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A polemic on principles: reflections on the Pittsburgh protocol.

The Pittsburgh protocol relies heavily on traditional moral distinctions, particularly the principle of double effect, to justify "managing" the dying process of a prospective organ donor in order to yield viable organs for transplantation. These traditional moral distinctions can be useful, particularly in casuistic or case-specific moral analysis, but their invocation here is unpersuasive, and potentially dangerous. The protocol relies on elaborate apologetics to avoid a candid confrontation with the moral challenge it poses--society's willingness to bring about the death of one patient (in isolation and with potential discomfort) in order to benefit another patient. Not only will this protocol fail to solve the problem it purports to address, it threatens to undermine the delicate social accommodations by which we distinguish the living from the dead, permissible "allowings to die" from impermissible killings, and those from whom organs may be removed from those whose bodies must remain inviolate.

Cause of Death↗

Are the patients who become organ donors under the Pittsburgh protocol for "non-heart-beating donors" really dead?

The University of Pittsburgh Medical Center (UPMC) "Policy for the Management of Terminally Ill Patients Who May Become Organ Donors after Death" proposes to take organs from certain patients as soon as possible after expected cardiopulmonary death. This policy requires clear understanding of the descriptive state of the donor's critical cardiopulmonary and neurologic functional capacity at the time interventions to sustain or harvest organs are undertaken. It also requires strong consensus about the moral and legal status of the donor during dying and confirmation of death. There has been no need for the clarity and precision that this policy relies upon, and thus the needed research and conceptual work has not previously been generated. The empiric base and societal consensus are both too frail to provide justification for this policy at this time.

Death↗

Development of the University of Pittsburgh Medical Center policy for the care of terminally ill patients who may become organ donors after death following the removal of life support.

In the mid 1980s it was apparent that the need for organ donors exceeded those willing to donate. Some University of Pittsburgh Medical Center (UPMC) physicians initiated discussion of possible new organ donor categories including individuals pronounced dead by traditional cardiac criteria. However, they reached no conclusion and dropped the discussion. In the late 1980s and the early 1990s, four cases arose in which dying patients or their families requested organ donation following the elective removal of mechanical ventilation. Controversy surrounding these cases precipitated open discussion of the use of organ donors pronounced dead on the basis of cardiac criteria. Prolonged deliberations by many committees in the absence of precedent ultimately resulted in what is, to our knowledge, the country's first policy for organ donation following elective removal of life support. The policy is intricate and conservative. Care was taken to include as many interested parties as possible in an effort to achieve representative and broad based support. This paper describes the development of the UPMC policy on non-heart-beating organ donation.

Attitude of Health Personnel↗

Apolipoprotein E Pittsburgh variant is not associated with the risk of late-onset Alzheimer's disease in a Spanish population.

The objective of this study was to assess whether the APOE(Pittsburgh) variant (APOE*4P) is associated to Alzheimer's disease (AD) in a population from Madrid (Spain). APOE*4P variant is caused by an exonic mutation which results in the substitution of proline-28 for leucine-28, only present in APOE*4 alleles. A study in a US population associated this APOE variant with an increased risk for AD, about five times higher than the risk attributed to APOE*4 carriers overall. One hundred and seventeen cases of late-onset AD and 121 matched control subjects from Madrid (Spain) were included. We studied the APOE polymorphism and the APOE*4P occurrence, by PCR and restriction analysis, and plasma lipids levels using standard protocols. As expected, APOE*4 was significantly overrepresented in AD cases. The APOE*4P mutation was observed in heterozygous state in four subjects, two AD (1.71%) and two controls (1.65%). APOE*4P did not confer higher risk for AD, globally (odds ratio 0.14; 95% confidence interval (CI) 0.02-1.12) or respect to APOE*4 carriers (odds ratio 0.14; 95% CI 0.02-1.24). There were no differences in plasma lipids levels among genotype groups. The mutation frequency in controls was higher in our sample than in the US one (1.65 and 0.18%, respectively; Fisher test P = 0.049). Our results suggest that this variant is not so uncommon in our population and is not directly related to AD, contrary to what has been proposed for other populations.

