Clinical and Statistical Considerations when Assessing Oxygen Levels in Tumors: Illustrative Results from Clinical EPR Oximetry Studies.

The success of treatment for malignancies, especially those undergoing radiation therapy or chemotherapy, has long been recognized to depend on the degree of hypoxia in the tumor. In addition to the prognostic value of knowing the tumor's initial level of hypoxia, assessing the tumor oxygenation during standard therapy or oxygen-related treatments (such as breathing oxygen-enriched gas mixtures or taking drugs that can increase oxygen supply to tissues) can provide valuable data to improve the efficacy of treatments. A series of early clinical studies of tumors in humans are ongoing at Dartmouth and Emory using electron paramagnetic resonance (EPR) oximetry to assess tumor oxygenation, initially and over time during either natural disease progression or treatment. This approach has the potential for reaching the long-sought goal of enhancing the effectiveness of cancer therapy. In order to effectively reach this goal, we consider the validity of the practical and statistical assumptions when interpreting the measurements made in vivo for patients undergoing treatment for cancer.

'Oxygen Level in a Tissue' - What Do Available Measurements Really Report?

The aim of the paper is to discuss what currently is feasible clinically to measure the level of oxygen and how that measurement can be clinically useful. Because oxygen in tissues is quite heterogeneous and all methods of measurement can only provide an average across heterogeneities at some spatial and temporal resolution, the values that are obtained may have limitations on their clinical utility. However, even if such limitations are significant, if one utilizes repeated measurements and focuses on changes in the measured levels, rather than 'absolute levels', it may be possible to obtain very useful clinical information. While these considerations are especially pertinent in cancer, they also pertain to most other types of pathology.

Skeletal Muscle Oxygenation Measured by EPR Oximetry Using a Highly Sensitive Polymer-Encapsulated Paramagnetic Sensor.

We have incorporated LiNc-BuO, an oxygen-sensing paramagnetic material, in polydimethylsiloxane (PDMS), which is an oxygen-permeable, biocompatible, and stable polymer. We fabricated implantable and retrievable oxygen-sensing chips (40 % LiNc-BuO in PDMS) using a 20-G Teflon tubing to mold the chips into variable shapes and sizes for in vivo studies in rats. In vitro EPR measurements were used to test the chip's oxygen response. Oxygen induced linear and reproducible line broadening with increasing partial pressure (pO2). The oxygen response was similar to that of bare (unencapsulated) crystals and did not change significantly on sterilization by autoclaving. The chips were implanted in rat femoris muscle and EPR oximetry was performed repeatedly (weekly) for 12 weeks post-implantation. The measurements showed good reliability and reproducibility over the period of testing. These results demonstrated that the new formulation of OxyChip with 40 % LiNc-BuO will enable the applicability of EPR oximetry for long-term measurement of oxygen concentration in tissues and has the potential for clinical applications.

Calculation of dose conversion factors for doses in the fingernails to organ doses at external gamma irradiation in air.

Absorbed doses to fingernails and organs were calculated for a set of homogenous external gamma-ray irradiation geometries in air. The doses were obtained by stochastic modeling of the ionizing particle transport (Monte Carlo method) for a mathematical human phantom with arms and hands placed loosely along the sides of the body. The resulting dose conversion factors for absorbed doses in fingernails can be used to assess the dose distribution and magnitude in practical dose reconstruction problems. For purposes of estimating dose in a large population exposed to radiation in order to triage people for treatment of acute radiation syndrome, the calculated data for a range of energies having a width of from 0.05 to 3.5 MeV were used to convert absorbed doses in fingernails to corresponding doses in organs and the whole body as well as the effective dose. Doses were assessed based on assumed rates of radioactive fallout at different time periods following a nuclear explosion.

The promise and pitfalls of explicitly rewarding physicians based on patient insurance.

In a large multi-specialty group practice treating approximately equal numbers of health maintenance organization (HMO) and fee-for-service (FFS) patients, we analyzed a natural experiment by the administration to introduce a dual incentive system for physicians. We examine the impact on care when they announced that each physician would be remunerated for HMO care based on a per capita budget, but for FFS care based on billable services. Data were 86,230 episodes for treating patients under age 65 with seven common illnesses. There was no evidence that the intended impact (reducing HMO care) occurred; instead, there were undesired and unintended effects (reduced care for FFS and upset physicians and threats to their corporate culture).

Key challenges in studying organizational issues in the delivery of healthcare to older Americans.

OBJECTIVE: Drawing from the articles presented in this special issue, to provide an overview of three key challenges facing researchers in the area of organizational issues in primary care delivery to older adults. CONCLUSIONS: To improve the quality of research done in this area we would recommend that researchers attend to the complexity of (1) defining an appropriate unit of analysis; (2) reframing our traditional models of service delivery to reflect ongoing changes in healthcare system actors and boundaries; and (3) reconceptualizing the outcomes of care to reflect adequately the reality of care for the aging patient.

How do HMOs achieve savings? The effectiveness of one organization's strategies.

