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In explaining why a patient has been struck with disease, health care professionals may turn to arguments from epidemiology, pointing to risk factors from lifestyle, diet, or genetics. Yet many patients build detailed narratives on why and when disease and illness overcame them. They can point to specific behaviors, of themselves or others, to stress, or fate. Such stories and health beliefs can help patients preserve mental health in the context of life-threatening diagnoses but stories can also be protective of physical health. There seems to be little room for "chance" in these narratives, which illustrates the apparent disparity between probabilistic descriptions and patients' need for explanations and meaning. Recent pleas for evidentiary pluralism and narrative-based medicine aim at closing this gap.

Diagnostic accuracy studies are, like other clinical studies, at risk of bias due to shortcomings in design and conduct, and the results of a diagnostic accuracy study may not apply to other patient groups and settings. Readers of study reports need to be informed about study design and conduct, in sufficient detail to judge the trustworthiness and applicability of the study findings. The STARD statement (Standards for Reporting of Diagnostic Accuracy Studies) was developed to improve the completeness and transparency of reports of diagnostic accuracy studies. STARD contains a list of essential items that can be used as a checklist, by authors, reviewers and other readers, to ensure that a report of a diagnostic accuracy study contains the necessary information. STARD was recently updated. All updated STARD materials, including the checklist, are available at http://www.equator-network.org/reporting-guidelines/stard. Here, we present the STARD 2015 explanation and elaboration document. Through commented examples of appropriate reporting, we clarify the rationale for each of the 30 items on the STARD 2015 checklist, and describe what is expected from authors in developing sufficiently informative study reports.

ObjectiveLiver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.DesignIndividual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.ResultsData were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (ConclusionSequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

Background Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. Methods In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. Discussion The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. Trial registration The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Additional file 1. SPIRIT checklist

Additional file 2. Imaging Protocols of The Radiological Society of the Netherlands

Background: A variety of study designs are available to evaluate the accuracy of tests, but the terms used to describe these designs seem to lack clarity and standardization. We investigated if this was the case in the diagnostic guidance of the National Institute of Care and Health Excellence (NICE), an influential source of advice on the value of tests. Objectives: To describe the range of study design terms and labels used to distinguish study designs in NICE Diagnostic Guidance and the underlying evidence reports. Methods: We carefully examined all NICE Diagnostic Guidance that has been developed from inception in 2011 until 2018 and the corresponding diagnostic assessment reports that summarized the evidence, focusing on guidance where tests were considered for diagnosis. We abstracted labels used to describe study designs and investigated what labels were used when studies were weighted differently because of their design (in terms of validity of evidence), in relevant sections. We made a descriptive analysis to assess the range of labels and also categorized labels by design features. Results: From a total of 36 pieces of guidance, 20 (56%) were eligible and 17 (47%) were included in our analysis. We identified 53 unique design labels, of which 19 (36%) were specific to diagnostic test accuracy designs. These referred to a total of 12 study design features. Labels were used in assigning different weights to studies in seven of the reports (41%) but never in the guidance documents. Conclusion: Our study confirms a lack of clarity and standardization of test accuracy study design terms. There seems to be scope to reduce and harmonize the number of terms and still capture the design features that were deemed influential by those compiling the evidence reports. This should help decision makers in quickly identifying subgroups of included studies that should be weighted differently because their designs are more susceptible to bias.

STUDY QUESTION: Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? SUMMARY ANSWER: We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. WHAT IS KNOWN ALREADY: A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. STUDY DESIGN, SIZE, DURATION: We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). PARTICIPANTS/MATERIALS, SETTING, METHODS: We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. MAIN RESULTS AND THE ROLE OF CHANCE: None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). LIMITATIONS, REASONS FOR CAUTION: Since this is the first large study that looked at potential treatment selection markers for IVF-SET compared to IUI-OS, we had no data on which to base a power calculation. The sample size was limited, making it difficult to detect any smaller associations. WIDER IMPLICATIONS OF THE FINDINGS: We could not identify couples with unexplained or mild male subfertility who would have had higher chances of a healthy child from immediate IVF-SET than from IUI-OS. As in the original trial IUI-OS had similar effectiveness and was less costly compared to IVF-SET, IUI-OS should remain the preferred first-line treatment in these couples. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from the Netherlands Organization for Health Research and Development, and a grant from the Netherlands' association of health care insurers. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: The trial was registered at the Dutch trial registry (NTR939).

