Abstract: Aim: To explore primary care physicians’ views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system. Methods: This descriptive study assessed the perspectives of 15 healthcare providers utilizing qualitative individual interviews. Results: Three main themes emerged: perceived value and utility of PGx testing; challenges to implementation in practice; and provider as well as patient needs. Conclusion: While providers in this study viewed benefits of PGx testing as avoiding side effects, titrating doses more quickly, improving shared decision-making and providing psychological reassurance, challenges will need to be addressed such as privacy concerns, cost, insurance coverage and understanding the complexity of PGx test results.

Abstract: A variety of health-related genetic testing is currently advertized directly to consumers. This article provides a timely overview of direct-to-consumer genetic testing (DTC GT) and salient ethical issues, as well as an analysis of the impact of the recently adopted regulation on in vitro diagnostic medical devices on DTC GT. DTC GT companies currently employ new testing approaches, report on a wide spectrum of conditions and target new groups of consumers. Such activities raise ethical issues including the questionable analytic and clinical validity of tests, the adequacy of informed consent, potentially misleading advertizing, testing in children, research uses and commercialization of genomic data. The recently adopted regulation on in vitro diagnostic medical devices may limit the offers of predisposition DTC GT in the EU market.

Abstract: Personalized medicine (PM) is an emerging approach to prevention, diagnosis, treatment and care. It helps to address the challenge of the aging of the population, an increase in chronic disease and increasing healthcare costs. The EU is developing policies to move toward PM. This is underpinned by a sustained and significant investment starting in 2010. So far, a total of €3.2 billion has been invested in PM research across the medical innovation cycle 'from bench to bedside'. This investment has come from the research framework programs FP7 and Horizon 2020. About a third of the total investment has been made in the context of the Innovative Medicines Initiative, the largest public-private partnership in life sciences globally.

Abstract: Aim Describe modifications to technical genomic terminology made by interpreters during disclosure of whole exome sequencing (WES) results. Patients & methods Using discourse analysis, we identified and categorized interpretations of genomic terminology in 42 disclosure sessions where Spanish-speaking parents received their child's WES results either from a clinician using a medical interpreter, or directly from a bilingual physician. Results Overall, 76% of genomic terms were interpreted accordantly, 11% were misinterpreted and 13% were omitted. Misinterpretations made by interpreters and bilingual physicians included using literal and nonmedical terminology to interpret genomic concepts. Conclusion Modifications to genomic terminology made during interpretation highlight the need to standardize bilingual genomic lexicons. We recommend Spanish terms that can be used to refer to genomic concepts.

Abstract: Aim: The effect of a gene-expression-based test on treatment of melanocytic neoplasms by dermatologists was evaluated. Patients & methods: Pathologists submitted diagnostically challenging melanocytic neoplasms to a clinical laboratory for testing accompanied by pretest surveys documenting the intended treatment recommendations. The actual treatment rendered by dermatologists was then documented after testing. Changes between the pretest recommendations and actual treatment were analyzed. Results: In 71.4% (55/77) of cases, there was a change from pretest recommendations to actual treatment. The majority of changes were consistent with the test result. There was an 80.5% (33/41) reduction in the number of biopsy site re-excisions performed for cases with a benign test result. Conclusion: The actual treatment of diagnostically challenging melanocytic neoplasms is influenced by the test.

Abstract: Personalized medicine (PM) is no longer an abstract healthcare approach. It has become a reality over the last years and is already successfully applied in the various medical fields. Although there are success stories of implementing PM, there are still many more opportunities to further implement and make full use of the potential of PM. We assessed the system readiness of healthcare systems in Europe to shift from the predominant ‘one size fits all’ healthcare approach to PM. We conclude that European healthcare systems are only partially ready for PM. Key challenges such as integration of big data, health literacy, reimbursement and regulatory issues need to be overcome in order to strengthen the implementation and uptake of PM.

Abstract: Personalized medicine is becoming routine in the treatment of common diseases such as cancer, but has lagged behind in the field of rare diseases. It is currently in the early stages for the treatment of Bardet-Biedl syndrome. Advances in the understanding of ciliary biology and diagnostic techniques have opened up the prospect of treating BBS in a patient-specific manner. Owing to their structure and function, cilia provide an attractive therapeutic target and genetic therapies are being explored in ciliopathy treatment. Promising avenues include gene therapy, gene editing techniques and splice-correcting and read-through therapies. Targeted drug design has been successful in the treatment of genetic disease and research is underway in the discovery of known and novel drugs to treat Bardet-Biedl syndrome.

