Relationship between pediatric blood and marrow transplant center volume and day +100 mortality: Pediatric Blood and Marrow Transplant Consortium experience.

The number of patients receiving a BMT is currently being used as a factor in the accreditation process in determining whether a center can provide a high-quality BMT. Such criteria particularly impact pediatric BMT centers as most of them perform a relatively small number of BMTs. To determine whether patient volume is a valid marker of pediatric BMT center's capabilities, the Pediatric Blood and Marrow Transplant Consortium (PBMTC) evaluated data from its registry to define the relationship between a pediatric transplant center's patient volume and day +100 mortality. The analyses evaluated 2575 transplants from 60 centers reporting to the PBMTC between the years 2002 and 2004. The volume-outcome relationship was evaluated while adjusting for 46 independent data categories divided between nine variables that were known- or suspected-mortality risk factors. We found no association between transplant center volume and day +100 mortality in several analyses. A calculated intraclass correlation coefficient also indicated that differences in individual transplant center volume contributed to only 1% of the variance in day +100 mortality within the PBMTC. The results of this study suggest that factors other than transplant center volume contribute to variation in day +100 mortality among pediatric patients.

Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis.

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods. RESULTS: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.

Certainty and mortality prediction in critically ill children.

OBJECTIVES: The objective of this study is to investigate the relationship between a physician's subjective mortality prediction and the level of confidence with which that mortality prediction is made. DESIGN AND PARTICIPANTS: The study is a prospective cohort of patients less than 18 years of age admitted to a tertiary Paediatric Intensive Care Unit (ICU) at a University Children's Hospital with a minimum length of ICU stay of 10 h. Paediatric ICU attending physicians and fellows provided mortality risk predictions and the level of confidence associated with these predictions on consecutive patients at the time of multidisciplinary rounds within 24 hours of admission to the paediatric ICU. Median confidence levels were compared across different ranges of mortality risk predictions. RESULTS: Data were collected on 642 of 713 eligible patients (36 deaths, 5.6%). Mortality predictions greater than 5% and less than 95% were made with significantly less confidence than those predictions <5% and >95%. Experience was associated with greater confidence in prognostication. CONCLUSIONS: We conclude that a physician's subjective mortality prediction may be dependent on the level of confidence in the prognosis; that is, a physician less confident in his or her prognosis is more likely to state an intermediate survival prediction. Measuring the level of confidence associated with mortality risk predictions (or any prognostic assessment) may therefore be important because different levels of confidence may translate into differences in a physician's therapeutic plans and their assessment of the patient's future.

Long-stay patients in the pediatric intensive care unit.

OBJECTIVE: Length of stay in the pediatric intensive care unit (PICU) is a reflection of patient severity of illness and health status, as well as PICU quality and performance. We determined the clinical profiles and relative resource use of long-stay patients (LSPs) and developed a prediction model to identify LSPs for early quality and cost saving interventions. DESIGN: Nonconcurrent cohort study. SETTING: A total of 16 randomly selected PICUs and 16 volunteer PICUs. PATIENTS: A total of 11,165 consecutive admissions to the 32 PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LSPs were defined as patients having a length of stay greater than the 95th percentile (>12 days). Logistic regression analysis was used to determine which clinical characteristics, available within the first 24 hrs after admission, were associated with LSPs and to create a predictive algorithm. Overall, LSPs were 4.7% of the population but represented 36.1% of the days of care. Multivariate analysis indicated that the following factors are predictive of long stays: age <12 months, previous ICU admission, emergency admission, no CPR before admission, admission from another ICU or intermediate care unit, chronic care requirements (total parenteral nutrition and tracheostomy), specific diagnoses including acquired cardiac disease, pneumonia, and other respiratory disorders, having never been discharged from the hospital, need for ventilatory support or an intracranial catheter, and a Pediatric Risk of Mortality III score between 10 and 33. The performance of the prediction algorithm in both the training and validation samples for identifying LSPs was good for both discrimination (area under the receiver operating characteristics curve of 0.83 and 0.85, respectively), and calibration (goodness of fit, p = .33 and p = .16, respectively). LSPs comprised from 2.1% to 8.1% of individual ICU patients and occupied from 15.2% to 57.8% of individual ICU bed days. CONCLUSIONS: LSPs have less favorable outcomes and use more resources than non-LSPs. The clinical profile of LSPs includes those who are younger and those that require chronic care devices. A predictive algorithm could help identify patients at high risk of prolonged stays appropriate for specific interventions.

Combining physician's subjective and physiology-based objective mortality risk predictions.

