Progression and Death as Competing Risks in Ovarian Cancer

Background: Progression of a cancer disease and dying without progression can be understood as competing risks. The Cause-Specific Hazards Model and the Fine and Gray model on cumulative incidences are common statistical models to handle this problem. The pseudo value approach by Andersen and Klein is also able to cope with competing risks. It is still unclear which model suits best in which situation.Methods: For a simulated dataset and a real data example of ovarian cancer patients who are exposed to progression and death the three models are examined. We compare the three models with regards to interpretation and modeling requirements.Results: In this study, the parameter estimates for the competing risks are similar from the Cause-Specific Hazards Model and the Fine and Gray model. The pseudo value approach yields divergent results which are heavily dependent on modeling details.Conclusions: The investigated approaches do not exclude each other but moreover complement one another. The pseudo value approach is an alternative that circumvents proportionality assumptions. As in all survival analyses, situations with low event rates should be interpreted carefully

The effect of family history on screening procedures and prognosis in breast cancer patients - Results of a large population-based case-control study

Background: The potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear.Methods: A large population-based case-control study on breast cancer in postmenopausal women in Germany recruited 2002-2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015.Results: A first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p &lt; 0.001). Patients with a first degree family history of breast cancer were more likely to have had &gt;10 mammograms (MG) (42.7% vs. 24.9%, p &lt; 0.001) and showed a higher rate of imaging-detected tumors (MG or ultrasound) (45.8% vs. 31.9%, p &lt; 0.001). A smaller tumor size at initial diagnosis (below 2 cm) was more likely in patients with a positive family history (OR 1.45, p &lt; 0.001) and a higher number of MG (&gt;= 10 MG: OR 2.29). After accounting for tumor characteristics, mammogram regularity (HR 0.72, p &lt; 0.001) and imaging-assisted tumor detection (HR 0.66, p &lt; 0.001) were associated with better overall survival but not with a positive family history.Discussion: Patients with a positive family history had a higher rate of imaging detected tumors with smaller size at initial diagnosis compared to patients without affected family members. Screening was associated with improved survival after a breast cancer diagnosis, irrespective of a positive family history. (C) 2020 The Authors. Published by Elsevier Ltd.</p

Intrusions related to indirectly experienced events in clinical offspring of World War Two survivors

Negative events may not only linger on in the form of intrusive memories in the minds of those directly exposed but also in those who are only indirectly confronted with these events. The aim of the present study was to investigate if intrusions referring to indirectly experienced traumatic events do indeed occur, and to compare their frequency and characteristics to intrusions about directly experienced negative events. Participants (N = 98) were adult postwar offspring of World War Two survivors currently in treatment in one of two clinics specialized in the treatment of war victims. We examined the frequency and characteristics of intrusions about indirectly experienced (i.e., parent war-related) events and two types of directly (self-) experienced events: Self-experienced traumatic events and negative events related to participants' upbringing. Intrusions referring to indirectly experienced traumatic events did indeed occur. The frequency as well as other characteristics of these intrusions did not differ from those of both types of intrusions about directly experienced events. The similarities between intrusions related to different types of events emphasize the (re)constructive nature of memory. Our findings indicate that traumatic events not only affect those directly involved but may also continue to plague the next generation

Time-dependent postural control adaptations following a neuromuscular warm-up in female handball players:A randomized controlled trial

Background: Female handball athletes are at a particular risk of sustaining lower extremity injuries. The study examines time-dependent adaptations of static and dynamic balance as potential injury risk factors to a specific warm-up program focusing on neuromuscular control. Methods: Fourty one (24.0 +/- 5.9 years) female handball athletes were randomized to an intervention or control group. The intervention group implemented a 15-min specific neuromuscular warm-up program, three times per week for eleven weeks, whereas the control group continued with their regular warm-up. Balance was assessed at five time points. Measures included the star excursion balance test (SEBT), and center of pressure (COP) sway velocity during single-leg standing. Results: No baseline differences existed between groups in demographic data. Adherence to neuromuscular warm-up was 88.7 %. Mean COP sway velocity decreased significantly over time in the intervention group (-14.4 %; p <.001), but not in the control group (-6.2 %; p = 0.056). However, these effects did not differ significantly between groups (p = .098). Mean changes over time in the SEBT score were significantly greater (p = .014) in the intervention group (+5.48) compared to the control group (+3.45). Paired t-tests revealed that the first significant balance improvements were observed after 6 weeks of training. Conclusions: A neuromuscular warm-up positively influences balance variables associated with an increased risk of lower extremity injuries in female handball athletes. The course of adaptations suggests that a training volume of 15 min, three times weekly over at least six weeks produces measurable changes

