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Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use.

Chemotherapy-induced nausea and vomiting (CINV) is commonly experienced by patients receiving antineoplastic agents prior to hemopoietic stem cell transplant (HSCT). Ondansetron, a 5-HT3 antagonist metabolized by CYP2D6, is an antiemetic prescribed to treat short-term CINV, but some patients still experience uncontrolled nausea and vomiting while taking ondansetron. Adult CYP2D6 ultrarapid metabolizers (UMs) are at higher risk for CINV due to rapid ondansetron clearance, but similar studies have not been performed in pediatric patients. We performed a retrospective chart review of 128 pediatric HSCT recipients who received ondansetron for CINV prevention and had CYP2D6 genotyping for 20 alleles and duplication detection. The number of emetic episodes for each patient was collected from the start of chemotherapy through 7 days after HSCT. The average age of the cohort was 6.6 years (range: 0.2-16.7) and included three UMs, 72 normal metabolizers, 47 intermediate metabolizers, and six poor metabolizers. Because UMs are the population at risk for inefficacy, we describe the course of treatment for these three patients, as well as the factors influencing emesis: chemotherapy emetogenicity, diagnosis, and duration of ondansetron administration. The cases described support guidelines recommending non-CYP2D6 metabolized antiemetics (e.g., granisetron) when a patient is a known CYP2D6 UM, but pediatric studies with a larger sample of CYP2D6 UMs are needed to validate our findings.

Historically, medical geneticists and genetic counselors have provided the majority of genetic services. Advances in technology, reduction in testing costs, and increased public awareness have led to a growing demand for genetic services in both clinical and direct-to-consumer spaces. Recent and anticipated changes in the workforce of genetic counselors and medical geneticists require a reexamination of the way we educate health-care providers and the means by which we provide access to genetic services. The time is ripe for rapid growth of genetic and genomic services, but to capitalize on these opportunities, we need to consider a variety of educational mechanisms to reach providers both within and beyond the traditional genetic counseling and medical genetics sectors, including nurses, physician assistants, and nongenetics physicians. This article summarizes the educational efforts underway in each of these professions.

The American College of Medical Genetics and Genomics supports parents’ opting in or out of secondary analysis of 59 genes when their child has clinical exome/genome sequencing. We explored the reasons adolescents choose to learn certain types of results and the reasons they want to involve or not involve parents in decision-making. Adolescents recruited without clinical indication were offered independent, followed by joint choices with a parent to learn genomic results. After making independent choices, adolescent/parent dyads were interviewed to explore the reasons for their choices. Interviews were audio-recorded and transcribed. The constant comparative method was used to analyze 64 purposefully selected transcripts that included 31 from adolescents who excluded some or all potential results. Three major themes informed adolescents’ choices: (1) actionability of information, (2) knowledge seeking, and (3) psychological impact. Of adolescents who independently excluded some conditions (n=31), 58% changed their initial choices during the joint interview due to parental influence or improved understanding. Nearly all adolescents (98%) wanted to be involved in the decision-making process, and 53% wanted to make choices independently. Our findings contribute empirical evidence to support the refinement of professional guidelines for adolescents’ engagement and preferences in genetic testing decisions.

Significant inter-individual variability in medication response can result in adverse drug reactions (ADRs) and increased health care costs. Based on ADR prevalence and mounting evidence linking genetics and pharmacokinetic variability, Cincinnati Children’s Hospital Medical Center (CCHMC) launched the Genetic Pharmacology Service (GPS) in 2004 and has since performed >25,000 tests. Herein, we describe how the service developed, launched, and has been updated along with how it is currently utilized, and key lessons learned.

In pediatric patients, the selective serotonin reuptake inhibitors (SSRIs) escitalopram and citalopram (es/citalopram) are commonly prescribed for anxiety and depressive disorders. However, pharmacogenetic studies examining CYP2C19 metabolizer status and es/citalopram treatment outcomes have largely focused on adults. We report a retrospective study of electronic medical record data from 263 youth < 19 years of age with anxiety and/or depressive disorders prescribed escitalopram or citalopram who underwent routine clinical CYP2C19 genotyping. Slower CYP2C19 metabolizers experienced more untoward effects than faster metabolizers (p = 0.015), including activation symptoms (p = 0.029) and had more rapid weight gain (p = 0.018). A larger proportion of slower metabolizers discontinued treatment with es/citalopram than normal metabolizers (p = 0.007). Meanwhile, faster metabolizers responded more quickly to es/citalopram (p = 0.005) and trended toward less time spent in subsequent hospitalizations (p = 0.06). These results highlight a disparity in treatment outcomes with es/citalopram treatment in youth with anxiety and/or depressive disorders when standardized dosing strategies were used without consideration of CYP2C19 metabolizer status. Larger, prospective trials are warranted to assess whether tailored dosing of es/citalopram based on CYP2C19 metabolizer status improves treatment outcomes in this patient population.

OBJECTIVE To determine the prevalence of abnormal thyroid-stimulating hormone (TSH) measures in youth with severe mood and anxiety disorders and to examine clinical and demographic predictors of abnormal TSH measures. METHODS We retrospectively examined screening TSH concentrations in psychiatrically hospitalized children and adolescents (3-19 years) with mood/anxiety disorders (DSM-IV and DSM-5 criteria) at a large, urban, pediatric hospital between September 2013 and April 2017. Symptoms were extracted from the medical record using adaptive natural language processing algorithms, and the utility of demographic, clinical, and treatment variables as predictors of abnormal TSH measures was evaluated using logistic regression. RESULTS In this sample (N = 1,017, mean ± SD age = 14.7 ± 2.24 years), 62 patients had a TSH concentration > 3.74 μIU/mL (5.3% [n = 6] of patients < 12 years of age and 6.2% [n = 56] of patients ≥ 12 years of age), and 7 patients had a TSH concentration < 0.36 μIU/mL. Elevated TSH concentrations were associated with a recent weight gain (odds ratio [OR] = 3.60; 95% CI, 1.13-9.61; P = .017), a history of thyroid disease (OR = 6.88; 95% CI, 2.37-10.7; P ≤ .0001), abnormal menstrual bleeding/menometrorrhagia (OR = 2.03; CI, 1.04-3.63; P = .024), and benzodiazepine treatment (OR = 2.29; 95% CI, 1.07-4.52; P = .02). No association was observed for sex, age, or body mass index z score. Among patients with elevated TSH measures, 12.9% (n = 8, mean ± SD age = 16.5 ± 1.5 years, 87.5% female) had an abnormal free/total thyroxine (T₄) level or other biochemical findings consistent with thyroid disease. Patients with thyroid disease (compared to those patients with elevated TSH and normal active thyroid hormone concentrations) were older (16.5 ± 1.5 vs 14.6 ± 2.3 years, P = .020) but did not differ in sex distribution (87.5% vs 63.6% female, P = .444). CONCLUSIONS TSH concentrations are abnormal in approximately 6% of psychiatrically hospitalized youth, although thyroid disease was present in < 1% of the total sample. Targeted screening should focus on patients with recent weight gain, those treated with benzodiazepines, and girls with a history of abnormal uterine bleeding/menometrorrhagia.

Objective Unpredictable interindividual variability in response to opioids results in inadequate analgesia and opioid-related adverse effects. The effects of the child's sex on opioid response have not been well studied. The aim of this study is to determine the effects of sex on opioid-related adverse effects in children undergoing tonsillectomy. Design Prospective observational clinical study. Setting Outpatient pediatric surgery. Subjects Two hundred and seventy five children between 6 and 15 years of age undergoing outpatient tonsillectomy. Methods All children received standard perioperative care with a standard intraoperative dose of morphine. Opioid-related analgesia and safety outcomes included incidences of respiratory depression (RD), postoperative nausea and vomiting (PONV) and incidence of prolonged stay in the, post-anesthesia recovery unit (PACU) due to opioid related adverse effects. Results Given the small sample of minority population, we focused our study on 219 white children. Significant morphine effect was observed in girls but not boys for PONV (P = 0.001) and prolonged PACU stay due to PONV (P = 0.010). Although the overall incidence of RD is not statistically different between boys and girls, the incidence of RD (52% vs 32%) and PONV (43% vs 4%) tended to be more in white girls than boys as the total perioperative morphine dose increased to 0.3 mg/kg or more. Conclusions This study demonstrates that child's sex influences morphine's dose response and adverse effects. White girls have an unequal burden with higher incidences of PONV, RD, and prolonged PACU stays following tonsillectomy from PONV and RD as total morphine doses are increased.

