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PubMed1995

Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up.

OBJECTIVES: To assess the evolution of cognitive dysfunction in early-onset multiple sclerosis, to identify clinical predictors of mental decline, and to determine its impact on a patient's everyday life. DESIGN: The cognitive performance of 50 patients with multiple sclerosis on a neuropsychological battery was compared with that of 70 control subjects initially and again after a 4-year interval. Clinical predictors of cognitive impairment and its effect on daily life were analyzed by stepwise linear regression. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: A consecutive sample of 50 inpatients and outpatients with multiple sclerosis (mean disease duration, 1.58 years) and 70 demographically matched healthy control subjects selected from the patients' relatives and friends. MAIN OUTCOME MEASURES: Mean psychometric test scores of both groups at the initial and follow-up testing. Regression coefficients measuring the relationship between clinical parameters and cognitive capacity and between mental decline and performance of common tasks measured by the Environmental and the Incapacity Status scales. RESULTS: Multiple sclerosis-related deficits in verbal memory and abstract reasoning on initial testing remained more or less stable on the retest, at which time linguistic disturbances on the Set and Token tests also emerged. A patient's initial disability level predicted decreased performance on only four of 13 cognitive variables, and disease duration did so on only two. Extent of intellectual decline on initial testing, initial disability level, and progressive course were independent determinants of handicap in a patient's work and social activities. CONCLUSIONS: Cognitive and neurological deficits appear not to develop in parallel. Yet cognitive dysfunction proves to be a predictor of handicap in everyday life, even in patients in the incipient phase of multiple sclerosis.

Adolescent↗

PubMed2006

Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.

OBJECTIVE: To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis. DATA SOURCES: We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles. STUDY SELECTION: We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort. DATA EXTRACTION: Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis. DATA SYNTHESIS: Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis. CONCLUSIONS: The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.

Adult↗

PubMed2004

Clinical predictors of quality of life in patients with head and neck cancer.

OBJECTIVE: To identify clinical predictors of quality of life (QoL) in a head and neck cancer patient population. DESIGN, PATIENTS, AND SETTING: A convenience sample of 570 patients with upper aerodigestive tract cancers were surveyed at a tertiary care oncology clinic and Veterans Affairs otolaryngology clinic. INTERVENTIONS: A self-administered health survey was constructed to collect demographic, health, smoking, alcohol, depression symptom, and QoL information. Tumor site and tumor stage, clinical, and treatment data were abstracted from the patient medical records. MAIN OUTCOME MEASURES: Quality of life was assessed using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the Head and Neck QoL (HNQoL) instrument. RESULTS: Of the 570 eligible respondents, the presence of a feeding tube had the most negative impact on QoL, with significant decrements in 6 of the 8 SF-36 scales and all 4 HNQoL scales (P<.01). In descending order of severity, medical comorbid conditions, presence of a tracheotomy tube, chemotherapy, and neck dissection were also associated with significant (P<.05) decrements in QoL domains. Patients who took the survey more than 1 year after diagnosis had improved QoL in 7 of 12 domains. Hospital site, age, education level, sex, race, and marital status were also significant predictors of QoL. CONCLUSION: There are at least 13 demographic and clinical characteristics that are significant predictors of QoL in patients with head and neck cancer, which should be considered when treating patients and conducting QoL studies in the future.

Adult↗

PubMed1997

Predictors of recurrent febrile seizures. A prospective cohort study.

