Application of the Failure Mode and Effects Analysis (FMEA) to identify vulnerabilities and opportunities for improvement prior to implementing a computerized prescription order entry (CPOE) system in a university hospital oncology clinic.

INTRODUCTION: Prior to implementing a new computerized prescription order entry (CPOE) application, the potential risks associated with this system were assessed and compared to those of paper-based prescriptions. The goal of this study is to identify the vulnerabilities of the CPOE process in order to adapt its design and prevent these potential risks. METHODS AND MATERIALS: Failure mode and effects analysis (FMEA) was used as a prospective risk-management technique to evaluate the chemotherapy medication process in a university hospital oncology clinic. A multidisciplinary team assessed the process and compared the critical steps of a newly developed CPOE application versus paper-based prescriptions. The potential severity, occurrence and detectability were assessed prior to the implementation of the CPOE application in the clinical setting. RESULTS: The FMEA led to the identification of 24 process steps that could theoretically be vulnerable, therefore called failure modes. These failure modes were grouped into four categories of potential risk factors: prescription writing, patient scheduling, treatment dispensing and patient follow-up. Criticality scores were calculated and compared for both strategies. Three failure modes were prioritized and led to modification of the CPOE design. Overall, the CPOE pathway showed a potential risk reduction of 51% compared to paper-based prescriptions. CONCLUSION: FMEA was found to be a useful approach to identify potential risks in the chemotherapy medication process using either CPOE or paper-based prescriptions. The e-prescription mode was estimated to result in less risk than the traditional paper mode.

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol.

OBJECTIVE: To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS: This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS: The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION: This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.

First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study.

OBJECTIVES: To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women. METHODS: We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth. RESULTS: Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75-0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%-73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%-37%). CONCLUSIONS: The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.

Knowledge and opinions of asymptomatic adolescents and their caregivers on celiac disease screening.

OBJECTIVES: Celiac disease (CD) is an immune enteropathy caused by sensitivity to gluten affecting one per cent of the general population. Most people with CD are asymptomatic and some may be affected from childhood. Despite the latest recommendations of paediatric gastroenterology societies, targeted screening is still uncommon in clinical paediatric settings. A poor understanding of the asymptomatic population's opinions creates obstacles for broader implementation of CD screening. This study aims to fill this gap by reporting on the knowledge and opinions of adolescents and caregivers of children on CD screening. METHODS: Adolescents with absence of classical symptoms of CD and caregivers of presumably asymptomatic children were asked about their knowledge and opinions of CD through a self-administered questionnaire. RESULTS: There were 227 respondents including 76 adolescents and 151 caregivers. A minority of respondents (8% of caregivers and 23% of adolescents) were identified as having a CD-associated condition (such as hypothyroidism, type 1 diabetes, Down syndrome, etc.). A majority of caregivers (84%) and half of adolescents (49%) already knew about CD. Half of the respondents (46%) were in favour of screening asymptomatic paediatric populations and this agreement increased to 81.7% when they were confronted with hypothetical risks of 10%. CONCLUSION: This study reveals an increased willingness to screen when participants were faced with increasing hypothetical risks. This suggests that screening recommendations targeting high-risk populations, such as those of paediatric and non-paediatric gastroenterology societies, may be more widely accepted.

Management of complex renal cysts in Canada: results of a survey study.

BACKGROUND: Bosniak III and IV cysts have a high risk of malignancy and have traditionally been managed surgically. However, growing evidence suggests that many can be managed by active surveillance. The main objective of this study was to characterize the use of surveillance in the management of complex renal cysts. METHODS: A web-based survey was sent to all registered, active members of the Canadian Urological Association (N = 583) in October 2018. RESULTS: The survey response rate was 24.7%. Management of Bosniak III cysts varied considerably. A large proportion of respondents (33.1%) offered active surveillance in > 50% of cases. Only 13.7% of respondents reported never or rarely (< 5% of cases) offering surveillance. In contrast, for Bosniak IV cysts, 60.1% of urologists never or rarely offered surveillance, while only 10.1% offer it in > 50% of cases. A significantly greater proportion of academic urologists, compared to non-academic urologists, viewed surveillance as a management option for patients with a Bosniak III or IV cyst. The most commonly reported barriers to a greater adoption of surveillance were concerns regarding its oncologic safety, the lack of data to support surveillance in this population, and the lack of triggers for discontinuation of active surveillance and intervention. CONCLUSIONS: Despite active surveillance being included as a management option in guidelines, many Canadian urologists are reluctant to offer surveillance to patients with Bosniak III or IV cysts. Practice patterns are heterogeneous among those offering surveillance. High-quality studies are required to better define the benefits and risks of cystic renal mass surveillance.

