Effect of different accessory devices on the dose delivered from pressurised metred-dose inhalers.

INTRODUCTIONS: Improved aerosol delivery of bronchodilators to chronic obstructive pulmonary disease (COPD) subjects is a cornerstone in the treatment approach. Drug delivery and response are improved with the use of accessory devices [spacers and valved holding chambers (VHCs)] with metred-dose inhalers (pMDIs). However, different accessory devices are available in the market with different properties that could affect aerosol delivery. Thus, this study aimed to assess the relative lung deposition and systemic bioavailability and compare bronchodilator response of salbutamol delivered using different accessory devices attached to pMDIs. METHODS: Twelve healthy subjects and twelve COPD subjects inhaled 300 µg salbutamol (3 pMDI puffs) using five different accessory devices with either masks or mouthpieces (Able, Aerochamber plus flow Vu, Dolphin chamber, Tipshaler spacer, and modified Drink bottle spacer). Urine samples were collected thirty minutes post-dosing and cumulatively for the next twenty-four hours, to determine and compare the relative lung deposition [0-0.5 hour excretion of urinary salbutamol (USAL0.5)] and systemic bioavailability [0.5-24 hours excretion of urinary salbutamol (USAL24)] of salbutamol from the selected accessory devices. Also, the difference between pre and post-inhalation forced expiratory volume in one second (ΔFEV1 %) of predicted was determined for each accessory device. RESULTS: Urinary excretion of salbutamol (both USAL0.5 and USAL24 samples) in COPD subjects was significantly (P < .05) lower than in healthy subjects for all accessory devices. USAL0.5 and USAL24 in non-antistatic spacers (modified Drink bottle spacer and Dolphin chamber spacers) were significantly lower (P < .05) than that for antistatic spacers (Aerochamber plus flow Vu, Able and Tips-haler). No significant difference in USAL0.5 and USAL24 was observed between facemasks and mouthpieces. There was a significant difference (P < .05) in ΔFEV1 % of predicted values between COPD subjects and healthy subjects. However, within the COPD group and the healthy group there was no significant difference in ΔFEV1 % of predicted values between all accessory devices or between with mouthpiece or with a mask. CONCLUSIONS: COPD subjects had lower aerosol delivered compared with healthy subjects. Anti-static accessory devices delivered a higher amount of aerosol compared with non-antistatic accessory devices. Even though the presence of a significant difference in aerosol delivery between non-antistatic and antistatic accessory devices no significant difference was found in the ΔFEV1 % between all accessory devices.

Developing a core outcome set for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study† ‡.

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

STUDY QUESTION: In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? SUMMARY ANSWER: A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. WHAT IS KNOWN ALREADY: Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. STUDY DESIGN, SIZE, DURATION: This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. MAIN RESULTS AND THE ROLE OF CHANCE: Ongoing pregnancy rate was 12.8% (25/195) for mild ovarian stimulation versus 13.6% (27/199) for conventional ovarian stimulation leading to a risk ratio of 0.95 (95% CI: 0.57-1.57), representing an absolute difference of -0.7% (95% CI: -7.4 to 5.9). This 95% CI does not extend below the predefined threshold of 10% for inferiority. The duration of ovarian stimulation was significantly lower in the mild ovarian stimulation strategy than in the conventional ovarian stimulation strategy (mean difference -1.2 days, 95% CI: -1.88 to -0.62). Also, a significantly lower amount of gonadotropins was used in the mild simulation strategy, with a mean difference of 3135 IU (95% CI: -3331 to -2940). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study was the lack of data concerning the cryopreservation of surplus embryos, so we are not informed on cumulative pregnancy rates. Another limitation is that we were not able to follow up on the ongoing pregnancies in all centers, so we are not informed on live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: The results are directly applicable in daily clinical practice and may lead to considerable cost savings as high dosages of gonadotropins are not necessary in women with poor ovarian reserve undergoing IVF. A health economic analysis of our data planned to test the hypothesis that mild ovarian stimulation strategy is more cost-effective than the conventional ovarian stimulation strategy is underway. STUDY FUNDING/COMPETING INTERESTS: This study was supported by NUFFIC scholarship (the Netherlands) and STDF short-term fellowship (Egypt). TRIAL REGISTRATION NUMBER: NTR2788 (Trialregister.nl). TRIAL REGISTER DATE: 01 March 2011. DATE OF FIRST PATIENT'S ENROLMENT: May 2011.

