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Covariance adjustment of survival curves based on Cox's proportional hazards regression model.

Cox's proportional hazards regression model is a useful statistical tool for the analysis of 'survival data' from longitudinal studies. This multivariate method compares the 'survival experience' between two or more exposure groups while allowing for simultaneous adjustment of confounding due to one or more covariates. In addition to the summary regression statistics, further insight on the exposure--response relationship can be gained by visually examining the covariates-adjusted survival curves in the respective comparison groups. Covariates-adjusted survival curves are usually computed by the 'average covariate method'. This method is, however, subject to potential drawbacks. A method that avoids these drawbacks is to estimate adjusted survival curves by the corrected group prognostic curves approach. We have written a computer program to construct survival curves by the latter method. The program is coded in the Interactive Matrix Language of SAS.

Humans↗

Lipoprotein(a) selectively impairs receptor-mediated endothelial vasodilator function of the human coronary circulation.

OBJECTIVES: We investigated the influence of lipoprotein(a) [Lp(a)] serum levels on different endothelium-dependent vasodilator stimuli representing different mechanisms of endothelium-dependent vasodilation. BACKGROUND: Lp(a) is an independent predictor for the development and progression of coronary artery disease. Impairment of endothelium-dependent vasodilation of epicardial arteries has been shown in patients with high levels of Lp(a). METHODS: In 108 patients with angiographically normal or minimally diseased coronary vessels, vasomotor responses to acetylcholine, cold pressor testing, increased blood flow and nitroglycerin were assessed. RESULTS: Lp(a) levels > or = 30 mg/dl were associated with significant dose-dependent enhancement of the vasoconstrictor response to acetylcholine [receptor-mediated vasodilation, p = 0.002; acetylcholine 10(-6) mol/liter, -29 +/- 21% vasoconstriction with Lp(a) levels > or = 30 mg/dl vs, -5.6 +/- 25% with Lp(a) levels < 30 mg/dl]. In addition, vasoconstrictor response to cold pressor test (receptor- and flow-mediated vasodilation) was significantly enhanced in patients with Lp(a) levels > or = 30 mg/dl (-13 +/- 12% vs. 1.2 +/- 16%, p = 0.005). In contrast, strictly endothelium-dependent, but non-receptor-mediated, flow-dependent dilation and endothelium-independent dilation with nitroglycerin were not compromised. Linear regression analysis revealed an inverse relation between Lp(a) and both acetylcholine-induced (r = -0.34, p = 0.0007) and cold pressor test-induced (r = -0.44, p = 0.0001) vasodilation. By multivariate analysis, Lp(a) was a strong and independent predictor of paradoxic vasoconstriction only in response to acetylcholine and cold pressor testing. Impairment of coronary blood flow increase in patients with Lp(a) levels > or = 30 mg/dl did not reach statistical significance. CONCLUSIONS: High Lp(a) levels are associated with a selective impairment of vasodilator capacity of receptor-mediated endothelial stimuli. Impaired dilator capacity of the coronary circulation associated with elevated Lp(a) levels may contribute to the pathogenesis of myocardial ischemia in response to trigger mechanisms involving receptor-mediated stimulation such as sympathetic activation.

Acetylcholine↗

Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India.

In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered.

Adult↗

Obesity and risk of nonfatal unintentional injuries.

BACKGROUND: Obesity is recognized as a risk factor for multiple chronic diseases. Yet, it is unclear whether obesity is also associated with an increased risk of nonfatal unintentional injury. METHODS: A population-based survey was conducted among adults aged > or = 18 years from January 1999 through October 2000. The relationship was investigated between body mass index (BMI), defined as weight in kilograms divided by the square of the height in meters (kg/m2), and risk of nonfatal unintentional injuries among 2575 respondents aged > or = 20 years by comparing percentage of adults between obese and nonobese respondents who had injuries. Multivariate logistic regression further examined this relationship by controlling for confounding demographics. RESULTS: A total of 370 respondents reported injuries in the previous year. We observed a linear dose-response trend among women. An estimated 7.0% of underweight individuals (BMI <18.5) reported injuries. In contrast, 26.0% of men and 21.7% of women with a BMI > or = 35.0 reported injuries. The odds ratio of injuries for individuals with a BMI > or = 35.0 was 2.00 (95% confidence interval=1.07-3.74, p<0.05) after controlling for gender, age, education level, marital status, family poverty status, and area of residence. CONCLUSIONS: A marginally significant association between extreme obesity and elevated risk of injuries was observed. Efforts to promote optimal body weight may reduce not only the risk of chronic diseases but also the risk of unintentional injury among overweight and obese individuals.

