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Biomedical subjects

J G Fryer

Publications and source records attributed to J G Fryer.

At least 19 recordsLinked to original sources

Treatment of advanced pancreatic carcinoma with a combination of protracted infusional 5-fluorouracil and weekly carboplatin: a Mid-Atlantic Oncology Program Study.

BACKGROUND: Advanced pancreatic cancer is a rapidly fatal disease whose course has been little influenced by chemotherapy. Earlier studies have shown some modest promise for the combination of protracted infusional 5-fluorouracil (PIF) and cisplatin. We sought to evaluate a regimen of possibly lesser toxicity, PIF plus weekly carboplatin. PATIENTS AND METHODS: Fifty-four patients with advanced adenocarcinoma of the pancreas were treated with a regimen of protracted infusional fluorouracil 300 mg/m2/day for 70 days and carboplatin 100 mg/m2/weekly on weeks 1 through 10 of a 12-week cycle. After a two-week rest, cycles were repeated until progression. RESULTS: Median duration on treatment was 82 days (range 4-490 days). Toxicity was mild. Grade 3-4 toxicities were anemia 11%, leukopenia 6%, thrombocytopenia 2%, nausea/ vomiting 7%, diarrhea 9%, mucositis 9%, and renal 2%. Response was evaluable in 47 patients. There were two complete and seven partial responses (17% overall objective response rate among all patients). Stable disease for greater than 12 weeks was seen in 19 patients (40%) and progression in 19 (40%). The median overall survival was 22 weeks (1-99), with 61 weeks median survival in responders (22-99). One-year survival was 13%. CONCLUSIONS: Response and survival results with this regimen are at least equal to the best combination regimens reported, and were obtained with a low overall rate of serious toxicity.

Adult↗

Acute severe low back pain. A population-based study of prevalence and care-seeking.

STUDY DESIGN: Telephone interviews were conducted with a random sample of adults in 4437 North Carolina households. The response rate was 79%. OBJECTIVE: The prevalence of low back pain and the correlates of care-seeking in a defined population were examined. SUMMARY OF BACKGROUND DATA: Previous research on low back pain has used varying definitions of the illness of low back pain, and has admixed patients with acute and chronic low back pain. Acute low back pain was examined in this study as a distinct phenomenon separate from chronic low back pain. METHODS: Respondents completed a detailed interview regarding the occurrence of and care sought for back pain in 1991. Acute back pain was defined as functionally limiting pain lasting less than 3 months. RESULTS: From this sample, 485 individuals had at least one occurrence of acute severe low back pain in 1991, representing 7.6% of the adult population. Symptoms were reported less commonly in individuals older than age 60 years (5% vs. 8.5%) and in nonwhites compared with whites (5% vs. 8.5%). Thirty-nine percent of those with back pain sought medical care; 24% sought care initially from an allopathic physician, 13% from a chiropractor, and 2% from other providers. More prolonged pain, more severe pain, and sciatica were associated with care-seeking. Gender, income, age, rural residence, and health insurance status did not correlate with the decision to seek medical care. Younger age, male gender, and nonjob-related pain did correlate with the decision to seek care from a chiropractor. CONCLUSIONS: Acute back pain is common. Care is often sought regardless of income and insurance status. Seeing a health care provider for acute back pain may not be discretionary from the perspective of the patient.

Acute Disease↗

Self-reported functional status in osteoarthritis of the knee in a rural southern community: the role of sociodemographic factors, obesity, and knee pain.

OBJECTIVE: This study examined the roles of sociodemographic factors (age, race, gender, education, marital status), obesity, and severity of radiographic knee osteoarthritis (OA) and knee pain on self-reported functional status. METHODS: The sample included 1,272 African-American and Caucasian individuals, aged 45 years or older, from the Johnston County Osteoarthritis Project. Analysis of variance was used to assess variation in mean Health Assessment Questionnaire (HAQ) scores by the above variables. RESULTS: Mean HAQ scores differed by severity of radiographic knee OA and knee pain, obesity, and all demographic factors (P < 0.0001), except race. Only age, female sex, obesity, and knee pain severity were independent effects (P < 0.0009). Disability associated with knee pain varied by both radiographic knee OA severity and obesity. CONCLUSIONS: Knee pain severity was more important than radiographic knee OA severity in determining disability. Obesity was independently associated with disability and compounded disability from knee pain. Studies of disability in knee OA should include assessment of obesity, severity of radiographic knee OA, and severity of knee pain, as well as their interactions.

