Comprehensive electronic medical record implementation levels not associated with 30-day all-cause readmissions within Medicare beneficiaries with heart failure.

BACKGROUND: Regulatory standards for 30-day readmissions incentivize hospitals to improve quality of care. Implementing comprehensive electronic health record systems potentially decreases readmission rates by improving medication reconciliation at discharge, demonstrating the additional benefits of inpatient EHRs beyond improved safety and decreased errors. OBJECTIVE: To compare 30-day all-cause readmission incidence rates within Medicare fee-for-service with heart failure discharged from hospitals with full implementation levels of comprehensive EHR systems versus those without. METHODS: This retrospective cohort study uses data from the American Hospital Association Health IT survey and Medicare Part A claims to measure associations between hospital EHR implementation levels and beneficiary readmissions. Multivariable Cox regressions estimate the hazard ratio of 30-day all-cause readmissions within beneficiaries discharged from hospitals implementing comprehensive EHRs versus those without, controlling for beneficiary health status and hospital organizational factors. Propensity scores are used to account for selection bias. RESULTS: The proportion of heart failure patients with 30-day all-cause readmissions was 30%, 29%, and 32% for those discharged from hospitals with full, some, and no comprehensive EHR systems. Heart failure patients discharged from hospitals with fully implemented comprehensive EHRs compared to those with no comprehensive EHR systems had equivalent 30-day readmission incidence rates (HR = 0.97, 95% CI 0.73 - 1.3). CONCLUSIONS: Implementation of comprehensive electronic health record systems does not necessarily improve a hospital's ability to decrease 30-day readmission rates. Improving the efficiency of post-acute care will require more coordination of information systems between inpatient and ambulatory providers.

HIV gp120- and methamphetamine-mediated oxidative stress induces astrocyte apoptosis via cytochrome P450 2E1.

HIV-1 glycoprotein 120 (gp120) is known to cause neurotoxicity via several mechanisms including production of proinflammatory cytokines/chemokines and oxidative stress. Likewise, drug abuse is thought to have a direct impact on the pathology of HIV-associated neuroinflammation through the induction of proinflammatory cytokines/chemokines and oxidative stress. In the present study, we demonstrate that gp120 and methamphetamine (MA) causes apoptotic cell death by inducing oxidative stress through the cytochrome P450 (CYP) and NADPH oxidase (NOX) pathways. The results showed that both MA and gp120 induced reactive oxygen species (ROS) production in concentration- and time-dependent manners. The combination of gp120 and MA also induced CYP2E1 expression at both mRNA (1.7±0.2- and 2.8±0.3-fold in SVGA and primary astrocytes, respectively) and protein (1.3±0.1-fold in SVGA and 1.4±0.03-fold in primary astrocytes) levels, suggesting the involvement of CYP2E1 in ROS production. This was further confirmed by using a selective inhibitor of CYP2E1, diallylsulfide (DAS), and CYP2E1 knockdown using siRNA, which significantly reduced ROS production (30-60%). As the CYP pathway is known to be coupled with the NOX pathway, including Fenton-Weiss-Haber (FWH) reaction, we examined whether the NOX pathway is also involved in ROS production induced by either gp120 or MA. Our results showed that selective inhibitors of NOX, diphenyleneiodonium (DPI), and FWH reaction, deferoxamine (DFO), also significantly reduced ROS production. These findings were further confirmed using specific siRNAs against NOX2 and NOX4 (NADPH oxidase family). We then showed that gp120 and MA both induced apoptosis (caspase-3 activity and DNA lesion using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay) and cell death. Furthermore, we showed that DAS, DPI, and DFO completely abolished apoptosis and cell death, suggesting the involvement of CYP and NOX pathways in ROS-mediated apoptotic cell death. In conclusion, this is the first report on the involvement of CYP and NOX pathways in gp120/MA-induced oxidative stress and apoptotic cell death in astrocytes, which has clinical implications in neurodegenerative diseases, including neuroAIDS.

Dexamethasone significantly attenuates sub-arachnoid hemorrhage-induced elevation in cerebrospinal fluid citrulline and leukocytes.

