scholarly journals Treatment effect of oil-based contrast is related to experienced pain at HSG: a post-hoc analysis of the randomised H2Oil study

2019 ◽  
Vol 34 (12) ◽  
pp. 2391-2398 ◽  
Author(s):  
N van Welie ◽  
K Dreyer ◽  
J van Rijswijk ◽  
H R Verhoeve ◽  
M Goddijn ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Pregnancy Rates ◽  
P Value ◽  
Ongoing Pregnancy ◽  
Research Grants ◽  
Enhancing Effect ◽  
Post Hoc Analysis ◽  
Infertile Women ◽  
Water Based ◽  
Post Hoc

Abstract STUDY QUESTION Does pain or volume of used contrast medium impact the effectiveness of oil-based contrast during hysterosalpingography (HSG)? SUMMARY ANSWER In women who report moderate to severe pain during HSG, the use of oil-based contrast resulted in more ongoing pregnancies compared to the use of water-based contrast, whereas in women who reported mild or no pain, no difference in ongoing pregnancies was found. WHAT IS KNOWN ALREADY We recently showed that in infertile women undergoing HSG, the use of oil-based contrast results in more ongoing pregnancies within 6 months as compared to the use of water-based contrast. However, the underlying mechanism of this fertility-enhancing effect remains unclear. STUDY DESIGN, SIZE, DURATION We performed a post-hoc analysis of the H2Oil study, a multicentre randomised controlled trial (RCT) evaluating the therapeutic effect of oil- and water-based contrast at HSG. Here, we evaluated the impact of pain experienced at HSG and volume of used contrast media during HSG on ongoing pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS In a subset of 400 participating women, pain during HSG by means of the Visual Analogue Scale (VAS) (range: 0.0–10.0 cm) was reported, while in 512 women, we registered the volume of used contrast (in millilitres). We used logistic regression analyses to assess whether pain and volume of used contrast media modified the effect of oil-based contrast on ongoing pregnancy rates. Data were analysed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE In 400 women in whom pain scores were reported, the overall median pain score was 5.0 (Interquartile range (IQR) 3.0–6.8) (oil group (n = 199) 4.8 (IQR 3.0–6.4); water group (n = 201) 5.0 (IQR 3.0–6.7); P-value 0.28). There was a significant interaction between pain (VAS ≤5 versus VAS ≥6) and the primary outcome ongoing pregnancy (P-value 0.047). In women experiencing pain (VAS ≥6), HSG with oil-based contrast resulted in better 6-month ongoing pregnancy rates compared to HSG with water-based contrast (49.4% versus 29.6%; RR 1.7; 95% CI, 1.1–2.5), while in women with a pain score ≤5, 6-month ongoing pregnancy rates were not significantly different between the use of oil- (28.8%) versus water-based contrast (29.2%) (RR 0.99; 95% CI, 0.66–1.5). In the 512 women in whom we recorded contrast, median volume was 9.0 ml (IQR 5.7–15.0) in the oil group versus 8.0 ml (IQR 5.9–13.0) in the water group, respectively (P-value 0.72). Volume of used contrast was not found to modify the effect of oil-based contrast on ongoing pregnancy (P-value for interaction 0.23). LIMITATIONS, REASONS FOR CAUTION This was a post-hoc analysis that should be considered as hypothesis generating. The RCT was restricted to infertile ovulatory women, younger than 39 years of age and with a low risk for tubal pathology. Therefore, our results should not be generalised to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS The underlying mechanism of the fertility-enhancing effect induced by HSG with the use of oil-based contrast remains unclear. However, these findings suggest a possible mechanistic pathway, that is increasing intrauterine pressure occurring prior to dislodging pregnancy hindering debris or mucus plugs from the proximal part of otherwise normal fallopian tubes. This information might help in the search of the underlying fertility-enhancing mechanism found by using oil-based contrast during HSG. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports consultancy for Guerbet. H.V. reports consultancy fees from Ferring. C.B.L. reports speakers’ fees from Ferring and research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflict of interests. TRIAL REGISTRATION NUMBER The H2Oil study was registered at the Netherlands Trial Registry (NTR 3270). TRIAL REGISTRATION DATE 1 February 2012. DATE OF FIRST PATIENT’S ENROLMENT 3 February 2012.

