Automatic Machine Learning to Differentiate Pediatric Posterior Fossa Tumors on Routine MR Imaging.

BACKGROUND AND PURPOSE: Differentiating the types of pediatric posterior fossa tumors on routine imaging may help in preoperative evaluation and guide surgical resection planning. However, qualitative radiologic MR imaging review has limited performance. This study aimed to compare different machine learning approaches to classify pediatric posterior fossa tumors on routine MR imaging. MATERIALS AND METHODS: This retrospective study included preoperative MR imaging of 288 patients with pediatric posterior fossa tumors, including medulloblastoma (n = 111), ependymoma (n = 70), and pilocytic astrocytoma (n = 107). Radiomics features were extracted from T2-weighted images, contrast-enhanced T1-weighted images, and ADC maps. Models generated by standard manual optimization by a machine learning expert were compared with automatic machine learning via the Tree-Based Pipeline Optimization Tool for performance evaluation. RESULTS: For 3-way classification, the radiomics model by automatic machine learning with the Tree-Based Pipeline Optimization Tool achieved a test micro-averaged area under the curve of 0.91 with an accuracy of 0.83, while the most optimized model based on the feature-selection method χ2 score and the Generalized Linear Model classifier achieved a test micro-averaged area under the curve of 0.92 with an accuracy of 0.74. Tree-Based Pipeline Optimization Tool models achieved significantly higher accuracy than average qualitative expert MR imaging review (0.83 versus 0.54, P < .001). For binary classification, Tree-Based Pipeline Optimization Tool models achieved an area under the curve of 0.94 with an accuracy of 0.85 for medulloblastoma versus nonmedulloblastoma, an area under the curve of 0.84 with an accuracy of 0.80 for ependymoma versus nonependymoma, and an area under the curve of 0.94 with an accuracy of 0.88 for pilocytic astrocytoma versus non-pilocytic astrocytoma. CONCLUSIONS: Automatic machine learning based on routine MR imaging classified pediatric posterior fossa tumors with high accuracy compared with manual expert pipeline optimization and qualitative expert MR imaging review.

Effect of letrozole on uterine artery Doppler flow indices prior to first-trimester termination of pregnancy: a randomized controlled trial.

OBJECTIVE: We previously demonstrated that a sequential regimen of letrozole and misoprostol resulted in a marked reduction in the serum estradiol concentration and in a higher efficacy of first-trimester termination of pregnancy than misoprostol alone. The aim of this study was to evaluate the effect of letrozole on uterine artery Doppler flow indices during early pregnancy. METHODS: This was a randomized controlled trial. Thirty women requesting termination of pregnancy up to 63 days' gestation were randomized into two groups: a letrozole group receiving 10 mg of letrozole, daily, for 3 days, and a control group receiving a placebo for 3 days. Serum estradiol, progesterone and human chorionic gonadotropin (hCG) concentrations were measured before drug administration and then daily for 6 days. Ultrasound scanning for fetal viability and measurement of the pulsatility (PI) and resistance (RI) indices of the uterine arteries was performed before drug administration, and then on day 3 and day 7 after starting letrozole or placebo. All pregnancies were terminated by surgical evacuation on day 7 or day 8. RESULTS: Uterine artery PI and RI decreased significantly in the letrozole group, but not in the control group. Serum estradiol concentrations were significantly lower in the letrozole group than in the control group from day 2 onwards. Serum progesterone and hCG concentrations were comparable for the two groups throughout the 7 days. There were significantly more women in the letrozole group with vaginal bleeding. CONCLUSION: We have demonstrated that the use of letrozole in the first trimester of pregnancy suppresses serum estradiol levels but results in an increase in blood flow to the uterus. Further studies should be carried out to elucidate the mechanism of letrozole pretreatment in medical abortion.

Notch mediated epithelial to mesenchymal transformation is associated with increased expression of the Snail transcription factor.

