Quantitative prediction and clinical evaluation of an unexplored herb-drug interaction mechanism in healthy volunteers.

Quantitative prediction of herb-drug interaction risk remains challenging. A quantitative framework to assess a potential interaction was used to evaluate a mechanism not previously tested in humans. The semipurified milk thistle product, silibinin, was selected as an exemplar herbal product inhibitor of raloxifene intestinal glucuronidation. Physiologically based pharmacokinetic (PBPK) model simulations of the silibinin-raloxifene interaction predicted up to 30% increases in raloxifene area under the curve (AUC0-inf) and maximal concentration (Cmax). Model-informed clinical evaluation of the silibinin-raloxifene interaction indicated minimal clinical interaction liability, with observed geometric mean raloxifene AUC0-inf and Cmax ratios lying within the predefined no effect range (0.75-1.33). Further refinement of PBPK modeling and simulation approaches will enhance confidence in predictions and facilitate generalizability to additional herb-drug combinations. This quantitative framework can be used to develop guidances to evaluate potential herb-drug interactions prospectively, providing evidenced-based information about the risk or safety of these interactions.

Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: methods and findings to date.

PURPOSE: To describe baseline and longitudinal findings of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. METHODS: The CLEK Study is an 8-year, multi-center, natural history study of 1209 patients with keratoconus who were examined annually for 8 years. Its goals are to prospectively characterize changes in vision, corneal curvature, corneal status, and vision-specific quality of life. RESULTS: CLEK Study subjects had a mean age at baseline of 39.3+/-10.9 years. At study entry, 65% of the patients wore rigid contact lenses, and 14% reported a family history of the disease. Subjects exhibited a 7-year decrease in high- (2.03 letters) and low- (4.06 letters) contrast, best-corrected visual acuity, with 19% demonstrating decreases of 10 or more letters in high-contrast, best-corrected acuity and 31% of subjects demonstrating decreases of 10 or more letters in low-contrast, best-corrected acuity in at least one eye. Subjects exhibited an average 8-year increase in corneal curvature of 1.60D in the flat corneal meridian, with 24% demonstrating increases of 3.00D or more. The 8-year incidence of corneal scarring was 20%, with younger age, corneal staining, steeper baseline corneal curvature, contact lens wear, and poorer low-contrast visual acuity predictive of corneal scarring. Data from the National Eye Institute Visual Function Questionnaire suggest that the effect of keratoconus on vision-specific quality of life is disproportionate to its low prevalence and clinical severity. CONCLUSION: Although we report measures of disease severity and visual function across the CLEK sample, clinicians can begin to envisage the course of keratoconus in individual patients by determining whether factors predictive of disease progression are present in those patients.

A summary of the findings from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. CLEK Study Group.

BACKGROUND: This summary of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study includes the study design and results to date. METHODS: The CLEK Study is a longitudinal, observational study of 1,209 patients with keratoconus. The study's main outcome measures are corneal scarring, visual acuity, corneal curvature, and quality of life. RESULTS: These patients' mean age at baseline was 39.3 +/- 10.9 years, and they had moderate to severe keratoconus. Ninety-five percent of the patients had steep keratometric readings of at least 45 D, and 78% had best-corrected visual acuity of 20/40 or better in both eyes. Sixty-five percent of the patients wore rigid gas-permeable contact lenses in both eyes, and most of those (73%) reported that their lenses were comfortable. Most rigid gas-permeable contact lens wearers were fitted with apical touch (88%). Fifty-three percent had corneal scarring in one or both eyes, and corneal scarring was associated with corneal staining, contact lens wear, age, the presence of a Fleischer's ring, and a steeper cornea. Corneal scarring was associated with decreased high- and low-contrast visual acuity. CONCLUSIONS: These results characterize keratoconus patients as rigid gas-permeable contact lens wearers with moderately steep corneas. Corneal scarring is associated with decreased vision in keratoconus.

A comparison of two methods of evaluating cornea-to-contact lens base curve fluorescein patterns in keratoconus.