OBJECTIVE: To examine how a group practice used organizational strategies rather than provider-level incentives to achieve savings for health maintenance organization (HMO) compared to fee-for-service (FFS) patients. DATA SOURCES/STUDY SETTING: A large group practice with a group model HMO also treating FFS patients. Data sources were all patient encounter records, demographic files, and clinic records covering 3.5 years (1986-1989). The clinic's procedures to record services and charges were identical for FFS and HMO patients. All FFS and HMO patients under age 65 who received any outpatient services during approximately 100,000 episodes of the seven study illnesses were eligible. STUDY DESIGN: Using an explanatory case design, we first compared HMO and FFS rates of resource utilization, in standardized dollars, which measured the impact of organizational strategies to influence patient and provider behavior. We then examined the effect of HMO insurance and organizational measures to explain total outpatient use. Key variables were standardized charges for all outpatient services and the HMO's strategies. PRINCIPAL FINDINGS: Patient and provider behavior responded to organizational strategies designed to achieve savings for HMO patients; for instance, HMO patients used midlevel providers and generalists more often and ER and specialists less often. Overall HMO savings, adjusted for case mix, were explained by the specialty of the physicians the patients first visited and appeared to affect patients with average health more than others. CONCLUSION: Organizational strategies, without resort to differential financial incentives to each provider, resulted in lower rates of outpatient services for HMO patients. Savings from outpatient use, especially for common diseases that rarely require hospitalization, can be substantial.

The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team.

OBJECTIVE: Routine screening for prostate cancer is controversial because of frequent false-positive results, the potential for slow, non-life-threatening growth of untreated cancer, the uncertainty regarding whether treatment can extend life, and the potential for treatment complications. This study examines how information about prostate-specific antigen (PSA) testing and the uncertain benefits of treating prostate cancer affects patients' desire for PSA testing. DESIGN: An educational videotape designed to inform men about the uncertainty surrounding PSA screening and the treatment of early-stage prostate cancer was presented to two groups of male patients 50 years of age or older. SETTING: Dartmouth-Hitchcock Medical Center. PATIENTS/PARTICIPANTS: For study 1, men seeking a free prostate cancer screening were preassigned to view the educational videotape (N = 184) or another videotape (N = 185). For study 2, men scheduled to visit a general internal medicine clinic viewed either the educational videotape (N = 103) or no videotape (N = 93). MEASUREMENTS AND MAIN RESULTS: The men's information and preferences about prostate cancer screening and treatment and actual choice of PSA test at the next test opportunity were measured. Men who viewed the educational videotape were: better informed about PSA tests, prostate cancer, and its treatment; preferred no active treatment if cancer were found; and preferred not to be screened (all significant at p < or = .002 in both studies). Men viewing the educational video were less likely to have a PSA test (p = .041, study 2). This tendency was not significant at the free-PSA clinic (p = .079). CONCLUSIONS: Preference regarding cancer screening and treatment is greatly affected by information about medical uncertainties. Because informed patient choices vary. PSA screening decisions should incorporate individual preferences.

International variation in intervention rates. What are the implications for patient selection?

While international variations in intervention rates are well recognized, little is known about their implications for patient selection. This paper describes an exploratory study in which the probability of undergoing an elective intervention (surgery for benign prostatic hyperplasia) in an area in the United Kingdom was compared with an area in the United States. It found that the area with high intervention rates was associated with higher levels of surgery in men with low levels of need who are unlikely to gain much benefit.

Through the lenses of organizational sociology: the role of organizational theory and research in conceptualizing and examining our health care system.

This paper reviews various theoretical perspectives on organizational change which have been and could be applied to medical organizations. These perspectives are discussed as both filters influencing our observations (research) and mirrors of the shifting dynamics of delivery system reform (policy). We conclude with an examination of how such theories can provide useful insights into our rapidly changing health care system.

No insurance, public insurance, and private insurance: do these options contribute to differences in general health?

This paper examines the validity of two of the basic assumptions made about health care insurance and health, namely that having any insurance is associated with better health and, in particular, that having public, welfare-based insurance has better health consequences for the poor than does having no insurance. These questions were addressed using data from the National Medical Expenditure Survey, a national household-based survey in 1987 of more than 36,000 people who were asked to report in detail about their medical care use and expenditures, health insurance coverage, and health and functional status. The results of the analysis indicate that being without insurance is associated with having poorer general health compared to persons with private insurance, and that the health of persons who qualify for public insurance is the poorest of any group--poorer even than those without insurance.

The role of expectations in patients' reports of post-operative outcomes and improvement following therapy.

