Atmospheric dispersion and transmission of Legionella from wastewater treatment plants: A 6-year case-control study.

Legionnaires Disease incidence has risen in the Netherlands in recent years. For the majority of the cases, the source of infection is never identified. Two Dutch wastewater treatment plants (WWTPs) have previously been identified as source of outbreaks of Legionnaires Disease (LD) among local residents. The objective of this study is to examine if LD patients in the Netherlands are more exposed to aerosols originating from WWTPs than controls. METHODS: An atmospheric dispersion model was used to generate nationwide exposure maps of aerosols from 776 WWTPs in the Netherlands. Municipal sewage treatment plants and industrial WWTPs were both included. Exposure of LD cases and controls at the residential address was compared, in a matched case-control design using a conditional logistic regression. Cases were notified LD cases with onset of disease in the period 2013-2018 in the Netherlands (n = 1604). RESULTS: Aerosols dispersed over a large part of the Netherlands, but modelled concentrations are estimated to be elevated in close proximity to WWTPs. A statistically significant association was found between LD and the calculated annual average aerosol concentrations originating from WWTPs (odds-ratio: 1.32 (1.06-1.63)). This association remained significant when the two outbreak-related WWTPs were removed from the analysis (odds-ratio: 1.28 (1.03-1.58)). CONCLUSION: LD cases were more exposed to aerosols from WWTPs than controls. This indicates that exposure to aerosols dispersed from WWTPs caused Legionnaires Disease in residents living near WWTPs in the period 2013-2018. In order to investigate which characteristics of WWTPs are associated with an increased LD risk, the WWTP database should be updated and more data is needed on the presence and survival of aerosolized Legionella bacteria to improve the Legionella dispersion modelling. Furthermore, it is recommended to further investigate how aerosol dispersion of WWTPs can effectively be reduced in order to reduce the potential health risk.

Climate change impacts on aflatoxin B1 in maize and aflatoxin M1 in milk: A case study of maize grown in Eastern Europe and imported to the Netherlands.

Various models and datasets related to aflatoxins in the maize and dairy production chain have been developed and used but they have not yet been linked with each other. This study aimed to investigate the impacts of climate change on aflatoxin B1 production in maize and its consequences on aflatoxin M1 contamination in dairy cow's milk, using a full chain modelling approach. To this end, available models and input data were chained together in a modelling framework. As a case study, we focused on maize grown in Eastern Europe and imported to the Netherlands to be fed-as part of dairy cows' compound feed-to dairy cows in the Netherlands. Three different climate models, one aflatoxin B1 prediction model and five different carryover models were used. For this particular case study of East European maize, most of the calculations suggest an increase (up to 50%) of maximum mean aflatoxin M1 in milk by 2030, except for one climate (DMI) model suggesting a decrease. Results from all combinations of carryover and climate models suggest a similar or slight increase (up to 0.6%) of the chance of finding aflatoxin M1 in milk above the EC limit of 0.05 µg/kg by 2030. Results varied mainly with the climate model data and carryover model considered. The model framework infrastructure is flexible so that forecasting models for other mycotoxins or other food safety hazards as well as other production chains, together with necessary input databases, can easily be included as well. This modelling framework for the first time links datasets and models related to aflatoxin B1 in maize and related aflatoxin M1 the dairy production chain to obtain a unique predictive methodology based on Monte Carlo simulation. Such an integrated approach with scenario analysis provides possibilities for policy makers and risk managers to study the effects of changes in the beginning of the chain on the end product.

Using a multihospital systems framework to evaluate and establish drug use policy.

