Perceptions about Aging and Ageism from 14 Cross-sectional Cohorts of Undergraduate Dental Students.

BACKGROUND: Although positive and negative views of aging and older adults exist, how undergraduate dental students imagine their lives to be as they grow older remains to be fully explored. This study aimed at determining the self-perceived views of being 65, 75, or 85 y of age, as expressed by undergraduate dental students at the University of British Columbia (UBC), Vancouver, Canada. METHODS: A 14-y cross-sectional study design was utilized involving third-year undergraduate dental students at UBC's Faculty of Dentistry. Brief individual essays (150 words) encompassing students' self-perceived views were gathered as part of a dental geriatric course from 2009 to 2022; however, essays were not mandatory. Saldaña's inductive coding and thematic analysis of textual data were used. Themes and categories of information were identified and matched with their excerpts while aiming for data saturation. RESULTS: Over the 14-y period, 657 students were enrolled in UBC's undergraduate dental geriatric course, and 561 essays were collected. Inductive coding and thematic analysis identified 5 main themes and 11 categories. While themes included "oral health, general health, and the mind" and "me, myself, and familial relationships," the categories focused on "(un)able bodies" and "general health." Positive views about the aging process were shared, while less optimistic ideas-and even ageism-were apparent when students saw themselves as not employable or living in isolation. Positive and negative views were not bound by the students' academic year but might have been influenced by the COVID-19 pandemic. CONCLUSION: Although the number of older adults already surpasses the number of children in many countries, ageism appears to have permeated through students' views of 3 older ages. More positive yet realistic views of growing older were also shared. Follow-up studies are needed to explore the impact of dental education on decreasing ageism. KNOWLEDGE TRANSFER STATEMENT: As the proportion of older adults in the global population steadily grows, it is important to educate heath care providers about normal and pathologic aging to avoid ageism-stereotypes, prejudices, and discrimination against older adults. This cross-sectional study involved 14 cohorts of undergraduate dental students exploring their self-perceived views of growing older. Although positive and negative views of aging were shared, dental education must focus on decreasing ageism.

Dental Service and Resource Needs during COVID-19 among Underserved Populations.

INTRODUCTION: In response to the coronavirus disease 2019 (COVID-19) outbreak, dental services in British Columbia, Canada, were restricted to urgent and emergency cases between March 16 and May 18, 2020. It is unclear how the curtailment of oral health services has affected underserved populations who already often have limited access to dental care due to cost, fear, stigma, and discrimination. OBJECTIVES: To explore the experiences of underserved populations and their community organizations when accessing oral health services and information in British Columbia and identify their coping mechanisms employed during the curtailment of oral health care services. METHODS: Semistructured, remote interviews were conducted with 13 staff and 18 members from 6 community-based organizations. These organizations serve men and women with a history of incarceration and/or experiencing poverty and homelessness, persons living with human immunodeficiency virus/AIDS, adults living with mental illness, and older adults in long-term care facilities. The interviews were audio-recorded, transcribed verbatim, and coded for emerging themes using NVivo 12 software. Thematic analysis was performed. RESULTS: The pandemic raised concerns and hesitancy among underserved populations and further reduced access to care. In turn, those with unmet dental needs resorted to coping mechanisms, including turning to community support or medical services, self-management of dental issues, and not dealing with dental issues altogether. Community organizers and members outlined needed resources such as assistance navigating the dental care system, having a contact for dental-related questions, and member preparation for dental service changes, while emphasizing the importance of positive relationships with dental providers. CONCLUSION: Underserved populations who already face barriers to oral health care services experienced increased difficulty in addressing their oral health needs and concerns during the beginning of the COVID-19 pandemic. Strategies aimed at reaching out to this population and those who support them are needed to help mitigate negative coping strategies and increased oral health disparities. KNOWLEDGE TRANSFER STATEMENT: This study depicts ways of addressing unmet oral health-related issues during the COVID-19 pandemic for underserved populations and their community organizations with policy implications as well as practical strategies.

An interprofessional model of care for oral health during pregnancy.