Notch signalling pathway has been implicated as an important contributor to epithelial to myofibroblast transformation (EMT) in tumourigenesis. However, its role in kidney tubular cells undergoing EMT is not defined. This study assessed Notch signalling and the downstream effects on Snail in cultured proximal tubular epithelial cells. EMT was induced by exposure to transforming growth factor beta-1 (TGFbeta(1)) and angiotensin II (AngII). The expressions of Notch1, Snail, E-cadherin and alpha-smooth muscle actin (alpha-SMA) were determined by Western blot. Matrix Metalloproteinase (MMP)-2 and -9 production were determined by zymography. The specific roles of Notch1-ICD and Snail were determined by gene expression or siRNA technique respectively. TGFbeta(1) and AngII resulted in EMT as characterized by the expected decrease in E-cadherin expression, an increase in alpha-SMA, MMP-2 and MMP-9 expression and associated increase of Notch1 and Snail. Over-expression of Notch1-ICD similarly resulted in increased Snail expression, loss of E-cadherin and increase dalpha-SMA. Inhibiting Snail degradation by pre-treatment with lithium chloride (LiCl) led to a further decrease in E-cadherin expression in cells concurrently exposed to TGFbeta(1)+AngII, confirming that Snail is a repressor of E-cadherin. Silencing of Snail blocked TGFbeta(1)+AngII induced EMT. Inhibition of Notch activation, by concurrent exposure to DAPT during the induction of EMT attenuated the decrease in E-cadherin expression, limited the increase in alpha-SMA and MMP-2 and -9 expression and decreased Snail expression. These results suggest a direct role for Notch signalling via the Snail pathway in the development of EMT and renal fibrosis.

Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomised factorial controlled equivalence trial.

OBJECTIVE: To compare the efficacy of 100 mg and 200 mg of mifepristone and 24- and 48-hour intervals to administration of 800 microg vaginal misoprostol for termination of early pregnancy. DESIGN: Placebo-controlled, randomized, equivalence trial, stratified by centre. SETTING: 13 departments of obstetrics and gynecology in nine countries. POPULATION: 2,181 women with 63 days or less gestation requesting medical abortion. METHODS: Two-sided 95% CI for the risk differences of failure to complete abortion were calculated and compared with 5% equivalence margin between two doses of mifepristone and two intervals to misoprostol administration. Proportions of women with adverse effects were compared between the regimens using standard testes for proportions. OUTCOME MEASURES: Rates of complete abortion without surgical intervention and adverse effects associated with the regimens. RESULTS: Efficacy outcome was analysed for 2,126 women (97.5%) excluding 55 lost to follow up. Both mifepristone doses were found to be similar in efficacy. The rate of complete abortion was 92.0% for women assigned 100 mg of mifepristone and 93.2% for women assigned 200 mg of mifepristone (difference 1.2%, 95% CI: -1.0 to 3.5). Equivalence was also evident for the two intervals of administration: the rate of complete abortion was 93.5% for 24-hour interval and 91.7% for the 48-hour interval (difference -1.8%, 95% CI: -4.0 to 0.5). Interaction between doses and interval to misoprostol administration was not significant (P = 0.92). Adverse effects related to treatments did not differ between the groups. CONCLUSIONS: Both the 100 and 200 mg doses of mifepristone and the 24- and 48-hour intervals have a similar efficacy to achieve complete abortion in early pregnancy when mifepristone is followed by 800 micrograms of vaginally administered misoprostol.

A randomized trial to compare two dosing intervals of misoprostol following mifepristone administration in second trimester medical abortion.

BACKGROUND: The conventional timing of misoprostol administration after mifepristone for second trimester medical abortion is 36-48 h, but simultaneous administration, which may make the regimen more convenient, has not been studied. The objective of this randomized comparison study is to compare two intervals of administration of misoprostol after pretreatment with mifepristone for second trimester medical abortion. METHODS: Eligible women with gestational age between 12 and 20 weeks were randomized to receive mifepristone 200 mg orally followed by 600 microg misoprostol vaginally either immediately or 36-38 h later, followed by 400 microg vaginal misoprostol every 3 h for a maximum of four doses. The primary outcome measure was the success rate at 24 h after the start of misoprostol treatment and the secondary outcome measures were the induction-to-abortion interval and the frequency of side effects. RESULTS: There was a significant difference in the success rate at 24 h (36-38 h: 100%; immediate: 91.5%). The median induction-to-abortion interval was significantly shorter in the 36-38 h regimen (4.9 h) compared with the immediate regimen (10 h). Side effects in terms of febrile episodes and chills/rigors were significantly higher in the immediate administration group. CONCLUSIONS: Simultaneous use of mifepristone and misoprostol for second trimester medical abortion is not as effective as the regimen using a 36-38 h dosing interval.

Misoprostol for the termination of pregnancy with a live fetus at 13 to 26 weeks.

A combination of mifepristone and misoprostol is the regimen of choice for termination of pregnancy between 13 to 26 weeks. In many countries, mifepristone is still not available, and misoprostol has to be used alone. Many misoprostol-alone regimens have been reported in the literature with apparently good results. Most of the trials were conducted in pregnancies between 13 and 22 weeks. For this gestational period, we recommend the regimen of 400 microg of vaginal misoprostol every 3 h up to 5 doses, as it appears to be effective without excessive side effects or complications. There is inadequate data to recommend a regimen for the gestational period of 23 to 26 weeks but it is advisable to reduce the dose and frequency of administration of misoprostol. Common side effects of misoprostol-induced termination of pregnancy include gastrointestinal side effects, abdominal cramps, bleeding, fever and chills. Complications may include infection or rarely rupture of uterus.

Cervical priming with misoprostol prior to transcervical procedures.

Cervical priming with misoprostol has shown to facilitate transcervical procedures and to reduce side-effects. Cervical priming is recommended by several evidence-based guidelines prior to surgical abortion, dilatation and curettage, hysteroscopy and intrauterine device insertion. It is effective in pregnant as well as in non-pregnant women while the results in post-menopausal women are conflicting. Misoprostol is the best suited prostaglandin for a number of reasons: it has a short half-life, few side effects, it is stable at room temperature, it is relatively cheap and the dosage can easily be adjusted according to the clinical need. Various doses, routes, and time intervals between misoprostol application and the intervention have been evaluated. A single dose of 400 microg given sublingually or vaginally 3h before the intervention has given the best efficacy with the least side effects. Higher doses or longer intervals do not improve the effect on the cervix. Pain is a frequent side effect, but usually responds well to NSAIDs. Other side effects are rare.

Misoprostol for the termination of pregnancy up to 12 completed weeks of pregnancy.

The aim was to review the current knowledge about the use of misoprostol alone for abortion induction during the first 12 weeks of pregnancy. Publications reporting experiences with misoprostol alone for pregnancy termination within the first 12 weeks of pregnancy were included in the analysis. Vaginal administration of 800 microg repeated up to three times at 6, 12 or 24 h intervals has an 85% to 90% effectiveness, defined as complete abortion, in most studies. Oral administration is less effective, but sublingual administration at 3-hour interval has the same effectiveness, with more frequent side effects. The oral and sublingual routes appear to be better accepted than vaginal administration. Most studies are limited to the first 9 weeks of pregnancy. The experience on pregnancy termination between 10 and 12 weeks is not yet sufficient for a recommendation.

Misoprostol: pharmacokinetic profiles, effects on the uterus and side-effects.

Misoprostol, a synthetic prostaglandin E1 analogue, is commonly used for medical abortion, cervical priming, the management of miscarriage, induction of labor and the management of postpartum hemorrhage. It can be given orally, vaginally, sublingually, buccally or rectally. Studies of misoprostol's pharmacokinetics and effects on uterine activity have demonstrated the properties of the drug after various routes of administration. These studies can help to discover the optimal dose and route of administration of misoprostol for individual clinical applications. Misoprostol is a safe drug but serious complications and teratogenicity can occur with unsupervised use.

Delivering results to clients: a question of satisfying needs or desires?

