Management of recurrent miscarriage: evaluating the impact of a guideline

BACKGROUND: Little is known on the actual diagnostic and therapeutic management of recurrent miscarriage and the impact of introducing guidelines on this topic. The objective of this study was to evaluate any changes in the management of recurrent miscarriage among Dutch gynaecologists after the introduction of the Dutch guideline 'Recurrent Miscarriage' in 1999. METHODS: Questionnaires were sent to all practices for obstetrics and gynaecology in the Netherlands. Data concerned definition, diagnosis and treatment of recurrent miscarriage. Results were compared with a similar study conducted before the introduction of the guideline and with the recommendations in the guideline. RESULTS: The response rate was 83%. Regarding gestational age, only 3% of the respondents used the definition as advised in the guideline. After the introduction of the guideline, thrombophilia factors were tested more frequently, anticoagulants were prescribed more frequently and more respondents reported to correct uterine malformations. Therapies not described in the guideline, e.g. donor insemination and oocyte donation, were still applied. CONCLUSIONS: The adherence to the Dutch guideline 'Recurrent Miscarriage' was rather poor, presumably due to guideline-related as well as physician-related barriers. Too many diagnostic tests and ineffective therapeutic interventions were performed. This study demonstrates the importance of appropriate implementation and revision.     

Exploring the predictive power of interaction terms in a sophisticated risk equalization model using regression trees

This study explores the predictive power of interaction terms between the risk adjusters in the Dutch risk equalization (RE) model of 2014. Due to the sophistication of this RE‐model and the complexity of the associations in the dataset (N = ~16.7 million), there are theoretically more than a million interaction terms. We used regression tree modelling, which has been applied rarely within the field of RE, to identify interaction terms that statistically significantly explain variation in observed expenses that is not already explained by the risk adjusters in this RE‐model. The interaction terms identified were used as additional risk adjusters in the RE‐model. We found evidence that interaction terms can improve the prediction of expenses overall and for specific groups in the population. However, the prediction of expenses for some other selective groups may deteriorate. Thus, interactions can reduce financial incentives for risk selection for some groups but may increase them for others. Furthermore, because regression trees are not robust, additional criteria are needed to decide which interaction terms should be used in practice. These criteria could be the right incentive structure for risk selection and efficiency or the opinion of medical experts.     

Anchoring molecular mechanisms to the adverse outcome pathway for skin sensitization: Analysis of existing data

Allergic contact dermatitis (ACD) is a hypersensitivity immune response induced by small protein-reactive chemicals. Currently, the murine local lymph node assay (LLNA) provides hazard identification and quantitative estimation of sensitizing potency. Given the complexity of ACD, a single alternative method cannot replace the LLNA, but it is necessary to combine methods through an integrated testing strategy (ITS). In the development of an ITS, information regarding mechanisms and molecular processes involved in skin sensitization is crucial. The recently published adverse outcome pathway (AOP) for skin sensitization captures mechanistic knowledge into key events that lead to ACD. To understand the molecular processes in ACD, a systematic review of murine in vivo studies was performed and an ACD molecular map was constructed. In addition, comparing the molecular map to the limited human in vivo toxicogenomic data available suggests that certain processes are similarly triggered in mice and humans, but additional human data will be needed to confirm these findings and identify differences. To gain insight in the molecular mechanisms represented by various human in vitro systems, the map was compared to in vitro toxicogenomic data. This analysis allows for comparison of emerging in vitro methods on a molecular basis, in addition to mathematical predictive value. Finally, a survey of the current in silico, in chemico, and in vitro methods was used to indicate which AOP key event is modeled by each method. By anchoring emerging classification methods to the AOP and the ACD molecular map, complementing methods can be identified, which provides a cornerstone for the development of a testing strategy that accurately reflects the key events in skin sensitization.     

Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?

OBJECTIVE—To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids.
PATIENTS AND METHODS—47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months.
RESULTS—After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p<0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: −2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p<0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: −2.5% (95% CI: −6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: −4.0% (95% CI: −6.6% to −1.4%; p<0.01). The difference between the groups was not significant: +1.5% (95% CI: −3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups.
CONCLUSION—The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.

     

Does comorbidity explain trends in prescribing of newer antihypertensive agents?

OBJECTIVE: Concerns exist about heavily prescribing of new drugs when the evidence on hard outcomes is still limited. This has been the case for the newer classes of antihypertensives, especially in hypertensive patients without additional comorbidity. The association between comorbidity and trends in prescribing of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) was examined for the period 1996-2000. DESIGN AND METHODS: Data were obtained from the Integrated Primary Care Information database, which contains medical records from more than 100 general practitioners in the Netherlands. Prevalent drug use in hypertensive patients was determined per calendar year. As initial treatment, the first antihypertensive drug prescribed within 1 year after diagnosis of hypertension was considered. Logistic regression was used to estimate the likelihood of receiving either ACE-I or ARBs. RESULTS: The overall prevalent ACE-I use remained stable (31%), but it increased from 33 to 41% in hypertensive patients with diabetes, heart failure, proteinuria and/or renal insufficiency. ARB use increased significantly from 2 to 12%; this trend did not differ between patients with or without specific comorbidities. Initial ACE-I use slightly decreased (from 29% to 24%), whereas initial ARB use significantly increased (from 4% to 12%). ACE-I were more likely to be the first treatment in patients with diabetes [odds ratio (OR)=3.9; 95% confidence interval (CI) 3.2-4.9] or hypercholesterolemia (OR=1.4; 95% CI 1.1-1.8). ARBs were more likely to be the initial treatment in patients with asthma/chronic obstructive pulmonary disease (OR=1.6; 1.2-2.3), diabetes (OR=2.1; 1.5-2.9) or hypercholesterolemia (OR=1.7; 1.2-2.4). CONCLUSIONS: The increased use of ACE-I is mostly restricted to hypertensive patients with comorbidities for which their use has been recommended. Trends in prescribing of ARBs are not related to relevant comorbidities.     