The study aim was to appraise the relevance and appropriateness of an interprofessional prenatal oral care model among pregnant women and healthcare providers in British Columbia (BC), Canada. Audio-recorded semi-structured interviews with 39 purposefully selected participants (13 pregnant women and 26 healthcare professionals) were used qualitatively to appraise relevance of an existing model. The existing model emphasizes communication and collaboration among multiple health providers for the delivery of integrated prenatal oral care. All interviews were transcribed verbatim and analyzed using an inductive thematic approach and N-Vivo® software. During the first round of interviews, most participants considered the existing model as simple and well-defined but not fully relevant to the BC context. The participants suggested revisions to Steven's model to incorporate facilitators of integrated care, including interprofessional education, oral health funding, and advocacy for oral healthcare. Participants suggested a different graphical portrayal for the revised model; an implementation guide was also suggested. A revised model based on participants' feedback, was shared with 14 of the initial participants during secondary interviews. Further evaluation of the appropriateness of the revised model is warranted.

Solitary osseous plasmacytomas in dogs: 13 cases (2004-2019).

OBJECTIVES: To further characterise solitary osseous plasmacytoma in dogs, an extremely rare disease. To describe diagnosis, disease progression and treatment outcomes in dogs with solitary osseous plasmacytoma. MATERIALS AND METHODS: Retrospective review of dogs with solitary osseous plasmacytomas that were diagnosed and treated at a single institution from 2005 to 2019. Kaplan-Meier single group survival analysis was used to estimate median survival time and progression-free interval. RESULTS: Thirteen dogs met the inclusion criteria for the study, and of those, 11 were treated. The median age at diagnosis was 8 years (range 4 to 11). Most solitary osseous plasmacytomas occurred in the vertebrae (n=8). Other sites included the maxilla (n=2), the mandible (n=1), the tibia (n=1) and the carpus (n=1). The median survival time for all dogs with solitary osseous plasmacytoma was 912 days (range 5 to 2179), and the progression-free interval for treated dogs was 310 days (range 22 to 2179). Most dogs were treated with radiation therapy (n=10) with nine of 10 receiving a definitive, daily fractionated protocol and with five of ten having had neoadjuvant surgery. Seven dogs received chemotherapy, which was initiated after progressive disease in five dogs. The median survival time for dogs that completed radiation therapy (n=9) was 1166 days (range 545 to 2179). While five dogs developed lesions at other sites, no dogs progressed to multiple myeloma. CLINICAL SIGNIFICANCE: Canine solitary osseous plasmacytomas can be managed long term with appropriate local therapy. This observation reflects the biologic behaviour observed in humans.

Lung ultrasound nodule sign for detection of pulmonary nodule lesions in dogs: Comparison to thoracic radiography using computed tomography as the criterion standard.

Thoracic radiography (TR), the most common screening test for pulmonary metastases in dogs, can fail to detect small lesions <3 mm. Lung ultrasonography (LUS) is a widely available imaging modality capable of detecting peripheral nodules but is underutilized for this purpose. Thoracic computed tomography (CT) is the criterion standard for diagnosis of lung metastases and nodular disease but is less practical for a variety of reasons. We hypothesized that LUS would be more sensitive but less specific at detecting nodules consistent with metastatic pulmonary disease in dogs compared to TR, using CT as the criterion standard. This was a masked, single-center prospective study of 62 client-owned dogs evaluated for respiratory signs or pulmonary metastatic neoplasia screening using TR, LUS and CT. Dogs were included if metastatic pulmonary disease was a differential. All imaging modalities were scored as having nodules (yes/no) and other types of pathologic lesions were recorded. Sensitivity (Se), specificity (Sp) and positive (LR+) and negative likelihood ratios (LR-) were determined for TR and LUS. For TR, Se and Sp were 64% and 73%, and LR+ and LR- were 2.37 and 0.49, respectively. For LUS, Se and Sp were 60% and 65% and LR+ and LR- were 1.71 and 0.62, respectively. The results of the study indicate that LUS had a similar Se to TR, with both modalities missing nodules when used for screening. The low Sp and LR- suggests caution should be used when assuming TR and LUS rule out the presence of nodules.

Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD.

BACKGROUND: Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters. METHODS: Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR. RESULTS: Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state. CONCLUSION: Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.

Pregnant women's perspectives on integrating preventive oral health in prenatal care.