Menstrual patterns and disorders among secondary school adolescents in Egypt. A cross-sectional survey.

BACKGROUND: To our knowledge, no large population - based studies have been performed on the topic of menstrual patterns among Egyptian adolescent in recent years. The aims of this study were to identify menstrual patterns and associated disorders as well as the sources of menstrual health knowledge among Egyptian adolescents. METHODS: A cross-sectional survey. A total of 800 questionnaires were administered to post-menarcheal Egyptian adolescents attending secondary schools in Giza, Egypt, from September 1, 2012, to December 1, 2013. Participants were asked to respond to a semi-structured questionnaire on menstrual health awareness. The questionnaire included items on girl's socio-demographic and menstrual pattern characteristics, concerning their age at menarche, menstrual cycle length and regularity, duration and amount of flow, type and severity of pain related to menstruation, need for analgesia; and symptoms suggestive of premenstrual syndrome (PMS) Main Outcome Measure: description of menstrual patterns, disorders and source of knowledge. RESULTS: Four hundred twelve (51.5 %) out of 800 adolescents completed the questionnaire. The mean age of the girls was 14.67 ± 1.7 years. Mean age at menarche was 12.49 ± 1.20 years. 382 respondents reported various menstrual disorders, giving a prevalence rate of 95 %. Dysmenorrhea was the most prevalent (93 %) menstrual disorder in our sample, followed by PMS (65 %), and abnormal cycle lengths (43 %). Menstrual disorders interfered with social and academic life of 33 and 7.7 % of respondents respectively. Most participants lacked menstrual health knowledge and only 8.9 % of girls reported consulting a physician. CONCLUSION: To the best of our knowledge, this is one of the largest studies on menstrual pattern and disorders among Egyptian adolescent girls. Our Findings of the present study are consistent with other studies and reported higher than expected prevalence of menstrual disorders.

Effects of Site Preparation for Pine Forest/Switchgrass Intercropping on Water Quality.

A study was initiated to investigate the sustainability effects of intercropping switchgrass ( L.) in a loblolly pine ( L.) plantation. This forest-based biofuel system could possibly provide biomass from the perennial energy grass while maintaining the economics and environmental benefits of a forest managed for sawtimber. Operations necessary for successful switchgrass establishment and growth, such as site preparation, planting, fertilizing, mowing and baling, may affect hydrology and nutrient runoff. The objectives of this study were (i) to characterize the temporal effects of management on nutrient concentrations and loadings and (ii) to use pretreatment data to predict those treatment effects. The study watersheds (∼25 ha each) in the North Carolina Atlantic Coastal Plain were a pine/switchgrass intercropped site (D1), a midrotation thinned pine site with natural understory (D2), and a switchgrass-only site (D3). Rainfall, drainage, water table elevation, nitrogen (total Kjedahl N, NH-N, and NO-N), and phosphate were monitored for the 2007-2008 pretreatment and the 2009-2012 treatment periods. From 2010 to 2011 in site D1, the average NO-N concentration effects decreased from 0.18 to -0.09 mg L, and loads effects decreased from 0.86 to 0.49 kg ha. During the same period in site D3, the average NO-N concentration effects increased from 0.03 to 0.09 mg L, and loads effects increased from -0.26 to 1.24 kg ha. This study shows the importance of considering water quality effects associated with intensive management operations required for switchgrass establishment or other novel forest-based biofuel systems.

Environmental impact assessement and determination of radiogenic heat production in the North Jabal Maghrabiyah area, Central Eastern Desert, Egypt.

