The National Cancer Institute and guideline development: lessons from the breast cancer screening controversy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Harris.
Explore the source record for details and available documents.
OBJECTIVE: To examine the stability of patients' choices for life-sustaining treatments. DESIGN: A longitudinal cohort study. SETTING: Primary care practices in central North Carolina. PATIENTS: Medicare recipients (n = 2536). INTERVENTION: Participants were asked about demographic characteristics, health status, well-being, depression, social support, use of a living will, and desire for life-sustaining treatment if they were to become terminally ill. These questions were repeated 2 years later (n = 2073, 82% follow-up). RESULTS: The population tended to choose to forego one more treatment at follow-up than they did at baseline. A choice to forego treatment was twice as stable as a choice to receive treatment. Patients with a living will were less likely to change their wishes (14%) than those without a living will (41%). Persons were more likely to want increased treatment at a later time if they had been hospitalized (23% compared with 18%), had had an accident (29% compared with 19%), had become more immobile (23% compared with 19%), had become more depressed (25% compared with 15%), or had less social support (25% compared with 14%). CONCLUSIONS: Most patients (85%) who had chosen to forego life-sustaining treatments did not change their choices. Nonetheless, these data suggest that it is important to review patients' preferences for life-sustaining treatments rather than to assume the stability of their choices.
Explore the source record for details and available documents.
BACKGROUND AND DESIGN: We studied the clinical and photobiologic features of 51 patients with chronic actinic dermatitis who were evaluated at three institutions. The following criteria for patient selection were used: (1) a persistent eczematous eruption in the sun-exposed areas of greater than 3 months' duration; (2) decreased phototest results; and (3) when available, histologic changes of a dermal infiltrate of lymphocytes and macrophages, with or without epidermal spongiosis and atypical mononuclear cells in the dermis and epidermis. RESULTS: The 51 patients had a mean age of 62.7 years, a male-to-female ratio of 2.6:1, and a mean duration of eruption of 5.8 years. The most common abnormal results of the phototests were decreased minimal erythema doses to both UV-A and UV-B, followed by decreased minimal erythema doses to UV-A alone. Patients with abnormally low responses to UV-A or visible light and normal minimal erythema doses to UV-B had the same clinical profile as the overall patient population. Aside from protection from sunlight, treatment modalities that have been used include PUVA (8-methoxypsoralen and UV-A) photochemotherapy, azathioprine, hydroxychloroquine sulfate, and, for recalcitrant cases, cyclosporine. CONCLUSIONS: Chronic actinic dermatitis is a persistent photodermatosis associated with abnormal phototest responses to UV-A, and/or UV-B, and/or increased sensitivity to visible light; histopathologic changes are consistent with photodermatitis. Treatment consists of combinations of topical and oral medications.
OBJECTIVE: To identify by specialty (family practice, general internal medicine, and general pediatrics) the number and ratios of generalist physicians per 100,000 population in nonmetropolitan counties in Ohio and to describe the trends in these data from 1975 through 1990. DESIGN: The data were compiled on a country basis by physician census takers residing in each county in Ohio. The US Office of Management and Budget's definition of nonmetropolitan counties formed the basis of the calculations. RESULTS: In nonmetropolitan counties of Ohio, generalist physician numbers and ratios improved between 1975 and 1990 in general internal medicine (from 5.9 to 10.2 per 100,000 population) and general pediatrics (from 2.6 to 4.9 per 100,000 population) but not in family practice, which experienced a decrease from 31.0 to 28.7 per 100,000 population. Eight counties with no hospitals were unable to attract general internists or general pediatricians. CONCLUSIONS: The results of this study indicate the importance of characterizing generalist physician workforce data by specialty and practice location on a state-wide basis and suggest that increasing the supply of physicians does not greatly improve the geographic distribution of the medical workforce. These findings should affect the development of local, state, and federal physician workforce policies aimed at addressing the problem of physician geographic maldistribution.
Explore the source record for details and available documents.