OBJECTIVES: To define the risk and identify predictors of single and multiple recurrent febrile seizures. METHODS: Children (n = 428) with first febrile seizures were prospectively identified and followed for 2 or more years. Parents were interviewed soon after their children's first febrile seizure and were called every 3 months to ascertain recurrent febrile seizures. Medical records of first and recurrent seizures were reviewed for additional information. RESULTS: A total of 136 children (31.8%) experienced recurrent seizures: 73 (17.1%) had only 1 recurrence, 38 (8.9%) had 2 recurrences, and 25 (5.8%) had 3 or more recurrences. Young age at onset, a history of febrile seizures in a first-degree relative, low degree of fever while in the emergency department, and a brief duration between the onset of fever and the initial seizure were strong independent predictors of recurrent febrile seizures. With these 4 factors combined, it is possible to define groups of children having very high and very low probabilities of having any recurrences (> 70% vs < 20%), having 2 or more recurrences (> 60% vs < 10%), and having 3 or more recurrence (12% vs about 0%). In children who had at least 1 recurrence, age at the time of the first recurrence and a family history of epilepsy were predictors of subsequent recurrences. CONCLUSIONS: In children who have had a first febrile seizure, recurrences are common. The risk for 1 or more recurrences can be meaningfully predicted at the time of the initial febrile seizure with a combination of the 4 factors identified in this study.

Child, Preschool↗

PubMed1977

Prediction of outcome in schizophrenia. III. Five-year outcome and its predictors.

Recent studies of schizophrenia have begun to demonstrate the complex nature of its outcome characteristics and their predictors. However, generalization of findings has been limited by methodological problems such as relatively short-term follow-up the use of retrospective data, or employment of evaluation techniques without demonstrated reliability. This report describes a prospective, five-year follow-up using reliable evaluation techniques to determine whether specific relations between predictors and outcome variables represent behavior patterns persisting over an extended period. Results demonstrate the prognostic importance and specificity of certain predictors over five years. These results support the view that outcome function is comprised of persisting open-linked systems of behavior.

Employment↗

PubMed2003

Predictors of mortality in eating disorders.

BACKGROUND: Anorexia nervosa, but not bulimia nervosa, has one of the highest mortality rates among psychiatric disorders. However, potential predictors of mortality, such as comorbid psychiatric illnesses, remain unclear. We sought to determine mortality ratios and predictors of fatal outcome in women diagnosed as having anorexia or bulimia nervosa. METHODS: Women (N = 246) diagnosed as having either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) between January 1, 1987, and December 31, 1991, participated in a prospective longitudinal study. Vital status was determined by ongoing contact and a National Death Index search as of December 1998 (overall ascertainment, 99.8%) and telephone contact as of October 2000 (ascertainment, 95.0%). RESULTS: Eleven women died. Standardized mortality ratios were elevated for all causes of mortality (11.6; 95% confidence interval, 5.5-21.3) and suicide (56.9; 95% confidence interval, 15.3-145.7) in anorexia nervosa but not for death (1.3; 95% confidence interval, 0.0-7.2) in bulimia nervosa. Predictors of mortality in anorexia nervosa included severity of alcohol use disorder during follow-up (P<.001). Hospitalization for an affective disorder before baseline assessment seemed to protect women from a fatal outcome (P<.001). CONCLUSIONS: Physicians treating patients with anorexia nervosa should carefully assess patterns of alcohol use during the course of care because one third of women who had alcoholism and died had no history of alcohol use disorder at intake.

Alcoholism↗

PubMed2000

Heart rate recovery and treadmill exercise score as predictors of mortality in patients referred for exercise ECG.

CONTEXT: Both attenuated heart rate recovery following exercise and the Duke treadmill exercise score have been demonstrated to be independent predictors of mortality, but their prognostic value relative to each other has not been studied. OBJECTIVE: To assess the associations among abnormal heart rate recovery, treadmill exercise score, and death in patients referred specifically for exercise electrocardiography. DESIGN AND SETTING: Prospective cohort study conducted in an academic medical center between September 1990 and December 1997, with a median follow-up of 5.2 years. PATIENTS: A total of 9454 consecutive patients (mean [SD] age, 53 [11] years; 78% male) who underwent symptom-limited exercise electrocardiographic testing. Exclusion criteria included age younger than 30 years, history of heart failure or valvular disease, pacemaker implantation, and uninterpretable electrocardiograms. MAIN OUTCOME MEASURES: All-cause mortality, as predicted by abnormal heart rate recovery, defined as failure of heart rate to decrease by more than 12/min during the first minute after peak exercise, and by treadmill exercise score, defined as (exercise time) - (5 x maximum ST-segment deviation) - (4 x treadmill angina index). RESULTS: Three hundred twelve deaths occurred in the cohort. Abnormal heart rate recovery and intermediate- or high-risk treadmill exercise score were present in 20% (n = 1852) and 21% (n = 1996) of patients, respectively. In univariate analyses, death was predicted by both abnormal heart rate recovery (8% vs 2% in patients with normal heart rate recovery; hazard ratio [HR], 4.16; 95% confidence interval [CI], 3.33-5.19; chi(2) = 158; P<.001) and intermediate- or high-risk treadmill exercise score (8% vs 2% in patients with low-risk scores; HR, 4.28; 95% CI, 3.43-5.35; chi(2) = 164; P<.001). After adjusting for age, sex, standard cardiovascular risk factors, medication use, and other potential confounders, abnormal heart rate recovery remained predictive of death (among the 8549 patients not taking beta-blockers, adjusted HR, 2.13; 95% CI, 1.63-2.78; P<.001), as did intermediate- or high-risk treadmill exercise score (adjusted HR, 1. 49; 95% CI, 1.15-1.92; P =.002). There was no interaction between these 2 predictors. CONCLUSIONS: In this cohort of patients referred specifically for exercise electrocardiography, both abnormal heart rate recovery and treadmill exercise score were independent predictors of mortality. Heart rate recovery appears to provide additional prognostic information to the established treadmill exercise score and should be considered for routine incorporation into exercise test interpretation. JAMA. 2000;284:1392-1398.

Adult↗

PubMed2001

Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.

CONTEXT: Several novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers. OBJECTIVE: To compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status-matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls. MAIN OUTCOME MEASURE: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100. RESULTS: In univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P =.001), triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP (P =.006), and the total cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P =.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P =.40) and homocysteine (P =.90) were observed. In multivariable analyses, the total cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001). CONCLUSIONS: Of 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.

Adult↗

PubMed2005

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents.

CONTEXT: Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. OBJECTIVE: To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. DESIGN, SETTING, AND PATIENTS: Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. INTERVENTIONS: Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. MAIN OUTCOME MEASURES: Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. RESULTS: At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR], 89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR, 6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR, 6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR, 3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR, 1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). CONCLUSIONS: The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.

Angioplasty, Balloon, Coronary↗

PubMed1996

Predictors of transcutaneous oxygen tension in the lower limbs of diabetic subjects.

We examined neuropathy, ankle pressure index (API), and other factors as predictors of transcutaneous oxygen (TcPO2) in the lower limbs of 657 diabetic subjects. Eligible subjects underwent a clinical assessment that included three standard measures of autonomic neuropathy. TcPO2 measurements were performed at 37 degrees C and 44 degrees C at four lower limb locations. Associations between potential predictors and TcPO2 were tested using univariate and multivariate statistics. Mean TcPO2 at any site did not differ by presence of autonomic neuropathy at either temperature, except for a significantly lower value at 44 degrees C below the knee (56.5 versus 59.2 mmHg, p = 0.021). In multivariate analysis, autonomic neuropathy was significantly and independently related to leg 44 degrees C TcPO2 only (coefficient = -2.6734, p = 0.0182). Much stronger associations were seen between TcPO2 and age, ankle blood pressure, and relative body weight on the plantar foot; and between API, glycosylated haemoglobin, ankle blood pressure, and pedal oedema on the dorsal foot and leg. We conclude that factors related to lower limb TcPO2 vary depending on measurement site. Autonomic neuropathy is not an important determinant of TcPO2 in the feet of diabetic subjects. Although several predictors of TcPO2 were identified, most of the variance of this measurement remains unexplained.

Algorithms↗

PubMed1996

Determinants of age at menarche as early life predictors of breast cancer risk.

Age at menarche is one of the few established risk factors for breast cancer; identification of its exogenous determinants could throw light on the origins of breast cancer. We have undertaken an epidemiologic study in Greece to ascertain whether: 1) energy intake, an indicator of physical activity, is associated with later age at menarche; 2) energy-adjusted fat intake is related to earlier age at menarche; and 3) other macronutrients and anthropometric variables are predictors of age at menarche. Anthropometric, socio-economic, familiar, nutritional and lifestyle predictors of age at menarche were studied by interviewing in person 345 female students 9 to 16 years old attending 8 schools of Greater Athens. Menarche was the outcome variable in a proportional hazards model assessing the mutually adjusted incidence rate ratio by a series of predictor variables. In a complementary analysis, age at menarche was the dependent variable among menstruating girls. Consistent results were derived from the main and the complementary analysis. Increased height and body mass index accelerate the occurrence of menarche. Maternal and daughter's ages at menarche are correlated, but there is no evidence of an association with paternal education. Various measures of moderate physical activity as well as increased total energy intake were associated with a delay in age at menarche. Energy-adjusted macronutrients were not associated with age at menarche. It appears that an alteration of energy balance in early life through increased physical activity could delay age at menarche and reduce the risk for breast cancer in later life.

Adolescent↗

PubMed1999

Classifying individuals based on predictors of random effects. Multicenter AIDS Cohort Study.

Often one wishes to describe individuals according to whether their average exposure over a period of time is above or below some meaningful threshold. In this article, we treat predictors of random effects as diagnostic tools to aid in such classification, given that the true unobservable mean exposure for each of a set of individuals is defined according to a mixed linear model. Viewing candidate predictors in this light engenders the consideration of a unique set of performance criteria, and invites the use of nomenclature commonly used by epidemiologists and decision analysts to evaluate diagnostic techniques. We describe these criteria analytically and graphically under a random effects analysis of variance model, with the expressed goal of classifying subjects with regard to their true mean. Given knowledge of the model parameters, we compare typical predictors and illustrate the fact that completely new alternatives can arise depending on the particular set of criteria emphasized. We include a brief simulation study in which we also compare prediction methods according to various classification criteria, after incorporating estimates of the unknown model parameters. We provide two examples using data from participants in the Multicenter AIDS Cohort Study. In the first example, we seek to classify HIV seronegative individuals based on their mean diastolic blood pressure. In the second, via a natural extension to a randomized regression model, we classify HIV seropositive individuals according to their CD4+ slope over time.

Analysis of Variance↗

PubMed1998

Evaluation of pretreatment computed tomography as a predictor of local control in T1/T2 pyriform sinus carcinoma treated with definitive radiotherapy.

BACKGROUND: This study was undertaken to determine whether pretreatment computed tomography (CT) findings can predict local control in pyriform sinus carcinoma treated with definitive radiotherapy (RT). METHODS: Twenty-three patients with pyriform sinus carcinoma (T1: n = 5; T2: n = 18) were treated with high-dose RT and followed for a minimum of 2 years. Tumor volumes and extent were determined on pretreatment CT studies. The specific CT parameters assessed were analyzed as predictors of local control. RESULTS: There was a significant decrease in local control rate for tumors over 6.5 mL (1 of 4 [25%]) relative to tumors under 6.5 mL (17 of 19 [89%]; p = .021). Sensitivity and specificity for local control using this cutoff were 94% and 60%, respectively. Tumor score, as a measure of anatomic extent, was also found to be a significant predictor of local control (p = .033). The local control rate was not influenced significantly by the presence of "minimal" apex disease (< 10 mm in greatest dimensions as measured on CT) but decreased significantly when "bulk" apex disease (> OR = 10 mm) was present (p = .027). Laryngeal cartilage sclerosis was not a significant predictor of outcome. CONCLUSION: Computed tomography can stratify pyriform sinus carcinomas into groups more or less likely to be locally controlled with definitive RT.

Carcinoma, Squamous Cell↗

PubMed1999

Childhood predictors of violent behavior.

