011. The overall TF rate was 10.2%. In a multivariable model, donor BMI ≥ 30 (HR 1.87, p = 0.005), donor Cr ≥ 2.5 (HR 3.16, p = 0.007), donor age >50 (HR 1.73, p = 0.082) and preservation time >20 h (HR 2.17, p < 0.001) were associated with TF. Bladder drainage of exocrine secretions was protective (HR 0.54, p = 0.002). We incorporated these factors in a Composite Risk Model. In this model the presence of one risk factor did not significantly increase risk of TF (HR 1.35, p = 0.346). Two risk factors in combination increased risk greater than threefold (HR 3.65, p < 0.001) and three risk factors increased risk greater than sevenfold (HR 7.66, p = <0.001). The analysis also identified many factors that were not predictive of TF, including previous transplants, immunosuppressive agent selection, and almost all recipient demographic parameters. While the model suggests that two or more risk factors predict TF, strategies to reduce preservation time may mitigate some of this risk.

Comparison of recipient outcomes following transplant from local versus imported pancreas donors.

The shortage of deceased donor organs for solid organ transplantation continues to be an ongoing dilemma. One approach to increase the number of pancreas transplants is to share organs between procurement regions. To assess for the effects of organ importation, we reviewed the outcomes of 1014 patients undergoing deceased donor pancreas transplant at a single center. We performed univariate and multivariate analyses of the association of donor, recipient and surgical characteristics with patient outcomes. Organ importation had no effect on graft or recipient survival for recipients of solitary pancreas transplants. Similarly, there was no effect on technical failure rate, graft survival or long-term patient survival for simultaneous kidney-pancreas (SPK) recipients. In contrast, there was a significant and independent increased risk of death in the first year in SPK recipients of imported organs. SPK recipients had longer hospitalizations and increased hospital costs. This increased medical complexity may make these patients more susceptible to short-term complications resulting from the longer preservation times of import transplants. These findings support the continued use of organ sharing to reduce transplant wait times but highlight the importance of strategies to reduce organ preservation times.

Anti-CD25 antibody (daclizumab) maintenance therapy in pancreas transplantation.

BACKGROUND: Calcineurin inhibitors (CNI) are the basis of contemporary immunosuppression in clinical pancreas transplantation (PT). Nevertheless, CNI toxicities, especially nephrotoxicity, have stimulated the search for CNI-sparing protocols. We performed a retrospective analysis of 25 PT patients with progressive CNI toxicities that were switched to a daclizumab (DAC)-based maintenance regimen. METHODS: From 2003 to 2007, 25 PT patients with progressive CNI toxicity (predominantly nephrotoxicity) were identified and switched from CNI to monthly DAC maintenance therapy. The DAC group was compared with matched control subjects (1:1) by transplant type and number, age, year of transplant, and duct management. RESULTS AND CONCLUSIONS: Results showed improved graft survival rates and decreased immunologic loss rates at 1, 3, and 5 years in the DAC group compared with the control group. There was no difference in patient survival rate between the 2 groups. Analysis demonstrates that DAC maintenance therapy is safe and effective for PT patients experiencing CNI toxicities. A randomized trial to compare DAC- and CNI-based regimens is needed in CNI-intolerant patients, with particular attention to the impact on renal function and patient morbidity (eg, infection rates).

Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation.

BACKGROUND: A scoring system was recently proposed to grade the severity of primary graft dysfunction (PGD), a frequent early complication of lung transplantation. The purposes of this study are to: (1) validate the PGD grading system with respect to patient outcomes; and (2) compare the performance of criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F) ratio to an alternative grading system employing the oxygenation index (OI). METHODS: We retrospectively reviewed the medical records of 402 patients having undergone lung transplantation at our institution from 1992 through 2004. The ISHLT PGD grading system was modified and grades were assigned up to 48 hours post-transplantation as follows: Grade 1 PGD, P/F > 300; Grade 2, P/F 200 to 300; and Grade 3, P/F < 200. A worst score T(0-48) was also assigned, which reflects the highest grade recorded between T0 and T48. RESULTS: The prevalence of severe PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48. Grouping patients by P/F grade at T48 demonstrated the clearest differentiation of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) (p = 0.0001). T48 OI grade also differentiates 90-day death rates. There was no difference in longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0 qualitatively improved differential mortality between Grades 1 and 2; however, the differences did not reach statistical significance. Patients with a worst score T(0-48) of Grade 3 PGD did have significantly decreased long-term survival, as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD. Significant risk factors for short- and long-term mortality in our multivariate model were P/F Grade 3 [worst score T(0-48) as well as T0 grade], single-lung transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary artery pressure. CONCLUSIONS: There is an increased risk of short- and long-term mortality and length of hospital stay associated with severe (Grade 3) PGD. The proposed ISHLT grading system can rapidly identify patients with poor outcomes who may benefit from early, aggressive treatment. Refinement of the scoring system may further improve patient risk stratification.

