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PubMedDate not supplied

A study of the characteristics of single-injection insulated block needles in a biologic model.

BACKGROUND AND OBJECTIVES: Single-injection block needles are manufactured in many different lengths, diameters, and tip designs, but the literature contains no reports of methods to assess clinical characteristics of regional-block needles. A novel animal model for the assessment of the characteristics of single-injection regional anesthesia needles is described. METHODS: Nine different needles designed for peripheral nerve blocks that were fitted with identical hubs were used. Pork bellies were used as the biologic model. The bellies were mounted such that the needles passed from inside to outside. The last layer to be penetrated was the skin. Ten experienced and blinded anesthesiologists scored the feel, resistance, and usability of the 9 needles during their passage through similarly prepared pork bellies. Two identical (index) needles were included in the study to assess the internal validity of the study. RESULTS: The overall scoring was acceptably consistent and repeatable and showed statistically significant differences between the needles tested. The needles that were judged the most usable were those with a moderate resistance to passage through the tissue and a high degree of feel, which was defined as the ability to appreciate the passage of the needle through the tissue planes. Needles with very high or very low resistances and those with poor feel scored poorly on the usability scale. Differences in individuals' assessment of the index needles suggested some within-subject variability during the study. CONCLUSIONS: This type of biologic model can be used for the quantifiable and repeatable assessment of different needle tip designs. Needles with moderate resistance and high feel were preferred.

Animals↗

PubMedDate not supplied

Evaluation of the rodent Hershberger assay using three reference endocrine disrupters (androgen and antiandrogens).

Three chemicals with known endocrine activities have been evaluated in the rat Hershberger assay for phase-2 of the international validation exercise within the Organization for Economic Cooperation and Development (OECD). The chemicals studied included the antiandrogens finasteride (FIN) and procymidone (PRO) and the androgen agonist 17alpha-methyltestosterone (MT). Castration of sexually immature Sprague-Dawley rats was performed between post-natal days 42 and 46 whilst dosing of the chemical over 10 days was performed between post-natal days 53 and 67. Rats were co-treated with testosterone propionate (TP) for the antiandrogenic activity evaluation. The endpoints examined for evaluation of the androgenic/antiandrogenic activity were changes in sex accessory tissue (SAT) weights supplemented with measurement of testosterone and luteinizing hormone (LH) levels at sacrifice. Changes in liver, adrenal, kidney and body weights were also monitored for general toxicity assessment. Statistically significant changes in the SAT weights were detected with the three chemicals tested. Hence, the rat Hershberger assay as defined by the OECD was demonstrated sensitive enough for the detection of the endocrine disrupting activity of the three reference chemicals evaluated.

Animals↗

PubMed2005

Reconstituted human corneal epithelium: a new alternative to the Draize eye test for the assessment of the eye irritation potential of chemicals and cosmetic products.

The aim of this study was to evaluate the interest of a new three-dimensional epithelial model cultivated from human corneal cells to replace animal testing in the assessment of eye tolerance. To this end, 65 formulated cosmetic products and 36 chemicals were tested by means of this in vitro model using a simplified toxicokinetic approach. The chemicals were selected from the ECETOC data bank and the EC/HO International validation study list. Very satisfactory results were obtained in terms of concordance with the Draize test data for the formulated cosmetic products. Moreover, the response of the corneal model appeared predictive of human ocular response clinically observed by ophthalmologists. The in vitro scores for the chemicals tested strongly correlated with their respective scores in vivo. For all the compounds tested, the response of the corneal model to irritants was similar regardless of their chemical structure, suggesting a good robustness of the prediction model proposed. We concluded that this new three-dimensional epithelial model, developed from human corneal cells, could be promising for the prediction of eye irritation induced by chemicals and complex formulated products, and that these two types of materials should be tested using a similar protocol. A simple shortening of the exposure period was required for the chemicals assumed to be more aggressively irritant to the epithelial tissues than the cosmetic formulae.

Animal Testing Alternatives↗

PubMed2004

Evaluation for reliability and feasibility of the draft protocol for the enhanced rat 28-day subacute study (OECD Guideline 407) using androgen antagonist flutamide.

