Munchausen syndrome by proxy: A narrative review and update for the dentist and other healthcare professionals.

Munchausen syndrome by proxy (MSbP) is a form of abuse in which a caregiver with Factitious Disorder Imposed on Another (FDIA) fabricates or induces signs or symptoms in a person under their care to satisfy a self-serving psychological need. Unnecessary clinical evaluations, procedures, and treatments that are initiated based on falsification by the abuser inadvertently add to the trauma experienced by the victim. It is a form of abuse and the impact on victims can be severe, sometimes fatal, and far-reaching such as prolonged neglect and extension to affected siblings. The long-term exposure to MSbP may predispose the victim to eventually developing factitious disorder imposed on self (FDIS). While MSbP often involves child victims, elderly, adults, and pets have also been reported as victims. MSbP can be a diagnostic challenge, and the important keys to timely identification of MSbP include the ability to detect deception by caregivers through awareness, clinical suspicion, and careful review of available health records; it also involves collecting collaborative information from other relevant healthcare providers including dentists, schoolteachers, and social workers. To date, there are limited published cases of MSbP with oral findings. This paper provides a narrative review of the current understanding of MSbP with a section on cases with oral findings. This paper aims to increase awareness about the clinical presentations and management considerations for MSbP among dentists and other healthcare professionals.

Land use diversification may mitigate on-site land use impacts on mammal populations and assemblages.

Land use is a major cause of biodiversity decline worldwide. Agricultural and forestry diversification measures, such as the inclusion of natural elements or diversified crop types, may reduce impacts on biodiversity. However, the extent to which such measures may compensate for the negative impacts of land use remains unknown. To fill that gap, we synthesised data from 99 studies that recorded mammal populations or assemblages in natural reference sites and in cropland and forest plantations, with or without diversification measures. We quantified the responses to diversification measures based on individual species abundance, species richness and assemblage intactness as quantified by the mean species abundance indicator. In cropland with natural elements, mammal species abundance and richness were, on average, similar to natural conditions, while in cropland without natural elements they were reduced by 28% and 34%, respectively. We found that mammal species richness was comparable between diversified forest plantations and natural reference sites, and 32% lower in plantations without natural elements. In both cropland and plantations, assemblage intactness was reduced compared with natural reference conditions, but the reduction was smaller if diversification measures were in place. In addition, we found that responses to land use were modified by species traits and environmental context. While habitat specialist populations were reduced in cropland without diversification and in forest plantations, habitat generalists benefited. Furthermore, assemblages were impacted more by land use in tropical regions and landscapes containing a larger share of (semi)natural habitat compared with temperate regions and more converted landscapes. Given that mammal assemblage intactness is reduced also when diversification measures are in place, special attention should be directed to species that suffer from land use impacts. That said, our results suggest potential for reconciling land use and mammal conservation, provided that the diversification measures do not compromise yield.

Towards credible, evidence-based environmental rating ecolabels for consumer products: A proposed framework.

Environmental rating ecolabels are a new generation of ecolabels. They are intended to enable consumers to compare the environmental impacts of multiple products and make more sustainable consumption choices. Falling outside of the three types defined in the ISO 14020 environmental label and declarations series, the recent proliferation of these business-to-consumer communication instruments has resulted in the creation of a plethora of methodologies to derive product performance ratings. Interest from consumers wanting more information on the products they purchase, as well as the promise of policy instruments aiming to increase transparency and combat greenwashing, are fuelling further multiplication of schemes. A move towards more credible, evidence-based environmental rating ecolabels is therefore urgently needed to promote assessment based on scientific understanding, gain consumer trust, and realise policy objectives. We propose a framework based on four core principles - i) relevance, ii) scientific robustness, iii) trust and transparency, and iv) feasibility (scalability, affordability) - with 18 guidelines that can be followed by rating scheme developers. We characterise the rise of environmental rating ecolabels in geographical Europe and build an inventory of 33 existing schemes, at various stages of development and implementation, to which we apply the framework. This reveals the potential for significant improvement in current schemes, indicating important areas for development. The framework provides a valuable guide for the development of new schemes or an evaluation grid for existing initiatives.

A longitudinal, narrative study of professional socialisation among health students.