Water extracts from Siberian thawing permafrost - from land to ocean

To better understand and quantify fluxes of dissolved elements upon permafrost thaw, water-soluble elements from Siberian permafrost samples covering a wide geographic range were determined by extraction. We measured the pH- and EC-values as well as the total dissolved major and secondary cation concentrations and anion concentrations for 270 water extracts from 12 different sites around the Laptev Sea. Cation concentrations were analyzed using inductively coupled plasma-optical emission spectrometry and anion concentrations by ion chromatography. Hydrogen carbonate concentrations were measured by potentiometric pH-value titration using an automatic titrator. Electrical conductivity and pH values were measured using a WTW MultiLab 540 multi-parameter device. As ground ice melts throughout Siberia with continued climate warming, drainage of the soils in many locations is improving and exposing mineral surfaces that were previously largely inert by their perennially frozen condition and unaffected by active weathering through seasonal wetting and drying cycles. Chemical analyses of water extracts allow an assessment of the potential interactions between mineral surfaces and pore melt water and the characteristics and biogeochemical and ecological consequences of the export of melt water from thawing permafrost. The (hydro-)chemical flux from permafrost sources into the riverine and marine realms is mainly defined by its source signatures and concentrations, which will be addressed in the present study. We compare our values with water data from lakes, rivers and the Arctic Ocean. The influence of terrestrial input from thawing permafrost including ground ice is expected to increase as coastal and river shore erosion as well as other permafrost degradation processes accelerate under Arctic warming and mobilize previously freeze-locked material. The increasing influx of dissolved elements influences transport and deposition processes in aquatic environments as well as nutrient supply, food chains and life cycles with largely understudied consequences for aquatic and coastal ecosystems in the Arctic

Propensity Scoring after Multiple Imputation in a Retrospective Study on Adjuvant Radiation Therapy in Lymph-Node Positive Vulvar Cancer

Propensity scoring (PS) is an established tool to account for measured confounding in non-randomized studies. These methods are sensitive to missing values, which are a common problem in observational data. The combination of multiple imputation of missing values and different propensity scoring techniques is addressed in this work. For a sample of lymph node-positive vulvar cancer patients, we re-analyze associations between the application of radiotherapy and disease-related and non-related survival. Inverse-probability-of-treatment-weighting (IPTW) and PS stratification are applied after multiple imputation by chained equation (MICE). Methodological issues are described in detail. Interpretation of the results and methodological limitations are discussed

A weighted combined effect measure for the analysis of a composite time-to-first-event endpoint with components of different clinical relevance

Composite endpoints combine several events within a single variable, which increases the number of expected events and is thereby meant to increase the power. However, the interpretation of results can be difficult as the observed effect for the composite does not necessarily reflect the effects for the components, which may be of different magnitude or even point in adverse directions. Moreover, in clinical applications, the event types are often of different clinical relevance, which also complicates the interpretation of the composite effect. The common effect measure for composite endpoints is the all-cause hazard ratio, which gives equal weight to all events irrespective of their type and clinical relevance. Thereby, the all-cause hazard within each group is given by the sum of the cause-specific hazards corresponding to the individual components. A natural extension of the standard all-cause hazard ratio can be defined by a weighted all-cause hazard ratio where the individual hazards for each component are multiplied with predefined relevance weighting factors. For the special case of equal weights across the components, the weighted all-cause hazard ratio then corresponds to the standard all-cause hazard ratio. To identify the cause-specific hazard of the individual components, any parametric survival model might be applied. The new weighted effect measure can be tested for deviations from the null hypothesis by means of a permutation test. In this work, we systematically compare the new weighted approach to the standard all-cause hazard ratio by theoretical considerations, Monte-Carlo simulations, and by means of a real clinical trial example