As part of an international validation project to establish a test protocol for the 'Enhanced OECD Test Guideline no. 407', a 28-day repeated dose study of flutamide was performed (1) to examine which of the current and/or additional parameters can detect endocrine effects of test chemicals most reliably and sensitively, (2) to investigate whether it is actually feasible to routinely include all additional parameters into the testing routine, and (3) to assess intra-laboratory variability by performing two identical studies (experiments A and B) in parallel using groups of five animals each per dose and sex. Groups of five male and five female CD(SD)IGS rats were treated by oral gavage with 0, 1, 10 and 100 mg flutamide/kg body weight for at least 28 days. The dose level considered to be around the MTD (100 mg/kg) exerted the expected antiandrogenic effects on androgen related tissues: significant decrease of the weights of androgen dependent organs and the sperm count and increase in histopathological lesions. At the middle dose (10 mg/kg), significant decrease of prostate weight (ventral and dorso-lateral parts combined) was observed and it was suggested that weight measurement of androgen dependent organs provides the most reliable and sensitive endpoint with this protocol. As for the feasibility, because of many items in this protocol, selection should be based on the sensitivity. From our data, addition of weight measurement of androgen dependent organs to the items of the existing OECD 407 guideline might allow accurate screening for endocrine disruptors. At the dose level considered to be around the MTD, the findings achieving statistical significance in one experiment with five animals/dose/sex could be reproduced in the second experiment, and evaluation with the small groups was consistent with findings using the combined groups of 10 animals/dose/sex. The results demonstrate that the protocol can reliably detect antiandrogenic effects of flutamide.

Androgen Antagonists↗

PubMed2004

The inhibition of the high sensitive peripheral nerve soluble esterases by mipafox. A new mathematical processing for the kinetics of inhibition of esterases by organophosphorus compounds.

In the study of organophosphorus (OP) sensitive enzymes, careful discrimination of specific components within a complex multienzymatic mixture is needed. However, standard kinetic analysis gives inconsistent results (i.e., apparently different kinetic constants at different inhibitor concentration) with complex multienzymatic mixtures. A strategy is now presented to obtain consistent kinetic parameters. In the peripheral nerve, soluble carboxylesterases measured with the substrate phenylvalerate (PV) are found with extremely high sensitivity to some inhibitors. Tissue preparations were preincubated with mipafox at nanomolar concentrations (up to 100 nM) for different inhibition times (up to 180 min). Inhibition data were analyzed with model equations of one or two sensitive (exponential) components, with or without resistant components. The most complex model was %act=A1e-k1It+A2e-k2It+AR (step 1). From the curve with the highest mipafox concentration (100 nM), the amplitude for the resistant component was determined as AR=15.1% (step 2). The model equation with a fixed AR value was again applied (step 3) to deduce the second-order inhibition rate constants (k1=2.6 x 10(6) M-1 min-1 and k2=0.28 x 10(6) M-1 min-1), being conserved consistently throughout all mipafox concentrations. Finally, using fixed values of AR, k1, and k2, the amplitudes for the two exponential (sensitive) components (A1 and A2) were re-estimated (A1=50.2% and A2=34.2%). The operational process was internally validated by the close similarity with values obtained by directly fitting with a three-dimensional model equation (activity versus time and inhibitor concentration) to the same inhibition data. Carboxylesterase fractions separated by preparative chromatography showed kinetic properties consistent with the kinetically discriminated components. As practical conclusion, for routine analysis of esterases in toxicological studies, a simplified procedure using the inhibition with mipafox at 30 nM, 1 microM, and 1 mM for 30 min is suggested to discriminate the main esterase components in soluble fraction preparations.

Animals↗

PubMed2006

Development of nomogram to predict acute urinary retention or surgical intervention, with or without dutasteride therapy, in men with benign prostatic hyperplasia.

