Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial.

Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ras mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta 2-microglobulin levels, labelling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P < .02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P < .02). To determine if the status of ras mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ras mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-alpha showed statistically significant survival differences between mutant and wildtype ras status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wild-type ras had a median survival of 4.0 years (P < .01).

Family planning, managed care, and rural America.

Within the United States, rural residents encounter a greater number of barriers in accessing health care services than their urban counterparts. In general, rural Americans have less access to both family planning services and managed care delivery systems. Given the rapid changes in health care, we reviewed the implications for the provision and integration of family planning and managed care services in rural areas, where there is limited experience in establishing working relationships between those services. In many instances, family planning services are well established in rural areas where managed care has not yet penetrated. Our case study in Minnesota suggests that, although managed care and family planning services are developing in rural areas, there is little evidence of collaboration. Several innovative and successful family planning projects do exist in rural areas, however, and serve as models of successful population-based programs that could work well with health plans. Although this study concentrated on the provision and utilization of subsidized family planning services, there is a compelling need for further work to determine accurately where rural residents are accessing such services and how the expansion of managed care will affect the delivery of reproductive health care.

Urban and rural differences in health insurance and access to care.

This study considers differences in access to health care and insurance characteristics between residents of urban and rural areas. Data were collected from a telephone survey of 10,310 randomly selected households in Minnesota. Sub-samples of 400 group-insured, individually insured, intermittently insured, and uninsured people, were asked about access to health care. Those with group or individual insurance were also asked about the costs and characteristics of their insurance policies. Rural areas had a higher proportion of uninsured and individually insured respondents than urban areas. Among those who purchased insurance through an employer, rural residents had fewer covered benefits than urban residents (5.1 vs 5.7, P < 0.01) and were more likely to have a deductible (80% versus 40%, P < 0.01). In spite of this, rural uninsured residents were more likely to have a regular source of care than urban residents (69% versus 51%, P < 0.01), and were less likely to have delayed care when they thought it was necessary (21% versus 32%, P < 0.01). These differences were confirmed by multivariate analysis. Rural residents with group insurance have higher out-of-pocket costs and fewer benefits. Uninsured rural residents may have better access to health care than their urban counterparts. Attempts to expand access to health care need to consider how the current structure of employment-based insurance creates inequities for individuals in rural areas as well as the burdens this structure may place on rural providers.

Preventive care for women. Does the sex of the physician matter?

BACKGROUND: Emphasis on ensuring women's access to preventive health services has increased over the past decade. Relatively little attention has been paid to whether the sex of the physician affects the rates of cancer screening among women. We examined differences between male and female physicians in the frequency of screening mammograms and Pap smears among women patients enrolled in a large Midwestern health plan. METHODS: We identified claims for mammography and Pap tests submitted by primary care physicians for 97,962 women, 18 to 75 years of age, who were enrolled in the health plan in 1990. The sex of the physician was manually coded, and the physician's age was obtained from the state licensing board. After identifying a principal physician for each woman, we calculated the frequency of mammography and Pap smears for each physician, using the number of women in his or her practice during 1990 as the denominator. Using unconditional logistic regression, we also calculated the odds ratio of having a Pap smear or mammogram for women patients with female physicians as compared with those with male physicians, controlling for the physician's and the patient's age. RESULTS: Crude rates for Pap smears and mammography were higher for the patients of female than male physicians in most age groups of physicians. The largest differences between female and male physicians were in the rates of Pap smears among the youngest physicians. For the subgroup of women enrolled in the health plan for a year who saw only one physician, after adjustment for the patient's age and the physician's age and specialty, the odds ratio for having a Pap smear was 1.99 (95 percent confidence interval, 1.72 to 2.30) for the patients of female physicians as compared with those of male physicians. For women 40 years old and older, the odds ratio for having a mammogram was 1.41 (95 percent confidence interval, 1.22 to 1.63). For both Pap smears and mammography, the differences between female and male physicians in screening rates were much more pronounced in internal medicine and family practice than in obstetrics and gynecology. CONCLUSIONS: Women are more likely to undergo screening with Pap smears and mammograms if they see female rather than male physicians, particularly if the physician is an internist or family practitioner.

Using claims data for epidemiologic research. The concordance of claims-based criteria with the medical record and patient survey for identifying a hypertensive population.

In this study, a method was developed to identify health plan members with hypertension from insurance claims, using medical records and a patient survey for validation. A sample of 2,079 patients from two study sites with medical service or pharmacy claims indicating a diagnosis of essential hypertension were surveyed, and the medical records of 182 of the 1,275 survey respondents were reviewed. Where the criteria to identify hypertensive patients used both the medical and pharmacy claims, there was 96% agreement with either the medical record or the patient survey. Where the criteria relied on medical claims alone, the agreement rate decreased to 74% with the medical record and 64% with the patient survey. Where the criteria relied on the pharmacy claims alone, the agreement rate was 67% with the medical record and 75% with the patient survey. Combined evidence from medical service and pharmacy claims yielded a high level of agreement with alternative, more costly sources of data in identifying patients with essential hypertension. As it is more thoroughly investigated, claims data should become a more widely accepted resource for epidemiologic research.

From data to policy ... to politics. The Minnesotans health care plan for universal access to care.