AIM: Cerebral vasospasm is a leading cause of death and disability following aneurysmal subarachnoid hemorrhage (SAH). Nitric oxide (NO) is a potent mediator of vasodilation, and citrulline is a known contributor to NO production. The leukocytosis inflammatory response can increase vasoconstrictive compounds that may also contribute to vasospasm. Dexamethasone is a glucocorticosteroid commonly administered after SAH, which may alter the production of leukocytes and citrulline. The goal of this project was to study the effects of dexamethasone on leukocytosis, citrulline, and angiographic vasospasm. METHODS: Experimental SAH was induced in 18 New Zealand white rabbits. Intravenous dexamethasone was administered to one group (N.=9) at 2 mg/kg/day. A placebo group (N.=9) was given a saline infusion with otherwise identical procedures. CSF citrulline, leukocytes, protein, and glucose, as well as plasma citrulline were measured at baseline and 3 days post-SAH in a blinded fashion. Basilar artery angiography was performed at baseline and repeated 3 days post-SAH. RESULTS: The change in CSF citrulline from day 0 to day 3 was significantly lower in the dexamethasone group compared to controls (P=0.002). The change in CSF white blood cells was also significantly lower (P=0.005). There was no significant change in plasma citrulline levels or angiographic vasospasm. CONCLUSION: Dexamethasone significantly decreases CSF citrulline and CSF leukocytosis after experimental SAH. It is possible this could lead to a relative vasoconstriction and vasodilation, respectively. These processes could cancel-out opposing effects of dexamethasone on cerebral vasospasm, partially contributing to the recognized, multifactorial, inconsistent effects of glucocorticoids on vasospasm.

Associations between the concurrent use of clinical decision support and computerized provider order entry and the rates of appropriate prescribing at discharge.

INTRODUCTION: Electronic health record systems used in conjunction with clinical decision support (CDS) or computerized provider order entry (CPOE) have shown potential in improving quality of care, yet less is known about the effects of combination use of CDS and CPOE on prescribing rates at discharge. OBJECTIVES: This study investigates the effectiveness of combination use of CDS and CPOE on appropriate drug prescribing rates at discharge for AMI or HF patients. METHODS: Combination use of CDS and CPOE is defined as hospitals self-reporting full implementation across all hospital units of CDS reminders, CDS guidelines, and CPOE. Appropriate prescribing rates of aspirin, ACEI/ARBs, or beta blockers are defined using quality measures from Hospital Compare. Multivariate linear regressions are used to test for differences in mean appropriate prescribing rates between hospitals reporting combination use of CDS and CPOE, compared to those reporting the singular use of one or the other, or the absence of both. Covariates include hospital size, region, and ownership status. RESULTS: Approximately 10% of the sample reported full implementation of both CDS and CPOE, while 7% and 17% reported full use of only CPOE or only CDS, respectively. Hospitals reporting full use of CDS only reported between 0.2% (95% CI 0.04 - 1.0) and 1.6% (95% CI 0.6 - 2.6) higher appropriate prescribing rates compared to hospitals reporting use of neither system. Rates of prescribing by hospitals reporting full use of both CPOE and CDS did not significantly differ from the control group. CONCLUSIONS: Although associations found between full implementation of CDS and appropriate prescribing rates suggest that clinical decision tools are sufficient compared to basic EHR systems in improving prescribing at discharge, the modest differences raise doubt about the clinical relevance of the findings. Future studies need to continue investigating the causal nature and clinical relevance of these associations.

Activity of fulvestrant in HER2-overexpressing advanced breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression increases the aggressiveness of breast cancer cells resulting in poorer prognosis. Patients with HER2-positive disease are less responsive to endocrine therapies. Trastuzumab monotherapy results in objective responses in only approximately 15% of patients. Fulvestrant retains activity in cells overexpressing HER2 that are resistant to other endocrine treatments. This retrospective study evaluated response to fulvestrant treatment among HER2-positive patients with advanced breast cancer (ABC). PATIENTS AND METHODS: Clinical experience data from 10 treatment centres were pooled. Postmenopausal patients with predominantly hormone receptor-positive and HER2-positive disease were included. Clinical benefit (CB) was defined as the proportion of patients achieving a response to treatment (partial or complete) or stable disease lasting >/=6 months. RESULTS: Data for 102 patients were analysed. Fulvestrant resulted in an overall CB rate of 42% (43/101) in HER2-positive patients and 40% (25/63) in patients with visceral disease. Median duration of treatment was 14.5 months (range 6-44 months). Fulvestrant showed activity up to the fourth line of endocrine therapy and up to the seventh line of overall therapy. CONCLUSIONS: Results indicate that fulvestrant may be a suitable treatment option in extensively pre-treated patients with HER2-positive, hormone receptor-positive ABC. Further exploration of its use in this patient population is warranted.

