Impact of postoperative radiation therapy and other perioperative factors on outcome after orthopedic stabilization of impending or pathologic fractures due to metastatic disease.

PURPOSE AND METHODS: We reviewed 64 orthopedic stabilization procedures in 60 consecutive patients diagnosed with metastatic disease to previously unirradiated femurs, acetabula, and humeri with pathologic or impending pathologic fracture. Thirty-five patients who received adjuvant postoperative radiation therapy were compared with 29 patients who were treated with surgery alone. Many potential perioperative and tumor prognostic variables were evaluated. RESULTS: On univariate analysis, surgery plus radiation therapy and prefracture functional status were the only significant predictors of patients who achieved normal use of the extremity (with or without pain) after surgery; on Cox multivariate analysis, only postoperative radiation therapy was significant (P = .02). Surgery-related factors such as use of methylmethacrylate, location of fracture, and type of surgery were not associated with improved functional status. The estimated probability of achieving normal use of the extremity (with or without pain) any time was 53% for postoperative radiation therapy versus 11.5% for surgery alone (P < .01). Second orthopedic procedures to the same site were more frequent in the group that received surgery alone. The actuarial median survival duration of the surgery-alone group was 3.3 months, compared with 12.4 months for the postoperative radiation therapy group (P = .02). CONCLUSION: While this study is limited by possible unaccountable selection biases, only postoperative radiation therapy was associated with patients regaining normal use of their extremity (with or without pain) and undergoing fewer reoperations to the same site. The improved overall survival associated with postoperative radiation therapy may represent selection bias.

Risk factors for Parkinson's disease.

Parkinson's disease (PD) has been associated with rural living, well-water consumption, and pesticide exposure; however, the individual risk contribution of these variables has not been established. We examined social and medical histories of predominantly rural populations to determine relative risk factors for PD. Patients and controls were surveyed regarding residency, occupation, medical history, and social and dietary habits. An initial multiple logistic regression model was confounded by excessive variable colinearity. Principal factor analysis yielded three factors: rural living (including years of rural residency and ground-water use), pesticide use, and male lifestyle (male gender, head trauma, male-dominated occupations). Other variables did not load in factor analysis and were entered separately, with the three factor scores, in a second multiple logistic regression model. Significant predictors of PD emerged (in order of strength): pesticide use, family history of neurologic disease, and history of depression. The predicted probability of PD was 92.3% (odds ratio = 12.0) with all three predictors positive. Pesticide use (distinguishable from rural living) can be considered a risk factor for the development of PD, with family history of neurologic disease and history of depression serving as weaker predictors of PD.

Role of postoperative radiation therapy after stabilization of fractures caused by metastatic disease.

PURPOSE: Although orthopedic stabilization is frequently performed for pathological fractures caused by metastatic disease, no data is available to support the value of postoperative radiation therapy (S+RT) in this setting. METHODS AND MATERIALS: We reviewed 64 orthopedic stabilization procedures in 60 consecutive patients with metastatic disease to previously unirradiated weight-bearing bones with pathological or impending pathological fracture (femur 91%). Thirty-five sites that received adjuvant S+RT were compared to 29 sites that were treated with surgery alone (SA). Many potential prognostic variables were evaluated. Endpoints were: functional status (FS) of the extremity (1 = normal pain free use; 2 = normal use with pain, 3 = significantly limited use; 4 = nonfunctional extremity), subsequent orthopedic procedures to the same site, and survival following surgery. RESULTS: At the univariate level, S+RT (p = 0.02) and prefracture FS (p = 0.04) were the only significant predictors of patients achieving an FS of 1 or 2 after surgery. On multivariate analysis, only postoperative RT was significantly (p = 0.02) associated with attaining FS of 1 or 2 after surgery. The predicted probability of achieving FS 1 or 2 at any time was 53% for S+RT vs. 11.5% or SA (multiple logistic regression, p < 0.01). Evaluation of FS following surgery revealed that S+RT group had significantly better function in the 1-3, 3-6, and 6-12 month postoperative periods (chi-square, p < 0.04 for each time period). Second orthopedic procedures to the same site were more common in the SA group than the S+RT group (log rank, p = 0.03). Actuarial median survival of S group was 3.3 months compared with 12.4 months for the S+RT group (log rank, p = 0.02), confirming the beneficial association with survival shown by the multivariate Cox regression analysis (p = 0.025). CONCLUSION: Although this retrospective study is subject to possible biases, several analyses adjusting for numerous prognostic factors uniformly indicate S+RT is the most important factor in patients achieving and maintaining normal functional status (+/- pain). Further, the S+RT group was associated with fewer orthopedic procedures as well as an improved overall survival. The improved survival may be due to (a) more favorable patients being referred for RT (possible section bias), or (b) improved functional status in the S+RT group. This study quantitatively supports the benefit of postoperative RT in this setting.

