Abnormal non-invasive prenatal test results concordant with karyotype of cytotrophoblast but not reflecting abnormal fetal karyotype.

We present a unique case in which non-invasive and invasive prenatal diagnoses showed abnormal, but discordant, results. A patient with abnormal non-invasive prenatal test (NIPT) results, indicating a 99% risk for monosomy X, was referred to our center for genetic counseling and confirmatory studies. Cytogenetic analysis of uncultured mesenchymal core of chorionic villi (CV) revealed a mosaic male karyotype consisting of two abnormal cell lines: one with monosomy X and the other with an isodicentric chromosome Y. Array analysis of the trophoblast confirmed the NIPT results. Based on the CV results, the patient opted for termination of pregnancy. After extensive counseling by a clinical geneticist about the possible outcomes and by a gynecologist about the risk of a second-trimester abortion procedure, the patient agreed to undergo early amniocentesis. Amniocentesis confirmed that the fetus had a male karyotype with an isodicentric chromosome Y, and the single nucleotide polymorphism (SNP) array profile suggested absence of the monosomy X cell line. The male infant was expected to be infertile. The patient finally decided to continue the pregnancy. Our case confirms that NIPT results are comparable with those of short-term cultured CV investigating the cytotrophoblast. Our patient was not aware that the NIPT results reveal the placental karyotype, which sometimes may be different from the fetal karyotype. Pretest counseling and providing the risk figures for false-positive and false-negative NIPT results are of great importance in order to discourage women from terminating pregnancies based on NIPT results alone.

Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

STUDY QUESTION: What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. STUDY DESIGN, SIZE, DURATION: A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time. PARTICIPANTS, SETTING, METHODS: From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial. MAIN RESULTS: We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations. WIDER IMPLICATIONS OF THE FINDINGS: Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women. BIAS, LIMITATION AND GENERALISABILITY: A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX. STUDY FUNDING: This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). TRIAL REGISTRATION: ISRCTN 48210491.

Guideline adherence in ectopic pregnancy management.

BACKGROUND: Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals. METHODS: A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals. RESULTS: Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals. CONCLUSIONS: The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

A systematic review of the effectiveness of training in emergency obstetric care in low-resource environments.

BACKGROUND: Training of healthcare workers can play an important role in improving quality of care, and reducing maternal and perinatal mortality and morbidity. OBJECTIVES: To assess the effectiveness of training programmes aimed at improving emergency obstetric care in low-resource environments. SEARCH STRATEGY: We searched Pubmed, Embase, Popline and selected websites, and manually searched bibliographies of selected articles. Language was not an exclusion criterion. SELECTION CRITERIA: All papers describing postgraduate training programmes aimed at improving emergency obstetric care in low-resource environments were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and classified these according to the level of the measured effects (reaction of participants, improved knowledge and skills, changes in behaviour and outcomes in practice). Any disagreements were resolved by discussion with a third author until agreement was reached. MAIN RESULTS: A total of 38 papers were selected. Training programmes vary considerably in length, content and design. The evaluation of effects is often hampered by inadequate study design and the use of non-validated measuring instruments. Most papers describe positive reactions, increased knowledge and skills, and improved behaviour after training. Outcome is assessed less frequently, and positive effects are not always demonstrated. Measures that can contribute to a positive effect of training programmes include hands-on practise, team approaches and follow-up on training efforts. AUTHOR'S CONCLUSIONS: Training programmes may improve quality of care, but strong evidence is lacking. Policymakers need to include evaluation and reporting of effects in project budgets for new training programmes.

Cardiac arrest in pregnancy: increasing use of perimortem caesarean section due to emergency skills training?

