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Biomedical subjects

D P Funch

Publications and source records attributed to D P Funch.

At least 19 recordsLinked to original sources

Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative disorder in renal transplant recipients.

Given its association with Epstein-Barr virus (EBV), there is considerable interest in assessing the impact of prophylactic anti-viral therapy on post-transplant lymphoproliferative disorder (PTLD). A recently completed multi center case-control study assessed the impact of immunosuppressive therapy on PTLD risk among renal transplant patients and collected information on the use of anti-viral therapy. Biopsy-confirmed PTLD cases (n = 100) were matched to 375 controls by center, date of transplant, and age. Data were collected on immunosuppression and rejection therapies, demographics, pre-transplant viral status, number of rejections, and anti-viral use. With adjustment for known risk factors, prophylactic anti-viral use was associated with up to 83% reduction in the risk of PTLD, depending on the anti-viral agent. These results were stronger for the first year post-transplant. For every 30 days of ganciclovir treatment, risk of PTLD during the first year was lower by 38% (Odds Ratio [OR]= 0.62; 95% confidence interval [CI]= 0.38-1.0); acyclovir effects were less striking (OR = 0.83; 95% CI = 0.59-1.16). Anti-viral therapy appears to play a role in reducing the risk of PTLD in renal transplant patients. Ganciclovir may be more potent than acyclovir.

Acyclovir↗

A combination study design to examine mycophenolate mofetil (MMF) and PTLD in renal transplant patients.

Renal transplant recipients who are chronically immunosuppressed by drugs are at a higher risk of developing malignancies. Commonly observed malignancies are several forms of posttransplant lymphoproliferative disorders (PTLD), skin, lip and gynaecological cancers. The risk is associated with many risk factors including the extent of immunosuppression. Mycophenolate mofetil (MMF) is an immunosuppressant, indicated for the prophylaxis of organ rejection in patients receiving allogenic renal and heart transplants. During the European approval of MMF for renal transplantation, the question was raised as to whether the use of MMF was associated with an increased risk of PTLD in comparison with alternate immunosuppressive regimens. In response, F. Hoffman-La Roche Ltd set up a prospective observational cohort study with a companion case-control study. This paper describes the objectives and the methods of these studies along with the rationale of the methodology.

Journal Article↗

Shop order fracture rate as a risk factor for strut fracture in Björk-Shiley CC60 degrees heart valves.

BACKGROUND AND AIMS OF THE STUDY: Previous studies have implicated a number of characteristics that predict strut fracture in Björk-Shiley convexo-concave heart valves, including valve size and position, opening angle, and weld date. This study examines whether the specific batch (shop order) with which a valve is associated during manufacture is related to the risk of fracture. MATERIAL AND METHODS: Our case-control study of CC60 degrees valves obtained detailed information on the manufacturing characteristics of 147 case and 1094 control valves used. Shop order fracture rate for each valve (percentage of other valves in the same shop order with a fracture) was obtained from the research database maintained by the valve manufacturer. RESULTS: Shop order was associated with fracture risk. Valves originating from shop orders with the highest two categories of fracture rate were at approximately twice the risk of fracture as other valves, after accounting for the effect of known risk factors. CONCLUSIONS: Shop order information may provide additional data for assessing the likelihood of valve fracture in individuals being considered for prophylactic explant of heart valves.

Analysis of Variance↗

Assessment of cellular telephone and other radio frequency exposure for epidemiologic research.

Epidemiologists are now embarking on the evaluation of the hypothesis that exposure to radio frequency energy from low-power wireless communication devices, such as portable cellular telephones, causes brain cancer and other adverse health outcomes. Even in the laboratory, exposures from radio frequency sources are difficult to quantify; their measurement in large populations for epidemiologic study is challenging. In this paper, we outline the nature and magnitude of these exposures and discuss the prospects for obtaining useful measures of exposure for epidemiologic research.

Brain Neoplasms↗

Utility of telephone company records for epidemiologic studies of cellular telephones.

We conducted a survey of over 5,000 telephone users who were customers of one large cellular telephone company covering four major geographical areas. Our primary goal was to assess the utility of ascertaining information on telephone use and type from telephone company records. We compared information from 3,949 respondents with corresponding data from company billing records. We found that 48% of the account holders were sole users, and 69% were the primary user, meaning that they accounted for at least 75% of the use. Respondent reports of amount of telephone use were highly correlated with data on the billing record (r = 0.74). Respondent reports of telephone type were similarly correlated with data from the manufacturer (r = 0.92). We also inquired about telephone holding patterns, since these have implications for exposure. Most users reported favoring one side of the head when using the telephone, but the side of the head used was not strongly associated with handedness.

Adult↗

Overall mortality of cellular telephone customers.

Unlike mobile cellular telephones, in which the antenna is not part of the handset, a portable cellular telephone exposes the user's head to radio frequency energy transmitted from the antenna. This exposure has prompted concerns about potential biological effects, including brain cancer. As a first step in a record-based mortality surveillance of cellular telephone customers, we report on overall mortality of a cohort of more than 250,000 portable and mobile telephone customers during 1994. We found age-specific rates to be similar for users of the two types of telephones. For customers with accounts at least 3 years old, the ratio of mortality rates in 1994 for portable telephone users, compared with mobile telephone users, was 0.86 (90% confidence interval = 0.47-1.53).

Adult↗

Patient factors associated with strut fracture in Björk-Shiley 60 degrees convexo-concave heart valves.

BACKGROUND: Previously established predictors of outlet strut fracture in Björk-Shiley convexo-concave (CC) valves include larger valve size, larger opening angle (70 degrees versus 60 degrees), younger age at implant, and date of manufacture. We sought to identify patient characteristics that might be predictive of strut fracture and to refine the estimates associated with previously identified predictors. METHODS AND RESULTS: We conducted a case-control study of CC60 degrees valves implanted in the United States and Canada and manufactured between January 1, 1979, and March 31, 1984. Cases included all valves with verified outlet strut fractures reported to the manufacturer from January 1979 through January 1992. Up to 10 controls were selected for each case. Control valves were matched according to implanting surgeon and were required to have been functioning at least as long as their matched case valves. Case and control medical records were reviewed for information on patient medical history before the valve implant. There were 96 case and 634 control valves for which clinical data were available. Patient age and valve size and implant position were confirmed as important determinants of fracture. There was a strong inverse gradient of risk with age. The risk of fracture was 42% lower for each 10-year increment of patient age at time of implant. Large mitral valves were at greatest risk of strut fracture, with the largest mitral valves (33 mm) estimated to be 33 times more likely to fracture than the smallest (21 to 25 mm) aortic valves. Date of manufacture was also associated with risk; valves welded from mid-1981 through March 1984 were more likely to fracture than those manufactured in 1979 and 1980. Body surface area < 1.5 m2 was associated with 1/16 the risk of body surface area > or = 2.0 m2. No other patient factor was strongly associated with the risk of strut fracture. CONCLUSIONS: Few patient features identifiable in the implant record are predictive of strut fracture. Our analysis supports previous work in identifying valve size, patient age, and date of manufacture as predictors of fracture and adds body surface area. A number of these associations suggest that conditions associated with higher cardiac output may also place patients at increased risk.

Adult↗

Manufacturing characteristics associated with strut fracture in Björk-Shiley 60 degrees Convexo-Concave heart valves.