Demand for genitourinary (GU) medicine services is outstripping supply. Improving efficiency can modulate the supply side of the equation, e.g. decreasing the number of clients having to return for their results. This survey explored how clients at two central London GU medicine clinics would like to receive their results and their views were reflected against what was offered by London GU medicine clinics. There was a significant difference between the result delivery services that the clients wanted and what the clinics provided (P <0.0001, chi(2)). Of the clients, 92% wanted to know their results regardless of outcome whereas 22% of London clinics would only inform clients of positive results. This study questions the importance and feasibility of patient choice, an important aspect of the National Strategy for Sexual Health and HIV. Clinics may not individually be able to provide choice but between them, they do provide a wide range of alternatives for the client.

A prospective, randomized, double-blind study to compare two doses of recombinant human chorionic gonadotropin in inducing final oocyte maturity and the hormonal profile during the luteal phase.

CONTEXT: Different doses of human chorionic gonadotropin (hCG) have been used in various in vitro fertilization (IVF) treatment protocols to achieve final oocyte maturation. There is as yet no agreement on the optimum dose required. OBJECTIVES: The objective of this study was to compare the effectiveness of 250 and 500 microg recombinant hCG (r-hCG), which represented the lower and upper limits of the dose range, in inducing final oocyte maturation during IVF and intracytoplasmic sperm injection cycles. DESIGN: This was a prospective, randomized, double-blind study. SETTING: This study was performed at an IVF clinic in a teaching hospital. PATIENTS: Sixty patients with an indication for intracytoplasmic sperm injection were studied. INTERVENTION: The treatment dose used was 250 or 500 microg r-hCG. MAIN OUTCOME MEASURES: The percentage of metaphase II oocytes retrieved per patient, as an indicator of oocyte maturation, and the hormone profiles of the treatment cycle starting from the day of hCG up to hCG+10 d were the main outcome measures. RESULTS: The percentage of metaphase II oocytes was similar in the two groups (89.3% vs. 86.0%; P = 0.326) despite higher serum and follicular fluid hCG levels on hCG+2 and hCG+4 d, as was the follicular fluid to serum hCG ratio in the 500-microg r-hCG group. Serum estradiol and progesterone levels were comparable initially, but became significantly higher in the 500-microg r-hCG group on hCG+10 d. CONCLUSION: The two doses of r-hCG were equally effective in inducing final oocyte maturation. It remains unclear whether the higher midluteal estradiol and progesterone levels in the 500-microg r-hCG group confer any benefit.

Estimating the proportion of cured patients in a censored sample.

There has been a recurring interest in modelling survival data which hypothesize subpopulations of individuals highly susceptible to some types of adverse events while other individuals are assumed to be at much less risk, like recurrence of breast cancer. A binary random effect is assumed in this article to model the susceptibility of each individual. We propose a simple multiple imputation algorithm for the analysis of censored data which combines a binary regression formulation for the probability of occurrence of an event, say recurrence of the breast cancer tumour, and a Cox's proportional hazards regression model for the time to occurrence of the event if it does. The model distinguishes the effects of the covariates on the probability of cure and on the time to recurrence of the disease. A SAS macro has been written to implement the proposed multiple imputation algorithm so that sophisticated programming effort can be rendered into a user-friendly application. Simulation results show that the estimates are reasonably efficient. The method is applied to analyse the breast cancer recurrence data. The proposed method can be modified easily to accommodate more general random effects other than the binary random effects so that the random effects not only affect the probability of occurrence of the event, but also the heterogeneity of the time to recurrence of the event among the uncured patients.

Intracervical sodium nitroprusside versus vaginal misoprostol in first trimester surgical termination of pregnancy: a randomized double-blinded controlled trial.

BACKGROUND: Results from small-scale randomized studies on the effectiveness of different preparations of nitric oxide donors in cervical priming before first trimester termination of pregnancies are not consistent. We compared sodium nitroprusside gel to misoprostol, the standard agent for cervical priming in this randomized double-blinded controlled trial. METHODS: Two hundred pregnant patients between 8 to 12 weeks admitted for surgical termination of pregnancy were recruited. They were randomized into either 400 microg vaginal misoprostol and intracervical placebo gel, or 10 mg intracervical sodium nitroprusside gel and placebo tablets 3 h before the procedure. The baseline cervical dilatation and cumulative force required to dilate the cervix from 4 to 9 mm were measured with a tonometer. Blood pressure was measured and side effects were assessed. RESULTS: The cumulative force to dilate the cervix from 4 to 9 mm was significantly higher in the sodium nitroprusside group, and the difference remained when a sub-group analysis was performed according to parity. Baseline cervical dilatation, duration of operation and operative blood loss were all in favour of misoprostol. Transient drop in blood pressure was observed after sodium nitroprusside treatment. CONCLUSIONS: Intracervical sodium nitroprusside is not as effective as misoprostol in cervical priming.

A pilot-randomized comparison of sublingual misoprostol with syntometrine on the blood loss in third stage of labor.

BACKGROUND: To compare sublingual misoprostol with intravenous syntometrine use during third stage of labor by measuring the blood loss. METHODS: Sixty women were randomized to receive either 600 micro g misoprostol sublingually or 1 ml syntometrine intravenously during the third stage of labor after spontaneous vaginal delivery. For those with risk factors of postpartum hemorrhage such as medical induction or augmentation of labor, previous third stage complications were excluded. The blood loss in labor was measured by the alkaline-hematin method, and differences in hemoglobin before and after delivery were compared. RESULTS: There was no significant difference in the median measured blood loss between the misoprostol group and the syntometrine group (280 versus 226 ml, p = 0.45). The change in hemoglobin was comparable between the two groups. There were more women in the misoprostol group who required additional oxytocics, but the difference was not statistically significant. A major complication occurred in one patient in the misoprostol group with blood loss in excess of 1000 ml. The incidence of side effects such as shivering and pyrexia in women receiving misoprostol was significantly higher than that in the syntometrine group. CONCLUSION: The use of sublingual misoprostol or intravenous syntometrine in spontaneous vaginal delivery resulted in a comparable amount of blood loss. Transient side effect such as fever and shivering which resolved within a day occurred more frequent to those who received sublingual misoprostol.

Ultrasound-guided embryo transfer: a prospective randomized controlled trial.

BACKGROUND: Recent reports suggested that ultrasound guidance during embryo transfer might improve the pregnancy rate. METHODS: A prospective randomized controlled trial was performed to compare embryo transfer under ultrasound guidance versus the clinical touch method. A total of 800 embryo transfers was studied; 400 were randomized to ultrasound-guided transfers and 400 were randomized to the clinical touch group. Of these, 441 were fresh cycles and 359 were frozen-thawed cycles. RESULTS: The clinical pregnancy rate was 26.0% in the ultrasound-guided group and 22.5% in the clinical touch group; the difference was not statistically significant. The ongoing pregnancy rate was 23.5% in the ultrasound-guided group compared with 19.0% in the clinical touch group and the difference was again not statistically significant. The implantation rate was slightly higher in the ultrasound-guided group (15.3%) than the clinical touch group (12.0%) (P = 0.048). There were no differences in the incidences of ectopic pregnancy, miscarriage and multiple pregnancy between the two groups. CONCLUSIONS: A significant improvement in implantation rate was observed following the use of ultrasound guidance during embryo transfer. The extent of improvement in the pregnancy rate may depend on the specific techniques and methods of embryo transfer used in individual centres.

Second trimester medical abortion with mifepristone and gemeprost: a review of 956 cases.

The treatment outcomes of 956 women undergoing second trimester termination of pregnancy with mifepristone and gemeprost were studied. The median gestational age was 16 weeks (range: 12-24 weeks). All women were treated with 200 mg mifepristone orally, followed 36 h later with 1 mg vaginal gemeprost administered every 6 h to a maximum of 4 doses in the first 24 h. A second course of 1 mg vaginal gemeprost was given 3-hourly in the next 12 h, if abortion had not occurred. Overall, 96.4% and 98.8% of the women aborted within 24 and 36 h, respectively. The median induction-to-abortion interval was 7.8 h (range: 0.5-109.9 h). The induction-abortion interval was longer in nulliparous women and women with a gestation age 17 weeks or above. Surgical evacuation of the uterus was performed in 11.5% of women for incomplete abortion or retained placenta. More multiparous women (16.7%) required surgical evacuation of uterus than did nulliparous women (7.3%; p <0.001). Ten (0.1%) women failed to abort with gemeprost and required other methods for abortion. In conclusion, a combination of mifepristone and gemeprost is a safe, effective, and noninvasive method of medical abortion for second trimester pregnancy.

