Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Médecine sociate en 2013: quand la précarité précède la pauvrete [Social medicine: does it still make sense in 2013?].

Social medicine is a medicine that seeks to understand the impact of socio-economic conditions on human health and diseases in order to improve the health of a society and its individuals. In this field of medicine, determining the socio-economic status of individuals is generally not sufficient to explain and/or understand the underlying mechanisms leading to social inequalities in health. Other factors must be considered such as environmental, psychosocial, behavioral and biological factors that, together, can lead to more or less permanent damages to the health of the individuals in a society. In a time where considerable progresses have been made in the field of the biomedicine, does the practice of social medicine in a primary care setting still make sense?

The Lausanne Institutional Biobank: a new resource to catalyse research in personalised medicine and pharmaceutical sciences.

Breakthrough technologies which now enable the sequencing of individual genomes will irreversibly modify the way diseases are diagnosed, predicted, prevented and treated. For these technologies to reach their full potential requires, upstream, access to high-quality biomedical data and samples from large number of properly informed and consenting individuals and, downstream, the possibility to transform the emerging knowledge into a clinical utility. The Lausanne Institutional Biobank was designed as an integrated, highly versatile infrastructure to harness the power of these emerging technologies and catalyse the discovery and development of innovative therapeutics and biomarkers, and advance the field of personalised medicine. Described here are its rationale, design and governance, as well as parallel initiatives which have been launched locally to address the societal, ethical and technological issues associated with this new bio-resource. Since January 2013, inpatients admitted at Lausanne CHUV University Hospital have been systematically invited to provide a general consent for the use of their biomedical data and samples for research, to complete a standardised questionnaire, to donate a 10-ml sample of blood for future DNA extraction and to be re-contacted for future clinical trials. Over the first 18 months of operation, 14,459 patients were contacted, and 11,051 accepted to participate in the study. This initial 18-month experience illustrates that a systematic hospital-based biobank is feasible; it shows a strong engagement in research from the patient population in this University Hospital setting, and the need for a broad, integrated approach for the future of medicine to reach its full potential.

Medication incidents in primary care medicine: protocol of a study by the Swiss Federal Sentinel Reporting System.

BACKGROUND/RATIONALE: Patient safety is a major concern in healthcare systems worldwide. Although most safety research has been conducted in the inpatient setting, evidence indicates that medical errors and adverse events are a threat to patients in the primary care setting as well. Since information about the frequency and outcomes of safety incidents in primary care is required, the goals of this study are to describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents. Label="METHODS AND ANALYSIS" ="METHODS"/> <AbstractText STUDY DESIGN AND SETTING: We will conduct a prospective surveillance study to identify cases of medication incidents among primary care patients in Switzerland over the course of the year 2015. PARTICIPANTS: Patients undergoing drug treatment by 167 general practitioners or paediatricians reporting to the Swiss Federal Sentinel Reporting System. INCLUSION CRITERIA: Any erroneous event, as defined by the physician, related to the medication process and interfering with normal treatment course. EXCLUSION CRITERIA: Lack of treatment effect, adverse drug reactions or drug-drug or drug-disease interactions without detectable treatment error. PRIMARY OUTCOME: Medication incidents. RISK FACTORS: Age, gender, polymedication, morbidity, care dependency, hospitalisation. STATISTICAL ANALYSIS: Descriptive statistics to assess type, frequency, seasonal and regional distribution of medication incidents and logistic regression to assess their association with potential risk factors. Estimated sample size: 500 medication incidents. LIMITATIONS: We will take into account under-reporting and selective reporting among others as potential sources of bias or imprecision when interpreting the results. ETHICS AND DISSEMINATION: No formal request was necessary because of fully anonymised data. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT0229537.

Sudden cardiac death in forensic medicine - Swiss recommendations for a multidisciplinary approach.

Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.

Traditional local medicines in the republic of Palau and non-communicable diseases (NCD), signs of effectiveness.