Björk-Shiley Convexo-Concave (CC) valves sometimes experience fracture of the outlet strut. Previously implicated valve characteristics that predict strut fracture include larger valve size, larger opening angle (70 degrees vs 60 degrees), remilling, weld date, and implant in the mitral position. While the associations between risk, size, and opening angle suggest that part of the elevated incidence of strut fracture might be due to the design of the Björk-Shiley valves, only a small fraction of implanted valves have experienced strut fracture. In consequence, previously unexamined variations in the manufacturing process have been suggested as possible factors affecting the failure risk of individual valves; materials, manufacturing steps, quality control, and specific workers have all been put forward as potential explanations for valve-to-valve variation in risk. We conducted a case-control study of CC60 degrees valves implanted in the USA and Canada and manufactured between January 1, 1979 and March 31, 1984. Cases included all verified strut fractures reported to the manufacturer from 1979 through January, 1992. up to 10 controls were selected for each case. Controls were matched to cases on implanting surgeon and were required to have been implanted and functioning at least as long as their respective case valves. We reviewed case and control manufacturing records. There were 150 cases and 1095 surgeon-matched controls. Large mitral valves were at greatest risk of strut fracture; 33mm mitral valves were estimated to be 23 times more likely to fracture than 21-25mm aortic valves. Valves welded in 1979 and 1980 were less likely to fracture than those welded in any other time period; however, no specific manufacturing procedures or personnel were uniquely associated with this time period. Valves with more flexible outlet struts, as determined by the hook deflection and load deflection tests during manufacture, appear to have been at higher risk than valves with more rigid outlet struts. There were three welders who had worked on a sufficient number of valves to allow separate estimation of the risk in the valves they welded. One welder's work was associated with about one-third the risk of valves worked on by the other two. Examination of receiver operating characteristic curves revealed, however, that welder identity added little to the discriminating information already available in the form of valve size and implant position. It is concluded that welder identity and strut flexibility appear to contribute to the risk of outlet strut fracture in Björk-Shiley CC60 degrees valves. Neither of these factors, however, is sufficient to account for much of the previously unexplained variation in risk. No other characteristic measurable in existing manufacturing records appears to predict risk of strut fracture in any useful way.

Canada↗

Depressive symptoms and headaches in relation to proximity of residence to an alternating-current transmission line right-of-way.

Electric power transmission lines have become objects of public controversy. Hypotheses have linked neurobehavioral effects to the electric and magnetic fields that these lines produce. The authors conducted a telephone interview survey in November 1987 to assess the prevalence of depressive symptoms and headache in relation to proximity of residence to an alternating-current transmission line in the United States. Proximity to the line, defined as residing on a property abutting the right-of-way or being able to see the towers from one's house or yard, was positively associated with a measure of depressive symptoms. The association was not explained by demographic variables associated with depression or by attitudes about power lines or other environmental issues. The estimated prevalence odds ratio was 2.8 (95% confidence interval (CI) 1.6-5.1). The estimate did not change appreciably when the definitions of depressive symptoms or of proximity to the line were altered. Nonmigraine headaches had a weaker association with proximity to the line (odds ratio = 1.5, 95% CI 0.76-2.8), and self-reported migraine headaches exhibited no association (odds ratio = 0.99, 95% CI 0.29-3.4). Additional studies of psychological and behavioral measures should be conducted in relation to electric and magnetic fields, with a strong emphasis on improved exposure assessment.

Adult↗

Bromocriptine and puerperal seizures.

Case reports have prompted concern that the use of bromocriptine mesylate to prevent lactation in the puerperium increases the risk of postpartum seizure. We conducted a record-based case-control study of postpartum seizures in three data bases to evaluate this relation. We identified 43 women who had a postpartum seizure, and we matched 319 controls individually by hospital of delivery, quinquenium of age, and time of delivery. Overall, women taking bromocriptine had a 22% lower risk for seizures, that is, the relative risk estimate was 0.78, with a 90% confidence interval of 0.29 to 1.87. A reduction in seizure risk is consistent with reports of antiseizure activity for bromocriptine in various species, including humans. We found a small positive association between bromocriptine use and seizures occurring more than 72 hours after delivery, with a relative risk estimate of 1.6 after controlling for seizure history. This association was offset by a strong negative association between bromocriptine use and early-occurring seizures. The pattern of an initial reduced risk followed by an increase to normal or above-normal levels of risk could result from an antiseizure activity of bromocriptine, with a rebound in risk when bromocriptine is withdrawn.

Adolescent↗

Predictors and consequences of symptom reporting behaviors in colorectal cancer patients.