Adolescent↗

Family history validation of a definition of mixed depression.

PURPOSE: The study aim was to test different definitions of mixed depression, defined as a depression with concurrent hypomanic symptoms. METHODS: Consecutive 245 non-tertiary care outpatients with bipolar II disorder (BP-II) and 189 non-tertiary care outpatients with major depressive disorder (MDD) were interviewed (off psychoactive drugs) using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders-Clinician Version, Hypomania Interview Guide (HIG), and Family History Screen when presenting for major depressive episode (MDE) treatment. Intra-MDE hypomanic symptoms were systematically assessed. Mixed depression was defined as an MDE with concurrent hypomanic symptoms. Receiver operating characteristic (ROC) analysis and multivariate analysis were used to test different definitions of mixed depression (dimensional and categorical ones). Factor analysis was also used. Bipolar family history was the validator. FINDINGS: Bipolar II disorder, vs MDD, had significantly more intra-MDE hypomanic symptoms (racing/crowded thoughts, irritable mood, psychomotor agitation, more talkativeness, and increased goal-directed and risky activities). Major depressive episode plus 3 or more hypomanic symptoms was present in 68.7% of BP-II and 42.3% of MDD. A "motor activation" factor, including psychomotor agitation and talkativeness, and a "mental activation" factor including racing/crowded thoughts were found. Different definitions (dimensional and categorical ones) of mixed depression were tested vs bipolar family history as validator (ie, MDE plus more than 1, 2, 3, and 4 concurrent hypomanic symptoms, MDE plus psychomotor agitation, MDE plus racing thoughts). Major depressive episode plus more than 1 hypomanic symptom had the highest sensitivity but the lowest specificity. Instead, MDE plus more than 4 hypomanic symptoms had the lowest sensitivity and the highest specificity. The better-balanced combination of sensitivity and specificity was shown by MDE plus more than 2 hypomanic symptoms. The same definition also showed the highest ROC area value. Multivariate regression of bipolar family history vs different mixed depression definitions found that the only strong and significant predictor was MDE plus more than 2 hypomanic symptoms. A dose-response relationship was found between the number of hypomanic symptoms during MDE and the bipolar family history loading. CONCLUSIONS: Mixed depression (MDE plus 3 or more hypomanic symptoms) was common in BP-II and MDD. A dimensional definition based on 3 or more hypomanic symptoms during depression was the most supported by using bipolar family history as validator. The study of mixed depression may be important for its possible impact on treatment (antidepressants could increase hypomanic symptoms, and mood stabilizers and antipsychotics could control hypomanic symptoms during antidepressant treatment).

Adult↗

Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer.

PURPOSE: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. METHODS AND MATERIALS: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-fluorouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. RESULTS: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. CONCLUSION: In multivariate analysis, statin use is associated with an improved pCR rate after neoadjuvant chemoradiation for rectal cancer. The low prevalence of statin use limits the power to detect a significant difference at a type I error threshold of p = 0.05 in this analysis. Although no definitive conclusions can be drawn on the basis of this retrospective study, the unusually high incidence of pCR after chemoradiation suggests that the use of statins in the treatment of rectal cancer warrants further evaluation.

Adult↗

Operative factors that contribute to post-operative atrial fibrillation: insights from a prospective randomized trial.