A recently released report by the Dutch Council for Public Health and Society ('Raad voor Volksgezondheid en Samenleving') is subtitled "About the illusion of evidence-based practice in healthcare". The author argues that this report is a sign of the times, a period of "post-truth medicine" and "alternative facts", in which "science offers nothing but a reduction". Although the report rightly - but superfluously - argues that having an evidence base is insufficient for delivering quality care (no decisions without considering context), its depiction of the illusory nature of evidence-based practice represents a brutal slap in the face of all those who turn to sound clinical and biomedical research to back up or refute claims about the effectiveness of healthcare interventions

The study design for randomised double-blind studies is powerful. Randomisation and blinding ensure that the groups that are compared are truly exchangeable. Any differences in health outcomes can be attributed rightfully to the one aspect on which the study groups differ: the treatment. In this commentary, we argue that the use of this powerful study design at the wrong moment can lead to undesirable situations.

The study design for randomised double-blind studies is powerful. Randomisation and blinding ensure that the groups that are compared are truly exchangeable. Any differences in health outcomes can be attributed rightfully to the one aspect on which the study groups differ: the treatment. In this commentary, we argue that the use of this powerful study design at the wrong moment can lead to undesirable situations

STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

Objective The ProTWIN Trial (NTR1858) showed that, in women with a multiple pregnancy and a cervical length < 25th percentile (38 mm), prophylactic use of a cervical pessary reduced the risk of adverse perinatal outcome. We investigated whether other maternal or pregnancy characteristics collected at baseline can improve identification of women most likely to benefit from pessary placement. Methods ProTWIN is a multicenter randomized trial in which 808 women with a multiple pregnancy were assigned to pessary or control. Using these data we developed a multivariable logistic model comprising treatment, cervical length, chorionicity, pregnancy history and number of fetuses, and the interaction of these variables with treatment as predictors of adverse perinatal outcome. Results Short cervix, monochorionicity and nulliparity were predictive factors for a benefit from pessary insertion. History of previous preterm birth and triplet pregnancy were predictive factors of possible harm from pessary. The model identified 35% of women as benefiting (95% CI, 32-39%), which is 10% more than using cervical length only (25%) for pessary decisions. The model had acceptable calibration. We estimated that using the model to guide the choice of pessary placement would reduce the risk of adverse perinatal outcome significantly from 13.5% when no pessary is inserted to 8.1% (absolute risk reduction, 5.4% (95% CI, 2.1-8.6%)). Conclusions We developed and internally validated a multivariable treatment selection model, with cervical length, chorionicity, pregnancy history and number of fetuses. If externally validated, it could be used to identify women with a twin pregnancy who would benefit from a pessary, and lead to a reduction in adverse perinatal outcomes in these women. Copyright (C) 2016 ISUOG. Published by John Wiley & Sons Ltd.

Background and study aims: The introduction of self-expandable metal stents has offered a promising alternative for palliation of malignant left-sided colonic obstruction. This randomized clinical trial aimed to assess whether a nonsurgical policy, with endoluminal stenting, is superior to surgical treatment in patients with stage IV left-sided colorectal cancer and imminent obstruction. Patients and methods: Patients with incurable left-sided colorectal cancer who fulfilled the study criteria were randomly assigned to nonsurgical or surgical treatment. The primary outcome measure was survival in good health out of hospital (World Health Organization performance scores 0 or 1). Results: A high number of serious adverse events in the nonsurgical arm led to premature closure of the trial. Ten patients were allocated to surgical treatment and 11 patients to nonsurgical palliation. The median survival in good health out of hospital during the first year was 56 days (inter-quartile range 7.5-338.5 days) in the surgical arm vs. 38 days (interquartile range 5.25-288.75 days) in the nonsurgical arm (p = 0.68). Eleven adverse events (six perforations) occurred in the nonsurgical arm vs. one adverse event in the surgical arm (p > 0.001). Of the six perforations, two were stent-related because they occurred at the proximal edge of the stent by erosion through a normal colon wall; one was probably stent-related (it was located in the region of the proximal half of the stent); one was a colon blowout; and two were late tumor perforations in patients on chemotherapy. Conclusions: The unexpected high rate of perforation in the nonsurgical arm might be specifically WallFlex-related or enteral stent-related in patients on chemotherapy and warrants attention