PURPOSE: The purposes of the study were as follows: (1) to compare the apical fitting relationship of habitual contact lens fluorescein patterns in keratoconus as determined by clinician assessment of on-eye patterns to those determined by photograph readers looking at slides of fluorescein patterns and (2) to determine the validity of the techniques used in assessing the apical fitting relationships of rigid corneal contact lenses on keratoconic corneas. METHODS: Central fluorescein patterns of rigid contact lens-wearing keratoconus patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were graded as "definite touch," "touch," "clearance," or "definite clearance" by certified clinicians. Photographs of these patterns were evaluated independently by certified, masked photograph readers using the same grading scale. RESULTS: Agreement between "re-reads" of the same fluorescein pattern slides by the photograph readers was substantial (weighted kappa = 0.751). Agreement between assessments of habitual fit fluorescein patterns at the baseline vs. the repeat visits was poor for the photograph readers (weighted kappa = 0.254) and moderate for the clinicians (kappa = 0.480). Agreement between clinicians' and photograph readers' assessment of the habitual contact lens fluorescein pattern at the baseline visit was fair (weighted kappa = 0.382). CONCLUSIONS: Repeatability and validity of this technique were fair to excellent. Many factors influence fluorescein pattern interpretation, and improvement of the objective method of fluorescein pattern assessment by photograph readers will require improved methodology that takes these factors into consideration.

Therapeutic drug monitoring: do the improved outcomes justify the costs?

In the 30 years that therapeutic drug monitoring (TDM) has moved from an abstract consideration to a routine intervention, issues remain over justifying the benefits in the light of the ever-increasing competition for budgetary resources. Resolving the issues is constrained by various methodological concerns. These include considerations such as: (i) the changed environment of knowledge and practice during the generation in which TDM has been used and evaluated; (ii) the predominance of studies using system-related rather than patient-centred outcomes; (iii) using a timeframe for analysis that is too short; (iv) a lack of rigour in many of the pharmacoeconomic analyses; and (v) excessive use of a site-specific rather than a societal perspective. Current observation suggests that the greatest benefit of TDM accrues from targeted or specialty populations: those with severely decompensated renal function, those at the extremes of age, and those using immunosuppressive, some antineoplastic, some psychotherapeutic and some anticonvulsant drugs. In these situations, safe and humane practice considers TDM a necessity without respect to cost. But for many routine situations with drugs for which TDM has commonly been used in the past, present reliance on the intervention may have become excessive in the light of today's knowledge base of practitioners.

Linking variation in the structure and process of bedside glucose testing programs with patient outcomes.

OBJECTIVE: The objective of this study was to determine if variation in compliance to standards listed in Ancillary (Bedside) Blood Glucose Testing in Acute and Chronic Care Facilities (ABBGT) was linked to variation in patient outcomes. DESIGN AND SETTING: A retrospective analysis examined 450 hospitalized patients with a diagnosis of diabetes from three hospitals with high, medium, and low assessment scores for compliance with ABBGT guidelines. Patients with a diagnosis of diabetes without surgical interventions or intensive care unit stays were selected for the study. MAIN OUTCOMES MEASURED: percent bedside glucose tests that were out of normal range and length of stay. RESULTS: Compliance with ABBGT guidelines explained the variation for out of range bedside glucose tests---1.4% and length CONCLUSION: Within a narrow range and high level of compliance with ABBGT guidelines, the compliance scores had a small effect upon the selected outcomes. The hypothesis that following ABBGT guidelines improves patient outcomes was neither proven nor disproven with this study.

Corneal scarring and vision in keratoconus: a baseline report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the correlation of corneal scarring with clinical and patient-reported variables at the baseline visit. METHODS: Patients completed a questionnaire on their vision, effect of glare, contact lens wear, and work-related issues. Clinical examination included high- and low-contrast visual acuity, refraction, assessment of corneal scarring by the clinician and by photography, and measurement of corneal curvature. The correlation of central corneal scarring with visual acuity and patient-reported variables was analyzed using multiple regression analysis and generalized estimating equations. RESULTS: High- and low-contrast visual acuity with habitual and optimal correction is reduced in scarred eyes. Multiple regression analyses controlling for age, contact lens wear, and disease severity show that central scarring is associated with poorer visual acuity and increased patient-reported symptoms of glare. Restrictions on day-to-day activities do not appear to be associated with corneal scarring above and beyond the effects of keratoconus alone. CONCLUSIONS: Corneal scarring in keratoconus is significantly associated with decreased high- and low-contrast visual acuity.