scholarly journals Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

2019 ◽  
Vol 2019 (3) ◽  
Author(s):  
Joukje van Rijswijk ◽  
Nienke van Welie ◽  
Kim Dreyer ◽  
Parvin Tajik ◽  
Cornelis B Lambalk ◽  
...  
Keyword(s):  
Contrast Medium ◽  
Live Birth ◽  
Treatment Effect ◽  
Ongoing Pregnancy ◽  
Research Grants ◽  
Infertile Women ◽  
Semen Volume ◽  
Water Based ◽  
Work Up ◽  
Tubal Pathology

Abstract STUDY QUESTION Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium? SUMMARY ANSWER In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple. WHAT IS KNOWN ALREADY We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium. STUDY DESIGN, SIZE, DURATION We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based (N = 557) or water-based (N = 562) contrast medium. PARTICIPANTS/MATERIALS, SETTING, METHODS We built logistic regression models to predict ongoing pregnancy and live birth (secondary outcome) as a function of the specific contrast, the specific marker, and marker-by-contrast-interaction. Markers considered were female age, maternal ethnicity, female smoking, body mass index (BMI), duration of infertility, infertility being primary or secondary, sperm quality, and previous appendectomy. MAIN RESULTS AND THE ROLE OF CHANCE The 6-month ongoing pregnancy rates in the overall population were 39.7% after use of oil-based contrast versus 29.1% after use of water-based contrast medium [relative risk (RR), 1.37; 95% confidence interval (CI), 1.16–1.61; P < 0.001]. Among the studied baseline characteristics, BMI (P = 0.002) and semen volume (P = 0.02) were statistically significant prognosticators. The treatment effect of oil-based contrast was stronger in women with a BMI ≤30 kg/m2 [RR, 1.54; 95% CI, 1.23–1.92; P = 0.002], and in women whose partner had a semen volume >3 ml [RR, 1.77; 95% CI, 1.28–2.46; P = 0.02]. Also, in women who smoked, the treatment effect of flushing with oil was stronger, but this interaction did not reach statistical significance (P = 0.066). We found no positive effect of oil-based contrast in obese women. We found similar but weaker associations for live birth, which was probably due to lower number of events resulting in less power. LIMITATIONS, REASONS FOR CAUTION The RCT was restricted to infertile ovulatory women younger than 39 years of age without endocrinological disorders and at low risk for tubal pathology. Our results should not be generalized to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS All infertile, ovulatory women younger than 39 years with a low risk for tubal pathology will benefit from an HSG with oil-based contrast; therefore, this should be offered to them after fertility work-up. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The study displayed in this paper was funded by an unconditional research grant from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). K.D. reports consultancy for Guerbet, during the conduct of the study, and also reports research grants from Guerbet. C.B.L. reports grants from Guerbet, during the conduct of the study, and grants from Ferring, grants from Merck, and personal fees from Ferring, outside the submitted work. P.H. reports grants from Guerbet, during the conduct of the study, and grants from Ferring and Merck, outside the submitted work. V.M. reports receiving travel and speakers fee as well as research grants from Guerbet. B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, and Guerbet, and research grants from Guerbet and Merck. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER NTR 3270 www.trialregister.nl TRIAL REGISTRATION DATE 1 February 2012. DATE OF FIRST PATIENT’S ENROLMENT 3 February 2012.

High Leptin Level Attenuates Embryo Development in Overweight/Obese Infertile Women by Inhibiting Proliferation and Promotes Apoptosis in Granule Cell

2017 ◽  
Vol 49 (07) ◽  
pp. 534-541 ◽  
Author(s):  
Xian-hua Lin ◽  
Hui Wang ◽  
Dan-dan Wu ◽  
Kamran Ullah ◽  
Tian-tian Yu ◽  
...  
Keyword(s):  
Embryo Development ◽  
Granulosa Cells ◽  
Peripheral Blood ◽  
Pregnancy Rates ◽  
Dependent Manner ◽  
Reproductive Outcomes ◽  
Ongoing Pregnancy ◽  
Infertile Women ◽  
Proliferation And Apoptosis

