Modeling of under-detection of cases in disease surveillance.

PURPOSE: Accurate epidemiological surveillance of leprosy is a matter of international public health concern. It often suffers, however, from potential problems of under-registration of reported cases, particularly in poorer and more socially deprived areas. Such problems also apply in the surveillance of many other communicable or transmissible diseases. We develop a Bayesian model for small-area disease rates that allows for censoring of case detection in suspect districts and can therefore be used to estimate under-reporting of cases in a given study region. METHODS: Such methods are applied to leprosy incidence in a municipality of Pernambuco State in North Eastern Brazil, using a social deprivation indicator as the basis for considering data from certain districts to be censored. The time period we consider was immediately prior to an extension of the coverage and efficacy of the control program and model predictions concerning under reporting can therefore be compared with more reliable data subsequently collected from the same region. RESULTS: The proposed method produces informative estimates of under detection of leprosy cases in the defined study region and these estimates compare well, both in size and in geographical location, with the numbers of cases subsequently detected. CONCLUSIONS: As illustrated by the application discussed in this article, the proposed model provides a general tool that may be used in spatial epidemiological surveillance situations where the available data is suspected to contain significant under-registrations of cases in certain geographical areas.

Surface hydration and its effect on fluorinated SAM formation on SiO2 surfaces.

Substrate hydration is demonstrated to be crucial to film quality during self-assembled (SA) film deposition of tridecafluoro-1,1,2,2,-tetrahydrooctyltrichlorosilane (FOTS) from the vapor phase. The surface hydration was studied by thermogravimetric analysis, and a model was developed to predict the conditions necessary to desorb all of the water adsorbed on a fused silica surface without significantly altering the concentration of the surface hydroxyl groups. The nature of the SA film was investigated as a function of the degree of rehydration of the dehydrated silica surface. The wettability and microstructure of the SA films were examined by water contact angle, ellipsometry, X-ray photoelectron spectroscopy, and atomic force microscopy. There is an optimum degree of substrate hydration, on the order of 1-1.2 monolayers of adsorbed water, required to produce a dense, durable and uniform FOTS film with high water repellency and a smooth surface.

Impact of a Web-based clinical information system on cisapride drug interactions and patient safety.

BACKGROUND: Most commercially available drug-interaction screening systems have important limitations that fail to protect patients from dangerous drug combinations. We attempted to overcome the limitations of our commercial program by developing a Web-based clinical information system to serve as a safety net. This system identifies drug interactions with newly marketed medications not screened by our commercial program, and generates a second alert on dangerous interactions that were overridden during order processing. METHODS: The Web-based system uses patient-specific pharmacy, laboratory, and demographic data to generate detailed alerts on patients receiving potentially dangerous drug combinations. The system's impact on the use of dangerous drug combinations and related adverse events was evaluated by a retrospective analysis of patients receiving cisapride with contraindicated medications in the 2 years before and after implementation. RESULTS: The rate of dangerous drug combinations declined by 66% after implementing the system, from 9.0% of cisapride orders in 1994 and 1995 to 3.1% in 1996 and 1997 (P<.001). The mean [SD] duration of contraindicated therapy (4.1 [3.8] vs 1.6 [1.4] days, P<.001) and proportion of patients being discharged under treatment with a dangerous drug combination (36.2% vs 7.7%, P<.001) was also significantly reduced during the study period. Three patients (1.7%) during the control period experienced serious adverse events that may have been related to the targeted drug interactions. No symptomatic cardiac events were identified during the study period (P = .21). CONCLUSIONS: An automated system running as a safety net can be an efficient method of detecting contraindicated drug combinations and serves an important role in the avoidance of potentially serious adverse drug events.

A prospective, randomized trial to assess the cost impact of pharmacist-initiated interventions.

BACKGROUND: Hospital pharmacists make many recommendations that improve patients' quality of care and/or reduce drug costs. While the impact of quality-of-care interventions is difficult to quantify, those limited to cost savings could be assessed in a prospective, randomized fashion. OBJECTIVE: To assess the impact of pharmacist-initiated interventions on cost savings. METHODS: Six pharmacists at a large university hospital recorded patient-specific recommendations for 30 days. All quality-of-care interventions were completed by the pharmacists, but those strictly aimed at reducing costs were stratified by drug class and randomized to an intervention or control group. Pharmacists contacted physicians with cost-saving recommendations in the intervention group, while control group patients were simply observed. MAIN OUTCOME MEASURE: Drug costs after randomization. RESULTS: Most (n=967 [79%]) of the 1226 interventions recorded were aimed at improving quality of care. The remaining 259 (21%) provided equivalent quality of care, but at less expense. These cost-saving interventions typically involved streamlining therapy to less expensive agents (39%), discontinuing an unnecessary medication (25%), or modifying the route of administration (24%). The group randomized to receive a pharmacist's intervention had drug costs that were 41% lower than those in the control group (mean, $73.75 vs $43.40; P<.001). Interventions involving anti-infective agents had the greatest cost savings (mean, $104.08 vs $58.45; P<.001). For our institution, this extrapolates to an annual savings of approximately $394,000 (95% confidence interval, $46,000-$742,000). As expected, these interventions had no impact on length of hospital stay, in-hospital mortality, 30-day readmissions, or the need to readminister the targeted medication or restart intravenous therapy. CONCLUSIONS: While interventions solely aimed at reducing costs represent a small portion of a pharmacist's activities, they can result in significant savings for an institution.

Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.

PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

Investigation of a computer virus outbreak in the pharmacy of a tertiary care teaching hospital.

OBJECTIVE: A computer virus outbreak was recognized, verified, defined, investigated, and controlled using an infection control approach. The pathogenesis and epidemiology of computer virus infection are reviewed. DESIGN: Case-control study. SETTING: Pharmacy of a tertiary care teaching institution. RESULTS: On October 28, 1991, 2 personal computers in the drug information center manifested symptoms consistent with the "Jerusalem" virus infection. The same day, a departmental personal computer began playing "Yankee Doodle," a sign of "Doodle" virus infection. An investigation of all departmental personal computers identified the "Stoned" virus in an additional personal computer. Controls were functioning virus-free personal computers within the department. Cases were associated with users who brought diskettes from outside the department (5/5 cases versus 5/13 controls, p = .04) and with College of Pharmacy student users (3/5 cases versus 0/13 controls, p = .012). The detection of a virus-infected diskette or personal computer was associated with the number of 5 1/4-inch diskettes in the files of personal computers, a surrogate for rate of media exchange (mean = 17.4 versus 152.5, p = .018, Wilcoxon rank sum test). After education of departmental personal computer users regarding appropriate computer hygiene and installation of virus protection software, no further spread of personal computer viruses occurred, although 2 additional Stoned-infected and 1 Jerusalem-infected diskettes were detected. CONCLUSIONS: We recommend that virus detection software be installed on personal computers where the interchange of diskettes among computers is necessary, that write-protect tabs be placed on all program master diskettes and data diskettes where data are being read and not written, that in the event of a computer virus outbreak, all available diskettes be quarantined and scanned by virus detection software, and to facilitate quarantine and scanning in an outbreak, that diskettes be stored in organized files.

Screening of physicians for tuberculosis.

OBJECTIVE: To determine the prevalence of tuberculous infection among a sample of physicians at Barnes Hospital and to determine the frequency of tuberculin skin testing and the adequacy of follow-up for physicians with positive tuberculin skin tests. DESIGN: Convenience sample. SETTING: 1,000-bed, university-affiliated tertiary care hospital. SUBJECTS: Physicians attending departmental conferences were screened for tuberculosis. Prior history of tuberculosis, antituberculous therapy, BCG vaccination, and previous tuberculin skin test results were obtained with a standardized questionnaire. Tuberculin skin tests were performed on those who were previously skin-test negative. OUTCOME MEASURE: Tuberculosis infection, prophylactic therapy. RESULTS: Eighty-six (24.5%) of 351 physicians in the study were skin test positive by history or currently performed skin test. Of 61 who reported a previously reactive skin test, 40 (66%) had been eligible for isoniazid prophylaxis, but only 15 (37.5%) of 40 had completed at least six months of therapy. Of 290 physicians reporting a previously negative skin test, 25 conversions (8.6%) were identified. Previously undiagnosed, asymptomatic pulmonary tuberculosis was identified in one physician. CONCLUSIONS: Infection with Mycobacterium tuberculosis is common among physicians. Physicians were screened irregularly for tuberculosis, and the use of prophylactic therapy was inconsistent. Aggressive tuberculosis screening programs for healthcare workers should be instituted (Infect Control Hosp Epidemiol 1994;15:95-100).

Impact of cytomegalovirus serology on graft survival in living related kidney transplantation: implications for donor selection.