OBJECTIVE: Management of cardiac arrest in pregnancy is recommended to include perimortem caesarean section (PMCS) in the Managing Obstetric Emergencies and Trauma (MOET) course. In this study, we aimed to assess maternal and neonatal outcome of all cases of PMCS in the Netherlands performed in the last 15 years, and to test the hypothesis that PMCS was used more often since the introduction of the MOET-course in 2004. DESIGN: Retrospective cohort study. SETTING: Nationwide assessment of all cases of PMCS inside or outside hospitals. POPULATION: All known cases of PMCS in the Netherlands from 1993 to 2008. METHODS: Data collection through contacting all Dutch obstetricians and all MOET and Advanced Trauma Life Support instructors. All cases of cardiac arrest during pregnancy were collected by cross-checking with data from the Dutch Maternal Mortality Committee and a nationwide severe maternal morbidity study. MAIN OUTCOME MEASURES: Incidence and case fatality rate of PMCS. Incidence of PMCS before and after introduction of the MOET course. Maternal and neonatal outcome and the process of the PMCS were analysed. RESULTS: During the study period, 55 women had a cardiac arrest, 12 of whom underwent a PMCS. Before the introduction of the MOET course, four PMCSs were performed (0.36/year), compared with eight cases after its introduction (1.6/year, P = 0.01). No PMCS was performed within the recommended 5 minutes after starting resuscitation. Eight of the twelve women (67%) regained cardiac output after PMCS, with two maternal and five neonatal survivors. Maternal case fatality rate was 83%. Neonatal case fatality rate was 58%. CONCLUSIONS: Since the introduction of the MOET course, the use of PMCS has increased. Outcome, however, was still poor. An important factor to improve outcome is more timely application of this potentially life-saving procedure.

Human papillomavirus type 18 and other risk factors for cervical cancer in Jakarta, Indonesia.

Infection with human papillomavirus (HPV) has now been established as a necessary cause of cervical cancer. Indonesia is a country with a high cervical cancer incidence and with the world's highest prevalence of HPV 18 in cervical cancer. No information exists about the prevalence of HPV 18 or other HPV types in the Indonesian population. We conducted a hospital-based case-control study in Jakarta, Indonesia. A total of 74 cervical carcinoma cases and 209 control women, recruited from the gynecological outpatient clinic of the same hospital, were included. All women were HPV typed by the line probe assay, and interviews were obtained regarding possible risk factors for cervical cancer. HPV was detected in 95.9% of the cases and in 25.4% of the controls. In the control group, 13.4% was infected with a high-risk HPV type. HPV 16 was detected in 35% of the case group and in 1.9% of the control group and HPV 18 was identified in 28% of the case group and in 2.4% of the control group, suggesting that the oncogenic potentials of HPV 16 and HPV 18 in Indonesia are similar. In addition to HPV infection, young age at first intercourse, having a history of more than one sexual partner, and high parity were significant risk factors for cervical cancer. Within the control group, we did not identify determinants of HPV infection. We hypothesize that the high prevalence of HPV 18 in cervical cancer in Indonesia is caused by the high prevalence of HPV 18 in the Indonesian population.

Postoperative radiation therapy improves prognosis in patients with adverse risk factors in localized, early-stage cervical cancer: a retrospective comparative study.

The objective of this study was to assess the role of postoperative radiotherapy (RT) in early-stage cervical carcinoma with risk factors other than positive nodes, parametrial invasion, or positive margins and to compare outcomes using the Leiden University Medical Center (LUMC) modification of the Gynecologic Oncology Group (GOG) system with the GOG prognostic scoring system itself. Between January 1984 and April 2005, 402 patients with early-stage cervical cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of the three risk factors and had pathologic tumor size (> or =40 mm), invasion (> or =15 mm), and capillary lymphatic space involvement, and were identified as the so-called high-risk (HR). We compared 34 patients who received RT based on the LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of three risk factors) and HR- (less than two out of three risk factors). Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free survival (DFS) between the HR group treated with RT (86%, 85%) and without RT (57%; 43%) were statistically significant. The LUMC criteria did not significantly differ from the GOG risk profile, concerning recurrence, CSS, and DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG system seems to be simpler and has a slightly higher threshold for the indication for RT but without a difference in outcome.

[The neglected control of proteinuria during pregnancy]. / De verzuimde controle op eiwit in de urine tijdens de zwangerschap.

In two women, primigravidae aged 29 and 27 years, no dipstick test for proteinuria was carried out despite symptoms of preeclampsia at 34 5/7 and 25 5/7 weeks of pregnancy, respectively. Both babies died in utero. The women were treated in the intensive care unit; the first woman died due to 'haemolysis, elevated liver enzymes, low platelet count' (HELLP) syndrome, while the second woman was able to return home in a reasonable condition on antihypertensive medication. Dipstick tests for proteinuria should always be carried out in pregnant women with symptoms of preeclampsia in order to avoid the death and serious morbidity which can be associated with eclampsia.

Can hysterosalpingocontrast-sonography replace hysterosalpingography in the assessment of tubal subfertility?

INTRODUCTION: Hysterosalpingo-contrastsonography (HyCoSy) is a new method for assessing tubal patency using transvaginal ultrasound. It is thought to have several advantages over conventional hysterosalpingography (HSG). We prospectively evaluated the performance of HyCoSy and HSG in the diagnosis of tubal pathology. METHODS AND PATIENTS: One-hundred consecutive subfertile women underwent both HyCoSy and HSG in randomised order. Results of both tests were related to findings at laparoscopy with dye, which was used as the reference test. Each woman was asked to score the pain exsperienced at both procedures on a visual analogue scale. RESULTS: When laparoscopy with dye was used as reference test, the likelihood ratios of HyCoSy were slightly inferior to those obtained for HSG. Since the performance of HyCoSy was dependent on experience, the results were recalculated omitting the 50 initial procedures from the analysis. In that calculation, results of HyCoSy and HSG were comparable. There were no differences in pain experienced during the procedure, as there appeared also to be no differences in patient preferences. CONCLUSION: There appear to be no strong arguments either to replace HSG by HyCoSy, or to reject the use of HyCoSy. Both procedures can be used in the evaluation of tubal pathology.

Instruments and methods for the quantitative measurement of factors affecting hygienist/dentist efforts during scaling and root planing of the teeth.

Manual calculus debridement through scaling accounts for a significant proportion of hygienist efforts in dental and periodontal practices. Despite this, little is quantitatively known concerning the effects of instruments, technique and treatments on debridement (scaling) efficiency or efficacy. The total work effort expended by therapists in calculus debridement results from the sum of the efforts associated with each scaling stroke. Each scaling stroke, in turn, is affected by a variety of physical forces, including those in the control of the therapist and those intrinsic to the calculus substrate. The development of procedures and treatments to facilitate easier calculus removal requires consideration of the physical and technique-related factors which contribute to hygienist effort. Instruments have recently been developed which can quantitatively measure force dynamics associated with scaling procedures, including both therapist-applied forces and forces developed due to the extreme hardness and tenacity of supra- and subgingival calculus deposits. The scaling instrument developed to quantitatively record developed forces in scaling, the Quanticalc, can be used for the assessment of techniques and treatments which can soften calculus, facilitating easier debridement. The device can also be used to instruct therapists on factors contributing to surface roughness and tactile response to these factors. The scaling instrument developed to quantitatively measure therapist applied forces in scaling, the Zappa device, can be used for assessment of techniques which can increase the efficiency of calculus removal with minimal damage to sound root substance. In this paper, the force dynamics associated with manual scaling procedures of dental professionals are defined. These force dynamics account for the total work expended by hygienists and other professionals in the important task of calculus removal. Using this as a foundation, the design, use, calibration and clinical applications of these newly developed scaling-force measurement systems are described.

Crest Tartar Control benefits assessed by Quanticalc: clinical method and three-month results.

In this paper, a method is described for applying the Quanticalc (QC) dental scaler to the clinical assessment of tartar control dentifrice effects on supragingival calculus formation and therapist efforts required in subsequent calculus debridement. In a 3-month, randomized cross-over study, subjects using Crest Tartar Control were observed to form 25% less calculus than they formed in a similar period using Crest Regular non-tartar control dentifrice as placebo. QC measurements likewise revealed 25% savings in the developed force used to scale the anterior lingual surfaces, coupled with a 27% reduction in the number of strokes required to clean these surfaces free of supragingival calculus in subjects using tartar control dentifrice. The quantitative savings in professional effort amounted to 3 kg (developed forces saved) per subject using tartar control dentifrice. White subjects using placebo dentifrice for 3 months developed less calculus than shown at baseline (29% less calculus), this was not complemented by decreases in total force and strokes used in cleaning. This supports the hypothesis that the surface area coverage of calculus (e.g., the planimetric "area" of supragingival calculus on the tooth) does not contribute alone to the amount of effort as forces and strokes required in subsequent debridement. These results demonstrate that: 1) the QC dental scaler can be effectively used in the clinical assessment of scaling forces/efforts associated with supragingival calculus debridement; and 2) a tartar control dentifrice containing soluble pyrophosphate is clinically effective in reducing both the surface coverage of calculus and the therapist effort required in subsequent calculus debridement.

Effects of a scaling gel on forces developed in debridement of supragingival calculus determined by means of a transducer-modified dental scaler: the Quanticalc.