In this study, prospective childhood data from birth to 7 years of age were used to determine predictors of subsequent violent behavior. The childhood predictors found for the girls accounted for more variance in the reported later violent offenses: 24.9% compared to 3.8% for the boys. This large difference may be due partly to the fact that violent behavior is more unusual among girls; thus, those girls who are violent are more readily differentiated from the others. The only two early childhood variables that were found to predict for both genders were: (a) less normal behavior and (b) presence of deviant or stereotyped behavior. Thus, abnormal behavior in childhood can be considered to be a fairly reliable predictor to greater likelihood of later violent behavior.

Adolescent↗

PubMed1997

The long-term course of severe anorexia nervosa in adolescents: survival analysis of recovery, relapse, and outcome predictors over 10-15 years in a prospective study.

OBJECTIVE: To assess the long-term course of recovery and relapse and predictors of outcome in anorexia nervosa. METHOD: A naturalistic, longitudinal prospective design was used to assess recovery and relapse in patients ascertained through a university-based specialty treatment program. Patients were assessed semiannually for 5 years and annually thereafter over 10-15 years from the time of their index admission. Recovery was defined in terms of varying levels of symptom remission maintained for no fewer than 8 consecutive weeks. RESULTS: Nearly 30% of patients had relapses following hospital discharge, prior to clinical recovery. However, most patients were weight recovered and menstruating regularly by the end of follow-up, with nearly 76% of the cohort meeting criteria for full recovery. Relapse after recovery was relatively uncommon. Of note, time to recovery was protracted, ranging from 57-79 months depending on definition of recovery. Among restrictors at intake, nearly 30% developed binge eating, occurring within 5 years of intake. A variety of predictors of chronic outcome and binge eating were identified. There were no deaths in the cohort. CONCLUSION: The course of anorexia nervosa is protracted. Predictors of outcome are surprisingly few, but those identified are in keeping with previous accounts. The intensive treatment received by these patients may account for the lower levels of morbidity and mortality when considered in relation to other reports in the follow-up literature.

Adaptation, Psychological↗

PubMedDate not supplied

Predictors of bereavement outcome for family carers of cancer patients.

AIMS: The psychological outcome of family carers after bereavement is an important issue in evaluating palliative care services. Palliative care services have the potential to provide preventive psychosocial intervention to family carers prior to bereavement, but are faced with the need to identify those who may have greatest risk of adverse outcome. This prospective study examines predictors of psychological outcome for family carers of cancer patients following bereavement based on factors identified at referral to a palliative care agency. METHODS: Cancer patients and their family carer were consecutively recruited and assessed on a range of clinical and psychological measures at referral to a palliative home care service in a metropolitan centre (Time 1). Carers were again assessed following the death of the patient, on average at 4 months post-bereavement (Time 2), using measures of bereavement symptoms and psychological morbidity. RESULTS: 178 carers were assessed on both occasions. The chief predictors of carer psychological symptoms and severity of grief at follow-up were psychological symptom scores at the time of referral (Time 1). Factors also measured at Time 1 were significant predictors of symptoms and grief scores at Time 2: greater number of adverse life events, carer's coping responses, past bereavement and separation experiences, the relationship with the patient, and greater severity of patient's illness at the time of palliative care referral. CONCLUSIONS: The findings indicate clinical risk factors for adverse short-term bereavement outcome that can be identified in family carers during palliative care treatment, that have implications for identifying the psychological needs of carers, and that form a potential basis for interventions to enhance the psychological outcome for family carers.

Adaptation, Psychological↗

PubMed1993

Image analysis of androgen receptor immunostaining in metastatic prostate cancer. Heterogeneity as a predictor of response to hormonal therapy.