The present study deals essentially with the establishment of the environmental natural radiation levels in the surveyed area. These will provide base-line information that can be used as a reference to detect and determine the amount and extent of any possible future variation or contamination in the natural radioactivity levels that might occur in the study area due to any potential incidents involving release of nuclear radiation or fallout of nuclear fission products that could affect both terrestrial and atmospheric radioactivity. A map of radiogenic heat production (RHP) was built from the airborne spectral gamma-ray data of North Jabal Maghrabiyah area, central Eastern Desert, Egypt. The area of study reflects radiogenic heat production varying from 0.03 to 6.44 µWm-3, averaging a value of 0.99 µWm-3, while their standard deviation reaches 0.61 µWm-3. The maximum values are associated with the acidic rocks in the northeastern, central, southeastern, northeastern and eastern parts of the area of study. Results showed several levels of radiation as follows: (less than 0.39 mSv/y), (from 0.39 to 0.59 mSv/y), (higher than 0.59 and reached to 2.01 mSv/y). The dose rate more than 1 mSv/y is considered the radioactivity hazard level which represented mainly with late to post tectonic Potassic calc-alkaline granitoids, calc-alkaline granitoids, Muꞌtiq group, Dukhan volcanic/subvolcanic group, Atallah felsite, Parts of Quaternary deposits, Hammamat sediments, parts of Tarif, Dakhlah and Duwwi Formations. Thus, the North Jabal Maghrabiyah area can be considered as high RHP, because of the relatively high radioactive concentrations. There are good relationships between the derived RHP and the three radioactive elements, equivalent Uranium (eU), equivalent Thorium (eTh) and Potassium (K), as represented by the binary relationship between any of two elements. The importance of radiogenic heat production is the source of ground thermal energy.

Evaluation of barium tungstate nanocrystals for the sorption of radioactive cobalt and europium from aqueous solutions.

Herein, barium tungstate BaWO4 nanocrystals were chemically prepared and then estimated as inorganic sorbent material to eliminate the radioactive cobalt and europium from the waste stream. The characterization of BaWO4 nanocrystals is completed over several analytical techniques. TEM and SEM images show the formation of sphere-shaped BaWO4 structures in the nanoscale range. Also, XRD and FTIR revealed the successful preparation of BaWO4. Optimum factors affected by the sorption process are determined using batch mode. Sorption equilibrium was achieved after 60 min with the initial concentration of metal ion at 100 mg/L and at optimum pH five for both radionuclides, respectively. The different kinetic models are applied. The obtained data shows that the sorption process followed a pseudo-second order. The sorption capacity for 60Co at pH of 5 and 25 °C is 310.6 mg g-1, and 152+154Eu is 409.9 mg g-1. The thermodynamic studies illustrated that the sorption process was spontaneous and endothermic.

Role of micro-RNAs 21, 124 and other novel biomarkers in distinguishing between group 1 WHO pulmonary hypertension and group 2, 3 WHO pulmonary hypertension.

BACKGROUND: Pulmonary hypertension "PH" is considered a serious cardiovascular disease. World Health Organization divided PH into groups depending on many factors like pathological, hemodynamic, and clinical pictures. Lately, various micro-RNAs "miRNAs" and other novel biomarkers like endoglin and asymmetric dimethylarginine "ADMA" might have a role in diagnosis of PH and may differentiate between pulmonary arterial hypertension "PAH" and non-PAH. The purpose of the study is to show the role of miR-21, miR-124, endoglin and ADMA in the diagnosis of PH and distinguishing between WHO group 1 PH and WHO group 2 and 3 PH and to identify patients who might benefit from non-invasive and inexpensive tools to diagnose PAH. RESULTS: miR-21 was upregulated in group 1 PH, and there was significant difference between group 1 PH as compared with group 2 PH, group 3 PH and control; miR-124 was down-regulated in group 1 PH with highly significant difference between group 1 and group 2 PH and control but no significant difference with group 3 PH, endoglin was elevated in group 1 PH with a significant difference as compared to group 2 PH, group 3 PH and control. ADMA was elevated in group 1 PH as compared to control; however, there was no significant difference between it and group 2, 3 PH. CONCLUSIONS: miR-21, miR-124, endoglin and ADMA are good biomarkers to diagnose PH; however, only miR-21 and endoglin could distinguish group 1 PH from group 2 and 3 PH.

Enhanced biosorption of europium and cesium ions from aqueous solution onto phalaris seed peel as environmental friendly biosorbent: Equilibrium and kinetic studies.

