Waiting list for kidney transplant. Some patients wait too long.

The selection of a kidney graft recipient should be made not only taking into account biological and clinical parameters, for assuring the maximum possible clinical success; the ethical objective to allow every patient equal opportunity of receiving a transplant should also be pursued. In every waiting list of transplant candidates a proportion of patients remains in the list for a particularly long time. The present analysis aimed to find out the factors associated with a prolonged waiting time, in order to allow the implementation of patient selection criteria able to balance unfavourable factors. The analysis of the waiting list of our kidney transplant centre allowed to observe that blood group 0, anti-HLA immunisation, presence of rare HLA antigens and, at a lesser extent, HLA homozygosity are associated with a longer waiting time for a kidney transplant.     

A Mathematical Framework for the Selection of an Optimal Set of Peptides for Epitope-Based Vaccines

Epitope-based vaccines (EVs) have a wide range of applications: from therapeutic to prophylactic approaches, from infectious diseases to cancer. The development of an EV is based on the knowledge of target-specific antigens from which immunogenic peptides, so-called epitopes, are derived. Such epitopes form the key components of the EV. Due to regulatory, economic, and practical concerns the number of epitopes that can be included in an EV is limited. Furthermore, as the major histocompatibility complex (MHC) binding these epitopes is highly polymorphic, every patient possesses a set of MHC class I and class II molecules of differing specificities. A peptide combination effective for one person can thus be completely ineffective for another. This renders the optimal selection of these epitopes an important and interesting optimization problem. In this work we present a mathematical framework based on integer linear programming (ILP) that allows the formulation of various flavors of the vaccine design problem and the efficient identification of optimal sets of epitopes. Out of a user-defined set of predicted or experimentally determined epitopes, the framework selects the set with the maximum likelihood of eliciting a broad and potent immune response. Our ILP approach allows an elegant and flexible formulation of numerous variants of the EV design problem. In order to demonstrate this, we show how common immunological requirements for a good EV (e.g., coverage of epitopes from each antigen, coverage of all MHC alleles in a set, or avoidance of epitopes with high mutation rates) can be translated into constraints or modifications of the objective function within the ILP framework. An implementation of the algorithm outperforms a simple greedy strategy as well as a previously suggested evolutionary algorithm and has runtimes on the order of seconds for typical problem sizes.     

A cost assignment policy for home care patients

The patient assignment problem in Home care (HC) consists of allocating each newly admitted patient to his/her reference operator, chosen among a set of possible operators. The continuity of care, where pursued, imposes that the assignment is not changed for a long period. The main goal of the assignment is to balance the workload among the operators. In the literature, the problem is usually solved with numerical approaches based on mathematical programming that do not consider the stochastic aspects of the problem. We derive a structural policy to assign a newly admitted patient while balancing the workload among the operators, by minimizing the expected value of a cost function that penalizes the overtime of operators. The workloads already loaded to the operators are assumed to be random variables as they are in the practice, while the demand related to the new patient is considered both deterministic and stochastic. Results show that the variability of the new patient’s demand is negligible with respect to the variability of the already assigned workloads and that similar assignments are obtained both in the presence or in the absence of this demand variability. A numerical comparison with the current practice of assigning the new patient to the operator with the highest expected available capacity shows that better balancings and cost savings can be reached by implementing the proposed policy.     

Waiting list management in general practice: a review of orthopaedic patients.

OBJECTIVE: To review all patients on a current general practice orthopaedic waiting list for outpatient appointments with regard to accuracy of the list, clinical priority, and need for further radiological investigation before hospital attendance. DESIGN: Record review by one general practitioner and a radiologist, and discussion with patients of management alternatives. SETTING: Six partner city centre urban fund-holding general practice, list size 8651 (29% low deprivation payment status). SUBJECTS: 116 adults on an orthopaedic waiting list. MAIN OUTCOME MEASURES: List accuracy (patient details and status on waiting list); clinical priority (severity of condition); further investigations (results of tests after radiological review). RESULTS: 32 patients (28%) were removed from the waiting list because of inaccuracies. 14 patients were considered to be high priority and referred to other hospitals by utilising waiting list initiative funds. Of these patients, five agreed to referral to another hospital (treatment completed on average within three months of rereferral), six did not wish to be rereferred, and two did not attend to discuss the offer and remained on the original waiting list. One prioritised patient had further radiological investigations, was reassured, and was taken off the waiting list. 10 patients had further investigations. These resulted in six patients being referred to other hospitals, three being taken off the waiting list, and one seeking private care. CONCLUSIONS: Systematic review of patients on an orthopaedic waiting list of one general practice, though time consuming, led to the identification of inaccuracies in the list and changes in management. Costs need further evaluation, but if the findings occur widely substantial benefits could be achieved for patients.     