OBJECTIVES: To develop a prediction model, or nomogram, that would predict the probability that a man with benign prostatic hyperplasia would experience acute urinary retention (AUR) or require surgical intervention (SI) within 2 years, with or without dutasteride therapy. METHODS: We modeled 4294 men treated in the Phase III dutasteride benign prostatic hyperplasia trials. These men were characterized at baseline by a number of parameters, including the American Urological Association Symptom Index, Benign Prostatic Hyperplasia Impact Index questionnaire, prior use of selective alpha1-blockers, prostate volume, prostate-specific antigen level, and maximal flow rate. Cox proportional hazards regression analysis was used to relate these baseline variables to their future probability of AUR/SI within 2 years. The nomogram was internally validated with bootstrapping to assess its discrimination and calibration. Discrimination was quantified as the concordance index. RESULTS: The nomogram appeared to be accurately calibrated and discriminating (concordance index 0.71, P <0.001). CONCLUSIONS: We constructed a nomogram for predicting the probability that a man would experience AUR or require SI within 2 years of benign prostatic hyperplasia diagnosis. At 24 months of follow-up, 7.4% of placebo patients and 3.7% of dutasteride patients had experienced AUR and/or SI, representing a 50% relative risk reduction and a 3.7% absolute risk reduction. For the greatest risk patient randomized to the Phase III dutasteride trial, the nomogram predicted a maximal risk of 27%, significantly greater than the median risk of the placebo-treated patients.

Acute Disease↗

PubMed2002

Characteristics of low speed accidents with buses in public transport.

Low-speed accidents with buses in public transport in the city of Uppsala during the years 1986-2000 are coded in 17 variables concerning mainly physical properties of the accident. The taxonomy uses classifications from existing schemes, but some are altered and some new are added to capture common features of reports of bus accidents in this population. It is found that side contacts and singles are the most common accidents, and that more than a quarter of all accident involvements occurs at bus stops. Inter-rater reliability calculations for the categories show that all except one have reliabilities above 80%. The level of internal validity, calculated as agreement of frequencies between time periods, is acceptable, despite many possible sources of change and bias. It is argued that the validity of this database far exceeds that of the, for research purposes normally used, non-company self-reports, state- and police-archives, due to more extensive reporting and corroborating evidence. The practical usefulness of these results and accident taxonomies in general is discussed.

Accidents, Traffic↗

PubMed1995

Cost management in community-acquired lower respiratory tract infection.

Pharmacoeconomic analysis must determine a credible cost model, including healthcare-related, non-healthcare-related, and intangible costs, and must identify important treatment outcomes. Outcomes can be ranked in terms of their sensitivity to different treatments or weighted in terms of cost. Two recent studies of community-acquired lower respiratory tract infection have shown that inadequate treatment is a frequent cause of repeat visits to the physician's office, involving extra costs that could presumably be avoided by more effective first-line treatment. When economic data are to be incorporated into clinical trials, it is important to collect data outside as well as within the trial center and to concentrate on data likely to be of significance to the decision makers the trial is designed to influence. The best way of achieving internal validity in such trials is through randomization, which minimizes bias, chance imbalance, and confounding factors. The three major determinants of the cost-effectiveness of treatment are efficacy, the value attached to preventing treatment failure, and the accuracy of diagnosis. The latter is important because a drug can only benefit patients if they have the disease for which it is an effective treatment.

Anti-Bacterial Agents↗

PubMed1998

The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma I: characteristics of patients enrolled and not enrolled. COMS report no. 9.

