Summary: Although the factors involved in the pathophysiology of endometriosis are probably multiple and interrelated, prostaglandins may play an important role in the infertility of women with mild disease. In the present study, prostaglandin F 2α (PGF 2α ) and 17β‐oestradiol were measured in the peritoneal fluid of a selected group of infertile women who had mild pelvic endometriosis (without anatomical distortion) and compared with those values in normal women who had no pelvic disease and in women with pelvic infection. Although there was a wide scatter of PGF 2α values, the mean (1,066 pg/ml) in the endometriosis group was significantly greater than that in the other 2 groups (542 pg/ml, normal and 688 pg/ml, pelvic infection); the increase was found in both phases of the menstrual cycle. The mean concentration of 17β oestradiol was markedly higher in the luteal than the follicular phase in all 3 groups; however, no significant differences were found between the groups. Interestingly, the mean value of PGF 2α and 17β‐oestradiol was higher in women with endometriosis who failed to conceive than in those who became pregnant. An estimation of PGF 2α in the peritoneal fluid may have prognostic value in the evaluation of infertile patients, especially those with mild endometriosis or in whom the problem is unexplained.
Introduction The German health technology assessment (HTA) rejected additional benefit of alectinib for second line (2L) ALK+ NSCLC, citing possible biases from missing ECOG performance status data and unmeasured confounding in real-world evidence (RWE) for 2L ceritinib that was submitted as a comparator to the single arm alectinib trial. Alectinib was approved in the US and therefore US post-launch RWE can be used to evaluate this HTA decision. Methods We compared the real-world effectiveness of alectinib with ceritinib in 2L post-crizotinib ALK+ NSCLC using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Using quantitative bias analysis (QBA), we estimated the strength of (i) unmeasured confounding and (ii) deviation from missing-at-random (MAR) assumptions needed to nullify any overall survival (OS) benefit. Results Alectinib had significantly longer median OS than ceritinib in complete case analysis. The estimated effect size (Hazard Ratio: 0.55) was robust to risk ratios of unmeasured confounder-outcome and confounder-exposure associations of <2.4. Based on tipping point analysis, missing baseline ECOG performance status for ceritinib-treated patients (49% missing) would need to be more than 3.4-times worse than expected under MAR to nullify the OS benefit observed for alectinib. Conclusions Only implausible levels of bias reversed our conclusions. These methods could provide a framework to explore uncertainty and aid decision-making for HTAs to enable patient access to innovative therapies.
Summary A consecutive series of 46 patients (110 tests) was studied to determine the relationship between the oestriol/creatinine ratios of 24‐hour and single urine specimens. A satisfactory correlation was found between the 2 ratios (correlation coefficient 0.86, P < 0.001). The single specimen urinary oestriol/creatinine ratio may have a place in the prediction of placental function, particularly at the onset of labour.
e18713 Background: When randomized trials are not available, observational real-world data can be used to emulate a (hypothetical) target trial. The procedure starts with the specification of the protocol of the target trial, whose components are then explicitly emulated using observational data. This approach prevents biases that are common when using more conventional methods for real-world data. Advanced pancreatic cancer represents an opportunity for trial emulation since two main frontline therapies, FOLFIRINOX and GN, have never been directly compared in a randomized fashion. The choice between the two regimens is largely based on physician discretion and patient preference rather than direct comparison of effectiveness. Methods: We emulated a target trial using linked data from the provincial cancer registry, electronic health records and various administrative databases from Alberta, Canada. Eligible individuals had locally advanced or metastatic pancreatic cancer diagnosed between Jan. 2015- Dec. 2018, no prior treatment, and adequate hematologic and serum creatinine values. They were followed from diagnosis until March 2020, death, or date of last known contact with the healthcare system. We estimated the effect of initiating FOLFIRINOX vs. GN within 8 weeks of diagnosis on overall survival. Cloning, artificial censoring, and inverse probability weighting were used to address unknown treatment assignment at baseline, non-adherence, and confounding. Adjusted Kaplan-Meier survival curves and hazard ratios were estimated. Results: Of 298 eligible individuals, 70 adhered to the FOLFIRINOX strategy and 147 to the GN strategy. The mean age was 65 years, 173 (58%) were male, and 247 (83%) had metastatic disease. The adjusted median survival, 1-year survival, and 2-year survival for FOLFIRNOX was 8.2 months (95% CI: 5.3 to 9.4), 36.9% (22.2 to 55.8), and 14.1% (4.8 to 32.2), respectively; and for GN was 4.8 months (3.3 to 5.3), 22.2% (13.6 to 35.9), and 4.7% (1.7 to 13.0), respectively. The adjusted difference in median survival was 3.4 months (0.6 to 11.1) and the adjusted hazard ratio was 0.79 (0.56 to 1.05). Conclusions: Target trial emulations can help to inform medical decision making in situations where head-to-head randomized trial data are unavailable or unfeasible. Findings from this real-world trial emulation suggest improved overall survival with FOLFIRINOX over GN.
In view of the reliance that is now placed on the level of urinary oestrogen in complicated pregnancies, it is important to record extraneous factors which may significantly alter laboratory findings. One substance which appears to act in this way is the urinary antiseptic drug, methenamine mandelate (Mandelamine). The effect of this drug is illustrated in the following 2 case reports which were collected within a short time of one another.
Based on indirect evidence it has been suggested that the liquefaction of human seminal plasma involves fibrinolytic and proteolytic enzymes and that the coagulum is formed by proteins. In this preliminary investigation evidence is presented for the involvement of seminal plasma sialyltransferase in liquefaction which suggests that the coagulum may be composed of glycoproteins. It is proposed that the glycoproteins form a polymer by the chelation of divalent metal ions via the carboxylic acid moieties of the sialic acid groups of the glycoproteins. The glycoprotein polymer may then be dismantled by the reduction of the meal ions by the oxidation of L-ascorbic acid, possibly allowing enzymes to complete the liquefaction process. A total of 100 semen samples from 30 male subjects whose semen profiles were considered "normal" by an independent assessor, were examined for the following: (i) liquefaction time of the seminal plasma; (ii) seminal plasma sialyltransferase activity; (iii) spermatozoal motility, defined as directional or nondirectional; (iv) spermatozoal count, and (v) seminal plasma content of free L-ascorbic acid, dehydroascorbic acid and glutathione. Linear regression analysis showed a significant correlation between sialyltransferase activity and the liquefaction time for seminal plasma. Similarly, multilinear regression analysis of the data showed that as the seminal plasma levels of L-ascorbic acid, total dehydroascorbic acid and glutathione increase, there is a decrease in spermatozoal motility and a decrease in the liquefaction time of the seminal plasma. The possible metabolic relationship of seminal plasma L-ascorbic acid and glutathione is discussed and a metabolic pathway is suggested.
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