During kidney transplantation, ischemia-reperfusion injury (IRI) induces oxidative stress. Short-term preoperative 30% dietary restriction (DR) and 3-day fasting protect against renal IRI. We ...investigated the contribution of macronutrients to this protection on both phenotypical and transcriptional levels. Male C57BL/6 mice were fed control food ad libitum, underwent two weeks of 30%DR, 3-day fasting, or received a protein-, carbohydrate- or fat-free diet for various periods of time. After completion of each diet, renal gene expression was investigated using microarrays. After induction of renal IRI by clamping the renal pedicles, animals were monitored seven days postoperatively for signs of IRI. In addition to 3-day fasting and two weeks 30%DR, three days of a protein-free diet protected against renal IRI as well, whereas the other diets did not. Gene expression patterns significantly overlapped between all diets except the fat-free diet. Detailed meta-analysis showed involvement of nuclear receptor signaling via transcription factors, including FOXO3, HNF4A and HMGA1. In conclusion, three days of a protein-free diet is sufficient to induce protection against renal IRI similar to 3-day fasting and two weeks of 30%DR. The elucidated network of common protective pathways and transcription factors further improves our mechanistic insight into the increased stress resistance induced by short-term DR.
Background
Treating elderly colorectal cancer patients can be challenging. It is very important to carefully weigh the risks and benefits of potential treatments in individual patients. This ...treatment decision making can be guided by geriatric consultation. Our aim was to assess the effect of a geriatric evaluation on treatment decisions for older patients with colorectal cancer.
Methods
Colorectal cancer patients who were referred for a geriatric consultation between 2013 and 2015 in three Dutch teaching hospitals were included in a prospective database. The outcome of geriatric assessment, non-oncological interventions and geriatricians’ treatment recommendations were evaluated.
Results
The total number of included referrals was 168. The median age was 81 years (range 60–94). Most patients (71%) had colon cancer and 49% had tumour stage III disease. The reason for geriatric consultation was uncertainty regarding the optimal oncologic treatment in 139 patients (83%). Overall 93% of patients suffered from geriatric impairments; non-oncological interventions that followed after geriatric consultation was mostly aimed at malnutrition. The geriatrician recommended the ‘more intensive treatment’ option in 69% and the ‘less intensive treatment’ option in 31% of which 63% ‘supportive care only’.
Conclusion
Geriatric consultation can be useful in treatment decision making in elderly patients with colorectal cancer. It may lead to changes in the treatment plan for individual cases and may result in an additional optimisation of patient’s health status prior to treatment.
Can predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol?
Common prognostic factors for high and low ...ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH.
Predictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles.
A retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial.
Infertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis.
In the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were prognostic for high ovarian response, and serum estradiol at stimulation Day 1 was associated with low ovarian response. The area under the receiver operating characteristic (ROC) curve (AUC) for the model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82 and 0.73; positive and negative predictive values were 0.40 and 0.95, respectively. The AUC for the model for a low ovarian response was 0.80. Sensitivity and specificity were 0.77 and 0.73, respectively; positive and negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of patients were high ovarian responders and 16.1% were low ovarian responders. The slope of the calibration line was 0.81 and 1.35 for high and low ovarian responses, respectively, both not statistically different from 1.0. In summary, common prognostic factors for high and low ovarian responses were female age, AFC and basal serum FSH and LH. Simple multivariable models are presented that are able to predict both a too low or too high ovarian response in patients treated with a GnRH antagonist protocol and daily rFSH.
Anti-Müllerian hormone was not included in the prediction modelling.
The findings will help with the identification of patients at risk of a too high or too low ovarian response and individualization of COS treatment.
Financial support for this study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and B.M.J.L.M. was an employee of MSD at the time of development of this manuscript.
NCT 00696800 and NCT00778999.
Previous research has found a genetic component of human reproduction and childlessness. Others have argued that the heritability of reproduction is counterintuitive due to a frequent ...misinterpretation that additive genetic variance in reproductive fitness should be close to zero. Yet it is plausible that different genetic loci operate in male and female fertility in the form of sexual dimorphism and that these genes are passed on to the next generation. This study examines the extent to which genetic factors influence childlessness and provides an empirical test of genetic sexual dimorphism. Data from the Swedish Twin Register (N=9942) is used to estimate a classical twin model, a genomic-relatedness-matrix restricted maximum likelihood (GREML) model on twins and estimates polygenic scores of age at first birth on childlessness. Results show that the variation in individual differences in childlessness is explained by genetic differences for 47% in the twin model and 59% for women and 56% for men using the GREML model. Using a polygenic score (PGS) of age at first birth (AFB), the odds of remaining childless are around 1.25 higher for individuals with 1 SD higher score on the AFB PGS, but only for women. We find that different sets of genes influence childlessness in men and in women. These findings provide insight into why people remain childless and give evidence of genetic sexual dimorphism.
Typing techniques are laboratory methods used in outbreak management to investigate the degree to which microbes found within an outbreak are related. Knowledge about relational patterns between ...microbes benefits outbreak management, but inevitably also tells us something about the relational patterns of the people hosting them. Since the technique is often used without explicit consent of all individuals involved, this may raise ethical questions. The aim of this study was to unravel the complex ethical deliberation of professionals over the use of such techniques. We organised group discussions (𝑛 = 3) with Dutch outbreak managers (𝑛 = 23). The topic list was based on previously identified ethical issues and discussions were analysed for recurrent themes. We found that outbreak managers first and foremost reflect on the balance of individual harm with public health benefit. This key question was approached by way of discussing four more specific ethical themes: (1) justification of governmental intervention, (2) responsibility to prevent infections, (3) scientific uncertainty and (4) legal consequences. The themes found in this study, rephrased into accessible questions, represent the shared ethical understanding of professionals and can help to articulate the ethical dimensions of using molecular science in response to infectious disease outbreaks.
Fishermen, scientists, national policy makers, and staff of environmental NGOs (ENGOs) hold different perceptions about temporal patterns in fish stocks. Perception differences are problematic in ...multi-stakeholder settings, because they elicit controversies and unbalanced disputes. These hinder effective participation, a prerequisite for ‘good governance’ and effective management of sustainable fisheries. This study shows that perceptions of change (‘does the stock increase or decrease?’) and of current status of a fish stock (‘is it doing well or not?’) are influenced by the capturing and processing of information, rather than by interests alone. We focused on the Dutch North Sea fishery on plaice and sole and examined (1) availability and accessibility of information on temporal patterns of these stocks and (2) perception differences between all parties. A first explanation for these differences is the use of different parameters as a measure for stock size. Fishermen focus on catch rates or catch-per-unit-effort (relative stock size), whereas scientists, policy makers, and ENGO-staff mainly use scientific assessments of spawning stock biomass (absolute stock size). Between-group perception differences are further explained by spatial aggregation levels of information, lengths of time series evaluated, and by modes of comparison to qualify the current status of fish stocks. Awareness of information differences and the development of shared information use and processing may release some of the tensions in multi-stakeholder settings debating fisheries management. However, comprehension problems amongst all parties on how spawning stock biomass is reconstructed and how it relates to catch rates in the fishery may pose an enduring barrier.
Objective: To assess barriers and facilitators to implementation of an occupational health guideline aimed at preventing weight gain. Methods: Barriers and facilitators to implementation were ...assessed among 14 occupational physicians (OPs) and employers and analyzed following a systematic approach using Atlas.ti. Results: Barriers and facilitators mentioned by OPs and employers were related to the sociopolitical context, organization, OP, and guideline. Recommendations include the formation of a linkage group, collaboration with other experts, formation of peer support groups, and communicating benefits of investments, expectations, and ethical considerations. Results of this study recommend incorporating these barriers and facilitators in the guideline, including strategies about how to overcome barriers and stimulate facilitators. Conclusions: The identified barriers and facilitators can be used to increase the chance of successful implementation of the final guideline into occupational health practices throughout the Netherlands.
•Facilitators and barriers for implementing PROMs in clinical practice were identified.•Facilitators were the presence of coordinators and motivation of involved professionals.•Other reported ...facilitator was the integration of PROMs in the EHR.•Commonly reported barriers were time constraints, IT-issues, language barriers in patients.•These results can guide the implementation of PROMs in healthcare institutions.
Objectives The aim of this study was to explore the perspectives of healthcare providers and researchers in a large academic hospital on facilitators and barriers for implementing patient-reported outcome measures (PROMs) in clinical care.
Methods A customized web-based questionnaire was developed and disseminated to healthcare providers and researchers across multiple medical departments involved in a value-based health care initiative in the hospital. Questionnaire statements were rated using a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. In addition, 8 open-ended questions were included allowing respondents to mention additional facilitators and barriers for implementing PROMs. Descriptive statistics were used to summarize the results.
Results In total, 61 participants from both surgical and non-surgical departments completed the survey. Most respondents (51%) were medical specialists and the median employment duration was 14 years. Frequently reported facilitators were the presence of a PROM coordinator in the (outpatient) clinic (85%), the integration of PROMs in the electronic health record (81%), and the intrinsic motivation of members involved in the implementation (N=9 open responses). Commonly reported barriers were language barriers (76%), IT issues (N=17 open responses), and time constraints (N=14 open responses).
Conclusions For the successful implementation of PROMs in clinical practice, it is imperative that healthcare organizations consider supporting motivated healthcare professionals, involving PROMs coordinators, and investing in an adequate IT infrastructure, and removal of language barriers.
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