PURPOSE: Interprofessional collaboration (IPC) among health professionals is well-recognised to enhance care delivery and patient outcomes. Emerging evidence suggests that the early socialisation of students in health professional programmes to teamwork may have a positive impact on their future as collaborative practitioners. With a purpose of contributing to growing evidence on the processes of professional identity construction, and to explore how early expectations and perceptions of IPC develop during professional socialisation and pre-licensure education, our study examined the early professional socialisation experiences among five groups of health professional students. METHOD: A qualitative, narrative approach was used to examine early professional socialisation among five programmes of health professional students (dentistry, medicine, nursing, pharmacy, physiotherapy) at an Atlantic Canadian University. In March and October 2016, students participated in interviews after first term (n = 44) and first year of study (n = 39). Interviews focused on participants' professional identify formation, as well as their perceptions and experiences of IPC. The authors analysed interview transcripts using narrative analysis. RESULTS: Findings identify that despite the espoused importance of IPC within health professional training, students have a limited understanding of their professional roles and are largely focused on developing a uniprofessional, vs. interprofessional identity. Clinical experiences, role models and exposure to teamwork are critical to contextualise collaborative practice and enhance the development of an interprofessional identity. CONCLUSIONS: Findings can be used to guide the development of curricula that promote interprofessional identity development and IPC during early professional socialisation.

Variability of Greenhouse Gas Footprints of Field Tomatoes Grown for Processing: Interyear and Intercountry Assessment.

Our study provides an integrated analysis of the variability of greenhouse gas (GHG) footprints of field-grown tomatoes for processing. The global farm-specific data set of 890 observations across 14 countries over a three-year period (2013-2015) was obtained from farms grown under Unilever's sustainable agricultural code. It represents on average 3% of the annual global production of processing tomatoes: insights can be used to help inform corporate sourcing strategies and certification schemes. The median GHG footprint ranged from 18 in Chile to 61 kg CO2-equiv per tonne of tomatoes in India, lower than results reported in other studies. We found that footprints are more consistent within countries than between them. Using linear mixed effect models, we quantified the relative influence of environmental conditions and farm management factors. Key variables were area of production and the method of fertilizer application. GHG footprints decreased with increasing area of production to a threshold of 17.4 ha. Farms using single fertilizer application methods in general had a larger GHG footprint than those using a combination of methods. We conclude that farm management factors should be prioritized for future data collection, and more stringent guidance on acceptable practices is required if greater comparability of outcomes is needed either within a scheme, such as the Unilever's sustainable agriculture code, or between schemes.

Spatial patterns of agricultural expansion determine impacts on biodiversity and carbon storage.

The agricultural expansion and intensification required to meet growing food and agri-based product demand present important challenges to future levels and management of biodiversity and ecosystem services. Influential actors such as corporations, governments, and multilateral organizations have made commitments to meeting future agricultural demand sustainably and preserving critical ecosystems. Current approaches to predicting the impacts of agricultural expansion involve calculation of total land conversion and assessment of the impacts on biodiversity or ecosystem services on a per-area basis, generally assuming a linear relationship between impact and land area. However, the impacts of continuing land development are often not linear and can vary considerably with spatial configuration. We demonstrate what could be gained by spatially explicit analysis of agricultural expansion at a large scale compared with the simple measure of total area converted, with a focus on the impacts on biodiversity and carbon storage. Using simple modeling approaches for two regions of Brazil, we find that for the same amount of land conversion, the declines in biodiversity and carbon storage can vary two- to fourfold depending on the spatial pattern of conversion. Impacts increase most rapidly in the earliest stages of agricultural expansion and are more pronounced in scenarios where conversion occurs in forest interiors compared with expansion into forests from their edges. This study reveals the importance of spatially explicit information in the assessment of land-use change impacts and for future land management and conservation.

A case of gamasoidosis associated with exposure to a wild lorikeet feeding tray.

Gamasoidosis (acariasis, avian-mite dermatitis or bird-mite dermatitis) is caused by members of the mite superfamily Dermanyssoidea. The mites lay their eggs on the nest of the birds they feed on. The also leave the nest and feed on humans if there is no bird host available. The bites result in urticated plaques and papules. Here we present a case of gamasoidosis from exposure to a wild lorikeet feeding tray.

The CYP2C19 Intron 2 Branch Point SNP is the Ancestral Polymorphism Contributing to the Poor Metabolizer Phenotype in Livers with CYP2C19*35 and CYP2C19*2 Alleles.

