Initial weight loss as a predictor of response to obesity drugs

BACKGROUND: Initial weight loss has been used as a predictor of long-term response to obesity drugs. Discontinuation of drugs has been recommended if weight loss is not > or =1.81 kg (4 lb) in the first month of treatment. OBJECTIVE: We compared the weight loss response at 6 months of patients losing > or =1.81 kg (responders) vs. < 1.81 kg (non-responders) in the first month of treatment with the combination of fenfluramine and phentermine. DESIGN: Outcomes at 6 months in 975 patients treated in a comprehensive program of phentermine (15-30 mg/d) d,l-fenfluramine (20-60 mg/d), were compared for responders vs. non-responders. RESULTS: In the total population, first month weight loss highly correlated with % reduction in body mass index (BMI) after 6 months of treatment (P<0.001). The reduction in baseline BMI after 6 months treatment was greater for the responders (15.9% vs. 10%, P<0.02). However, the North American Association for the Study of Obesity (NAASO) guidelines for drug treatment of obesity state that a 5% weight loss produces significant health benefits, and may be used as a criteria for success. At 6 months, 76%, 37% and 14% of the non-respondents had lost > or = 5%, > or = 10% and > or = 15% of baseline BMI, respectively. After 6 months treatment the reductions in serum cholesterol, triglycerides and LDL-cholesterol were 0.55, 0.31 and 0.42 mmol/L, respectively, (P< or =0.006), for the non-responders. Adverse effects after 6 months of treatment and the dropout rates after 1 y of treatment were not significantly different for the two groups. CONCLUSIONS: Although, the first month weight loss predicted the long-term response to phen-fen treatment, it was inadequate in identifying the non-responders and may unnecessarily preclude potential beneficiaries of the treatment.     

Naloxone challenge as a biological predictor of treatment outcome in opiate addicts

Thirty seven consecutive applicants to methadone maintenance were assessed for depression and for level of opiate dependence using a 0.8-mg naloxone challenge. Nineteen of the applicants met DSM-III-R criteria for current major depression. At 3-month follow-up, high naloxone challenge test (NCT) scores at intake (high levels of opiate addiction) were found to predict poor program retention and elevated symptoms of depression at follow-up. Reports of heavy current drug use at intake were also associated with poor program retention and with high frequencies of positive urine screens for illicit substances during treatment. Level of addiction and reported amount of drug use at intake independently predicted program retention with a multiple correlation of 0.46 (P less than .01). Although NCT predicted depression at follow-up, depression at intake did not significantly predict treatment outcome, and NCT score predicted outcome independently of psychopathology.     

EuroSCORE as a predictor for complications and outcome

OBJECTIVE: The purpose of this study was to evaluate the usefulness of EuroSCORE in terms of prediction of the outcome as a result of preoperative information in a cohort of patients. Methods: We analyzed the data from 751 patients treated between Jan 1 and Dec 31, 1998. We used contingency tables and applied methods of discriminant analysis for the evaluation. RESULTS: Compared to the 14.799 patients from whose data the EuroSCORE system had originally been derived [1,2], we had a smaller portion of patients in the low-risk group (24.5% vs. 30.6%), a comparable portion of patients in the medium-risk group (42.2% vs. 40.5%) and a higher proportion of patients in the high-risk group (33.2% vs. 29.0%). This difference in the risk distributions was highly significant (p < 0.001). The application of the EuroSCORE system showed that deaths only occurred in the high-risk group in our hospital. We had 36 deaths amongst the patients, which gives an overall mortality rate of 4.9% and a mortality rate of 1.6% in the medium-risk group and of 12.4% in the high-risk group. The discriminant analysis showed that with the EuroSCORE as single predicting variable - virtually all survivors were classified correctly (giving a specificity of 99.0%). The sensitivity was rather low at only 25%; however, this means that many of the high-risk patients in our clinic survived. The total misclassification rate, however, was 12.7%. Additionally, we found that a higher score value predicts a significantly higher probability for perioperative complications and also results in significantly increased average times for the bypass and total time for surgery. CONCLUSION: The EuroSCORE is a valuable score system for the prediction of the overall outcome of patients following open heart surgery, and is easy to use. As far as perioperative complications are concerned, however, some specifications seem desirable.     