AbstractObesity appears to be associated with female reproductive dysfunction and infertility. Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality, decreased embryo development, and poor pregnancy outcome. However, the mechanism linking obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate these findings with poor reproductive outcomes in infertile women with overweight or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral blood and FF as well. In vitro cell model was used to explore the potential effect of high leptin on the proliferation and apoptosis in granulosa cells. Results showed reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent IVF compared to control with normal BMI. On the other hand, leptin levels presented significant increase in peripheral blood and FF in overweight/obese women. Leptin level in FF was negatively correlated to good quality embryo rate. Importantly, in vitro study showed that leptin inhibited cells proliferation and promoted apoptosis by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose dependent manner. These observations suggest that leptin may acts as a local mediator to attenuate embryo development and reduce fertility in obese patients.

scholarly journals PENGARUH PESTISIDA NABATI TERHADAP KEMATIAN LALAT RUMAH (MUSCA DOMESTICA)

2019 ◽  
Vol 13 (1) ◽  
pp. 11
Author(s):  
Novie Elvinawaty Mauliku
Keyword(s):  
Musca Domestica ◽  
Statistical Test ◽  
Lemon Juice ◽  
Effective Concentration ◽  
P Value ◽  
Test Results ◽  
House Flies ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
True Experiment

House flies (Musca domestica) are a vector that caused diary so it needs to be controlled by using plant-based insecticide such as Lime (Citrus aurantifolia). Lime had active contains such as saponins, tannins, flavonoids and essential oils. This study was to impact of lemon juice to the death of house flies (Musca domestica). This study design is the True Experiment. The lime was defined  with three concentrations there are 25%, 27% and 29% of the death of house flies (Musca domestica) which is given three repetitions to 300 samples. Data was analyzed using univariate, bivariate used Kruskal Wallis and post hoc analysis used bonferonni tests to determine the effectiveness of concentration. The results found out that the percentage of dead houseflies (Musca Domestica) at a concentration of 25% on average by 53%, the concentration of 27% on average by 71% and 29% concentrations by an average of 92%. Statistical test results obtained that there are differences in various concentrations of lime juice to the death of house flies (Musca Domestica) with a p value (0.014). The  effective concentration was at a 29% concentration against houseflies death 92%..

scholarly journals OR30-06 Assessment of Dulaglutide Safety in Older Patient Populations in Rewind

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Manige Konig ◽  
Hertzel C Gerstein ◽  
Mark C Lakshmanan ◽  
Denis Xavier ◽  
Charles Atisso ◽  
...  
Keyword(s):  
Adverse Events ◽  
Group Treatment ◽  
Cardiovascular Events ◽  
Severe Hypoglycemia ◽  
P Value ◽  
Older Patient ◽  
Post Hoc Analysis ◽  
Safety Outcome ◽  
First Occurrence ◽  
Post Hoc

Abstract Background: Dulaglutide (DU) was superior to placebo (PL) in reducing the incidence of Major Adverse Cardiovascular Events in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND Study) broad patient population. The safety of DU treatment is also of interest to health care providers who treat an older patient population (≥65 years of age). Aims: The primary objective of this post-hoc analysis was to evaluate DU safety in the REWIND patient subgroup populations categorized by age (≥ 65 and &lt; 65 years) with regards to the occurrence of the composite safety outcome of overall mortality and severe hypoglycemia. One of the key secondary objectives was first occurrence of severe hypoglycemia. Methods: Patients were grouped into two age groups: ≥65 and &lt;65 years. Time-to-event for the composite safety endpoint as well as individual variables were analyzed using Cox proportional hazards regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for between group treatment differences were also calculated. Results: Of the 9,901 patients randomized in REWIND, a total of 5,256 (DU, 2,619; PL, 2,637) were aged ≥65 years. The incidence of the composite safety outcome for patients aged ≥65 years was 399 of 2619 (15.2%) for DU-treated patients and 425 of 2,637 (16.1%) for PL-treated patients. The incidence of the composite safety outcome for those aged &lt;65 years was 188 of 2,330 (8.1%) for DU-treated patients and 224 of 2,315 (9.7%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.94 (0.82, 1.08) for patients ≥65 years of age and 0.82 (0.68, 1.00) for patients &lt;65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged ≥65 years was 46 of 2619 (1.8%) for DU-treated patients and 49 of 2,637 (1.9%) for PL-treated patients. The incidence of this outcome for patients &lt;65 years was 18 of 2,330 (0.8%) for DU-treated patients and 25 of 2,315 (1.1%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.95 (0.63, 1.42) for patients ≥65 years of age and 0.71 (0.39, 1.31) for patients &lt;65 years of age; interaction p-value = 0.443. The safety profile of DU was reviewed based upon the results of subgroup analysis of treatment emergent adverse events and serious adverse events by preferred terms for comparing PL and DU for age subgroups (≥65 years of age versus &lt;65 years). None of the results indicated that DU has a different safety profile across the age subgroups evaluated in this post-hoc analysis. Conclusions: Treatment with DU demonstrated similar safety in REWIND patients aged ≥65 years and those aged &lt;65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.