First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study.

BACKGROUND: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. SUBJECTS AND METHODS: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11-13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). RESULTS: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57-0.65) and preterm PE (AUC = 0.73, 95% CI 0.64-0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62-0.71; AUC for preterm PE 0.81, 95% CI 0.72-0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. CONCLUSION: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.

First Trimester Screening for Fetal Aneuploidies Using Placental Growth Factor: The Great Obstetrical Syndrome (GOS) Study.

OBJECTIVE: This study sought to estimate the ability of first trimester maternal serum placental growth factor (PlGF) to identify fetal aneuploidies. METHODS: A prospective cohort study of singleton pregnancy at 11 to 13 weeks was conducted. Maternal serum PlGF concentration was measured using BRAHMS PlGF plus KRYPTOR automated assays (Thermo Scientific BRAHMS, Hennigsdorf, Germany). PlGF and nuchal translucency were log-transformed and reported as multiples of the median (MoM) adjusted for crown-rump length. Detection rates were calculated using receiver-operator characteristic curves. RESULTS: The study observed 21 cases of fetal aneuploidies (0.4%) out of 4765 participants. Trisomy 21 (13 cases; 0.85 MoM; interquartile range [IQR] 0.80-0.93), trisomy 18 (two cases; 0.77 MoM; IQR 0.66-0.87) and trisomy 13 (two cases; 0.68 MoM; IQR 0.61-0.75) were associated with low PlGF concentrations. The low PlGF values observed in the cases of monosomy X (two cases; 0.85 MoM; IQR 0.82-0.88, P = 0.05), triploidy (0.78 MoM, P = 0.11), and 47,XX,i(22)(p10) (0.18 MoM, P = 0.08) were not statistically different from the controls. A model including maternal age, nuchal translucency, and PlGF could have identified all (95% CI 83%-100%) cases of trisomy 21 and six of the other fetal aneuploidies (75%) at a false-positive rate of 9%. CONCLUSION: Low first trimester PlGF is associated with an increased risk of fetal aneuploidy. PlGF combined with first trimester ultrasound (nuchal translucency, uterine artery Doppler, and early fetal anatomy) could identify not only women at high risk for preeclampsia, but also fetuses at high risk of aneuploidy for optimal further testing (non-invasive testing for common aneuploidy screening or chorionic villus sampling for full screening and diagnosis).

Maternal Characteristics for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes (GOS) Study.

OBJECTIVE: Low-dose aspirin started in early pregnancy significantly reduces the risk of preeclampsia (PE) in high-risk women, especially preterm PE. This study aimed to evaluate the influence of maternal characteristics on the risk of PE in nulliparous women. METHODS: The Great Obstetrical Syndromes (GOS) study recruited nulliparous women with singleton pregnancies at 11 to 13 weeks. The following maternal characteristics were collected: age, BMI, ethnicity, chronic diseases, smoking, and assisted reproductive technologies. Relative weight analyses were conducted, and predictive multivariate proportional hazard models were constructed. Receiver operating characteristic curve analyses with their area under the curve (AUC) were used to evaluate the value of each factor for the prediction of PE and preterm PE. The study also evaluated the SOGC guidelines for identification of women at high risk of PE. RESULTS: Of 4739 participants, 232 (4.9%) developed PE, including 30 (0.6%) with preterm PE. In univariate analyses, only BMI was significantly associated with the risk of PE (AUC 0.60; 95% CI 0.55-0.65) and preterm PE (AUC 0.64; 95% CI 054-0.73). Adding other maternal characteristics to BMI had a non-significant and marginal impact on the discriminative ability to the models for PE (AUC 0.62; 95% CI 0.58-0.66) and preterm PE (AUC 0.65; 95% CI 0.56-0.74). At a false-positive rate of 10%, maternal characteristics could have predicted 23% of PE and 19% of preterm PE. The SOGC guidelines were not discriminant for PE (detecting 96% of PE and 93% of preterm PE with a 94% false-positive rate). CONCLUSION: In nulliparous women, BMI is the most discriminant maternal characteristic for the prediction of PE. Maternal characteristics should not be used alone to identify nulliparous women at high risk of PE.

Comparison of first-tier cell-free DNA screening for common aneuploidies with conventional publically funded screening.

OBJECTIVE: This study evaluates the impact of offering cell-free DNA (cfDNA) screening as a first-tier test for trisomies 21 and 18. METHODS: This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies. RESULTS: A total of 1198 pregnant women were recruited. The detection rate of trisomy 21 with standard screening was 83% with a false positive rate (FPR) of 5.5% compared with 100% detection and 0% FPR for cfDNA screening. The FPR of cfDNA screening for trisomies 18 and 13 was 0.09% for each. Two percent of women underwent an invasive diagnostic procedure based on screening or ultrasound findings; without the cfDNA screening, it could have been as high as 6.8%. Amongst the 640 women with negative cfDNA results and a nuchal translucency (NT) ultrasound, only 3 had an NT greater or equal to 3.5 mm: one had a normal outcome and two lost their pregnancy before 20 weeks. CONCLUSIONS: cfDNA screening has the potential to be a highly effective first-tier screening approach leading to a significant reduction of invasive diagnostic procedures. For women with a negative cfDNA screening result, NT measurement has limited clinical utility.

Reliability of First-Trimester Ultrasonic Biopsy for the Evaluation of Placental and Myometrial Blood Perfusion and the Prediction of Preeclampsia.

OBJECTIVE: Low placental vascularization measured by three-dimensional (3-D) ultrasound with power Doppler can predict preeclampsia. We evaluated the reliability and reproducibility of the ultrasonic sphere biopsy (USSB) technique to evaluate placental and subplacental myometrium vascularization in the first trimester. METHODS: We performed a secondary analysis of a case-control study nested in a prospective cohort of women with a singleton pregnancy undergoing ultrasound at 11 to 14 weeks' gestation. Women who developed preeclampsia (n = 20) and randomly selected controls (n = 60) were compared. Other controls (n = 60) were also randomly selected to evaluate intra- and inter-observer reproducibility. Using 3-D power Doppler, the vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured from the volume of the whole placenta and the subplacental myometrium and from their respective USSB. Pearson's correlation coefficients (cc) with their P-values were calculated. RESULTS: We observed that USSB is reliable in estimating the vascularization of the whole placenta in the first trimester (cc of VI 0.83; of FI 0.62; and of VFI 0.78; P < 0.001 for all) but was not as reliable for estimating subplacental myometrium vascularization (cc of VI 0.71; of FI 0.35; and of VFI 0.73). Measurement of placental vascularization using USSB showed good to excellent intra- and inter-observer reproducibility (cc of VI 0.86 and 0.85, respectively; of FI 0.75 and 0.75, respectively; and of VFI 0.83 and 0.83, respectively; P < 0.001 for all). Finally, we observed that women who subsequently developed preeclampsia had lower placental USSB VI (2.1 vs 4.8, P = 0.02), FI (32.4 vs. 42.5, P = 0.002), and VFI (0.8 vs. 2.1, P = 0.01) than controls. CONCLUSION: First-trimester USSB of the placenta using 3-D power Doppler is a reliable and reproducible procedure for estimating placental vascularization and could be used to predict preeclampsia.

Periodontal Disease and Adverse Pregnancy Outcomes: A Prospective Study in a Low-Risk Population.