PURPOSE: In order to develop rational drug purchasing and use policy for a class of pharmaceuticals used in a consortium system of 14 university based hospitals, the antiemetic use patterns of inpatients receiving cancer chemotherapy were evaluated to assess the comparative effectiveness of granisetron, ondansetron, and conventional antiemetics. PATIENTS AND METHODS: A prospective, observational study was conducted in 14 academic health centers linked under research and purchasing consortium arrangements from October to December 1994. The use of antiemetics was evaluated in hospitalized patients receiving cancer chemotherapy agents with a known propensity for causing, alone or in combination, varying degrees of nausea or vomiting. Clinical outcomes measured were the impact of chemotherapy administration on the functional status of patients, and the occurrence of post-treatment vomiting. RESULTS: The most often prescribed cancer chemotherapy regimens consisted of cisplatin, paclitaxel, etoposide and cyclophosphamide, and the most often prescribed antiemetics were the 5-hydroxytryptamine subtype-3 antagonists (5-HT3 antagonists, granisetron and ondansetron), dexamethasone and lorazepam. Of the 439 patients studied, 329 (75%) reported no episodes of emesis. Of the patients receiving highly emetogenic chemotherapy, those receiving 5-HT3 antagonists experienced better overall outcomes (as measured by functional health status and the absence of vomiting) than patients receiving conventional (non-5-HT3 antagonist) antiemetics. In contrast, patients receiving chemotherapy associated with moderate or low emetogenicity experienced similar outcomes, regardless of the antiemetic regimen selected. No statistical difference was seen between granisetron and ondansetron in achieving positive patient outcomes. CONCLUSION: The study results suggest that 5-HT3 antagonists are associated with better clinical outcomes than other antiemetics in patients receiving highly emetogenic chemotherapy. Less costly conventional antiemetic therapy (or, in some cases, no antiemetic therapy) provide comparable outcomes in patients receiving chemotherapy associated with moderate or low emetogenic potential. Granisetron and ondansetron were found to be clinically comparable.

Pharmacotherapy with botulinum toxin: harnessing nature's most potent neurotoxin.

Botulinum toxin (BTX), a potent biologic neurotoxin, commonly is associated with lethal outbreaks of food poisoning; however, it also plays a role as a therapeutic agent. Since the 1970s physicians have investigated BTX therapy in patients with neurologic disorders. The number of applications greatly expanded over the years to include certain focal dystonias (blepharospasm, torticollis, laryngeal dystonias, writer's cramp), strabismus, and a wide variety of other indications (gastrointestinal disorders, cosmetic wrinkle correction, spasticity, hyperhidrosis). BTX's safety and efficacy are reviewed.

Clinical and humanistic outcomes in patients with gastroesophageal reflux disease converted from omeprazole to lansoprazole.

BACKGROUND: Omeprazole and lansoprazole are 2 proton pump inhibitors (PPIs) currently available in the United States. Both PPIs are approved for the treatment of gastroesophageal reflux disease (GERD) and are commonly converted in therapeutic interchange programs. OBJECTIVE: To measure clinical and humanistic outcomes in patients with GERD converted from treatment with omeprazole to treatment with lansoprazole through a managed care plan policy. METHODS: Patients with heartburn or GERD receiving omeprazole covered by a local health plan were surveyed by telephone. Data collected included symptom frequency, severity, over-the-counter heartburn preparation use, diet, lifestyle, and overall satisfaction. Patients were then converted to therapy with lansoprazole and again interviewed after at least 30-day use of the new PPI. Demographic data were obtained from the health plan database for analysis. RESULTS: A total of 105 patients completed both telephone surveys. After the conversion, 37% of the patients experienced more frequent symptoms while awake. Symptom severity score was significantly higher (more severe) after conversion (mean score of 1.34 vs 2.26). Thirty-three percent of study patients consumed more over-the-counter heartburn preparations, and 13% changed their diet more frequently due to heartburn symptoms after conversion. Overall patient satisfaction score decreased significantly (less satisfied) after conversion (mean score of 9.0 vs 7.2). There were no significant differences in alcohol and tobacco consumption before and after conversion, while patients consumed significantly less caffeine after conversion. CONCLUSIONS: After the PPI therapeutic interchange from omeprazole to lansoprazole, patients with GERD or heartburn previously stabilized while receiving omeprazole experienced more severe symptoms and expressed decreased patient satisfaction. These results suggest a need to monitor symptoms after similar interchange programs.

Comparative effectiveness of low-molecular-weight heparins after therapeutic interchange.

Management Case Studies describe approaches to real-life management problems in health systems. Each installment is a brief description of a problem and how it was dealt with. The cases are intended to help readers deal with similar experiences in their own work sites. Problem solving, not hypothesis testing, is emphasized. Successful resolution of the management issue is not a criterion for publication-important lessons can be learned from failures, too.

Cost-offset analysis of aprotinin in high-risk coronary artery bypass.