P6271The effect of semaglutide once weekly on MACE and blood pressure by race and ethnicity: SUSTAIN 6 post hoc analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Desouza ◽  
S C Bain ◽  
T Gondolf ◽  
T Hansen ◽  
I Holst ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
African American ◽  
Race And Ethnicity ◽  
P Value ◽  
Black African ◽  
Treatment Difference ◽  
Post Hoc Analysis ◽  
Fatal Stroke ◽  
Post Hoc

Abstract Background In SUSTAIN 6, subcutaneous semaglutide once weekly added to standard of care significantly reduced major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke or death) vs placebo over 2 years in T2D subjects. Purpose Assess the effect of semaglutide vs placebo on MACE and blood pressure (BP) by race and ethnicity in a post hoc analysis of SUSTAIN 6. Methods Subjects were randomised to semaglutide 0.5 mg, 1.0 mg or volume-matched placebo. Data for the two semaglutide-dose groups were pooled and compared to the pooled placebo groups. Time-to-event data were analysed with a Cox proportional hazards model. Changes from baseline to week 104 were analysed using analysis of covariance. The interaction between treatment and subgroup was added to the models. Results Overall, 3,297 patients received treatment. Subgroups included Caucasian, Asian, Black/African American, Other (race), and Hispanic, non-Hispanic (ethnicity). Mean baseline characteristics were similar across subgroups (age 64.7 years, HbA1c 8.7%, diabetes duration 14.2 years). Time to composite MACE and individual components were improved with semaglutide across all subgroups. Semaglutide affected BP similarly across race and ethnicity, except for systolic BP in Black/African American subjects (Table). Race Ethnicity Caucasian Asian Black/African American Other Interaction p-value Hispanic Non-Hispanic Interaction p-value Semaglutide (n) 1,384 121 108 35 256 1,392 Placebo (n) 1,352 152 113 32 254 1,395 MACE and individual outcomes   MACE HR [95% CI] 0.76 [0.58; 1.00] 0.58 [0.25; 1.34] 0.72 [0.23; 2.28] 0.46 [0.08; 2.50] 0.8793 0.67 [0.33; 1.36] 0.74 [0.57; 0.96] 0.7978   CV death HR [95% CI] 0.98 [0.63; 1.50] 0.32 [0.04; 2.85] 1.01 [0.06; 16.20] n/a† 0.8089 0.79 [0.31; 2.00] 1.00 [0.63; 1.59] 0.6521   Non-fatal MI HR [95% CI] 0.69 [0.45; 1.07] 0.97 [0.36; 2.60] 1.37 [0.31; 6.12] 0.31 [0.03; 3.00] 0.6637 0.65 [0.18; 2.31] 0.74 [0.50; 1.10] 0.8562   Non-fatal stroke HR [95% CI] 0.70 [0.42; 1.16] 0.31 [0.04; 2.77] n/a‡ n/a‡ 0.9176 0.73 [0.16; 3.27] 0.60 [0.36; 0.99] 0.7995 Blood pressure at week 104   Systolic BP* ETD (mmHg) [95% CI] −1.92 [−3.09; −0.74] −4.98 [−8.61; 1.35] 4.47 [0.15; 8.79] −11.02 [−18.45; −3.60] 0.0008 −3.22 [−5.93; −0.51] −1.81 [−2.98; −0.64] 0.3489   Diastolic BP* ETD (mmHg) [95% CI] 0.36 [−0.32; 1.04] −1.31 [−3.43; 0.80] −0.07 [−2.56; 2.43] −3.41 [−7.73; 0.92] 0.1871 −0.18 [−1.75; 1.39] 0.16 [−0.52; 0.83] 0.6981 *Treatment difference between semaglutide and placebo (pooled 0.5 and 1.0 mg values for each treatment group) at week 104. †No events in the placebo group; ‡No events in the semaglutide group. BP, blood pressure; CI, confidence interval; ETD, estimated treatment difference; HR, hazard ratio; MACE, major adverse cardiovascular event; MI, myocardial infarction. Conclusion Overall there was no evidence of a differential effect of semaglutide on risk reduction in MACE and its components and on BP across race and ethnicity subgroups in this post hoc analysis. Acknowledgement/Funding Novo Nordisk A/S