Vaginal misoprostol as medical treatment for first trimester spontaneous miscarriage.

BACKGROUND: Misoprostol is effective for cervical priming prior to suction evacuation in first trimester pregnancy termination. This is the first randomized study to compare vaginal misoprostol versus expectant treatment in women presenting with spontaneous miscarriage. METHODS: Sixty women presenting with spontaneous miscarriage were recruited to the study at the Queen Mary Hospital between 1998 and 1999. They were randomized to group 1: misoprostol; and group 2: expectant management. Women in the misoprostol group received vaginal misoprostol 400 microg on days 1, 3 and 5. The expectant group was followed up according to the same schedule. Suction evacuation was performed if there was excessive bleeding or abdominal pain; or if a gestational sac was detected by transvaginal scan on day 15. RESULTS: Fifty-nine women completed the trial. Those who did not require suction evacuation up to the time of return of normal menstruation were considered to be successful. The incidence of side-effects was comparable between the two groups. Three women in the expectant group and one in the misoprostol group underwent emergency suction evacuation because of excessive bleeding. The mean duration of vaginal bleeding was similar for both groups (14.6 days in the misoprostol group versus 15.0 days in the expectant group). The successful rate in the misoprostol group was significantly higher than that of the expectant group (83.3 versus 48.3%, P < 0.05). CONCLUSION: We recommend repeated vaginal misoprostol 400 microg given on days 1, 3 and 5 as a treatment option for women with first trimester spontaneous miscarriage.

Paracervical block with and without conscious sedation: a comparison of the pain levels during egg collection and the postoperative side effects.

OBJECTIVE: To compare the pain levels during egg collection and the subsequent postoperative side effects in patients receiving a paracervical block (PCB) with and without conscious sedation. DESIGN: A prospective, randomized, double-blind, and placebo-controlled study. SETTING: A tertiary assisted reproduction unit. PATIENT(S): 150 patients undergoing egg collection. INTERVENTION(S): Randomized to receive PCB only (control group) and PCB in conjunction with conscious sedation (sedation group). MAIN OUTCOME MEASURE(S): Vaginal and abdominal pain levels; severity of postoperative side effects. RESULT(S): The median pain levels during vaginal punctures were 12.0 (2.5th--97.5th centiles: 0--84.3) and 30.0 (2.5th--97.5th centiles: 0--100) in the sedation and placebo groups, respectively. The corresponding median abdominal pain levels were 16.5 (2.5th--97.5th centiles: 0--100) and 43.0 (2.5th--97.5th centiles: 0--100). The pain levels were significantly higher in the placebo group than the sedation group. There were no significant differences between the two groups in the severity of nausea, vomiting, dizziness, and drowsiness. CONCLUSION(S): Patients who received only a PCB during the egg collection experienced 2.5 times higher levels of vaginal and abdominal pain as compared to those who received both PCB and conscious sedation. The use of PCB along is not recommended for all patients but it may be considered with selected patients after they have been given extensive counseling.

In vitro fertilization and embryo transfer during natural cycles.

OBJECTIVE: To report the results of in vitro fertilization and embryo transfer (IVF/ET) performed during natural cycles. STUDY DESIGN: A prospective clinical study. RESULTS: Thirty-two cycles were started in 19 patients who had regular ovulatory cycles and tubal factors or unexplained infertility only as the cause of infertility. Egg collection was performed in 12 cycles, and four pregnancies resulted from ET in eight cycles. The pregnancy rates were 12.5% per cycle initiated, 33.3% per retrieval cycle and 50% per transfer. CONCLUSION: Natural cycle IVF/ET offers a low-cost alternative to patients with infertility.