OBJECTIVE: None of the currently available physiology-based mortality risk prediction models incorporate subjective judgements of healthcare professionals, a source of additional information that could improve predictor performance and make such systems more acceptable to healthcare professionals. This study compared the performance of subjective mortality estimates by physicians and nurses with a physiology-based method, the Pediatric Risk of Mortality (PRISM) III. Then, healthcare provider estimates were combined with PRISM III estimates using Bayesian statistics. The performance of the Bayesian model was then compared with the original two predictions. DESIGN: Concurrent cohort study. SETTING: A tertiary pediatric intensive care unit at a university affiliated children's hospital. PATIENTS: Consecutive admissions to the pediatric intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each of the 642 consecutive eligible patients, an exact mortality estimate and the degree of certainty (continuous scale from 1 to 5) associated with the estimate was collected from the attending, fellow, resident, and nurse responsible for the patient's care. Bayesian statistics were used to combine the PRISM III and certainty weighted subjective predictions to create a third Bayesian estimate of mortality. PRISM III discriminated survivors from nonsurvivors very well (area under curve [AUC], 0.924) as did the physicians and nurses (AUCs attendings, 0.953; fellows, 0.870; residents, 0.923; nurses, 0.935). Although the AUCs of the healthcare providers were not significantly different from the AUCs of PRISM III, the Bayesian AUCs were higher than both the healthcare providers' AUCs (p < or = .09 for all) and PRISM III AUCs. Similarly, the calibration statistics for the Bayesian estimates were superior to the calibration statistics for both the healthcare providers and PRISM III models. CONCLUSIONS: The results of this study demonstrated that healthcare providers' subjective mortality predictions and PRISM III mortality predictions perform equally well. The Bayesian model that combined provider and PRISM III mortality predictions was more accurate than either provider or PRISM III alone and may be more acceptable to physicians. A methodology using subjective outcome predictions could be more relevant to individual patient decision support.

Prognostication and certainty in the pediatric intensive care unit.

OBJECTIVE: Prognostication is central to developing treatment plans and relaying information to patients, family members, and other health care providers. The degree of confidence or certainty that a health care provider has in his or her mortality risk assessment is also important, because a provider may deliver care differently depending on their assuredness in the assessment. We assessed the performance of nurse and physician mortality risk estimates with and without weighting the estimates with their respective degrees of certainty. METHODS: Subjective mortality risk estimates from critical care attendings (n = 5), critical care fellows (n = 9), pediatric residents (n = 34), and nurses (n = 52) were prospectively collected on at least 94% of 642 eligible, consecutive admissions to a tertiary pediatric intensive care unit (PICU). A measure of certainty (continuous scale from 0 to 5) accompanied each mortality estimate. Estimates were evaluated with 2 x 2 outcome probabilities, the kappa statistic, the area under the receiver operating characteristics curve, and the Hosmer and Lemeshow goodness-of-fit chi(2) statistic. The estimates were then reevaluated after weighting predictions by their respective degree of certainty. RESULTS: Overall, there was a significant difference in the predictive accuracy between groups. The mean mortality predictions from the attendings (6.09%) more closely approximated the true mortality rate (36 deaths, 5.61%) whereas fellows (7.87%), residents (10.00%), and nurses (16.29%) overestimated the mean overall PICU mortality. Attendings were more certain of their predictions (4.27) than the fellows (4.01), nurses (3.79), and residents (3.75). All groups discriminated well (area under receiver operating characteristics curve range, 0.86-0.93). Only PICU attendings and fellows did not significantly differ from ideal calibration (chi(2)). When mortality predictions were weighted with their respective certainties, their performance improved. CONCLUSIONS: The level of medical training correlated with the provider's ability to predict mortality risk. The higher the level of certainty associated with the mortality prediction, the more accurate the prediction; however, high levels of certainty did not guarantee accurate predictions. Measures of certainty should be considered when assessing the performance of mortality risk estimates or other subjective outcome predictions.

Decision support issues using a physiology based score.

OBJECTIVE: As physiology based assessments of mortality risk become more accurate, their potential utility in clinical decision support and resource rationing decisions increases. Before these prediction models can be used, however, their performance must be statistically evaluated and interpreted in a clinical context. We examine the issues of confidence intervals (as estimates of survival ranges) and confidence levels (as estimates of clinical certainty) by applying Pediatric Risk of Mortality III (PRISM III) in two scenarios: (1) survival prediction for individual patients and (2) resource rationing. DESIGN: A non-concurrent cohort study. SETTING: 32 pediatric intensive care units (PICUs). PATIENTS: 10608 consecutive patients (571 deaths). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: For the individual patient application, we investigated the observed survival rates for patients with low survival predictions and the confidence intervals associated with these predictions. For the resource rationing application, we investigated the maximum error rate of a policy which would limit therapy for patients with scores exceeding a very high threshold. For both applications, we also investigated how the confidence intervals change as the confidence levels change. The observed survival in the PRISM III groups >28, >35, and >42 were 6.3, 5.3, and 0%, with 95% upper confidence interval bounds of 10.5, 13.0, and 13.3%, respectively. Changing the confidence level altered the survival range by more than 300% in the highest risk group, indicating the importance of clinical certainty provisions in prognostic estimates. The maximum error rates for resource allocation decisions were low (e. g., 29 per 100000 at a 95% certainty level), equivalent to many of the risks of daily living. Changes in confidence level had relatively little effect on this result. CONCLUSIONS: Predictions for an individual patient's risk of death with a high PRISM score are statistically not precise by virtue of the small number of patients in these groups and the resulting wide confidence intervals. Clinical certainty (confidence level) issues substantially influence outcome ranges for individual patients, directly affecting the utility of scores for individual patient use. However, sample sizes are sufficient for rationing decisions for many groups with higher certainty levels. Before there can be widespread acceptance of this type of decision support, physicians and families must confront what they believe is adequate certainty.