Abstract: The 'Theory of Planned Behavior' (TPB) has been tested and validated in the scientific literature across multiple disciplines and is arguably the most widely accepted theory among behavior change academics. Despite this widespread acceptability, the TPB has yet to be incorporated into personalized healthcare behavior change research. Several prominent personalized healthcare researchers suggest that personalizing healthcare recommendations have a positive impact on changes in lifestyle habits. However, research in this area has demonstrated conflicting findings. We provide a scientific and theoretical basis to support a proposed expansion of the TPB to include personalization, and call to action-personalized healthcare behavior change researchers to test this expansion. Specific recommendations for study design are included.

Abstract: This perspective addresses whether physicians have a duty to recontact former or current patients to update clinical advice based on newly discovered genomic information. Genetic information is unique compared with other medical data in that the underlying data do not appreciably change during the patients' lifetime, but the clinical significance of that information will continue to evolve. Based on relevant case law and guidelines, there is no general, established legal duty for physicians to affirmatively recontact former or current patients to update clinical advice based on newly discovered genetic information. However, integration of genomics into clinical practice is advancing quickly, and there may be limited, specific situations where a physician may have a duty to provide updated genetic information.

Abstract: In circadian rhythm sleep-wake disorders precision medicine is less developed than in other medical disciplines mainly because homeostatic sleep and circadian timing have a very complex phenotype with multiple genetic regulation mechanisms. However, biomarkers, phenotyping and psychosocial characteristics are increasingly used. Devices for polysomnography, actigraphy and sleep-tracking applications in mobile phones and other consumer devices with eHealth technologies are increasingly used. Also sleep-related questionnaires and the assessment of co-morbidities influencing sleep in circadian rhythm sleep-wake disorders are major contributors to precision sleep medicine. To further strengthen the (pharmaco-)genetic and biomarker pillar, technology needs to be evolved further. Routinely measuring treatment results using patient-reported outcome measures and clinical neurophysiological instruments will boost precision sleep medicine.

Abstract: The Genetic Information Nondiscrimination Act (GINA) was intended to protect individuals in the USA from discrimination based on their genetic data, but does not apply to life, long-term care or disability insurance. Patient advocates and ethicists have argued that GINA does not go far enough. Others express concerns for the viability of insurance companies if millions of potential customers know more than professional actuaries. Here we discuss the exclusion of certain insurance types from GINA. We explore the ethical and economic implications of this distinction, and potential paths forward. We suggest that because long-term care and disability insurance can be essential for well-being, there is no good reason to place them in a class with life insurance and therefore beyond GINA's reach.

Abstract: Aim: Identify solutions to the most important policy barriers to the clinical adoption of next-generation sequencing. Materials & methods: Four-round modified policy Delphi with a multistakeholder panel of 48 experts. The panel deliberated policy solutions to (previously reported) challenges deemed most important to address. Results: The group advocated using consensus panels to promote consistency in payer policies and to standardize test reporting, and favored making genomic data-sharing a condition of regulatory clearance, certification, or accreditation processes. They were split on the role of US FDA. Conclusion: Panelists found common ground on solutions for health plan coverage policy consistency, data-sharing, and standardizing reporting, but were sharply divided on the role of the FDA in mitigating risks to patients.

Abstract: Aim This study aimed to examine pharmacogenomic test results and patient perspectives at an academic cardiovascular medicine clinic. Patients & methods Test results for three common cardiovascular drug-gene tests (warfarin-CYP2C9-VKORC1, clopidogrel-CYP2C19 and simvastatin-SLCO1B1) of 208 patients in the Ohio State University-Coriell Personalized Medicine Collaborative were examined to determine the incidence of potentially actionable test results. A post-hoc, anonymous, patient survey was also conducted. Results Potentially actionable test results for at least one of the three drug-gene tests were determined in 170 (82%) patients. Survey responses (n = 134) suggested that patients generally considered their test results to be important (median of 7.5 on a 10-point scale of importance) and were interested (median of 7.3 on a 10-point scale of interest) in a Clinical Pharmacogenomic Service. Conclusion Attitudes toward pharmacogenomic testing were generally favorable, and potentially actionable test results were not uncommon in this cardiovascular medicine cohort.

