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A program for the optimization of cyclosporine therapy using population kinetics modeling.

Cyclosporine is one of the most widely used immunosuppressive agents in organ transplantation. Due to large inter- and intra-individual variations, its behavior in the specific patient is still difficult to predict. Dosage optimization is thus mainly performed on a trial-and-error basis. In this paper, we present a new program based on the population kinetics approach, which was designed to help physicians in the difficult task of adjusting patient specific cyclosporine dosing regimens. Dose optimization is carried out by model simulation, using a two-compartment mathematical model of cyclosporine kinetics to predict the drug behavior in the patient. Two of the model parameters are assumed from the literature, the other two are estimated from the patient data through a Bayesian estimation procedure. Previous information needed by the Bayesian algorithm is derived by a population analysis, performed beforehand and based on a nonlinear mixed effect model. A user-friendly graphical interface written in Delphi under Windows makes the program easily accessible to physicians. A preliminary retrospective validation of the program, performed on data from 18 renal transplanted patients, yielded very satisfactory results.

Algorithms↗

Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research.

STUDY OBJECTIVE: To develop guidelines for the care of infants and children from birth to 36 months of age with fever without source. PARTICIPANTS AND SETTING: An expert panel of senior academic faculty with expertise in pediatrics and infectious diseases or emergency medicine. DESIGN AND INTERVENTION: A comprehensive literature search was used to identify all publications pertinent to the management of the febrile child. When appropriate, meta-analysis was used to combine the results of multiple studies. One or more specific management strategies were proposed for each of the decision nodes in draft management algorithms. The draft algorithms, selected publications, and the meta-analyses were provided to the panel, which determined the final guidelines using the modified Delphi technique. RESULTS: All toxic-appearing infants and children and all febrile infants less than 28 days of age should be hospitalized for parenteral antibiotic therapy. Febrile infants 28 to 90 days of age defined at low risk by specific clinical and laboratory criteria may be managed as outpatients if close follow-up is assured. Older children with fever less than 39.0 C without source need no laboratory tests or antibiotics. Children 3 to 36 months of age with fever of 39.0 C or more and whose WBC count is 15,000/mm3 or more should have a blood culture and be treated with antibiotics pending culture results. Urine cultures should be obtained from all boys 6 months of age or less and all girls 2 years of age or less who are treated with antibiotics. CONCLUSION: These guidelines do not eliminate all risk or strictly confine antibiotic treatment to children likely to have occult bacteremia. Physicians may individualize therapy based on clinical circumstances or adopt a variation of these guidelines based on a different interpretation of the evidence.

Algorithms↗

Length-based endotracheal tube and emergency equipment in pediatrics.

HYPOTHESIS: Pediatric endotracheal (ET) tubes can be accurately selected based on body length using a specialized emergency tape. POPULATION: Derivation set: Two hundred five children undergoing elective surgery. Validation set: Two hundred thirteen children undergoing elective surgery. Each child served as his or her own control. METHODS: Derivation phase: Two hundred twenty-one children undergoing ET intubation for elective surgery had their body length and leak pressures measured. The 205 children who had leak pressures between 10 and 40 cm H2O constituted the derivation set. The body length for a given ET tube size was derived from the interquartile range of patient lengths in this derivation set. Sizes for other resuscitative equipment items were chosen by a panel of experts using a modified Delphi technique. This information was placed by length on a color-coded tape. Validation phase: The tape was validated by using it to select ET tube size in another group of 203 children undergoing elective surgery. Criteria for acceptable fit in this group included leak pressure as above and the anesthesiologists' decision to accept the tube size or to retintubate. In the validation phase, length-based ET tube selections were compared with age-based rules: (age + 16)/4, and (age + 18)/4. RESULTS: The tape selected the appropriate ET tube size by leak pressure criterion in 77% of the cases and was within +/- 0.5 mm of the "correct" size 99% of the time. This was significantly better (P less than .005) than two widely used age-based rules, which gave the correct initial size in only 47% and 9% of these cases, and were within +/- 0.5 mm for 86% and 59%. The anesthesiologists chose to continue with the tape-sized tube rather than to reintubate in 89% of cases. CONCLUSION: A system for length-based selection of emergency equipment represents a significant adjunct to emergency physicians and paramedics who must deal with critically ill children. Length-based ET tube selection is clearly superior to age-based rules, which are difficult to remember and require accurate estimation of a patient's age.