ObjectiveHaving failed to achieve adequate influenza vaccination rates among employees through voluntary programmes, healthcare organisations have adopted mandatory ones. Some programmes permit religious exemptions, but little is known about who requests religious objections or why.MethodsContent analysis of applications for religious exemptions from influenza vaccination at a free-standing children’s hospital in Cincinnati, Ohio, USA during the 2014–2015 influenza season.ResultsTwelve of 15 260 (0.08%) employees submitted applications requesting religious exemptions. Requestors included both clinical and non-clinical employees. All requestors voluntarily identified their religious affiliation, and most were Christian (n=9). Content analysis identified six categories of reasons used to justify an exemption: risks/benefits, ethical/political, lack of direct patient contact, providence, purity and sanctity of life. Individuals articulated reasons in 1–5 (mean 2.6) categories. The most frequently cited category (n=9) was purity; the vaccine and/or its mode of administration were impure, or receiving the vaccine would make the individual impure. Two individuals asserted that the vaccine contained cells derived from aborted human fetuses. Individuals (n=6) also volunteered information supporting the sincerity of their beliefs including distress over previous vaccination and examples of behaviour consistent with their specific objection or their general religious commitment. All requests were approved.ConclusionsLess than 0.1% of employees requested religious exemptions. Partnering with religious leaders and carefully correcting erroneous information may help address requestors’ concerns.

Background Oliver–McFarlane syndrome is characterised by trichomegaly, congenital hypopituitarism and retinal degeneration with choroidal atrophy. Laurence–Moon syndrome presents similarly, though with progressive spinocerebellar ataxia and spastic paraplegia and without trichomegaly. Both recessively inherited disorders have no known genetic cause. Methods Whole-exome sequencing was performed to identify the genetic causes of these disorders. Mutations were functionally validated in zebrafish pnpla6 morphants. Embryonic expression was evaluated via in situ hybridisation in human embryonic sections. Human neurohistopathology was performed to characterise cerebellar degeneration. Enzymatic activities were measured in patient-derived fibroblast cell lines. Results Eight mutations in six families with Oliver–McFarlane or Laurence–Moon syndrome were identified in the PNPLA6 gene, which encodes neuropathy target esterase (NTE). PNPLA6 expression was found in the developing human eye, pituitary and brain. In zebrafish, the pnpla6 curly-tailed morphant phenotype was fully rescued by wild-type human PNPLA6 mRNA and not by mutation-harbouring mRNAs. NTE enzymatic activity was significantly reduced in fibroblast cells derived from individuals with Oliver–McFarlane syndrome. Intriguingly, adult brain histology from a patient with highly overlapping features of Oliver–McFarlane and Laurence–Moon syndromes revealed extensive cerebellar degeneration and atrophy. Conclusions Previously, PNPLA6 mutations have been associated with spastic paraplegia type 39, Gordon–Holmes syndrome and Boucher–Neuhauser syndromes. Discovery of these additional PNPLA6 -opathies further elucidates a spectrum of neurodevelopmental and neurodegenerative disorders associated with NTE impairment and suggests a unifying mechanism with diagnostic and prognostic importance.

Background: The success of personalized medicine depends on factors influencing the availability and implementation of its new tools to individualize clinical care. However, little is known about physicians' views of the availability of personalized medicine across racial/ethnic groups and the relationship between perceived availability and clinical implementation. This study examines physicians' perceptions of key elements/tools and potential barriers to personalized medicine in connection with their perceptions of the availability of the latter across subpopulations. Methods: Study subjects consisted of physicians recruited from Cincinnati Children's Hospital Medical Center and UC Health. An electronic survey conducted from September 2012 to November 2012 recruited 104 physicians. Wilcoxon rank sum analysis compared groups. Results: Physicians were divided about whether personalized medicine contributes to health equality, as 37.4% of them believe that personalized medicine is currently available only for some subpopulations. They also rated the importance of racial/ethnic background almost as high as the importance of genetic information in the delivery of personalized medicine. Actual elements of personalized medicine rated highest include family history, drug-drug interaction alerts in medical records, and biomarker measurements to guide therapy. Costs of gene-based therapies and genetic testing were rated the most significant barriers. The ratings of several elements and barriers were associated with perceived availability of personalized medicine across subpopulations. Conclusion: While physicians hold differing views about the availability and implementation of personalized medicine, they likewise establish complex relationships between race/ethnicity and personalized medicine that may carry serious implications for its clinical success.

Family health history (FHH) can identify families at increased risk for disease. Purpose. To learn mothers’ (1) perceptions of the benefits of FHH and (2) willingness to complete a FHH tool, My Family Health Portrait (MFHP). Methods. Qualitative in-depth interviews were conducted with mothers recruited through Cincinnati Children’s Hospital. Deductive and inductive codes were developed. Results. A total of 25 mothers were interviewed. Perceived benefits included keeping the pediatrician informed (n = 12; 48%) and preventive screenings recommended based on FHH (n = 10; 40%). Participants had positive impressions of MFHP and felt that it was user-friendly (n = 17; 68%). Lack of FHH knowledge was the most common challenge to completing MFHP, but most respondents stated that they would be able to complete MFHP prior to their child’s medical appointment (n = 23; 92%). Conclusion. Mothers are interested in and may be motivated to complete a parent-generated FHH prior to a pediatric appointment. Future research should focus on FHH implementation in practice.

There is a need to explore feasible means of accruing an appropriate study cohort to help fill the knowledge gap between pharmacogenetic contributions to drug response and clinical application in the pediatric population.The aim of this study was to identify factors affecting recruitment of eligible subjects in pharmacogenetic studies at a large Midwestern pediatric academic medical center. The objectives were to evaluate recruitment success of ongoing trials and ascertain contributors to differential recruitment rates. We hypothesized that studies with good recruitment of eligible subjects would share characteristics not present in studies with lower than anticipated recruitment. The goal was to better understand barriers to good recruitment in pharmacogenetic studies to help inform future trial and infrastructure design.Investigators designed a survey with proposed elements of success, which was then completed by lead and/or site investigators of all pharmacogenetics studies at the institution. Results were evaluated using an investigator-developed likelihood of success scoring system.Two studies recruited95% of the approached eligible patients; 4 studies were consistent with investigator-anticipated recruitment (50%), and 1 study did not meet expected recruitment. A study's total score on the investigator-devised scoring tool correlated well with the proportion of approached patients recruited (Pearson's correlation, r = 0.82; P0.001). Multiple factors impacted successful recruitment into these pharmacogenetic studies. Features of studies with successful recruitment included standardized clinical care, an ongoing team-patient relationship, severe and/or life-threatening outcome measures, study coordinator with experience in clinical research, a study medication with few or no alternative treatment options, and active involvement of the research team in clinical care.A scoring system for study characteristics may be useful to calculate the risk of failure for successful recruitment, allow discrimination among characteristics contributing to the risk, and permit study design alterations to improve likelihood of successful recruitment in pediatric pharmacogenetic studies.

Objectives. The purpose of this study was to describe how pediatric providers collect and use family health history (FHH) and their perceptions about My Family Health Portrait (MFHP) as a pediatric health promotion and disease prevention tool. Study design.A random sample of 148 pediatric providers was invited to participate in a semistructured qualitative interview. Transcripts were reviewed by 2 coders, and interrater reliability was determined. Results. In all, 21 providers were interviewed. All participants collected FHH at new visits and when patients presented with a symptom or complaint. Most providers believed that collecting FHH of chronic disease benefits the pediatric population. Time was the most commonly cited barrier to FHH collection; collecting FHH prior to the office visit was the most frequently cited facilitator. Providers believed that the use of MFHP would improve FHH collection and allow targeted education and preventive recommendations. Respondents also identified logistical and other issues that must be resolved to integrate MFHP into clinical practice. Conclusion. This research suggests that pediatric primary care presents many opportunities to collect and discuss FHH and that providers are optimistic about the clinical use of a parent-generated FHH collection tool. Future research should assess parent perspectives about the use of MFHP.

Family health history is one of the best predictors of an individual's risk for common disease, yet it is underutilized in routine care. Although the Surgeon General has recommended consumers record their family health history and share it with their health care provider, providers' perceptions of patient-generated family histories are unknown. To learn more about providers' experience with and perceptions about patient-generated family histories, we mailed surveys to 301 providers and had a response rate of 24% (n = 68). Seventy-three percent felt a patient-generated computer pedigree would improve their ability to assess risk as compared to their current methods. Seventy percent felt a patient-generated computer pedigree would either have no effect on or would increase the number of patients that could be seen in a day. Results suggest that providers appreciate the potential benefits of patient-generated family histories. Genetic counselors and nurses are in a prime position to promote and facilitate the use of patient-generated family health histories in routine care.

The aim of this study was to examine the association between the CYP2D6 and CYP2C19 genotype-predicted combined phenotypes and short-term measures of psychotropic efficacy and toxicity.A rater-blinded, retrospective genotype association design examined a cohort of hospitalized pediatric psychiatric patients genotyped for CYP2D6 and CYP2C19 as part of clinical care. These combined genotypes were used to predict a combined phenotype. The primary efficacy outcome measure was the behavior intervention score (BIS), a function of the number of recorded timeouts/seclusions, therapeutic holds, and physical restraints. Drug tolerability was defined as the total number of recorded adverse drug reactions.Primary analysis was performed on 279 pediatric patients taking CYP2D6- or CYP2C19- dependent psychotropics. Combined phenotype was associated with BIS (p = 0.01) and number of adverse drug reactions (p = 0.03). Combined poor metabolizers treated with psychotropics had the lowest BIS (highest efficacy) and the highest number of adverse drug reactions. Combined ultrarapid metabolizers had the highest BIS (lowest efficacy) and the lowest number of adverse drug reactions.Common variants in CYP2D6 and CYP2C19 are associated with the short-term efficacy and tolerability of psychotropic medications in hospitalized pediatric patients.

Differences in drug responses due to gene alterations are rapidly being identified. Gene alterations may inhibit the function of an enzyme so that an active drug accumulates, causing adverse reactions with normal doses. Alternatively, gene alterations may accelerate enzymatic function so that an active drug is rapidly eliminated, causing subtherapeutic responses to normal doses. Mutations and polymorphisms have been identified that affect a person's response to many currently prescribed medications including cardiovascular, anti-infective, chemotherapeutic, psychiatric, and analgesic drugs. The potential exists for drug therapy to be optimized by selecting medication and doses based on a person's genotype rather than by trial and error. In the near future, advanced practice nurses in the acute care setting may be expected to order, provide patient education about, and explain results of genetic tests before initiating a specific drug therapy. Advanced practice nurses must be knowledgeable about what genetic tests are analyzing and their benefits, limitations, and risks.

Ask the Expert provides research-based answers to practice questions submitted by JSPN readers. Where possible, evidence from research is used to support the experts' recommendations.

The responses to regular intravenous enzyme infusions were compared in two sibs with Gaucher disease type 2, the acute neuronopathic variant. Enzyme administration was begun at 7 months in patient 1 who had severe progressive visceral and neuronopathic disease. No significant effect of enzyme infusions was noted. Death occurred at 9 months. Patient 2 was prenatally diagnosed and enzyme infusions were initiated at age 4 days. Overall development progressed at a rate similar to her unaffected full sib until her death at 15.1 months. Slowly progressive esotropia, ocular paresis and dysphagia began at 8 months as did infiltrative pulmonary disease. Comparison of these clinical courses show significant visceral and neurologic effects of anticipatory enzyme therapy, but with unaltered outcome, for Gaucher disease type 2.

purpose.To describe the responses of mothers and fathers who were offered bone marrow transplantation (BMT) for their children with genetic disorders design.Qualitative setting.Private hospital rooms/offices participants.Six mothers and 4 fathers of children with genetic disorders results.The basic social-psychological problem confronting the parents was the conflicting alternatives of life versus death for their children. It was certain that these children would die from their genetic disorders but without having to endure the pain and suffering of a BMT. The BMT would be difficult, possibly resulting in death, but with a chance of survival. conclusions.Parents believed that BMT was the only chance of survival for their children, leaving them no choice except to pursue the BMT treatment

Objectives/Hypothesis To prospectively determine factors associated with codeine's adverse drug reactions (ADRs) at home in a large homogenous population of children undergoing outpatient tonsillectomy. Study Design Prospective, genotype blinded, observational study with a single group and repeated ADR measures documented by parents at home. Methods A total of 249 children 6 to 15 years of age scheduled for tonsillectomy were enrolled. The primary outcome was number of daily codeine-related ADRs. We examined the number and type of ADR by race and by days and further modeled factors potentially associated with ADR risk in a subcohort of white children. Sedation following a dose of codeine was a secondary outcome measure. Parents recorded their children's daily ADRs and sedation scores during postoperative days (POD) 0 to 3 at home. Results Diaries were returned for 134 children, who were given codeine. A total of 106 (79%) reported at least one ADR. The most common ADRs were nausea, lightheadedness/dizziness for white children and nausea, and vomiting for African American children. In a subcohort of white children ≤ 45 kg, increased ADR risk was associated with the presence of one or more full function CYP2D6 alleles (P

Objectives To review pharmacogenetics as it relates to cancer therapy and to describe pharmacogenetic tests that are clinically available and relevant to cancer drug selection or dosing or both. Data Sources Peer-reviewed, evidence-based literature. Conclusions Genetic predispositions and enzyme specific inhibitors and inducers are critical factors in patients’ responses to cancer drugs. Implications for Nursing Practice Nurses need to incorporate knowledge about pharmacogenetics when administering cancer drugs and monitoring patients’ responses. Nurses also have an important role in assuring that patients are informed about the purpose and limitations of pharmacogenetic testing.

Objective To assess parental perspectives on effective interventions and to summarize parents’ suggestions for health care professionals to improve the care provided to their children born with cleft lip and/or palate. Design Qualitative interviews. Setting Comprehensive craniofacial center at a Midwest pediatric hospital. Participants Seventeen parents of children under the age of 1 who were born with CL/P. Results Interventions that parents identified as effective included repetition of information, showing pictures of other children (before and after surgery), and anticipatory guidance about surgeries and their child's development. Despite the high level of satisfaction, parents expressed a desire for health care professionals to use more written and visual information, to have more contact with other parents of children born with clefts, and for health care professionals outside the Craniofacial Center to be more knowledgeable about CL/P. Conclusions Although parents of children with CL/P were for the most part satisfied with their children's care, the parents who were interviewed for this study suggested attainable changes that may result in more constructive and positive involvement of parents as integral members of the craniofacial team.

Pharmacogenetic testing is currently not routine in critical care settings but recent changes in the warfarin label are likely to lead to critical care nurses encountering physician or nurse practitioner orders for such testing. Although the science for pharmacogenetics is complex, the components of patient teaching are not beyond that which nurses already provide about other laboratory, disease, and treatment-based information. It is reasonable to expect that as the science of pharmacogenetics and pharmacogenomics expands and discoveries are translated in clinical settings, the additional information from pharmacogenetic test results will help prescribers select or adjust medication doses to reduce the risk for adverse drug reactions and improve the chances of achieving therapeutic targets in a timely fashion.

There is considerable variability in the effectiveness and toxicity of psychotropics used to treat mental health disorders in children and adolescents. Pharmacogenetic (PG) testing is beginning to be used to decrease the time it takes to reach therapeutic response and decrease the occurrence of adverse drug reactions in children and adolescents treated with psychotropics. This article reviews the pharmacogenetics literature and uses a clinical scenario to illustrate the essential genetic/genomics competencies pediatric nurses need to meet when providing care to patients whose medication therapy is being guided by PG testing.

Familial adenomatous polyposis, an inherited condition, can lead to colon cancer if left untreated. Patients seeking treatment for symptoms of this disorder are often found to have cancer already. Because surgical treatment in symptom-free persons with familial adenomatous polyposis greatly reduces their future risk of cancer, presymptomatic identification of the disorder can save lives. Because the disorder is inherited, knowledge of its familial pattern can help nurses recommend candidates for screening. A case study of one family demonstrates the value of genetic analysis and the role nurses can play.

5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting. CYP2D6 polymorphisms can influence the metabolism of some of these drugs (i.e. ondansetron and tropisetron) thereby affecting drug efficacy. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for ondansetron and tropisetron based on CYP2D6 genotype (updates at www.pharmgkb.org ).