CYP2C19 rs12769205 alters an intron 2 branch point adenine leading to an alternative mRNA in human liver with complete inclusion of intron 2 (exon 2B). rs12769205 changes the mRNA reading frame, introduces 87 amino acids, and leads to a premature stop codon. The 1000 Genomes project (http://browser.1000genomes.org/index.html) indicated rs12769205 is in linkage disequilibrium with rs4244285 on CYP2C19*2, but found alone on CYP2C19*35 in Blacks. Minigenes containing rs12769205 transfected into HepG2 cells demonstrated this single nucleotide polymorphism (SNP) alone leads to exon 2B and decreases CYP2C19 canonical mRNA. A residual amount of CYP2C19 protein was detectable by quantitative proteomics with tandem mass spectrometry in CYP2C19*2/*2 and *1/*35 liver microsomes with an exon 2 probe. However, an exon 4 probe, downstream from rs12769205, but upstream of rs4244285, failed to detect CYP2C19 protein in livers homozygous for rs12769205, demonstrating rs12769205 alone can lead to complete loss of CYP2C19 protein. CYP2C19 genotypes and mephenytoin phenotype were compared in 104 Ethiopians. Poor metabolism of mephenytoin was seen in persons homozygous for both rs12769205 and rs4244285 (CYP2C19*2/*2), but with little effect on mephenytoin disposition of CYP2C19*1/*2, CYP2C19*1/*3, or CYP2C19*1/*35 heterozygous alleles. Extended haplotype homozygosity tests of the HapMap Yorubans (YRI) showed both haplotypes carrying rs12769205 (CYP2C19*35 and CYP2C19*2) are under significant natural selection, with CYP2C19*35 having a higher relative extended haplotype homozygosity score. The phylogenetic tree of the YRI CYP2C19 haplotypes revealed rs12769205 arose first on CYP2C19*35 and that rs4244285 was added later, creating CYP2C19*2. In conclusion, rs12769205 is the ancestral polymorphism leading to aberrant splicing of CYP2C19*35 and CYP2C19*2 alleles in liver.

Strategies and indicators to integrate health equity in health service and delivery systems in high-income countries: a scoping review.

OBJECTIVE: The objective of this review was to describe how health service and delivery systems in high-income countries define and operationalize health equity. A secondary objective was to identify implementation strategies and indicators being used to integrate and measure health equity. INTRODUCTION: To improve the health of populations, a population health and health equity approach is needed. To date, most work on health equity integration has focused on reducing health inequities within public health, health care delivery, or providers within a health system, but less is known about integration across the health service and delivery system. INCLUSION CRITERIA: This review included academic and gray literature sources that described the definitions, frameworks, level of integration, strategies, and indicators that health service and delivery systems in high-income countries have used to describe, integrate, and/or measure health equity. Sources were excluded if they were not available in English (or a translation was not available), were published before 1986, focused on strategies that were not implemented, did not provide health equity indicators, or featured strategies that were implemented outside the health service or delivery systems (eg, community-based strategies). METHODS: This review was conducted in accordance with the JBI methodology for scoping reviews. Titles and abstracts were screened for eligibility followed by a full-text review to determine inclusion. The information extracted from the included studies consisted of study design and key findings, such as health equity definitions, strategies, frameworks, level of integration, and indicators. Most data were quantitatively tabulated and presented according to 5 secondary review questions. Some findings (eg, definitions and indicators) were summarized using qualitative methods. Most findings were visually presented in charts and diagrams or presented in tabular format. RESULTS: Following review of 16,297 titles and abstracts and 824 full-text sources, we included 122 sources (108 scholarly and 14 gray literature) in this scoping review. We found that health equity was inconsistently defined and operationalized. Only 17 sources included definitions of health equity, and we found that both indicators and strategies lacked adequate descriptions. The use of health equity frameworks was limited and, where present, there was little consistency or agreement in their use. We found that strategies were often specific to programs, services, or clinics, rather than broadly applied across health service and delivery systems. CONCLUSIONS: Our findings suggest that strategies to advance health equity work are siloed within health service and delivery systems, and are not currently being implemented system-wide (ie, across all health settings). Healthy equity definitions and frameworks are varied in the included sources, and indicators for health equity are variable and inconsistently measured. Health equity integration needs to be prioritized within and across health service and delivery systems. There is also a need for system-wide strategies to promote health equity, alongside robust accountability mechanisms for measuring health equity. This is necessary to ensure that an integrated, whole-system approach can be consistently applied in health service and delivery systems internationally. REVIEW REGISTRATION: DalSpace dalspace.library.dal.ca/handle/10222/80835.