Body Height↗

[Test on knowledge about climacteric: development and validation process].

OBJECTIVE: To construct and validate a test of knowledge about the menopause. SETTING: The context for use of this test is the Autonomous Community of Andalusia. METHOD: 1. Construction of the theoretical universe through the Delphi Technique. 2. Weighting of each of the dimensions of the theoretical universe. 3. Formulation and selection of the conceptual elements to introduce into the questionnaire and formulation of the corresponding items. 4. Selection of items and analysis of their internal consistency, homogeneity, stability and equivalence after a pilot study. PARTICIPANTS: The questionnaire's pilot study was run with 150 Andalusian women, chosen through sampling by quotas of age, habitat and educational background. MEASUREMENTS AND RESULTS: A questionnaire with 56 true and false (T/F) items grouped in four dimensions was obtained: biological aspects (14 items), psychological and social aspects (14), health risks linked to the menopause (6), care and preventive and health-improvement activities at the menopause (22). Its validity and reliability were determined by the following results: internal consistency and overall homogeneity (Cronbach's alpha = 0.86); stability or absence of significant differences at the moment the questionnaire is run (Student's t = 1.09; p = 0.28); intra-class correlation coefficient (ICC) = 0.753; equivalence or absence of bias of the questioners (Student's t = 1.09; p = 0.28), ICC = 0.761. CONCLUSIONS: The results lead us to conclude that the instrument is stable, allowing for the independence of the time and questioner variables, with high internal consistency and representing well the conceptual elements that shape the theoretical universe.

Adult↗

[Principal requirements in medical training for certification of deaths in Spain].

OBJECTIVE: To know the training need priorities in Spanish physicians in death certification. DESIGN: Study of needs by consensus technique Delphi. SETTING: Health care and medical-legal institutions in Spain. PARTICIPANTS: Physicians who ask for information in death certification, after reading an article in a medical magazine (n=38), and agree to participate (n=33). METHODS: Priorities were established by means of a list of items, based on teaching experience and professional advice. The scores obtained for each priority were hierarchized, and the participants professional profiles were described. An analysis of hierarchical clusters was done to determine profiles of training. RESULTS: The median age of the participants was 42 years, with 18 years experience in general/family, emergency or forensic medicine, which usually certified in median 8 death a year (rank from 0 to 50). The maximum training priorities were how to register a death and which doctor should make out the official documents. Intermediate priorities included the role of doctors in violent or accidental deaths. In the main three grouping needs were, in one, include certification as a degree subject and learn how different documents are made out; although in the others two, were how to register a death, which physician make out the documents, and when it should certify the family doctor and when the coroner. CONCLUSIONS: The priorities in certification training are how to register a death and who should make out the documents, pointing out that the shortcoming continues in medical training in death certification.

Adult↗

[Hospitalizations preventable by timely and effective primary health care].

OBJECTIVE: To know the specific health problems referred as ambulatory care sensitive conditions (ACSC) and to identify the primordial interventions of primary health care (PHC) in reducing hospitalisations due to ACSC. DESIGN: Descriptive study of hospital discharges generated in Catalonia during 1998-1999, and a Delphi study to reach information about PHC primordial interventions. MEASURES: Diagnostic codes of ACSC selected as markers of PHC effectiveness were used. We analysed hospital discharge distribution by age groups and overall, and hospitalisation rates with its 95% confidence intervals. Descriptive analysis of consensus reached by experts using self-administrated questionnaires was done. RESULTS: The 8.42% of total discharges were due to ACSC. The majority of these (86.9%) fell in 4 of the 13 diagnostic categories included in the ACSC list. A great variety of pathologies with different frequencies were identified. Primary prevention and early diagnoses and treatment were considered as primordial interventions. Chronic health problems needed multimodal interventions. CONCLUSIONS: Diagnostic codes included in each diagnostic category were congruent with the diseases identified. Interventions that could prevent hospitalisations due to ACSC are contemplated as role of PHC. Indicator validity to assess PHC effectiveness is maintained by both results.

Ambulatory Care↗

[Qualitative research: a valid alternative].

