Predicting health-related quality of life in dialysis patients: Factors related to negative outcome expectancies and social support

ObjectivesDialysis patients report a low health-related quality of life (HRQOL) due to high disease burden and far-reaching consequences of dialysis treatment. This study examined several cognitive-behavioral and social factors, with a focus on negative outcome expectancies, that might be relevant for HRQOL in end-stage kidney disease (ESKD) patients treated with dialysis.MethodsPatients treated with hemodialysis or peritoneal dialysis were recruited from Dutch hospitals and dialysis centers. Patients completed self-report questionnaires at baseline (n = 175) and six months follow-up (n = 130). Multiple regression analyses were performed.ResultsHigher scores on factors related to negative outcome expectancies at baseline, especially helplessness and worrying, and less perceived social support were significantly related to worse HRQOL six months later. When controlling for baseline HRQOL, besides sex and comorbidity, helplessness remained significantly predictive of worse HRQOL six months later, indicating that helplessness is associated with changes in HRQOL over time.ConclusionsNegative outcome expectancies and social support are relevant markers for HRQOL and/or changes in HRQOL over time.Practice implicationsNegative outcome expectancies could be prevented or diminished by enhanced treatment information, an improved patient-clinician relationship, and interventions that promote adaptive and realistic expectations. Additionally, increasing supportive social relationships could be a relevant treatment focus.     

Effect of BH4 on blood phenylalanine and tyrosine variations in patients with phenylketonuria

BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.     

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.     

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.     

Intrauterine insemination: simultaneous with or 36 h after HCG? A randomized clinical trial

Research questionDoes intrauterine insemination (IUI) carried out simultaneously with HCG triggering (‘simultaneous IUI’) increase the ongoing pregnancy rate compared with IUI 32–36 h after HCG triggering (‘regular IUI’)?Study designAn open-label randomized clinical trial was conducted in seven Dutch fertility clinics. One hundred and sixty-six couples were randomized to receive simultaneous IUI and 208 couples to receive regular IUI. Treatment was allocated using a computer-based randomization algorithm using sealed opaque envelopes. Data were analysed according to the intention-to-treat principle. Couples with unexplained or mild-to-moderate male factor subfertility were eligible. Exclusion criteria were female age 42 years or older, female body mass index 35 kg/m² or over, double-sided tubal pathology or severe male factor subfertility.Mild ovarian stimulation was carried out by subcutaneous FSH self-administration. ‘Simultaneous IUI’ was carried out at the point of HCG triggering for ovulation. ‘Regular IUI’ was carried out 32–36 h after HCG triggering.ResultsThe cumulative ongoing pregnancy rate after a maximum of four cycles was 26.2% for simultaneous IUI (43 ongoing pregnancies) and 33.7% for regular IUI (70 ongoing pregnancies) (RR 0.78 95% CI 0.57 to 1.07). Ongoing pregnancy rates per cycle in the simultaneous IUI group were 6.8%, 10.5%, 9.5% and 7.4% for the first, second, third and fourth IUI cycle. In the regular IUI group, ongoing pregnancy rates were 8.3%, 16.4%, 13.5% and 9.0% for the first, second, third and fourth IUI cycle.ConclusionsThis multicentre randomized controlled trial did not demonstrate that IUI carried out at the point of HCG triggering increases pregnancy rates compared with IUI carried out around the time of ovulation.     

Decreased human semen quality and organochlorine compounds in blood

BACKGROUND: Various studies have been performed in which potential effects of xenoestrogens on fertility or sperm parameters were investigated by comparing groups of subjects exposed to different levels of these chemicals. METHODS: In our study we used an alternative approach, as we selected one group of men with very poor semen quality and another group with normal semen quality and determined the blood organochlorine contents in order to determine whether a difference in these levels could be established. Organochlorine compounds, including polychlorinated biphenyls (PCB) and PCB metabolites, were detected using gas chromatography. The concentrations were compared between both groups, and related to semen parameters. RESULTS: A comparison of both groups did not reveal significant differences in organochlorine levels. Linear relationships were found when PCB and metabolite concentrations were related to the age of the volunteers. Focusing on the subgroup of men with normal semen quality showed that sperm count and sperm progressive motility were inversely related to the concentrations of PCB metabolites within this group. CONCLUSIONS: The finding of a significantly decreased sperm count in relation to an elevated PCB metabolite level within the subgroup of men with normal semen quality is important. This is the first time that a correlation between exposure to environmental pollutants with endocrine-disrupting capacity and human sperm quality has been observed.     

Becoming an eCoach: Training therapists in online cognitive-behavioral therapy for chronic pain

Objective

Online cognitive-behavioral therapy (iCBT) is effective in supporting patients’ self-management. Since iCBT differs from face-to-face CBT on several levels, proper training of therapists is essential. This paper describes the development and evaluation of a therapist training based on theoretical domains that are known to influence implementation behavior, for an iCBT for chronic pain.

The asthma knowledge and perceptions of older Australian adults: Implications for social marketing campaigns

Objective

The purpose of this research is to gain an understanding of the asthma perceptions of older adults and identify gaps in their asthma knowledge.

Methods

In regional New South Wales, Australia, a stratified, random sample of 4066 adults, aged 55 years and over, both with and without an asthma diagnosis, completed a survey based on the Health Belief Model about asthma knowledge and perceptions.

Results

Almost half of the sample had experienced symptoms of breathlessness in the past four weeks. Breathlessness was a predictor of lower health ratings and poorer mood. Older adults reported low susceptibility to developing asthma. The sample demonstrated poor knowledge of key asthma symptoms including shortness of breath, tightness in the chest and a cough at night.

Conclusion

There is a general lack of asthma awareness in this age group. This could result in not seeking medical help, and thus a reduced quality of life.

Practical Implications

Older adults should be made aware of key symptoms and the prevalence of asthma in the older adult population, and be empowered to take control of their respiratory health. Audience segmentation for an intervention should be based on recent experience of breathlessness and asthma diagnosis.     

Novel Mutations Including Deletions of the Entire OFD1 Gene in 30 Families with Type 1 Orofaciodigital Syndrome: A Study of the Extensive Clinical Variability

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability.     

Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers

BACKGROUND: To reduce the twin pregnancy rate, elective single embryo transfer (eSET) is increasingly implemented. Improvement of the results obtained with eSET can be achieved by better selection of the most viable embryo. This study investigated the predictive value of early cleavage (EC) as an additional parameter for selecting the embryo with the highest implantation potential by using data from SET's. METHODS: Data from 165 SET's were retrospectively evaluated. Cleavage to the 2-cell stage was determined 23-26 h after injection or 25-28 h after insemination. Selection of the embryo to be transferred was based on cell morphology and cell number on the day of transfer, not on the EC status. Additional information on the predictive value of EC on developmental potential was obtained by analysing 253 transfers with two embryos (double embryo transfer, DET) and blastocyst formation of 1160 surplus embryos. Logistic regression was used to determine the predictors of pregnancy or blastocyst development. RESULTS: A significantly higher pregnancy rate was observed after transfer of single EC embryos compared to single non-EC embryos (46 versus 18%). This result was confirmed by the significantly higher pregnancy rate after DET with two EC embryos as compared to DET with two non-EC embryos (45 versus 25%) and the blastocyst formation of EC embryos compared to non-EC embryos (66 versus 40%). Logistic regression showed that EC is an independent predictor for both pregnancy and blastocyst development in addition to cell morphology and cell number. CONCLUSIONS: In order to improve the selection of the embryo with the highest implantation potential, selection for transfer should not be based on cell number and morphology on the day of transfer alone, but also on early cleavage status.