Atrial fibrillation (AF) is the most common complication following cardiac surgery and is associated with significant increases in postoperative morbidity, length of stay and cost of care. In a randomized study we assessed the impact of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) (off-pump, n = 100), compared to conventional (on-pump, n = 100) CABG, on the frequency of postoperative AF. Arrhythmias were detected using an automated arrhythmia detector for the first 72 hours following surgery and by four hourly clinical observations thereafter. AF was defined as an irregular narrow complex rhythm (in the absence of bundle branch block) with absence of discrete P waves lasting greater then 10 minutes. There was a significant reduction in the incidence of postoperative AF in the off-pump group (11% versus 45%, P < 0.001) in addition to significant reductions in blood usage, postoperative pneumonia, inotrope requirements, and hospital and intensive care unit stay. Univariate analysis identified all these variables as risk factors for AF, however multivariate regression analysis identified CPB and cardioplegic arrest as the only independent predictor of postoperative AF (OR 7.4; 95% CI 3.4 to 17.9). This study therefore suggests that the inflammatory response to bypass, myocardial ischaemia and atrial cannulation are significant contributory factors to the development of AF following cardiac surgery. In the light of more recent trials it is apparent that this benefit may be most marked in patients with multiple perioperative risk factors for postoperative AF.

Adrenergic beta-Antagonists↗

Prevalence and correlates of paediatric asthma and wheezing in a largely rural USA population.

OBJECTIVE: The prevalence of asthma among children has been increasing in the United States and it is estimated that there are approximately 5 million children with asthma. This cross-sectional survey sought to estimate the prevalence of asthma and asthma symptoms and potential risk factors among children aged 16 and younger, in a largely rural population in the USA. METHODS: This study was a telephone survey of 1500 households in the South Plains/Panhandle region of Texas. Parents of children were interviewed with a response rate of 64%. Having been diagnosed with asthma by a physician and a report of wheezing in the last 12 months were used as dependent variables in multivariate logistic regressions with several sociodemographic and environmental factors as potential confounders. RESULTS: The age-adjusted prevalence of asthma and wheezing among children were approximately 15 and 18%, respectively. The prevalence of asthma was highest (20%) among children aged 11-16 (P < 0.001). Living in urban areas was associated significantly with asthma and wheezing. Non-Hispanic blacks reported significantly increased odds of asthma in their children (adjusted odds ratio (OR) = 2.04, 95%CI 1.02-4.08), whereas Mexican-Americans reported significantly reduced odds of asthma (adjusted OR = 0.48, 95%CI 0.29-0.78) and wheezing (adjusted OR = 0.58, 95%CI 0.37-0.89) in their children. The odds of asthma (adjusted OR = 1.78, 95%CI 1.09-2.92) and wheezing (adjusted OR = 2.45, 95%CI 1.52-3.95) was highest among children in the highest body mass index quartile. No significant association with pet ownership and exposure to second-hand smoke with asthma and wheezing was observed in this study. CONCLUSION: Urban residence, non-Hispanic black and Mexican-American race/ethnicity, and being overweight were significantly associated with the increased risk of asthma and/or wheezing.

Adolescent↗

Structural vs non-structural flood-alleviation measures in the Yangtze Delta: a pilot survey of floodplain residents' preferences.

This study was initiated to test if structural flood-alleviation measures were more popular than non-structural measures among the floodplain residents of the Yangtze Delta, because of the long tradition of "living with embankments and other flood control structures'. The results of a pilot questionnaire survey among 239 respondents from four sample villages of two typical floodplains of the delta indicated that, contrary to expectations, the non-structural measure of flood insurance attracted more favourable responses (97 per cent) than any one of the structural measures, although the latter were also frequently selected by the respondents (64-92 per cent). A number of multivariate logit regressions between each of the preferred flood-alleviation measures and the respondents' flood adaptations identified some of the determinants of these preferences. For a more complete explanation of the causes of popularity of various flood-alleviation measures, further research should incorporate a behavioural model with trade-offs for alternative measures.

Adult↗

Comparing survey data on functional disability: the impact of some methodological differences.