The efficacy of a calculus scaling gel, SofScale (Dentsply, York, PA), has been examined in two protocols by the measurement of scaling forces developed in supragingival calculus debridement from the anterior dentition using hand scaling with a transducer-modified dental scaler, the Quanticalc. In one protocol, the effects of the scaling gel were compared to a placebo gel composed of conventional toothpaste in a double-blind, split-mouth design. In another protocol, the effects of the scaling gel were determined in comparison to non-treated calculus. Results demonstrated that the scaling gel had no apparent effects on the physical forces (work) involved in calculus removal. These results suggest that the application of the scaling gel provides no quantitative benefits in facilitating calculus debridement during manual tooth scaling.

Effect of xylitol and sorbitol in chewing-gums on mutans streptococci, plaque pH and mineral loss of enamel.

Seventeen subjects with more than 3 x 10(5) mutans streptococci per millilitre of saliva completed this randomised, cross-over study. Four different chewing-gums, containing: (1) 70% xylitol, (2) 35% xylitol + 35% sorbitol, (3) 17.5% xylitol + 52.5% sorbitol, and (4) 70% sorbitol, were tested. The participants used 12 pieces of each gum per day for 25 days. During the four experimental periods, they wore a removable palatinal plate containing two demineralised enamel samples, and brushed their teeth with a non-fluoridated toothpaste. The results showed that an increased concentration of xylitol in the gum resulted in a lower number of mutans streptococci in both saliva and dental plaque, although the decreases were only significant in the saliva samples (p < 0.01). The pH drop in plaque, measured in vivo after a 1-min mouthrinse with a 10% sorbitol solution, was least pronounced after the 70% xylitol gum and most pronounced after the 70% sorbitol gum period (p < 0.01). No significant differences were found after a mouthrinse with a 10% sucrose solution. All demineralised enamel samples lost mineral during the experimental periods. However, the lesion depth as well as the mineral loss values, assessed microradiographically, did not differ significantly between the four chewing-gums.

Rate and mechanism of enamel demineralization in situ.

In this paper, data are presented on the in situ demineralization of human enamel as a function of the demineralization period. To quantify the mineral loss parameters versus time, it is important to obtain information on the kinetics, and thus on the mechanism of dental caries. The results show that for in situ enamel demineralization, the lesion depth as well as the mineral loss parameter both vary linearly with the demineralization time. This is in contrast to in vitro lesion formation where the third power, or the square power of the lesion depth is linearly related to the demineralization time. In in situ demineralization, the rate-determining step of the demineralization process is the inhibitor-controlled dissolution process at the enamel crystallite surfaces, while the inhibitor content (F-, proteins etc.) in the lesion originating from the plaque, saliva and enamel is high. Furthermore, the study indicates that in in situ demineralization, interprismatic mineral loss is very important.

Effect of fluoride release from a fluoride-containing composite resin on secondary caries: an in vitro study.

The effect of fluoride, released from a fluoride-containing composite resin, on secondary caries was investigated by quantitative microradiography. In all teeth investigated, less demineralization was found near the composite resin than was found at a distance of a few millimeters from the material after an acid attack. The presence of the fluoride-releasing composite resin reduced the lesion depth measured after an acid attack by about 35%. Therefore, in vivo, a reduction of recurrent caries may be expected around fluoride-containing composite resins.

Remineralization of human enamel in situ after 3 months: the effect of not brushing versus the effect of an F dentifrice and an F-free dentifrice.

The in situ remineralization of 100-microns-deep enamel lesions positioned in a full prosthesis just under the first molar was determined in 13 participants after 3 months. The outer surface of the samples was always flush with the acrylic surface: there was no measurable plaque accumulation on the samples. The effect of not brushing of the samples (A) is compared with the effect of brushing with a nonfluoridated dentifrice (B) or with a fluoridated paste (C) containing 1,250 ppm F. The results show that lesion depth (and mineral loss) data increase by about 50% (case A), do not change statistically in case B and decrease by about 40% in case C. The increase of lesion depth in case A is most likely due to acidic food and/or beverage intake by the participants. With respect to nonbrushing, the remineralization effect of brushing with an F-free paste is about 50% and with the fluoridated paste about 90% in 3 months. It is suggested that the remineralization efficacy of fluoridated pastes is due to the cleaning effect of the brushing by the dentifrice (presumably on the pellicle) as well as due to the fluoride effect on mineral nucleation and growth.