American translation, modification, and validation of the St. George's Respiratory Questionnaire.

BACKGROUND: The St. George's Respiratory Questionnaire (SGRQ) is a 50-item health status survey specific for chronic obstructive pulmonary disease (COPD) and other respiratory diseases that is available in British English but not American English. The SGRQ's symptom-reporting component requires a 1-year reporting period, which may be too long for reliable and accurate patient recall. OBJECTIVES: The objectives of the present study were to translate the SGRQ from British to American English, modify the reporting period of the symptom-reporting component from 1 year to 1 month, and assess the reliability, validity, and sensitivity to change of this translated modified version in a sample of patients with COPD. METHODS: Based on input from American patients with COPD and health professionals, the SGRQ was translated into American English (SGRQ-A) and then translated back to British English. For SGRQ-A reliability and validity studies, patients were asked to report symptoms experienced over 1 year (reporting period in the original SGRQ) and 1 month (modification made to SGRQ-A). We evaluated 102 patients with COPD (50% female; mean age, 68 years; mean forced expiratory volume in 1 second [FEV1], 1.01 L) at an administrative session before and after completion of a pulmonary rehabilitation program. The SGRQ-A, Chronic Respiratory Disease Questionnaire (CRQ), 36-Item Short Form Health Survey (SF-36), 6-minute walk (6MW), Medical Research Council (MRC) Dyspnea scale, and pulmonary function tests (FEV1 and % predicted FEV1) were used in the assessment battery. RESULTS: The SGRQ-A showed good agreement with the original SGRQ when translated back to British English. Internal reliability (Cronbach alpha) was > 0.70 for all SGRQ-A components except the 1-year symptom-reporting component. Test-retest intraclass correlations were 0.795 to 0.900. Construct validity was strengthened when all SGRQ-A components (except 1-year symptoms and most 1-month symptoms) correlated (P < or = 0.01) with the MRC Dyspnea scale, 6MW, all SF-36 concept scores, and 80% of CRQ domains (r = 0.30-0.72). Discriminate validity was demonstrated when all components of the SGRQ-A with the modified 1-month symptom-reporting period were shown to discriminate better between disease-severity groups (based on patient self-reports of disease severity) than did pulmonary function tests and the 6MW. Responsiveness of the SGRQ-A to change in health status was demonstrated when scores on the Symptoms-1 month and Total-1 month components detected significant improvements in patients' health status (P = 0.02 and P = 0.04, respectively). CONCLUSION: The SGRQ-A with a modified 1-month symptom-reporting period demonstrated reliability and validity in this sample of patients with COPD. Key words: chronic obstructive pulmonary disease, St. George's Respiratory Questionnaire, American translation, reliability, validity, symptom recall.

Factors associated with corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the factors associated with corneal scarring at baseline. METHODS: We defined corneal scarring as scars that had been detected both by the clinician examining the patient with the slit-lamp biomicroscope and by masked readers of corneal photographs at the CLEK Photography Reading Center. We investigated associations between corneal scarring and patient variables including gender, ethnicity, a family history of keratoconus, a history of ocular trauma, eye rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal findings (such as curvature, Vogt's striae, Fleischer's ring, and central/apical staining). Multiple logistic regression analysis using generalized estimating equations to adjust for the correlation between eyes was used for analysis. RESULTS: The following factors were found to increase the odds of corneal scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) = 3.40, 95% confidence interval 2.53-4.59), contact lens wear (OR = 3.51, 95% confidence interval 2.27-5.45), Fleischer's ring (OR = 1.63, 95% confidence interval 1.11-2.40), steeper first definite apical clearance lens base curve radius (per diopter, OR = 1.29, 95% confidence interval 1.25-1.33), and age (per decade, OR = 1.54, 95% confidence interval 1.35-1.75). CONCLUSIONS: These baseline data suggest that corneal scarring in keratoconus is associated with corneal staining, contact lens wear, Fleischer's ring, a steeper cornea, and increasing age. The factors that imply added risk for corneal scarring that may be affected by practitioner intervention are staining of the cornea, contact lens wear, and the contact lens fitting relationship.

Overnight orthokeratology.

