Linn Getz

Ultrasound screening in pregnancy: advancing technology, soft markers for fetal chromosomal aberrations, and unacknowledged ethical dilemmas

Fetal ultrasound screening has become routine practice in many western countries. During the last decade, such screening has led to frequent situations characterised by clinical uncertainty due to the disclosure of soft markers in the unborn child. Soft markers are minor anatomical variations indicating a somewhat increased likelihood that the fetus has a chromosomal aberration, most frequently trisomy 21 (Down syndrome). This paper presents the results of a comprehensive literature search of the National Library of Medicine with emphasis on the chronological development of scientific knowledge in relation to soft markers and the link between advancing imaging technology and clinical counselling dilemmas. An analysis of the literature makes evident that many ultrasound examiners have counselled individual pregnant women on the basis of insufficient data. Moral dilemmas have thus emerged as a direct result of advancing medical technology, and healthy fetal lives prove to have been lost due to invasive diagnostic testing aimed at resolving clinical uncertainty. Ultrasound examiners have warned against a policy of disclosing all findings of soft markers to expectant parents, but no exploration of experiential aspects linked to the disclosure of fetal soft markers has yet been published in the medical literature. The emotional reactions of mothers are important to consider given their potential impact on the biological development of the fetus. In conclusion, this paper stresses the need for paying close attention to the crucial distinction between technology development and technology implementation in relation to prenatal testing. Furthermore, it provides strong arguments for scrutinising the interface between prenatal testing and human experience.

Estimating the high risk group for cardiovascular disease in the Norwegian HUNT 2 population according to the 2003 European guidelines: modelling study

Abstract Objective To estimate the high risk group for cardiovascular disease in a well defined Norwegian population according to European guidelines and the systematic coronary risk evaluation system. Design Modelling study. Setting Nord-Tröndelag health study 1995-7 (HUNT 2), Norway. Participants 5548 participants of the Nord-Tröndelag health study 1995-7, aged 40, 50, 55, 60, and 65. Main outcome measures Distribution of risk categories for cardiovascular disease, with emphasis on the high risk group. Main results At age 40, 22.5% (95% confidence interval 19.3% to 25.7%) of women and 85.9% (83.2% to 88.6%) of men were at high risk of cardiovascular disease. Corresponding numbers at age 50 were 39.5% (35.9% to 43.1%) and 88.7% (86.3% to 91.0%) and at age 65 were 84.0% (80.6% to 87.4%) and 91.6% (88.6% to 94.1%). At age 40, one out of 10 women and no men would be classified at low risk for cardiovascular disease. Conclusion Implementation of the 2003 European guidelines on prevention of cardiovascular disease in clinical practice would classify most adult Norwegians at high risk for fatal cardiovascular disease.

Is opportunistic disease prevention in the consultation ethically justifiable

Medical resources are increasingly shifting from making patients better to preventing them from becoming ill. Genetic testing is likely to extend the list of conditions that can be screened for. Is it time to stop and consider whom we screen and how we approach it Most medical experts and health authorities consider consultations in primary health care ideal for opportunistic health promotion and disease prevention. Doctors are thus expected to discuss preventive measures even when they are not among the reasons for contact. But are such opportunistic initiatives ethically justifiable in contemporary Western medicine? We argue that doctors should maintain a clear focus on each patients reasons for seeking help rather than be distracted by an increasing list of standardised preventive measures with unpredictable relevance to the individual. ![][1] The cornerstone of medical practice is the consultation between a patient who seeks help and a doctor whomthe person trusts.1 Several theoretical models have been developed to analyse and improve the quality of the consultation. In 1979, Stott and Davis presented an influential model that elicited four potentials of the encounter between patient and doctor: management of presenting problems, modification of help seeking behaviour, management of continuing problems, and opportunistic health promotion.2 Since then, opportunistic preventive initiatives have become considered to be part of good medical practice. From a moral point of view, preventive medicine– that is, initiatives to improve health among people who are currently free of symptoms–is fundamentally different from curative medicine, which is offered to patientswho seek medical help. The two disciplines imply different promises and have different obligations to the individuals whose lives they modify.3 When Stott and Davis developed their model, the number of relevant opportunistic initiatives was limited and seemed both technically feasible and ethically justifiable. However, interest in risk factors in healthy … [1]: /embed/graphic-1.gif

Body Configuration as a Predictor of Mortality: Comparison of Five Anthropometric Measures in a 12 Year Follow-Up of the Norwegian HUNT 2 Study

Background Distribution of body fat is more important than the amount of fat as a prognostic factor for life expectancy. Despite that, body mass index (BMI) still holds its status as the most used indicator of obesity in clinical work. Methods We assessed the association of five different anthropometric measures with mortality in general and cardiovascular disease (CVD) mortality in particular using Cox proportional hazards models. Predictive properties were compared by computing integrated discrimination improvement and net reclassification improvement for two different prediction models. The measures studied were BMI, waist circumference, hip circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). The study population was a prospective cohort of 62,223 Norwegians, age 20–79, followed up for mortality from 1995–1997 to the end of 2008 (mean follow-up 12.0 years) in the Nord-Trøndelag Health Study (HUNT 2). Results After adjusting for age, smoking and physical activity WHR and WHtR were found to be the strongest predictors of death. Hazard ratios (HRs) for CVD mortality per increase in WHR of one standard deviation were 1.23 for men and 1.27 for women. For WHtR, these HRs were 1.24 for men and 1.23 for women. WHR offered the greatest integrated discrimination improvement to the prediction models studied, followed by WHtR and waist circumference. Hip circumference was in strong inverse association with mortality when adjusting for waist circumference. In all analyses, BMI had weaker association with mortality than three of the other four measures studied. Conclusions Our study adds further knowledge to the evidence that BMI is not the most appropriate measure of obesity in everyday clinical practice. WHR can reliably be measured and is as easy to calculate as BMI and is currently better documented than WHtR. It appears reasonable to recommend WHR as the primary measure of body composition and obesity.

Ethical dilemmas arising from implementation of the European guidelines on cardiovascular disease prevention in clinical practice. A descriptive epidemiological study.

Objective – Our first objective is to describe total, age- and gender-specific prevalences of subjects in a well-defined population for whom medical follow-up is indicated due to unfavourably high blood pressure and/or cholesterol levels, as defined by the 2003 European guidelines on cardiovascular disease prevention in clinical practice. Our second objective is to highlight scientific questions and ethical dilemmas relating to implementation of the guidelines. Design, setting, and participants – Cross-sectional population study comprising 62 104 adult Norwegians aged 20–79 years who participated in The Nord-Tröndelag Health Study 1995–97. Main outcome measures – Total, age- and gender-specific point prevalences of individuals with total cholesterol ≥5 mmol/l and/or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or taking antihypertensive medication. Main results – In total, 76% of individuals aged 20–79 years have an “unfavourable” cardiovascular disease risk profile, according to guideline definitions. The point prevalence of individuals with cholesterol and/or blood pressure above the recommended cut-off points increases with age. By age 24, the prevalence reaches 50%. By age 49, it reaches 90%. Men below 50 years of age have higher combined risk prevalence than women. Conclusions and implications – Implementation of the 2003 European guidelines on CVD prevention would label a large majority of Norwegian adults as having unfavourably high cholesterol and/or blood pressure levels. The current biomedical standards appear to invalidate demographic health statistics. The theoretical basis on which the guidelines rest should thereby be scrutinized with regard to scientific methodology and consistency. Important ethical dilemmas arise at the point of guideline implementation, relating to risk labelling and medicalization, as well as resource allocation and sustainability within the healthcare system.

The human biology - saturated with experience

BACKGROUND The human being is a self-reflecting, relationship-oriented, goal-directed organism in search of meaning. The process of coordinating and developing knowledge about how experience associated with self-conscience, relationships and values can contribute to development of health and disease is a great challenge for the medical profession. MATERIAL AND METHODS We present a theory-guided synthesis of new scientific knowledge from fields such as epigenetics, psycho-neuro-endocrino-immunology, stress research and systems biology. The sources are articles in acknowledged journals and books, chosen to provide insight into associations between life history (biography) and the human body (biology) in a wide sense. RESULTS Research shows that information about biography, i.e. experienced meaning and relationships, is literally incorporated into the human organism. Epigenetics illustrates the fundamental biological potential for context-dependent adaptation. Further, studies have shown that different types of existential strain may disturb systems for human physiological adaptation, affect structures in the brain and subsequently render the organism vulnerable for disease. However, a sense of belonging and a perception of being supported and acknowledged can contribute to strengthening or restoring health. INTERPRETATION The traditional approach to increasing biomedical knowledge has prevented insight into the medical significance of experience. The new knowledge necessitates a reorientation of theory and practice within the medical profession both with respect to individuals and society.

The new holism: P4 systems medicine and the medicalization of health and life itself.

The emerging concept of systems medicine (or ‘P4 medicine’—predictive, preventive, personalized and participatory) is at the vanguard of the post-genomic movement towards ‘precision medicine’. It is the medical application of systems biology, the biological study of wholes. Of particular interest, P4 systems medicine is currently promised as a revolutionary new biomedical approach that is holistic rather than reductionist. This article analyzes its concept of holism, both with regard to methods and conceptualization of health and disease. Rather than representing a medical holism associated with basic humanistic ideas, we find a technoscientific holism resulting from altered technological and theoretical circumstances in biology. We argue that this holism, which is aimed at disease prevention and health optimization, points towards an expanded form of medicalization, which we call ‘holistic medicalization’: Each person’s whole life process is defined in biomedical, technoscientific terms as quantifiable and controllable and underlain a regime of medical control that is holistic in that it is all-encompassing. It is directed at all levels of functioning, from the molecular to the social, continual throughout life and aimed at managing the whole continuum from cure of disease to optimization of health. We argue that this medicalization is a very concrete materialization of a broader trend in medicine and society, which we call ‘the medicalization of health and life itself’. We explicate this holistic medicalization, discuss potential harms and conclude by calling for preventive measures aimed at avoiding eventual harmful effects of overmedicalization in systems medicine (quaternary prevention).

Self Reported Childhood Difficulties, Adult Multimorbidity and Allostatic Load. A Cross-Sectional Analysis of the Norwegian HUNT Study

Background Multimorbidity receives increasing scientific attention. So does the detrimental health impact of adverse childhood experiences (ACE). Aetiological pathways from ACE to complex disease burdens are under investigation. In this context, the concept of allostatic overload is relevant, denoting the link between chronic detrimental stress, widespread biological perturbations and disease development. This study aimed to explore associations between self-reported childhood quality, biological perturbations and multimorbidity in adulthood. Materials and Methods We included 37 612 participants, 30–69 years, from the Nord-Trøndelag Health Study, HUNT3 (2006–8). Twenty one chronic diseases, twelve biological parameters associated with allostatic load and four behavioural factors were analysed. Participants were categorised according to the self-reported quality of their childhood, as reflected in one question, alternatives ranging from ‘very good’ to ‘very difficult’. The association between childhood quality, behavioural patterns, allostatic load and multimorbidity was compared between groups. Results Overall, 85.4% of participants reported a ‘good’ or ‘very good’ childhood; 10.6% average, 3.3% ‘difficult’ and 0.8% ‘very difficult’. Childhood difficulties were reported more often among women, smokers, individuals with sleep problems, less physical activity and lower education. In total, 44.8% of participants with a very good childhood had multimorbidity compared to 77.1% of those with a very difficult childhood (Odds ratio: 5.08; 95% CI: 3.63–7.11). Prevalences of individual diseases also differed significantly according to childhood quality; all but two (cancer and hypertension) showed a significantly higher prevalence (p<0.05) as childhood was categorised as more difficult. Eight of the 12 allostatic parameters differed significantly between childhood groups. Conclusions We found a general, graded association between self-reported childhood difficulties on the one hand and multimorbidity, individual disease burden and biological perturbations on the other. The finding is in accordance with previous research which conceptualises allostatic overload as an important route by which childhood adversities become biologically embodied.

Immediate surge in female visits to the cardiac emergency department following the economic collapse in Iceland: an observational study

Objective To study potential changes in attendance at emergency departments (ED) in Reykjavík immediately following the swift economic meltdown in Iceland in October 2008. Methods Using electronic medical records of the National University Hospital in Reykjavík, a population-based register study was conducted contrasting weekly attendance rates at Reykjavík ED (cardiac and general ED) during 10-week periods in 2006, 2007 and 2008. The weekly number of all ED visits (major track), with discharge diagnoses, per total population at risk were used to estimate RR and 95% CI of ED attendance in weeks 41–46 (after the 2008 economic collapse) with the weekly average number of visits during weeks 37–40 (before the collapse) as reference. Results Compared with the preceding weeks (37–40), the economic collapse in week 41 2008 was associated with a distinct increase in the total number of visits to the cardiac ED (RR 1.26; 95% CI 1.07 to 1.49), particularly among women (RR 1.41; 95% CI 1.17 to 1.69) and marginally among men (RR 1.15; 95% CI 0.96 to 1.37). A similar increase was not observed in week 41 at the general ED in 2008 or in either ED in 2007 or 2006. In week 41 2008, visits with ischaemic heart disease as discharge diagnoses (ICD-10: I20–25) were increased among women (RR 1.79; 95% CI 1.01 to 3.17) but not among men (RR 1.07; 95% CI 0.71 to 1.62). Conclusion The dramatic economic collapse in Iceland in October 2008 was associated with an immediate short-term increase in female attendance at the cardiac ED.

Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study

Rationale, aims and objectives Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. Methods We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20–74, who participated in the Nord-Trøndelag Health Study (HUNT 2, 1995–1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total). Results Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89–0.99 per 1.0 mmol L−1 increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88–1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92–1.24) was not linear but seemed to follow a ‘U-shaped’ curve, with the highest mortality <5.0 and ≥7.0 mmol L−1. Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98–1.15) and in total (HR: 0.98; 95% CI: 0.93–1.03) followed a ‘U-shaped’ pattern. Conclusion Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the ‘dangers’ of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.