Aprotinin, a naturally occurring protease inhibitor derived from bovine lung, is used prophylactically to minimize the amount of perioperative blood loss in patients undergoing coronary artery bypass graft surgery who are at high risk for excessive bleeding. A retrospective multicenter evaluation of aprotinin use was performed in high-risk coronary artery bypass graft patients treated either with aprotinin or according to usual-care to assess (1) differences in demographic and medical history characteristics, and (2) clinical and economic outcomes associated with their care. This study suggests that in many cases, the cost of aprotinin is offset by reductions in overall cost. Additional study is required to better understand this potential. In other cases, however, a more conservative approach to aprotinin use appears to be warranted.

Multifaceted approach to medication use policy development: the restriction of meperidine.

As institutions continue to expand their drug policy development efforts in order to improve care and reduce cost, the use of multifaceted approaches offer several benefits. Population data on drug use support the need for policy action. The use of institutional outcomes data in conjunction with published evidence augments the process, and the consensus approach to guideline development engenders medical staff support. Such efforts, however, require significant dedication of human resources. Institutions with limited personnel to allocate to drug policy activities may consider increasing the depth of their efforts (using a multifaceted approach) while limiting the breadth of their efforts (only attempting one or two major targets per year, and doing them well).

Economic evaluations of clinical pharmacy services--1988-1995. The Publications Committee of the American College of Clinical Pharmacy.

The objectives of this effort were to summarize and critique original economic assessments of clinical pharmacy services published from 1988-1995, and to make recommendations for future work in this area. A literature search was conducted to identify articles that were than blinded and randomly assigned to reviewers to confirm inclusion, abstract information, and assess the quality of study design. The 104 articles fell into four main categories based on type of service described: disease state management (4%), general pharmacotherapeutic monitoring (36%), pharmacokinetic monitoring services (13%), and targeted drug programs (47%). Articles were categorized by type of evaluation; 35% were considered outcome analyses, 32% outcome descriptions, and 18% full economic analyses. A majority (89%) of the studies reviewed described positive financial benefits from the clinical services evaluated; however, many (68%) did not include the input costs of providing the clinical service as part of the evaluation. Studies that were well conducted were most likely to demonstrate positive results. Commonly, results were expressed as net savings or costs avoided for a given time period or per patient. Seven studies expressed results as a benefit:cost ratio (these ranged from 1.08:1 to 75.84:1, mean 16.70:1). Overall this body of literature contains a wealth of information pertinent to the value of the clinical practice of pharmacy. Future economic evaluations of clinical pharmacy services should incorporate sound study design and evaluate practice in alternative settings.

Albumin and nonprotein colloid solution use in US academic health centers.

BACKGROUND: Crystalloids, nonprotein colloids (NPCs), and albumin are used for many indications. The use of the least costly agent in situations where these products are clinically interchangeable can reduce health care costs. OBJECTIVES: To characterize the prescribing of albumin and NPC. To evaluate the appropriateness and cost implications of their use. METHODS: An observational study conducted in 15 academic health centers from April 11 through May 6, 1994, to assess the appropriateness of albumin and NPC use, based on "model" consensus-derived indication guidelines. RESULTS: A total of 969 case report forms were evaluated. Albumin and NPCs were administered in 83% and 17% of the cases, respectively. Albumin and NPCs were administered mostly in the intensive care (50%) or operating room (31%) settings. The most common prescribers of these products were surgeons (45%) and anesthesiologists (20%). In 87% of cases, albumin or NPC was administered to reach a defined end point (eg, to achieve a target physiological state or to resolve a pathophysiological condition). Only one albumin recipient experienced an adverse event; no adverse events were noted with NPC administration. Approximately $203,000 was spent on albumin and NPC therapy for the 969 cases; $49,702 (24%) was spent on appropriate administrations, $124,939 (62%) on inappropriate administrations, and $28,014 (14%) on unevaluated indications. CONCLUSIONS: Evaluated against model guidelines, most of the albumin and NPC use in the study was found to be inappropriate. The need for institutions to define and implement guidelines that focus on the cost-efficient use of these agents is recommended in an increasingly cost-conscious health care environment.

Surveillance of colony-stimulating factor use in US academic health centers.