OBJECTIVE: To describe the main qualitative research techniques through systematic review of Spanish studies published during the previous 5 years. DESIGN: Systematic review. DATA SOURCES: The Indice Médico Español (bibliographic database of items published in Spanish health sciences journals) was searched, and systematic searches of the journals Atención Primaria, Gaceta Sanitaria, and Revista de Calidad Asistencial were done. Study selection. We included studies carried out with any type of qualitative research technique. Also included were studies that reviewed qualitative research techniques. We excluded studies that used a qualitative technique but were based mainly on quantitative research techniques. The review was done during the period from April 1997 to April 2002. RESULTS: Most of the studies we reviewed used only one technique (80.5%). When more than one technique was used in combination (19.5% of the articles we reviewed), focus groups and interviews were usually used. The techniques identified were focus group (used in 34% of the articles reviewed), interview (24%), the Delphi technique (10%), content analysis (8%), nominal group (8%), metaplan (2%), and Philips 6/6 (2%). CONCLUSIONS: Qualitative research is a valid alternative, and if used with appropriate methodological rigor it can be of considerable use to health care professionals.

Biomedical Research↗

[Qualitative techniques for public health research and the development of health care services: more than just another technique].

Regarding the debate on the existence of two current focuses on health science research (qualitative and quantitative), the paper states the need for complementing the techniques which contribute to a better knowledge of populations and communities, and the need for offering effective solutions to different problems. The article analyses the usefulness of qualitative methods, describes the techniques and procedures more frequently used to guarantee the validity and reliability of research findings and ends bringing up the need for using qualitative and quantitative approaches. This way of working together or learning from each other will enrich research and interventions on public heath and health management fields. Qualitative methods are useful for sound understanding of a given issue that is being investigated or evaluated taking into account the point of view of the participants under research. Key techniques, listed from the most structured to the less structured are among others: structured interview, Delphi, nominal group, case study, semistructured interview, focal group, brainstorming, discussion group, in depth interview, life story and participant observation.

Health Services Administration↗

[Three-dimensional 3D modeling: First applications in radioanatomy and interventional radiology under CT guidance].

PURPOSE: To model vertebrae in 3D to improve radioanatomic knowledge of the spine with the vascular and nerve environment and simulate CT-guided interventions. METHOD AND MATERIALS: Vertebra acquisitions were made with multidetector CT. We developed segmentation software and specific viewer software using the Delphi programming environment. RESULTS: This segmentation software makes it possible to model 3D high-resolution segments of vertebrae and their environment from multidetector CT acquisitions. Then the specific viewer software provides multiplanar reconstructions of the CT volume and the possibility to select different 3D objects of interest. DISCUSSION: This software package improves radiologists' radioanatomic knowledge through a new 3D anatomy presentation. Furthermore, the possibility of inserting virtual 3D objects in the volume can simulate CT-guided intervention. CONCLUSION: The first volumetric radioanatomic software has been born. Furthermore, it simulates CT-guided intervention and consequently has the potential to facilitate learning interventions using CT guidance.

Algorithms↗

An insight into the epidemiology of dolphin morbillivirus worldwide.

Serum samples from 288 cetaceans representing 25 species and originating from 11 different countries were collected between 1995 and 1999 and examined for the presence of dolphin morbillivirus (DMV)-specific antibodies by an indirect ELISA (iELISA) (N = 267) or a plaque reduction assay (N = 21). A total of 35 odontocetes were seropositive: three harbour porpoises (Phocoena phocoena) and a common dolphin (Delphinus delphis) from the Northeastern (NE) Atlantic, a bottlenose dolphin (Tursiops truncatus) from Kent (England), three striped dolphins (Stenella coeruleoalba), two Risso's dolphins (Grampus griseus) and a bottlenose dolphin from the Mediterranean Sea, one common dolphin from the Southwest (SW) Indian Ocean, three Fraser's dolphins (Lagenodelphis hosei) from the SW Atlantic, 18 long-finned pilot whales (Globicephala melas) and a bottlenose dolphin from the SW Pacific as well as a captive bottlenose dolphin (Tursiops aduncus) originally from Taiwan. The presence of morbillivirus antibodies in 17 of these animals was further examined in other iELISAs and virus neutralization tests. Our results indicate that DMV infects cetaceans worldwide. This is the first report of DMV-seropositive animals from the SW Indian, SW Atlantic and West Pacific Oceans. Prevalence of DMV-seropositives was 85.7% in 21 pilot whales from the SW Pacific and both sexually mature and immature individuals were infected. This indicates that DMV is endemic in these animals. The same situation may occur among Fraser's dolphins from the SW Atlantic. The prevalence of DMV-seropositives was 5.26% and 5.36% in 19 common dolphins and 56 harbour porpoise from the NE Atlantic, respectively, and 18.75% in 16 striped dolphins from the Mediterranean. Prevalence varied significantly with sexual maturity in harbour porpoises and striped dolphins; all DMV-seropositives being mature animals. The prevalence of seropositive harbour porpoise and striped dolphins appeared to have decreased since previous studies. These data suggest that DMV is not endemic within these populations, that they are losing their humoral immunity against the virus and that they may be vulnerable to new epidemics.