STUDY OBJECTIVE: To examine the impact of some differences in survey methodology on the prevalence of functional disability in population based surveys of the elderly. DESIGN AND METHODS: Nine surveys of Dutch people aged 55 years and older were compared to investigate the differences in the methods of data collection (proxy questioning, yes/no; interview versus self administered questionnaire) and construction of the questionnaire (wording of introductory text, activities, and response categories). The effect of these differences on prevalences in three domains of functional disability--activities of daily living, mobility, and communication--were studied. Both univariate analyses and multivariate logistic regression were used to quantify the methodological influences. RESULTS: No effect of proxy questioning could be shown. Self administered questionnaires yielded higher prevalences of disability than interviewer administered questionnaire--in particular for mobility (odds ratio (OR) 1.4, 95% confidence interval (95% CI) 1.3, 1.6) and communication (OR = 1.7, 95% CI 1.5, 1.9), resulting in prevalence differences of 9 and 11 percentage points respectively. Seemingly minor differences in the structure and wording of the questionnaires resulted in major differences (up to 15.6 percentage points) in prevalence estimates of functional disability. These differences were associated with the severity level of the disability indicated by the wording of the questions. CONCLUSIONS: Differences in survey methodology have a substantial effect on the prevalence estimates of disability in the elderly. These differences should be taken into account when making international comparisons and studying time trends based on survey data.

Activities of Daily Living↗

What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease?

OBJECTIVES: Few studies have attempted to identify what premortem features best differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). These studies are limited by small sample size, clinical heterogeneity, or lack of postmortem validation. We evaluated the sensitivity and specificity of different clinical features in distinguishing pathologically established MSA from PD. METHODS: One hundred consecutive cases of pathologically confirmed PD and 38 cases of pathologically confirmed MSA in one Parkinson's disease brain bank were included. All cases had their clinical notes reviewed by one observer (AH). Clinical features were divided into two groups: those occurring up to 5 years after onset of disease and those occurring up to death. Statistical analysis comprised multivariate logistic regression analysis to choose and weight key variables for the optimum predictive model. RESULTS: The selected early features and their weightings were: autonomic features (2), poor initial levodopa response (2), early motor fluctuations (2), and initial rigidity (2). A cut off of 4 or more on the ROC curve resulted in a sensitivity of 87.1% and specificity of 70.5%. A better predictive model occurred if the following features up to death were included: poor response to levodopa (2), autonomic features (2), speech or bulbar dysfunction (3), absence of dementia (2), absence of levodopa induced confusion (4), and falls (4). The resulting ROC curve based on individual scores showed a best cut off score of at least 11 of 17 (sensitivity 90.3%, specificity 92.6%). CONCLUSIONS: Predictive models may help differentiate MSA and PD premortem. Hitherto poorly recognised features, suggestive of MSA, included preserved cognitive function and absence of psychiatric effects from antiparkinsonian medication. Diagnostic accuracy was higher in those models taking into account all clinical features occurring up to death. Further studies need to be based on new incident cohorts of parkinsonian patients with subsequent neuropathological evaluation.

Adult↗

Prevalence and risk factors associated with obesity in the elderly in Barbados.

This article's objective is to examine the epidemiology of obesity in the urban elderly population of Barbados. A random sample of adults >/= 60 years underwent comprehensive interviews and measurement of their weight, height, and waist circumference (WC). Outcomes of interest were obesity (body mass index [BMI] > 30 kg/m2), high-risk WC (men >/= 102 cm; women >/= 88 cm), and high risk of disease comorbidity (from BMI and WC criteria). Total, 1,508 persons participated (80% response). Women had higher rates of obesity (31% vs. 11.9%), high-risk WC (61.9% vs. 13.9%), and disease co-morbidity risk (51.1% vs. 17.5%) compared to men. Multivariate regression confirmed female gender as an independent predictor of outcomes (p < 0.001). Other predictors were less consistent: self-reported fair/poor health status and eating two (vs. three) meals daily were associated with obesity, whereas semiprofessional occupation and unmarried status predicted high-risk WC. Obesity is highly prevalent among elderly Barbadians. Public health interventions must target this group, particularly women.

Age Factors↗

Factors affecting the efficacy of intraarticular corticosteroid injection of knees in juvenile idiopathic arthritis.