Early therapeutic alliance as a predictor of treatment outcome for adolescent cannabis users in outpatient treatment

The association of early alliance to treatment attendance and longitudinal outcomes were examined in 356 adolescents participating in a randomized clinical trial targeting cannabis use. Both patient and therapist views of alliance were examined, and outcomes were evaluated over 12 months after numerous other sources of variance were controlled. Patient-rated alliance predicted a reduction in cannabis use at three and six months and a reduction in substance-related problem behaviors at six months. Therapist-rated alliance did not predict outcomes. Neither patient nor therapist alliance ratings were associated with attendance. The findings support the important and often overlooked role that alliance can play in treating substance abusing, often delinquent, adolescents.     

Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease.

Apolipoprotein E (apoE) is critical in the modulation of cholesterol and phospholipid transport between cells of different types. Human apoE is a polymorphic protein with three common alleles, APO epsilon 2, APO epsilon 3, and APO epsilon 4. ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD). Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects. To characterize the possible impact of the apoE4 allele on cholinergic markers in AD, we examined the effect of apoE4 allele copy number on pre- and postsynaptic markers of cholinergic activity. ApoE4 allele copy number showed an inverse relationship with residual brain ChAT activity and nicotinic receptor binding sites in both the hippocampal formation and the temporal cortex of AD subjects. AD cases lacking the apoE4 allele showed ChAT activities close or within age-matched normal control values. The effect of the apoE4 allele on cholinomimetic drug responsiveness was assessed next in a group (n = 40) of AD patients who completed a double-blind, 30-week clinical trial of the cholinesterase inhibitor tacrine. Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline. These results strongly support the concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients.     

Self-reported functional status as a predictor of coronary artery bypass graft surgery outcome in elderly patients

BACKGROUND: Surgeons have traditionally relied mainly on clinical intuition in the selection of elderly candidates for coronary artery bypass grafting (CABG). The overall increasing number of patients undergoing CABG and limited resources require that a more rational approach be used to screen out candidates who are least likely to benefit from the surgery. Hypothesis: Preoperative functional status is a more sensitive predictor of mortality and poor postoperative functional status than age. PATIENTS AND METHODS: Retrospective preoperative and postoperative geriatric assessment was obtained for 123 patients who had undergone CABG at the Montreal General Hospital. Montreal, Quebec. Preoperative and postoperative health and functional status were assessed using the Canadian version of the Medical Outcomes Study 36-Item Short-Form (SF-36) 1 to 1.5 years following surgery. The questionnaires were compiled according to the method described by Stewart et al and scores were transformed linearly to a 0 to 100 scale. In addition to functional status, the presence of comorbidities and other risk factors known to influence the outcome of CABG were recorded. RESULTS: There was no significant difference in the likelihood of having a poor functional status before or after surgery, or death as an outcome of CABG in the young elderly group versus the old elderly group. Preoperative functional status was found to predict postoperative functional status; however, there was no significant association between preoperative functional status and the presence of comorbidity. The presence of comorbidity did not affect the postoperative functional status, but increased the likelihood of death. CONCLUSION: Functional status was demonstrated to be a significant predictor of CABG outcome. When compared with age, functional status was also found to be a more reliable predictor of CABG outcome, which had not been previously demonstrated. Women were found to be more likely to have a poor preoperative functional status than their male counterparts. This may account in part for the decreased success rate of CABG in elderly women.     