The comparative validity of eleven alcoholism typologies.

OBJECTIVE: This study directly compared the clinical validity of 11 empirically defined alcoholism typologies to determine whether some typologies are clinically more valid than others. METHOD: A sample of 360 hospitalized alcoholic men were extensively evaluated at entry into the study and again 1 year later. Twenty-three measures of clinical validity were employed; 15 were postdictive and 8 were predictive. Postdictive retrospective measures obtained at entry into the study included family history, age of onset and lifetime course characteristics associated with alcoholism severity, general psychopathology and psychosocial functioning. Predictive outcome measures drawn from information obtained during the 1-year follow-up included: abstinence, alcoholism severity and clinician ratings of outcome. The measures were subjected to various statistical analyses, including factor analysis. RESULTS: We found that all of the alcoholism typologies met at least 7 of the 23 a priori measures of clinical validity. The correlations between these conceptually and methodologically disparate typologies were often striking. Exploratory factor analysis, which explained 35% of the variance, suggested three possible underlying dimensions to account for the overlap among typologies: (1) age and its correlates, including age-of-alcoholism onset; (2) "pure" alcoholism versus psychiatrically heterogeneous alcoholism that encompassed antisocial personality disorder; and (3) current severity of psychiatric distress, impairment and dysfunction. CONCLUSIONS: No single method of subtyping alcoholics clearly emerged as superior. All demonstrated some degree of predictive and postdictive clinical validity. Most methods of subtyping correlated positively with each other at moderate, but typically significant, levels.

Factors predictive of heightened third-day bilirubin levels: a multiple stepwise regression analysis.

The purpose of this research was to prospectively study the variables contributing to the variance in third-day bilirubin levels in healthy, full-term newborns. The study subjects were 252 full-term, healthy infants born at the University of Kansas Medical Center over a four-month period. Using a multiple stepwise regression analysis, six factors were found to be significant predictors of higher third-day bilirubin levels: higher cord bilirubin level; lower total serum protein in the infant on admission to the nursery; sex of the child; administration of promethazine hydrochloride during labor; greater weight loss in the infant; and breast-feeding. Several other factors which have been implicated previously--including use of oxytocin for induction or augmentation of labor, previous use of birth control pills by the mother, prolonged rupture of membranes prior to delivery, type of delivery, race, and epidural anesthesia--were not found to be significant predictors of third-day bilirubin levels once the six variables listed had been taken into consideration. The results are discussed in terms of past research as well as implications for clinical practice.

The relationship of breast feeding to third-day bilirubin levels.

The purpose of this study was to determine the relationship of feeding method to serum bilirubin levels on the third day of life. Two hundred eighty-one apparently healthy full-term neonates had third-day bilirubin levels drawn between 58 and 82 hours of age. Mean serum bilirubin levels were 5.6 mg/dL for formula-fed, 6.9 mg/dL for mixed-fed, and 7.5 mg/dL for breast-fed infants. The difference was statistically significant (P less than .01) between the formula-fed and breast-fed groups. Breast-fed infants lost more weight by the third day than formula-fed infants (mean weight loss 180 g for breast-fed infants, 100 g for formula-fed infants). A third-day bilirubin levels among the feeding groups were then compared using an analysis of covariance with weight loss as the covariate. By this method, type of feeding was still a significant predictor of third-day bilirubin levels (P = .04) as was weight loss (P = .03).

Personality and depression in Parkinson's disease.

The Parkinson's disease (PD) patient has been characterized as having a distinctive personality with introverted features. These personality traits are said to predate motor symptoms and are theorized to serve as a subtle clue to latent PD. To examine this hypothesis, we compared remote and current personality features in 35 PD subjects and 35 controls. Subjects' spouses completed a personality inventory (PI) characterizing patients' premorbid and current status. The premorbid PI of PD subjects differed from that of controls in being more "quiet," "generous," "cautious," and "even-tempered," and less "flexible." The characterization of the PD subjects' current personality differed greatly from reported premorbid personality features, i.e., significant change in 13 of 24 PI items. Personality inventory responses regarding both the PD subjects' premorbid and current personality correlated to symptoms of depression and disease severity. Cognition, tobacco use, alcohol consumption, and rural versus urban residency did not correlate with PI responses. We conclude that PD patients are apt to be viewed as introverts premorbidly, and, with disease onset, more striking personality changes are recognized. These perceptions appear to be closely linked to depressed affect and correlate with motor impairment to a lesser extent.