BACKGROUND: The impact of cytomegalovirus in living related kidney transplantation remains controversial. This study considers the implications of donor and recipient cytomegalovirus (CMV) serology for the selection of living related donor. METHODS: Graft survival was estimated by using the bivariate Kaplan-Meier method and multivariate Cox proportional hazards analysis for 7659 living related first transplantations performed in the United States between 1989 and 1994. The effects of donor CMV serology were estimated with respect to recipient CMV serology and compared with human leukocyte antigen (HLA) matching, transplantation, donor, and recipient characteristics. The implications of these estimates for the selection of living related donors were considered. RESULTS: From Kaplan-Meier estimates, donor CMV-seropositive kidneys were associated with significantly reduced graft survival for CMV-seronegative recipients (p = 0.0002) but not CMV-seropositive recipients (p = 0.1623). These findings were verified by use of Cox proportional hazards analysis accounting for covariate factors. The impact of donor CMV-seropositive kidneys on CMV-seronegative recipients was similar to one HLA-DR match, greater than one HLA-B match, and significantly greater than one HLA-A match (p = 0.0331). CONCLUSIONS: Results identify donor CMV serology as an important determinant of transplantation outcome for living related first kidney transplant recipients who are themselves CMV seronegative. Consideration should be given to donor and recipient CMV serology when selecting an appropriate donor for living related kidney transplantation.

Statistical process control methods for expert system performance monitoring.

The literature on the performance evaluation of medical expert system is extensive, yet most of the techniques used in the early stages of system development are inappropriate for deployed expert systems. Because extensive clinical and informatics expertise and resources are required to perform evaluations, efficient yet effective methods of monitoring performance during the long-term maintenance phase of the expert system life cycle must be devised. Statistical process control techniques provide a well-established methodology that can be used to define policies and procedures for continuous, concurrent performance evaluation. Although the field of statistical process control has been developed for monitoring industrial processes, its tools, techniques, and theory are easily transferred to the evaluation of expert systems. Statistical process tools provide convenient visual methods and heuristic guidelines for detecting meaningful changes in expert system performance. The underlying statistical theory provides estimates of the detection capabilities of alternative evaluation strategies. This paper describes a set of statistical process control tools that can be used to monitor the performance of a number of deployed medical expert systems. It describes how p-charts are used in practice to monitor the GermWatcher expert system. The case volume and error rate of GermWatcher are then used to demonstrate how different inspection strategies would perform.

Analysis of various creatinine clearance formulas in predicting gentamicin elimination in patients with low serum creatinine.

Predicted gentamicin elimination rate constants (kelS) using creatinine clearance (Clcr) estimates from seven equations were compared with kelS calculated from steady-state serum gentamicin concentrations in 186 hospitalized patients. In predicting kel, the equations varied significantly in precision (mean absolute percentage error), and were particularly imprecise among patients with serum creatinine values of 71 mumol/L or less. Significant differences in bias (mean prediction error) were also observed. All equations using serum creatinine as an element showed improved precision, and most showed reduced bias when a minimum value of 71 mumol/L was used. The Cockcroft-Gault normalized to 72 kg and the Hull equations are among the simplest to calculate and, when using a minimum serum creatinine of 71 mumol/L, had significantly greater precision and less bias than several of the equations. We recommend one of these two methods for predicting gentamicin kel in patients with low serum creatinine values.

A randomized, prospective evaluation of an interventional program to discontinue intravenous antibiotics at two tertiary care teaching institutions.

To evaluate a program to discontinue intravenous antibiotics at two teaching hospitals, 102 inpatients meeting eligibility criteria were randomly assigned to two groups. In one group, patients' physicians were contacted by pharmacists with recommendations to discontinue intravenous antibiotic therapy; in the other, patients were simply observed. Measured outcomes were antibiotic costs, length of stay, need to restart intravenous antibiotics, in-hospital mortality, and 30-day readmissions. The intervention significantly reduced mean antibiotic costs per patient ($19.82 vs $35.84, p = 0.03), but related labor costs exceeded this benefit. Readmissions were significantly more frequent in the intervention group than in the control group (29% vs 9.8% p = 0.02), but they were not infection related. No impact was demonstrated on the other measured outcomes. Institutions considering such programs or with one in place should conduct similar evaluations.

Interactive spatial data analysis in medical geography.

Interactive spatial data analysis involves the use of software environments that permit the visualization, exploration and, perhaps, modelling of geographically-referenced data. Such systems are of obvious value in epidemiological research, both of an environmental and geographical nature. There is an increasing number of such software environments available on a variety of platforms and operating systems. This paper considers the use of the proprietary Geographical Information System, ARC/INFO, in a spatial analysis context, showing how the spatial analytic tools that may be added to it can be exploited by geographical epidemiologists; such tools include those for modelling possible raised incidence of disease around suspected sources of pollution. The paper also reviews the use of systems such as S-Plus and XLISP-STAT, statistical programming environments to which spatial analysis functions or libraries may be added. The use of INFO-MAP, a system designed to aid in the teaching of interactive spatial data analysis, is also highlighted. The various software environments are illustrated with reference to examples concerned with: clustering of childhood leukaemia in part of Lancashire, England; Burkitt's lymphoma in Uganda; larynx cancer in Lancashire; and childhood mortality in Auckland, New Zealand.

Automated system for identifying potential dosage problems at a large university hospital.