Excursion of the flexor digitorum profundus tendon: a kinematic study of the human and canine digits.

The most common problem following primary flexor tendon repair is the failure of the tendon apparatus to glide, secondary to the formation of adhesions. Early motion following tendon repair has been shown to be effective in reducing adhesions between the tendon and the surrounding sheath. Therefore, it is important to determine the amount of flexor tendon excursion along the digit during joint motion. In this study, the excursion between the flexor digitorum profundus (FDP) tendon and the sheath was examined in both human and canine digits. Based on roentgenographic measurements and joint kinematic analysis, the motion of the bones, the FDP tendon, and the sheath were measured with respect to joint rotations. It was found that the canine flexor tendon apparatus behaved similarly to that of the human for the motions studied. The amount of tendon excursion was very small in regions distal to the joint in motion (approximately 0.1 mm/10 degrees of joint rotation). There was little displacement of the sheath (0.2-0.3 mm), except at the metacarpal joint region during metacarpophalangeal (MCP) joint motion and at the proximal interphalangeal (PIP) joint region during PIP joint motion. Tendon excursion relative to the tendon sheath was the largest in zone II during PIP joint rotation (1.7 mm/10 degrees of joint rotation). These results suggest that PIP joint motion may be most effective in reducing adhesions following tendon repair in zone II.

The effects of transection of the anterior cruciate ligament on healing of the medial collateral ligament. A biomechanical study of the knee in dogs.

The effect of concurrent injury to the anterior cruciate ligament on the healing of injuries of the medial collateral ligament was studied in dogs. In Group I, isolated transection of the medial collateral ligament was performed; in Group II, transection of the medial collateral ligament with partial transection of the anterior cruciate ligament; and in Group III, complete transection of both the medial collateral ligament and the anterior cruciate ligament. The three groups of animals were examined six and twelve weeks postoperatively with respect to varus-valgus rotation of the knee and tensile properties of the femur-medial collateral ligament-tibia complex. The varus-valgus rotation of the knee was found to be the largest in Group-III specimens at all time-periods and was 3.5 times greater than the control values at twelve weeks. Group-I and Group-II specimens also showed large varus-valgus rotations at time zero, but the rotations returned to the control values by twelve weeks. For the structural properties of the femur-medial collateral ligament-tibia complex, the values for ultimate load for Groups I and II reached the control values by twelve weeks, while that for Group III remained at only 80 per cent of the control value. Both energy absorbed at failure and linear stiffness for all three groups were less than those for the controls at six weeks, and only linear stiffness returned to the control values by twelve weeks. For the mechanical (material) properties of the healed ligament substance, the values for modulus and tensile strength were markedly lower than the control values for all groups at six weeks. By twelve weeks, the tensile strength of Group-I specimens had increased to 52 per cent of the control value, while those of Groups II and III were only 45 and 14 per cent, respectively. Our results demonstrate that healing of the transected medial collateral ligament is adversely affected by concomitant transection of the anterior cruciate ligament. Both varus-valgus rotation and mechanical properties of the healed ligament failed to recover in knees that had combined transection of the anterior cruciate and medial collateral ligaments. The structural properties of the femur-medial collateral ligament-tibia complex in tension recovered more rapidly as a consequence of the large mass of reparative tissue that formed in the medial collateral ligament of the anterior cruciate-deficient knees.

A new device to measure the structural properties of the femur-anterior cruciate ligament-tibia complex.

Previous studies of biomechanical properties of femur-anterior cruciate ligament-tibia complex (FATC) utilized a wide variety of testing methodologies, particularly with respect to ligament orientation relative to loading direction. A new device was designed and built to test the anterior-posterior displacement of the intact porcine knee at 30 and 90 deg of flexion, as well as the tensile properties of the FATC at any loading direction and flexion angle. Tensile tests were performed with the knees at 30 and 90 deg of flexion with the loading direction along either the axis of the tibia (tibial axis) or the axis of the anterior cruciate ligament (ligament axis). The results showed that the stiffness, ultimate load and energy absorbed were all significantly increased when the FATC was tested along the ligament axis. This study demonstrates the importance of alignment in the evaluation of the biomechanical characteristics of the femur-ACL-tibia complex.