PURPOSE: To describe the baseline characteristics and status of patients enrolled in the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of large choroidal melanoma conducted in the United States and Canada, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who were not enrolled in order to assess the generalizability of findings from the clinical trial. METHODS: For all patients evaluated for the clinical trial at COMS centers from November 1986 through December 15, 1994, selected data were transmitted to the COMS Coordinating Center. For patients who enrolled in the clinical trial, ophthalmic and medical history, examination findings, and visual acuity measurements were recorded prior to enrollment. Standardized A-scan and contact B-scan echographic examinations were performed prior to enrollment, and photoechograms were submitted for central review for consistency with the diagnosis, independent measurement of the apical height of the tumor, and description of tumor configuration and internal reflectivity for each patient enrolled. Until January 1992, wide-angle fundus photographs and fluorescein angiograms taken prior to enrollment also were submitted for central review to confirm consistency with the diagnosis. All data were integrated and analyzed at the COMS Coordinating Center. RESULTS: Of 6,078 patients with choroidal melanoma evaluated in COMS centers, 1,860 had tumors of eligible size; of these, 1,302 (70%) were eligible for the clinical trial, and 1,003 (77% of eligible patients) enrolled. The two principal reasons for ineligibility were other primary cancer and predominantly ciliary body melanoma. Ineligible patients were older than eligible patients, had larger choroidal melanoma, and had poorer visual acuity at the time of evaluation for the COMS (P < .01, Wilcoxon rank sum tests). Patients eligible for the clinical trial had a mean age of 60 years; 56% were male; almost all (97%) were non-Hispanic whites. Among eligible patients, mean tumor apical height was 9.5 mm and mean longest basal diameter was 17.2 mm. Eligible patients who enrolled in the trial were similar to eligible patients who did not enroll with respect to most factors considered. Those who enrolled had longer tumor basal diameter and better visual acuity in the fellow eye, more often had their primary residence in Canada, and less often had education beyond high school than did eligible patients who did not enroll (P < .05, Wilcoxon rank sum tests and chi2 tests, respectively). CONCLUSIONS: The COMS clinical trial of pre-enucleation radiation was designed to yield internally valid treatment comparisons through random treatment assignment at time of enrollment. Findings also have high external validity because a majority (54%) of all patients with tumors of eligible size, and a large majority (77%) of all eligible patients, were enrolled. Furthermore, patient characteristics are similar to those of patients included in other evaluations of this method of treating large choroidal melanoma. Thus, findings from this clinical trial apply to all patients who have large choroidal melanoma and satisfy COMS eligibility criteria.

Adult↗

PubMed2001

Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases.

BACKGROUND: A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown. METHODS: Systemic plasma MMP levels were measured in patients (n = 28, 63 +/- 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay. RESULTS: The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis. CONCLUSIONS: A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.

Aged↗

PubMed1996

Functional outcome measures to assess interventions for spasticity.

PURPOSE: Clinicians use functional loss as a criterion to treat spasticity, but the connection between function and severity of spasticity is not well established for monitoring spasticity treatment effect. Studies were reviewed which have implemented outcome measures to assess functional changes relative to changes in spasticity. Criteria for review included the reliability and internal validity of the functional measures used and the strengths/weaknesses of the study designs that likely affected the external validity of the measures for this application. Guidelines are provided for the use and development of functional outcome measures in futures studies of spasticity treatment based on this review. DATA IDENTIFICATION: An English-language literature search using MEDLINE and bibliographies of published articles and textbooks was conducted. RESULTS: Very few functional measures demonstrated changes concurrent to a reduction in spasticity. There were multiple potential confounding factors in study protocols, reporting of results, and data analysis that might account for the limited number of measures shown to be valid for this application. Selected standardized ordinal functional outcome scales (the PECS and PEDI) and specific functional tasks were identified as measures that show promise for assessing changes concurrent with altered spasticity level. CONCLUSION: Based on a review of previous studies, functional measures involving posture, positioning, balance, and certain mobility skills have potential, with further test development, to provide needed information regarding the impact of spasticity on functional outcome.

Disability Evaluation↗

PubMed2000

Methodological issues in developing new acute treatments for patients with bipolar illness.

One important aim of the recent reorganization of the National Institute of Mental Health (NIMH) is to streamline the development of new treatments for patients with severe mental illnesses, such as bipolar disorder. Researching new treatments for patients with bipolar disorder presents specific problems not readily addressed by traditional efficacy trial methodologies that aim to maximize internal validity. This article reexamines several assumptions that have guided the design of these efficacy trials but that also create obstacles for studies of bipolar disorder and suggests potential solutions. This article draws on literature from neurology and psychiatry and discussions at a MacArthur Foundation-sponsored Conference on Longitudinal Methodology in 1992 (David J. Kupfer, M.D., Chair), which brought together investigators to consider alternative designs for patients with severe and persistent mental illness. In addition, we benefited from discussions at two NIMH-sponsored conferences, one held in 1989 (Prien and Potter 1990) and the other in 1994 (Prien and Rush 1996), at which investigators and methodologists discussed issues surrounding the development and conduct of informative efficacy trials for patients with bipolar disorder. Based on these discussions and recent literature reviews, we 1) outline common problems in the development and evaluation of effective acute treatments for bipolar disorder and 2) suggest possible solutions to these impediments. We also discuss alternative designs by which to build a sequence of acute treatment studies from which efficacy, safety, and the comparative value of different treatments can be established.