scholarly journals Complications after hysterosalpingography with oil- or water-based contrast: results of a nationwide survey

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Inez Roest ◽  
Nienke van Welie ◽  
Velja Mijatovic ◽  
Kim Dreyer ◽  
Marlies Bongers ◽  
...  
Keyword(s):  
The Netherlands ◽  
Antibiotic Prophylaxis ◽  
Contrast Medium ◽  
Conflicts Of Interest ◽  
Unexplained Infertility ◽  
P Value ◽  
Complication Rates ◽  
Research Grants ◽  
Water Based ◽  
Clinical Consequences

Abstract STUDY QUESTION What is the incidence of complications after hysterosalpingography (HSG) using oil-based contrast versus water-based contrast? SUMMARY ANSWER Among 5165 women undergoing HSG, the most frequently reported complication after HSG with oil- and water-based contrast was intravasation of contrast medium (4.8% versus 1.3%, respectively), which was without further consequences, and pulmonary embolization or death did not occur. WHAT IS KNOWN ALREADY An HSG with oil-based contrast increases pregnancy rates in women with unexplained infertility. However, there have been some concerns regarding complications, including the risks of intravasation of the contrast medium, oil embolism and infection. Here, we present the incidence of complications after HSG with different types of contrast media used in the Netherlands in the year 2017. STUDY DESIGN, SIZE, DURATION In January 2018, an electronic survey was sent to all 73 clinics in the Netherlands that perform HSG. The survey consisted of 12 questions addressing the number of HSGs performed in 2017, the amount and type of contrast medium used, the occurrence of post-procedural complications and what their clinical consequences were. Non-responding clinics were sent multiple reminders. PARTICIPANTS/MATERIALS, SETTING, METHODS We calculated the incidence of the complications and reported on their clinical consequences. Furthermore, we examined the average amount of contrast used as well as the administration of prophylactic antibiotics. MAIN RESULTS AND THE ROLE OF CHANCE The response rate was 96% (67/70) (during the study, one site closed and was not included while two clinics no longer performed HSGs). In the 67 clinics, 3289 HSGs with oil-based contrast and 1876 HSGs with water-based contrast were performed in 2017. The median amount of contrast used was 8.0 ml (interquartile range (IQR) 7.0–10.0) for oil-based contrast and 10.0 ml for water-based contrast (IQR 10.0–10.0). Antibiotic prophylaxis was administered in 61% (41/67) of the clinics. Intravasation occurred in 4.8% of the HSGs performed with oil-based contrast and in 1.3% of the HSGs with water-based contrast (relative risk (RR), 3.6; CI, 2.4–5.4). Pulmonary embolism or death was not reported. Pelvic inflammatory disease (PID) occurred in 0.3% of the HSGs performed with oil-based contrast versus 0.4% with water-based contrast. PID occurred in 0.3% of the HSGs in clinics using antibiotic prophylaxis and 0.2% in clinics not using antibiotic prophylaxis. Allergic reactions were reported in one HSG performed with oil-based contrast (0.03%) compared with two HSGs performed with water-based contrast (0.1%). Anaphylactic reactions did not occur. The overall complication rate was 5.1% in the clinics that used oil-based contrast versus 1.8% in the clinics that used water-based contrast (RR, 2.8; CI, 1.9–4.0; P-value, &lt;0.0001). LIMITATIONS, REASONS FOR CAUTION Half of the clinics did not routinely register complications, and the incidence of the complications in their clinic was based on the recall of the clinician. Estimated complication rates in the clinics with and without systematic registration did not significantly differ. The survey asked about the frequency of intravasation but no classification system is being used in daily practice, which may create differences in reporting. There was no standard screening of post-HSG thyroid function for the mother and the foetus. WIDER IMPLICATIONS OF THE FINDINGS In this nationwide cohort study, the complication rates after HSG were low. Intravasation occurred more frequently with the use of oil-based contrast compared with water-based contrast but did not lead to any problems or symptoms in any of the women. We therefore conclude that safety concerns should not be a reason to deny the use of oil-based contrast in women with unexplained infertility. The data also support that fluoroscopy appears to be an essential safety measure during HSG. STUDY FUNDING/COMPETING INTEREST(S) This work was partly funded by Guerbet, France. I.R. reports receiving travel fee for presenting at the Congress of the American Society for Reproductive Medicine 2019 from Guerbet. V.M. reports receiving travel and speaker’s fee as well as research grants from Guerbet. K.D. reports receiving travel and speaker’s fee from Guerbet. B.W.M. is supported by an National Health and Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER N19.056.