Resolution of trigeminal neuralgia after palliative embolization of a cerebellopontine angle arteriovenous malformation.

BACKGROUND: Trigeminal neuralgia (TN) is a syndrome with debilitating paroxysmal facial pain, one cause of which is thought to be vascular compression of the nerve root entry zone causing ephaptic transmission. Arteriovenous malformations (AVM) have been reported to cause TN, including AVMs in the cerebellopontine (CP) angle. These lesions have been successfully treated with endovascular coiling, ethylene-vinyl alcohol copolymer (Onyx) and surgery for decompression. CASE DESCRIPTION: We present a case of TN caused by AVM in the CP angle in a patient who was not a candidate for microsurgery and who did not want radiofrequency treatment or other destructive procedures because he would not tolerate facial numbness. The patient's symptoms were successfully treated by embolization using an ethylene-vinyl alcohol copolymer. After 17 months he had a recurrence of pain which was again treated with palliative embolization and again experienced resolution of his symptoms. CONCLUSION: This case demonstrates that palliative embolization is a safe and effective option for the treatment of trigeminal neuralgia pain in patients for whom surgery of the AVM is not an option.

The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype.

Inferring CYP2D6 phenotype from genotype is increasingly challenging, considering the growing number of alleles and their range of activity. This complexity poses a challenge in translational research where genotyping is being considered as a tool to personalize drug therapy. To simplify genotype interpretation and improve phenotype prediction, we evaluated the utility of an "activity score" (AS) system. Over 25 CYP2D6 allelic variants were genotyped in 672 subjects of primarily Caucasian and African-American heritage. The ability of genotype and AS to accurately predict phenotype using the CYP2D6 probe substrate dextromethorphan was evaluated using linear regression and clustering methods. Phenotype prediction, given as a probability for each AS group, was most accurate if ethnicity was considered; among subjects with genotypes containing a CYP2D6*2 allele, CYP2D6 activity was significantly slower in African Americans compared to Caucasians. The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations.

The use of skull X-rays in the accident and emergency department.

The notes of all patients attending the accident and emergency department at the Royal Berkshire Hospital with a head injury from 1-30 September 1999 were analysed for the indications for skull X-ray, the report on film, and the outcome of the consultation. Using the existing Royal Berkshire Hospital guidelines, 50% (193/385) of all patients had skull X-rays performed. One fracture was detected. If the recent guidelines from The Royal College of Surgeons of England Working Party for the use of skull X-rays in institutions which possess a CT scanner were applied, the number of skull X-rays performed would reduce from 193 to 14 without detriment to any patient.

Is the randomized clinical trial the gold standard of research?

All research has flaws. Some flaws are so trivial that the research can still stand as the definitive study. Other flaws prevent a study from being definitive, but the study still provides useful guidance in the context of other research. Some flaws are so serious that the research provides no useful information at all. The tricky part is not finding flaws in the research but in deciding to what extent the flaws erode the credibility of the research. In general, the use of RCTs can add substantial credibility to a research study. There are calls for greater use of RCTs in many areas, such as surgery (Baum, 1999) and psychiatry (Andrews, 1999). Of course, nonrandomized trials are an important complement to RCTs when the latter are ethically inappropriate or logistically impossible (Black, 1996). Failure to use randomization or blinding, however, is not a fatal flaw. Furthermore, the artificial nature of RCTs will often restrict their applicability to overly simple interventions. When RCTs focus on narrow patient groups or exclude important segments of the population, there may be difficulty in generalizing their results. So it would be a mistake to label the RCT as a gold standard for all research. A silver standard may be a more appropriate label.

Creatinine excretion rates for renal clearance studies.

