Prediction of the Levodopa Challenge Test in Parkinson's Disease Using Data from a Wrist-Worn Sensor.

The response to levodopa (LR) is important for managing Parkinson's Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson's Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies

The influence of social factors on gender health

Male births exceed female births by 5-6% (for a sex ratio at birth of 1.05-1.06) while a women's life expectancy, on a global scale, is about 6 years longer. Thus within various age groups the male:female ratio changes over time. Until age 50 years men outnumber women; thereafter their numbers show a sharp decline. Consequently at age 80 years, there are many more women than men. An estimated 25% of this male excess mortality is due to biological causes, the rest being explained by behavioural, cultural and environmental factors. For both women and men, the main health risks related to lifestyle are smoking, alcohol, unhealthy diet and physical inactivity. In the year 2010, overweight (BMI: 25-29 kg/m2) and obesity (BMI: >30 kg/m2) were responsible for over 3 million deaths, with similar relative risks in men and women for overweight and obesity. Smoking and alcohol are the major causes of the global gender gap in mortality. For women in some parts of the world however pregnancy is also hazardous. On a global scale, in 2013 about 300 000 deaths were related to pregnancy, with sub-Saharan Africa registering the highest maternal mortality: over 500 maternal deaths per 100 000 births. Additional woman's health risks arise from gender discrimination, including sex-selective abortion, violence against women and early child marriage. Providers should be aware of the effect that these risks can have on both reproductive and general health. © 2016 The Author

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study)

Background. Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. Methods/design. Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. Discussion. The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. Trial registration. Current Controlled Trials ISRCTN46462267

Efficacy and cost-effectiveness of a web-based and mobile stress-management intervention for employees: design of a randomized controlled trial

Background: Work-related stress is associated with a variety of mental and emotional problems and can lead to substantial economic costs due to lost productivity, absenteeism or the inability to work. There is a considerable amount of evidence on the effectiveness of traditional face-to-face stress-management interventions for employees; however, they are often costly, time-consuming, and characterized by a high access threshold. Web-based interventions may overcome some of these problems yet the evidence in this field is scarce. This paper describes the protocol for a study that will examine the efficacy and cost-effectiveness of a web-based guided stress-management training which is based on problem solving and emotion regulation and aimed at reducing stress in adult employees. Methods. The study will target stressed employees aged 18 and older. A randomized controlled trial (RCT) design will be applied. Based on a power calculation of d=.35 (1-β of 80%, α =.05), 264 participants will be recruited and randomly assigned to either the intervention group or a six-month waitlist control group. Inclusion criteria include an elevated stress level (Cohen's Perceived Stress Scale-10 ≥ 22) and current employment. Exclusion criteria include risk of suicide or previously diagnosed psychosis or dissociative symptoms. The primary outcome will be perceived stress, and secondary outcomes include depression and anxiety. Data will be collected at baseline and seven weeks and six months after randomization. An extended follow up at 12 months is planned for the intervention group. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective and will include both direct and indirect health care costs. Data will be analyzed on an intention-to-treat basis and per protocol. Discussion. The substantial negative consequences of work-related stress emphasize the necessity for effective stress-management trainings. If the proposed internet intervention proves to be (cost-) effective, a preventative, economical stress-management tool will be conceivable. The strengths and limitations of the present study are discussed. Trial registration. German Register of Clinical Studies (DRKS): DRKS00004749. © 2013 Heber et al.; licensee BioMed Central Ltd

Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

Dutch Oncology COVID-19 consortium:Outcome of COVID-19 in patients with cancer in a nationwide cohort study

Aim of the study: Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods: This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients' characteristics, cancer diagnosis and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results: Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045) and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥65 years). Conclusion: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to severe acute respiratory syndrome coronavirus 2, whereas treatment adjustments and prioritising vaccination, when available, should also be considered