scholarly journals Safety and Efficacy of Apixaban Versus Enoxaparin/Warfarin in Patients with Extremes of Body Weight: Post-Hoc Analysis of the AMPLIFY Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1152-1152 ◽  
Author(s):  
Theodore Lee ◽  
Sharon Pan ◽  
Wonkyung Byon ◽  
Bushra S Ilyas
Keyword(s):  
Body Weight ◽  
Major Bleeding ◽  
P Value ◽  
Bleeding Events ◽  
Employment Equity ◽  
Safety And Efficacy ◽  
Post Hoc Analysis ◽  
Equity Ownership ◽  
Clinically Significant ◽  
Post Hoc

BACKGROUND: Guidelines recommend avoiding direct oral anticoagulants (DOACs) in patients who weigh >120 kg due to limited clinical data in this population. OBJECTIVES: The objective of this post-hoc analysis of the AMPLIFY trial was to evaluate the efficacy, safety, and exposure of apixaban for the treatment of VTE in patients across the following weight categories: ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg and ≥ 120 kg. METHODS: This analysis evaluated the efficacy (VTE/VTE related deaths) and safety (Major and composite of Major and Clinically Relevant Non-Major [CRNM] bleeds) of apixaban versus enoxaparin/warfarin in patients for the following four body weight categories: ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg and ≥ 120 kg. Patients were randomized to apixaban or enoxaparin /warfarin and treated for 6 months and were followed up 30 days after the end of the intended treatment period. The exposure of apixaban across the sub-groups of weight was also evaluated. RESULTS: Of the 5356 patients randomized and included in the safety analysis with body weights recorded, there were 473, 3844, 749, and 290 patients in body weight categories ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg, and ≥ 120 kg, respectively. The rates of VTE/VTE-related death for apixaban versus enoxaparin/warfarin were similar across the sub-groups of weight with relative risks (RR) and 95% confidence intervals (CI) of 0.63 (95% CI: 0.23, 1.72), 0.99 (95% CI: 0.65, 1.50), 0.77 (95% CI: 0.34, 1.72), and 0.20 (95% CI: 0.02, 1.72) for ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg, and ≥ 120 kg, respectively (treatment by weight interaction P-value = 0.44). There was a reduction in Major Bleeding events in the >60 to <100 kg sub-group on apixaban compared to enoxaparin/warfarin with RR=0.41 (95% CI; 0.21, 0.77). Due to the low numbers of Major Bleeding events (apixaban: 0/377, enoxaparin/warfarin: 7/372), the RR in the subgroup of weight ≥ 100 to < 120 kg was not estimable. The RRs for ≤ 60 kg, and ≥ 120 kg weight sub-groups were 0.15 (95% CI: 0.02, 1.15), and 0.34 (95% CI: 0.04, 3.22), respectively. For the composite end-point of Major and CRNM bleeds, apixaban-treated patients had less events compared to enoxaparin/warfarin-treated patients across sub-groups of weight [RR of 0.46 (95% CI: 0.24, 0.89) for ≤ 60 kg, RR of 0.49 (95% CI: 0.38, 0.63) for >60 to <100 kg, RR of 0.30 (95% CI: 0.16, 0.58) for ≥ 100 to < 120 kg, and RR of 0.28 (95% CI: 0.12, 0.66) for ≥ 120 kg weight categories (treatment by weight interaction P-value = 0.36)]. A total of 281 patients had apixaban plasma concentrations measured. There was a small non-clinically significant decrease (<30%) in the median predicted exposure across weight sub-groups (2990, 2734, 2239 and 2006 ng*hr/ml in the ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg and ≥ 120 kg weight categories, respectively). The exposure range was similar among weight categories with overlapping quartiles. CONCLUSION: In this post-hoc analysis, the safety and efficacy of apixaban in patients with extremes of body weight are consistent with the main results of the AMPLIFY trial. Across sub-groups of body weight including extremes of body weight, apixaban compared with enoxaparin/warfarin resulted in similar rates of recurrent VTE/VTE-related death, and reductions in the rates of the composite of Major and CRNM bleeds. There were also no clinically significant differences in apixaban exposure in patients with extremes of body weight compared to those in the >60 to <100 kg weight category. Disclosures Lee: Pfizer Inc.: Employment, Equity Ownership. Pan:Pfizer: Employment. Byon:Pfizer: Employment, Equity Ownership. Ilyas:Pfizer: Employment, Equity Ownership.