A total of 637 timed-urine collections for creatinine excretion rates obtained from 295 children over 14 years have been analyzed. The children ranged in age from 2.8 to 21.7 years at the time of the clearance study. The data analyzed included only one study from a child during any 6-month period. The objective is to provide data defining the expected range of creatinine excretion for renal clearance studies. One hundred forty-two studies were conducted on children not pretreated with cimetidine and 495 on those pretreated with cimetidine. Analysis showed that pretreatment with cimetidine for creatinine clearance studies does not alter creatinine excretion rates (P=0.080; 95% CI -0.03 to 1.61). Creatinine excretion rates in urine collections obtained at home (roughly 24-h collections) were compared with 2-h supervised collections in the Children's Kidney Center. The supervised urine collections resulted in creatinine excretion rates 1.38 mg/kg/24 h greater than home collections (P=0.001; 95% CI 0.76-2.00). Using regression equations for creatinine excretion rate with age, tables have been prepared showing the expected rate of creatinine excretion for renal clearance studies in children 3-21 years of age.

Understanding the odds ratio and the relative risk.

Both the odds ratio and the relative risk compare the relative likelihood of an event occurring between two groups. The relative risk is easier to interpret and is consistent with general intuition. Some designs, however, allow only for the calculation of the odds ration. Covariate adjustment is easier for an odds ratio. Finally, the odds ratio avoids ambiguity by being invariant to lthe labeling of the outcome measure. The Table summarizes the advantages and disadvantages of the odds ratio and relative risk. Whe reading research that summarizes data using odds ratios, or relative risks, be aware of the limitations of booth of these measures.

Should all infertile males undergo urologic evaluation before assisted reproductive technologies? Two cases of testicular cancer presenting with infertility.

OBJECTIVE: To report two cases of testicular cancer in patients presenting with infertility. DESIGN: Case reports. SETTING: University-affiliated urology practice. PATIENT(S): Two men presenting with infertility. INTERVENTION(S): Complete history and physical, hormonal assays, semen analysis, scrotal ultrasound, radical orchiectomy. MAIN OUTCOME MEASURE(S): Testicular pathology specimens. RESULT(S): Testicular cancer was diagnosed in two men sent to a urology clinic for infertility treatment. CONCLUSION(S): A thorough evaluation should be completed in all males in couples presenting with infertility.

Interpreting positive studies.

When examining the results of a positive research study, one needs to consider two issues of clinical relevance. First, is the outcome measure of direct interest to patients, or is it clearly linked to a measure of direct interest to patients? Second, is the difference large enough to lie outside the range of clinical indifference? Don't accept the findings of a positive research study without a careful consideration of clinical relevance.

Normal urinary calcium/creatinine ratios in African-American and Caucasian children.

A random urine calcium/creatinine ratio (UCa/Cr) is of practical use in screening for hypercalciuria. However, due to worldwide variations, reference values for the pediatric population are not yet well established. Furthermore, no study has been conducted to establish normal UCa/Cr values in young African-American (AA) children. It has also been previously reported that an elevated UCa/Cr is related to a high urine Na/K ratio (UNa/K). The objectives of the present study were: (1) to set normal values of random UCa/Cr by age and race in the pediatric population of Metropolitan Kansas City, (2) to identify potential racial differences in UCa/Cr between Caucasian (CS) and AA children, and (3) to determine the relationship between UCa/Cr and UNa/K in healthy children. A total of 368 healthy children of both genders were enrolled in the study. They were divided into four age groups as follows: (1) <7 months, (2) 8-18 months, (3) 19 months to 6 years, and (4) 7-16 years. Each group was subdivided into AA and CS. A non-fasting random urine specimen from each subject was analyzed for Ca, Na, K and creatinine. The median UCa/Cr values for AA were: (1) 0.13, (2) 0.09, (3) 0.06, and (4) 0.04 and for CS they were (1) 0.26, (2) 0.11, (3) 0.10, and (4) 0.09. The data showed a strong inverse relationship between UCa/Cr and age, the youngest children demonstrating the highest UCa/Cr. In each age group, UCa/Cr in CS exceeded the corresponding value in AA. The age-dependent 95th percentiles of UCa/Cr values for CS were (1) 0.70, (2) 0.50, (3) 0.28, and (4) 0.20 and for AA they were (1) 0.38 and (3) 0.24. Due to outliers, the 95th percentile could not be established for the other two AA subgroups. The relationship between UCa/Cr and UNa/K was found to be extremely weak in both AA (r2=0.00005) and CS (r2=0.02). On the other hand, a strong linear correlation was observed between UNa/K and age (CS r2=0.23, P<0.001, AA r2=0.19, P<0.001), explaining in part the lack of correlation between UNa/K and UCa/Cr. We conclude that the child's age, ethnicity and geographic location should be taken into consideration when assessing UCa/Cr ratio. Contrary to what has previously been reported in hypercalciuric children, no significant relationship was found between UCa/Cr and UNa/K in healthy children.

