Complete diagnostic evaluation in colorectal cancer screening: research design and baseline findings.

BACKGROUND: While indicated by guidelines, complete diagnostic evaluation, or CDE (i.e., colonoscopy or combined flexible sigmoidoscopy plus barium enema X ray), is often not recommended and performed for persons with an abnormal screening fecal occult blood test (FOBT) result. We initiated a randomized trial to assess the impact of a physician-oriented intervention on CDE rates in primary care practices. METHODS: In 1998, we identified 1,184 primary care physicians (PCPs) in 584 practices whose patients received FOBTs that are mailed annually by a managed care organization screening program. A total of 470 PCPs in 318 practices completed a baseline survey. Practices were randomly assigned either to a Control Group (N = 198) or to an Intervention Group (N = 120). Control Group practices received the screening program. Intervention Group practices received the screening program and the intervention (i.e., CDE reminder-feedback plus educational outreach). Practice CDE recommendation and performance rates are the primary outcomes to be measured in the study. RESULTS: Baseline CDE recommendation and performance rates were low and were comparable in Control and Intervention Group practices (54 to 57% and 39 to 40%, respectively). PCPs in the practices tended to view FOBT screening and CDE favorably, but had concerns about screening efficacy, time involved in CDE, and patient discomfort and adherence. Control Group physicians were more likely than Intervention Group physicians to believe that a mail-out FOBT screening program helps in the practice of medicine. CONCLUSIONS: We were able to enroll a high proportion of targeted primary care practices, measure practice characteristics and CDE rates at baseline, and develop and implement the intervention. Study outcome analyses will take into account baseline differences in practice characteristics.

Measuring complete diagnostic evaluation in colorectal cancer screening.

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.

Physician intention to recommend complete diagnostic evaluation in colorectal cancer screening.

Primary care physicians (PCPs) often do not recommend complete diagnostic evaluation (CDE; i.e., diagnostic colonoscopy or the combination of flexible sigmoidoscopy and barium enema X-ray procedures) for patients with an abnormal screening fecal occult blood test (FOBT+) result. Information is needed to understand why PCPs do not recommend CDE. In the spring of 1994, a telephone survey was carried out using a random sample of 520 PCPs in Pennsylvania or New Jersey who had patients that were targeted for an FOBT screening program. Survey data were obtained from 363 (70%) PCPs on physician practice characteristics; personal background; perceptions concerning FOBT screening, CDE performance, and patient behavior; social influence related to CDE; and intention to recommend CDE for FOBT+ patients. Physician CDE intention scores were distributed as follows: low (22%), moderate (51%), and high (27%). Multivariate analyses demonstrate that physician board certification status, time in practice, belief in CDE efficacy, and belief that CDE is standard practice were positively associated with CDE intention, whereas concern about CDE-related costs was negatively associated with CDE intention. Among physicians in larger practices, perceived FOBT screening efficacy was negatively associated with CDE intention, and belief in the benefit of CDE was positively associated with outcome. There is substantial variability in CDE intention among PCPs. Physician perceptions about FOBT screening and follow-up are associated with CDE intention, are likely to influence CDE performance, and may be amenable to educational intervention. Additional research is needed to evaluate the impact of educational interventions on CDE intention and performance.

Early metabolic alterations in edematous perihematomal brain regions following experimental intracerebral hemorrhage.

OBJECT: The authors previously demonstrated, in a large-animal intracerebral hemorrhage (ICH) model, that markedly edematous ("translucent") white matter regions (> 10% increases in water contents) containing high levels of clot-derived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the concentrations of high-energy phosphate, carbohydrate substrate, and lactate in these and other perihematomal white and gray matter regions during the early hours following experimental ICH. METHODS: The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a physiologically controlled model in pigs (weighing approximately 7 kg each) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water contents were then measured in white and gray matter located ipsi- and contralateral to the hematomas, and metabolite concentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentrations increased two- to fivefold compared with control during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5 hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 micromol/g) at all times. In gyral gray matter overlying the hematoma, water contents and glycogen levels were significantly increased at 5 and 8 hours, whereas lactate levels were increased two- to fourfold at all times. CONCLUSIONS: These results, which demonstrate normal to increased high-energy phosphate and carbohydrate substrate concentrations in edematous perihematomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present, lactate accumulation in edematous white matter is not caused by stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the blood entering the brain's extracellular space during ICH are several-fold higher than normal levels, the authors speculate, on the basis of work reported by Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced aerobic glycolysis and lactate is generated at a rate that exceeds utilization.

Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter.

BACKGROUND AND PURPOSE: The mechanisms underlying brain injury from intracerebral hemorrhage (ICH) are complex and poorly understood. To comprehensively examine pathophysiological and pathochemical alterations after ICH and to examine the effects of hematoma removal on these processes, we developed a physiologically controlled, reproducible, large-animal model of ICH in pigs (weight, 6 to 8 kg). METHODS: We produced lobar hematomas by pressure- controlled infusions of 1.7 mL of autologous blood into the right frontal hemispheric white matter over 15 minutes. We froze brains in situ at 1, 3, 5, and 8 hours after hematoma induction and cut coronal sections of hematoma assessment, morphological brain examination, and immunohistochemical and water content determinations. RESULTS: At 1 hour after blood infusion, "translucent" white matter areas were present directly adjacent to the hematoma. These markedly edematous regions had a greater than 10% increase in water content (>85%) compared with the contralateral white matter (73%), and this increased water content persisted through 8 hours. In addition, these areas were strongly immunoreactive for serum proteins. Intravascular Evans blue dye failed to penetrate into the brain tissue at all time points, demonstrating that this serum protein accumulation and edema development were not due to increased blood-brain barrier permeability. CONCLUSIONS: Experimental lobar ICH in pigs models a prominent pathological feature of human ICH, ie, early perihematomal edema. Our findings suggest that serum proteins, originating from the hematoma, accumulate in adjacent white matter and result in rapid and prolonged edema after ICH. This interstitial edema likely corresponds to the low densities on CT scans and the hyperintensities on T2-weighted MR images that surround intracerebral hematomas acutely after human ICH.

Screening for colorectal neoplasia: physicians' adherence to complete diagnostic evaluation.

This prospective study was done in a health maintenance organization colorectal cancer screening program to determine whether 166 persons found to have abnormal fecal occult blood test results typically underwent complete diagnostic evaluation (i.e., either colonoscopy or barium enema x-ray plus flexible sigmoidoscopy). Chart audit data show that 137 (82%) subjects contacted a physician to discuss follow-up. A complete diagnostic evaluation was recommended to only 52 (38%) patients who talked with a physician. Forty-two (81%) patients who were advised to get a complete diagnostic evaluation actually complied. Significant differences in clinical findings were observed for patients who did and did not have a complete diagnostic evaluation.

Fetal brain injury after maternal carbon monoxide intoxication. Clinical and neuropathologic aspects.

In a model of brain damage in the rhesus monkey fetus, carbon monoxide inhalation by the mother was used to produce graded fetal hypoxia. Four fetuses with aterial oxygen contents of 2.1 to 2.4 ml per 100 ml during the most severe insult hour appeared neurologically normal, and their brains contained no lesions. A single animal with an intermediate degree of hypoxia was moderately abnormal; its brain showed extensive necrosis of the basal ganglia. Four fetuses with arterial oxygen contents of 1.6 to 1.8 ml per 100 ml during the most severe insult hour showed profound clinical deficits, and on postmortem examination the brains were markedly swollen and showed an extensive hemorrhagic necrosis. The fetal brain exhibits a high threshold to the effects of sustained hypoxia, but once a critical level of deoxygenation is exceeded, extensive brain damage with early death results.

Fetal asphyxia due to umbilical cord compression. Metabolic and brain pathologic consequences.

Term monkey fetus 1620 sustained 50 min of rapidly developing severe asphyxia which began immediately after its in utero version. The arterial blood pO2 decreased from a normal value of 34 to 11-12 mm Hg while the blood pH fell from 7.35 to 6.70. During this asphyxia, hemoglobin-oxygen saturations below 5% were recorded. The complete collapse of the umbilical circulation several minutes prior to the reoxygenation of the fetus added an episode of total asphyxia. With reoxygenation following delivery, fetal cardiovascular performance improved rapidly though over an hour was required for recovery from the severe acidosis. The animal prospered but was found moribund on the 13th postnatal day due to dehydration. Brain examination after euthanasia revealed severe paracentral cortical and basal ganglia damage. Damage also appeared symmetrically in nuclei in the lower brain stem and in thalamus. These three zones of injury are attributed to the partial, the partial combined with the total, and the total asphyxia, respectively. The present case makes clear that compression of the umbilical cord may cause damage of a variety of types depending on the severity and duration of the asphyxia induced. It also demonstrates the possibility of recovery from a systemic acidosis where the pH values have fallen to levels below 6.70 for up to an hour.