Animal Diseases↗

Organizational restructuring in health care: a successful approach.

The process of redesigning the internal organization structure of the Hamilton Civic Hospitals provides a successful example of this type of transformation. Based on a strategic approach to change, this multiphased process used a modified delphi technique to allow maximum participation in a total redesign of the structure during a four-month time frame. Implementation, which followed over the next year, resulted in a 40 percent reduction in management positions and the integration of the two sites of the hospital.

Efficiency, Organizational↗

Voices from practice: mental health nurses identify research priorities.

Through a collaborative research project, nurse clinicians and nurse academics identified and prioritized the most important research questions arising from the current and future practice of mental health nurses in an eastern Canadian region. Study methods included the Delphi technique and a nominal group survey approach. Nine categories of research questions emerged. The top four categories are discussed under the headings: Preparation of Helpers, the Service System, Caregiver Needs, and Clients With Major Behavior Problems. This timely study offers explicit direction for psychiatric and mental health nursing practice and research, and for the development of social policy.

Attitude of Health Personnel↗

Preoperative preparation. Value, perspective, and practice in patient care.

Preanesthesia preparation will continue to stimulate creativity and debate. Strategies for process improvement will take various shapes and require tools previously unfamiliar to many medical managers. At UNC Health System, anesthesiologists currently are committed to the centralized preanesthesia clinic approach used in PreCare. To date, their strategies have been validated by their institutional measures of success: a 0.7% first-case AM work-up rate, a 5% no PreCare visit rate, a 5% consent problem rate, and a 0% rejected specimen rate, with a 43% blood-draw rate for all patients. As their health system expands, however, other strategies and preparation modalities may become necessary. Telemedicine and Internet-dependent processes are appealing in the highly educated and technologically sophisticated marketplace. As the region becomes increasingly urbanized, local employment patterns prevent easy access to services, and functional compromises, such as bypassing PreCare or reliance on telephone or on-line interviews for preparation, may become necessary. The need to expand PreCare in the near future is already evident. As was found during initial planning, process improvement and space planning are enhanced by computer modeling. UNC Health System employed a proprietary animated simulation modeling (ASM) tool, MedModel, (ProModel, Orem, UT), although other techniques exist for the same purpose. Use of ASM as a strategy management tool allowed generation of ideal space-time-personnel scenarios that could expose potential problems before resources and physical restructuring occurred. ASM also can be used to compare data obtained from real-time observations to any reference scenario, including any that looks at economic measures of process, to help refine strategic visions before instituting tactical solutions. Used in this manner, ASM can reveal physical, temporal, personnel, and policy-related factors not otherwise seen as exerting effects on overall preprocedural preparation processes. Coupled with other classic planning techniques, such as time-motion studies, modified Delphi techniques, customer satisfaction surveys, benchmarking studies, and financial analysis and growth projections, ASM has helped enhance total quality management efforts in PreCare and other planning projects at UNC Health System. Other researchers have used other simulation techniques to assess clinic functions. Operational challenges that exist in preanesthesia preparation clinics place these clinics on the same level as other kinds of medical service clinics. The lessons learned in most clinic settings may be applied in a cross-wise manner to the preanesthesia clinic. Dexter contends that efficient delivery of care that respects patients' time and needs does more than assist the procedural preparation process; it also supports the physician's ethical obligation to the patient to give the best possible care. Documenting patient medical information, education efforts, and maintaining the medical-legal integrity of the preanesthesia preparation materials is another area of increasing concern and research. When hand-held computers capable of linking by way of infrared technologies or that use rented downloadable software to run specific applications become commonly used, the complexity of ensuring privacy will grow. The complexity, however, will not be insurmountable. Privacy problems exist in any information management system, whether paper-based (i.e., reducing redundant forms, eliminating indiscriminant photocopying of records), electronic-based (i.e., encryption, server access, system failure), or both. Electronic conveyance of medical information faces more legal and economic than technical hurdles. The penetration in US households of Internet services presently is less than 40%, whereas the penetration of personal computers is just over 50%. These figures are compared with penetration of corded telephones, televisions, and radios at levels greater tha

Anesthesiology↗

Cost-effectiveness of mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in austria.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen). The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity. The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost. Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58, 787 and ATS 61,851 per patient respectively. Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant. In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.

