Exploring health equity integration among health service and delivery systems in Nova Scotia: perspectives of health system partners.

BACKGROUND: Achieving health equity is important to improve population health; however, health equity is not typically well defined, integrated, or measured within health service and delivery systems. To improve population health, it is necessary to understand barriers and facilitators to health equity integration within health service and delivery systems. This study aimed to explore health equity integration among health systems workers and identify key barriers and facilitators to implementing health equity strategies within the health service and delivery system in Nova Scotia, ahead of the release of a Health Equity Framework, focused on addressing inequities within publicly funded institutions. METHODS: Purposive sampling was used to recruit individuals working on health equity initiatives including those in high-level leadership positions within the Nova Scotia health system. Individual interviews and a joint interview session were conducted. Topics of discussion included current integration of health equity through existing strategies and perceptions within participant roles. The Consolidated Framework for Implementation Research (CFIR) was used to guide coding and analysis, with interviews transcribed and deductively analyzed in NVivo. Qualitative description was employed to describe study findings as barriers and facilitators to health equity integration. RESULTS: Eleven individual interviews and one joint interview (n = 5 participants) were conducted, a total of 16 participants. Half (n = 8) of the participants were High-level Leaders (i.e., manager or higher) within the health system. We found that existing strategies within the health system were inadequate to address inequities, and variation in the use of indicators of health equity was indicative of a lack of health equity integration. Applying the CFIR allowed us to identify barriers to and facilitators of health equity integration, with the power of legislation to implement a Health Equity Framework, alongside the value of partnerships and engagement both being seen as key facilitators to support health equity integration. Barriers to health equity integration included inadequate resources devoted to health equity work, a lack of diversity among senior system leaders and concerns that existing efforts to integrate health equity were siloed. CONCLUSION: Our findings suggest that health equity integration needs to be prioritized within the health service and delivery system within Nova Scotia and identifies possible strategies for implementation. Appropriate measures, resources and partnerships need to be put in place to support health equity integration following the introduction of the Health Equity Framework, which was viewed as a key driver for action. Greater diversity within health system leadership was also identified as an important strategy to support integration. Our findings have implications for other jurisdictions seeking to advance health equity across health service and delivery systems.

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.

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.

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.

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.

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.

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.

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.

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.

Clinically Relevant Cytochrome P450 3A4 Induction Mechanisms and Drug Screening in Three-Dimensional Spheroid Cultures of Primary Human Hepatocytes.

Cytochrome P450 (CYP) 3A4 induction is an important cause of drug-drug interactions, making early identification of drug candidates with CYP3A4 induction liability in drug development a prerequisite. Here, we present three-dimensional (3D) spheroid cultures of primary human hepatocytes (PHHs) as a novel CYP3A4 induction screening model. Screening of 25 drugs (12 known CYP3A4 inducers in vivo and 13 negative controls) at physiologically relevant concentrations revealed a 100% sensitivity and 100% specificity of the system. Three of the in vivo CYP3A4 inducers displayed much higher CYP3A4 induction capacity in 3D spheroid cultures as compared with in two-dimensional (2D) monolayer cultures. Among those, we identified AZD1208, a proviral integration site for Moloney murine leukemia virus (PIM) kinase inhibitor terminated in phase I of development due to unexpected CYP3A4 autoinduction, as a CYP3A4 inducer only active in 3D spheroids but not in 2D monolayer cultures. Gene knockdown experiments revealed that AZD1208 requires pregnane X receptor (PXR) to induce CYP3A4. Rifampicin requires solely PXR to induce CYP3A4 and CYP2B6, while phenobarbital-mediated induction of these CYPs did not show absolute dependency on either PXR or constitutive androstane receptor (CAR), suggesting its ability to switch nuclear receptor activation. Mechanistic studies into AZD1208 uncovered an involvement of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in CYP3A4 induction that is sensitive to the culture format used, as revealed by its inhibition of ERK1/2 Tyrosine 204 phosphorylation and sensitivity to epidermal growth factor (EGF) pressure. In line, we also identified lapatinib, a dual epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) inhibitor, as another CYP3A4 inducer only active in 3D spheroid culture. Our findings offer insights into the pathways involved in CYP3A4 induction and suggest PHH spheroids for preclinical CYP3A4 induction screening.