OBJECTIVE: To determine in a prospective analysis whether baseline demographic, clinical, and laboratory variables predict the outcome of intraarticular corticosteroid (IAC) injection of the knees in children with juvenile idiopathic arthritis (JIA). METHODS: We studied consecutive patients who met the criteria for the diagnosis of JIA and received their initial injection of triamcinolone hexacetonide in one or both knees. Predictor variables included sex, age, age at onset of JIA, onset subtype, disease duration, drug therapy at the time of IAC injection, physician and parent global assessment of disease status, Childhood Health Assessment Questionnaire disability index, erythrocyte sedimentation rate (ESR), C-reactive protein, involvement of other joints besides knees, amount of fluid aspirated, and dose of IAC injected. The primary outcome measure was persistence of complete clinical response at 6 months, i.e., no evidence of synovitis clinically. RESULTS: Ninety-four patients were available for analysis. At 6 months after the IAC injection, 65 (69%) patients showed a sustained complete clinical response, whereas 29 (31%) had had a recurrence of joint inflammation. Univariate statistical analyses showed that patients who had a sustained clinical response had a significantly higher ESR than those who did not (p = 0.023). The ESR was the only variable that remained in the best-fit model from multivariate logistic regression analysis (OR 2.61, p = 0.049). CONCLUSION: Our findings indicate that patients with JIA who have a higher ESR are more likely to benefit from IAC injection of the knees.

Adrenal Cortex Hormones↗

[Prognosis and treatment strategies of primary B-cell and NK/T-cell nasopharyngeal non-Hodgkin's lymphoma at early stage].

BACKGROUND & OBJECTIVE: Nasopharynx is a commonly involved site of non-Hodgkin's lymphoma (NHL), but the differences of clinical characteristics, prognosis, and treatment strategy between B-cell and NK/T-cell nasopharyngeal NHL have seldom been reported. This study was to investigate the clinical manifestations and treatment outcomes of primary B-cell and NK/T-cell nasopharyngeal NHL at early stage, and evaluate the prognostic differences, so as to provide evidences for treatment optimization. METHODS: Clinical data of 80 patients with previously untreated nasopharyngeal NHL at early stage, admitted from May 1987 to Nov. 2003, were reviewed. Of the 80 cases, 48 were B-cell original (B group), 32 were NK/T-cell original (T group). Of the 80 patients, 42 received chemoradiotherapy, 31 received chemotherapy alone, and 7 received radiotherapy alone. Most chemotherapy-treated patients received CHOP regimen (cyclophosphamide, vincristine, adriamycin, and prednisone) for 1-10 cycles (median 5 cycles). Radiotherapy was given with high energy photon beams combined with high energy electron beams in conventional fractionation, with the total dose of 30-70 Gy (median 52 Gy). Treatment patterns of the 2 groups were similar, but B group received more chemotherapy cycles than T group did. RESULTS: The 5-year overall survival rate and 5-year progression-free survival rate were significantly higher in B group than in T group (69.5% vs. 35.5%, P=0.003; 53.3% vs. 28.9%, P=0.032). Cox multivariate regression analysis suggested that B-cell phenotype, no B symptoms, and local control were independent favorable predictors of overall survival, while B-cell phenotype and good treatment response were independent favorable predictors of progression-free survival. Univariate stratified analysis with Kaplan-Meier method showed that, for B group, the cumulative 5-year overall survival rate was 68.1% in the 19 patients received chemotherapy alone, 61.7% in the 25 patients received chemoradiotherapy, and 100% in the 4 patients received radiotherapy alone (P=0.311); for T group, the cumulative 5-year overall survival rate was 0% in the 12 patients received chemotherapy alone, 44.1% in the 17 patients received chemoradiotherapy, and 33.3% in the 3 patients received radiotherapy alone (only 1 patient survived for 60 months)(P=0.020). CONCLUSIONS: Among the patients with primary nasopharyngeal NHL at early stage, those with B-cell phenotype may have better prognosis as compared with those with NK/T-cell phenotype. The patients with NK/T-cell phenotype often suffered from B symptoms, with poor response to chemotherapy. Radiotherapy or chemoradiotherapy should be more emphasized in this group of patients.

