Sander M. J. van Kuijk

Hypertension After Preeclampsia Is Preceded by Changes in Cardiac Structure and Function

Preeclampsia is associated with a 4-fold higher risk for developing remote chronic hypertension. Preeclampsia is accompanied by left ventricular hypertrophy and decreased diastolic function, which may or may not resolve postpartum. We tested the hypothesis that increased measures of cardiac geometry and decreased cardiac function persisting for ≥6 months postpartum in normotensive women with a history of preeclampsia precede the development of later chronic hypertension. Formerly preeclamptic women (n=652) underwent echocardiography at 9 months (range, 6–19) postpartum. We excluded women with preexisting hypertension (n=42), hypertension at the postpartum screening (n=133), and those that did not return any checklist (n=128). Eventually, 349 women were included. Remote health was evaluated by a biennially checklist. We used Cox regression for analysis. Twenty-seven (8%) normotensive women had developed chronic hypertension during a medium follow-up period of 6 years. At screening they differed from their counterparts who remained normotensive by hazard ratio for left ventricular mass index (1.11; 95% confidence interval [CI], 1.03–1.18), diastolic blood pressure (1.13; 95% CI, 1.06–1.20), systolic blood pressure (1.07; 95% CI, 1.02–1.11), mean arterial pressure (1.11; 95% CI, 1.05–1.18), heart rate (1.05; 95% CI, 1.01–1.10), and E/A ratio (0.22; 95% CI, 0.06–0.85). Backward stepwise analysis showed independent hazard ratio for left ventricular mass index and diastolic blood pressure 1.08 (95% CI, 1.01–1.16) and 1.13 (95% CI, 1.06–1.21), respectively. In conclusion, the development of later chronic hypertension in initially normotensive formerly preeclamptic women is preceded by increased left ventricular mass index and diastolic blood pressure at postpartum screening.

Index event bias-a numerical example

Studies of determinants of recurrent disease often give unexpected results. In particular, well-established risk factors may seem not to have much influence on the recurrence risk. Recently, it has been argued that such paradoxical findings may be because of the bias caused by the selection of patients based on the occurrence of an earlier episode of the disease. This bias was referred to as index event bias. Here, we give a theoretical quantitative example of index event bias, showing that, as a result of selection of patients on the basis of previous disease: (1) risk factors become inversely associated when they are not in the unselected population, and (2) the crude association between the risk factor of interest and disease becomes biased toward the null.

Long-Term Risk to Develop Hypertension in Women With Former Preeclampsia: A Longitudinal Pilot Study

Introduction: Women with former preeclampsia (exPE) develop chronic hypertension 4 times more often than healthy parous controls. Women, destined to develop remote chronic hypertension, had increased left ventricular mass index (LVMI) and diastolic blood pressure (BP) prior to the onset of hypertension as compared to those remaining normotensive. However, longitudinal data on the progress of this increased LVMI in women destined to develop hypertension are lacking. Methods: We included 20 women with exPE and 8 parous controls. At both 1- and 14-year postpartum (pp), we performed cardiac ultrasound and determined circulating levels of the metabolic syndrome variables. Of 14-year pp, 7 (35%) former patients had developed chronic hypertension. We compared these 7 former patients with both the 13 former patients who remained normotensive and the 8 parous controls using the Mann-Whitney U test and Kruskal-Wallis analysis. Results: Women with hypertensive exPE differed from their normotensive counterparts by a higher incidence of early-onset preeclampsia (PE) in their index pregnancy and a higher rate of recurrence in next pregnancies. At 1-year pp, they also had high/normal BP and higher fasting insulin levels. At 14 years pp, the relative left ventricular wall thickness was higher, and the E/A ratio was lower, in the hypertensive group relative to those remaining normotensive. Conclusion: Women with exPE are at increased risk of developing chronic hypertension, when (1) the PE in the index pregnancy had an early-onset and/or recurred in next pregnancies and (2) the 1-year pp. Blood pressure was high normal. We also noticed that at 14 years pp, the hypertensive group showed signs of concentric left ventricular remodeling along with a decreased E/A ratio.

Anatomical Cystocele Recurrence: Development and Internal Validation of a Prediction Model.