隐性高血压病人中心动脉压及增强指数

目的探讨“隐性高血压”与中心动脉压及动脉硬化的关系。方法采用脉搏波分析仪记录89例临床诊断为血压正常(偶测血压<140/90 mm Hg)及75例高血压(偶测血压≥140/90 mm Hg或正在服用降压药物者)患者的桡动脉脉搏波,经计算机自动转换为相应的中心动脉脉搏波,并分析中心动脉压力及反映全身动脉硬化的增强指数(AIx)。结果小样本人群中,隐性高血压的患病率为15.7%。与血压正常(偶测血压<140/90 mm Hg及白昼动态血压<135/85 mm Hg)组相比,隐性高血压组的血浆总胆固醇及低密度脂蛋白胆固醇浓度、饮酒的比例显著增高;中心动脉收缩压、舒张压、收缩末期压及中心动脉增强压分别增加14.8 mm Hg(CI5.6~24.0 mm Hg)、9.1 mm Hg(CI3.1~15.1 mm Hg)、14.0mm Hg(CI5.8~22.2)及4.2(CI0.6~7.8 mm Hg),增强指数增加11.9%(CI2.8%~20.9%)。虽然隐性高血压组的偶测血压显著低于高血压组,经年龄、性别及身高调整后,两组的白昼动态血压、中心动脉收缩压、舒张压、增强压及增强指数均无显著差异。结论隐性高血压患者的中心动脉压力及增强指数升高,提示动脉顺应性下降,动脉硬化。这些血液动力学的改变可能增加心血管病危险,对其进行评价有助于偶测血压正常者的危险分层。     

Aortic valvuloplasty of calcific aortic stenosis with monofoil and trefoil balloon catheters: practical considerations

Summary In order to evaluate the relation between balloon design (monofoil, trefoil) and valvular configuration, experimental aortic valvuloplasty was performed in four post-mortem hearts with calcific aortic stenosis of various morphology. The degree of obstruction of the aortic orifice was assessed by computed axial tomography during inflation of monofoil 15 and 19 mm and trefoil 3×12 mm balloon catheters. We also evaluated the hemodynamic repercussion of balloon inflation (fall in systolic aortic pressure) in four elderly patients with acquired aortic stenosis who underwent a percutaneous transluminal aortic balloon valvuloplasty, with stepwise increasing balloon sizes of 15 mm, 19 mm and 3×12 mm, as during ourin vitro experiments, and who underwent aortic valve replacement later on. In these patients, we correlated the anatomy of the excised aortic valves with the retrospective analysis of aortic pressure curves recorded during previous valvuloplasty procedures.Our experimental and clinicopathological observations showed that the degree of obstruction of the aortic orifice in post-mortem specimens and the tolerance to balloon inflation in live patients are dependent of the valvular configuration. Although trefoil balloons have the theoretical advantage to avoid complete obstruction of the aortic orifice during inflation, we observed that in presence of a tricuspid configuration, they could be potentially more occlusive than monofoil balloons since each of the 3 individual components of the trefoil balloon occupied the intercommissural spaces while inflated. However, they offered more residual free space when inflated in aortic valves with a bicuspid configuration (i.e. congenitally bicuspid valves or tricuspid valves with one fused commissure).In our opinion, these observations are relevant, since degenerative disease of the aortic valve (i.e. tricuspid valve without commissural fusion) is now recognized as the most common etiology of aortic stenosis in the elderly.Abbreviations AS aortic stenosis - AVA aortic valve area - PTAV percutaneous transluminal aortic balloon valvuloplasty A video supplement to this article has been published in Cardiac Imaging Video Journal volume 2, nr. 4, 1989, see Reference 29.     

Patient Versus Professional Based Psychosocial Risk Factor Screening for Adverse Pregnancy Outcomes

To identify Psychopathology, Psychosocial problems and substance use (PPS) as predictors of adverse pregnancy outcomes, two screen-and-advice instruments were developed: Mind2Care (M2C, self-report) and Rotterdam Reproductive Risk Reduction (R4U, professional’s checklist). To decide on the best clinical approach of these risks, the performance of both instruments was compared. Observational study of 164 pregnant women who booked at two midwifery practices in Rotterdam. Women were consecutively screened with M2C and R4U. For referral to tailored care based on specific PPS risks, inter-test agreement of single risks was performed in terms of overall accuracy and positive accuracy (risk present according to both instruments). With univariate regression analysis we explored determinants of poor agreement (<90 %). For triage based on risk accumulation and for detecting women-at-risk for adverse birth outcomes, M2C and R4U sum scores were compared. Overall accuracy of single risks was high (mean 93 %). Positive accuracy was lower (mean 46 %) with poorest accuracy for current psychiatric symptoms. Educational level and ethnicity partly explained poor accuracy (p < 0.05). Overall low PPS prevalence decreased the statistical power. For triage, M2C and R4U sum scores were interchangeable from sum scores of five or more (difference <1 %). The probability of adverse birth outcomes similarly increased with risk accumulation for both instruments, identifying 55–75 % of women-at-risk. The self-report M2C and the professional’s R4U checklist seem interchangeable for triage of women-at-risk for PPS or adverse birth outcomes. However, the instruments seem to provide complementary information if used as a guidance to tailored risk-specific care.