Publication bias in reproductive research

Publication bias is defined as any tendency on the part of investigators or editors to fail to publish study results on the basis of the direction or strength of the findings. This may lead to overestimation of treatment effects in published work. Inappropriate decisions about patient management may result. We investigated what proportion of abstracts at the European Society of Human Reproduction and Embryology (ESHRE) annual meeting eventually reached full publication, what was the time to publication, and which factors might have affected publication. Among the 2691 abstracts of six ESHRE annual meetings, 151 (5.6%) reporting randomized controlled trials (RCT) were identified. Comprehensive searches of electronic databases and handsearching of the two major journals in the field yielded 79 full publications pertaining to these abstracts. Kaplan-Meier analysis estimated 56% of RCT abstracts to be eventually published in full, the median time to publication being 32.5 months. Positive outcome (i.e. significant results) did not affect the publication rate, and neither did sample size, the subject category, or the native language (English/non-English) of the country of origin. Oral presentations resulted in eventual full publication significantly more frequently (69%) than posters (42%). It is concluded that a considerable publication deficit, but not a publication bias, exists for RCT in reproductive research.     

Morphological changes in mesothelial cells induced by shed menstrual endometrium in vitro are not primarily due to apoptosis or necrosis

In a previous study on the pathogenesis of endometriosis, we observed that constituents of menstrual effluent induce morphological alterations in human mesothelial cells. In this study, we investigated whether these alterations were associated with apoptosis or necrosis or were the result of cellular remodelling. After overnight incubation of confluent monolayers of human omental mesothelial cells (HOMEC) with conditioned media prepared from menstrual effluent shed anterogradely, severe alterations in morphology were observed. Typical polygonal mesothelial cell cultures at confluency acquired elongated spindle morphology, resulting in gaps between the cells. In contrast, mesothelial cells from the control groups receiving culture medium only, retained a normal morphology. Immunofluorescence staining revealed that cytokeratin, vimentin and actin filaments were still present, homogeneously distributed in the cell cytoplasm following changes in morphology. To evaluate whether the morphological alterations were associated with apoptosis and/or necrosis, the cells were stained with the M30 CytoDeath antibody or annexin V with propidium iodide and analysed using flow cytometry. The results showed that only a small percentage (1-7%) of the affected HOMEC were undergoing apoptosis or necrosis. We conclude that the profoundly altered morphology of HOMEC is a result of cellular remodelling and that the role of apoptosis and necrosis is negligible. Soluble paracrine factors released by cells isolated from menstrual effluent shed anterogradely may induce a reorganization of the cytoskeleton. As a result, the underlying basement membrane will be exposed and the mesothelium may no longer prevent implantation of endometrium shed retrogradely into the peritoneum, thus facilitating the development of endometriosis.     

Perceptions of sexuality and sexual health among young people in the Netherlands

Sexual health problems are not uncommon among young people in the Netherlands and finding the proper treatment for such problems is often challenging. More insight regarding young people's perceptions of sexuality and its associated problems is needed to improve both treatment and education. This qualitative study of 22 young people (aged 13 to 25 years) explored perceptions of sexuality and sexual health. The results show that sexuality is narrowly defined by young people, with focus clearly being placed on physical aspects of sexuality, and sexual intercourse in particular. Sexual problems are usually defined as physical or medical problems. The data show that participants had limited knowledge regarding sexual problems associated with sexual functioning. Schools, parents and culture all appear to play a role in perceptions of sexuality and sexual health. In their totality, the findings suggest that knowledge about the complexity of sexuality and sexual health is lacking among young people in the Netherlands. We recommend broader sexual health education programs in schools that include the discussion of multiple aspects of sexuality, including pleasure. We also suggest that parents take a more prominent role in educating their children about sexuality.     

Targeted molecular therapy of the PI3K pathway: therapeutic significance of PI3K subunit targeting in colorectal carcinoma

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K) pathway promotes cancer cell proliferation and survival. The authors determined the pattern of distribution of PI3K pathway components (ie, the p85alpha regulatory subunit, p110alpha catalytic subunit, Akt1, Akt2, and the tumor suppressor PTEN) in human colorectal cancer. In addition, inhibition of in vitro proliferation and in vivo liver metastasis by p85alpha or p110alpha siRNA treatment was analyzed. SUMMARY BACKGROUND DATA: Small interfering RNA (siRNA) molecules suppress expression of target genes and may have therapeutic applications as target-specific therapies for cancer. Therefore, the purpose of this study was 2-fold: 1) to analyze the distribution pattern of PI3K pathway components in human normal colorectal cancers, and 2) to determine whether targeted inhibition of PI3K inhibits colon cancer growth in vitro and suppresses metastatic growth in vivo. METHODS: Immunohistochemical analysis was performed on colorectal adenocarcinomas and adjacent normal mucosa for PI3K pathway components, including p85alpha, p110alpha, Akt1, Akt2, and the tumor suppressor PTEN, which inhibits PI3K. HT29 and KM20 human colon cancer cells were treated with siRNA directed to p85alpha or p110alpha, and cell viability and apoptosis assessed. HT29 cells, transfected with a plasmid containing green fluorescent protein (GFP), were injected into the spleen of athymic nude mice to establish liver metastases; mice were randomized to receive either nontargeting control (NTC), p85alpha or p110alpha siRNA. RESULTS: PI3K pathway components p85alpha and Akt2 were highly expressed in glandular elements of colon cancers, with a correlation between staining intensity and clinical stage; PTEN expression was decreased in the colon cancers of all stages. PI3K-specific siRNA treatment decreased cell viability in vitro and suppressed metastatic tumor growth in vivo. CONCLUSIONS: Selective targeting of PI3K pathway components may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment of selected colorectal cancers.     