Abstract: The novel genome-wide assays of epigenetic marks have resulted in a greater understanding of how genetics and the environment interact in the development and inheritance of diabetes. Chronic hyperglycemia induces epigenetic changes in multiple organs, contributing to diabetic complications. Specific epigenetic-modifying compounds have been developed to erase these modifications, possibly slowing down the onset of diabetes-related complications. The current review is an update of the previously published paper, describing the most recent advances in the epigenetics of diabetes.

Abstract: This study assessed perspectives on whole-genome sequencing (WGS) for rare disease diagnosis and the process of receiving genetic results. Semistructured interviews were conducted with adult patients and parents of minor patients affected by idiopathic diseases (n = 10 cases). Three main themes were identified through qualitative data analysis and interpretation: perceived benefits of WGS; perceived drawbacks of WGS; and perceptions of the return of results from WGS. Findings suggest that patients and their families have important perspectives on the use of WGS in diagnostic odyssey cases. These perspectives could inform clinical sequencing research study designs as well as the appropriate deployment of patient and family support services in the context of clinical genome sequencing.

Abstract: Aim: To evaluate whether SNPs (n = 15) in ten candidate genes (ADRB2, ADH5, ARGI, CRHR1, STIP1, LTA4H, LTC4S, ALOX5, ABCC1 and OATP2B1) are associated with asthma in Jordanian population of Arab descent. Methods: A case–control study included 245 adult asthmatics and 249 controls. Results: Significant genetic association was identified at the rs2236647 (T/C) SNP in STIP1 and risk of asthma (p < 0.001). The C allele and CC genotype of this SNP were significantly higher in asthmatics compared with controls. The rs1141370 SNP (Val34Met) in ADRB2 is not polymorphic in our cohort. Conclusion: The rs2236647 SNP could act as a reliable tool to identify individuals at risk of developing asthma and provision of early intervention in population of Arab descent.

Abstract: Aim: Since whole-genome sequencing (WGS) information can have positive and negative personal utility for individuals, we examined predictors of willingness to pay (WTP) for WGS. Patients & methods: We surveyed two independent populations: adult patients (n = 203) and college seniors (n = 980). Ordinal logistic regression models were used to characterize the relationship between predictors and WTP. Results: Sex, age, education, income, genomic knowledge and knowing someone who had genetic testing or having had genetic testing done personally were associated with significantly higher WTP for WGS. After controlling for income and education, males were willing to pay more for WGS than females. Conclusion: Differences in WTP may impact equity, coverage, affordability and access, and should be anticipated by public dialog about related health policy.

Abstract: Aim: To examine genomic medicine (GM) practice and associated factors (i.e., attitudes, intention, self-efficacy, previous training in genomics, and demographic characteristics) among Taiwanese physicians. Methods: A survey was distributed to physicians attending an internal training workshop at a large medical center in Taiwan. Data were analyzed using structural equation modeling. Results: A total of 137 physicians comprised our final sample; less than a third of them had practiced GM. Yet, participants overall had positive intention, favorable attitudes, and high self-efficacy in GM practice. Moreover, intention, attitudes, self-efficacy, educational level, and continuing education in GM were positively and significantly associated with participants’ GM practice. Conclusion: Offering continuing education for Taiwanese physicians is needed to enhance their practice in GM.

Abstract: AIM Genetic variations present within Wnt and AhR pathway might be related to the lung cancer susceptibility. METHODS A total of 555 subjects were genotyped using PCR-RFLP technique for polymorphic sites in DKK4, DKK3, DKK2, sFRP3, sFRP4, Axin2 and AhR. Multifactor dimensionality reduction method and classification and regression tree analysis was used. RESULTS Overall sFRP4rs1802073 which has a cross validation consistency of 10/10, prediction error = 0.43 (p > 0.0001) is the best factor model. The second best model was sFRP4rs1802073 and DKK2rs419558 with cross validation consistency of 9/10 and prediction error = 0.40. In classification and regression tree analysis, DKK2 rs419558 came out to be a significant factor; DKK2rs17037102 (M)/DKK2rs419558 (M) showed a tenfold risk of acquiring lung cancer, p = 0.0001. DKK2rs17037102 (M)/AhRrs2066853 (W)/AhRrs10250822 (M) showed an 11-fold risk of developing lung cancer, p = 0.00001. CONCLUSION Both DKK2 and sFRP4 polymorphisms are found to play a crucial role; especially for smokers towards modulating risk for lung cancer. AhR variants are contributing maximally toward lung cancer risk.