Age of Onset↗

Demography and evolution of an urban ethnic community: Polish Hill, Pittsburgh.

Polish Hill is an urban, ethnic enclave of approximately 3000 residents residing in a 25-block area of Pittsburgh. This paper documents changes in the fertility, morbidity, and mortality patterns in the community from the turn of the century to the present. The demographic reconstruction is based upon baptismal and marriage records, the administration of demographic proformae and population censuses. The high mortality, morbidity, and fertility variance suggest that the immigrant population has experienced a period of high opportunity for selection in the early 1900's and that Crow's index was gradually reduced to its present level.

Adolescent↗

Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.

This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94-fold, p = 0.0001). Large increases also were observed in parietal (1.71-fold, p = 0.0002), temporal (1.52-fold, p = 0.002), and occipital (1.54-fold, p = 0.002) cortex and the striatum (1.76-fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 +/- 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F-fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.

Adult↗

Liver procurement for orthotopic transplantation: an analysis of the Pittsburgh experience.

The incidence of prospective organ donors in the United States and the techniques which are to used to guarantee their optimal use after identification are analyzed. Attitudes of the public and health professionals toward organ donation are discussed. The organization of the Pittsburgh Organ Procurement Agency and its relationship to other such agencies is described. Finally, the presently used techniques of liver salvaging and preservation are outlined.

Adolescent↗

The Pittsburgh diabetes mellitus study. 3: An increased prevalence with older maternal age.

A series of patients having onset of Type I (insulin-dependent) diabetes mellitus before age 17 years was identified from consecutive admissions to the Children's Hospital of Pittsburgh. Family history data were obtained yielding 1006 families (1085 cases) with complete information. The prevalence of diabetes among the children differed by birth order, with a greater number than expected among first born. There was also an increased prevalence among children born to mothers older than 35 years, as well as an increased prevalence among children of very young mothers. The increased prevalence of diabetes among offspring of older mothers was apparent even after life table age corrections were made. However, both the increased prevalence among first born children and the increased prevalence among children of very young mothers could be attributed to an older attained age of these children in this particular population. This indicated that the maternal age effect was present but a birth order effect was absent when age was taken into account.

Actuarial Analysis↗

Comparison of University of Wisconsin and University of Pittsburgh solutions for heart transplantation.

The effectiveness of University of Wisconsin (UW) and University of Pittsburgh (UP) solutions for the preservation of rat hearts was compared. Lewis rat hearts were preserved with UW (group A, n = 45) or UP (group B, n = 45) solution for 0 or 24 h and then transplanted heterotopically into the recipients' abdomen. Ten recipients in each group were observed to obtain 1-week graft survival rates. Tissue water content and tissue content of adenine nucleotides were measured 2 h after transplantation in six grafts from each group. Six hearts preserved for 0 h and seven hearts preserved for 24 h were taken from each group 24 h after grafting for histopathology. The 1-week graft survival rates of groups A24 and B24 were 60% and 10%, respectively. In the 24-h preserved grafts, adenosine triphosphate (ATP) and energy charge [(ATP + adenosine diphosphate/2)/(ATP + adenosine diphosphate + adenosine monophosphate)] of groups A and B were 0.972 +/- 0.165 and 0.200 +/- 0.123 mg/g wet tissue (P < 0.05) and 74.4% and 61.1% (P < 0.05), respectively. The tissue water content of group A24 was 71.7%, whereas that of group B24 was 74.1% (P < 0.05). Histopathology revealed more severe muscle edema and necrosis and infiltration of polymorphonuclear cells in group B24 than in group A24. We conclude that UW solution is more appropriate for rat heart preservation than UP solution.

Abdomen↗

The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study.