Frailty-aware surgical care: Validation of Hospital Frailty Risk Score (HFRS) in older surgical patients.

Introduction: Frailty has an important impact on the health outcomes of older patients, and frailty screening is recommended as part of perioperative evaluation. The Hospital Frailty Risk Score (HFRS) is a validated tool that highlights frailty risk using 109 International Classification of Diseases, 10th revision (ICD-10) codes. In this study, we aim to compare HFRS to the Charlson Comorbidity Index (CCI) and validate HFRS as a predictor of adverse outcomes in Asian patients admitted to surgical services. Method: A retrospective study of electronic health records (EHR) was undertaken in patients aged 65 years and above who were discharged from surgical services between 1 April 2022 to 31 July 2022. Patients were stratified into low (HFRS <5), interme-diate (HFRS 5-15) and high (HFRS >15) risk of frailty. Results: Those at high risk of frailty were older and more likely to be men. They were also likely to have more comorbidities and a higher CCI than those at low risk of frailty. High HFRS scores were associated with an increased risk of adverse outcomes, such as mortality, hospital length of stay (LOS) and 30-day readmission. When used in combination with CCI, there was better prediction of mortality at 90 and 270 days, and 30-day readmission. Conclusion: To our knowledge, this is the first validation of HFRS in Singapore in surgical patients and confirms that high-risk HFRS predicts long LOS (≥7days), increased unplanned hospital readmissions (both 30-day and 270-day) and increased mortality (inpatient, 10-day, 30-day, 90-day, 270-day) compared with those at low risk of frailty.

Types and distribution of congenital heart defects associated with trisomy 21 in Singapore.

AIM: Atrioventricular septal defect (AVSD) is widely accepted as the most common type of congenital heart defect in trisomy 21. Most of these studies, however, were conducted in Caucasian communities. The few Asian studies that had been conducted on this subject yielded different results. In the largest study of its kind in Asia, we described the distribution of types of congenital heart defects associated with trisomy 21 in Singapore. METHODS: Five hundred and eighty-eight patients with trisomy 21 born in 1996-2010, and confirmed by karyotyping, were included in the study. The diagnosis of congenital heart defects were made on echocardiography. Variables extracted for analysis were demographics (race and gender) and the types of congenital heart defects. Except for complex cyanotic heart defects, haemodynamically significant lesions were accounted for separately in cases where more than one type of congenital heart defect coexisted in a patient. RESULTS: Ventricular septal defect (VSD) (39.2%) was the most common congenital heart defect associated with trisomy 21 in our study, followed by patent ductus arteriosus (34.3%), secundum atrial septal defect (23.4%) and AVSD (15.6%). This study validates previous smaller Asian studies identifying VSD as the most common cardiac lesion associated with trisomy 21. A high proportion (25.0%) of trisomy 21 patients with tetralogy of Fallot also had AVSDs. Coarctation of the aorta was uncommon. CONCLUSION: VSD was the most common congenital heart defect seen in trisomy 21 in our study. A high proportion (25.0%) of trisomy 21 patients with tetralogy of Fallot also had AVSDs.

Projecting global oil palm expansion under zero-deforestation commitments: Direct and indirect land use change impacts.

In the last three decades, global production of oil palm has boomed, which has partly come at the expense of tropical rainforests. Recognizing this, many companies operating in the palm oil industry have committed to eliminate deforestation from their operations, often referred to as zero-deforestation commitments (ZDCs). Here, we estimate that if ZDCs are fully adopted and enforced across all sectors and geographies, the global extent of oil palm plantations may be 11 M ha or 40% smaller in 2030 than in a business-as-usual (BAU) scenario that assumes no compliance with ZDCs. As a result of such land-sparing effects, we estimate that 96 M ha of forests are saved from conversion, of which, 17% would otherwise have been converted (directly or indirectly) due to expanding oil palm plantations. Overall, these figures suggest that ZDCs have the potential to deliver major environmental benefits if they are fully adopted and enforced.

Databases in the area of pharmacogenetics.

