The compatibility of standardisation and innovation.
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Biomedical subjects
Publications and source records attributed to Richard Moore.
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BACKGROUND: While the question of whether the trials of breast cancer screening have resulted in a reduction in breast cancer death has been the subject of much scrutiny, there has been less attention to the reduction in tumor size achieved by screening. METHODS: Size data for invasive breast tumors were assembled from a variety of sources. The health consequences that can be expected from finding tumors of various sizes were determined using a recently developed mathematical method for relating tumor size to death rate. RESULTS: First, in both the Swedish two-country trial and at the MGH Breast Imaging Division, the sizes of the invasive breast cancers in the screening population (those masses seen at screening together with those found as palpable masses after screening examinations) were sufficiently smaller than the cancers found among women who had not used screening to have lead to considerable reductions in death. Second, the lack of reduction in death rates detected in both Canadian National Breast Screening Studies could be ascribed to the small reductions in tumor size achieved in these studies. Third, radiographic density had a small effect, whereas age had a negligible effect, on the capacity of mammographic screening to find breast carcinomas at smaller, and thus less lethal, sizes. CONCLUSIONS: Prompt attendance at annual mammographic screening offers the potential to reduce tumor size and, presumably, breast carcinoma death, in women of all ages and density groups.
OBJECTIVE: To model the effects of antiretroviral therapy (ART) and HIV vaccines on HIV transmission using empirical data from studies in Rakai, Uganda. DESIGN: A stochastic simulation model estimated HIV incidence, probabilities of transmission per coital act and the reproductive number (R0) with ART and HIV vaccines. Model inputs included Rakai data on HIV transmission probabilities per coital act by HIV viral load, age and gender, and sexual behaviors. The impacts of therapy were derived from US programs, and vaccine assumptions included preventive efficacies ranging from 25 to 75%. Component projection models estimated the numbers of HIV-infected persons over 20 years. RESULTS: The model incidence [1.57/100 person years (PY)] closely fitted empirical data (1.5/100 PY). Simulations of ART using DHHS treatment guidelines, predicted declines in HIV incidence, but R0 remained > 1.0, and the numbers of HIV-positive persons did not change substantially over 20 years. Preventive vaccines with > 50% efficacy and > 50% population coverage could reduce R0 to < 1.0, and substantially reduce the number of HIV-infected persons over 20 years. Concurrent ART and a preventive vaccine can have substantial impact at lower levels of population coverage and would markedly reduce the HIV infected population over 20 years. However, behavioral disinhibition with increased numbers of sexual partners in either ART or vaccine recipients, increased HIV incidence and diminished intervention impact. CONCLUSION: ART alone cannot control the HIV epidemic in mature epidemics such as Rakai, and persons in need of therapy will increase over time. ART in combination with a low efficacy vaccine could control the epidemic, if behavioral disinhibition is prevented.
BACKGROUND: There has been great debate regarding the importance of ductal carcinoma in situ (DCIS) in the breast. Autopsy results that demonstrate a much greater number of these lesions compared with the number of invasive carcinomas, and the numbers of deaths from breast carcinoma each year have been cited as evidence that DCIS rarely leads to invasion and death. These analyses have overlooked the fact that, to sustain a rate of detection each year, there would have to be a reservoir of undetected breast carcinomas growing in the population. The authors developed a simple model that makes this clear. In addition, complex phenomena have been suggested to explain why invasive breast disease may grow more rapidly among very young women and more slowly among the very old. A simple model provides some insight that may simplify the explanation of these observations. METHODS: The simple model of breast carcinoma growth assumes that there are three types of breast carcinoma that begin each year in a cohort of women. It assumes that all breast carcinomas begin as DCIS and take 9 years to go from a single cell to an invasive lesion for the slowest growing lesions, 6 years for intermediate growing DCIS lesions, and 3 years for fast-growing DCIS lesions. Furthermore, once an invasive clone forms, the model assumes that it will double in 60 days for fast-growing lesions, 120 days for intermediate growing lesions, and 180 days for slow-growing lesions. Three new tumors begin to grow in each successive year (one of each type). The model uses simple vectors that are defined by the size of the tumors and the time since tumor initiation, and it assumes that all tumors are detected when they reach 2 cm in greatest dimension. The model can be used to show graphically how many undetected tumors (DCIS as well as invasive carcinomas) there may be in the population to sustain the detection of three invasive tumors each year. RESULTS: Using the assumptions described above, the model showed that, by the time the first slow-growing breast carcinoma reaches 2 cm in greatest dimension, there will be 29 other slow-growing tumors that have not reached that size (9 DCIS and 20 smaller invasive carcinomas), 19 moderately growing tumors (6 DCIS and 13 smaller invasive carcinomas), and 9 fast-growing tumors (3 DCIS and 6 smaller invasive carcinomas). This means that, for every three breast tumors that reach 2 cm, the model predicted that there would be another 57 tumors (39 smaller invasive carcinomas and 18 DCIS) that would be undetected "below the surface". The model showed clearly that faster growing tumors would be expected to predominate among the youngest women, because they are the first to "reach the surface"; and, if the number of newly initiated tumors decreases with age, then there will be more of the slowest growing tumors that are left to reach the surface among the oldest women in the population. CONCLUSIONS: Even if the authors' assumptions are incorrect, their model made it clear that, to diagnose several breast carcinomas per 1000 women each year means that there have to be many more undetected carcinomas in the population to sustain the rate of detection. Although the model did not prove that DCIS may become potentially invasive and lethal, it did demonstrate that, even if all of these in situ lesions become invasive and lethal, many more DCIS lesions would have to be expected in the population than the number of invasive carcinomas detected each year and the number of deaths from breast carcinoma each year. Furthermore, the model provided a simple, purely mechanical illustration that may explain the preponderance of faster growing breast carcinomas among very young women and the preponderance of slower growing tumors among elderly women.
BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. RESULTS: The adjusted mean total hospital charges varied from 69 429 dollars to US237 898 dollars across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72). CONCLUSION: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level.
Considerable advances in understanding of the disease caused by Burkholderia mallei have been made employing a combination of tools including genetic techniques and animal infection models. The development of small animal models has allowed us to assess the role of a number of putative virulence determinants in the pathogenesis of disease due to B. mallei. Due to the difficulties in performing active immunization studies in small animals, and due to the fact that the horse is the target mammalian species for glanders, we have initiated experimental studies on glanders in horses. Intratracheal deposition of B. mallei produced clinical glanders with organisms being recovered from tissues of infected horses. The model should prove to be of considerable value in our ongoing studies on the pathogenesis and vaccine development for glanders.
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OBJECTIVE: To assess the resource utilization associated with sepsis syndrome in academic medical centers. DESIGN: Prospective cohort study. SETTING: Eight academic, tertiary-care centers. PATIENTS: Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges. RESULTS: The mean LOS for patients with sepsis was 27.7 +/- 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 +/- 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 +/- 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community-acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post-onset LOS and 12 correlates of total charges were identified. CONCLUSIONS: These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions.
BACKGROUND: Most patients admitted to the hospital from the emergency department (ED) with syncope do not have a myocardial infarction (MI), yet a common practice is to draw serial cardiac enzymes. METHODS: To assess the value of serial cardiac enzymes in elderly patients who present to the ED with syncope, a retrospective chart review was performed on consecutive patients aged 65 and older with syncope in an urban teaching hospital ED between July 1, 1998 and June 30, 1999. Charts were screened for presenting history, cardiac risk factors, testing, and outcomes including acute coronary syndromes, MI, death, and patients returning to the ED or admitted within 72 hours of discharge. RESULTS: 319 patients met the study criteria of syncope with confirmed loss of consciousness in the absence of seizure or stroke. 141 of 228 admitted patients (62%) had creatine phosphokinase (CPK) drawn and 5% of these had Troponin I (TnI). 3 of 141 patients, or 2.1% (95% CI [confidence interval]: 0.04%-6.09%), had positive cardiac enzymes during their hospitalization. CPK was positive in all 3, and TnI, drawn in 1 patient, was also positive. Two of these patients had chest discomfort and ST segment and T-wave abnormalities on electrocardiogram (ECG) in addition to a syncopal event. The third patient had dementia and could not recall the details surrounding her syncopal event. In addition, her baseline ECG demonstrated a left bundle branch block, limiting ECG interpretation. CONCLUSIONS: Cardiac enzymes may be of little additional value if drawn routinely on elderly patients with syncope who are admitted to the hospital from the ED, unless they have other signs or symptoms suggestive of myocardial ischemia.
OBJECTIVE: To examine the relationship of pulmonary artery catheter (PAC) use to patient outcomes, including mortality rate and resource utilization, in patients with severe sepsis in eight academic medical centers. DESIGN: Case-control, nested within a prospective cohort study. SETTING: Eight academic tertiary care centers. PATIENTS: Stratified random sample of 1,010 adult admissions with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were in-hospital mortality, total hospital charge, and length of stay (LOS) for patients with and without PAC use. The case-matched subset of patients included 141 pairs managed with and without the use of a PAC. The mortality rate was slightly but not statistically significantly lower among the PAC use group compared with those not using a PAC (41.1% vs. 46.8%, p =.34). Even this trend disappeared after we adjusted for the Charlson comorbidity score and sepsis-specific Acute Physiology and Chronic Health Evaluation (APACHE) III (adjusted odds ratio, 1.02; 95% confidence interval, 0.61-1.72). In linear regression models adjusted for the Charlson comorbidity score, sepsis-specific APACHE III, surgical status, receipt of a steroid before sepsis onset, presence of a Hickman catheter, and preonset LOS, no significant differences were found for total hospital charges (139,207 US dollars vs. 148,190, adjusted mean comparing PAC and non-PAC group, p =.57), postonset LOS (23.4 vs. 26.9 days, adjusted mean, p =.32), or total LOS in intensive care unit (18.2 vs. 18.8 days, adjusted mean, p =.82). CONCLUSIONS: Among patients with severe sepsis, PAC placement was not associated with a change in mortality rate or resource utilization, although small nonsignificant trends toward lower resource utilization were present in the PAC group.
This review presents an evidence-based analysis of the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in patients with chronic renal disease. It considers the characteristics and incidence of dyslipidaemia among specific patient types and describes the available data concerning the ability of statin therapy to regulate dyslipidaemia in the renal disease population as well as early results for an anti-inflammatory effect in this group. The clinical impact of statins in terms of reduced morbidity and mortality is also discussed. The relative merits of different statin agents are reviewed in terms of efficacy and safety, together with the role of aggressive intervention as compared with standard approaches to care. Finally, a proposed algorithm for the initiation and monitoring of statin therapy in chronic renal disease patients is presented.
Luer connectors and issues relating to their use are being closely scrutinised by several standards project groups.
The first of a series of articles on the important practicalities of standardisation. This month, some "dos and don'ts" when considering writing a standard.
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Exciting developments are taking place that present a complex challenge for regulations and standards.
A change in thinking and methodology is on the way as environment protection is applied of standards.