A hospital's experience with an automated system for screening drug orders for potential dosage problems is described. DoseChecker was developed by the hospital pharmacy department in collaboration with a local university. Pharmacy, laboratory, and patient demographic data are transferred nightly from the hospital's mainframe system to a database server; DoseChecker uses these data and user-defined rules to (1) identify patients receiving any of 35 targeted medications, (2) evaluate the appropriateness of current dosages, and (3) generate alerts for patients potentially needing dosage adjustments. The alert reports are distributed to satellite pharmacists, who evaluate each patient's condition and make recommendations to physicians as needed. One of the system's primary purposes is to calculate creatinine clearance and verify that dosages are properly adjusted for renal function. Between May and October 1995, the system electronically screened 28,528 drug orders and detected potential dosage problems in 2859 (10%). The system recommended a lower daily dose in 1992 cases (70%) and a higher daily dose in 867 (30%). Pharmacists contacted physicians concerning 1163 (41%) of the 2859 alerts; in 868 cases (75%), the physicians agreed to adjust the dosage. The most common dosage problem identified was failure to adjust dosages on the basis of declining renal function. An automated system provided an efficient method of identifying inappropriate dosages at a large university hospital.

Spatial statistical methods in health.

The study of the geographical distribution of disease incidence and its relationship to potential risk factors (referred to here as "geographical epidemiology") has provided, and continues to provide, rich ground for the application and development of statistical methods and models. In recent years increasingly powerful and versatile statistical tools have been developed in this application area. This paper discusses the general classes of problem in geographical epidemiology and reviews the key statistical methods now being employed in each of the application areas identified. The paper does not attempt to exhaustively cover all possible methods and models, but extensive references are provided to further details and to additional approaches. The overall aim is to provide a picture of the "current state of the art" in the use of spatial statistical methods in epidemiological and public health research. Following the review of methods, the main software environments which are available to implement such methods are discussed. The paper concludes with some brief general reflections on the epidemiological and public health implications of the use of spatial statistical methods in health and on associated benefits and problems.

Viral infection and HIV disease.

HIV-positive patients are at risk for a number of serious viral infections. The author presents on overview of some common viral infections these patients are susceptible to and stresses the importance of early diagnosis for appropriate treatment.

Specialty costs in English hospitals--a statistical approach based upon a cost component model.

A previous paper in this Journal compared various regression models designed to relate hospital recurrent expenditure to corresponding measures of hospital activity and services provided. The paper concluded by discussing briefly an alternative approach designed to avoid some of the criticisms raised and to reconcile the differing viewpoints inherent in the existing models. The objective of the present paper is to describe this alternative approach in more detail. The model introduced is concerned with the separate modelling of a number of broad components of hospital inpatient expenditure, rather than with the total expenditure in isolation. A system of simultaneous regression models is proposed, each related to a particular area of expenditure, the structure of each being determined by means of empirical analyses based upon data from some 1505 English hospitals. It is shown that when the total costs generated by aggregating the cost components are considered, the models provide a better representation of the cost structure of English hospitals than the models based upon total costs published in the recent literature. Various applications of the models in the management and planning of hospital services involving the use of micro- or other computers are discussed.

Evaluation and financial impact of imipenem/cilastatin dosing in elderly patients based on renal function and body weight.

OBJECTIVE: To evaluate the financial impact of adjusting imipenem/cilastatin (IC) dosages in elderly patients based on estimated creatinine clearance (Cl cr) and body weight. DESIGN: Retrospective cost-savings analysis. SETTING: A 500-bed, university-affiliated, tertiary-care hospital. MAIN OUTCOME MEASURES: All courses of IC administered to patients over age 60 during a four-month period were retrospectively assessed for appropriateness based on both dosing interval and dosage. Manufacturer's guidelines for adjusting the IC dosage based on estimated CL cr and body weight were used to define appropriate dosing. The cost savings that could have been realized by appropriately adjusting IC dosage was calculated for the study period and extrapolated to project an annual cost savings. RESULTS: Only 37 percent of patient days of therapy and 32 percent of therapy courses were judged as appropriate based on both dose amount and interval. The projected annual cost savings that could have been realized by appropriately adjusting IC dosage based on estimated Cl cr and body weight was $11,500. CONCLUSIONS: Adjustment of IC dosages in elderly patients based on estimated Cl cr and body weight can result in significant cost savings.

Mycobacterium tuberculosis associated chylous ascites in HIV-infected patients: case report and review of the literature.

Chylous ascites (CA) is a rare manifestation of tuberculosis. We report a case of CA due to tuberculosis in an HIV-infected patient and review the literature on CA in HIV disease. This patient was successfully treated with large volume abdominal paracentesis, antituberculous drugs, and parenteral medium chain triglycerides.