Limitations of the pelvic examination for evaluation of the female pelvic organs.

OBJECTIVE: To assess factors influencing an accurate pelvic examination under the best possible circumstances. METHODS: Before undergoing laparoscopy or laparotomy, 84 women under general anesthesia underwent pelvic examinations by an attending gynecologist, a gynecology resident, and a medical student blinded to the indication for surgery. Surgical findings were compared with the examiners' findings. Dependent variables (uterine size, uterine contour, and presence of adnexal masses) and effect modifiers (examiner experience and body mass index) were analyzed. RESULTS: The overall pelvic examination was accurate 70.2% of the time for attending gynecologists, 64.0% for residents, and 57.3% for medical students. The sensitivity to detect adnexal masses was much lower than the sensitivity to assess uterine size or uterine contour. Obesity noticeably reduced detection of adnexal masses. CONCLUSION: The bimanual examination appears to be a limited screening test for the female upper genital tract even under the best possible circumstances. Uterine assessment appears to be more accurate than adnexal assessment.

The Knee Society Index of Severity for failed total knee arthroplasty: development and validation.

Compared with primary knee replacement, total knee arthroplasty revision surgery is a more complex procedure and accounts for greater expenditures of healthcare resources at each clinical stage. Overall, patients having revision procedures have poorer functional outcomes and higher complication rates than patients having primary arthroplasty. Despite the expanded scope of revision problems and the rapidly emerging technology in revision surgery, the long-term success of any method remains in question. Because there is little consensus on the timing of revision surgery, optimal surgical reconstruction, and the type of prosthesis to be implanted, the Knee Society began development of an Index of Severity for Failed Total Knee Arthroplasty. Fifty-four percent of Knee Society members completed an 82-item questionnaire that determined their clinical impression about potential risk factors for the outcomes of revision surgery for failed total knee replacements. Using these results, a consensus group developed the final version of the index. The result of the nominal group process was the Knee Society Index of Severity, which was based on eight distinct domains. Each domain was divided into attributes and weights based on the questionnaire responses and consensus meeting. Actual case scenarios from five institutions were used to test interrater reliability and validity. The interrater reliability of the average score of all ratings was 0.95; the correlation of the criterion rating with the mean rating was 0.77. When three outliers were not included, the Pearson product correlation increased to 0.92. These data support the application of the Knee Society Index of Severity as a critical component of risk factor studies, effectiveness research, and cost-effectiveness analysis involving revisions of total knee replacements.

The Knee Society Index of Severity for failed total knee arthroplasty: practical application.

Previous classifications of severity for total knee arthroplasty revisions have been based largely on bone loss of the femur and tibia. These approaches failed to address the more technically difficult issues in revision surgery such as surgical exposure, contractures, extremity alignment, implant removal, soft tissue stability (in the anteroposterior and in the sagittal planes), extensor mechanism integrity, and patellar revisability. Through the Knee Society, the authors developed a severity index that incorporated these latter factors into one measure. The current authors describe the application of the Knee Society Index of Severity for failed total knee arthroplasty and its method of scoring.

Relationship of disability prevention to patient health status and satisfaction with primary care provider.

A sample of 625 patients aged 18 to 65 with primary care visits was used to explore the relationship of disability prevention to patient health status and satisfaction with health care provider. Disability prevention and the patient-provider relationship, the latter a potential mediating factor, were measured using reliable and valid scales. The joint effects of disability prevention and a strong patient-provider relationship were associated with decreased risks for poor physical health, as measured by the Medical Outcomes Study 12-item short-form health survey, decreased restricted activity days, and overall satisfaction with their primary care provider. Patient-provider relationship was independently associated with increased patient satisfaction with the provider overall and endorsement of the provider to family or friends. The evidence questions the conventional wisdom among some primary care providers that incorporating disability prevention principles into their daily practice jeopardizes patient satisfaction. These results suggest that primary care providers with strong patient-provider relationships can successfully add disability prevention to their practice.

Accuracy of the pelvic examination in detecting adnexal masses.