BACKGROUND: Oral diseases are considered a silent epidemic including among pregnant women. Given the prevalence of oral conditions among pregnant women and the reported association with adverse pregnancy outcomes, there have been suggestions for the inclusion of preventive oral care in routine prenatal care. However, due to the different administrative and funding structure for oral health and prenatal care in Canada, progress towards this integration has been slow. Our study sought to qualitatively explore the views of pregnant women in British Columbia (BC) on the strategies for integrating preventive oral health care into prenatal care services. METHODS: A qualitative approach was utilized involving semi-structured interviews with fourteen (14) purposefully selected pregnant women in Vancouver and Surrey, BC. The interviews were audio-recorded and transcribed. The transcripts were analyzed using an inductive thematic approach. Study validity was ensured via memoing, field-notes, and member checking. RESULTS: Interviews ranged from 28 to 65 min producing over 140 pages of transcripts. Analysis resulted in three major themes: oral health experiences during pregnancy, perspectives on integration and integrated prenatal oral care, and strategies for addressing prenatal oral health care. A majority of participants were supportive of integrating preventive oral care in routine prenatal services, with referrals identified as a critical strategy. Oral health education was recognized as important before, during, and after pregnancy; oral health assessments should therefore be included in the prenatal care checklist. Limited funding was acknowledged as a barrier to oral health care access, which may explain why few participants visited their dentists during pregnancy. Interprofessional education surfaced as a bridge to provide prenatal oral health education. CONCLUSION: Pregnant women interviewed in this study support the inclusion of educational and preventive oral care during prenatal care, although their views differed on how such inclusion can be achieved in BC. They advocated the establishment of a referral system as an acceptable strategy for providing integrated prenatal oral health care.

The HIV and SARS-CoV-2 Parallel in Dentistry from the Perspectives of the Oral Health Care Team.

OBJECTIVES: The aim of this study was to unravel the professional and social consequences of COVID-19 as compared with the AIDS pandemic according to oral health care providers, staff, and administrators. METHODS: An exploratory qualitative inquiry via at-a-distance, semistructured interviews engaged a purposefully recruited sample of oral health care team workers in British Columbia. Interviews took place between April 20 and May 15, 2020; they were audio recorded, transcribed verbatim, and deidentified for interactive thematic analysis. An inductive process of coding was used to identify themes, subthemes, and categories of information. RESULTS: Forty-five interviews were conducted with 18 dentists, 12 dental hygienists, 6 certified dental assistants, and 9 administrators; 22 were females. Interviews each lasted an average of 48 min. After the transcripts were coded, 3 subthemes emerged: 1) personal protective equipment and universal precautions as commonsense approaches to care during both pandemics; 2) an (un)collapsed world in terms of global lockdowns; and 3) social unrest in terms of the potential for stigma and discrimination caused by both pandemics. These subthemes made up the COVID-19-AIDS parallel theme. CONCLUSION: This study explored the extent to which the current COVID-19 pandemic is leading to professional and social consequences when a parallel is drawn with the AIDS pandemic. This is the first qualitative study that identifies the potential social unrest of the pandemic from the perspective of oral health care providers and administrators. Future studies should include other providers across Canada, as well the patients receiving oral health care during this pandemic. KNOWLEDGE TRANSFER STATEMENT: The COVID-19 pandemic has unraveled potential societal implications in a parallel to the HIV/AIDS era from the perspectives of oral health care providers and their staff. Such implications are changing the way that oral health care is delivered; it may also be leading to social unrest in the form of stigma and discrimination. This study discusses some of these implications from the perspective of oral health care providers and administrators.

A Qualitative Study of Health Care Providers' Views on Integrating Oral Health into Prenatal Care.