The sorption characteristics of Eu(III) and Cs(I) removal from aqueous solution were estimated using phalaris seeds peel powder (PSP), a novel biosorbent that is economical and low-cost. Batch equilibrium experiments were carried out to investigate the effects of contact time, initial metal concentration, media pH, and interference ions on the sorption of Eu(III) and Cs(I). PSP powder characterization via Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG/DSC), X-ray diffraction (XRD), and scanning electron microscope (SEM) revealed some changes before and after the adsorption process. This indicates that most likely, adsorption has taken place between the metal ions and the adsorbents in the aqueous solution. The obtained results show that Eu(III) has a higher selectivity than Cs(I). The kinetics of the adsorption of Eu3+ and Cs+ have been discussed. It was shown that the second-order kinetic equation could describe the sorption and was found to be the best fitted model (R2 = 0.999) for two metal ions. Langmuir and, Dubinin-Radushkevich (D-R), isotherm were found to best fit (R2 = 0.99) in this study. The separation factor (RL) value of less than 1.0 indicates that the biosorption of both metal ions on PSP is favorable. Thermodynamic parameters, such as ΔHo, ΔGo, and ΔSo, have been calculated by using the thermodynamic equilibrium coefficient obtained at different temperatures. The obtained results indicated the endothermic nature of the sorption process for both metal ions onto PSP. PSP powder has the potential to be used as a low-cost biosorbent for the removal of Eu(III) and Cs(I) from wastewater, according to the findings.

Batch kinetics of 134Cs and 152+154Eu radionuclides onto poly-condensed feldspar and perlite based sorbents.

Sorption of fission products onto polycondensed aluminosilicates (PC-AS(s)) is a relatively recent and gets out the mechanisms by which the formers are trapped. Here, PC feldspar (PC-FD), perlite (PC-PR) and their blend (PC-FDPR) were synthesized by the alkaline activation using Na-/K-silicates at Si-modulus of 1.35. XRD patterns revealed the semi-crystalline natures of sorbents. Na- and K-feldspars were detected in PC-FD while Na-based carbonate crystals were detected in others. Components of the poly(sialate-disiloxo) structure were detected in FT-IR spectra. Thermographs were deconvoluted and the amounts of the sticking and zeolitic water were estimated. Kinetic batches for sorption of 134Cs and 152+154Eu onto the elaborated yields were constructed. Ranking of sorbed amounts (qe) was varied from 134Cs (PC-FDPR>PC-FD>PC-PR) to 152+154Eu (PC-PR>PC-FD>PC-FDPR). Maximum qe was recorded at elevated temperature (323 K) to be 4.28 and 1.45 mg/g for 134Cs/PC-FDPR and 152+154Eu/PC-PR, respectively. Along all batches, chemi-sorption mechanism is common denominator. The effective diffusion coefficients (Di) were in the order of 10-14 m2/s. Both PC-FD and PC-FDPR recorded greater Di values of 134Cs than 152+154Eu. The low values of Ea (kJ/mol) reflected the weak adsorbats-adsorbents interactions. While, the high negative values of ∆S‡ suggested that the studied radionuclides were sorbed in associative reaction mechanism.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study.

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements, and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines, and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms, and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. Ernest Ng reports research sponsorship from Merck. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Developing a core outcome set for future infertility research: an international consensus development study.

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Comparison between traditional and nontraditional add-on devices used with pressurised metered-dose inhalers.

Add-on devices that are attached to metered-dose inhalers (MDIs) were introduced to improve aerosol delivery. The objective of this study was to determine the efficacy of drug delivery from an MDI when attached to different add-on devices at different inhalation volumes. The total emitted dose (TED) of salbutamol was estimated for the MDI alone and the MDI connected to five different add-on devices (Able valved holding chamber, Tips-haler valved holding chamber, Aerochamber plus flow Vu valved holding chamber, Dolphin chamber, and a handmade water bottle spacer), at inhalation flow of 28.3 L·min-1 with flow volume of 1, 2 and 4 L, assuming young child (aged <6 years), old child (>6 years) and adult inhalation volumes, respectively. The TED% ranged between 84.1% and 87.2% at all inhalation volumes from the MDI alone, which was significantly greater than all MDI add-on device combinations (p<0.05). The TED% delivered to MDI sampling apparatus by a homemade water bottle spacer and Dolphin chamber, as non-antistatic add-on devices, ranged between 30.5% and 35.3%. However, washing these non-antistatic add-on devices with a light detergent before use improved their TED to range between 47.6% and 51.2%. Non-antistatic add-on devices had significantly lower TED (p<0.05) than that delivered by most antistatic add-on devices, which ranged from 51.3% to 71.6%. This study suggests that antistatic add-on devices delivered much more aerosol than non-antistatic add-on devices. However, it may be advised to still use a non-antistatic add-on device, for the sake of solving the coordination problem, and wash it with light detergent before use to improve TED.