Sequenzierung aus einzelnen Epithelzellen

The smallest morphologically defined unit of biological trace evidence is a single cell. In most cases these are exfoliated epithelial cells or cells from secretions. With the aid of a micromanipulator, such as is used for intracytoplasmic sperm injections (ICSI) and self-made pipettes single cells were isolated, or lifted from smear preparations and both hypervariable regions (HV1 and HV2) of mitochondrial DNA (mtDNA) were subsequently amplified and sequenced. In total 175 single epithelial cells from 6 different subjects were examined. Single PCR for the HV1 region was performed for 57 of the single cells and PCR products could be demonstrated in 77% of cases. This procedure was also performed for the HV2 region from 22 single cells with PCR products being demonstrated in 90% of cases. For a further 96 single cells combined amplification of the HV1 and HV2 regions was performed in one PCR reaction and PCR products could be demonstrated in 80% of cases. During all experimental settings no contamination occurred meaning that none of the samples examined yielded any other sequence than the expected one and did not show a mixture of samples. The presented method can be applied to cases in which STR typing and conventional sequencing of mtDNA is limited or impossible. This particularly applies to mixed stains and examinations assessing heteroplasmy in mtDNA.     

The wobbly evidence base of reproductive medicine

In assisted reproduction, there is strong evidence for some things done, but no or only very weak evidence for others. There are several reasons for this. Most assisted reproduction procedures have small signal-to-noise ratios. This means that their treatment effect is sometimes only little better than the spontaneous conception rate, or the conception rate with traditional treatment. Hence, large trials are required. These demand complex multicentre logistics. The latter require substantial funding and funding for reproductive medicine in most countries is notoriously difficult to obtain (as opposed, for example, to oncology research or cardiovascular research). Apart from these funding issues, the creation of embryos specifically for research is only allowed in a limited number of European countries, thus tempting clinicians to skip preclinical studies altogether and go directly for clinical application in their patients, raising an ethical issue. Introducing new treatments into the clinic without proper evidence, however, is perhaps even more of an ethical issue. Subfertile couples are very vulnerable and should not be exploited.In assisted reproduction, we have strong evidence for some things we do, but no or only very weak evidence for others. There are several reasons for this. Most assisted reproduction procedures have small signal-to-noise ratios. Which means that their treatment effect is sometimes only little better than the spontaneous conception rate, or the conception rate with traditional treatment. Hence large trials are required. These demand complex multicentre logistics. The latter require substantial funding and funding for reproductive medicine in most countries is notoriously difficult to obtain (as opposed to, for example, oncology research or cardiovascular research). Apart from these funding issues, the creation of embryos specifically for research is only allowed in a limited number of European countries, thus tempting clinicians to skip preclinical studies altogether and go directly for clinical application in their patients, an ethical issue. Introducing new treatments into the clinic without proper evidence, however, is perhaps even more of an ethical issue. Subfertility couples are very vulnerable, they should not be exploited.VIDEO LINK: http://sms.cam.ac.uk/media/1401622     

Cost-effectiveness of nutritional intervention in elderly subjects after hip fracture. A randomized controlled trial

Summary

Hip fracture patients can benefit from nutritional supplementation during their recovery. Up to now, cost-effectiveness evaluation of nutritional intervention in these patients has not been performed. Costs of nutritional intervention are relatively low as compared with medical costs. Cost-effectiveness evaluation shows that nutritional intervention is likely to be cost-effective.

Introduction

Previous research on the effect of nutritional intervention on clinical outcome in hip fracture patients yielded contradictory results. Cost-effectiveness of nutritional intervention in these patients remains unknown. The aim of this study was to evaluate cost-effectiveness of nutritional intervention in elderly subjects after hip fracture from a societal perspective.

Methods

Open-label, multi-centre randomized controlled trial investigating cost-effectiveness of intensive nutritional intervention comprising regular dietetic counseling and oral nutritional supplementation for 3 months postoperatively. Patients allocated to the control group received care as usual. Costs, weight and quality of life were measured at baseline and at 3 and 6 months postoperatively. Incremental cost-effectiveness ratios (ICERs) were calculated for weight at 3 months and quality adjusted life years (QALYs) at 6 months postoperatively.

Results

Of 152 patients enrolled, 73 were randomized to the intervention group and 79 to the control group. Mean costs of the nutritional intervention was 613 Euro. Total costs and subcategories of costs were not significantly different between both groups. Based on bootstrapping of ICERs, the nutritional intervention was likely to be cost-effective for weight as outcome over the 3-month intervention period, regardless of nutritional status at baseline. With QALYs as outcome, the probability for the nutritional intervention being cost-effective was relatively low, except in subjects aged below 75 years.

Conclusion

Intensive nutritional intervention in elderly hip fracture patients is likely to be cost-effective for weight but not for QALYs. Future cost-effectiveness studies should incorporate outcome measures appropriate for elderly patients, such as functional limitations and other relevant outcome parameters for elderly.