Activities of Daily Living↗

Ethnic differences in self-reported functional status in the rural south: the Johnston County Osteoarthritis Project.

OBJECTIVE: We examined ethnic differences in self-reported functional status in a rural, population-based sample in North Carolina. METHODS: Data from 1,197 African-American and Caucasian participants, aged 45 and older, in the Johnston County Osteoarthritis Project were analyzed using multiple logistic regression to examine differences in difficulty performing tasks of the Health Assessment Questionnaire (HAQ) and in risk factor profiles associated with difficulty. RESULTS: Forty-three percent reported difficulty in one or more HAQ tasks. African-Americans were more likely than Caucasians to report difficulty performing 3 tasks (P < 0.04); these differences were minimal after adjustment for confounders. For some tasks, risk factor profiles included body mass index in African-Americans only, and age and female gender more often in Caucasians. Low educational attainment was part of the risk factor profile for walking in African-Americans. CONCLUSIONS: Differences in proportions of African-Americans and Caucasians reporting difficulty in performance of HAQ tasks were minimal, but risk factor profiles for difficulty appeared to vary by ethnicity.

Activities of Daily Living↗

The impact of arthritis in rural populations.

OBJECTIVE: Rural residents may experience more arthritis and disability than urban dwellers. This paper reviews data on arthritis in rural areas and describes a new study, the Johnston County Osteoarthritis Project, a population-based study of osteoarthritis [OA] of the knee and hip in rural North Carolina. METHODS: Published reports of urban and rural comparisons of arthritis were reviewed. Data from the first 1,432 African-American and Caucasian participants in the Johnston County Osteoarthritis Project were analyzed. Radiographic knee and hip OA were defined as a Kellgren-Lawrence grade > or = 2. Functional ability was assessed by the Health Assessment Questionnaire, timed chair stands, and 8-foot walk time. Unweighted prevalences of knee and hip OA were calculated for age, sex, and racial groups. Associations between hip and knee OA, and hip and knee pain and functional ability were examined. RESULTS: Hip OA was present in 27.9% and knee OA in 38.4% of participants. Both were strongly related to age (P < 0.0001), but only knee OA to female sex (odds ratio = 1.33, 95% confidence interval 1.05, 1.68). Neither hip OA nor knee OA was related to race. Hip OA, hip pain, knee OA, and knee pain was each associated with self-reported and observed functional ability. CONCLUSION: Residents in rural areas may experience more arthritis and disability than previously expected. Contrary to other studies, African-American and Caucasian residents of rural Johnston County, North Carolina, have similar high rates of knee and hip OA. Further study is needed to address urban/rural differences in arthritis and its impact, with adequate control of confounders, standard definitions of rural/urban and of disease, and assessment of multiple arthritis outcomes.

Activities of Daily Living↗

Calculation of received dose intensity for combinations of drugs using small-cell lung carcinoma treatment regimens as examples.

Programs are presented for the calculation of received dose intensity in combination chemotherapy regimens. These provide methods for determining the final dose intensity, the mean cumulative dose intensity together with its standard error, and other tabular and graphic summaries. Two ways of dividing patients into high and low received-dose-intensity groups are proposed. Methods are illustrated using data from Mid-Atlantic Oncology Program (MAOP) 2183, a phase III evaluation of a six-drug alternating combination vs a three-drug "standard" combination treatment for extensive small-cell lung cancer. Comparisons of received dose intensity with demographic and outcome variables are presented.

Antineoplastic Combined Chemotherapy Protocols↗

A study of oral etoposide, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small-cell lung cancer. A Mid-Atlantic Oncology Program study.