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this survey was to describe which traditional medicines (TM) are most commonly used for non-communicable diseases (NCD - diabetes, hypertension related to excess weight and obesity) in Pacific islands and with what perceived effectiveness. NCD, especially prevalent in the Pacific, have been subject to many public health interventions, often with rather disappointing results. Innovative interventions are required; one hypothesis is that some local, traditional approaches may have been overlooked. MATERIALS AND METHODS: The method used was a retrospective treatment-outcome study in a nation-wide representative sample of the adult population (about 15,000 individuals) of the Republic of Palau, an archipelago of Micronesia. RESULTS: From 188 respondents (61% female, age 16-87, median 48,), 30 different plants were used, mostly self-prepared (69%), or from a traditional healer (18%). For excess weight, when comparing the two most frequent plants, Morinda citrifolia L. was associated with more adequate outcome than Phaleria nishidae Kaneh. (P=0.05). In case of diabetes, when comparing Phaleria nishidae (=Phaleria nisidai) and Morinda citrifolia, the former was statistically more often associated with the reported outcome "lower blood sugar" (P=0.01). CONCLUSIONS: Statistical association between a plant used and reported outcome is not a proof of effectiveness or safety, but it can help select plants of interest for further studies, e.g. through a reverse pharmacology process, in search of local products which may have a positive impact on population health.

LE || TIERS LIVRE || Des Faicts et Dicts || Heroïques du bon Pantagruel : || Composé par M. Fran. || Rabelais docteur || en Medi- || cine. || Reueu, & corrigé par l'Autheur, sus || la censure antique. || L'Autheur susdict || supplie les Lecteurs beneuoles, soy || reseruer a rire au soixante || & dixhuytiesme || Liure. || A Paris, || De l'imprimerie de Michel Fezandat, au mont || S. Hilaire, a l'hostel d'Albret. || 1552. Il Auec priuilege du Roy. In-8 de 160 f. inexactement chiffr. (le dernier coté 170), 3 f. non chiffr. et 1 f. blanc. — LE || QVART LIVRE || des faicts et || dicts Heroiques du bon || Pantagruel. || Composé par M. François Rabelais || docteur en Medicine. || A Paris, || De l'imprimerie de Michel Fezandat, au mont || S. Hilaire, a l'hostel d'Albret. || 1552. || Auec priuilege du Roy. — [A la fin de la Table :] Acheué d'imprimer le XXVIII. de || Ianuier M.D.LII [1552]. In-8 de 19 f. non chiffr., 144 f. chiffr. et 14 f. non chiffr. — Ensemble 2 vol. in-8, mar. citr., fil., dos ornés, tr. dor. (Anc. rel.). Rothschild 1514 (2)

Rabelais (François). Tiers Livre (1552)

The use of relaxation therapy as an adjunct to traditional psoriasis therapy /

This research investigated the impact of stress management and relaxation techniques on psoriasis. It had a dual purpose to see if stress management and relaxation techniques, as an adjunct to traditional medical treatment, would improve the skin condition of psoriasis. In addition it attempted to provide psoriasis patients with a sense of control over their illness by educating them about the connection between mind and body through learning stress management and relaxation techniques. The former purpose was addressed quantitatively, while the latter was addressed qualitatively. Using an experimental design, the quantitative study tested the efficacy of stress management and relaxation techniques on 38 dermatological patients from St. John's, Newfoundland. The study which lasted ten weeks, suggested a weak relationship between psoriasis and stress. These relationships were not statistically significant. The qualitative data were gathered through unstructured interviews and descriptive/interpretative analysis was used to evaluate them. Patients in the experimental group believed in the mind body connection as it related to their illness and stress. The findings also showed that the patients believed that the stress reduction and relaxation techniques improved their quality of life, their level of psoriasis, and their ability to live with the condition. Based on the contradictory nature of the findings, further research is needed. It is posited that replication of this study would be vastly improved by increasing the sample size to increase the possibility of significant findings. As wel~ increasing the length of time for the experiment would control for the possibility of a lag effect. Finally, the study looked at linear relationships between stress and psoriasis. Further study should ascertain whether the relationship might be nonlinear