Reporting guidelines have been developed for randomized clinical trials, systematic reviews, and many other types of studies. Most of these have a checklist of essential items that have to be included in every study report. Describing these essential items enables readers to better judge the validity, relevance and applicability of study findings. The website of the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network now lists more than 200 such reporting guidelines. While they have been endorsed by many journals and other organizations, uptake has been incomplete. The implicit assumption in many guidelines was that editors of scientific journals would police authors, thereby enforcing the use of the checklists. We argue that the groups responsible for reporting guidelines could put more effort into the development of tools for authors, reviewers and editors to facilitate the implementation of these guidelines. This would contribute to completeness and transparency in reporting clinical and biomedical research

BACKGROUND: Since 2005, the International Committee of Medical Journal Editors (ICMJE) requires researchers to prospectively register their clinical trials in a publicly accessible trial registry. The Consolidated Standards of Reporting Trials (CONSORT) statement has supported this policy since 2010. We aimed to evaluate to what extent biomedical journals have incorporated ICMJE's clinical trial registration policy into their editorial and peer review process. METHODS: We searched journals' instructions to authors and performed an internet survey among all journals publishing reports of randomised controlled trials that follow ICMJE's Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals (n = 695), and/or that endorse the CONSORT statement (n = 404) accessed in January 2011. Survey invitations were sent to the email addresses of the editorial offices and/or editors-in-chief of included journals in June 2011. RESULTS: For 757 ICMJE and/or CONSORT journals, we identified that they published RCT reports. We could assess the instructions to authors of 747 of these; 384 (51%) included a statement of requiring trial registration, and 33 (4%) recommended this. We invited 692 editorial offices for our survey; 253 (37%) responded, of which 50% indicated that trial registration was required; 18% cross-checked submitted papers against registered records to identify discrepancies; 67% would consider retrospectively registered studies for publication. Survey responses and specifications in instructions to authors were often discordant. CONCLUSION: At least half of the responding journals did not adhere to ICMJE's trial registration policy. Registration should be further promoted among authors, editors and peer reviewers.

We systematically reviewed the evidence concerning the ability of five systemic treatments to induce remission in patients with severe psoriasis: ultraviolet B (UVB), photochemotherapy (PUVA), methotrexate (MTX), retinoids (RET) and cyclosporin A (CYA). An elaborate literature search was performed, the validity of studies was assessed, and data were analysed. In total, 89, 193, 101, 155 and 127 studies (n = 665) concerning UVB, PUVA, MTX, RET and CYA were found. The exclusion rate was high, mainly because of concomitant antipsoriatic therapy, outdated dosages or inadequate documentation. No study on MTX could be included. A total of 129 patient series was included in the analysis, reporting on 13,677 patients. Study size-weighted averages of the proportions of patients with clearance and good, moderate and poor response (defined, respectively, as 95-100%, 75-100%, 50-75% and < 50% reduction in the outcome measurements as compared with baseline) were calculated. PUVA therapy was associated with the highest average proportion of patients with clearance (70%), and the highest proportion of patients with good response (83%), followed by UVB (68%) and CYA (64%). Incidence of side-effects per week was highest in the RET group and lowest in the phototherapy groups. This review may provide a basis for the development of guidelines for the treatment of psoriasis. Trials comparing oral modalities applied according to currently accepted standards should also be carried out

Accurate diagnostic tests have a key role in patient management and the control of most infectious diseases. Unfortunately, in many developing countries, clinical care is often critically compromised by the lack of regulatory controls on the quality of these tests. The information available on the performance of a diagnostic test can be biased or flawed because of failings in the design of the studies which assessed the performance characteristics of the test. As a result, diagnostic tests are sold and used in much of the developing world without evidence of effectiveness. Misdiagnosis leading to failure to treat a serious infection or wasting expensive treatment on people who are not infected remains a serious obstacle to health.

