Evidence-based medicine in primary care: qualitative study of family physicians

BACKGROUND: The objectives of this study were: a) to examine physician attitudes to and experience of the practice of evidence-based medicine (EBM) in primary care; b) to investigate the influence of patient preferences on clinical decision-making; and c) to explore the role of intuition in family practice. METHOD: Qualitative analysis of semi-structured interviews of 15 family physicians purposively selected from respondents to a national survey on EBM mailed to a random sample of Canadian family physicians. RESULTS: Participants mainly welcomed the promotion of EBM in the primary care setting. A significant number of barriers and limitations to the implementation of EBM were identified. EBM is perceived by some physicians as a devaluation of the 'art of medicine' and a threat to their professional/clinical autonomy. Issues regarding the trustworthiness and credibility of evidence were of great concern, especially with respect to the influence of the pharmaceutical industry. Attempts to become more evidence-based often result in the experience of conflicts. Patient factors exert a powerful influence on clinical decision-making and can serve as trumps to research evidence. A widespread belief that intuition plays a vital role in primary care reinforced views that research evidence must be considered alongside other factors such as patient preferences and the clinical judgement and experience of the physician. DISCUSSION: Primary care physicians are increasingly keen to consider research evidence in clinical decision-making, but there are significant concerns about the current model of EBM. Our findings support the proposed revisions to EBM wherein greater emphasis is placed on clinical expertise and patient preferences, both of which remain powerful influences on physician behaviour

Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis.

BACKGROUND: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. METHODS: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. RESULTS: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10(-6)). CONCLUSION: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk.This study was supported by MRC grant MC_UU_12015/1 and by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372 (contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies). ANECS recruitment was supported by project grants from the National Health and Medical Research Council of Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and ID#457636). SEARCH recruitment was funded by a programme grant from Cancer Research UK [C490/A10124]. Case genotyping was supported by the National Health and Medical Research Council (ID#552402). Control data was generated by the Wellcome Trust Case Control Consortium (WTCCC), and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. Funding for this project was provided by the Wellcome Trust under award 085475. Recruitment of the QIMR controls was supported by the National Health and Medical Research Council of Australia (NHMRC). The University of Newcastle, the Gladys M Brawn Senior Research Fellowship scheme, The Vincent Fairfax Family Foundation, the Hunter Medical Research Institute and the Hunter Area Pathology Service all contributed towards the costs of establishing the Hunter Community Study. K.T.N. was supported by the Gates Cambridge Trust. R.K.S. is supported by the Wellcome Trust (grant number WT098498). A.B.S. is supported by the National Health and Medical Research Council (NHMRC) Fellowship Scheme. D.F.E. is a Principal Research Fellow of Cancer Research UK. A.M.D is supported by the Joseph Mitchell Trust.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/jnci/djv17

Using human genetics to understand the disease impacts of testosterone in men and women.

Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1 s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR) = 1.37 (95% confidence interval (95% CI): 1.22-1.53)) and polycystic ovary syndrome (OR = 1.51 (95% CI: 1.33-1.72)) in women, but reduces type 2 diabetes risk in men (OR = 0.86 (95% CI: 0.76-0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses.A.R.W. and T.M.F. are supported by the European Research Council grant: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. R.B. is funded by the Wellcome Trust and Royal Society grant 104150/Z/14/Z. J.T. is supported by the Academy of Medical Sciences Springboard award which is supported by the Wellcome Trust and GCRF [SBF004\1079]. This work was supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

An exploration of influences on women’s birthplace decision-making in New Zealand: a mixed methods prospective cohort within the Evaluating Maternity Units study

BACKGROUND: There is worldwide debate surrounding the safety and appropriateness of different birthplaces for well women. One of the primary objectives of the Evaluating Maternity Units prospective cohort study was to compare the clinical outcomes for well women, intending to give birth in either an obstetric-led tertiary hospital or a free-standing midwifery-led primary maternity unit. This paper addresses a secondary aim of the study – to describe and explore the influences on women’s birthplace decision-making in New Zealand, which has a publicly funded, midwifery-led continuity of care maternity system. METHODS: This mixed method study utilised data from the six week postpartum survey and focus groups undertaken in the Christchurch area in New Zealand (2010–2012). Christchurch has a tertiary hospital and four primary maternity units. The survey was completed by 82% of the 702 study participants, who were well, pregnant women booked to give birth in one of these places. All women received midwifery-led continuity of care, regardless of their intended or actual birthplace. RESULTS: Almost all the respondents perceived themselves as the main birthplace decision-makers. Accessing a ‘specialist facility’ was the most important factor for the tertiary hospital group. The primary unit group identified several factors, including ‘closeness to home’, ‘ease of access’, the ‘atmosphere’ of the unit and avoidance of ‘unnecessary intervention’ as important. Both groups believed their chosen birthplace was the right and ‘safe’ place for them. The concept of ‘safety’ was integral and based on the participants’ differing perception of safety in childbirth. CONCLUSIONS: Birthplace is a profoundly important aspect of women’s experience of childbirth. This is the first published study reporting New Zealand women’s perspectives on their birthplace decision-making. The groups’ responses expressed different ideologies about childbirth. The tertiary hospital group identified with the ‘medical model’ of birth, and the primary unit group identified with the ‘midwifery model’ of birth. Research evidence affirming the ‘clinical safety’ of primary units addresses only one aspect of the beliefs influencing women’s birthplace decision-making. In order for more women to give birth at a primary unit other aspects of women’s beliefs need addressing, and much wider socio-political change is required

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

BACKGROUND: Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury. METHODS: Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine) or saline-vehicle were administered i.p. before ischemia. Plasma cytokine tumor necrosis factor (TNF)-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT) and liver histopathology. RESULTS: A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR. CONCLUSION: Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury

Resolving the paradox of shame: differentiating among specific appraisal-feeling combinations explains pro-social and self-defensive motivation

Research has shown that people can respond both self-defensively and pro-socially when they experience shame. We address this paradox by differentiating among specific appraisals (of specific self-defect and concern for condemnation) and feelings (of shame, inferiority, and rejection) often reported as part of shame. In two Experiments (Study 1: N = 85; Study 2: N = 112), manipulations that put participants’ social-image at risk increased their appraisal of concern for condemnation. In Study 2, a manipulation of moral failure increased participants’ appraisal that they suffered a specific self-defect. In both studies, mediation analyses showed that effects of the social-image at risk manipulation on self-defensive motivation were explained by appraisal of concern for condemnation and felt rejection. In contrast, the effect of the moral failure manipulation on pro-social motivation in Study 2 was explained by appraisal of a specific self-defect and felt shame. Thus, distinguishing among the appraisals and feelings tied to shame enabled clearer prediction of pro-social and self-defensive responses to moral failure with and without risk to social-image

The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study

<p>Abstract</p> <p>Background</p> <p>Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of <it>KIF6 </it>(719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or <it>KIF6 </it>variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older.</p> <p>Methods</p> <p>Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).</p> <p>Results</p> <p>Among white participants the FRS was improved by addition of <it>KIF6 </it>719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).</p> <p>Conclusions</p> <p>While none of these risk markers individually or in combination improved risk prediction among women, a combination of <it>KIF6 </it>719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.</p

Nurses' experiences, expectations, and preferences for mind-body practices to reduce stress

BACKGROUND: Most research on the impact of mind-body training does not ask about participants\u27 baseline experience, expectations, or preferences for training. To better plan participant-centered mind-body intervention trials for nurses to reduce occupational stress, such descriptive information would be valuable. METHODS: We conducted an anonymous email survey between April and June, 2010 of North American nurses interested in mind-body training to reduce stress. The e-survey included: demographic characteristics, health conditions and stress levels; experiences with mind-body practices; expected health benefits; training preferences; and willingness to participate in future randomized controlled trials. RESULTS: Of the 342 respondents, 96% were women and 92% were Caucasian. Most (73%) reported one or more health conditions, notably anxiety (49%); back pain (41%); GI problems such as irritable bowel syndrome (34%); or depression (33%). Their median occupational stress level was 4 (0 = none; 5 = extreme stress). Nearly all (99%) reported already using one or more mind-body practices to reduce stress: intercessory prayer (86%), breath-focused meditation (49%), healing or therapeutic touch (39%), yoga/tai chi/qi gong (34%), or mindfulness-based meditation (18%). The greatest expected benefits were for greater spiritual well-being (56%); serenity, calm, or inner peace (54%); better mood (51%); more compassion (50%); or better sleep (42%). Most (65%) wanted additional training; convenience (74% essential or very important), was more important than the program\u27s reputation (49%) or scientific evidence about effectiveness (32%) in program selection. Most (65%) were willing to participate in a randomized trial of mind-body training; among these, most were willing to collect salivary cortisol (60%), or serum biomarkers (53%) to assess the impact of training. CONCLUSIONS: Most nurses interested in mind-body training already engage in such practices. They have greater expectations about spiritual and emotional than physical benefits, but are willing to participate in studies and to collect biomarker data. Recruitment may depend more on convenience than a program\u27s scientific basis or reputation. Knowledge of participants\u27 baseline experiences, expectations, and preferences helps inform future training and research on mind-body approaches to reduce stress

Micro-spectroscopic investigation of selenium-bearing minerals from the Western US Phosphate Resource Area

Mining activities in the US Western Phosphate Resource Area (WPRA) have released Se into the environment. Selenium has several different oxidation states and species, each having varying degrees of solubility, reactivity, and bioavailability. In this study we are investigating the speciation of Se in mine-waste rocks. Selenium speciation was determined using bulk and micro-x-ray absorption spectroscopy (XAS), as well as micro-x-ray fluorescence mapping. Rocks used for bulk-XAS were ground into fine powders. Shale used for micro-XAS was broken along depositional planes to expose unweathered surfaces. The near edge region of the XAS spectra (XANES) for the bulk rock samples revealed multiple oxidation states, with peaks indicative of Se(-II), Se(IV), and Se(+VI) species. Micro-XANES analysis of the shale indicated that three unique Se-bearing species were present. Using the XANES data together with ab initio fitting of the extended x-ray absorption fine structure region of the micro-XAS data (micro-EXAFS) the three Se-bearing species were identified as dzharkenite, a di-selenide carbon compound, and Se-substituted pyrite. Results from this research will allow for a better understanding of the biogeochemical cycling of Se in the WPRA