Exploring Chinese-Canadians' perspectives on health : a quantitative study

Chinese have unique perspectives on health and illness, which is mostly umecognized by western medicine. Immigration may contribute to problems with health consultations, inconvenience, and dissatisfaction. As the largest visible minority in Canada, Chinese- Canadians' perspectives on health should be studied in order to help Chinese immigrants adapt to a new health-care and health-promotion system, and keep them healthy. A quantitative questionnaire was designed based on the findings from a pilot study and previous literature. A hundred participants were recruited from Toronto, Vancouver, Halifax, and St. Catharines. Descriptive analysis and correlation analysis were used to investigate the structure of the variables. Findings indicated that most oftheir attitudes and corresponding practices to the different health aspects were positive. The relation between dietary practices and attitude was only found in small cities. Their attitudes were impacted by their length of stay in Canada. Their attitudes to regularly timed meals and psychological consultation were related to their acculturation level, as was the regularity of their practice of dental flossing. Their self-evaluated general health levels were also found to be affected by their medical history, education level, feeling to talk about • sexual health, and smoking, particularly in the male subjects of the study. In conclusion, they realized that each health aspect w~s important to their health. However, their practices did not bear a strong relation to their beliefs. Traditional thoughts about health reseeded with time. Acculturation level did not affect most of their attitudes or practices. Under pressure, the priority of the daily health practices decreased. Older persons, those with low incomes, lower education levels or families under stress need to pay more attention to their health level. In-depth future research was recommended.

The Relationship between Dementia Family Caregivers' Traditional Values and Beliefs about Caregiving and Well-being

Introduction: Canada’s aging population is diverse and this diversity will continue to grow for the next two decades (Government of Canada, 2002; Katz, 2005; Statistics Canada, 2010). Objective: to examine the relationship between dementia family caregivers’ traditionally-based beliefs about caregiving, their caregiving experience, and their well-being. Method: exploratory secondary data analysis of cross-sectional survey data from 76 community caregivers of persons with dementia in Ontario. Results: traditional values for caregiving was independently associated with coping resources and health status but not depression symptoms. Caregiver self-efficacy and social support both partially mediated the relationship between beliefs about caregiving and caregiver health status. Discussion: Findings from this exploratory study are consistent with stress process models of culture and caregiving. The finding that self-efficacy was associated with traditional values and that it mediated the relationship between traditional values and caregiver well-being is new to the literature.

Ojibwe Elders' Experiences of Peace: To Teach Our Well-Being With the Earth

This research focuses on exploring the Anishinaabek/Ojibwe worldview founded upon the spiritual relationship with Mother Earth as the Anishinaabek view of peace to teach our well-being with earth. This research explores the experiences of four 21st century traditional Anishinaabek elders through describing their ways of knowing and of being as it relates to the Anishinaabek worldview of respect and peace with nature. This respect for Mother Earth and respecting earth’s way−akii-bimaadizi is articulated and shared regarding elders’ experiences of teaching our well-being with earth−Akinomaage mino akii-ayaa and is based upon Anishinaabek spirituality. This research details the Anishinaabek worldview from the elders’ shared experiences of earth as teacher and elder. Ten themes emerged from the data. These themes included (a) going back to our original gifts and instructions/building your sacred bundle/sharing your sacred bundle, (b) wisdom−nbwaakaawin: connecting the dots/original instructions/medicine−mshkiki/environmental consciousness, (c) sacred teachings/learning from the elders, (d) relationships/honoring elders/eldership, (e) political experiences and awareness, (f) a way of being in Anishinaabek research, (g) survival, (h) peace is our worldview demonstrated, (i) be aware of colonialistic thinking, (j) Akinomaage: earth as context. The researcher also shares her reflections as a researcher and as an Anishinaabekwe: Ojibwe woman.