Exploratory subset analysis according to prior endocrine treatment of two randomized phase II trials comparing gefitinib (G) with placebo (P) in combination with tamoxifen (T) or anastrozole (A) in hormone receptor-positive (HR+) metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1014-1014
Author(s):  
M. Cristofanilli ◽  
R. Schiff ◽  
V. Valero ◽  
R. Iacona ◽  
J. Yu ◽  
...  
Keyword(s):  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Cox Proportional Hazards Model ◽  
Endocrine Treatment ◽  
P Value ◽  
Phase Ii Trials ◽  
Egfr Inhibition ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Interaction Test

1014 Background: Preclinical and clinical data suggest that increased EGFR and HER-2 activity contribute to acquired resistance to endocrine therapy. Strata of two clinical trials recently showed that the addition of G to T or A in HR+ MBC prolonged progression free-survival (PFS). Certain preclinical data also suggested that G should be combined with T or A from the start of endocrine therapy rather than waiting for resistance to develop. To examine this clinically a post hoc analysis compared the subsets of patients (pts) who had received prior endocrine therapy (may have already upregulated HER receptors) to those that were endocrine therapy naïve (not yet upregulated HER receptors). Methods: One trial evaluated G (250 mg/day orally) + A (1 mg/day orally) versus A+P ( NCT00077025 ) and one trial evaluated G (250 mg/day orally) + T (20 mg/day orally) versus T+P ( NCT00229697 ). Post hoc analysis of PFS was performed in two pt subgroups; previously treated with endocrine therapy (ET) and endocrine naïve (EN). The PFS HR and associated 95% CI and p-value for G relative to P were estimated using the Cox proportional hazards model along with interaction test for treatment by subset. Results: In the ET subgroup of the G+A versus A+P study, 31 PFS events were reobserved in 51 pts (hazard ratio [HR] 0.65 95% CI 0.32, 1.33; median PFS: G+A 11.2 mo, A+P 7.1 mo). In the EN subgroup, 23 PFS events were reobserved in 42 pts (HR 0.39, 95% CI 0.16, 0.97; median PFS: G+A 20.2 mo, A+P 8.4 mo). The interaction test p-value was 0.28. In the ET subgroup of the G+T versus T+P study, 95 PFS events were reobserved in 131 pts (HR 1.22, 95% CI 0.81, 1.86; median PFS: G+T 9.4 mo, T+P 10.9 mo). In the EN subgroup, 106 PFS events were reobserved in 158 patients (HR 0.78, 95% CI 0.52, 1.15; median PFS: G+T 12.1 mo, T+P 8.9 mo). The interaction test p-value was 0.13. Conclusions: The EN pt subgroups of both trials demonstrated prolonged PFS when G was combined with A or with T compared with A or T alone, respectively. A further prospective clinical trial of EGFR inhibition combined with endocrine therapy in EN pts with HR+ MBC is warranted on the basis of these findings. [Table: see text]

scholarly journals Correlation of ultrasonographic estimated fetal weight with actual birth weight at a rural setting