AIMS/HYPOTHESIS: Recent findings suggest the potential involvement of adiponectin in obesity, diabetes and cardiovascular disease. We assessed the prospective association between adiponectin concentration and coronary artery disease in individuals with type 1 diabetes. METHODS: Participants were identified from the Pittsburgh Epidemiology of Diabetes Complications cohort, a prospective follow-up study of childhood-onset type 1 diabetes. At baseline, subjects had a mean age of 28 years, and a mean diabetes duration of 19 years. Cases (determined by physician-diagnosed angina, confirmed myocardial infraction, stenosis >or=50%, ischemic ECG or revascularization) were matched to the control subjects with respect to sex, age and diabetes duration. Samples and risk factors for analyses were identified from the earliest exam prior to incidence in cases. Sera and information on all covariates were available for 28 cases and 34 control subjects. Proportional hazards models were constructed including matching variables. RESULTS: Compared with those in men, adiponectin concentrations were elevated in females (p=0.009) and among individuals with macroalbuminuria (p=0.04). In multivariable analyses (adjusting for standard risk factors as well as lipoprotein measurements determined by nuclear magnetic resonance spectroscopy, E-selectin or antioxidants), adiponectin inversely predicted the incidence of coronary artery disease (hazard ratio=0.37 per 1 SD increase, 95% CI 0.19-0.73, p=0.004). CONCLUSIONS/INTERPRETATION: The results suggest that increased adiponectin concentration is prospectively associated with a lower risk of coronary artery disease type 1 diabetes. The potential of adiponectin determination as a useful marker of, and potential therapeutic target for, coronary artery disease prevention in type 1 diabetes should be further explored.

Adiponectin↗

Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects.

In order to effectively study the population experiencing insomnia, it is important to identify reliable and valid tools to measure sleep that can be administered in the home setting. The purpose of this study was to assess psychometric properties for the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in community-dwelling adults with primary insomnia. The CPSQI had an overall reliability coefficient of 0.82 -0.83 for all subjects. "Subjective sleep quality" was the component most highly correlated with the global score. Overall, the CPSQI showed acceptable test-retest reliability over a 14- to 21-day interval with a coefficient of 0.85 for all subjects and 0.77 for primary insomniacs. The two contrasting groups had significantly different global and component scores. A CPSQI of greater than 5 yielded a sensitivity and specificity of 98 and 55% in primary insomniacs vs. controls. A CPSQI of greater than 6 resulted in a sensitivity and specificity of 90 and 67%. Results suggest that the CPSQI is a psychometrically sound measure of sleep quality and disturbance for patients with primary insomnia. It may not be an effective screening tool because of its low specificity, but it can be a sensitive, reliable, and valid outcome assessment tool for use in community-based studies of primary insomnia.

Adult↗

The Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) study. HLA antigens and haplotypes as risk factors for the development of IDDM in IDDM patients and their siblings.

The relationships between HLA antigens, sex, age at diagnosis, season of onset and insulin-dependent diabetes mellitus (IDDM) were studied in a consecutive admissions series of newly-diagnosed IDDM patients at Children's Hospital of Pittsburgh. In agreement with the findings of others, the strongest positive associations between IDDM and HLA antigens were seen with DR3 and DR4 (odds ratios (OR) of 3.5 and 4.4, respectively), while a very strong negative association was observed with DR2 (OR of 0.1). Male patients were significantly more likely than female patients to possess DR3 while female patients were significantly more likely to be DR4+. No consistent relationships were found between HLA antigens and either age at diagnosis or season of onset. Using a life table approach, the cumulative risk of IDDM by age 24 in HLA-identical siblings of IDDM patients was estimated to be 10.3%. This risk was significantly greater than the risks to either HLA-haploidentical siblings (2.2%) or to HLA-nonidentical siblings (1.0%), whose risks were not significantly different. B7 + HLA-identical siblings of patients appeared to be protected from the effects of HLA-identicality--their cumulative risk by age 24 was estimated to be only 2.3%.