BACKGROUND: Reliable predictors of the response of prostate cancer to androgen ablation therapy are lacking. The goals of this study were to determine whether nuclear androgen receptor (AR) concentrations in metastatic prostate cancer varied within and between specimens and to correlate this information with the response to therapy. METHODS: AR concentration was evaluated by computer-assisted image analysis of immunohistochemical staining intensity in 200 malignant epithelial nuclei of each of 17 specimens of Stage D2 prostate cancer obtained before hormonal therapy. The data were correlated with the time to tumor progression (relapse) after hormonal therapy. RESULTS: AR staining intensity varied within specimens, and the variance of staining intensity was significantly greater (P = 0.03) in the poor responders (n = 8; time to progression, < 20 months) than in the good responders (n = 9; time to progression, > or = 20 months). The kurtosis was significantly lower in poor responders (P = 0.04). However, the mean AR staining intensity was not significantly different among patients. The frequency distribution plots of good responders were generally uniform and unimodal, but those of poor responders were flattened (more platykurtic), dispersed, and highly variable. Thus, the AR concentration per cell was significantly more heterogeneous in poor responders. Variance was a significant predictor of response. Five of 6 patients with a high variance (defined as variance greater than the mean) were poor responders, whereas 8 of 11 patients with a low variance were good responders (an overall classification accuracy of 13 of 17, 76%). CONCLUSIONS: The greater AR heterogeneity in poor responders may reflect a greater genetic instability in tumors that have progressed further toward androgen independence and may be a valuable predictor of progression.

Antibodies, Neoplasm↗

PubMed2001

Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck.

BACKGROUND: The objective of this study was to determine prognostic factors for response and survival on three consecutive institutional trials utilizing concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck (SCCHN). METHODS: Since 1985, patients with locally advanced SCCHN at the University of Maryland have been managed with concurrent chemotherapy and radiation therapy (RT). Three consecutive pilot studies have been performed evaluating the utility of weekly chemotherapy with standard fractionated RT. Chemotherapy consisted of carboplatin either alone (28 patients) or in combination with bleomycin (23 patients) or paclitaxel (60 patients). In all three studies, RT was given to 70.2 gray (Gy) at 1.8 Gy/fraction/day to the primary site. All patients had locally advanced SCCHN and were believed to be poor surgical candidates. Sixty-seven percent of patients had T4 disease, and 21% had T3 disease. Seventy-five percent of patients had N2-N3 disease. One hundred eleven patients were examinable for toxicity, response, and survival analysis. Factors including age, race, gender, primary site location, histologic grade, T classification, N classification, and treatment regimen were evaluated to identify predictors of these endpoints. RESULTS: The median follow-up for patients treated on study 1 (carboplatin and RT) and study 2 (carboplatin and bleomycin [C + B]/RT) was 98 months, and it was 30 months for study 3 (carboplatin and paclitaxel [C + P]/RT). The complete response rates were 54%, 52%, and 70% respectively (P = 0.01). Multivariate analysis identified length of treatment break (< 1 week vs. > 1 week) as the only predictor of complete response to therapy. The local control for the entire group was 50%. The local control for C + P/RT was 63%, versus 32% and 36% for C/RT and C + B/RT respectively (P = 0.004). The 2-, 3-, and 5-year disease free and overall survivals for the entire population were 41%, 41%, and 35% and 42%, 36%, and 33%, respectively. The 3-year overall survival rates by treatment regimen were 18% (C/RT), 35% (C + B/RT), and 47% (C + P/RT; P = 0.01). On univariate analysis, age younger than 50 years (P = 0.01), treatment with C + P/RT (P = 0.005), and treatment break of 5 days or fewer (P < 0.05) were also predictive of improved overall survival. On multivariate analysis, only complete response (P < 0.0001) and treatment with C + P/RT (P = 0.02) remained statistically significant. CONCLUSIONS: Chemoradiation provides patients with locally advanced SCCHN the opportunity for long term survival. Among the three chemoradiation regimens studied, C + P/RT was associated with the best complete response and survival rates. Complete response to therapy was the single most important predictor of overall survival. These three consecutive concurrent chemotherapy and radiation trials achieved a 5-year survival of greater than 30% for the entire population. These results support the use of this nonoperative approach for this group of patients with a historically poor prognosis.

Adult↗