OBJECTIVE: To estimate sensitivity, specificity, positive predictive value, Youden J statistic, and likelihood ratio of pelvic examination in adnexal assessment under ideal circumstances. METHODS: One hundred forty women consented to have pelvic examinations under general anesthesia before laparoscopy or laparotomy. They were assigned to examiners masked to indications for surgery, including attending gynecologists, gynecology residents, and medical students. Surgeons' findings were compared with examiners' findings. Variables assessed included adnexal diameter, presence of adnexal masses, and effect modifiers such as examiner experience and body mass index. RESULTS: Forty-nine left adnexal and 33 right adnexal masses were found during surgery. Examiners tended to underestimate adnexal size. Sensitivity of pelvic examinations for detecting left adnexal masses was 0.23-0.36 and for right adnexal masses was 0.15-0.28. Positive predictive value was low for left adnexal masses (0.50-0. 69) and right adnexal masses (0.26-0.39). Differences among examiner groups were not statistically significant. Patient obesity noticeably reduced detection of adnexal masses on either side. CONCLUSION: Bimanual pelvic examination has marked limitations for evaluating adnexa, even with ideal circumstances. Experience during postgraduate training in gynecology did not seem to improve examination accuracy. Patient characteristics such as obesity, uterine size, and abdominal scars limit the accurate palpation of the adnexa.

A framework for selecting outcome measures for ambulatory care research.

Selecting outcome measures must be considered in the context of the application the researcher has in mind, that is, describing the health of a population, predicting health status, or evaluating health outcomes. Most important, the outcome measure selected must be conceptually defensible--it needs to make sense. A general framework for selecting measures is discussed in the context of five critical characteristics: (1) sensibility, (2) reliability, (3) validity, (4) responsiveness, and (5) burden. A commonsense approach to outcome measurement selection weighs the relative importance of each of these characteristics with the framework and application clearly in mind.

Impact of geriatric nurse practitioners on nursing-home residents' functional status, satisfaction, and discharge outcomes.

This study evaluated the impact of geriatric nurse practitioners (GNP) employed by nursing homes on quality of patient care and residents' outcomes during a 12-month study period. Quality of care was assessed in standardized interviews of 525 residents in five nursing homes with GNPs and 323 residents in five other nursing homes without GNPs. Each resident was interviewed up to four times during the study period (at baseline, and 3, 6, and 12 months later) to determine functional status, satisfaction with care, and physical condition at each of these points. The only significant difference between groups was that fewer newly admitted residents were hospitalized from GNP homes than from those without a GNP. The results of this interview study showed that the GNP as a nursing home employee had little impact on residents' functional status, physical condition, or satisfaction.

Career paths of geriatric nurse practitioners employed in nursing homes.

The career paths of geriatric nurse practitioners (GNPs) trained with support from the W. K. Kellogg Foundation through the Mountain States Health Corporation (MSHC) were studied. Under this program, GNPs were recruited from sponsoring nursing homes and returned to GNP positions in the sponsoring facilities following training. Training was carried out under a continuing education model offered through six university-based schools of nursing. Questionnaires were sent to the 111 GNPs trained. Of the 102 respondents, 97 provided complete information about past and present education, work experience, and job functions. The GNPs were women with a median age of 45 years, and they were employed in rural settings in the western United States. More than 45 percent of the nurses had at least a baccalaureate degree at the time of GNP training. The GNPs remained employed in long-term care positions that implemented the practitioner role. The median length of GNP employment in their first jobs after training was more than 4.5 years. The resignation rate from this first position was 1.66 resignations for each 10 years of GNP employment. Job changes were likely to be attributed to organizational changes with subsequent positions shifting toward a diversification of the GNP role. The study demonstrates the success of the MSHC program in introducing and retaining GNPs in nursing homes.

Effects of a geriatric nurse practitioner on process and outcome of nursing home care.

We compared measures of quality of care and health services utilization in 30 nursing homes employing geriatric nurse practitioners with those in 30 matched control homes. Information for this analysis came from reviews of samples of patient records drawn at comparable periods before and after the geriatric NPs were employed. The measures of geriatric nurse practitioner impact were based on comparisons of changes from pre-NP to post-NP periods. Separate analyses were done for newly admitted and long-stay residents; a subgroup of homes judged to be best case examples was analyzed separately as well as the whole sample. Favorable changes were seen in two out of eight activity of daily living (ADL) measures: five of 18 nursing therapies; two of six drug therapies; six of eight tracers. There was some reduction in hospital admissions and total days in geriatric NP homes. Overall measures of medical attention showed a mixed pattern with some evidence of geriatric NP care substituted for physician care. These findings suggest that the geriatric NP has a useful role in nursing home care.