Redesigning Primary Care Processes to Improve the Offering of Mammography: The Use of Clinic Protocols by Nonphysicians

OBJECTIVE: To develop, within the framework of continuous quality improvement, new processes for offering mammography and determine whether protocols executed completely by nonphysicians would increase mammography utilization. DESIGN: A prospective follow-up study with patients from an intervention clinic and two control clinics. SETTING: Three general internal medicine clinics in a large, urban teaching hospital in Detroit, Michigan. PATIENTS/PARTICIPANTS: A total of 5,934 women, aged 40 through 75 years, making 16,546 visits to one of the clinics during the study period (September 1, 1992, through November 31, 1993). INTERVENTION: Medical assistants and licensed practical nurses in the intervention clinic were trained to identify women due for screening mammography, and to directly offer and order a mammogram if patients agreed. MEASUREMENTS AND MAIN RESULTS: Patients were considered up-to-date with screening if they had a mammogram within 1 year (if age 50-75) or 2 years (if age 40-49) prior to the visit or a mammogram within 60 days after the visit. The proportion of visits each month in which a woman was up-to-date with mammography was calculated using computerized billing records. Prior to the intervention, the proportion of visits in which women were up-to-date was 68% (95% confidence interval [CI] 63%, 73%) in the intervention clinic and 66% (95% CI 61%, 71%) in each of the control clinics. At the end of the evaluation, there was an absolute increase of 9% (95% CI 2%, 16%) in the intervention clinic, and a difference of 1% (95% CI -5%, 7%) in one of the control clinics and -2% (95% CI -3%, 5%) in the other. In the intervention clinic, the proportion of visits in which women were up-to-date with mammography increased over time and was consistent with a linear trend (p = .004). CONCLUSIONS: Redesigning clinic processes to make offering of mammography by medical assistants and licensed practical nurses a routine part of the clinic encounter can lead to mammography rates that are superior to those seen in physicians' usual practice, even when screening levels are already fairly high. Physicians need not be considered the sole, or even the primary, member of the health care team who can effectively deliver some preventive health measures.     

An anti-C3b(i) mAb enhances complement activation,C3b(i) deposition,and killing of CD20+ cells by rituximab

We investigated deposition of the complement protein fragment C3b and its breakdown products (collectively designated as C3b(i)) on CD20-positive cells treated with rituximab (RTX) in the presence of normal human serum (NHS). Radioimmunoassay (RIA) demonstrates that about 500 000 C3b(i) molecules deposit per cell, and fluorescence microscopy reveals that C3b(i) colocalizes with bound RTX. Use of mAb 3E7, specific for C3b(i) bound to substrates, enhances C3b(i) deposition; > 1 million C3b(i) deposit when cells are incubated with NHS, RTX and mAb 3E7. Treatment of Raji cells in NHS plus RTX leads to robust cell killing (95%) after 24 to 48 hours, and mAb 3E7 significantly enhances RTX-mediated killing of Raji and DB cells. A cynomolgus monkey model based on intravenous infusion of RTX followed by mAb 3E7 demonstrated that RTX rapidly binds to B cells and promotes complement activation and C3b(i) deposition; fluorescence microscopy analyses revealed the same pattern of colocalization of C3b(i) on cell-bound RTX in vivo as observed in vitro. Preliminary in vitro studies with blood samples from patients with chronic lymphocytic leukemia lead to similar findings. These experiments suggest that complement plays a key role in the mechanism of action of RTX; moreover, the in vivo molecular form of RTX (and possibly other antitumor mAbs) in the circulation or in tissues may include C3b(i) molecules covalently bound to the therapeutic mAb, thus allowing it to interact with cells containing both Fc and complement receptors.     

Sulfated and nonsulfated glycosaminoglycans and glycopeptides are synthesized by kidney in vivo and incorporated into glomerular basement membranes

The biosynthesis of glycosaminoglycans (GAG) and glycopeptides was studied in rat kidney cortex, glomeruli, and isolated glomerular basement membranes (GBM). Rats were given four intraperitoneal injections of [³⁵S]sulfate and [³H]glucosamine (over 10 hr) and sacrificed 14 hr after the last injection. Fractions of kidney glomeruli and purified GBM were prepared. The percent of the label incorporated into specific GAG or into glycopeptides was determined by selective degradative techniques in conjunction with gel filtration chromatography using the methods of Hart [Hart, G. W. (1976) J. Biol. Chem. 251, 6513-6521; Hart, G. W. (1978) Dev. Biol. 62, 78-98]. After digestion with Pronase and chromatography on Sephadex G-50, ≈68% of the total ³⁵S radioactivity and 10-15% of the total ³H radioactivity incorporated into cortex, glomeruli, or GBM was found in the GAG fraction, and the remainder (≈32% of ³⁵S radioactivity and 85-90% of the ³H radioactivity) was found in glycopeptide fractions. Treatment of GAG fractions isolated from the three sources (cortex, glomeruli, and GBM) with nitrous acid (which degrades heparan sulfates) indicated that the majority (85%, 65%, and 87%) of the ³⁵S radioactivity as well as the majority (60%, 50%, and 91%) of the ³H radioactivity from all three sources was degraded by this treatment. When nitrous acid-resistant GAG from GBM were subjected to digestion with Streptomyces hyaluronidase (which degrades hyaluronic acid), ≈6% of the ³H-labeled material was sensitive to this treatment. The remaining ³⁵S- and ³H-labeled GAG isolated from GBM were digested with chondroitinase ABC (which degrades chondroitin sulfates A and C and dermatan sulfate). Although the ratios of the types of GAG synthesized by all three sources were similar, in GBM the ratios of ³⁵S- to ³H-labeled GAG and of ³H-labeled glycopeptides to ³H-labeled GAG were higher (2.5 times) than those found for glomeruli. The data demonstrate the synthesis of both sulfated and nonsulfated GAG by rat kidney cortex and glomeruli and their transport to and incorporation into the GBM. Heparan sulfate is the major GAG synthesized by glomeruli, but the glomeruli also synthesize smaller amounts of hyaluronic acid and chondroitin sulfates, which are in part incorporated into GBM. In addition, the renal cortex and the glomeruli synthesize glycopeptides, some of which are sulfated, and incorporate them into GBM.     

Preventable Major Cardiovascular Events Associated With Uncontrolled Glucose,Blood Pressure,and Lipids and Active Smoking in Adults With Diabetes With and Without Cardiovascular Disease: A Contemporary Analysis

OBJECTIVEThe objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking.RESULTSMean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD.CONCLUSIONSAdditional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.