Abstract: Adolescent idiopathic scoliosis (AIS) is a common complex multifactorial disease and one of the most prevalent childhood deformities worldwide [1,2]. On average, AIS affects 4% of the global pediatric population [3]. It represents a serious and chronic health condition affecting individuals all throughout their lives. More than 7 million patients in the USA are diagnosed with scoliosis (over 350,000 in Canada). Most are diagnosed with scoliosis between the ages of 10 and 15 years, and one out of every six children will have a progressive curve that requires active treatment. Due to its persistently idiopathic nature, the standard care for AIS has not significantly changed in decades. Current patients are treated by observation, bracing and, as a last resort, spinal-fusion surgery. Because of the patients’ discomfort and risk, the application of current treatments is delayed until a significant deformity or progression is detected. This results in suboptimal treatment, significant psychological sequelae and heavy economic burdens for the families and healthcare systems (∼US$2.7 billion in USA annually).

Abstract: Some articles have reported severe toxicities induced by cisplatin/5-fluorouracil regimens, nevertheless, severe and lethal liver toxicity has not been previously reported. In this article, we report the case of a 72-year-old woman, who developed fulminant hepatitis, hypoglycemia and hypotension with atrial fibrillation not responding to treatment. After ruling out all other possible causes of hepatitis, the toxicity was more likely attributed to 5-fluorouracil. Genotyping was performed and the patient was found to be a homozygote carrier of the T variant of the MTHFR gene. The patient died two days later. Several factors, including genetic factors, could explain this severe toxicity. The present case discusses the importance of personalized medicine in oncology based on pharmacogenetic analysis of polymorphisms.

Abstract: During the era of classical psychiatry, doctors already suspected that heredity might well be the main driving force behind mental disorders. Today, with an estimated heritability of 46.3% for neuropsychiatric disorders in general [1], and of 70% for schizophrenia [2], the genomics era has proved those 19th century pioneers right, and instilled much optimism with regard to genetic tests enabling us to diagnose specific disorders, predict treatment responses to psychotropic substances and prevent side effects. And yet precisionhealth approaches are still rare in clinical psychiatry, with only few disorders – other than Huntington’s disease and 22q11 deletion syndrome – lending themselves for genetic testing. With hundreds of causal genetic variants unearthed so far, and thousands suspected to exist, it is easy to blame this on the polygenic and pleiotropic nature of genetic contributions to psychiatric disease. And yet there is more. It is also due to the fact, as famously stated by Kenneth Kendler, that “patterns of underlying genetic liability do not map well onto current DSM [Diagnostic and Statistical Manual of Mental Disorders] categories – that is, our genes seem neither to have read DSM-IV nor to particularly respect the diagnostic boundaries it established” [3]. Since that insightful remark, the DSM has moved on to its fifth edition [4], but matching its numerous disorders with findings from genetic studies has remained an ongoing challenge, and the personalized approach has remained a rather futuristic ideal in psychiatry. Which is a pity, since psychiatry once had a head start in the area of personalized medicine, long before the term had even been invented. Around the turn of the 19th century, the literature in my discipline brimmed with clinical descriptions, neuropathological findings and novel disease concepts that were readily applicable to individuals with highly specific symptoms and syndromes. I would have loved to be a doctor during that pivotal era, and browse through the freshly printed issues of scientific journals providing the exciting first descriptions of autoscopy [5], peduncular hallucinosis [6], Capgras’ syndrome [7], Alzheimer’s disease [8], dissociation [9], cryptomnesia [10], Riddoch’s phenomenon [11] and many other symptoms, syndromes and disorders, only few of which eventually made it into the DSM. Given the phenomenal richness of that innovative period, we may ask ourselves – and should in fact ask ourselves – what happened during the intervening time to make us end up with diagnostic tools such as the DSM-5, which either lump those specific clinical disorders together into broad disease categories or fail to mention them at all. The answer to that question is quite sobering. For lack of any specific therapeutic interventions, 19th century psychiatric Psychiatry is warming up to personalized medicine 2.0