Synthesis and sorption potential study of Al2O3ZrO2CeO2 composite material for removal of some radionuclides from radioactive waste effluent.

Increasing in the use of various radioactive elements in many applications over the past few decades has accompanied with an increase radioactive waste. Therefore, preparation of Al2O3ZrO2CeO2 nanocomposite material by sol-gel polymeric method is carried out. The nanocomposite material was characterized by some analytical techniques such as Fourier transform infrared (FTIR), Thermograviemtric & differential thermal analysis (TGA & DTA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Separation of 134Cs and 90Sr/90Y as a fission product present in radioactive waste effluents using the prepared nanocomposite was investigated. The result showed that removal of 94%, 44% and 8.5% for 134Cs, 90Sr and 90Y, respectively. The experimental results are fitted with pseudo-second-order kinetic model. Isotherm models of sorption process are calculated and it can be concluded that the Langmuir model more fitted than Freundlich model. The calculated thermodynamic functions exhibited that sorption behavior of 134Cs and 90Sr ions are spontaneous in nature and the positive value of ΔHo value indicates that the sorption is endothermic. The results demonstrated that the % sorption of 134Cs(I) and 90Sr(II) is sharply decreased in the presence of coexisting ions (Na, Mg and Cr) using nanoparticles of Al2O3 ZrO2CeO2.

Sorption behavior of Eu(III) from an aqueous solution onto modified hydroxyapatite: kinetics, modeling and thermodynamics.

Nano-pore hydroxyapatite (HAP) was prepared using physical activation of raw and chemically modified [using Acid; HNO3 (HAPA) or Base; NaOH (HAPB)] bone char (BC) by heating at 900°C for 1 hr to obtain HAP9, HAPA9 and HAPB9, respectively. Investigation the effects of thermal and chemical treatment of prepared nano-hydroxyapatite on elemental analysis, FTIR, scanning electron microscopy, surface area and consequently, the sorption behavior of Eu (III) ions onto the prepared nano-pore hydroxyapatite. Batch adsorption technique was used and the obtained results revealed that the optimum pH = 5.0. The % removal of europium (III) using HAPA9 and HAPB9 reach to 100% within 15 min, while HAP9 after 180 min and the pseudo-second-order was found to be fit to the experimental data. According to Langmuir model, the maximum sorption capacities (qm) were 123.8, 384.9 and 74.2 mg g-1 for HAP9, HAPA9 and HAPB9, respectively. The reaction is spontaneous according to ΔG° value. HCl (0.5 M) was the most efficient desorbing agent for recovery of Eu(III) and regeneration of adsorbents. Finally, nano-pore hydroxyapatite (HAP) was low cost and very effective adsorbent for sorption or recovery of Eu(III) from aqueous solutions and remediation of environmental pollution.

A protocol developing, disseminating and implementing a core outcome set for infertility.

STUDY QUESTIONS: We aim to produce, disseminate and implement a core outcome set for future infertility research. WHAT IS KNOWN ALREADY: Randomized controlled trials (RCTs) evaluating infertility treatments have reported many different outcomes, which are often defined and measured in different ways. Such variation contributes to an inability to compare, contrast and combine results of individual RCTs. The development of a core outcome set will ensure outcomes important to key stakeholders are consistently collected and reported across future infertility research. STUDY DESIGN SIZE DURATION: This is a consensus study using the modified Delphi method. All stakeholders, including healthcare professionals, allied healthcare professionals, researchers and people with lived experience of infertility will be invited to participate. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including people with lived experience of infertility, healthcare professionals, allied healthcare professionals and researchers, has been formed to guide the development of this core outcome set. Potential core outcomes have been identified through a comprehensive literature review of RCTs evaluating treatments for infertility and will be entered into a modified Delphi method. Participants will be asked to score potential core outcomes on a nine-point Likert scale anchored between one (not important) and nine (critical). Repeated reflection and rescoring should promote convergence towards consensus 'core' outcomes. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This project is funded by the Royal Society of New Zealand Catalyst Fund (3712235). BWM reports consultancy fees from Guerbet, Merck, and ObsEva. R.S.L. reports consultancy fees from Abbvie, Bayer, Fractyl and Ogeda and research sponsorship from Ferring. S.B. is the Editor-in-Chief of Human Reproduction Open. The remaining authors declare no competing interests.