Data from a sample of 294 colorectal cancer patients were used to examine factors influencing symptom reporting. The number of symptoms reported spontaneously by the subjects in response to open-ended questions was compared with the total number of symptoms reported using this technique plus a variety of other techniques. Fifty-four percent of the total number of symptoms were reported spontaneously by the subjects. Subject and symptom characteristics were examined for an association with symptom reporting patterns. Subject characteristics associated with spontaneous reporting were socioeconomic status (SES), prior health status, and psychological status at the time of the interview; age and sex were not related to symptom reporting. The best predictors of symptom reporting were symptom characteristics, with symptoms that were severe, unusual, and developed quickly reported more often. Incomplete symptom reports also were associated with inaccurate estimates of patient delay. Implications of these findings for medical practice and for future research are discussed.

Adult↗

Predicting treatment completion in a behavioral therapy program for chronic temporomandibular pain.

The aim of this study was to identify factors useful in predicting whether chronic temporomandibular pain patients would complete a behavioral treatment program. Detailed clinical examination and interviews regarding demographic and social factors were given to 78 patients on week prior to treatment. They also completed a number of personality measures (depression, anxiety, locus of control) at that time and kept a pain diary during the following week to establish baseline levels. Motivation was also assessed. Patients were classified as completing (54%) or failing to complete (46%) the program. Social factors (family and generalized others' attitudes towards the patient's pain) were the only significant predictors of treatment completion. In a multiple regression analysis, these factors accounted for 43% of the variance. These results suggest the usefulness of including social-environmental factors when considering patient compliance. Implications for the conceptualization of social support are discussed.

Adult↗

Assessment of a short scale to measure social support.

A wide variety of measures have been used to assess the effects of social support on both physical and psychological status. Information on the reliability and validity of many of these instruments is unavailable; other instruments appear to be reasonably valid but involve large numbers of questions and require considerable time for completion. This study examines the properties of a short, self-administered social support scale (SSS). Data are available from 3 samples: HMO clients in a weight loss program (N = 268); chronic facial pain patients (N = 92); and colorectal cancer patients (N = 318). Three scoring strategies measuring two dimensions (structural and perceptual) of social support are compared with respect to internal consistency and criterion and construct validity. One of these strategies results in a measure that behaves in a way consistent with other, longer instruments and appears to possess acceptable reliability and validity. Scores can be broken down by source (e.g. spouse, friends), and wording can be modified to measure either general support or support for a specific situation.

Adult↗

Diagnostic delay in symptomatic colorectal cancer.

Previous research on colorectal cancer patients has suggested that considerable delay can occur once the patient has sought medical care. However, little information has been available on the possible components of this delay. In this study, detailed information on diagnostic delays was collected from 294 symptomatic patients. Of these patients, 46% reported experiencing at least one delay. Three types of diagnostic delay were identified and were associated with different lengths of delay. Of all the delays, 31% were due to difficulties in scheduling initial or subsequent office visits or laboratory tests; these were associated with an average delay of 3 weeks. Physician-related delays (e.g., misdiagnosis or observation of symptoms without specific action) comprised 46% of all diagnostic delays and resulted in an average delay of 18 weeks. The remainder of the delays were patient-related and resulted in an average delay of 12 weeks. There was no association between any of these three delay types, suggesting that attempts to reduce diagnostic delay should encompass all three types in order to be maximally effective.

Adolescent↗

Self-reliance as a modifier of the effects of life stress and social support.

A variable was introduced which classified 151 women with breast cancer into those with perceived self- or other-reliance regarding their recovery from breast surgery. While this factor played no direct role in psychological adjustment, it did serve as a modifier of the relationships between stress, social support, and adjustment. Life stress assumed more and support assumed less importance for those who were self-reliant. It is suggested that self-reliance is related to locus of control. The implications of this suggestion are applied to these findings.

Adult↗

Factors associated with successful outcome from behavioral therapy for chronic temporomandibular joint (TMJ) pain.

A total of 42 chronic temporomandibular joint pain patients completed behavioral therapy for their pain. The role of clinical, sociodemographic, and psychosocial factors was examined in relation to treatment outcome (immediately following treatment and at 2-yr follow-up). Psychosocial factors were better predictors of treatment outcome than clinical and demographic factors. Patients who had the most successful outcomes (both short- and long-term) were more motivated and less depressed than other patients and were internal with respect to their health locus of control.

Behavior Therapy↗