BACKGROUND: Periodontal disease has been associated with systemic inflammation and adverse pregnancy outcomes, including preeclampsia and preterm birth. OBJECTIVE: To examine the relationship between periodontal disease in early pregnancy and the risk of amniotic inflammation, preterm birth, and preeclampsia. METHODS: We performed a prospective cohort study of women undergoing amniocentesis for fetal karyotype between 15 and 24 weeks' gestation. Participants underwent periodontal examination by a certified dentist, and a sample of amniotic fluid was collected. Periodontal disease was defined as the presence of one or more sites with probing depths ≥ 4 mm and ≥ 10% bleeding on probing. Matrix metalloproteinase-8 and interleukin-6 concentrations in the amniotic fluid were measured. Medical charts were reviewed for perinatal outcomes. Univariate and multivariate logistic regression analyses were used to assess the association between periodontal disease and adverse pregnancy outcomes. RESULTS: We recruited 273 women at a median gestational age of 16 weeks (range 15 to 24), and 258 (95%) agreed to undergo periodontal examination. Periodontal disease was observed in 117 of the participants (45%). We observed no significant association between periodontal disease and preterm birth (relative risk [RR] 2.27; 95% CI 0.74 to 6.96) or spontaneous preterm birth (RR 0.90; 95% CI 0.20 to 4.11). However, women with periodontal disease were more likely to develop preeclampsia, and this association remained significant after adjustment for potential confounders (adjusted RR 5.89; 95% CI 1.24 to 28.05). Periodontal disease was not associated with significant differences in the intra-amniotic concentration of matrix metalloproteinase-8 (13.0 ± 46.6 vs 5.7 ± 10.4 ng/mL, P = 0.098) or interleukin-6 (3.3 ± 20.3 vs 1.0 ± 1.6 ng/mL, P = 0.23), although a non-significant trend was observed. CONCLUSION: Periodontal disease is associated with preeclampsia but not with spontaneous preterm birth. The current study cannot exclude an association between periodontal disease and intra-amniotic inflammation.

Vaginal Fluid Inflammatory Biomarkers and the Risk of Adverse Neonatal Outcomes in Women with PPROM.

Objective The purpose of this study was to evaluate the predictive value of vaginal fluid biomarkers for chorioamnionitis and adverse perinatal outcomes in women with preterm premature rupture of membranes (PPROM). Methods We recruited women with PPROM, without clinical chorioamnionitis, between 22 and 36 weeks' gestation. Vaginal fluid was collected on admission for the measurement of metalloproteinase-8 (MMP-8), interleukin-6 (IL-6), lactate, and glucose concentration. Placental pathology and neonatal charts were reviewed. Primary outcomes were histological chorioamnionitis and adverse neonatal neurological outcomes (intraventricular hemorrhage grade 2 or 3, periventricular leukomalacia, or hypoxic/ischemic encephalopathy). Linear regression analyses were used to adjust for gestational age at PPROM. Results Twenty-seven women were recruited at a mean gestational age of 31.6 ± 3.1 weeks, including 25 (93%) with successful collection of vaginal fluid sample. Histological chorioamnionitis and adverse neonatal neurological outcomes were observed in nine (33%) and four (15%) cases, respectively. In univariate analysis, MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid were associated with the risk of chorioamnionitis but not anymore after adjustment for gestational age at PPROM. MMP-8 concentration was the only biomarker associated with adverse neurological outcome, and it remained significant after adjustment for gestational age at PPROM (p = 0.02). Conclusion Vaginal fluid inflammatory biomarkers at admission for PPROM could predict adverse perinatal outcomes.

First-Trimester Placental and Myometrial Blood Perfusion Measured by Three-Dimensional Power Doppler in Preeclampsia.

OBJECTIVE: The study aims to evaluate first-trimester vascularization of the placenta and subplacental myometrium in women who subsequently develop preeclampsia. STUDY DESIGN: A case-control study nested in a prospective cohort was conducted in women with singleton pregnancy between 11 and 14 weeks' gestation. Three-dimensional standardized acquisition of the placenta and subplacental myometrium volumes with and without power Doppler was undertaken, and all participants were followed up until delivery. Each woman diagnosed with preeclampsia was matched with three controls who delivered at term without pregnancy complications. First-trimester volume, vascularization index (VI), flow index (FI), and vascular flow index (VFI) of the entire placenta and subplacental myometrium were measured separately. The results were stratified for preterm and term preeclampsia, respectively. RESULTS: A total of 1,034 women were recruited, including 16 (1.5%) who developed term preeclampsia and 4 (0.4%) who developed preterm preeclampsia. Preeclampsia was associated with a significantly lower placental VI, placental VFI, subplacental VI, and subplacental VFI in the first trimester than with the controls (all p < 0.05). All cases (4/4) of preterm preeclampsia, 56% (9/16) of term preeclampsia, and 28% (17/60) of the controls had a subplacental VI below 18% (p < 0.01). CONCLUSION: First-trimester placental and subplacental myometrium vascularizations are significantly reduced in women who subsequently develop preeclampsia.