Actuarial Analysis↗

Methodologic evaluation of incidence rates for hypertension: calculated for Pittsburgh's MRFIT usual care men.

Methodologic limitations in the calculation of incidence rates for hypertension and in the assessment of associations between rates of change in attributes and the development of hypertension were examined for Pittsburgh's MRFIT Usual Care population. In a group of normotensive middle-aged men at high risk for the development of coronary heart disease, the incidence of hypertension ranged from 6.2 to 15.5 per 100 man years, depending on the definition of hypertension. A simulation study showed that the magnitude of these incidence rates could be explained by random variation in the measurement of blood pressure. Controlling for these random effects, the development of hypertension was associated with high normal baseline diastolic blood pressure and with a reported past diagnosis of hypertension, but not with age or baseline body mass index. Finally, a method, estimating the relative risk associating weight gain and the development of hypertension, was presented.

Adult↗

The impact of the apolipoprotein E polymorphism on the lipoprotein profile in insulin-dependent diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study IX.

The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.

Adult↗

The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research.

Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.

Adult↗

The progression of retinopathy over 2 years: the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study.

This study examined potential risk factors for the incidence and progression of retinopathy in a large representative cohort of childhood onset insulin-dependent diabetic patients. Participants in the Epidemiology of Diabetes Complications (EDC) Study underwent a full clinical examination at baseline and again at a 2-year follow-up. Retinopathy status was ascertained using stereo fundus photographs graded according to the modified Airlie House System. The study population is based on a large cohort of childhood-onset insulin-dependent diabetic patients, seen within 1 year of diagnosis at the Children's Hospital of Pittsburgh between January 1950 and May 1980. A total of 657 subjects participated at baseline (1986-1988), with 80% of eligible survivors taking part in the follow-up examination. This report concerns risk factors associated with the progression of diabetic retinopathy over a 2-year period, and the interaction of these factors with the presence of nephropathy. Analyses showed that baseline diastolic blood pressure was significantly associated with the incidence of any retinopathy, while glycosylated hemoglobin, baseline severity of retinopathy, serum triglycerides, and, to a lesser extent, higher levels of low-density lipoprotein (LDL) cholesterol and fibrinogen were associated with the progression of retinopathy. Progression to proliferative retinopathy was related to higher LDL cholesterol, fibrinogen, serum triglycerides, albumin excretion rate, and glycosylated hemoglobin (GHb). Risk factors varied with the presence of nephropathy. In the absence of nephropathy, GHb was a significant predictor of progression, whilst this was not the case in the presence of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The Pittsburgh Rehabilitation Participation Scale: reliability and validity of a clinician-rated measure of participation in acute rehabilitation.

OBJECTIVE: To demonstrate interrater reliability and predictive validity of the Pittsburgh Rehabilitation Participation Scale (PRPS), a clinician-rated 6-point Likert-type item measuring patient participation in inpatient rehabilitation sessions. DESIGN: Prospective measurement of patient participation in physical and occupational therapy sessions during inpatient rehabilitation. SETTING: University-based, freestanding acute rehabilitation hospital. PARTICIPANTS: Two hundred forty-two inpatients, primarily elderly, with a variety of impairment diagnoses (eg, stroke), who were admitted for inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Change in the 13 motor items from the FIM trade mark instrument, from admission to discharge. RESULTS: The PRPS had high interrater reliability (intraclass correlation coefficient [ICC]=.91 for occupational therapists; ICC=.96 for physical therapists). The subjects had mean PRPS scores +/- standard deviation of 4.73+/-0.76. Mean PRPS scores predicted rehabilitation outcome (N=242, r=.32, P<.0001), as measured by change in motor FIM. The strength of this association did not change in a multivariate model that controlled for age, gender, race, impairment group, medical comorbidity count, length of stay, and admission FIM. CONCLUSIONS: Patient participation during acute inpatient rehabilitation can be easily and reliably measured, and PRPS scores predict functional outcome. The PRPS may have applicability in clinical and research outcome measurement.

Adult↗