scholarly journals Individualized ovarian stimulation in IVF/ICSI treatment: it is time to stop using high FSH doses in predicted low responders

2019 ◽  
Vol 35 (9) ◽  
pp. 1954-1963 ◽  
Author(s):  
Jori A Leijdekkers ◽  
Helen L Torrance ◽  
Nienke E Schouten ◽  
Theodora C van Tilborg ◽  
Simone C Oudshoorn ◽  
...  
Keyword(s):  
Live Birth ◽  
Causal Relation ◽  
Standard Dose ◽  
Risk Difference ◽  
Cross Sectional ◽  
Low Responders ◽  
Intermediate Outcomes ◽  
Starting Dose ◽  
Beneficial Impact ◽  
Dosing Strategy

ABSTRACT In IVF/ICSI treatment, the FSH starting dose is often increased in predicted low responders from the belief that it improves the chance of having a baby by maximizing the number of retrieved oocytes. This intervention has been evaluated in several randomized controlled trials, and despite a slight increase in the number of oocytes—on average one to two more oocytes in the high versus standard dose group—no beneficial impact on the probability of a live birth has been demonstrated (risk difference, −0.02; 95% CI, −0.11 to 0.06). Still, many clinicians and researchers maintain a highly ingrained belief in ‘the more oocytes, the better’. This is mainly based on cross-sectional studies, where the positive correlation between the number of retrieved oocytes and the probability of a live birth is interpreted as a direct causal relation. If the latter would be present, indeed, maximizing the oocyte number would benefit our patients. The current paper argues that the use of high FSH doses may not actually improve the probability of a live birth for predicted low responders undergoing IVF/ICSI treatment and exemplifies the flaws of directly using cross-sectional data to guide FSH dosing in clinical practice. Also, difficulties in the de-implementation of the increased FSH dosing strategy are discussed, which include the prioritization of intermediate outcomes (such as cycle cancellations) and the potential biases in the interpretation of study findings (such as confirmation or rescue bias).

scholarly journals Efficacy and Tolerability after Unusually Low Doses of Dasatinib in Chronic Myeloid Leukemia Patients Intolerant to Standard-Dose Dasatinib Therapy

2010 ◽  
Vol 4 ◽  
pp. CMO.S6413 ◽  
Author(s):  
Mariana Serpa ◽  
Sabri S. Sanabani ◽  
Israel Bendit ◽  
Fernanda Seguro ◽  
Flávia Xavier ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Chronic Phase ◽  
Patient Treatment ◽  
Hematological Toxicity ◽  
Drug Discontinuation ◽  
Once Daily ◽  
Starting Dose

We report our experience in 4 patients with chronic myeloid leukemia (CML) who had discontinued imatinib as a result of adverse events and had switched to dasatinib. The chronic phase ( n 2) and accelerated phase ( n 2) CML patients received dasatinib at starting dose of 100 and 140 mg once daily, respectively. Reappearance of hematological toxicity was observed in 3 patients and pancreatitis in one patient. Treatment was given at a lower dose and patients were followed. The median follow-up was 13 months and the median dose of dasatinib until achievement of complete cytogenetic remission (CCyR) was 60 mg daily (range = 20 to 120 mg). All four patients had achieved CCyR at a median of 4 months (range = 3 to 5 months) and among them, three had also achieved major molecular remission. We conclude that low-dose dasatinib therapy in intolerant patients appears safe and efficacious and may be tried before drug discontinuation.

scholarly journals Long-Term Testosterone Administration Increases Visceral Fat in Female to Male Transsexuals1

1997 ◽  
Vol 82 (7) ◽  
pp. 2044-2047 ◽  
Author(s):  
Jolanda M. H. Elbers ◽  
Henk Asscheman ◽  
Jacob C. Seidell ◽  
Jos A. J. Megens ◽  
Louis J. G. Gooren
Keyword(s):  
Confidence Interval ◽  
Visceral Fat ◽  
Causal Relation ◽  
Magnetic Resonance Images ◽  
Visceral Fat Area ◽  
Cross Sectional ◽  
Fat Depots ◽  
Testosterone Administration ◽  
The Mean