A cDNA encoding a soluble sialidase from Chinese hamster ovary (CHO) cells has been cloned and expressed. Completely degenerate oligonucleotide primers, which were based on the amino acid sequence of peptides obtained from the purified sialidase (Warner et al., Glycobiology, 3, 455-463, 1993), and the polymerase chain reaction, with single-stranded cDNA template, were employed to generate a unique oligonucleotide probe. The unique probe of 93 bp was used for screening a lambda gt 10 CHO cell cDNA library. A single clone, which contained a 1.4 kb insert, was isolated after screening 450,000 recombinants. The complete coding region of the protein, 1137 nucleotides, was contained in the isolated clone and it predicted a protein of 379 amino acids. The insert had a 186 bp 5' non-coding leader sequence and a 40 bp 3' non-coding region. No signal peptide was identified in the insert, suggesting a cytosolic localization for the protein. No significant primary sequence identities were observed when the deduced amino acid sequence of the CHO cell sialidase was compared with other mammalian proteins or microbial sialidases. However, the protein had significant sequence alignment similarity with several bacterial sialidases. Two 'Asp box' motifs in the CHO cell sialidase had a remarkable alignment positioning in the protein sequence with the similar motifs of the Salmonella LT2 and Clostridium perfringens sialidases. High levels of the enzyme were expressed in Spodoptera frugiperda cells infected with a modified Autographa californica nuclear polyhedrosis virus harbouring the sialidase cDNA.
Explore the source record for details and available documents.
Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p < 0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p < 0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counselees reported a deterioration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.
Diagnosis of autosomal dominant adult polycystic kidney disease (APKD) is possible by ultrasonographic scanning (USS) or by using DNA markers linked to the PKD1 locus. Ultrasonography is complicated by the age dependent penetrance of the gene and linkage studies are subject to recombination errors owing to meiotic crossing over and locus heterogeneity. This study draws on data collected from a voluntary family register of APKD over 10 years. Records of 150 families were examined, ultrasound reports were obtained from 242 people at 50% prior risk, and 37 families were typed for DNA markers. The fraction of APKD resulting from loci unlinked to PKD1 (designated PKD2 here) was calculated at 2.94% (upper confidence limit 8.62%). Some subjects who were negative on initial scan later gave a positive scan, but there was no example of a definite gene carrier aged over 30 giving a negative scan. In families large enough for linkage analysis, most people who were at 50% prior risk could be given a final risk below 5% or above 95%, by using combined ultrasound and DNA studies.
This study investigated MMPI characteristics of adult female outpatients in a behavior therapy clinic (N = 110). Those reporting histories of childhood sexual or physical abuse or both differed from those who did not on global Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1943) indices of psychopathology and on Scales F, K, L, 4, 7, and 8. Subjects reporting abuse also reported high rates of other early traumas: witnessing family violence, parental alcohol abuse, and parental divorce. Physical abuse history was the best predictor of adult maladjustment as assessed by the MMPI. Findings suggest the potential utility of the MMPI for assessing long-range trauma effects and highlight the importance of considering multiple early-risk factors for the development of psychological disturbance.
This study provides data on empathy for 82 adolescent male sex-offenders and 108 male nonoffenders. No statistically significant association was found between scores on a 4-item measure of empathy and sex-offender status.
The present study provides data on the prevalence of prior adult sexual contact among a sample of 47 adolescent male sex offenders and 109 male nonoffenders. Offenders (61.7%) reported a higher rate of sexual touching by an adult than did nonoffenders (19.3%).
BACKGROUND: Over the past 30 years, eight major randomized controlled trials of breast cancer screening--with mammography and/or clinical breast examination--have been conducted. Results from several trials have been updated during the past year, and initial results of three other trials have been reported. PURPOSE: The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world's most recent clinical trial data on breast cancer screening, consider the new evidence, assess the current state of knowledge, and identify issues needing further research. METHODS: Investigators representing the eight randomized controlled trials of breast cancer screening in women aged 40-74 presented published and unpublished data. Evidence relating to the effectiveness of breast cancer screening in different age groups, especially women aged 40-49, was presented. RESULTS: For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry. A meta-analysis of six trials found a relative risk of 1.08 (95% confidence interval = 0.85-1.39) after 7 years' follow-up. After 10-12 years of follow-up, none of four trials have found a statistically significant benefit in mortality; a combined analysis of Swedish studies showed a statistically insignificant 13% decrease in mortality at 12 years. Only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results show a 25% decrease in mortality at 10-18 years. Statistical significance of this result is disputed, however. In women aged 50-69, all studies show mortality reductions; three of four studies show reductions of about 30% at 10-12 years after study entry. Results from two of these trials were statistically significant. Too few women over age 70 have been included in studies for adequate analysis. CONCLUSIONS: For women aged 40-49, randomized controlled trials of breast cancer screening show no benefit 5-7 years after entry. At 10-12 years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50-69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening. IMPLICATIONS: Randomized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer. However, much still needs to be learned. Periodic gatherings of scientists in the field should speed the process.