OBJECTIVE: To develop a prediction model that estimates the risk of anatomical cystocele recurrence after surgery. METHODS: The databases of two multicenter prospective cohort studies were combined, and we performed a retrospective secondary analysis of these data. Women undergoing an anterior colporrhaphy without mesh materials and without previous pelvic organ prolapse (POP) surgery filled in a questionnaire, underwent translabial three-dimensional ultrasonography, and underwent staging of POP preoperatively and postoperatively. We developed a prediction model using multivariable logistic regression and internally validated it using standard bootstrapping techniques. The performance of the prediction model was assessed by computing indices of overall performance, discriminative ability, calibration, and its clinical utility by computing test characteristics. RESULTS: Of 287 included women, 149 (51.9%) had anatomical cystocele recurrence. Factors included in the prediction model were assisted delivery, preoperative cystocele stage, number of compartments involved, major levator ani muscle defects, and levator hiatal area during Valsalva. Potential predictors that were excluded after backward elimination because of high P values were age, body mass index, number of vaginal deliveries, and family history of POP. The shrinkage factor resulting from the bootstrap procedure was 0.91. After correction for optimism, Nagelkerkes R2 and the Brier score were 0.15 and 0.22, respectively. This indicates satisfactory model fit. The area under the receiver operating characteristic curve of the prediction model was 71.6% (95% confidence interval 65.7–77.5). After correction for optimism, the area under the receiver operating characteristic curve was 69.7%. CONCLUSION: This prediction model, including history of assisted delivery, preoperative stage, number of compartments, levator defects, and levator hiatus, estimates the risk of anatomical cystocele recurrence.

Predicting the coexistence of an endometrial adenocarcinoma in the presence of atypical complex hyperplasia: immunohistochemical analysis of endometrial samples.

Objective This study aimed to determine whether immunohistochemical markers in complex atypical endometrial hyperplasia could predict the presence of a concurrent endometrial carcinoma. Methods Endometrial biopsies of 39 patients with complex atypical hyperplasia were selected retrospectively between 1999 and 2006. Only patients who underwent a hysterectomy were included. A coexisting endometrial carcinoma was present in 25 patients (64%). Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded sections of the endometrial biopsies, using antibodies for MIB-1, β-catenin, E-cadherin, p53, PTEN, CD44, HER2-neu, survivin, COX-2, tenascin, and bcl-2. To evaluate the potential utility of these markers, a prediction model was constructed. Results In the univariate analysis, expressions of both PTEN and HER2-neu were significantly different between the groups with and without a coexisting endometrial carcinoma (P < 0.05). Loss of PTEN staining was found in 13 (54%) and 1 (7%) of the patients with and without a coexistent carcinoma, respectively (odds ratio, 16.55; 95% confidence interval [CI], 1.87–146.65). HER2-neu expression was found in only 2 (8.6%) and 6 (43%) patients with and without a coexistent carcinoma, respectively, and was excluded from further analysis because of its low expression. A prediction model containing PTEN expression only showed an area under the curve of 73.4% (95% CI, 57.3%–89.6%). After adding MIB-1 and p53, discriminative power improved to 87.2% (95% CI, 75.1%–99.3%). Conclusions This study showed that PTEN expression in complex endometrial hyperplasia is a promising factor for the prediction of the presence of a coexisting endometrial carcinoma, and prediction may even better when MIB-1 and p53 expressions are considered simultaneously.

Cost-effectiveness of recurrence risk guided care versus care as usual in women who suffered from early-onset preeclampsia including HELLP syndrome in their previous pregnancy (the PreCare study)

BackgroundPreeclampsia and HELLP syndrome may have serious consequences for both mother and fetus. Women who have suffered from preeclampsia or the HELLP syndrome, have an increased risk of developing preeclampsia in a subsequent pregnancy. However, most women will develop no or only minor complications. In this study, we intend to determine cost-effectiveness of recurrence risk guided care versus care as usual in pregnant women with a history of early-onset preeclampsia.Methods/designWe developed a prediction model to estimate the individual risk of recurrence of early-onset preeclampsia and the HELLP syndrome. In a before-after study, pregnant women with preeclampsia or HELLP syndrome in their previous pregnancy receiving care as usual (before introduction of the prediction model) will be compared with women receiving recurrence risk guided care (after introduction of the prediction model).Eligible and pregnant women will be recruited at six university hospitals and seven large non-university tertiary referral hospitals in the Netherlands.The primary outcome measure is the recurrence of early-onset preeclampsia or HELLP syndrome in women allocated to the regular monitoring group.For the economic evaluation, a modelling approach will be used. Costs and effects of recurrence risk guided care with those of care as usual will be compared by means of a decision model. Two incremental cost-effectiveness ratios will be calculated: 1) cost per Quality Adjusted Life Year (mother unit of analysis) and 2) cost per live born child (child unit of analysis).DiscussionThis is, to our knowledge, the first study that evaluates prospectively the efficacy of a multivariable prediction rule for recurrent hypertensive disease in pregnancy. Results of this study could either be integrated into the current guideline on Hypertensive Disorders in Pregnancy, or be used to develop a new guideline.

Respiratory adverse effects of opioids for breathlessness : a systematic review and meta-analysis

Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. The aim of this study was to systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness. PubMed, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible. We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in carbon dioxide tension (0.27 kPa, 95% CI 0.08–0.45 kPa,) and no significant change in oxygen tension and oxygen saturation (both p>0.05). Nonserious respiratory depression (definition variable/not stated) was described in four out of 1064 patients. One cancer patient pretreated with morphine for pain needed temporary respiratory support following nebulised morphine for breathlessness (single case study). We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed. There is no evidence of clinically relevant respiratory adverse effects of opioids for chronic breathlessness http://ow.ly/J6l730eQNCR

Can neonatal sepsis be predicted in late preterm premature rupture of membranes? Development of a prediction model

OBJECTIVE Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women. STUDY DESIGN We used multivariable logistic regression to develop a prediction model. Data were obtained from two recent randomized controlled trials on induction of labor versus expectant management in late preterm PROM (PPROMEXIL trials, (ISRCTN29313500 and ISRCTN05689407). Data from randomized as well as non-randomized women, who consented to the use of their medical data, were used. We evaluated 13 potential antepartum predictors for neonatal sepsis. Missing data were imputed. Discriminative ability of the model was expressed as the area under the receiver operating characteristic (ROC) curve and a calibration with both a calibration plot and the Hosmer and Lemeshow goodness-of-fit test. Overall performance of the prediction model was quantified as the scaled Brier score. RESULTS We studied 970 women. Thirty-three (3.4%) neonates suffered neonatal sepsis. Maternal age (OR 1.09 per year), maternal CRP level (OR 1.01 per mmol/l), maternal temperature (OR 1.80 per °C) and positive GBS culture (OR 2.20) were associated with an increased risk of neonatal sepsis. The model had an area under the ROC-curve of 0.71. The model had both a good calibration and accuracy. CONCLUSIONS Antepartum parameters aid in the more precise prediction of the risk of neonatal sepsis in women with late preterm PPROM.

Near-Infrared Fluorescence Imaging for Real-Time Intraoperative Guidance in Anastomotic Colorectal Surgery: A Systematic Review of Literature

PURPOSE The aims of this review are to determine the feasibility of near-infrared fluorescence (NIRF) angiography in anastomotic colorectal surgery and to determine the effectiveness of the technique in improving imaging and quantification of vascularization, thereby aiding in decision making as to where to establish the anastomosis. METHODS A systematic literature search of PubMed and EMBASE was conducted. Searching through the reference lists of selected articles identified additional studies. All English language articles presenting original patient data regarding intraoperative NIRF angiography were included without restriction of type of study, except for case reports, technical notes, and video vignettes. The intervention consisted of intraoperative NIRF angiography during anastomotic colorectal surgery to assess perfusion of the colon, sigmoid, and/or rectum. Primary outcome parameters included ease of use, added surgical time, complications related to the technique, and costs. Other relevant outcomes were whether this technique changed intraoperative decision making, whether effort was taken by the authors to quantify the signal and the incidence of postoperative complications. RESULTS Ten studies were included. Eight of these studies make a statement about the ease of use. In none of the studies complications due to the use of the technique occurred. The technique changed the resection margin in 10.8% of all NIRF cases. The anastomotic leak rate was 3.5% in the NIRF group and 7.4% in the group with conventional imaging. Two of the included studies used an objective quantification of the fluorescence signal and perfusion, using ROIs (Hamamatsu Photonics) and IC-Calc® respectively. CONCLUSIONS Although the feasibility of the technique seems to be agreed on by all current research, large clinical trials are mandatory to further evaluate the added value of the technique.

Computed Tomography Imaging Features in Acute Uncomplicated Stanford Type-B Aortic Dissection Predict Late Adverse EventsCLINICAL PERSPECTIVE

Background— Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable. Methods and Results— The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247–1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29–6.72; P=0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01–1.04, P=0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02–1.18, P=0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998–1.000; P=0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80–0.98; P=0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%. Conclusions— Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection.