Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB)

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20–29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999–2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017.After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 μg/L in 2010 to twice the concentration in 2011 (0.31 μg/L) with further increases in 2013 (0.37 μg/L), 2015 (0.59 μg/L) and 2017 (0.70 μg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other.For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 μg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 μg/kg bw/d) was a factor of more than 20 below the TDI.The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.     

Communication Between HIV Patients and Their Providers: A Qualitative Preference Match Analysis

Since the introduction of cART (combination antiretroviral therapy), HIV has evolved into a chronic disease such that it requires lifelong medical treatment to which patients must adhere. