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Atrial fibrillation (AF) is the most common rhythm disorder with a worldwide prevalence of 2–4%, which is expected to more than double over the next decades mostly due to general ageing [1].

Background: To prevent early postoperative dislocation following a total hip arthroplasty (THA) procedure, patients must adhere to restrictions. Restrictive protocols are common if THA surgery is performed using the posterior approach, but scientific evidence form larger studies that supports these restrictions are scarce. In this large cohort study we compare the <90-days dislocation rate between patients receiving posterior approach THA managed with minimal versus extensive restrictions.Methods: Prospective cohort (n= 1049) of consecutive elective primary hip replacement surgery procedures (September 2014–July 2017) managed with minimal postoperative restrictions. Hospital charts were prospectively reviewed for patient demographics, risk factors and any hip dislocation. Control (n= 1102) consecutive primary elective THAs (January 2011–August 2014) managed with a traditional restrictive protocol. A posterior surgical approach was used in all procedures.Results: Minimal restrictions group: 17 dislocations <90 days (1.6%); Restricted group: 28 (2.5%), chi-square p= 0.1. Testing the hypothesis of inferiority by a minimum of 1% increase in ⩽90 days dislocation risk: p= 0.14 (test for difference) and p< 0.001 (non-inferiority test), allowing us to discard the null hypothesis (absolute increase in risk of ⩾1% with minimal restrictions). The proportion of surgeries performed with a femoral head size ⩾32 mm was higher in the minimal restrictions group.Conclusions: Patients can be managed safely with minimal restrictions following posterior approach THA if combined with frequent use of larger femoral heads.

ObjectivesProphylactic surgery for prevention of acute type A aortic dissection (ATAAD) is reserved for patients with an ascending aortic aneurysm ≥55 mm. Identification of additional risk predictors is warranted since over 70% of patients presenting with ATAAD have a non-dilated aorta or an aneurysm that would not have met the diameter criterion for preventative surgery. Aim of the study was to evaluate ascending aortic elongation as a risk factor for ATAAD and to compare aortic lengths between ATAAD patients and healthy controls.MethodsAortic lengths and diameters of ATAAD patients were measured on three-dimensional modelled computed tomography and adjusted to predissection dimensions in this cross-sectional single-centre study. Logistic regression was used to evaluate the relation between ATAAD and aortic dimensions. Lengths of different aortic segments were compared with a healthy control group using propensity score matching.ResultsTwo-hundred and fifty patients were included in the study (ATAAD, n=40; controls, n=210). Ascending aortic length and diameter proved to be independent predictors for ATAAD (OR=5.3, CI 2.5 to 11.4, p<0.001 and OR=8.6, CI 2.4 to 31.0, p=0.001). Eighty patients were matched based on propensity scores (ATAAD n=40, controls n=40). The ascending aorta was longer and more dilated in ATAAD patients compared with healthy controls (78.6±8.8 mm vs 68.9±7.2 mm, p<0.001, 34.4 mm ±3.2. vs 39.4 mm ±5.7, p<0.001, respectively). No differences were found in lengths of the aortic arch and descending aorta.ConclusionsAscending aortic length could serve as an independent predictor for ATAAD. Future studies addressing indications for prophylactic surgery should also investigate aortic length.

ObjectivesDifferentiation between normal and abnormal features of vascular ageing is crucial, as the latter is associated with adverse outcomes. The normal aortic ageing process is accompanied by gradual luminal dilatation and reduction of vessel compliance. However, the influence of age on longitudinal aortic dimensions and geometry has not been well studied. This study aims to describe the normal evolution of aortic length and shape throughout life.MethodsA total of 210 consecutive patients were prospectively enrolled in this cross-sectional single-centre study. All subjects underwent CT on a third-generation dual-source CT scanner. Morphometric measurements, including measurements of segmental length and tortuosity, were performed on three-dimensional models of the thoracic aorta.ResultsThe length of the thoracic aorta was significantly related to age (r=0.54) and increased by 59 mm (males) or 66 mm (females) between the ages of 20 and 80 years. Elongation was most pronounced in the proximal descending aorta, which showed an almost 2.5-fold length increase during life. The lengthening of the thoracic aorta was accompanied by a marked change of its geometry: whereas the aortic apex was located between the branch vessels in younger patients, it shifted to a more distalward position in the elderly.ConclusionsThe normal ageing process is accompanied by gradual aortic elongation and a notable change of aortic geometry. Part II of this two-part article investigates the hypothesis that excessive elongation could play a role in the occurrence of acute aortic dissection.

The rise of genetic techniques presents a great promise as well as some difficult dilemma's about how genetics will affect the way we will be able to live our lives. For this reason, in many countries, public debates are organized to reflect upon the development of predictive medicine. In this essay we focus on economist A. Hirschman's work on “exit, voice and loyalty” to analyse and enrich these public debates. We first introduce Hirschman's triad of concepts and focus on the concept of “voice,” which refers to an institution's ability to allow clients to give feedback about products or services, and its ability to listen to the feedback given. We argue that voice is particularly important for the health care system in which predictive medicine is developing. Voice is crucial because how predictive medicine will become institutionalised is now in the process of becoming determined. However, in public debates about predictive medicine, voice tends to be reduced to providing people with the option of making a choice whether to use genetic techniques or not. We argue that this reduction of voice to choice is not very informative about predictive medicine and suggest an amendment of Hirschman's concept of voice, which we call “hesitant voice.” Hesitant voice attempts to be informative about the uncertainty people experience in addressing predictive medicine and topicalises the gradual, the embodied, the tentative character of voice in developing situations like that of predictive medicine.

It is important and urgent to question therelationship between evidence-based medicineand power shifts in health care systems.Although definitions of EBM are phrased as ascientific approach to medicine, EBM is anormative concept: it aims to improve medicineand health care. Both proponents and opponentsuse a normative concept. More particularly,they provide particular views on positions,responsibilities, possibilities, norms andrelationships between professionals, patientgroups, governments and other parties in healthcare and society. From this perspective, wewant to analyse the role of EBM in modernwestern societies. By using citizenshiptheory, we will argue that the role of EBM isnot fixed but depends on the relation betweenstate and society. We will first analyse thefundamental change in western societies duringthe past decades, from modern to post-modernsocieties. Then, we will elaborate a fourfoldmodel of possible relationships between stateand society, and discuss the issue of how EBM mayfit in, by giving some examples of the practiceof EBM in different European countries. On thisbasis, we conclude to consider EBM as a publicforum where proponents and opponents of EBMdiscuss diverse and possibly conflicting waysof changing medicine, health care, and healthpolicy. This requires the incorporation of theperspective of citizens and their socialnetworks, professionals with practical andtacit knowledge, and diverse public views onwhat is regarded as `a good life'. Inasmuch asEBM is expected to be practically relevant, itought to be tied to rather than separated fromthe normative world of emancipated patients anddiverse health care practices. Proponents andopponents of EBM should be prepared to defendthe normative claims and power effects that areinherently tied to any presentation ofevidence.

Objectives: To study considerations used by professional and academic leaders to assess the position of new cardiovascular drugs in the therapeutic regimen in relationship to professional characteristics and the level of prescribing. Methods: Interviews with 39 internists, cardiologists, general practitioners, and hospital pharmacists about considerations regarding the therapeutic position and prescribing of a new cardiovascular drug (losartan or atorvastatin) and professional characteristics. Considerations were classified according to Rogers' characteristics of an innovation, i.e., referring to the drug's relative advantage, compatibility, or complexity. Proportions of respondents mentioning advantageous, comparable, and/or disadvantageous characteristics were used to construct patterns to analyze an overall evaluation of the drugs in relation to professional characteristics and level of prescribing. Results: The majority of considerations referred to the degree of relative advantage, but different subjects were emphasized for both drugs. Overall patterns of evaluation were generally intermediate and negative. The respondents' profession, mentioning commercial sources of information and self-qualification as a (moderately) early adopter of new drugs differentiated the overall evaluation of the drugs, in contrast to expertness and academic affiliation. The level of prescribing differentiated the overall evaluation only in the case of losartan. Conclusions: These professional and academic leaders critically evaluated the claims when assessing the position of the drugs in the therapeutic regimen but did not show consensus in their considerations. Accepted principles for prescribing were considered when assessing the therapeutic position of the drugs but resulted in varied tendencies for prescribing.

To examine discrepancies between co-morbidity of patients included in pre-marketing clinical trials of cardiovascular drugs and patients from daily practice, representing the actual users after marketing, and to investigate the availability of data regarding co-morbidity in registration files. Data were collected from phase III trials of registration files of 16 drugs, registered in the Netherlands in the period 1985 through 1994 for the indications hypertension, angina pectoris or hypercholesterolemia, and from a general practitioners database. Patients were selected who used drugs from the same therapeutic classes for the same indication as the patients in the pre-marketing trials. Prevalences of concomitant cardiovascular, endocrine and metabolic diseases were compared between pre- and postmarketing populations. Discrepancies were defined as more than 10% difference in prevalences. Data regarding co-morbidity were present in 13 out of 16 registration files and differed in format of reporting. For all indications, coexisting cardiovascular, endocrine and metabolic diseases were less prevalent in the pre-marketing populations, except ischemic heart disease, which was more prevalent coexisting with angina pectoris and hypercholesterolemia. Discrepancies were found for hypertensive disease, heart failure, diabetes mellitus and myocardial infarction. Phase III trials testing cardiovascular drugs included patients with concomitant cardiovascular, endocrine and metabolic diseases, but discrepancies were present with patients in daily practice. Development of guidelines for uniform collection and reporting of co-morbidity data in pre-marketing trials is recommended, as well as further utilization of data. Copyright © 2000 John Wiley & Sons, Ltd.

Phase III trials from registration files of cardiovascular drugs were analyzed to study the inclusion of patients with concomitant morbidity and medication. For this purpose, 15 drugs were selected which were registered in the Netherlands during the period 1985–1994 for the indications hypertension, angina pectoris, hypercholesterolemia, or myocardial infarction. The results show that preregistration trials are performed in populations which present with comorbidity and comedication. Cardiovascular, endocrine, and metabolic diseases were the most prevalent coexisting diseases. Large variation was found between registration files in the reporting of data and in patterns of comorbidity. Differences in mean comorbidity and comedication per patient were found between trials performed in different regions. The impact of various definitions of patient selection criteria on the actual inclusion of patients with coexisting morbidity was analyzed. Differences in definitions resulted in different levels of inclusion. Also, trials were found to include patients when this was not allowed and vice versa. The results are discussed in relation to the question of whether the generalizability of preregistration trials can be enhanced by further utilization of data from these heterogeneous populations. The issue to study is variability between safety and efficacy in patient groups with different patterns of comorbidity and comedication. In order to allow registration authorities to consider patterns of comorbidity and comedication during the evaluation of registration files, development of guidelines for uniform reporting of data in preregistration trials is recommended. Drug Dev. Res. 51:159–168, 2000. © 2001 Wiley-Liss, Inc.

Phase III trials from registration files of cardiovascular drugs were analyzed to study the inclusion of patients with concomitant morbidity and medication. For this purpose, 15 drugs were selected which were registered in the Netherlands during the period 1985–1994 for the indications hypertension, angina pectoris, hypercholesterolemia, or myocardial infarction. The results show that preregistration trials are performed in populations which present with comorbidity and comedication. Cardiovascular, endocrine, and metabolic diseases were the most prevalent coexisting diseases. Large variation was found between registration files in the reporting of data and in patterns of comorbidity. Differences in mean comorbidity and comedication per patient were found between trials performed in different regions. The impact of various definitions of patient selection criteria on the actual inclusion of patients with coexisting morbidity was analyzed. Differences in definitions resulted in different levels of inclusion. Also, trials were found to include patients when this was not allowed and vice versa. The results are discussed in relation to the question of whether the generalizability of preregistration trials can be enhanced by further utilization of data from these heterogeneous populations. The issue to study is variability between safety and efficacy in patient groups with different patterns of comorbidity and comedication. In order to allow registration authorities to consider patterns of comorbidity and comedication during the evaluation of registration files, development of guidelines for uniform reporting of data in preregistration trials is recommended. Drug Dev. Res. 51:159–168, 2000. © 2001 Wiley‐Liss, Inc.

In a medical information extraction system, we use common word association techniques to extract side-effect-related terms. Many of these terms have a frequency of less than five. Standard word-association-based applications disregard the lowest-frequency words, and hence disregard useful information. We therefore devised an extraction system for the full word frequency range. This system computes the significance of association by the log-likelihood ratio and Fisher's exact test. The output of the system shows a recurrent, corpus-independent pattern in both recall and the number of significant words. We will explain these patterns by the statistical behavior of the lowest-frequency words. We used Dutch verb-particle combinations as a second and independent collocation extraction application to illustrate the generality of the observed phenomena. We will conclude that a) word-association-based extraction systems can be enhanced by also considering the lowest-frequency words, b) significance levels should not be fixed but adjusted for the optimal window size, c) hapax legomena, words occurring only once, should be disregarded a priori in the statistical analysis, and d) the distribution of the targets to extract should be considered in combination with the extraction method.

In reference to the different approaches in philosophy(of medicine) of the nature of (medical) technology,this article introduces the topic of this specialissue of Theoretical Medicineand Bioethics, that is,the way the different forms of medical technologyfunctionin everyday medical practice. The authorselaborate on the active role technology plays inshaping our views on disease, illness, and the body,whence in shaping our world.

To describe how developments in the pharmacy profession in The Netherlands converged into the current movement toward pharmaceutical care.

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.

Design research programs attempt to bring together the properties of available materials and the demands derived from intended applications. The logic of problem states and state transitions in such programs, including assessment criteria and heuristic principles, is described in settheoretic terms, starting with a naive model comprising an intended profile and the operational profile of a prototype. In a first concretization the useful distinction between structural and functional properties is built into the model. In two further concretizations the inclusion of potential applications is motivated and described for the case of drug research as well as the inclusion of potential realizations for the case of complex products. Next, another line of concretization of the naive model, the incorporation of potentially relevant properties, is sketched. Then the partial analogy between “product-” and “truth-approximation” is indicated. We conclude with some remarks about the usefulness of our models for products reaching the market in comparison to the the so-called social construction of technology approach.