Adolescent↗

Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group.

Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed for hepatocyte growth factor (HGF). HGF was elevated at diagnosis in 43% of myeloma patients compared with healthy controls (median 1.00 ng/mL and 0.44 ng/mL, respectively; P < .00001). In the group with elevated HGF levels 46% of the patients reached plateau phase, as compared with 60% of the patients with low HGF levels (P = .005), and the median survival time was 21 and 32 months, respectively (P = .002). In a univariate Cox regression analysis, HGF was a significant predictor of mortality (P = .02). In the subgroup of patients with beta 2-microglobulin levels less than or equal to 6 mg/L, high versus low HGF was a prognostic factor when a multivariate Cox regression analysis was performed. In serial samples HGF was higher at the time of diagnosis and relapse (median 0.57 ng/mL and 0.52 ng/mL, respectively; P = .0018) than at response (median 0.24 ng/mL, P = .008). We conclude that HGF may be a useful follow-up parameter in myeloma patients. Measurement of HGF may identify a group of patients with poor response to melphalan-prednisone treatment and short survival. HGF was a prognostic factor in patients with high levels of beta 2-microglobulin.

Adult↗

Patient-reported medication symptoms in primary care.

BACKGROUND: Little is known about the prevalence and character of medication-related symptoms in primary care and their relationship to adverse drug events (ADEs) or about factors that affect patient-physician communication regarding medication symptoms. METHODS: The study included 661 patients who received prescriptions from physicians at 4 adult primary care practices. We interviewed patients 2 weeks and 3 months after the index visit, reviewed patients' medical records, and surveyed physicians whose patients identified medication-related symptoms. Physician reviewers determined whether medication symptoms constituted true ADEs. We used multivariable regression to examine factors associated with patients' decision to discuss symptoms with a physician and with physicians' decision to alter therapy. RESULTS: A total of 179 patients identified 286 medication-related symptoms but discussed only 196 (69%) with their physicians. Physicians changed therapy in response to 76% of reported symptoms. Patients' failure to discuss 90 medication symptoms resulted in 19 (21%) ameliorable and 2 (2%) preventable ADEs. Physicians' failure to change therapy in 48 cases resulted in 31 (65%) ameliorable ADEs. In multivariable analyses, patients who took more medications (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.04-1.08; P<.001) and had multiple medication allergies (OR = 1.07; 95% CI = 1.03-1.11; P = .001) were more likely to discuss symptoms. Male physicians (OR = 1.20, 95% CI = 1.09-1.26; P = .002) and physicians at 2 practices were more likely to change therapy (OR = 1.24; 95% CI = 1.17-1.28; P<.001; and OR = 1.17; 95% CI = 1.08-1.24; P = .002). CONCLUSION: Primary care physicians may be able to reduce the duration and/or the severity of many ADEs by eliciting and addressing patients' medication symptoms.

Adult↗

A dose and time response analysis of the treatment of Hodgkin's disease with MOPP chemotherapy.

A dose-response analysis of the results of MOPP chemotherapy in 132 patients with Hodgkin's disease was carried out. Complex statistical methods were utilized including 40 different dose-time variables and multivariate logistic analyses of 21 clinical variables, both simply and in stepwise regression. These covariates were not independent, and in stepwise regression analysis only B-symptoms and the mean three-cycle rate of drug delivery significantly influenced complete remission attainment. Two parameters, bone marrow involvement (negative) and lung involvement (positive), significantly influenced the duration of complete remission. Survival was influenced adversely by pleural involvement (effusion), advanced age, and B-symptoms. Analyses indicate that the dose of all three drugs (mustard, vincristine, and procarbazine), and the rate of drug delivery during the first three cycles are important in achieving maximal complete response rates, especially for patients with B-symptoms.

Adult↗

Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study.

OBJECTIVE: Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS: Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS: Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION: The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

Carcinoma, Squamous Cell↗