Acute Disease↗

PubMed2002

Biphasic versus triphasic oral contraceptives for contraception.

Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic oral contraceptive pills compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We examined this potential disadvantage by conducting a systematic review comparing biphasic oral contraceptives with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation because of side effects. We included randomized, controlled trials comparing any biphasic oral contraceptive with any triphasic oral contraceptive when used to prevent pregnancy. Only two trials of limited quality met our inclusion criteria. Larranaga compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation because of medical problems was similar with all three pills. Percival-Smith compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important that the phasic regimen in determining bleeding patterns.

Contraception↗

PubMedDate not supplied

[Distinction, limits and complementarity between efficacy and effectiveness studies: new perspectives for psychotherapy research].

Perron et al. (2004) criticize the collective expertise conducted by the INSERM on the efficacy of different psychotherapy methods for different mental disorders. They say the work is biased in favour of Cognitive and Behavioral Therapies (CBT), while there is a negative bias regarding other methods, in particular psychodynamic therapies. Philippe Cialdella, a specialist of methodology and quantitative analysis in psychiatry, exposes an counter-argument in 10 points and brings welcome clarifications on the methodology and statistics. There is neither statistical bias in the INSERM report (which anyway is not a meta-analysis, but a literature analysis), nor in the first or second level studies on which it is based, mainly Randomised Controlled Trials (RCT). Though some arguments of P. Cialdella could be discussed in detail, his work comes to the conclusion that we can thus trust the results of the INSERM on one point: positive results can be obtained by psychotherapy with the experimental patients involved in the RCTs, and these findings are reliable. This is an important result in favour of psychotherapy, but it does not answer a very fundamental question: do we have reliable evidence that there is no systematic difference between the population constituted of patient-treatment-therapist (as a whole) found in RCTs, and the population constituted of patient-treatment-therapist (as a whole) in real contexts? A detailed analysis of what are efficacy studies and their methodology shows that this is not the case, and that it is hence not possible to generalize the results obtained by RCTs to clinical practice in real situations. Comorbidities and complex pathologies, choice of the therapist by the patient, interpersonal factors, conditions of use of manuals, contextual and social parameters, amongst other parameters make the real situation radically different from the RCT one, and the results impossible to generalize. Effectiveness studies in real situations do not solve the problem either. They have low internal validity, and though the population studied is close to a real one, too many uncontrolled parameters make the results unreliable. Moreover, outcome studies, whether they are efficacy or effectiveness studies, generally test a therapy "as a whole" versus another one, as defined in a manual, or by psychotherapy "trademarks". This design totally fails to offer a detailed view of what really happens during the therapy between the patient and the therapist, and it gives no possible insights into the change process elements. Only clinically highly representative quasi-experimental prospective studies can help us to understand change processes in real situations and incrementally improve treatment procedures. Daniel B. Fishman in the year 2000 made an ambitious and really interesting proposal about using pragmatic case studies in a systematic and scientific manner. Numerous reliable methodological tools, such as the Psychotherapy Process Q-Sort for example, as well as the tremendous innovations made in information and communication technologies make it possible today to implement such a proposal. It will enable us to really compare the resulting differences between the different approaches used in clinical settings, in relations with the type of intervention carried or in the real therapies, during clinically significant periods of time, and with various and ecologically valid samples. This is a possible solution to the difficult question of the use of outcome research to improve psychotherapy practice.

Cognitive Behavioral Therapy↗

PubMed2003

A single-degree-of-freedom dynamic model predicts the range of human responses to impulsive forces produced by power hand tools.