OBJECTIVE: To characterize and evaluate hematopoietic colony-stimulating factor (CSF) use, including cost implications, in US academic health centers. DESIGN: An observational study of patients who received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) from September 1 to October 15, 1993. SETTING: Thirty academic health centers in the US. PARTICIPANTS: Five hundred sixty-five patients were evaluated. MAIN OUTCOME MEASURES: The appropriateness of CSF use was assessed, based on consensus-derived indication guidelines and the Food and Drug Administration-approved product labeling. Indication, type of CSF, and dosage were considered in determining the appropriateness of CSF therapy. RESULTS: Based on indication evaluation criteria, 71% of CSF use was appropriate, 7% was inappropriate, and 22% was unproven, although the majority of unproven use was deemed promising by the expert panel. Based on dosage evaluation criteria, 51% of CSF use was appropriate, 27% was inappropriate, and 22% was for promising and other unproven indications. More than 90% of the patients studied received G-CSF. Approximately 3.4% of patients who received G-CSF had an adverse event, compared with 22% of those who received GM-CSF. Approximately $791,000 was spent on CSF therapy in the 565 patients: $401,000 (51%) on appropriate indications and doses, $160,000 (20%) on inappropriate doses for appropriate indications, $124,000 (16%) on promising indications, and $106,000 (13%) on unproven or inappropriate indications. CONCLUSIONS: Substantial costs are incurred currently for CSF therapy without adequate literature support. Further studies are warranted to justify promising but unproven uses of CSFs, as well as to clarify proper dosing, monitoring, and relative safety of CSFs.

A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions.

OBJECTIVE: To develop contemporary, comprehensive guidelines for the appropriate and efficient use of albumin, nonprotein colloid, and crystalloid solutions. DESIGN: A systematic, literature-based, consensus exercise employing a modified Delphi method. PARTICIPANTS: Thirty-one medical and allied health professionals from 26 University Hospital Consortium (Oak Brook, Ill) member institutions were initially chosen to participate. Participants were selected on the basis of their recognized research in the use of albumin, nonprotein colloid, and crystalloid solutions, and/or experience in the review of appropriateness of such use. A total of 24 participants completed the exercise. MAIN OUTCOME MEASURES: Group responses were statistically analyzed in an iterative consensus development process. Five separate questionnaire rounds were designed to establish criteria for the appropriate use of albumin, nonprotein colloid, and crystalloid solutions. RESULTS: Consensus guidelines were developed outlining the appropriate use of these products for 12 clinical indications, including hemorrhagic shock, nonhemorrhagic (maldistributive) shock, hepatic resection, thermal injury, cerebral ischemia, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis. CONCLUSIONS: The Delphi method, a systematic, literature-based consensus process, was shown to be useful in the development of complex clinical practice guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. It is anticipated that the guidelines will assist health care providers to develop local institutional policies and procedures for the appropriate and efficient use of albumin and albumin alternatives. Institutions reviewing and updating existing local guidelines may use the University Hospital Consortium guidelines as a model for comparison.

Comparison of automated medication-management systems.

Automated devices for managing medication distribution are described. Shrinking operating budgets are causing many departments of pharmacy to consider automation to maximize the cost-effective use of professional personnel. Many devices and systems that are currently available or under development can help with (1) distribution of medication to and from the patient care area, (2) distribution of medication directly to the patient, (3) inventory control, (4) management of controlled substances, or (5) documentation of medication administration. Medication-management devices based in the patient care unit (Lionville CDModule, Access, Meditrol, Argus, MedStation, Sure-Med, and SelecTrac-Rx) are designed to replace manual filling of unit dose carts or to increase control over floor-stock medications and controlled substances. They provide immediate access to medications but can take extra time to fill. Centrally located medication-management systems (Automated Pharmacy Station, ATC-212, and Medispense) are designed to replace or improve a manual system for filling unit dose carts. They may have financial and practical advantages over systems based in the patient care unit because they avoid redundant inventories. However, a manual system is still needed for some medications, particularly those that need refrigeration. Several point-of-care information systems also have medication-management components (MedTake, CliniCare, Automated Medication Administration Tracking, and MedLynk). They provide rapid access to patient information and facilitate documentation. Many incorporate bar-code technology and radio-frequency transmission of data. An automated management system can combine increased efficiency with decreased risk of error. Descriptions of available systems may help pharmacists choose a system that meets their needs.