OBJECTIVE: To determine, in people who participated in the Netherlands Heart Foundation's National Cholesterol Test in supermarkets, risk factors for cardiovascular disease and expectations concerning the test result using a questionnaire, and to compare their cholesterol levels with reference values. DESIGN: Descriptive study and questionnaire survey. METHOD: Participants who underwent the National Cholesterol Test in 9 supermarkets during the summer of 2007 were invited to complete a short questionnaire about risk factors for cardiovascular disease and expectations concerning the test result. Statements about the intention to change behaviour were offered, and the measured total cholesterol level was recorded. RESULTS: The average age of the 684 respondents was 57 years (SD: 16); 72% were female. Participants had on average a lower risk of cardiovascular disease than the general population; they suffered less frequently from diabetes, hypertension and being overweight, and smoked less. The measured cholesterol level was 5.0-6.5 mmol/l in 37% and > 6.5 mmoll in 11%. Elevated cholesterol levels were less common in this group than in the general population. The intention to change behaviour was substantial. CONCLUSION: The results of this study showed that the National Cholesterol Test reached relatively many healthy, somewhat worried people. The intention to change behaviour was substantial.

OBJECTIVE: Intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH) is commonly used as treatment of first choice in couples with unexplained subfertility. This treatment should only be applied when there is a realistic increase in chance of pregnancy, particularly because it carries the increased risk of multiple pregnancies. We evaluated the effectiveness of IUI with COH relative to expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy. DESIGN: Multicentre randomised clinical study. METHOD: 253 couples with unexplained subfertility and a probability of a spontaneous ongoing pregnancy of 30% to 40% within 12 months, were randomly assigned to IUI with COH for 6 months or expectant management for 6 months. The primary endpoint of our study was ongoing pregnancy within 6 months. Analysis was carried out according to the intention to treat principle. This study was registered with the Dutch Trial Register and has the International Standard Randomised Clinical Trial number ISRCTN72675518. RESULTS: Of the 253 couples included, 127 couples were allocated to IUI with COH and 126 to expectant management. In the intervention group, 42 women (33%) conceived, of which 29 pregnancies were ongoing (23%). In the expectant management group, 40 women (32%) conceived, of which 34 pregnancies were ongoing (27%) (relative risk: 0.85; 95% CI: 0.63-1.1). In the expectant management group one twin pregnancy occurred and in the intervention group one woman conceived twins and one a triplet. CONCLUSION: A substantial beneficial effect of IUI with COH in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for a period of 6 months therefore appears justified in these couples

In evidence-based medicine, decisions about patient care are based on the results of sound clinical research. Yet, even in evidence-based medicine, science does not directly dictate practice. Making decisions requires setting priorities and making trade-offs. The results of scientific research limit rather than prescribe the available options. When a treatment is known to be ineffective, it cannot be selected for its efficacy. When a treatment has been shown to produce a particular effect, opting for that particular treatment should be based on the desirability of the demonstrated effect and trade-offs between that effect and other effects. Guidelines for clinical practice should reflect the results of clinical research, as well as the priorities that have been set and the trade-offs that have been made.

OBJECTIVE: To identify additional risk factors and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages. DESIGN: Nested case-control study. METHOD: In 6 centres for clinical genetics in the Netherlands, data were collected from couples referred for karyotyping after 2 2 miscarriages from 1992-2000. Factors influencing the probability of carrier status were examined. The corresponding probability of carrier status was calculated for the various combinations of these factors. RESULTS: In total 279 carrier couples and 428 non-carrier couples were included. 4 independent factors influencing the probability of carrier status were identified: a younger maternal age at the time of second miscarriage, a history of > or = 3 miscarriages, a history of > 2 miscarriages in a brother or sister of either partner, and a history of> 2 miscarriages in parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages, varied between 0.5-10.2%. In 18% of couples included, the risk was found to be so low (< 2.2%), that in couples with comparable risk factors, it may not be necessary to perform karyotyping. CONCLUSION: This study demonstrated that the probability of carrier status in couples with > or = 2 miscarriages is modified by additional factors. Selective chromosome analysis would result in a more effective referral policy and therefore decrease the number of chromosome analyses and lower the costs.