In the area of pharmacogenetics and personalized health care it is obvious that databases, providing important information of the occurrence and consequences of variant genes encoding drug metabolizing enzymes, drug transporters, drug targets, and other proteins of importance for drug response or toxicity, are of critical value for scientists, physicians, and industry. The primary outcome of the pharmacogenomic field is the identification of biomarkers that can predict drug toxicity and drug response, thereby individualizing and improving drug treatment of patients. The drug in question and the polymorphic gene exerting the impact are the main issues to be searched for in the databases. Here, we review the databases that provide useful information in this respect, of benefit for the development of the pharmacogenomic field.

Intronic polymorphisms of cytochromes P450.

The cytochrome P450 enzymes active in drug metabolism are highly polymorphic. Most allelic variants have been described for enzymes encoded by the cytochrome P450 family 2 (CYP2) gene family, which has 252 different alleles. The intronic polymorphisms in the cytochrome P450 genes account for only a small number of the important variant alleles; however, the most important ones are CYP2D6*4 and CYP2D6*41 , which cause abolished and reduced CYP2D6 activity, respectively, and CYP3A5* 3 and CYP3A5*5 , common in Caucasian populations, which cause almost null activity. Their discoveries have been based on phenotypic alterations within individuals in a population, and their identification has, in several cases, been difficult and taken a long time. In light of the next-generation sequencing projects, it is anticipated that further alleles with intronic mutations will be identified that can explain the hitherto unidentified genetic basis of inter-individual differences in cytochrome P450-mediated drug and steroid metabolism.

The Human Cytochrome P450 (CYP) Allele Nomenclature website: a peer-reviewed database of CYP variants and their associated effects.

Pharmacogenetics affects both pharmacokinetics and pharmacodynamics, thereby influencing an individual's response to drugs, both in terms of response and adverse reactions. Within the area of pharmacogenetics, findings of genetic variation influencing drug levels have been more prevalent, and variation in the cytochrome P450 (CYP) enzymes is one of the most common causes. Much of the work concerning sequence variations in CYPs aims at finding biomarkers of use for individualised treatment, thereby increasing the treatment response, lowering the number of side effects and decreasing the overall cost of treatment regimens. For over ten years, the Human Cytochrome P450 Allele Nomenclature (CYP-allele) website (http://www.cypalleles.ki.se/) has offered a database of genetic information on CYP variants, along with effects at the molecular as well as clinical level. Thus, this database serves as an assembly of past, current and soon-to-be published information on CYP alleles and their outcome effects. The website is used by academic researchers and companies (eg as a tool in drug development and for outlining new research projects). By providing peer-reviewed genetic information on CYP enzymes, the CYP-allele website has become increasingly popular and widely used. Recently, NADPH cytochrome P450 oxidoreductase (POR), the electron donor for CYP enzymes, was included on the website, which already contains 29 CYP genes, hence POR alleles are now also designated using the star allele (POR*) nomenclature. Although most CYPs on the CYP-allele website are involved in the metabolism of xenobiotics, polymorphic enzymes with endogenous functions are also included. Each gene on the CYP-allele website has its own webpage that lists the different alleles with their nucleotide changes, their functional consequences and links to publications in which the allele has been identified and/or characterised. Thus, the CYP-allele website offers a rapid online publication of new alleles, as well as providing an overview of peer-reviewed data.

Intracranial sclerosing extramedullary haematopoietic tumour mimicking meningioma in a patient with myelofibrosis: Case report.

Sclerosing extramedullary hematopoietic tumour is a rare tumour which can occur in certain myeloproliferative diseases, typically myelofibrosis. Typically these tumours present as a discrete retroperitoneal mass or masses, however they can occur in other sites within the body. In this case report we describe a 61-year old woman who underwent stealth guided bi-temporal craniotomy for resection of what was expected to be a large falx meningioma, however histopathology revealed the lesion to be a sclerosing extramedullary hematopoietic tumour. Following surgery, the patients post-operative recovery was complicated by intracerebral haemorrhage which required emergency evacuation and the patient remained in intensive care on a ventilator for 3 weeks. At one year follow up the patient reports her presenting symptoms of headaches, nausea, and vertigo had resolved.

Breastfeeding experiences among mothers living with food insecurity in high resource, Western countries: a qualitative systematic review protocol.