Effects of different anesthetic techniques on antidiuretic hormone secretion during laparoscopic cholecystectomy.

BACKGROUND: With the advent of minimally invasive surgery, laparoscopic cholecystectomy has become the standard treatment for symptomatic gallbladder disease. This study aimed to evaluate the effects of using high- versus low-pressure pneumoperitoneum with different anesthetic techniques on hemodynamics and antidiuretic hormone (ADH) secretion. METHODS: For this prospective study, 60 patients scheduled for elective laparoscopic cholecystectomy were randomly recruited. They were classified into four equal groups: group 1 received general anesthesia with low insufflation pressure (7-9 mmHg); group 2 received general anesthesia with high insufflation pressure (13-15 mmHg); group 3 received general anesthesia in addition to epidural analgesia with low insufflation pressure; and group 4 received general anesthesia in addition to epidural analgesia with high insufflation pressure. Routine intraoperative monitoring was done. The study parameters included heart rate per minute, mean blood pressure (mmHg), and ADH levels (via blood samples) before anesthesia, after induction, 30 and 45 min after abdominal insufflation, and finally, 2 h postoperatively. RESULTS: The heart rate showed significant increases after pneumoperitoneum in group 2, as compared with the other three groups. Significant differences in mean blood pressure were observed between the study groups. In groups 1 and 4, mean arterial pressure (MAP) significantly decreased after 15 min, and this decrease persisted until the end of the study. In group 2, MAP significantly increased after 15, 30, 45, and 60 min and after 60 min postoperatively. In group 3, MAP significantly decreased after 30 min, and this decrease persisted 1 h after surgery. There were no significant differences in ADH levels before and after induction of anesthesia among any of the study groups. In groups 1 and 4, no statistically significant changes in ADH levels were observed throughout the study period except a mild increase in ADH levels 30 and 45 min after abdominal insufflation. In group 2, after pneumoperitoneum, there was statistically significant increase in ADH levels from the baseline value of 6.422 +/- 0.551 pmol/l to 7.749 +/- 0.635 pmol/l at 30 min and to 6.457 +/- 0.450 pmol/l at 45 min. In group 3, there was a statistically significant decrease in ADH levels from the baseline value of 6.551 +/- 0.356 pmol/l to 6.125 +/- 0.618 pmol/l at 30 min, to 6.118 +/- 0.491 pmol/l at 45 min, and to 6.169 +/- 0.676 pmol/l at 2 h after abdominal insufflation. CONCLUSION: Pneumoperitoneum can affect several homeostatic systems, leading to hemodynamic and hormonal stress responses. The use of general anesthesia plus epidural analgesia with low insufflation pressure, general anesthesia with low insufflation pressure, or general anesthesia plus epidural analgesia with high insufflation pressure is safe and effective in attenuating these responses.

Laparoscopically assisted balloon vaginoplasty for management of vaginal aplasia.

OBJECTIVE: To report the intra-operative and post-operative results of laparoscopically assisted balloon vaginoplasty, a new technique for management of vaginal aplasia. METHODS: Eight women with vaginal aplasia due to Mullerian agenesis who were referred for apareunia, dyspareunia. All had a poor penetration score and sexual satisfaction score. A Foley's catheter was laparoscopically inserted in the space between the urethra and rectum. Gradual traction and distension were used to create a neovagina. Outcomes measured were intra-operative complications, post-operative complications, length of the neovagina and post-operative complications and sexual satisfaction score in both partners. RESULTS: Mean operative time was 25.5+/-5.5 min. No operative complications were recorded. Pain scores ranged from zero to 30 points at rest and from 30 to 60 points during dressing, traction and distension. Penetration and satisfaction scores increased significantly after the operation. CONCLUSIONS: Balloon vaginoplasty is a simple, safe and satisfactory technique for management of blind vagina.