Assignment of orthologous genes via genome rearrangement

The assignment of orthologous genes between a pair of genomes is a fundamental and challenging problem in comparative genomics. Existing methods that assign orthologs based on the similarity between DNA or protein sequences may make erroneous assignments when sequence similarity does not clearly delineate the evolutionary relationship among genes of the same families. In this paper, we present a new approach to ortholog assignment that takes into account both sequence similarity and evolutionary events at a genome level, where orthologous genes are assumed to correspond to each other in the most parsimonious evolving scenario under genome rearrangement. First, the problem is formulated as that of computing the signed reversal distance with duplicates between the two genomes of interest. Then, the problem is decomposed into two new optimization problems, called minimum common partition and maximum cycle decomposition, for which efficient heuristic algorithms are given. Following this approach, we have implemented a high-throughput system for assigning orthologs on a genome scale, called SOAR, and tested it on both simulated data and real genome sequence data. Compared to a recent ortholog assignment method based entirely on homology search (called INPARANOID), SOAR shows a marginally better performance in terms of sensitivity on the real data set because it is able to identify several correct orthologous pairs that are missed by INPARANOID. The simulation results demonstrate that SOAR, in general, performs better than the iterated exemplar algorithm in terms of computing the reversal distance and assigning correct orthologs.     

A Bayesian approach to the identification of panmictic populations and the assignment of individuals

We present likelihood-based methods for assigning the individuals in a sample to source populations, on the basis of their genotypes at co-dominant marker loci. The source populations are assumed to be at Hardy-Weinberg and linkage equilibrium, but the allelic composition of these source populations and even the number of source populations represented in the sample are treated as uncertain. The parameter of interest is the partition of the set of sampled individuals, induced by the assignment of individuals to source populations. We present a maximum likelihood method, and then a more powerful Bayesian approach for estimating this sample partition. In general, it will not be feasible to evaluate the evidence supporting each possible partition of the sample. Furthermore, when the number of individuals in the sample is large, it may not even be feasible to evaluate the evidence supporting, individually, each of the most plausible partitions because there may be many individuals which are difficult to assign. To overcome these problems, we use low-dimensional marginals (the 'co-assignment probabilities') of the posterior distribution of the sample partition as measures of 'similarity', and then apply a hierarchical clustering algorithm to identify clusters of individuals whose assignment together is well supported by the posterior distribution. A binary tree provides a visual representation of how well the posterior distribution supports each cluster in the hierarchy. These methods are applicable to other problems where the parameter of interest is a partition of a set. Because the co-assignment probabilities are independent of the arbitrary labelling of source populations, we avoid the label-switching problem of previous Bayesian methods.     

Long distance travel for routine elective surgery: questionnaire survey of patients' attitudes.

OBJECTIVE--To carry out an audit and assess the acceptability of long distance travel to patients on a lengthy surgical waiting list. DESIGN--Audit and questionnaire survey. SETTING--Military hospital in Wiltshire. PATIENTS--116 Patients on a general surgical waiting list at Leighton Hospital near Crewe. INTERVENTIONS--Preselection for medical fitness at a waiting list review clinic. RESULTS--Roughly half of patients offered the facility of travelling 120 miles (190 km) for their routine elective operation at the health authority''s expense accepted. The average waiting list time declared by the patients who travelled was 28 months, and 13 patients stated that their condition prevented them from working. Only four patients regretted their decision to participate in the scheme. Lack of visitors did not cause undue concern. CONCLUSIONS--Some patients did not agree to travel for their operation but almost all of those who did so found the scheme satisfactory. Some minor problems were encountered but these could probably be overcome by ensuring use of appropriate transport, extending the postoperative stay when necessary, and more careful selection of patients for an anaesthetic. For efficient use of theatre time in such schemes it is crucial that the operating consultant surgeon should be in charge of case selection.     