OBJECTIVE: The objectives of this review are to identify, appraise, and synthesize the qualitative evidence on the breastfeeding experiences of mothers living with food insecurity in high-resource, Western countries. INTRODUCTION: Breastfeeding and food insecurity are inter-related health issues. Globally, breastfeeding augments food security at individual, household, and community levels, but a growing body of evidence from high-resourced countries also suggests that a mother's breastfeeding practice may be negatively impacted by the additional experience of food insecurity. This protocol outlines a systematic approach to understanding the experiences of breastfeeding from the perspective of mothers living with food insecurity. Findings will provide much-needed evidence toward guiding policies and practices that support mothers to breastfeed. INCLUSION CRITERIA: The review will consider studies that explore the breastfeeding experiences of mothers aged 18 years and older who self-identify, or are classified using a screening tool, as food insecure. Papers that will be included in this review will consider all qualitative methodologies and will be limited to studies from countries identified as being within the United Nations classification of Western European and Other States Group (WEOG). METHODS: The authors will conduct a three-step search process across both published and gray literature to identify relevant studies for inclusion. A preliminary search using the PubMed database was undertaken in January 2020. Studies published in English from 1981 to 2020 will be included. The recommended JBI methodology for qualitative systematic review for study selection, critical appraisal, data extraction, and data synthesis will be followed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020183652.

Estimating greenhouse gas emissions from direct land use change due to crop production in multiple countries.

Greenhouse gas (GHG) emissions from direct land use change (LUC) in GHG footprint studies of crops are often estimated using national land use change statistics, as in many cases the exact location of crop cultivation and land use history is unknown. As such, these studies neglect spatial variability in land use change (amount and configuration) at the sub-national level as well as spatial variability in natural carbon stocks. For this reason, a spatial approach that enables consistent implementation of LUC emissions of crop production at different locations is developed and applied in this study. The dataset of crop production covers 69 crops cultivated on 1885 farms in 33 countries, spanning North and South America, Asia, Australia and Oceania, Europe and Africa, in the year 2014. Of the 1885 farms, 33% (619 farms) were identified to have LUC emissions when estimated at the local scale. LUC emissions of farms, derived using local scale location information, were found to have little correlation with those estimated at coarser spatial scales (such as the province or country level) using the spatial approach in this study or estimated using accounting approaches based on national statistics. Analysis at coarser spatial scales typically overestimated the LUC emissions of crops, as LUC in other regions can heavily influence these estimates. Therefore, it is concluded that local scale LUC emissions better represent local LUC dynamics, thereby improving the reliability of GHG footprint studies.

Molecular genetics and epigenetics of the cytochrome P450 gene family and its relevance for cancer risk and treatment.

The cytochromes P450 (CYPs) are very efficient catalysts of foreign compound metabolism and are responsible for the major part of metabolism of clinically important drugs. The enzymes are important in cancer since they (a) activate dietary and environmental components to ultimate carcinogens, (b) activate or inactivate drugs used for cancer treatment, and (c) are potential targets for anticancer therapy. The genes encoding the CYP enzymes active in drug metabolism are highly polymorphic, whereas those encoding metabolism of precarcinogens are relatively conserved. A vast amount of literature is present where investigators have tried to link genetic polymorphism in CYPs to cancer susceptibility, although not much conclusive data have hitherto been obtained, with exception of CYP2A6 polymorphism and tobacco induced cancer, to a great extent because of lack of important functional polymorphisms in the genes studied. With respect to anticancer treatment, the genetic CYP polymorphism is of greater importance, where treatment with tamoxifen, but also with cyclophosphamide and maybe thalidomide is influenced by CYP genetic variants. In the present review we present updates on CYP genetics, cancer risk and treatment and also epigenetic aspects of interindividual variability in CYP expression and the use of these enzymes as targets for cancer therapy. We conclude that the CYP polymorphism does not predict cancer susceptibility to any large extent but that this polymorphism might be an important factor for optimal cancer therapy using selected anticancer agents.

Pharmacogenetic biomarkers as tools for improved drug therapy; emphasis on the cytochrome P450 system.

Important interindividual differences in drug pharmacokinetics cause absence of drug response or adverse drug reactions in significant fractions of the populations. The identification of the major enzymes participating, and the elucidation of the genetic basis for this variation in particular among cytochromes P450, provide tools for a personalized medicine treatment, which can make drug therapy much more effective at a lower cost. Much of the pioneering work linking drug metabolizing phenotype to genetic polymorphism among the P450 enzymes has been carried out at Karolinska Institutet. In this review we give a background and description of this work as well as the important implications for future medicine.