2020 ◽  
Vol 9 (7) ◽  
pp. 2973
Author(s):  
Elnazeer A. Hashim ◽  
Elsir A. Saeed ◽  
Elsadig Y. Mohamed ◽  
Elabbas M. Ebaid ◽  
Hussam Zain ◽  
...  
Keyword(s):  
Fetal Weight ◽  
Rural Setting ◽  
P Value ◽  
Sonographic Examination ◽  
Cross Sectional ◽  
Post Hoc Analysis ◽  
Vaginal Deliveries ◽  
Newborn Weight ◽  
Post Hoc ◽  
Estimated Fetal Weight

Background: Ultrasound estimation of fetal weight in term pregnancies is used to determine fetal growth. The objective of this study was to assess the precision of sonographic estimation of fetal weight in normal vaginal deliveries at a rural setting.Methods: The study was cross-sectional. A group of 74 pregnant women delivered normally in Muglad hospital in West Kordofan, Sudan, were considered in the study. Fetal weight was estimated by Hadlock and shephards formulae within one week prior to delivery and then newborn weight was taken within 24 hours after delivery. Data were collected by a questionnaire and medical examination as well as sonographic examination. Data analysis was done by SPSS version 23 and Kruskal Wallis Test (post-hoc analysis) Pearson’s correlation coefficient within 95% confidence interval. p value <0.05 was considered as statistically significant.Results: The correlation, by Paired sample, to assess fetal weight was as follows: between Hadlock and shephards was 0.901 (p < 0.001), between Hadlock and AFW was 0.908 (p < 0.001) and between Shephards and AFW was 0.781 (p < 0.001).Conclusions: Estimation of fetal weight by Hadlock has been more correlated with actual fetal weight (AFW) than that done with shephards. The study recommends using Hadlock formula which is more accurate in estimation of fetal weight by sonography.

scholarly journals Statistical Analysis of Leading Goal Scoring Pattern of Europe’s Top Five Football Leagues

2020 ◽  
Vol 9 (4) ◽  
pp. 517-521
Keyword(s):  
Statistical Analysis ◽  
Analysis Of Variance ◽  
P Value ◽  
Microsoft Excel ◽  
Post Hoc Analysis ◽  
Premier League ◽  
European Football ◽  
Post Hoc ◽  
The Relationship ◽  
Frequency Counts

Previous researchers have discussed goal-scoring patterns of different football leagues, but little has been done on leading or top goal scorer. In this study, the focus is on the relationship between leading goal scoring and final league position for the top five European leagues (Premier League, La Liga, Serie A, Bundesliga and Ligue 1). The five leagues are the current top leagues in Europe as ranked by the Union of European Football Association (UEFA). The data were obtained from the respective leagues’ football association websites. The data were entered into Microsoft Excel spreadsheet to create frequency counts. Thereafter correlation and analysis of variance (ANOVA) was done using Minitab 18.0 and SPSS version 23. From the result, it was observed that there is a significant relationship between leading goal scoring and league positions for La Liga at a p value equals 0.013 and Germany at a p value equals 0.042, but no relationship for the remaining three leagues. Choosing the last 20 seasons only, the analysis of variance (ANOVA) revealed that the final league positions of the clubs that produced the leading goal scorers are the same across the leagues at p value = 0.349. However, the opposite is the case of the goal-scoring pattern and p value < 0.005 were obtained. Further investigation using the Post Hoc analysis revealed that the goal-scoring pattern of leading goal scores in Spanish La Liga is significantly different from others.

Sign in / Sign up

Export Citation Format

Share Document