Cytogenetic status pre-transplant as a predictor of outcome post bone marrow transplantation for chronic myelogenous leukaemia

We have analysed pre-transplant cytogenetic findings in 418 patients with CML in pre-blastic phase who underwent allogeneic BMT between February 1981 and January 1998. Five different patient groups were identified: A = Philadelphia (Ph)+; B = Ph-, BCR-ABL+; C = variant Ph (VPh); D = Ph chromosome plus at least one of: trisomy 8, +Ph, chromosome 17 abnormalities and E = other abnormalities in addition to the Ph chromosome. There were two principal conclusions. Firstly, Ph- patients showed a better outcome, and VPh patients a worse outcome, than those with a standard Ph, both in terms of leukaemia-free survival (LFS) (76.9%, 22.1% and 31.9%) and the risk of treatment failure relative to those with a standard Ph (relative risks of 0.49 and 1.92, respectively). One contributing factor may be relapse: no Ph- patients relapsed, whereas all other groups showed similar probabilities of relapse at 5 years (range 33.0-44. 0%). Secondly, those with the additional changes of +8, +Ph and i(17q) did not show a worse outcome than those with no additional changes (5 year survival of 44.7% vs 51.8%; 5 year LFS of 40.6% vs 31.9%), whereas those with other additional changes may fare worst of all (40.4% and 16.0%, respectively). Bone Marrow Transplantation (2000) 25, 143-146.     

High molecular weight adiponectin as a predictor of long-term clinical outcome in patients with coronary artery disease

Adiponectin is an adipocyte-specific secretory protein that is highly and specifically expressed in adipose tissue, and low plasma levels of adiponectin are associated with coronary artery disease (CAD). It has been suggested that high molecular weight (HMW) adiponectin is more important for vascular protection than total amount of adiponectin. To establish the clinical relevance of HMW adiponectin, we measured its serum levels in 149 patients with CAD. The levels were lower in vasospastic angina pectoris (3.4 +/- 2.4 microg/ml, p <0.01), stable angina pectoris (3.3 +/- 2.6 microg/ml, p <0.001), and healed myocardial infarction (3.8 +/- 2.9 microg/ml, p <0.01) than chest pain syndrome (controls) (6.6 +/- 5.4 microg/ml). The levels were also lower in multivessel CAD (3.4 +/- 2.4 microg/dl) compared with single vessel CAD (4.2 +/- 2.7 microg/ml, p <0.05) or no organic stenosis (5.1 +/- 3.5 microg/ml, p <0.01). In univariate analysis, diabetes mellitus (p = 0.03), insulin resistance (p = 0.06), high-sensitivity C-reactive protein levels (p = 0.0012), and low HMW adiponectin levels (p = 0.0001) predicted cardiovascular events during 7 years of follow-up. However, multivariate analysis showed that only HMW adiponectin levels were an independent predictor of cardiovascular events (relative risk 2.79, 95% confidence interval 1.49 to 5.24, p = 0.0014). In conclusion, serum HMW adiponectin levels may serve as a predictor of future cardiovascular events in patients with CAD as well as a marker for severity of CAD.     

Heart rate as predictor of outcome

The importance of resting heart rate in predicting the development of hypertension and cardiovascular morbidity and mortality has been demonstrated in a large number of studies. The relationship between high heart rate and cardiovascular mortality held true in studies performed in hypertensive participants. In most epidemiologic studies, the predictive power of resting heart rate for all-cause mortality was equal to or even greater than that of total cholesterol, smoking, or systolic blood pressure. Data obtained with ambulatory or home measurement did not show any advantage of heart rate measured out of the office over clinic heart rate, but the available evidence is still limited and more research is needed.     

Usefulness of B-type natriuretic peptide as a predictor of treatment outcome in pulmonary arterial hypertension

We examined the utility of early modulation B-type natriuretic peptide (BNP) levels in 20 pulmonary arterial hypertension patients as a marker of response to epoprostenol therapy. The baseline BNP level was 828+/-217 pg/mL. A total of 19 hospitalizations and one death occurred in nine patients during 11.0+/-1.8 months. At baseline, a trend toward higher BNP level was observed among the event-free (Group A) as compared with clinical event patients (Group B) (1090+/-372 vs. 510+/-235 pg/mL, respectively; p=0.08). After 3 months on epoprostenol, a significant reduction among Group A occurred while Group B demonstrated an increase (288+/-92 vs. 610+/-121 pg/mL, p=0.04). A comparison of percent reduction in BNP level demonstrated a -70+/-7% change among Group A and an 11+/-19% increase in Group B (p=0.005). A decrease in BNP level of > or =50% during the first 3 months on epoprostenol was strongly predictive of event-free survival (p=0.003). This investigation establishes the utility of BNP for predicting response to epoprostenol therapy in pulmonary arterial hypertension.     