The amount of intraabdominal (visceral) fat is an important determinant of disturbances in lipid and glucose metabolism. Cross-sectional studies in women have found associations between high androgen levels and visceral fat accumulation. The causal relation between these phenomena is unknown. We, therefore, studied prospectively the effect of testosterone administration on body fat distribution in 10 young, nonobese, female to male transsexuals undergoing sex reassignment. Before, after 1 yr, and after 3 yr of testosterone administration, magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify both sc and visceral fat depots. After 1 yr of testosterone administration, sc fat depots at all levels showed significant reductions compared to baseline measurements. The mean visceral fat area did not change significantly, but subjects who gained weight in the first year after testosterone administration showed an increase in visceral fat. After 3 yr of testosterone administration, sc fat depots were no longer significantly lower compared to pretreatment measurements, but the mean visceral fat depot had increased significantly by 13 cm2 (95% confidence interval, 4–22 cm2), a relative increase of 47% (95% confidence interval, 8–91%) from baseline. The increase in visceral fat was most pronounced in those subjects who had gained weight. We conclude that long term testosterone administration in young, nonobese, female subjects increases the amount of visceral fat. In addition, an increase in weight in this hyperandrogenic state leads to a preferential storage of fat in the visceral depot.

The effectiveness of leadership: meta-analysis of trial, cross-sectional, and before after studies

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
V Restivo ◽  
M Gaeta ◽  
A Odone ◽  
C Trucchi ◽  
A Battaglini ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Evidence Based Practice ◽  
Meta Analysis ◽  
Healthcare Setting ◽  
Risk Difference ◽  
Audit And Feedback ◽  
Evidence Based ◽  
Cross Sectional ◽  
Cross Sectional Studies ◽  
Private Setting

Abstract Background The clinical and surgical procedures are often based on scientifical evidence but 30-40% of patients do not receive treatment according to evidence based medicine. The main aim of this review and meta-analysis is to assess the effectiveness of leadership in healthcare setting. Methods It was conducted a literature research on MEDLINE, Pubmed and Scopus with publication year between 2015 and 2019. The inclusion criteria were studies involving healthcare workers that evaluated effectiveness of opinion leaders in improving behaviour of healthcare workers, according to clinical or patient related outcomes. The quality of studies were assesed with the NHLBI for before after studies and the NOS for other study designs. The effect of leadership was assessed as risk difference for all studies with the exception of cross sectional studies. For the last it was evaluated correlation between leadership level and outcome measurment. Results A total of 3,155 articles were screened and 284 were fully assessed including 22 of them in the final database: 1 randomized trial, 9 cross sectional and 12 before after studies. For the cross-sectional studies there was a correlation of 0.22 (95% CI 0.15-0.28) between leadership level and outcome measurment. In the metaregression analysis the only factor that increased the correlation was private setting (meta regression coefficent =0.52, p = 0.022). The pooled efficacy was 24% (95% CI 10%-17%) for before after studies. Furthermore, a higher effectiveness was revealed in studies conducted on multi professional (24%) than single professional (9%) healthcare workers. Conclusions According to results, the guidelines adherence and task performance increased in a setting with leadership implementation. The leadership effectiveness appears comparable to other strategies as audit and feedback used to implement evidence-based practice in worldwide healthcare. Key messages The translation of evidence into clinical practice is often difficult but this study suggests that leaderhip can had higher effectiveness in multiprofessional healthcare workers and private setting. The effectiveness of leadership in this review suggests that it can be of help in order to make aware healthcare professionals about effectiveness of comply with evidence-based practice.

scholarly journals Correlation of Patient Weight and Cross-Sectional Dimensions with Subjective Image Quality at Standard Dose Abdominal CT

2003 ◽  
Vol 4 (4) ◽  
pp. 234 ◽  
Author(s):  
Mannudeep K. Kalra ◽  
Michael M. Maher ◽  
Srinivasa R. Prasad ◽  
M. Sikandar Hayat ◽  
Michael A. Blake ◽  
...  
Keyword(s):  
Image Quality ◽  
Standard Dose ◽  
Abdominal Ct ◽  
Cross Sectional ◽  
Subjective Image Quality ◽  
Patient Weight

The Janus-Face of Digitalization: The Relation Between Internet Use and Civic Engagement Reconsidered

2019 ◽  
pp. 089443931986196
Author(s):  
Julian Erhardt ◽  
Markus Freitag
Keyword(s):  
Civic Engagement ◽  
Social Engagement ◽  
Internet Use ◽  
Causal Relation ◽  
Causal Effect ◽  
Negative Effects ◽  
Cross Sectional ◽  
Internet Studies ◽  
The Social ◽  
Robust Evidence