On the assignment of fitness to parents and offspring: whose fitness is it and when does it matter?

There has been a long‐standing conceptual debate over the legitimacy of assigning components of offspring fitness to parents for purposes of evolutionary analysis. The benefits and risks inherent in assigning fitness of offspring to parents have been given primarily as verbal arguments and no explicit theoretical analyses have examined quantitatively how the assignment of fitness can affect evolutionary inferences. Using a simple quantitative genetic model, we contrast the conclusions drawn about how selection acts on a maternal character when components of offspring fitness (such as early survival) are assigned to parents vs. when they are assigned directly to the individual offspring. We find that there are potential shortcomings of both possible assignments of fitness. In general, whenever there is a genetic correlation between the parental and direct effects on offspring fitness, assigning components of offspring fitness to parents yields incorrect dynamical equations and may even lead to incorrect conclusions about the direction of evolution. Assignment of offspring fitness to parents may also produce incorrect estimates of selection whenever environmental variation contributes to variance of the maternal trait. Whereas assignment of offspring fitness to the offspring avoids these potential problems, it introduces the possible problem of missing components of kin selection provided by the mother, which may not be detected in selection analyses. There are also certain conditions where either model can be appropriate because assignment of offspring fitness to parents may yield the same dynamical equations as assigning offspring fitness directly to offspring. We discuss these implications of the alternative assignments of fitness for modelling, selection analysis and experimentation in evolutionary biology.     

The effect of single-nucleotide polymorphism marker selection on patterns of haplotype blocks and haplotype frequency estimates

The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation.     

Shortening waiting lists in orthopaedic surgery outpatient clinics.

There is a long waiting list for orthopaedic outpatient appointments in South Glamorgan Area Health Authority as elsewhere. A detailed study of that waiting list was undertaken to identify factors that might lead to its better management and reduction. One-third of patients on the list failed to attend when appointments were offered. A postal-questionnaire to all those listed as waiting confirmed that many no longer sought specialist orthopaedic consultation. Another third of the patients reported that they had been treated previously for the same orthopaedic problem. It is concluded that improved management of long outpatient waiting lists could be achieved by correspondence with referring general practitioners to weed out those patients who no longer wish to attend, to reduce the burden of reviews and re-referrals of patients with "chronic" conditions, and to request priorities fairly so that earlier appointments may be offered to truly "new" patients with treatable or with potentially serious conditions.     

Graphical analysis of NMR structural quality and interactive contact map of NOE assignments in ARIA

Background  

The Ambiguous Restraints for Iterative Assignment (ARIA) approach is widely used for NMR structure determination. It is based on simultaneously calculating structures and assigning NOE through an iterative protocol. The final solution consists of a set of conformers and a list of most probable assignments for the input NOE peak list.     

Hierarchical protein folding pathways: a computational study of protein fragments

We have previously presented a building block folding model. The model postulates that protein folding is a hierarchical top-down process. The basic unit from which a fold is constructed, referred to as a hydrophobic folding unit, is the outcome of combinatorial assembly of a set of "building blocks." Results obtained by the computational cutting procedure yield fragments that are in agreement with those obtained experimentally by limited proteolysis. Here we show that as expected, proteins from the same family give very similar building blocks. However, different proteins can also give building blocks that are similar in structure. In such cases the building blocks differ in sequence, stability, contacts with other building blocks, and in their 3D locations in the protein structure. This result, which we have repeatedly observed in many cases, leads us to conclude that while a building block is influenced by its environment, nevertheless, it can be viewed as a stand-alone unit. For small-sized building blocks existing in multiple conformations, interactions with sister building blocks in the protein will increase the population time of the native conformer. With this conclusion in hand, it is possible to develop an algorithm that predicts the building block assignment of a protein sequence whose structure is unknown. Toward this goal, we have created sequentially nonredundant databases of building block sequences. A protein sequence can be aligned against these, in order to be matched to a set of potential building blocks.     

Diabetes Mellitus and Prediabetes on Kidney Transplant Waiting List- Prevalence,Metabolic Phenotyping and Risk Stratification Approach

Background

Despite a significant prognostic impact, little is known about disturbances in glucose metabolism among kidney transplant candidates. We assess the prevalence of diabetes mellitus (DM) and prediabetes on kidney transplant waiting list, its underlying pathophysiology and propose an approach for individual risk stratification.