Cognitive training gain as a predictor of mental status

We examined the association of proximal and distal training gain to subsequent mental status ratings in 302 participants (M = 76.62 years) trained on inductive reasoning or spatial orientation in the Seattle Longitudinal Study. Only training effects on reasoning ability were predictive of mental status group membership. Participants subsequently rated as probably demented did not significantly differ from nondemented participants in magnitude of reasoning training gain 14 years prior to assessment, but they did 7 years prior to status ratings. Proximal training gain 1 year prior to assessment was 0.40 SD for nondemented participants, compared with 0.25 and 0.10 SD for at-risk and probably demented participants, respectively. The combination of reasoning ability training and increased proximal training gain on reasoning ability was associated with a decreased likelihood of being rated as probably demented.     

Neutral theory as a predictor of avifaunal extinctions after habitat loss

The worldwide loss of natural habitats leads not only to the loss of habitat-endemic species but also to further and protracted extinctions in the reduced areas that remain. How rapid is this process? We use the neutral theory of biodiversity to answer this question, and we compare the results taken with observed rates of avifaunal extinctions. In the neutral model, we derive an exact solution for the rate of species loss in a closed community. The simple, closed-form solution exhibits hyperbolic decay of species richness with time, which implies a potentially rapid initial decline followed by much slower rates long term. Our empirical estimates of extinction times are based on published studies for avifaunal extinctions either on oceanic islands or in forest fragments, which span a total of six orders of magnitude in area. These estimates show that the time to extinction strongly depends on the area. The neutral-theory predictions agree well with observed rates over three orders of magnitude of area (between 100 and 100,000 ha) both for islands and forest fragments. Regarding the species abundance distribution, extinction times based on a broken-stick model led to better agreement with observation than if a log-series model was used. The predictions break down for very small or very large areas. Thus, neutrality may be an affordable assumption for some applications in ecology and conservation, particularly for areas of intermediate size.     

Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma

AIM: To correlate cyclooxygenase-2 (COX-2) expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma (CRC).METHODS: Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94 patients with CRC. Patients were diagnosed and treated at the Departments of Surgery and Oncology, King Abdulaziz University Hospital, Saudi Arabia.RESULTS: Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression, whereas 44% of cases were completely COX-2-negative. There were no significant correlations between COX-2 expression and sex, age, grade or tumor location. However, COX-2 expression revealed a significant correlation with tumor stage (P = 0.01) and distant metastasis (P = 0.02), and a borderline association with lymph node involvement (P = 0.07). Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression (P < 0.009). In univariate Kaplan-Meier survival analysis, there was a significant (P = 0.026) difference in disease-free survival between COX-2-positive and negative tumors in favor of the latter. COX-2 expression did not significantly predict disease-specific survival, which was much shorter for COX-2-positive tumors. In multivariate (COX) models, COX-2 did not appear among the independent predictors of disease-free survival or disease-specific survival.CONCLUSION: COX-2 expression seems to provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease.     

Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis.

OBJECTIVE. To determine the clinical and serologic risk factors for digital ischemic events in patients with systemic sclerosis (SSc). METHODS. Retrospective review of clinical and laboratory data and review of current clinical status of 98 patients with SSc, seen between 1985 and 1990. RESULTS. Amputation of 1 or more digits due to ischemia occurred in 20.4% of the patients; 9.2% had multiple digit loss. Sclerodactyly alone and anticentromere antibody (ACA) were associated with loss of 1 or more digits. Age, smoking status, duration of disease, or duration of Raynaud's phenomenon were not predictive for loss of digits. CONCLUSION. Patients with limited SSc who are positive for ACA have an increased risk of major peripheral vascular occlusive disease.