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.

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.

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.

Sepsis and hyperoxia effects on the pulmonary surfactant system in wild-type and iNOS knockout mice.

Alterations of pulmonary surfactant and increases in inducible nitric oxide synthase (iNOS) have been implicated in the pathophysiology of acute lung injury. It was hypothesised that these two observations are related and that alterations of the endogenous surfactant, due to either sepsis or hyperoxia, would be reduced in mice lacking the iNOS gene compared to wild-type mice. Wild-type and iNOS (-/-) mice were randomised into sham or sepsis, and in a separate experiment animals were randomised to normoxia or hyperoxia exposure for 48 h. Lungs were lavaged and analysed for total surfactant levels and surfactant subfractions (large (LA) and small (SA) aggregates). Both sepsis groups had decreased SA compared to sham groups with no significant difference between the two genotypes. Mice exposed to hyperoxia had a decreased amount of total surfactant when compared to normoxia controls and there was no significant difference between the two genotypes. It is concluded that inducible nitric oxide synthase does not influence the amount of pulmonary surfactant or surfactant subfractions recovered in lavage after 18 h of sepsis or 48 h of hyperoxia.

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.

Using information systems technology to improve antibiotic prescribing.

The selection of antimicrobial agents in the hospital setting is still a largely manual task and, therefore, fraught with the potential for error. This includes the choice of agents, dosage regimens, and monitoring for response and toxicity. The authors describe current and future strategies to use information technology to improve the process of antimicrobial selection and to avoid dosing errors and contraindicated drug combinations. The possible role of decision support in preventing the emergence of resistance is also discussed.

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.

Notification of real-time clinical alerts generated by pharmacy expert systems.

We developed and implemented a strategy for notifying clinical pharmacists of alerts generated in real-time by two pharmacy expert systems: one for drug dosing and the other for adverse drug event prevention. Display pagers were selected as the preferred notification method and a concise, yet readable, format for displaying alert data was developed. This combination of real-time alert generation and notification via display pagers was shown to be efficient and effective in a 30-day trial.

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.

Cytomegalovirus and HLA-A, B, and DR locus interactions: impact on renal transplant graft survival.

Graft failure rates for renal transplantations performed between 1989 and 1994 and recorded in the US Renal Data System database were retrospectively evaluated for interactions between cytomegalovirus and HLA-A, B, and DR loci. Twelve significant interactions were observed. There were significantly greater risks of graft failure for the total effect of cytomegalovirus and donor or matched HLA-DR9, recipient or matched HLA-B-51, and matched HLA-B13. We conclude that further study of renal transplants with these combinations of cytomegalovirus and HLA loci is needed to determine whether the observed interactions should be taken into consideration when matching donors with recipients.

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.

A meta-analysis of extended-interval dosing versus multiple daily dosing of aminoglycosides.

We conducted a meta-analysis of 22 randomized, controlled trials in which extended-interval dosing of aminoglycosides was compared with multiple daily dosing. When we classified intermediate outcomes as successes, we found that patients receiving extended-interval dosing were at significantly reduced risk of clinical treatment failure (risk difference, -3.4%; 95% confidence interval [CI], -6.7% to -0.2%; P = .039) and that there was a trend toward reduced risk of bacteriologic failure (risk difference, -1.7%; 95% CI, -5.4% to +2.1%; P = .38). Reclassification of intermediate outcomes as failures yielded similar results. There was significant heterogeneity among the trials, necessitating cautious interpretation of these outcomes. There were negligible differences in the risk of nephrotoxicity (risk difference, -0.6%; 95% CI, -2.4% to +1.1%; P = .46) and ototoxicity (risk difference, +0.3%; 95% CI, -1.2% to +1.8%; P = .71). We conclude that for many indications, extended-interval dosing of aminoglycosides appears to be as effective as conventional dosing, with similar rates of toxicity. The added convenience of extended-interval dosing makes it an attractive alternative to conventional dosing.

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.

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.

The effects of cytomegalovirus serology on graft and recipient survival in cadaveric renal transplantation: implications for organ allocation.

The potential benefits from allocating donated cadaveric kidneys based on donor and recipient cytomegalovirus (CMV) serology remain controversial. We estimated graft survival and recipient survival using bivariate Kaplan-Meier models and multivariate Cox proportional hazards models for 24,543 first cadaveric renal transplantations performed in the United States between 1989, coinciding with the introduction of ganciclovir, and 1994. The effects of donor and recipient CMV serology were estimated, and the implications of these estimates for CMV-based allocation of cadaveric kidneys were considered. From Kaplan-Meier estimates, the 3-year impact of CMV-seropositive donor kidneys was a 3.6% reduction in graft survival and a 2.4% reduction in recipient survival for CMV-seronegative recipients, and a 3.9% reduction in graft survival and a 3.0% reduction in recipient survival for CMV-seropositive recipients. Multivariate Cox analysis demonstrated an adverse impact of donor CMV seropositivity regardless of recipient CMV status. D-/R- CMV serologic pairs had the best 3-year outcomes, with 73.4% graft survival and 87.7% recipient survival. D+/R+ CMV serologic pairs were found to have the worst 3-year outcomes, with 68.4% graft survival and 83.1% recipient survival, and were significantly worse than D+/R- pairs in terms of recipient survival. The maximum estimated impact of a program allocating donor kidneys to maximize the number of D-/R- CMV serologic pairs, assuming no impact on HLA mismatches, was a 0.1% reduction in aggregate 3-year graft survival and a 0.2% reduction in aggregate recipient survival. An alternative program allocating donor kidneys to minimize the number of D+/R+ pairs had no estimated effect on either graft or recipient survival. We conclude that during the ganciclovir era, CMV continues to have an important impact on first cadaveric renal transplantation. However, even under ideal conditions, CMV-based kidney allocation to either maximize the number of D-/R- pairs or minimize the number of D+/R+ pairs is likely to provide little benefit to the population of cadaveric renal transplant recipients.

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.

Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). AIDS Clinical Trials Group.

SUMMARY: Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

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.

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.