Methods

All patients on active kidney transplant waiting list of a large European university hospital transplant center were metabolically phenotyped.

Results

Of 138 patients, 76 (55%) had disturbances in glucose metabolism. 22% of patients had known DM, 3% were newly diagnosed. 30% were detected to have prediabetes. Insulin sensitivity and-secretion indices allowed for identification of underlying pathophysiology and risk factors. Age independently affected insulin secretion, resulting in a relative risk for prediabetes of 2.95 (95%CI 1.38–4.83) with a cut-off at 48 years. Body mass index independently affected insulin sensitivity as a continuous variable.

Conclusions

The prevalence of DM or prediabetes on kidney transplant waiting list is as high as 55%, with more than one third of patients previously undiagnosed. Oral glucose tolerance test is mandatory to detect all patients at risk. Metabolic phenotyping allows for differentiation of underlying pathophysiology and provides a basis for early individual risk stratification and specific intervention to improve patient and allograft outcome.     

Waiting times: monitoring the total postreferral wait.

OBJECTIVES--To determine whether the period spent on the true inpatient waiting list is a valid indication of the total time that patients have to wait for an operation; and to assess the feasibility of monitoring the total "postreferral waiting time" by using existing computerised information systems. SETTING--Three randomly selected Scottish hospitals. SUBJECTS--Waiting list patients admitted to hospital for operations during June to August 1993 in six major specialties, separate attention being focused on cataract operations and hip and knee replacements. MAIN OUTCOME MEASURE--The total time that patients have to wait for an operation after the initial general practitioner referral--the postreferral waiting time--compared with that spent at the final stage of the process on the true inpatient waiting list. RESULTS--In the specialties investigated roughly half (58 days; 53%) of the average postreferral wait of 110 days was spent on the true inpatient waiting list, one third (35 days; 32%) being spent on the outpatient waiting list and one sixth (17 days; 15%) waiting between waiting lists. Only a quarter of cataract patients (73/292) were treated within three months of general practitioner referral compared with over three quarters (228/292) within three months of being placed on the inpatient waiting list. Nevertheless, within a year over 99% of patients (290) had been treated whichever date was taken as the starting point. CONCLUSIONS--Monitoring postreferral waiting times would provide a much more accurate picture for purchasers and patients of waiting times for treatment than is obtained by focusing exclusively on the true inpatient waiting list and facilitate fairer comparisons between NHS trusts in national league tables. Stringent national and local monitoring is essential to ensure (a) that future reductions in the time waiting on true inpatient waiting lists are not gained at the expense of longer periods waiting to be placed on the lists, and (b) that no increases occur in the number of patients placed instead on deferred waiting lists or exempted from the normal maximum waiting time guarantees.     

Level scheduling under limited resequencing flexibility

A mixed-model assembly line requires the solution of a short-term sequencing problem, which decides on the succession of different models launched down the line. A famous solution approach stemming from the Toyota Production System is the so-called Level Scheduling (LS), which aims to distribute the part consumption induced by a model sequence evenly over the planning horizon. LS attracted a multitude of different researchers, who, however, invariably treat initial sequence planning where all degrees of freedom in assigning models to production cycles exist. In the real-world, conflicting objectives and restrictions of preceding production stages, i.e., body and paint shop, simultaneously need to be considered and perturbations of an initial sequence will regularly occur, so that the sequencing problem often becomes a resequencing problem. Here, a given model sequence is to be reshuffled with the help of resequencing buffers (denoted as pull-off tables). This paper shows how to adapt famous solution approaches for alternative LS problems, namely the Product-Rate-Variation (PRV) and the Output-Rate-Variation (ORV) problem, if the (re-)assignment of models to cycles is restricted by the given number of pull-off tables. Furthermore, the effect of increasing re-sequencing flexibility is investigated, so that the practitioner receives decision support for buffer dimensioning, and the ability of the PRV in reasonably approximating the more detailed ORV in a resequencing environment is tested.     

Access to adult liver transplantation in Canada: a survey and ethical analysis.

OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and because the primary limiting factor is organ supply, increased organ acquisition efforts are needed.     

Waiting list statistics. I: Relation between admissions from waiting list and length of waiting list.