Outcomes research typically focuses on the technical capabilities associated with treatment that predicts patients' post-therapy outcomes adjusting for health-related factors. Research on the ability of placebo therapy to alter outcomes suggests that a patient's expectations about therapy can also influence outcomes. Few studies have examined the effects of expectations and their implications for assessing outcomes. This study followed 348 patients who had surgery for benign prostatic hyperplasia. Four hypotheses are tested: whether positive expectations about improvement influence: 1) patients' postoperative reports of symptoms; 2) their belief that they have improved; 3) their overall health after treatment; and 4) whether these effects persist during the year following treatment. Using step-wise regression to control for sociodemographic and clinical factors, we found positive expectations did not appear to strongly influence a patient's report of postoperative symptoms or their overall health. However, we found strong support for positive expectations increasing the likelihood of reporting they felt better after surgery, even after controlling for symptom changes. This effect persisted throughout the postoperative year. We conclude that positive expectations result in a more optimistic view of improvement after surgery rather than altering reports of outcomes or health.

Criterion validation of the Nottingham Health Profile: patient views of surgery for benign prostatic hypertrophy.

As part of a prospective cohort study of 388 men undergoing TURP for benign prostatic hypertrophy, the Nottingham Health Profile (NHP) was self-administered before and at 3, 6 and 12 months after surgery. By comparison of pre- and post-operative NHP scores with other patient-reported health measures the criterion validity of the Profile was examined. Before surgery, statistically significant linear trends were observed for increasing NHP score (i.e. having more health problems) with both worsening self-rated general health and increasing severity of prostatic symptoms. One year after surgery, the extent of reduction in NHP score was significantly linearly associated with a perceived favourable outcome of surgery and to a lesser extent with a reduction in prostatic symptoms. In addition, changes in NHP scores during follow-up were associated with perceived changes in operative outcome during the same period, patients with the greatest reduction in NHP score tending to report more successful surgery at 12 months than at the 3 month assessment.

Patient-perceived health status before and up to 12 months after transurethral resection of the prostate for benign prostatic hypertrophy.

As part of a prospective cohort study of 388 men undergoing transurethral resection of the prostate (TURP) for benign prostatic hypertrophy, the perceived physical, social and emotional health before and 3, 6 and 12 months after surgery was assessed using the Nottingham Health Profile. Before surgery, 88% of patients reported one or more specific health problems, most commonly concerning sleep (75%). The areas of daily life considered by the patients to be most affected by their health status were employment (by 33% of those currently in work), sex life (31%), social life (29%) and holidays (29%). Comparisons with other patient groups are described. Three months after surgery the proportion of patients reporting at least one health problem had fallen to 66%. Significant improvements occurred in all aspects of health, particularly sleeping problems. The improvements persisted for all aspects during the year following surgery with the exception of physical mobility, which deteriorated. These improvements were reflected in a significant reduction in perceived limitations in the patients' daily lives, with a tendency for the patients to perceive fewer limitations 1 year after surgery than at the 3-month assessment.

Assessing symptom improvement after elective prostatectomy for benign prostatic hypertrophy.

BACKGROUND: Elective surgery for benign prostatic hypertrophy requires estimates of likely improvement. METHODS: Data are from a prospective study of all patients without cancer who underwent transurethral prostatectomy. After eliminating patients for whom surgery was not elective, we examined symptom improvement. RESULTS: Surgery was effective in reducing symptoms for all but those with very mild preoperative symptoms. For the remainder, the average level of postoperative outcomes achieved was independent of the initial symptom severity. CONCLUSIONS: Elective prostatectomy is effectiveness for improving symptoms. The improvement is typically sustained, and for some symptoms improvement continues during the first year after surgery. Patients with severe symptoms were as likely to achieve the same level of postoperative improvement as were patients with less severe problems initially. However, patients with very mild symptoms benefited little or none from surgery.

Mortality, morbidity and complications following transurethral resection of the prostate for benign prostatic hypertrophy.

A total of 388 men undergoing transurethral resection of the prostate for benign prostatic hypertrophy during 1988 entered a prospective cohort study designed to examine the outcome of surgery during postoperative year 1. Self-administered questionnaires were completed preoperatively, and at 3, 6 and 12 months postoperatively. The surgeons completed 1 questionnaire shortly after surgery and another questionnaire 3, 6 or 12 months later. The mortality rate during the 12 months of followup was 2.8% (11 deaths). The surgeons reported perioperative complications in 14% of the patients and immediate postoperative complications, excluding urinary tract infections, in 17%. During the first 3 months postoperatively 38% of the patients reported incontinence and 25% had a urinary tract infection. Between 6 and 12 months postoperatively only 12% of the patients were troubled by either condition. The postoperative prevalence of impotence (24%) did not alter during followup and was similar to that reported preoperatively (22%). Of the patients 74% reported feeling better and 78% experienced a decrease in the overall level of symptoms postoperatively. The improvement in symptom levels was greatest in those with the most severe preoperative symptoms, and obstructive symptoms were alleviated slightly more than irritative symptoms.

Peaks and pits of using large data bases to measure quality of care.

This review of the advantages (peaks) and problems (pits) of large data bases to study quality contrasts their suitability with randomized control trials. Researchers need to advise policymakers and others about when statistically significant differences in quality are also politically and socially significant and deserve responsible reactions.