A comprehensive planetary boundary-based method for the nitrogen cycle in life cycle assessment: Development and application to a tomato production case study.

Existing methods that apply the planetary boundary for the nitrogen cycle in life cycle assessment are spatially generic and use an indicator with limited environmental relevance. Here, we develop a spatially resolved method that can quantify the impact of nitrogen emissions to air, soil, freshwater or coastal water on "safe operating space" (SOS) for natural soil, freshwater and coastal water. The method can be used to identify potential "planetary boundary hotspots" in the life cycle of products and to inform appropriate interventions. The method is based on a coupling of existing environmental models and the identification of threshold and reference values in natural soil, freshwater and coastal water. The method is demonstrated for a case study on nitrogen emissions from open-field tomato production in 27 farming areas based on data for 199 farms in the year 2014. Nitrogen emissions were modelled from farm-level data on fertilizer application, fuel consumption and climate- and soil conditions. Two sharing principles, "status quo" and "gross value added", were tested for the assignment of SOS to 1 t of tomatoes. The coupling of models and identification of threshold and reference values resulted in spatially resolved characterization factors applicable to any nitrogen emission and estimations of SOS for each environmental compartment. In the case study, tomato production was found to range from not transgressing to transgressing its assigned SOS in each of the 27 farming areas, depending on the receiving compartment and sharing principle. A high nitrogen use efficiency scenario had the potential to reverse transgressions of assigned SOS for up to three farming locations. Despite of several sources of uncertainty, the developed method may be used in decision-support by stakeholders, ranging from individual producers to global governance institutions. To avoid sub-optimization, it should be applied with methods covering the other planetary boundaries.

Mechanical versus Chemical Pleurodesis after Bullectomy for Primary Spontaneous Pneumothorax: A Systemic Review and Meta-Analysis.

INTRODUCTION: Primary spontaneous pneumothorax (PSP) and its high recurrence rate pose a therapeutic challenge to both patients and their managing surgeons. Mechanical or chemical pleurodesis can be used to prevent recurrence, but the optimal treatment often remains a matter of debate. This meta-analysis aims to compare the outcomes between mechanical and chemical pleurodesis following bullectomy for PSP. MATERIALS AND METHODS: Studies published up to 2019 were searched from Medline, Embase, Google Scholar, and Cochrane databases. A meta-analysis of randomized controlled trials (RCTs) and observational cohort studies (OCSs) comparing outcomes between mechanical and chemical pleurodesis for PSP was performed. RESULTS: Seven studies (one RCT and six OCSs) were included, comprising 1,032 cases of mechanical (799 abrasions, 202 pleurectomies, and 31 unspecified abrasions/pleurectomies/both), and 901 cases of chemical (643 talc, 69 minocycline, and 189 unspecified talc/kaolin) pleurodesis. The recurrence rate of pneumothorax after chemical pleurodesis (1.2%) was significantly lower than mechanical pleurodesis (4.0%) (pooled odds ratio [OR] = 3.00; 95% confidence interval [CI] = 1.59-5.67; p = 0.0007; I 2 = 19%). Hospital stay was also slightly shorter in the chemical pleurodesis group (pooled mean difference [MD] = 0.42 days; 95% CI = 0.12-0.72; p = 0.005; I 2 = 0%). There was no statistically significant difference in postoperative complications (pooled OR = 1.18; 95%CI = 0.40-3.48; p = 0.76; I 2 = 71%) and operative time (pooled MD = 3.50; 95%CI = -7.28 to 14.28; p = 0.52; I 2 = 99%) between these two groups. CONCLUSION: Chemical pleurodesis is superior to mechanical pleurodesis following bullectomy for PSP in reducing hospital stay and recurrence rate. However, more RCTs with longer follow-up are necessary to demonstrate the benefit of chemical pleurodesis for PSP.

Greenhouse gas footprints of palm oil production in Indonesia over space and time.