Delivering preventive care in a primary care practice is often more difficult for rural than for urban practices. First, rural compared with urban patients tend to be older, poorer, and less well insured, all characteristics associated with lower levels of preventive care. Second, there are many more patients per physician in rural than urban settings. Third, the distance from sources of preventive care is much greater for rural than for urban people. Fourth, rural practices tend to be smaller, with fewer resources to perform high-quality preventive care. Long-term programs to increase recruitment and retention of primary care physicians and improve insurance coverage for rural people may eventually improve preventive care utilization. A more immediate approach is to change the organization of medical practice, including developing satellite clinics, redefining the roles of nurses and nurse practitioners, and using organized systems within practices to reach and follow-up underserved groups. Initial impressions from the North Carolina Prescribe for Health project indicate that an organized approach to preventive care within physicians' offices may improve utilization of carefully designed packages of preventive care. More information is needed to understand the differences among rural, urban, and suburban areas in delivering preventive care to primary care patients.
OBJECTIVE: To assess the feasibility of genetic counselling in general practice by using cystic fibrosis carrier screening at the booking appointment as an integral part of routine antenatal care and as a paradigm for the wider participation of general practitioners in medical genetics. DESIGN: Maternal testing (male partner tested only if woman screens positive) and couple testing for cystic fibrosis carrier status in the antenatal population attending one general practice and, later, in a further six (outreach) practices also. SETTING: Two partner urban training practice (pilot practice) in south Manchester, and six north west practices (two inner city, three urban, one rural dispensing). SUBJECTS: Total practice population of 50,000 (pilot practice plus six outreach practices) with an estimated 500-800 pregnancies per year. MAIN OUTCOME MEASURES: (a) Proportion of carriers of cystic fibrosis identified, counselled, and appropriately managed within the first trimester of pregnancy; (b) questionnaire and interview measures of patient satisfaction and stress. RESULTS: Eleven carriers of cystic fibrosis were detected including one carrier couple. This carrier couple, after extensive counselling, elected to have prenatal diagnosis by chorionic villus biopsy. The fetus was homozygous normal. CONCLUSIONS: General practitioners can successfully integrate genetic counselling and cystic fibrosis carrier screening into the first antenatal booking appointment. When a carrier couple is identified clinical geneticists can help with the discussion of reproductive options, and prenatal diagnosis by chorionic villus biopsy can be completed within the first trimester. The results suggest that general practitioners will have an increasingly important role in medical genetics, subject to continuing evaluation of patient acceptability and stress.
The synthesis of porcine plasma kallikrein (pPK) segment (11-23), of sequence Phe-Phe-Arg-Gly-Gly-Asp-Val-Ser-Ala-Met-Tyr-Thr-Pro, present in the first tandem repeat sequence of the regulatory chain of PK, has been accomplished following the peptide fragments (5 + 4 + 4) condensation strategy in solution, as well as by fluorenylmethoxycarbonyl solid-phase chemistry. This and another synthetic PK segment of residues (328-343) present in the fourth tandem repeat sequence [Cys(ACM)-Ser-Leu-Arg-Leu-Ser-Thr-Asp-Gly-Ser-Pro-Thr-Arg-Ile-Thr-Tyr] and synthesized by a solid-phase method, were fully characterized by 1H nuclear magnetic resonance, fast atom bombardment mass spectrometry, amino acid composition and reversed-phase high-performance liquid chromatography. Proteolysis of these peptides by either rat PK (rPK) or trypsin resulted in cleavages between Arg decreases Gly for pPK (11-23) and between Arg decreases Leu and Arg decreases Ile for rPK (328-343). Kinetic studies revealed that for peptide pPK (11-23), the catalytic efficiency (kcat/Km) of rPK is congruent to 9-fold higher than that of trypsin, but for the other peptide, rPK (328-343), kcat/Km of trypsin is congruent to 49-fold higher than that of rPK. The facile cleavage of pPK (11-23) by rPK confirms the Arg13 decreases Gly14 position as the site of autolytic degradation of PK and also explains its special preference for Phe-Phe-Arg sequence.