Factors influencing infant visits to emergency departments.

OBJECTIVES: To follow the 1995 birth cohort of infants, born in the State of Missouri, through their first birthday to: 1) examine their rates of visits to emergency departments (EDs), 2) identify predictors of any ED visit, 3) examine rates of nonurgent ED visits, and 4) identify predictors of nonurgent visits. METHODS: This was a retrospective population cohort study. Using deterministic linkage procedures, 2 databases at the Missouri Department of Health (DOH; (the patient abstract database and the birth registry database) were linked by DOH personnel. International Classification of Diseases, Ninth Revision-Clinical Modification codes for ED visits were classified as emergent, urgent, or nonurgent by 2 researchers. Eight newborn characteristics were chosen for analysis. Negative binomial regression was used to examine the rates and predictors of both total and nonurgent ED visits. RESULTS: There were 935 total ED visits and 153 nonurgent ED visits per 1000 infant years. The average number of visits was.94, with 59% of infants having no visits, 21% having 1 ED visit, and 20% having 2 or more visits. Factors associated with increases in both total and nonurgent ED visits were Medicaid, self-pay, black race, rural region, presence of birth defects, and a nursery stay of >2 days. Significant interactions were found between Medicaid and race and Medicaid and rural regions on rates of ED use and nonurgent use. The highest rate of ED use, 1.8 per person year, was seen in white, rural infants on Medicaid, and the lowest rate (.4 per person year) was seen in urban white infants not on Medicaid. The highest rates of nonurgent use,.3 per person year, were among urban and rural Medicaid infants of both races and among black infants on commercial insurance. The lowest nonurgent rate,.04 per person year, was seen in white urban infants on commercial insurance. CONCLUSION: Infants in the State of Missouri have high rates of ED visits. Nonurgent visits are only a small portion of ED visits and cannot explain large variations in ED usage. Increased ED use by Medicaid patients may reflect continuing difficulties in accessing primary care.

Semen quality and hormone levels among radiofrequency heater operators.

Approximately 9,000,000 US workers are occupationally exposed to radiofrequency (RF) radiation; over 250,000 operate RF dielectric heaters. Our purpose was to determine whether male RF heater operators experience increased adverse reproductive effects reflected in reduced semen quality or altered hormone levels. We measured incident RF heater radiation exposures and RF-induced foot currents at four companies. For 12 male heater operators and a comparison group of 34 RF-unexposed men, we measured 33 parameters of semen quality and four serum hormones. Despite wide variation in individual exposure levels, near field strengths and induced foot currents did not exceed current standard levels and guidelines. We observed minor semen quality and hormonal differences between the groups, including a slightly higher mean follicle-stimulating hormone level for exposed operators (7.6 vs 5.8 mIU/mL). Further occupational studies of RF-exposed men may be warranted.

Transitioning preterm infants with nasogastric tube supplementation: increased likelihood of breastfeeding.

OBJECTIVE: To compare nasogastric tube and bottle supplementation as two means of transitioning preterm infants to breastfeeding within an established breastfeeding support program. DESIGN: Prospective, randomized controlled trial; mothers and health care providers, who were not blinded. SETTING: Metropolitan private regional perinatal center; 40-bed intensive-care nursery. PARTICIPANTS: Eighty-four preterm breastfed infants whose birth weight was 1,000-2,500 g. MAIN OUTCOME MEASURES: Rates of exclusive and partial breastfeeding at discharge from the intensive-care nursery, and at 3 days, 3 months, and 6 months after discharge. RESULTS: Compared with infants receiving bottle supplements, infants receiving nasogastric tube supplements were more likely to be breastfeeding at discharge and at 3 days, 3 months and 6 months, after adjusting for confounding variables. Odds ratios (confidence intervals = 95%) showed that the group receiving nasogastric supplements was 4.5 times (1.4 to 15) more likely to be breastfed at discharge and 9.4 times more likely to be fully breastfed (3.1 to 28.4). There were significantly fewer apnea and bradycardia episodes in the group receiving nasogastric supplements, although they had more episodes that required stimulation for resolution. Groups were not different with respect to length of hospitalization and infant weight at discharge. CONCLUSIONS: Using nasogastric tube supplementation during transition to oral feedings increases the likelihood of breastfeeding at discharge, 3 days, 3 months, and 6 months. This intervention requires a program with skilled personnel and an environment that allows the mother and infant to be in close physical proximity. Further study should investigate differences in the effects on maternal confidence, imprinting, and suck mechanism when preterm infants are bottle fed and breastfed.

High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood.

In recent adult literature, there have been reports of an increasing incidence of focal segmental glomerulosclerosis (FSGS) among patients with nephrotic syndrome. To examine whether this observation is also relevant to the pediatric population we utilized our hospital computerized database to analyze the data on children with primary nephrotic syndrome seen first between the years 1984 and 1995. A questionnaire was also sent to all metropolitan Kansas City pediatricians to identify possible patients outside the database. The inclusion criteria were clinical nephrotic syndrome or proteinuria with a kidney biopsy. A total of 148 patients (group A) were identified; 86 of them from metropolitan Kansas City (group B). In group A the incidence of minimal change disease (MCD) and FSGS was 52.7% [95% confidence interval (CI) 44%-60%] and 23.0% (95% CI 16-29%), respectively and in group B 54.7% (95% CI 44%-65%) and 24.5% (95% CI 15%-33%), respectively. Those numbers were significantly different from the International Study of Kidney Disease in Children (IS-KDC) reported incidence of 76.4% for MCD and 6.9% for FSGS. Similar to the ISKDC, in our population children over 6 years had a higher incidence of FSGS than younger children (32.8% vs. 16.7%, P = 0.028). The annual incidence rate for nephrotic syndrome in group B was 2.2 cases/10(5) children per year, of which MCD comprised 1.22 cases/10(5) children per year and FSGS 0.5 cases/10(5) children per year. The annual incidence rates of both primary nephrotic syndrome (3.6) and FSGS (1.6) were significantly higher in African-Americans, than Caucasians (1.8 and 0.3 cases/10(5) children per year, respectively). Our study indicates nearly no change in the annual incidence of pediatric primary nephrotic syndrome, but a higher incidence of FSGS with reciprocal decline in the incidence of MCD. The possibility of primary nephrotic syndrome being caused by a non-MCD entity is further raised among African-American and in children over 6 years. We conclude that our perception of primary nephrotic syndrome of childhood as a benign condition has to be carefully reexamined and a more-guarded prognostic approach adopted in our geographic area.

Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data.

Cytochrome P4502D6 (CYP2D6) is a highly polymorphic gene locus with > 50 variant alleles which lead to a wide range in enzymatic activity. So called poor metabolizers are carriers of any two non-functional alleles of the CYP2D6 gene. CYP2D6 genotyping is cumbersome and the question of how much genotyping is necessary for an accurate phenotype prediction is still debated. The goal of this study was to determine the optimum amount of genotyping required to accurately predict the phenotype at a reasonable cost in a white North American population. To address this issue, we designed a polymerase chain reaction (PCR)/restriction fragment length polymorphism-based genotyping strategy to detect 'key' mutations linked to extensive metabolizer or poor metabolizer associated alleles in combination with extra-long PCR (XL-PCR). All mutations with the exception of gene deletions and duplications are detectable by simple restriction digestion analysis and agarose gel electrophoresis. In addition, we utilized a genotyping algorithm based on our own and published allele frequency data and phenotype analysis to calculate the probability of a correct genotype (and thus, phenotype) assignment. As little as one XL-PCR reaction followed by a maximum of six reamplification reactions allows an accurate prediction of an individual's genotype to 99.15%. As few as four reamplification reactions identify 97.9% of poor metabolizer individuals. We evaluated our model in 208 white North Americans by testing for the presence of 'key' mutations linked to CYP2D6*2, *3, *4, *6, *7, *8, *9, *10, *11, *12, *15, *17 and *18 alleles and the *5, *13 and *16 gene deletions. For all individuals, the correct phenotype has been predicted. Discordant phenotype assignment occurred in only two individuals which subsequently was attributed to CYP2D6 inhibition by concomitant drug therapy.