PURPOSE: Orthokeratology is defined as the temporary reduction in myopia by the programmed application of rigid gas-permeable contact lenses. New reverse geometry contact lens designs and materials have led to a renewed interest in this field. The purpose of this study is to assess visual, refractive, topographic, and corneal thickness changes in subjects undergoing overnight orthokeratology. METHODS: Ten myopic subjects (mean age, 25.9+/-3.9 years) were recruited for a 60-day trial of overnight orthokeratology using reverse geometry rigid contact lenses. After commencing lens wear, subjects were examined on days 1, 7, 14, 30, and 60 at several times throughout the day. High- and low-contrast logarithm of the minimum angle of resolution (logMAR) visual acuity, monocular subjective refraction, autorefraction, autokeratometry, corneal topography, corneal thickness, and slit lamp examinations were performed at each session. RESULTS: Eight subjects completed the study. Both high- and low-contrast uncorrected visual acuity improved significantly by day 7. The mean change in uncorrected high contrast visual acuity at day 60 was -0.55+/-0.20 logMAR (mean at day 60, -0.03+/-0.16; Snellen equivalent, 20/19). The mean change in uncorrected low-contrast visual acuity at day 60 was -0.48+/-0.26 logMAR (mean at day 60, +0.22+/-0.23; Snellen equivalent, 20/33). The mean subjective refraction and autorefraction were significantly reduced from baseline at day 60 (mean change in subjective refraction, +1.83+/-1.23 D; mean change in autorefraction, +0.64+/-0.52 D). Corneal topography showed significant central flattening (mean change in apical radius, +0.20+/-0.9 mm; mean change in shape factor, -0.11+/-0.18 at day 60). The central cornea also showed significant thinning (mean change, -12+/-11 microm at day 60). All visual, refractive, and topographic outcomes were sustained over the course of an 8-h day. CONCLUSIONS: Overnight orthokeratology is an effective means of temporarily reducing myopia. The possible mechanism of corneal remodeling through central corneal thinning is discussed.

Rigid contact lens fitting relationships in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group.

PURPOSE: Although the influence of flat-fitting contact lenses on corneal scarring in keratoconus is frequently debated, the current standard of care with regard to the apical fitting relationship in keratoconus remains undocumented. METHODS: Patients were examined at baseline in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study (N = 1209). Patients wearing a rigid contact lens in one or both eyes (N = 808) had their habitual rigid contact lenses analyzed, and the fluorescein patterns and base curves were compared to the first definite apical clearance lens (FDACL). The FDACL is the flattest lens in the CLEK Study trial lens set that exhibits an apical clearance fluorescein pattern. For patients wearing a rigid contact lens in both eyes, one eye was selected randomly for analysis. RESULTS: Twelve percent of the rigid contact lens-wearing eyes were wearing lenses fitted with apical clearance based upon the clinician's fluorescein pattern interpretation. The remainder (88%) was wearing lenses fitted with apical touch. For mild (steep keratometric reading <45 D) keratoconus corneas, the mean estimate of the base curve to cornea-fitting relationship was 1.18 D flat (SD +/- 1.84 D); moderate (steep keratometric reading: 45 to 52 D) corneas were fitted on average 2.38 D flat (SD +/- 2.56 D); and severe (steep keratometric reading > 52 D) corneas were fitted an average of 4.01 D flat (SD +/- 4.11 D). CONCLUSIONS: Despite the potential risk for corneal scarring imposed by flat-fitting rigid contact lenses, most CLEK Study patients wear flat-fitting lenses. Overall, rigid lenses were fitted an average of 2.86 D (SD +/- 3.31 D) flatter than the FDACL.

Corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: baseline prevalence and repeatability of detection.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the prevalence of corneal scarring in these patients. We also report on the test-retest repeatability of corneal scar documentation at the slit-lamp biomicroscope by trained clinicians and by masked photograph readers and on the scarring-status agreement at baseline between clinicians and photograph readers. METHODS: Clinicians and masked photograph readers graded each cornea as to scarring status. Patients were examined by clinicians, and their corneas were photographed at baseline (2,297 nongrafted eyes of 1,209 patients) and at a repeated visit (258 nongrafted eyes of 138 patients). These photographs were evaluated by the masked readers at the CLEK Photography Reading Center (CPRC). Clinicians reported corneal scars in right eyes at baseline as "definitely not present" in 53.9%, "probably not present" in 8.4%, "probably present" in 8.2%, and "definitely present" in 29.4% of patients. A weighted kappa statistic of 0.83 (95% confidence interval from 0.78 to 0.88) indicates that agreement is excellent between baseline and repeated assessments for the presence of a corneal scar by clinicians. RESULTS: Agreement is very good between baseline and repeated photograph-reader assessments for the presence of a scar, with a weighted kappa of 0.77 (95% confidence interval, 0.72-0.82). The kappa statistic comparing photograph-reader scarring assessments with clinician results was 0.69 (95% confidence interval, 0.66-0.71). CONCLUSION: The data also suggest better agreement between clinicians and readers when Vogt's striae and corneal nerves were observed. The data also suggest better agreement when corneal staining was not observed by the photograph readers. The CLEK Study protocol for determining the presence of scars is highly repeatable.

Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: To describe the baseline findings in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. METHODS: This is a longitudinal observational study of 1209 patients with keratoconus enrolled at 16 clinical centers. Its main outcome measures are corneal scarring, visual acuity, keratometry, and quality of life. RESULTS: The CLEK Study patients had a mean age of 39.29+/-10.90 years with moderate to severe disease, assessed by a keratometric-based criterion (95.4% of patients had steep keratometric readings of at least 45 D) and relatively good visual acuity (77.9% had best corrected visual acuity of at least 20/40 in both eyes). Sixty-five percent of the patients wore rigid gas-permeable contact lens, and most of those (73%) reported that their lenses were comfortable. Only 13.5% of patients reported a family history of keratoconus. None reported serious systemic diseases that had been previously reported to be associated with keratoconus. Many (53%) reported a history of atopy. Fifty-three percent had corneal scarring in one or both eyes. CONCLUSIONS: Baseline findings suggest that keratoconus is not associated with increased risk of connective tissue disease and that most patients in the CLEK Study sample represent mild to moderate keratoconus. Additional follow-up of at least 3 years will provide new information about the progression of keratoconus, identify factors associated with progression, and assess its impact on quality of life.

Effect of topical anesthetic use on initial patient satisfaction and overall success with rigid gas permeable contact lenses.

BACKGROUND: Rigid gas permeable (RGP) contact lenses have numerous benefits; however, RGP lens use is not increasing in the United States. An important factor for this trend has been initial comfort. Studies have demonstrated that how RGPs are presented to patients, in addition to lens design, can play an important role in the initial comfort process. Another important factor could be the use of a topical anesthetic during the fitting and dispensing visits. The purpose of this study was to use a multicenter format to determine if topical anesthetic use increased the likelihood of patient satisfaction and success. METHODS: A total of 80 subjects, with no previous rigid lens wear experience, was entered into this 1-month study, including 20 subjects from each of 4 institutions. Subjects were randomly divided into the following two groups: (A) anesthetic or (B) placebo, with the former group receiving one drop of a topical anesthetic before lens insertion at both the diagnostic fitting and dispensing visits, whereas the latter group received a placebo. Subjects completed a questionnaire on their perception of rigid lens wear both immediately before fitting and at the 1-month visit. After diagnostic fitting with rigid lenses, subjects completed an adaptation questionnaire after 15 min, 1 week, 2 weeks, and 1 month of lens wear. RESULTS: Seventy of the 80 subjects completed the study and, of the 10 subjects who discontinued, 8 were in the placebo group. In all categories evaluated, the anesthetic group experienced a more optimum adaptation experience at each visit vs. the placebo group. Specifically, overall comfort was rated significantly higher at both dispensing and 2 weeks. In addition, the anesthetic group exhibited significantly greater overall satisfaction with rigid lens wear at 2 and 4 weeks. Also, the anesthetic group perceived their adaptation, sensitivity, and adaptation time to be significantly better at the 1-month visit. There was no significant difference in corneal staining between these two groups at each visit, with the exception of a greater amount of staining in the central quadrant for the placebo group at the 1-month visit. CONCLUSIONS: The use of a topical anesthetic at the fitting and dispensing visits for first-time wearers of RGP lenses resulted in significantly fewer dropouts, improved initial comfort, an enhanced perception of the adaptation process, and greater overall satisfaction after 1 month of lens wear as compared to the use of a nonanesthetizing placebo at those visits. This result, in combination with both presenting RGP lenses in a nonthreatening manner and optimizing the lens design and fitting relationship, should result in a positive adaptation process and successful wear of RGP contact lenses.