Intrapatient Intermetastatic Heterogeneity Determined by Triple-Tracer PET Imaging in mCRPC Patients and Correlation to Survival: The 3TMPO Cohort Study.

Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. Methods: This was a multisite prospective observational study in which mCRPC patients underwent both 18F-FDG and 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT scans. A third scan with 68Ga-DOTATATE, a potential biomarker of neuroendocrine differentiation, was performed if an 18F-FDG-positive/68Ga-PSMA-negative lesion was found. Per-tracer lesion positivity was defined as having an uptake at least 50% above that of the liver. IIH prevalence was defined as the percentage of participants having at least 2 lesions with discordant features on multitracer PET. Results: IIH was observed in 81 patients (82.7%), and at least 1 18F-FDG-positive/68Ga-PSMA-negative lesion was found in 45 patients (45.9%). Of the 37 participants who also underwent 68Ga-DOTATATE PET/CT, 6 (16.2%) had at least 1 68Ga-DOTATATE-positive lesion. In total, 12 different combinations of lesion imaging phenotypes were observed. On the basis of our prespecified criteria, 52 (53.1%) participants were determined to be eligible for PSMA RPT, but none for DOTATATE RPT. Patients with IIH had a significantly shorter median overall survival than patients without IIH (9.5 mo vs. not reached; log-rank P = 0.03; hazard ratio, 2.7; 95% CI, 1.1-6.8). Conclusion: Most mCRPC patients showed IIH, which was associated with shorter overall survival. On the basis of a triple-tracer PET approach, multiple phenotypic combinations were found. Correlation of these imaging phenotypes with genomics and treatment response will be relevant for precision medicine.

Mid-trimester microbial invasion of the amniotic cavity and the risk of preterm birth.

OBJECTIVE: To evaluate the rate of mid-trimester microbial invasion of the amniotic cavity (MIAC) in asymptomatic women and its association with preterm birth. STUDY DESIGN: This is a prospective cohort study of asymptomatic women undergoing mid-trimester amniocentesis for genetic testing between 14 and 24 weeks of gestation. For each participant, a sample of amniotic fluid was incubated in an aerobic and anaerobic facultative culture media and another sample was tested for the presence of specific Mycoplasma species (Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis) using quantitative-PCR. Results were not revealed to the participants or their health care providers. All participants were followed until delivery. MIAC was defined by a positive culture or a positive PCR for Mycoplasma species. The primary outcome was a spontaneous preterm birth or preterm premature rupture of membranes before 35 weeks of gestation. RESULTS: We included 812 women at a median gestational age of 16 5/7 (interquartile: 15 6/7-17 4/7) weeks. Twenty-six (3.2%) had a spontaneous delivery before 35 weeks. We observed no case of positive PCR for Mycoplasma species and 4 (0.5%) cases of positive culture that were all considered to be skin contaminants. None of those four cases was associated with preterm birth. Nulliparity, low family income and history of preterm birth were associated with spontaneous delivery before 35 weeks. CONCLUSION: We found no case of mid-trimester MIAC using a combination of culture and Mycoplasma-specific PCR techniques in a large cohort of low-risk asymptomatic pregnant women. We estimate that mid-trimester MIAC is rare in low-risk population but more sensitive and broad-range microbiologic techniques, such as 16S DNA detection by PCR, could be further evaluated.

Patients' perceptions on active surveillance for the treatment of small renal masses.