A combination of oral etoposide, infusional cisplatin (24-hr) and infusional 5-fluorouracil (5-day) was used to treat 87 patients with non-small-cell lung cancer in a Phase II trial. Twenty-six patients were Stage IIIB, and 61 patients were Stage IV (new international classification). The regimen was well tolerated, with 49% grade 3 or 4 toxicities of all types. Response rates, partial and complete, were 40%, (95% confidence interval: 30%, 51%) for Stage IV patients and 20% (95% confidence interval: 10%, 32%), in Stage IIIB. An additional 68% of patients in Stage IIIB and 45% of patients in Stage IV achieved stable disease and had a median survival of 8.8 months, similar to that of patients in partial remission. Median survival was 5.6 months (95% confidence interval: 4.4 months, 10.8 months) for Stage IV patients and 11.0 months (95% confidence interval: 8.8 months, 12.4 months), for Stage IIIB. Of interest was the finding of a higher response rate in patients with a shorter duration of symptoms (less than 6 months versus greater than 6 months).

Administration, Oral↗

A prospective randomized comparison of protracted infusional 5-fluorouracil with or without weekly bolus cisplatin in metastatic colorectal carcinoma. A Mid-Atlantic Oncology Program study.

One hundred eighty-four patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to assess the value of weekly cisplatin (20 mg/m2) when added to a protracted schedule of 5-fluorouracil (5-FU) infusion (PIF) at 300 mg/m2/d for 10 weeks of every 12 weeks. The liver was the primary indicator lesion in approximately 75% of the study group. All tumor measurements required radiographic confirmation. The response rate in the PIF alone arm was 35% (29 of 83; 95% confidence interval [CI], 25% to 46%) compared with 33% (28 of 85; 95% CI, 23% to 44%) for the arm in which weekly cisplatin was added to PIF. The median survival times were 11.8 and 11.2 months in the two groups. Weekly cisplatin does not appear to add to the effectiveness of PIF in colorectal carcinoma.

Aged↗

A study of infusional cisplatin and infusional fluorouracil for locally advanced or metastatic non-small-cell lung cancer: a Mid-Atlantic Oncology Program study.

A combination of cisplatin administered as a 24-hour infusion and fluorouracil administered as a 5-day infusion was used to treat 97 patients with non-small-cell lung (NSCLC) cancer in a phase II trial. Thirty patients had stage IIIB disease; 67 patients, stage IV disease (new international classification). Patients with stage IIIB disease also received thoracic radiation after chemotherapy. The regimen was well tolerated, with 24% or less grade 3 or greater toxicities of all types. One toxic death was attributed to fluid overload. The response rate, partial and complete, was 43% (95% confidence interval, 27% to 63%), and median survival was 13.8 months for patients with stage IIIB disease. Response rates refer to the chemotherapy response. For patients with stage IV disease, the response rate was 34% (95% confidence interval, 24% to 47%), and median survival was 6.2 months. On this regimen, stable-disease patients with stage IV disease had survivals at least equal to responders.

Adult↗

Comparison of cyclophosphamide, doxorubicin, and vincristine with an alternating regimen of methotrexate, etoposide, and cisplatin/cyclophosphamide, doxorubicin, and vincristine in the treatment of extensive-disease small-cell lung carcinoma: a Mid-Atlantic Oncology Program study.

An alternating regimen for the treatment of extensive-disease small-cell lung cancer (SCLC) was compared with standard treatment with cyclophosphamide, doxorubicin, and vincristine (CAV) in 170 patients. Overall severity of toxicity was similar in both arms, with four toxic deaths in each arm (4.7%). Response results were also similar, with 54% complete and partial responses with the standard regimen and 53% complete and partial responses with the alternating regimen. Median survival time was 6.9 months with the standard regimen and 9.2 months with the alternating regimen (P = .078). The 2-year survival rate was 1.2% for the standard regimen and 4.7% for the alternating regimen. Survival benefit for treatment with the alternating regimen reached statistical significance only in those subsets of patients with poorer prognosis (male sex, performance status 3, liver metastases, bone marrow metastases, and oat cell histologic subtype).

Antineoplastic Combined Chemotherapy Protocols↗

The importance of confounding factors in the evaluation of neuropsychological changes in patients infected with human immunodeficiency virus.

There are conflicting reports on the early effects of human immunodeficiency virus (HIV) infection on the nervous system. Some studies have suggested that there may be early cognitive impairment, while others have refuted this. We describe the results of extensive neuropsychological testing in a group of 40 infected subjects. These indicate that the degree of impairment is closely related to confounding factors other than the infection itself. Our conclusion is that the early stages of HIV disease are not associated with a high frequency of cognitive impairment if these confounding variables are taken into consideration.

AIDS-Related Complex↗

On the construction of cross-sectional statistical standards for growth.

Cross-sectional growth studies generally produce standardizing groups which are too small to permit the direct construction of standards. This problem can be circumvented by the introduction of appropriate structural assumptions. The two key papers in the literature which focus on this issue, Healy (1962) and Goldstein (1972), give methodologies which involve somewhat different premises. Healy takes the ages of individuals to be uniformly distributed over a well-defined interval (but their precise levels unknown). Goldstein by comparison supposes age levels to be known exactly. Both authors postulate that the characteristic of interest follows a Gaussian density whose mean and variance are each linear functions of time, a + bt and c + dt, say. In this paper we begin to explore the robustness of the two methods. Our results show that Healy's original moment solution to the estimation of (a, b, c and d) may be quite insensitive to departures from a uniform distribution for ages provided that this distribution remains symmetric about the interval mid-point. Moreover, the distribution of the characteristic of interest may deviate from the Gaussian without too much effect, provided that symmetry about the mean a + bt is retained. However, there is much more doubt about asymmetric departures in both cases especially with regard to the estimation of b and d. Opting for simple 'interpolated' estimates of these two parameters (when possible) rather than Healy's original formula-based versions will strongly aid robustness in general.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

An approach to the estimation of growth standards: the univariate case.

This paper shows how reference values can be determined when the underlying characteristic (say, weight) follows a distribution that is not too distant from the Gaussian. Application of the normalizing Box-Cox power transformation is the basis of our approach. This transformation is monotonic and hence invertible, so offering the choice of two scales of measurement on which to work--the original and the Gaussian. Modified versions of the procedure are provided allowing use of the basic transformation in the presence of certain deficiencies in the data, principally measurement error and misclassification. It is shown that application of Box-Cox to a cohort at several points in time can be quite revealing. When the data are already symmetrical the Box-Cox transformation has no effect: in this case the John-Draper modulus transformation and modifications of it are shown to be helpful. All of this is illustrated by using data from the Swedish Longitudinal Growth Study.

Female↗

Modelling of reference values for size at birth.

Data from the Swedish Medical Birth Registration, 1977-1981 were used to apply methods of constructing reference standards for size at birth. Using clinical information a 'healthy' sub-population was extracted. The conditional distributions of birthweight (BW) and birthlength (BL) for each week of Gestational age, and the conditional distribution of birthweight given birthlength were modelled using truncated Normal distributions, after making use of Box-Cox power transformations. Spline functions were then used in conjunction with a multiplicative method to obtain appropriate percentage point curves. Examples of this analysis are given.

Birth Weight↗

A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.

One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5-FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination.

Adenocarcinoma↗

Some points on the use of 'independent Bayes' to diagnose acute abdominal pain.

This paper outlines some of the difficulties encountered when using independent Bayes as a statistical decision aid for acute abdominal pain. Methods of reducing the resultant problems are suggested. Restriction of the number of facets in the system reduces violation of the simplifying assumption of symptom independence without adversely affecting efficiency. Introduction of a realistic utility structure is investigated as is the potential transportability of the decision aid. Generalizations of the results are discussed and potential uses of medical decision aids are considered.

Abdomen↗

Semen parameters and fertilization of human oocytes in vitro: a multivariable analysis.

Semen parameters in 195 couples undergoing in vitro fertilization and embryo transfer were studied using multivariable analysis. Semen parameters that correlated most closely with reduced ability to fertilize apparently mature oocytes were a slow rate of foreward progression of sperm and the presence of excess numbers of white cells in semen. In men with semen parameters within the normal range, the hamster egg penetration assay (HEPA) test did not add additional predictive power. In men with suspected semen abnormalities, however, a low attachment rating added some, but minimal, predictive value. None of the predictive methods reported thus far in this or other studies offers sufficient accuracy to reliably identify the men who will prove infertile for in vitro fertilization treatment.

Analysis of Variance↗