Calls for major reform of the health care delivery system have been sounded at both the state and federal level. However, given the lack of consensus on health care reform at a federal level, more than half of the states are developing initiatives for universal access to care. In 1989, the Minnesota legislature created the Health Care Access Commission to develop a blueprint for universal access in Minnesota. To assist this effort, we studied the extent and nature of uninsurance and underinsurance within the state. In this article we report the findings of that study and discuss how the findings were first used to develop recommendations for universal access legislation. We then describe the fate of the legislation. Finally, we describe the veto and the creation of HealthRight, the recently enacted plan for health care reform bill in Minnesota. This plan simultaneously expands access to care and aims to contain health care costs.

Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients.

One of the distinguishing features of multiple myeloma (MM) is the proliferation of plasma cells that home to the bone marrow (BM). However, there still remains some uncertainty concerning the presence of related malignant cells in the peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we amplified the third complementary determining region (CDR3) of rearranged immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain reaction (PCR). From the sequences of the products, we derived allele-specific oligonucleotides (ASO), and these were used in subsequent amplification reactions to detect malignant clones in the peripheral blood of myeloma patients. This method is highly specific and sensitive to 1 malignant cell in the background of 10(5) normal cells. Using this method we detected circulating malignant cells in 13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to artificial titrations of initial BM DNA sample into normal peripheral blood lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the amount of tumor in the patient PBL. We observed a wide variation in the amount of circulating tumor between patients. In addition, we found that the incidence of circulating tumor cells was independent of BM tumor burden and stage of disease. The detection and quantitation of circulating tumor cells in the PBL of MM patients may offer an alternative assessment of the disease and may be an important consideration in the use of peripheral stem cells in bone marrow transplantation.

T-cell receptor gene rearrangement analysis: cutaneous T cell lymphoma, peripheral T cell lymphoma, and premalignant and benign cutaneous lymphoproliferative disorders.

T-cell receptor gene rearrangement analysis is a useful technique to detect clonality and determine lineage of lymphoid neoplasms. We examined 103 patients with mycosis fungoides, Sézary syndrome, peripheral T cell lymphoma, potentially malignant lymphoproliferative disorders including pre-Sézary syndrome, large plaque parapsoriasis, lymphomatoid papulosis and follicular mucinosis, and various benign inflammatory infiltrates. A clonal rearrangement was detected in skin samples in 20 of 24 patients with mycosis fungoides and in peripheral blood samples in 19 of 21 patients with Sézary syndrome. A clonal population was also detected in seven of eight cases classified as peripheral T cell lymphoma. The potentially malignant dermatoses tended to have clonal rearrangement, with the exception of large plaque parapsoriasis, and further follow-up is needed to correlate clonality with the disease course. These studies demonstrate the value of molecular genetics as an adjunct to morphology in the examination of patients with cutaneous lymphoproliferative disease.

Quality screening and management using claims data in a managed care setting.

Quality screening and management (QSM), developed by United HealthCare Corporation for its own health plans but applicable to other settings, analyzes health care provided to an enrolled population using claims and administrative data supplemented, when necessary, with medical record review. For selected topics/conditions, QSM compares the care received by patients to that recommended by established practice guidelines and also reports and describes quality through incidence rates, condition-specific process and outcome measures, occurrence of adverse events, and use of preventive services. Results of the analyses are linked to appropriate quality management actions and are used to identify strategies for improvement. Data permit health plans to make performance comparisons on individual indicators and longitudinal comparisons on the effectiveness of quality improvement initiatives.

Medical malpractice claims in obstetrics and gynaecology: comparisons between the United States and Britain.

Obstetricians and gynaecologists have been particularly affected by the increase in the cost and number of medical malpractice claims in Britain. US obstetricians and gynaecologists have experienced a disproportionately higher rate of claim than other practitioners in that country. This article reviews the US experience of obstetrics and gynaecology malpractice claims and questions the validity of showing comparisons between the US and UK. However, even if British malpractice claims do not reach the level of American claims, the effects of claims on the National Health Service, recruitment to obstetrics and gynaecology, and clinical practice are significant.

Medical malpractice in perspective. II--The implications for Britain.

The "malpractice crisis" in the United States cannot be understood in isolation. Litigation is precipitated by features of the American health care and social security systems. Relative to the United Kingdom, there are fewer barriers of access to the courts, although the role of contingency fees has probably been exaggerated. Given the great institutional differences between the UK and the USA, the crisis seems unlikely to be replicated here unless there are further moves towards privatising both the costs of providing health care and the costs of its failures. It is concluded that a marginal change in the frequency or average cost of claims could have a serious impact on National Health Service resources, the medical defence societies, recruitment to specialties, and clinical practice. Debate over possible reforms is compromised by the dearth of good empirical data. Any changes, however, must address both the deterrence of bad practice and the compensation of injured patients.

Medical malpractice in perspective. I--The American experience.

Concern over the possibility of an American style medical malpractice "crisis" in the United Kingdom has recently been voiced by members of both medical and legal professions. The validity of such fears is examined by reviewing the conditions that have given rise to the current American difficulties. It is argued that the rise in malpractice insurance premiums and associated restrictions in availability should be seen against the background of underwriting problems specific to medical liability in conjunction with a general decline in reinsurance cover. The evidence in relation to the clinical and resource implications of malpractice is analysed. In particular, arguments that increased litigation has influenced the practice of "defensive" medicine and the choice of specialty are critically examined. Medical malpractice claims and insurance are only part of a professional environment which is undergoing dramatic social and economic changes, many of which seem more plausible candidates to be treated as important influences on the nature and organisation of health care in the United States.