Risk factors for dementia in Parkinson's disease: effect of education.

Cognitive deficits are common in Parkinson's disease (PD), but the pathophysiology and relationship to Alzheimer's disease (AD) are not understood. We used a case-control format to investigate putative risk factors for the development of dementia in patients with Parkinson's disease. We compared 52 cognitively intact patients with PD to 43 PD patients with dementia with regard to factors previously suggested as relevant to either AD or PD. Multiple logistic regression yielded the following significant predictors of dementia in PD: lack of education (less than a high school graduate) (OR 21); severity of motor deficit (UPDRS total motor score greater than 20; OR 6.34), and PD onset at greater than 60 years of age (OR 4.12). The predictive probability of dementia in our subjects when all three variables were positive was 97.9%. We conclude that education may modify the risk of cognitive decline in PD. Protective effects of educational attainment, independent of dementia etiology, may be due to greater functional brain reserve.

Gene-toxin interaction as a putative risk factor for Parkinson's disease with dementia.

We had previously examined environmental, sociodemographic and clinical variables as predictors for Parkinson's disease with dementia (PD + D) and found that lower educational attainment, greater motor impairment and advanced age at disease onset were more common in PD + D than in subjects with Parkinson's disease without dementia (PD-D). We now explore the hypothesis that genetic traits coupled with nongenetic factors may raise the risk of development of PD + D. The study cohort of 43 PD + D and 51 PD-D subjects was analyzed examining environmental, sociodemographic and clinical variables along with 3 candidate gene markers: poor debrisoquine metabolizer allele (CYP 2D6 29B+), monoamine oxidase B allele 1, and apolipoprotein E epsilon 4 allele. Variables were initially entered into a multivariate model singly. Again lower education, age at onset and motor impairment appeared as predictors of PD + D while other variables (including allele status) failed to emerge as significant individual risk factors for dementia. We then examined environmental and genetic variables analyzed in tandem to look for potential variable interactions. Subjects who had pesticide exposure and at least 1 copy of the CYP 2D6 29B+ allele had 83% predicted probability of PD + D (stepwise logistic regression model: p = 0.0491). This case-control study provides preliminary evidence that a gene-toxin interaction may play an etiological role in PD + D. Further assessment of the role of these putative risk factors in incident dementia in PD is indicated.

Patterns of failure after curative resection of pancreatic carcinoma.

Thirty-six patients underwent curative resection of a primary pancreatic carcinoma from January 1977 to September 1987; 26 had Whipple resections, seven had total pancreatectomies, and three had distal pancreatectomies. Twenty-six patients manifested recurrent disease, four died of intercurrent disease, and six were apparently cured. Median survival was 11.5 months with actuarial survival at 2 and 5 years of 32% and 17%, respectively. Of the eventual recurrences, 19% were local only (pancreatic bed, regional nodes, adjacent organs, and immediately adjacent peritoneum) and 73% had a component of local failure. All patients failing did so with a component in the intraabdominal cavity. Peritoneal (42%) and hepatic failures (62%) were common. Extraabdominal metastases were documented in only 27%, but never as a sole site. Fourteen patient and tumor characteristics were evaluated for any relationships with failure or survival. No single variable independently predicted for local failure. However, a group of three (age greater than 60 years, T2 or T3 stage, and location of tumor in the body or tail) was associated with a substantial local failure risk (85% of all patients with local failure). Multivariate analysis showed that low tumor grade (P = 0.002), female sex (P = 0.002), and adjuvant radiation (P = 0.02) were all independent predictors of prolonged survival. Ten patients were treated in an adjacent setting. Those given 55 Gy or greater had improved local control (50% versus 25%) and cure (33% versus none) when compared with patients treated to lower doses. The authors conclude that local failure after curative resection remains a significant problem and further efforts to improve local control are warranted. However, peritoneal and hepatic relapses occur frequently. Thus, adjuvant treatment strategies using wide-field radiation techniques or intraperitoneal therapy, in combination with local tumor bed irradiation and chemotherapy, should be explored.