Amitriptyline↗

Decision analysis in obstetrics and gynaecology.

Decision analysis has its weaknesses: it may oversimplify problems, and probability and utility estimates may be biased. However, the alternative--decision-making by intuition--is likely to oversimplify problems even more and to be subject to even greater bias. Clinicians and patients often ignore major items of data, they handle probabilistic information badly, and their decisions are subject to a number of well-documented biases (Tversky and Kahnemann, 1974). Concern over these problems is not a reason to avoid decision analysis. Probably the greatest virtue of the decision tree and the other components of decision analysis is that the method forces decision-makers to make the bases for their decisions explicit. Generating the information often clarifies problems, and the source of difference of opinion can then be elucidated. Most of the benefits of decision analysis come to the decision-maker in the early part of the analysis as the problem is formulated and probabilities and values are estimated. Only occasionally is it necessary to perform new research, formally measure experts' opinions by the Delphi method, or do elaborate sensitivity analysis.

Bias↗

Electrostatic activation of Escherichia coli methionine repressor.

BACKGROUND: The three-dimensional structure of the Escherichia coli methionine repressor (met repressor) is relatively unperturbed by the binding of its corepressor, S-adenosylmethionine (SAM), and of operator DNA. The positively charged corepressor binds to sites on the repressor remote from the DNA-binding site, and despite the lack of induced structural change is able to raise the affinity for operator DNA by a factor of up to 1000. Neutral corepressor analogues also bind to the repressor, but do not increase operator affinity. These observations suggest that the corepressor effect may be electrostatic. RESULTS: Using the program DELPHI, we have calculated electrostatic potentials for the repressor and its complexes, and have obtained results consistent with an electrostatic model for repressor activation. The positive potential originating from the corepressor is propagated through the repressor-operator complex, and is significant at DNA phosphate groups buried in the protein-DNA interface. The rank order of calculated electrostatic interaction energies for complexes with SAM, and two closely-related analogues, is in agreement with experimental measurements of the corresponding repressor-operator affinities. CONCLUSION: Long-range (> 10 A) electrostatic interactions between bound corepressor and operator phosphate groups in the repressor-operator complex may be sufficient to explain repressor activation Met repressor could, therefore, be an electrostatically triggered genetic switch.

Apoproteins↗

New features of the IC(4) code and comparison of internal conversion coefficient calculations.

The IC(4) software developed to compare calculated internal conversion coefficients (ICC) has been enhanced by adding new features through the use of Borland Delphi and TeeChart. Particularly, the 3D-graph option enhances the possibilities of analyzing calculated ICC values. For example, the comparison between the results given by three sets of theoretical ICC tables for any arbitrary pair of calculated ICC can be presented in a much clearer manner. Their differences can be displayed as energy vs. atomic number surfaces. Results from the analyses of K-shell and total ICCs for E2, E3, M2, M3, and M4 multipolarity are discussed.

Journal Article↗

Australian nurses and device use: the ideal and the real in clinical practice.

Clinical nurses use an increasing number of technological devices when providing care. While the clinical devices themselves must undergo rigorous multidimensional assessment, it is the proficiency of the user that ultimately determines the devices' efficacy. Thus, the knowledge, skills and attitudes that nurses bring to their decision-making and use of technology are crucial elements in the technology assessment process. Technological proficiency is imperative in the current climate of rapid patient throughput in complex technological environments. This paper reports some of the findings of an Australian study, using two national Delphi panels, whose primary objective was to determine the knowledge, skills and attitudes required of expert clinicians for practice in cardiac care. Panels of 28 educators and 42 cardiac nurse clinicians completed a questionnaire indicating the importance of 107 characteristics of expert cardiac practice for both the 'real' and 'ideal' worlds of practice. Comparative results will be reported for 29 items within the thematic groups. Effective use of technology, Informed decisions regarding equipment and Critical approach to the use of technology. Both panels accepted all 29 items in these three thematic groups but indicated differences in the level of agreement on the importance of items between the 'real' and 'ideal' worlds of practice. Discussion centres around those areas where improvement is needed.

Australia↗