Palm oil, the most widely used vegetable oil, is one of the largest drivers of greenhouse gas (GHG) emissions from global land use and land cover change. Here, we provide fine-resolution (100 m × 100 m) estimates of GHG footprints of current (2015) and potential future scenarios (2030) of crude palm oil (CPO) production in Indonesia. The current estimated average GHG footprint excluding production on Java is 5.7 t CO2 eq t-1 CPO; ranging from 0.7 t CO2 eq t-1 CPO in Hulu Sungai Tengah, Kalimantan to 26.0 t CO2 eq t-1 CPO in Pontianak, Kalimantan, and these vast differences are only discernible at fine spatial scales. The future GHG footprint of Indonesian CPO could be reduced by 42% without compromising increased output by limiting expansion to non-forest and non-peat land. Our fine-scale analysis provides a spatial screening approach to inform new oil palm concessions and sourcing decisions, before more cost-intensive patch analysis and carbon stock assessments are conducted.

Complete evagination of a patent vitellointestinal duct and adjacent ileal limbs from an omphalocele sac: an extreme presentation.

Vitellointestinal duct (VID) anomalies have been described extensively in the literature. However, an everted VID with prolapse of ileum arising from an omphalocele is rare, and its appearance at birth can be alarming and can present a diagnostic challenge. We describe a baby born to a teenage diabetic mother who was noted to have a strange exophytic mass arising from the abdominal wall. Antenatal scans had revealed multiple other malformations but not an omphalocele. He was operated on early, and the diagnosis of a patent VID with prolapse of the ileum arising from an omphalocele was only confirmed intraoperatively. The duct was resected, the ileum closed primarily and primary closure of the abdominal wall was performed without tension. He recovered well postoperatively. A brief review of similar cases is included.

Breast cancer metastasis to gynaecological organs: a clinico-pathological and molecular profiling study.

Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathological and molecular features of these metastases to better understand whether this pattern of dissemination is organotropic or a consequence of wider metastatic dissemination. Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy-number profiling, and targeted sequencing of 386 cancer-related genes. The median age of primary tumour diagnosis amongst patients with gynaecological metastases was significantly younger compared to a general breast cancer population (46.5 versus 60 years; p < 0.0001). Median age at metastatic diagnosis was 54.4, time to progression was 4.8 years (range 0-20 years), and survival following a diagnosis of metastasis was 1.95 years (range 0-18 years). Patients had an average of five involved sites (most frequently ovary, fallopian tube, omentum/peritoneum), with fewer instances of spread to the lungs, liver, or brain. Invasive lobular histology and luminal A-like phenotype were over-represented in this group (42.8 and 87.5%, respectively) and most patients had involved axillary lymph nodes (p < 0.001). Primary tumours frequently co-expressed oestrogen receptor cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24, and 11q13. In terms of phenotype conversion, oestrogen receptor status was generally maintained in metastases, FOXA1 increased, and expression of progesterone receptor, androgen receptor, and GATA3 decreased. ESR1 and novel AR mutations were identified. Metastasis to gynaecological organs is a complication frequently affecting young women with invasive lobular carcinoma and luminal A-like breast cancer, and hence may be driven by sustained hormonal signalling. Molecular analyses reveal a spectrum of factors that could contribute to de novo or acquired resistance to therapy and disease progression.

Pharmacogenetic impact of docetaxel on neoadjuvant treatment of breast cancer patients.

AIM: This study aimed to investigate the effect of CYP3A4 and CYP3A5 genotypes on clinical outcomes of docetaxel treatment. PATIENTS & METHODS: In the PROMIX trial, 150 breast cancer patients received docetaxel preoperatively. CYP3A4 and CYP3A5 genotype combinations were transformed into total CYP 3A phenotypes. RESULTS: Seven patients were characterized as poor metabolizer (PM), 22 patients as extensive metabolizer and 121 patients as intermediate metabolizer. The frequency of grade 3/grade 4 adverse events was higher in the PM group (p = 0.002). One PM subject who basically lacked enzyme activity died from typhlitis. Total 45 recurrences were reported after a median of 5-year follow-up; none of these was PM. CONCLUSION: The allelic variants CYP3A4*22 and CYP3A5*3 contribute to the interpatient variations of docetaxel.