BACKGROUND: Most patients diagnosed with a small renal mass (SRM) are treated with definitive treatments such as surgery or thermal ablation. Given that some SRMs are benign or have low metastatic potential, active surveillance seeks to reduce the overtreatment and the potential complications. Active surveillance is an alternative that is being increasingly considered. Active surveillance has already been shown to be effective, but there is a current knowledge gap regarding patients' perceptions of active surveillance and factors influencing their decision. OBJECTIVE: To describe patients' perceptions of active surveillance of SRMs and to identify factors influencing those perceptions. DESIGN, SETTING, AND PARTICIPANTS: This multicenter descriptive qualitative study recruited patients diagnosed with a renal mass from three institutions, using purposeful sampling. Data were collected using focus group discussions, which were recorded and transcribed. A mixed thematic analysis was performed. RESULTS: Six focus group discussions were conducted with a total of 24 participants. Participants perceived active surveillance as an option to avoid definitive treatments and their potential risks. Active surveillance was, however, perceived to be a temporary solution that would affect their chance of survival and their quality of life. Seven factors were documented as influencing patients' perceptions of active surveillance, the most important being their physician's recommendation. CONCLUSIONS: Perceptions of patients with SRMs toward active surveillance varies among individuals. The development of more patient-oriented information tools is needed to educate patients, to reduce physician influence on the decision-making process and to ensure that the patients' decision reflects their own values and preferences.

Midtrimester intra-amniotic sludge and the risk of spontaneous preterm birth.

We examined the association between midtrimester intra-amniotic sludge and spontaneous preterm birth (PTB) in asymptomatic women undergoing amniocentesis. We performed a prospective cohort study of women having an amniocentesis for fetal karyotyping between 14 and 24 weeks' gestation. Cervical length and the presence of amniotic sludge were assessed by transvaginal ultrasound. Amniotic fluid concentrations of matrix metalloproteinase-8, glucose and lactate were measured. Early (<32 weeks) and late (32 to 36 weeks) preterm premature rupture of membranes (PPROM) and spontaneous PTB constituted primary outcomes. Nonparametric analyses were conducted. Three hundred ten women, including 94 (30%) with free-floating echogenic particles and 16 (5%) with dense amniotic sludge, were recruited. Dense amniotic sludge was linked with early (13%) but not with late (0%) primary outcome ( P < 0.01). Two women with combined dense amniotic sludge and short cervix delivered 4 and 10 weeks later (at 20 and 25 weeks, respectively) and had a higher median amniotic lactate concentration than controls ( P < 0.05). A third woman with dense amniotic sludge at 15 weeks was diagnosed with a short cervix and an intra-amniotic infection at 22 weeks that was eradicated with intravenous antibiotics. Midtrimester dense amniotic sludge is associated with early PPROM and spontaneous PTB.

Study protocol for the Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI): a multicentre, cluster-randomised, parallel-group, superiority trial of a multifaceted community-family-mother-child intervention to prevent childhood overweight and obesity.

INTRODUCTION: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk. METHODS AND ANALYSIS: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study. ETHICS AND DISSEMINATION: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation. TRIAL REGISTRATION NUMBER: ChiCTR1800017773. PROTOCOL VERSION: November 11, 2020 (Version #5).

Bacteriology of amniotic fluid in women with suspected cervical insufficiency.

OBJECTIVE: To determine the prevalence of mid-trimester microbial invasion of the amniotic cavity (MIAC) in women with suspected cervical insufficiency. METHODS: A prospective observational cohort study was performed in women with suspected cervical insufficiency and visible fetal membranes who were undergoing amniocentesis to rule out MIAC between 16 and 26 weeks of gestation. Women with preterm premature rupture of membranes, regular uterine contractions, or who had a cervical cerclage were excluded. Gram staining of amniotic fluid, glucose and lactate dehydrogenase (LDH) levels in amniotic fluid, and aerobic and anaerobic amniotic fluid cultures were performed, along with polymerase chain reaction (PCR) for the detection of Ureaplasma and Mycoplasma species. RESULTS: Fifteen women with a mean gestational age of 22.6 +/- 2.3 weeks were included in the study. The diagnosis of MIAC was confirmed in 47% (7/15), of whom 20% (3/15) were infected with more than one bacterial strain and 33% (5/15) with Ureaplasma species. According to receiver-operator curve analyses, amniotic fluid levels of glucose were associated with MIAC (P = 0.02), but not amniotic fluid LDH (P = 0.25). CONCLUSION: MIAC is present in approximately one half of women with suspected cervical insufficiency and visible fetal membranes at speculum examination.

Photonic-crystal waveguide biosensor.

A photonic-crystal waveguide sensor is presented for biosensing. The sensor is applied for refractive index measurements and detection of protein-concentrations. Concentrations around 10 mug/ml (0.15muMolar) are measured with excellent signal to noise ratio, and a broad, dynamic refractive index sensing range extending from air to high viscous fluids is presented.