Patient and technique survival of diabetics on peritoneal dialysis: one-center's experience and review of the literature.

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD). This retrospective study investigated the long-term patient and technique survival and sought to identify the predictors of mortality in diabetic patients receiving PD. METHODS: Patients, aged 17 years or more who commenced home PD between January 31, 1994, and December 31, 2001 were included. Clinical data were available for 358 patients out of 418 total patients who started PD during this period. They were followed until cessation of PD, death, or to January 31, 2003. Survival probabilities were generated according to the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 358 patients were enrolled in the study. Among them, 139 patients (38.8%) were diabetics. The 1-, 2-, 3- and 5-year patient survival rates were 91%, 76%, 66% and 47% in diabetics and 94%, 89%, 84% and 69% in non-diabetics, respectively. Median actuarial patient survival for diabetic patients (51.8 months; 95% CI 36.0 â 67.5 months) was significantly shorter than that of non-diabetic patients (log rank 14.117, p < 0.001). Death-censored technique survival rates at 1-, 2-, 3- and 5-year were 90%, 83%, 67% and 58% in diabetic, and 94%, 87%, 77% and 70% in non-diabetic patients, respectively. Similar to patient survival, the median technique survival time was significantly shorter for diabetic patients (63.9 months; 95% CI 35.7 - 92.2 months) than that of non-diabetic patients (log rank 4.884, p = 0.027). Multivariate Cox regression analysis showed that advancing age was the only independent predictor of death in the diabetic patients, whereas higher age and wider pulse pressure were associated with mortality in non-diabetic patients. CONCLUSION: Long-term patient and technique survival for diabetic patients on PD seem to be improved compared to our previous report and other studies. The mortality of diabetic patients was predicted predominantly by advancing age. PD remains a viable form of long-term renal replacement therapy for diabetic patients with ESRD.

Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis.

INTRODUCTION: The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. METHODS: A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. RESULTS: Compared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999/QALM gained. Assuming a willingness-to-pay (WTP) of $4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%. CONCLUSION: The addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable.

Decision analysis as an aid to determining the management of early low rectal cancer for the individual patient.

PURPOSE: Because there are no data available from randomized controlled trials (RCT), a decision analysis was performed to aid in the decision of which option, a local excision with or without radiotherapy or an abdominal perineal resection (APR), should be offered to medically fit patients with early (suspected T1/T2) low (< 5 cm) rectal cancer. METHODS: All clinically relevant outcomes, including complications of surgery and radiotherapy, cure, salvageability after local recurrence, distant disease, and death, were modeled for both options. The probabilities of complications and outcomes after radiotherapy and/or local excision were derived from weighted averages of results from studies conducted between 1969 and 1997. The probabilities for the APR option were extracted from relevant RCTs. Long- and short-term patient-centered utilities for each complication and outcome were extracted from the literature and from expert opinion. RESULTS: The expected utility of local excision (EU = 0.81) for the base case was higher than the expected utility for APR (EU = 0.78). Although the result was sensitive to all variables, local excision was always favored over APR within the plausible ranges of the variables taken one, two, or three at a time. The model illustrated the tension between the patient's perception of a colostomy and the higher recurrence rates with local excision. CONCLUSION: The results of this decision analysis suggest that local therapy for early low rectal cancer is the preferred method of treatment. However, there must be careful preoperative assessment, patient selection, and consideration of patient concerns. In addition, decision analysis may be useful in providing patient information and assisting in decision making.

Bacterial phagocytosis and intracellular killing by alveolar macrophages in BB rats.

Diabetic patients and animals show an increased susceptibility to bacterial infections due to impaired bactericidal function of various host-defense mechanisms. In our study, we examined the ability of alveolar macrophages (AMs) of the diabetic BB rat to phagocytize and kill Staphylococcus aureus bacteria. Groups of spontaneously diabetic BB rats with variable severity of diabetes were used and compared with non-diabetes-prone BB rats. AMs obtained from diabetic insulin-deficient BB rats showed a markedly decreased capacity to phagocytize and kill bacteria, a defect that was partially corrected after a period of aggressive insulin treatment. Glucose-intolerant BB rats and diabetes-prone BB rats who did not develop diabetes showed a normal AM function compared to non-diabetes-prone BB rats. The impaired phagocytotic and bactericidal functions of AMs appeared to be caused by a cellular abnormality associated with the degree of insulin deficiency.

Psychotic symptoms in Parkinson's disease patients with dementia.

OBJECTIVE: To assess the prevalence of psychotic symptoms in a group of patients with Parkinson's disease (PD) and dementia and examine the association of psychotic symptoms with neuropsychiatric problems, the level of distress reported by caregivers, and cognitive and functional impairment. DESIGN: The psychotic and nonpsychotic patients with PD dementia were compared on a series of demographic, neuropsychiatric, behavioral, caregiver complaint, and cognitive measures. SETTING: The database from nine university-based State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTCs). PARTICIPANTS: 101 patients diagnosed with PD. RESULTS: A total of 36 of the 101 patients (35.6%) had either hallucinations, delusions, or both. The psychotic patients had significantly more insomnia, confusion, agitation, personality changes, and self-care problems and were noted by their caregivers to be significantly more unmanageable at home than their nonpsychotic counterparts. On cognitive scales, psychotic patients were significantly more impaired. CONCLUSION: Many patients with PD and dementia experience psychosis. Psychotic symptoms in PD dementia patients are associated with major behavioral, cognitive, and functional problems.

Primer on medical decision analysis: Part 3--Estimating probabilities and utilities.

This paper describes how to estimate probabilities and outcome values for decision trees. Probabilities are usually derived from published studies, but occasionally are derived from existing databases, primary data collection, or expert judgment. Outcome values represent quantitative estimates of the desirability of the outcome states, and are often expressed as utility values between 0 and 1. Utility values for different health states can be derived from the published literature, from direct measurement in appropriate subjects, or from expert opinion. Methods for assigning utilities to complex outcome states are described, and the concept of quality-adjusted life years is introduced.

Primer on medical decision analysis: Part 5--Working with Markov processes.

Clinical decisions often have long-term implications. Analysis encounter difficulties when employing conventional decision-analytic methods to model these scenarios. This occurs because probability and utility variables often change with time and conventional decision trees do not easily capture this dynamic quality. A Markov analysis performed with current computer software programs provides a flexible and convenient means of modeling long-term scenarios. However, novices should be aware of several potential pitfalls when attempting to use these programs. When deciding how to model a given clinical problem, the analyst must weigh the simplicity and clarity of a conventional tree against the fidelity of a Markov analysis. In direct comparisons, both approaches gave the same qualitative answers.

Primer on medical decision analysis: Part 1--Getting started.

This paper is Part 1 of a five-part series covering practical issues in the performance of decision analysis. The intended audience is individuals who are learning how to perform decision analyses, not just read them. The series assumes familiarity with the basic concepts of decision analysis. It imparts many of the recommendations the authors have learned in teaching a one-semester course in decision analysis to graduate students. Part 1 introduces the topic and covers questions such as choosing an appropriate question, determining the tradeoff between accuracy and simplicity, and deciding on a time frame.

Primer on medical decision analysis: Part 2--Building a tree.

This part of a five-part series covering practical issues in the performance of decision analysis outlines the basic strategies for building decision trees. The authors offer six recommendations for building and programming decision trees. Following these six recommendations will facilitate performance of the sensitivity analyses required to achieve two goals. The first is to find modeling or programming errors, a process known as "debugging" the tree. The second is to determine the robustness of the qualitative conclusions drawn from the analysis.

Primer on medical decision analysis: Part 4--Analyzing the model and interpreting the results.

This paper is the fourth of a five-part series that describes the principles of construction and evaluation of valid decision models. In this review, the authors describe the key principles of detecting and eliminating structural and programming errors in decision trees (debugging). In addition, they offer guidelines to facilitate the interpretation of analytic results of decision models.

Guidelines for verbal presentations of medical decision analyses.

Individuals new to decision analysis often have difficulty with oral presentations of original research projects. This article provides general guidelines on how to present effectively. Points include: 1) articulating the research issue, 2) reviewing current beliefs, 3) portraying the study question, 4) listing the main assumptions, 5) presenting the base-case analysis, 6) showing sensitivity analyses, and 7) discussing the implications. The guidelines comment on what to exclude from presentation and how best to handle audience questions. The guidelines do not replace general instruction in public speaking (or rigorous training in decision analysis), but may help students present research projects effectively.

Late renal transplant failure: an adverse prognostic factor at initiation of peritoneal dialysis.

BACKGROUND: Early renal transplant failure necessitating a return to dialysis has been shown to be a poor prognostic factor for survival. Little is known about the outcome of patients with late transplant failure returning to dialysis. It was our clinical impression that late transplant failure (>2 months) carries an increased morbidity and mortality risk in patients returning to dialysis. OBJECTIVE: To determine whether patients with a failed renal transplant have an outcome different to those on dialysis who have never received a kidney transplant. SETTING: Peritoneal dialysis (PD) unit in a teaching hospital. PATIENTS AND DESIGN: All failed renal transplant patients (fTx) in the Toronto Hospital Peritoneal Dialysis program between 1989 and 1996 were identified. This cohort of 42 fTx patients was compared with a cohort of randomly selected never-transplanted PD patients (non-Tx). The PD program was selected because of the availability of well-documented patient archival material. The non-Tx group was matched for age and presence of diabetes. Data were collected until retransplantation, change of dialysis modality or center, death, or until June 1998. RESULTS: There was no difference at initiation of PD between groups in serum albumin, residual renal function, or mean serum parathyroid hormone level. The mean low-density lipoprotein level was significantly higher in the fTx cohort. The duration of dialysis before Tx in fTx patients accounted for the increased total length of dialysis in fTx (mean 15 months). However, post-Tx the duration of PD was similar for both groups (30.7 months for fTx vs 31.6 months for non-Tx). The fTx group had a considerably worse outcome than the non-Tx group. The time to first peritonitis, subsequent episodes of peritonitis, catheter change, or transfer to hemodialysis occurred at a much faster rate in fTx patients. The most dramatic difference was in survival. There were 3 deaths in the non-Tx group and 12 in the fTx group (p < 0.01). The mean age at time of death in the fTx group was 47.5 years. Deaths were due mainly to gram-negative peritonitis and cardiovascular disease. CONCLUSIONS: We conclude that late failed renal transplant patients starting dialysis are at increased risk of complications and have strikingly higher mortality rates than non-Tx patients. A previously failed kidney transplant can be considered an adverse prognostic factor for patients commencing PD; these patients need to be closely monitored. Although this study was limited to PD patients, the same principles likely apply to fTx patients returning to any form of renal replacement therapy.

A replication study of obsessional followers and offenders with mental disorders.

The purpose of this study was to compare certain demographic, clinical, and criminal variables within subgroups of obsessional followers, and compare them to a group of offenders with mental disorders to attempt to replicate earlier findings. A static group archival design utilized a non-random group of convenience and a randomly selected comparison group. Sixty-five obsessional followers and 65 offenders with mental disorders were evaluated by psychiatrists and psychologists for court ordered reasons during their criminal proceedings. Both groups were evaluated during the same period, in the same court diagnostic clinic, and generally for sentencing determinations. The obsessional followers were measured on demographic, diagnostic, pursuit, victim, threat, violence, emotional, motivational, and defense variables. Inferential comparisons that used parametric and nonparametric statistics were done within and between groups on select variables. The obsessional followers had significantly greater estimated IQ than the offenders with mental disorders, but were neither older nor better educated. There were no significant differences in the high prevalence of both DSM-IV Axis I and II diagnoses. Obsessional followers who stalked prior sexual intimates were significantly more likely to have a substance abuse or dependence diagnosis. Obsessional followers who stalked strangers or acquaintances were more likely to be delusional. The majority of the obsessional followers, primarily motivated by anger, both threatened and were violent toward person or property. The modal obsessional follower is an average or above IQ, unemployed, unmarried male in his fourth decade of life. chronically pursuing a prior sexually intimate female. He is diagnosed with substance abuse or dependence and a personality disorder NOS, and has a prior psychiatric, criminal and substance abuse history. He is angry, likely to threaten her, and assault her person or property without causing serious injury.