Research on the influence of digital technology on civic engagement debates whether Internet use leads to the decline of civic engagement or enables new social contacts and exchanges. We argue that whether Internet use has positive or negative effects on our civic engagement depends on how we use the Internet: Social Internet use and Internet use for information strengthen civic engagement, while private Internet use and Internet use for entertainment erode civic engagement. Data from the Longitudinal Internet Studies for the Social sciences (LISS) Panel and the Swiss Household Panel (SHP) allow us to employ differentiated measures of Internet use. In particular, their panel structure helps diminish the endogeneity problems of cross-sectional studies. By employing an autoregressive cross-lagged panel design, we are able to disentangle the relation between Internet use and associational participation and estimate the causal effect between the two variables in both directions. Analyzing associational participation as a pivotal pillar of the civil society, we show that social Internet use for information, in particular exchanging e-mails, but also being active on social network sites in the SHP, increases the likelihood of becoming or remaining active in an organization. At the same time, we fail to find consistent and robust evidence for the negative effects of Internet use. However, the causal relation also works the other way round: Associational participation was shown to increase the time respondents spend with writing e-mails, leading to a virtuous circle, whereby online and off-line forms of social engagement complement and enhance each other.

A single-arm, open-label, multicenter phase I/II study of the combination of panobinostat (pan) and carfilzomib (cfz) in patients (pts) with relapsed/refractory multiple myeloma (RR MM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8115-TPS8115
Author(s):  
Jesus G. Berdeja ◽  
Joseph Mace ◽  
Ruth E. Lamar ◽  
Victor Gian ◽  
Patrick Brian Murphy ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Histone Deacetylase Inhibitors ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Current Status ◽  
Open Label ◽  
Starting Dose

TPS8115 Background: Despite novel therapies, MM remains an incurable disease. Changes in histone modification are commonly found in human cancers including MM. Preclinical studies demonstrate synergistic anti-MM activity with histone deacetylase inhibitors (HDACi) and proteasome inhibitors (PI) through the dual inhibition of the proteasome and aggresome pathways. Pan is an oral pan-HDACi which has shown synergy with bortezomib in clinical studies. Cfz is a 2nd generation PI which has shown marked anti-MM activity with an improved safety profile. In this trial we evaluate the safety and efficacy of the combination of pan and cfz in pts with RR MM. Methods: This multi-center US study plans to enroll up to 52 adults with RR MM. The phase I study will determine the MTD of the combination of cfz and pan and follow a standard dose escalation design. Pan will be administered orally three times weekly during weeks 1 and 3 of each 28-day cycle (Days 1, 3, 5, 15, 17, 19) at a starting dose of 20 mg. Cfz will be administered intravenously on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Cfz starting dose will be 20mg on days 1,2 of cycle 1 with escalation to the corresponding dose level beginning at 27 mg , if well tolerated. Dose modifications will not be permitted during cycle 1 unless a pt experiences a DLT. A maximum of four dose levels will be evaluated. Approximately 24 pts will be enrolled during the phase I portion to establish the MTD. In the phase II portion of this study, pts with RR MM will receive treatment with the optimal dose of pan and cfz established during phase I. Pts will be assessed for response to treatment after each cycle (4 weeks). Pts with objective response or stable disease will continue treatment until disease progression or unacceptable toxicity occurs. The primary endpoint is to establish the optimal doses of cfz and pan that can be administered to pts with RR MM (phase I) and to evaluate the overall response rate (phase II). Secondary endpoints include time-to-progression, progression-free survival, overall survival and safety. Approximately 25 pts are planned for the phase II portion. Current status: As of 1/27/12 3 patients have been enrolled.

The Educative Effects of Extreme Television Media

2016 ◽  
Vol 45 (1) ◽  
pp. 3-32 ◽  
Author(s):  
J. Benjamin Taylor
Keyword(s):  
Political Knowledge ◽  
Control Groups ◽  
Cross Sectional ◽  
Citizen Competence ◽  
Media Environment ◽  
Lab Experiments ◽  
Beneficial Impact ◽  
Survey Finding ◽  
Television Media ◽  
Extreme Media

This article investigates whether exposure to extreme television media informs citizens about politics. Using lab experiments with both student and non-student samples, I find that extreme media produce higher levels of political knowledge and that they also produce higher levels of negative affect among viewers compared with control groups. I also show that extreme media are at least as informative as traditional news. This research adds to the growing literature on media effects in a polarized media environment, showing that extreme television media can have a beneficial impact on at least one important area of U.S. politics: citizen competence. To account for external validity and popular conceptions on extreme media’s non-informative nature, I use cross-sectional data from the 2008 National Annenberg Election Survey finding that extreme television viewership correlates with greater political knowledge, while controlling for other known predictors.