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Because of its limitations and risks, alternatives are being developed for liver biopsy as the first-line method for evaluating liver injury. Many markers and several imaging methods have been developed as non-invasive alternatives. Although these methods have been evaluated in studies published in peer-reviewed journals, the methodological rigor of the design, execution and analysis of these studies leaves much to be desired. In addition, some of the inventors of these methods, who have become shareholders of the companies that market these tests, can be found frequently in the list of authors. The way in which new medical tests are evaluated can be improved, as well as the level of independence from conflicting interests

A marked increase in the availability of diagnostic tests for use at home has been observed in recent years. There are regulations concerning the development and application of these tests. The question whether the increased use of self-tests is a positive or negative development cannot be answered easily. In some cases serious diseases may be detected in people who are reluctant to consult a physician. In other cases false negative test results may delay necessary treatment. Further exploration of the use, sensitivity, specificity, benefits and harms of specific tests is warranted

OBJECTIVE: To identify additional risk factors and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages. DESIGN: Nested case-control study. METHOD: In 6 centres for clinical genetics in the Netherlands, data were collected from couples referred for karyotyping after 2 2 miscarriages from 1992-2000. Factors influencing the probability of carrier status were examined. The corresponding probability of carrier status was calculated for the various combinations of these factors. RESULTS: In total 279 carrier couples and 428 non-carrier couples were included. 4 independent factors influencing the probability of carrier status were identified: a younger maternal age at the time of second miscarriage, a history of > or = 3 miscarriages, a history of > 2 miscarriages in a brother or sister of either partner, and a history of> 2 miscarriages in parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages, varied between 0.5-10.2%. In 18% of couples included, the risk was found to be so low ( or = 2 miscarriages is modified by additional factors. Selective chromosome analysis would result in a more effective referral policy and therefore decrease the number of chromosome analyses and lower the costs

The objective of the 'Standards for Reporting of Diagnostic Accuracy' (STARD) initiative is to improve the reporting of studies of diagnostic accuracy, so as to allow readers to assess the potential for bias in a study and to evaluate the generalibility of its results. - The group searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies. This was used to draw up a list of potential items. During a consensus meeting, a group of researchers, medical journal editors, and members of professional organisations reduced this list to a usable checklist. Wherever possible, evidence from the literature was used to justify the decisions made. - The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which a list of 75 potential items was extracted. At the consensus meeting, participants shortened the list to a 25-item checklist. A generic flow diagram was drawn up to provide guidance on the method for including patients, the order in which tests were to be conducted and the number of patients to undergo the test being evaluated, the reference standard, or both. - A scientific publication can only be assessed when the reporting is both correct and complete. Use of the checklist and flow diagram will improve the quality of reports produced, to the advantage of clinicians, researchers, reviewers, journal editors and other interested parties.

OBJECTIVE: To evaluate a program for the local development and implementation of evidence based guidelines in the Academic Medical Center in Amsterdam, the Netherlands. DESIGN: Retrospective evaluation study. METHOD: In the period 1992-2001, 50 guideline projects had received funding. Two questionnaires were developed to monitor aspects of development and implementation of guidelines. The first questionnaire was based on the 'Appraisal of Guidelines for Research & Evaluation' (AGREE) instrument. In total 39 projects of which the original application form as well as the final report was accessible, were scored by 3 researchers. A second questionnaire was developed on the basis of an implementation model by Grol and was filled out by 46 applicants. RESULTS: The primary motive for the development of a guideline were doubts about the effectiveness of a procedure. In 79% researchers (partly) collected their own data. The future users of the guideline were involved in an early stage of the development project in 72% of all cases. In 28% potential obstructing factors were identified. Introduction of the guideline was done through oral presentations in 42% without the use of an extensive implementation strategy. Of all subsidized projects, 24% was ongoing and 74% had been implemented successfully. CONCLUSION: In the AMC-program subsidized projects often led to successfully developed guidelines, which subsequently were introduced in practice

Forty years after the first mammograms were made, doubts are cast on the effectiveness of population screening for breast cancer. Disease-specific and overall mortality appear to have diminished, but any real effect is small. Proponents of breast cancer screening point at the possibility of saving lives and at the obligation to do so, whereas opponents emphasise that the screening may do more harm than good and that the large funds involved might be better spent in other health care areas. If the experts cannot decide on the effectiveness, simply leaving the choice of whether or not to take part up to citizens offers no solution. These complex health care matters require complex answers, which have to be found before any population screening for cancer of prostate, colon or lung can be implemented.