The relation between changes in inpatient workload, measured as increases or decreases in the number of inpatients admitted from the waiting list, and the overall length of the waiting list was studied. Overall trends in admissions from the waiting list, the influence of seasonal patterns, and the impact of industrial action on admissions were also studied. The hypothesis was that when admissions from the waiting list increased the length of the waiting list would decrease and vice versa. No such simple relation was found. In fact, if anything, as the number of admissions from the waiting list increased so did the length of the waiting list. This result could be due to inconsistencies in compiling waiting list data or to the use of waiting lists to improve organisational efficiency. It is also possible, and perhaps likely, that the ability to meet need in admitting patients to hospital influences patients and their doctors to translate previously unmet need into demand for hospital services.     

Coronary artery bypass graft surgery in Newfoundland and Labrador

BACKGROUND: Newfoundland and Labrador, like other health care jurisdictions, is faced with widening gaps between the demands for health care and a strained ability to supply the necessary resources. The authors carried out a study to determine the rates of appropriate and inappropriate coronary artery bypass grafting (CABG) in the province and the waiting times for this surgery. METHODS: This retrospective cohort study was performed in the tertiary care hospital that receives all referrals for coronary angiography and coronary artery revascularization for Newfoundland and Labrador. By reviewing the hospital records, the authors identified 2 groups of patients: those in whom critical coronary artery disease was diagnosed on the basis of coronary angiography and who were referred for CABG between Apr. 1, 1994, and Mar. 31, 1995, and those who actually underwent the procedure during that period. By applying specific criteria developed by the RAND Corporation, the authors determined the appropriateness and necessity of CABG in each case. They also compared waiting times for CABG with optimal waiting times; as determined by a consensus-based priority score. RESULTS: A total of 338 patients underwent CABG during the study period. The cases were characterized by multivessel disease and late-stage angina symptoms. Almost all of the patients had high appropriateness scores (7-9), and nearly 95% had high necessity scores (7-9). However, during the study period, the waiting list increased by about 20%, because a total of 391 patients were referred by the weekly cardiovascular surgery conference; the authors identified these and an additional 31 patients as having necessity scores of 7 or more. Only 7 (23%) of 31 patients for whom CABG was considered very urgent underwent surgery within the recommended 24 hours, and only 30 (24%) of the 122 patients for whom CABG was considered urgent underwent surgery within the recommended 72 hours. INTERPRETATION: These results provide evidence that the cardiac surgery program in Newfoundland and Labrador is performing CABG in patients for whom surgical revascularization is highly appropriate and necessary. Access to CABG is less than ideal, however, since the waiting list continues to expand, and many patients wait beyond the recommended time for surgery.     

Nest Turnover Rates and List-Frame Decay in Bald Eagles: Implications for the National Monitoring Plan

ABSTRACT In accordance with federal regulations, the United States Fish and Wildlife Service developed a postdelisting monitoring plan for the bald eagle (Haliaeetus leucocephalus) designed to detect a change in the number of occupied nests on a national scale. The plan employs a dual-frame approach to the survey design where a list frame (list of known nests) and an area frame (set of survey plots) are used in concert to estimate the number of occupied nests in 5-year intervals over a 20-year period. The plan offers no provisions for changes in list-frame integrity, nor does it contemplate the impact of such changes on survey performance. We used a long-term data set to quantify occupancy patterns for nests in Virginia, USA, and evaluated their influence on integrity of the list frame and performance of the proposed dual-frame monitoring approach. The average annual turnover rate for nests was 0.261, resulting in a rapid decay of the list frame. Decay of the list frame leads to a functional collapse of the dual-frame approach, down to the area-frame survey alone, early within the monitoring time horizon. This early decay of the list frame implies that the area-frame coverage needed to maintain the same statistical power as stated in the monitoring plan would have to be increased by a factor of 3 to 5 beyond that recommended in the current plan. Remedies for this deficiency undermine the cost benefit associated with inclusion of the list frame. We examined response of the dual-frame survey to variation in nest turnover rates and population growth rates and defined a state space where time to collapse is beyond the proposed 20-year time horizon. Because, under realistic estimates of turnover rates, the dual-frame approach collapses to the area frame within the proposed monitoring window, we recommend that the costs of list-frame maintenance be included in the procedure to optimize allocation of survey effort.