scholarly journals Synthesis and Physicochemical Properties of Polyamideimide Membranes Containing ZIF-8 and CMS Particles for Potential Gas Separation Applications

2021 ◽  
Author(s):  
Sasikumar Balaguru ◽  
Yohannan Subin Sabilon ◽  
Arthanareeswaran Gangasalam
Keyword(s):  
Physicochemical Properties ◽  
Gas Separation ◽  
Molecular Sieves ◽  
Metal Cluster ◽  
Precipitation Reaction ◽  
Zeolitic Imidazolate Frameworks ◽  
Cross Sectional ◽  
Phase Inversion Technique ◽  
Beneficial Impact

Abstract The present study involves the fabrication and characterization of Polyamideimide (PAI) membrane holding ZIF-8 and CMS particles for potential gas separation applications. Zeolitic imidazolate frameworks-8 (ZIF-8) nanocrystals were prepared by a precipitation reaction with Zinc metal cluster and 2-methylimidazole, whereas the carbon molecular sieves (CMS) were synthesized by pyrolysis of polyamideimide (PAI) polymer. ZIF-8 and CMS particles were characterized comprehensively for the functional group, crystallinity, and morphological analyses. The successful formation of ZIF-8 nanocrystals was evident from the rhombic octahedron shape, and EDX confirms the presence of Zn metal cluster and methylimidazole linker. The ZIF-8 and CMS nanoparticles incorporated PAI membranes were prepared using phase inversion technique with varying loading wt.% of 1, 2, and 3%. PAI/ZIF-8 and PAI/CMS membranes cross-sectional morphology confirmed that synthesized nanoparticles were well embedded through the PAI membrane. The PAI/ZIF-8 (3 %) membrane, thin dense skin top layer, and well-defined honeycomb porous substructure were observed. Furthermore, the ZIF-8 and CMS particles incorporation have a beneficial impact on the mechanical properties of PAI at the low loading of nanoparticles. Thus, the inclusion of ZIF-8 and CMS particles in the PAI matrix positively altered the physicochemical properties of the resulting hybrid membranes, which could help them achieve remarkable gas permeance and selectivity.

scholarly journals Reduced live birth rates in frozen versus fresh single cleavage stage embryo transfer cycles: A cross-sectional study

2020 ◽  
Author(s):  
Wan Tinn Teh ◽  
Alex Polyakov ◽  
Claire Garrett ◽  
David Edgar ◽  
Peter Adrian Walton Rogers
Keyword(s):  
Multivariate Analysis ◽  
Embryo Transfer ◽  
Live Birth ◽  
Frozen Embryo Transfer ◽  
Confounding Factors ◽  
Cleavage Stage ◽  
Cross Sectional ◽  
Live Birth Rates ◽  
Cleavage Stage Embryo ◽  
Stage Embryo

Background: Studies have suggested that embryo-endometrial developmental asynchrony caused by slow-growing embryos can be corrected by freezing the embryo and transferring it back in a subsequent cycle. Therefore, we hypothesized that live birth rates (LBR) would be higher in frozen embryo transfer (FET) compared with fresh embryo transfers. Objective: To compare LBR between fresh and FET cycles. Materials and Methods: A cross-sectional analysis of 10,744 single autologous embryo transfer cycles that used a single cleavage-stage embryo was performed. Multivariate analysis was performed to compare LBR between FET and fresh cycles, after correcting for various confounding factors. Sub-analysis was also performed in cycles using slow embryos. Results: Both LBR (19.13% vs 14.13%) and clinical pregnancy (22.48% vs 16.25%) rates (CPR) were higher in the fresh cycle group (p < 0.00). Multivariate analysis for confounding factors also confirmed that women receiving a frozen-thawed embryo had a significantly lower LBR rate compared to those receiving a fresh embryo (OR 0.76, 95% CI 0.68-0.86, p < 0.00). In the sub-analysis of 1,154 cycles using slow embryos, there was no statistical difference in LBR (6.40% vs 6.26%, p = 0.92) or CPR (8.10% vs 7.22%, p = 0.58) between the two groups. Conclusion: This study shows a lower LBR in FET cycles when compared to fresh cycles. Our results suggest that any potential gains in LBR due to improved embryo-endometrial synchrony following FET are lost, presumably due to freeze-thaw process-related embryo damage. Key words: Fresh, Frozen embryo transfer, Live birth, Embryo, Transfer.

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