OBJECTIVE: Providing preventive oral health during prenatal care is a recognized strategy for improving pregnant women's access to oral health care. This study sought to qualitatively explore the views of health care providers in British Columbia (BC), Canada, on strategies for integrating preventive oral health into prenatal care. METHODS: Twenty-four purposefully selected health care providers (13 oral health and 11 prenatal care providers) in Vancouver and Surrey BC participated in audio-recorded semistructured interviews. Interviews lasted from 31 to 61 min, were transcribed verbatim, and were analyzed using an inductive thematic analysis with N-Vivo software. Study validity was ensured via memoing, fieldnotes, member checking, and external audit. RESULTS: Thematic analysis revealed 5 major themes: perception of integrated care, relevance of integrated prenatal oral health, strategies for achieving integrated prenatal oral health, drivers of the integration process, and barriers to integrating oral health during pregnancy. Interprofessional collaboration based on information sharing and communication was identified as a critical factor for integrated care. Oral health checks should be a component of prenatal assessments for achieving integrated prenatal oral health. Participants recommended that prenatal providers should offer oral health education and use screening questions to identify the pregnant woman's oral health needs. The establishment of referral systems was advocated, while dental assessments and oral prophylaxis via the medical services plan were proposed. The inclusion of dental providers in prenatal teams and educating health care providers on interprofessional collaboration were also supported. CONCLUSION: Oral health and prenatal providers in BC are positively disposed to adopting integrated preventive prenatal oral health care based on interprofessional collaborative practices. The inclusion of oral health providers in prenatal teams was suggested. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by policymakers for advocacy and decision making when planning care delivery programs for women during pregnancy. Including the suggested strategies could lead to increased access to, and utilization of, oral health services among pregnant women.

Perspectives of socially disadvantaged women on oral healthcare during pregnancy.

Oral health is considered important during pregnancy, however many pregnant women, especially socially disadvantaged women such as immigrants, working poor and homeless have difficulty accessing oral healthcare. OBJECTIVE: To explore the perceptions of a sample of socially disadvantaged women on oral healthcare provision during pregnancy. BASIC RESEARCH DESIGN: Qualitative study via focus group discussions with seventeen pregnant women or new mothers receiving care at a local maternity clinic that serves a culturally diverse population facing social challenges. PARTICIPANTS: Women who met at least one of the following criteria: low socio-economic status, new immigrant or refugee, homeless or at risk of homelessness, history of incarceration or substance abuse or at risk of abuse. Discussions were audio-recorded, transcribed verbatim and analyzed thematically using the NVivo 11© software programme for coding and thematic analysis. RESULTS: All participants reported unmet oral healthcare needs. The analysis revealed three main themes: knowledge of the importance and value of oral health during pregnancy, experiences with oral healthcare and provision of oral health services to socially disadvantaged pregnant women. Participants favoured inclusion of preventive oral healthcare provided by either dental or prenatal healthcare professionals in routine prenatal care. DISCUSSION: Socially disadvantaged pregnant women did not access the oral healthcare they needed due to cost, dental fear and anxiety; some faced stigma and discrimination. They were disposed to receiving community-based, primary preventive dental services as part of prenatal care from either dental or prenatal allied healthcare professionals.

Orofacial cleft management by short-term surgical missions in South America: literature review.

There is a growing demand for surgical care in South America, particularly for patients with congenital orofacial clefts (OFCs). Short-term surgical missions (STSMs) have emerged as a means to deliver surgical expertise and alleviate this demand. The aim of this study was to review the quantity and quality of peer-reviewed reports on OFC repairs performed by STSMs in South America. A literature search was conducted using the PubMed, Embase, Web of Science, and SciELO databases. The search was limited to articles published in English and Spanish. Descriptive statistics were used for the data analysis. The search yielded 65 studies related to OFCs. Eight (12.3%) were selected for full-text review. Only five (7.7%) articles met the inclusion criteria. The diverse study designs and heterogeneous types of data assessment among the selected studies hindered a comparison between them. This review found a sparse number of publications pertaining to OFC missions to South America. The articles that were included demonstrated inconsistencies in reporting patient care data. There is a need for a more efficient, streamlined method of reporting humanitarian missions for OFC repairs in order for healthcare professionals to fulfill research and ethical obligations and offer the best practices in patient-centered care.

'For me it's about not feeling like I'm on a diet': a thematic analysis of women's experiences of an intermittent energy restricted diet to reduce breast cancer risk.

BACKGROUND: Weight-loss programmes requiring intermittent energy restriction offer an alternative to continuous energy restriction programmes that typically have low adherence. We reported greater weight loss, better adherence and spontaneous reduced energy intake on healthy eating days with intermittent as opposed to continuous energy restriction. The present study aims to explore why intermittent energy restriction diets exert these positive effects. METHODS: Semi-structured interviews were carried out with 13 women aged 39-62 years, who followed a 4-month intermittent energy restriction (2 days of low energy/low carbohydrate, 5 days of healthy eating). Nine of the 13 women successfully lost >5% of their total body weight. Data were analysed using thematic analysis. RESULTS: The intermittent regimen redefined the meaning of dieting and normal eating. Women reconceptualised dieting as only two low energy days per week, even though this often differed from their pre-diet eating patterns. Women reported that they could adhere more closely to the rules of the intermittent diet compared to previously attempted continuous diets. They found that the intermittent diet was less cognitively demanding because the restrictive and clear rules of the intermittent diet were easier to understand and easier to follow than with continuous dieting. CONCLUSIONS: Many participants found intermittent dieting preferable to previous experiences of continuous dieting. The findings provide some insight into the ways in which intermittent dieting is successful, and why it could be considered a viable alternative to continuous energy restriction for weight loss.

Characteristics of people with high visit-to-visit glycaemic variability in Type 2 diabetes.

AIMS: Increased visit-to-visit glycaemic variability is independently associated with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient characteristics associated with raised visit-to-visit glycaemic variability in people with Type 2 diabetes. METHODS: A case-control study was conducted to establish associations between HbA1c variability and clinical covariates in 10 130 people with Type 2 diabetes. Variability was calculated by two metrics [sd and coefficient of variation (CV)] from a minimum of four HbA1c readings obtained over a 4-year period. High and low variability groups were defined as the top and bottom tertile of the sd or CV, and used in logistic regression analyses including a number of clinical and biochemical covariates. The analyses were stratified into low mean (< 53 mmol/mol; 7%) and high mean (≥ 53 mmol/mol; 7%) HbA1c groups. RESULTS: Findings were consistent across both HbA1c groups and variability metrics. Treatment, independent of other factors, was the most strongly associated covariate for the risk of high HbA1c variability. A six-fold increased risk was observed in the low HbA1c group, between the most and least intense treatment regimens (P < 0.001). Similar findings were present in the high HbA1c group with a three-fold increase in risk (P < 0.001). In addition, male gender, younger age, reduced HDL-cholesterol and increased BMI were all found to be independently associated with raised visit-to-visit glycaemic variability. CONCLUSIONS: Intensive treatment resulting in low mean HbA1c was associated with marked increase in HbA1c variability. Irrespective of diabetes control, the greatest visit-to-visit variability was observed in young, insulin resistant men.

Oral health of older residents in care and community dwellers: nursing implications.

BACKGROUND: Poor oral health is associated with a reduced quality of life and serious illnesses. Consequently, nurses need to be more aware of oral health to improve the general health of residents in care. AIM: To evaluate and compare oral health behaviours and levels of salivary haemoglobin and dental biofilm acidogenicity, which can be used to evaluate oral disease activity, between residents and community dwellers in South Korea. METHODS: This cross-sectional study included 133 participants: 64 residents and 69 community dwellers. All participants completed a questionnaire and tests to measure their salivary haemoglobin and dental biofilm acidogenicity. RESULTS: A higher percentage of community dwellers than of residents brushed their teeth three times a day, cleaned their tongue, used interdental cleaning devices and had visited a dental clinic within 1 year. The levels of salivary haemoglobin and dental biofilm acidogenicity tended to be higher in residents than in community dwellers. CONCLUSION: Residents showed poorer oral health behaviours and higher levels of gingival bleeding and acid production by oral bacteria than did community dwellers. IMPLICATIONS FOR NURSING PRACTICE: Nursing staff should enhance their monitoring of oral hygiene status and provide quality oral care to residents through cooperation with dental professionals. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Policymakers should be aware that oral health is an essential component of improving general health and well-being and therefore strive to develop policies to promote oral care services provided to residents. Nursing policies, such as mandating oral care and hands-on training in oral care for nursing staff, are important. We also suggest that factors related to oral care be added to the establishment or accreditation standards of care facilities.

A novel flow cytometric-based method to measure kinase inhibition in sputum from COPD subjects.