The human operator is modelled as a single-degree-of-freedom dynamic mechanical system for predicting the response to impulsive torque reaction forces produced by rotating spindle power hand tools such as nutrunners or screwdrivers. The model uses mass, spring and damping elements to represent the standing operator supporting the tool in the hand. It was hypothesized that these mechanical elements are affected by work location and vary among individuals. These elements were ascertained by measuring the resulting frequency and amplitude of a freely oscillating defined mechanical system when externally loaded using maximal effort to oppose its motion. Twenty-five subjects (13 female, 12 male) participated in the full factorial experiment that measured the effects of gender, vertical and horizontal work location for various tool shapes (in-line, pistol, right angle), and orientations (horizontal and vertical). The mean operator stiffness decreased from 1721 to 1195 N/m when the horizontal work location increased from 30 to 90 cm in front of the ankles for a pistol-grip handle used on a vertical surface. Males had greater mass moment of inertia of (0.0099 kg m2) than females (0.0072 kg m2) for an in-line handle used on a horizontal surface. Internal validation by independently measuring apparatus torque found that the model satisfactorily explained the measured operator dynamics with an average error of 2.86%. Group variance reflects the range of operator capacities to react against power hand tool generated forces for the sample group and therefore it may also be useful for understanding the range of capacities among a group of operators performing similar tasks.

Adult↗

PubMedDate not supplied

Issues in conducting intervention research in long-term care settings.

Originally we proposed a straightforward experimental design using quantitative data to test a series of hypotheses about how changes in the mealtime context and mealtime interactions would influence self-feeding behaviors and imposed disability. The design was clean and the interventions carefully delineated. We used a number of strategies for reducing threats to internal validity, some of which worked and some of which did not. Many of the problems we encountered in operationalizing this clinical experiment arose, not from the particular environment in which we worked, but from the nature of long-term care settings and the staffing patterns within those settings. To some degree, the problems we encountered are inherent to field experimentation in nursing in general. Often field experiments are reported as if no problems arose in implementation, yet no study is problem free. We believe acknowledging and understanding some of the sources of field noise in field experiments are almost as important as understanding the results of the study itself. The field noise is an indispensable part of the results.

Aged↗

PubMed2000

A clinical prediction rule for nerve-function impairment in leprosy patients.

BACKGROUND: Nerve-function impairment (NFI) commonly occurs during or after chemotherapy in leprosy and is the key pathological process leading to disability and handicap. We describe the development of a simple clinical prediction rule for estimating the risk of NFI occurrence. METHODS: New leprosy cases who presented to a centre in Bangladesh were recruited and followed up for 2 years in a field setting. We used multivariable regression analysis by Cox's proportional hazards model to identify predictive variables for NFI. Discriminative ability was measured by a concordance statistic. Internal validity was assessed with bootstrap resampling techniques. FINDINGS: 2510 patients were followed up for 2 years, 166 developed NFI. A simple model was developed with leprosy group (either paucibacillary leprosy [PB] or multibacillary leprosy [MB]) and the presence of any nerve-function loss at registration as predictive variables. Patients with PB leprosy and no nerve-function loss had a 1.3% (95% CI 0.8-1.8%) risk of developing NFI within 2 years of registration; patients with PB leprosy and nerve-function loss, or patients with MB leprosy and no nerve-function loss had a 16.0% (12-20%) risk; and patients with MB leprosy with nerve-function loss had a 65% (56-73%) risk. INTERPRETATION: Our prediction rule can be used to plan surveillance of new leprosy patients. Patients at low risk of NFI may need no follow-up beyond their course of chemotherapy (6 months); patients with intermediate risk need a minimum of 1 year of surveillance; and patients with high risk should have at least 2 years of surveillance for new NFI. Current recommendations for surveillance of patients with leprosy (for the duration of chemotherapy only) exclude an important group of patients who are at risk of developing NFI after completion of treatment.

Adolescent↗

PubMedDate not supplied

The future of pharmacoeconomics: bridging science and practice.

In the context of new challenges, issues facing the science, practice, and future of pharmacoeconomics will be discussed. Certain methodologic weaknesses have been observed in published pharmacoeconomic studies, and compromises need to be made between developing an "ideal" method and allowing a study to remain practicable. The objective is to reach a balance between clinical trial-based studies and projective models; trials have high internal validity but low external validity, while models can help explore relevance to real-life settings. Cross-national differences also have an important impact on pharmacoeconomic data; however, using some basic standardized guidelines results from pharmacoeconomic studies may be generalized to other settings. The use of pharmacoeconomic results by decision makers in the United Kingdom has been restrained by unclear priorities within their authority and by the limited availability of credible studies. The future of pharmacoeconomics lies in developing both trial-based and modeling studies, improving their credibility, and meeting the needs of decision makers.

Clinical Trials as Topic↗