Economic and outcome issues for therapeutic drug monitoring in medicine.

Outcome and economic studies pertaining to the use of therapeutic drug monitoring (TDM) are summarized. The studies were classified by a 2 x 2 matrix comprised of process, outcome, system-related variables, and patient-centered variables. Two hundred forty-seven studies conducted from 1974 to 1994, culled from eight summary sources, were reviewed. Almost 75% of the studies reported system-related, not patient-centered, measures for assessing the value of TDM; nearly the same percentage evaluated processes as opposed to outcome measures. Studies comparing TDM to non-TDM populations generally showed that TDM as an intervention reduced the rate of undesirable system-related variables by 50% and increased the rate of desirable system-related variables by 100%. For patient-centered variables, TDM was less dramatic, decreasing the rate of undesirable variables by 15% to 50%. Only 8% of the studies examined economic variables. TDM-influenced changes in process variables resulted in a projected mean annual savings of $37,000. The few studies available of cost-benefit analysis focused on aminoglycosides and showed that TDM yielded a range from 4:1 to 52:1 in benefit-to-cost ratio. Most studies have limitations that include small sample size, short study periods to predict long-term outcomes, no long-term follow-up, and designs for noncontrolled study.

Repeatability and agreement of two corneal-curvature assessments in keratoconus: keratometry and the first definite apical clearance lens (FDACL). CLEK Study Group. Collaborative Longitudinal Evaluation of Keratoconus.

PURPOSE: This study was conducted to determine the agreement and test-retest repeatability of two methods for measuring corneal curvature in keratoconus: keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in the FDACL procedure stems from the important contact lens-fitting information and documentation of disease progression provided by the FDACL trial lenses and observation of fluorescein patterns. METHODS: The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is an observational study that has enrolled 1,209 keratoconus patients to characterize the progression of keratoconus, to determine factors associated with its progression, and to assess its impact on quality of life. Ten percent of the patients were randomly selected at baseline for a retest examination. The baseline examination, which included keratometry and FDACL, was repeated in this sample. The FDACL is the flattest lens in the standardized CLEK trial lens set that vaults the apex of the cone. FDACL provides an estimate of the sagittal height of the cone. RESULTS: The correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001) and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest repeatability as measured by the intraclass correlation coefficient (ICC) was high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high in advanced disease. CONCLUSION: FDACL provides a repeatable new procedure for determining disease severity in keratoconus.

Total testing process applied to therapeutic drug monitoring: impact on patients' outcomes and economics.

The Total Testing Process (TTP) refers to the sequence of 11 steps of laboratory testing, beginning with a clinical question prompted by the patient-clinician encounter and concluding with the impact of the test result on patient care. TTP when applied to therapeutic drug monitoring (TDM) emphasizes that TDM must be considered a process involving a series of steps and interrelated activities and not viewed simply as a numerical value for a serum drug concentration. TTP is also an ideal format for organizing and identifying the system-related and patient-centered variables used in outcomes assessment of TDM, as well as providing a template for collecting the cost data needed for economic analyses. Examples are provided for improving application of TDM by practitioners, clinical laboratories, and educators.

Development of a quantitative weighted scoring instrument to evaluate bedside blood glucose testing programs.

The present assessment of laboratory quality is primarily a qualitative summary process. The objective of our study is to convert a qualitative standards document into a quantitative, weighted scoring system. We selected a laboratory testing standards document, Ancillary (Bedside) Blood Glucose Testing in Acute and Chronic Care Facilities, C30, developed by the National Committee for Clinical Laboratory Standards (NCCLS), as our prototype and used a two-stage, modified delphi technique. Sixty-nine criteria were identified from the C30 document. Using a two-stage, modified delphi technique, members of the NCCLS committee that developed the guideline weighted the relative importance of each criteria. This weighting system then was used to evaluate the quality of bedside glucose testing at the 14 general hospitals located within the city limits of Boston.