INTRODUCTION: Janus kinases (JAKs) regulate inflammatory gene expression through phosphorylation of signal transducer and activator of transcription (STAT) proteins. Expression of STAT proteins is increased in chronic obstructive pulmonary disease (COPD), and may be involved in driving chronic inflammation. Oral JAK inhibitors are effective as anti-inflammatory therapy but exhibit dose-limiting adverse effects. Development of inhaled compounds would be enhanced by robust biomarkers that directly reflect the anti-inflammatory and pharmacological activity in the lung. METHODS: A novel flow cytometry assay was developed to measure STAT1 phosphorylation in sputum inflammatory cells. The standard sputum processing method was refined to improve sputum cell viability. The flow cytometric assay was used to assess the reproducibility of the measurement of STAT1 phosphorylation and the in vitro activity of a pan JAK-inhibitor on three separate visits in patients with COPD. RESULTS: Upregulation of STAT1 phosphorylation was measured following in vitro IFNγ stimulation of sputum macrophages (stimulated/unstimulated ratio 1.57; p<0.00001). Upregulation was inhibited following in vitro preincubation with a pan JAK-inhibitor (inhibited+stimulated/unstimulated ratio 0.97). STAT1 phosphorylation activity could only be measured in macrophages. CONCLUSIONS: Sputum from patients with COPD can be used to reproducibly measure phospho-STAT expression in sputum macrophages. The flow cytometry-based method can be used to evaluate kinase inhibitors in vitro and subsequently in ex vivo studies. The assay is particularly useful for the assessment of inhaled compounds where whole blood assays may not be relevant.

Evaluation of histological grade and histologically tumour-free margins as predictors of local recurrence in completely excised canine mast cell tumours.

Completeness of mast cell tumour (MCT) excision is determined by assessment of histologically tumour-free margins (HTFM). The HTFM width necessary to prevent local recurrence (LR), recognized as histologic safety margin (HSM) in human oncology, has not been defined. We hypothesized that HTFM width would correlate with risk for LR and high-grade tumours would require wider HTFM than low-grade tumours. Records of dogs with completely excised MCTs were included. Signalment, two-tier tumour grade, tumour size, HTFM width, recurrence and therapy data was collected. High-grade (n = 39) tumours were more likely to recur than low-grade (n = 51) tumours (35.9% versus 3.9%), P < 0.0001, with no association between HTFM width and LR. Twenty-nine percent of low-grade tumours had HTFM less than 3 mm; none recurred. Narrow (≤3 mm) histologic margins are likely adequate to prevent LR of low-grade tumours. High-grade tumours have significant risk of LR regardless of HTFM width.

A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain.

BACKGROUND: Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population. METHOD: We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets. RESULTS: After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10(-7) at rs17428041. The narrow-sense heritability of this phenotype was 11.00%. CONCLUSION: This genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.

Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

BACKGROUND: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. METHODS: All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. RESULTS: Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. CONCLUSIONS: Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events.

The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10(-5)) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.

Reproductive decision-making in young female carriers of a BRCA mutation.

STUDY QUESTION: How do young women, who were identified as carrying a BRCA gene mutation before they had children, approach reproductive decision-making and what are their attitudes towards reproductive genetic testing? SUMMARY ANSWER: Reproductive decision-making within the context of cancer risk is complex and influenced by personal experiences of cancer. Younger women were not concerned with reproductive decision-making at the time of their genetic test; however, the impact on subsequent reproductive decision-making was considerable and left them with unanticipated dilemmas, such as having children who would be at risk of inheriting cancer predisposition, timing risk-reducing surgery and changing perceptions of responsibility. WHAT IS KNOWN ALREADY: Individuals carrying gene mutations predisposing to hereditary breast/ovarian cancer have concerns about passing on the gene mutation to children. STUDY DESIGN, SIZE, DURATION: Qualitative methodology and thematic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected through semi-structured interviews with 25 women aged 18-45 who had received a positive result for a BRCA1 or BRCA2 gene mutation while childless. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis revealed four central themes: (i) the impact of cancer on reproductive decision-making; (ii) motivation for genetic testing; (iii) risk management and timing of planning children; and (iv) optimism for future medical advancements. LIMITATIONS, REASONS FOR CAUTION: This study explores the views of female BRCA carriers. Further research should explore the views of couples, men, and include samples with greater ethnic and social diversity. WIDER IMPLICATIONS OF THE FINDINGS: This evidence highlights the need for reproductive decision-making to be addressed at the time of pretest genetic counselling. More information should be provided on reproductive options as well as counselling/support to guide women's reproductive decision-making and prenatal testing options at the time they undertake genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Cancer Research UK (Number C1226 A7920) and NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and RMH. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.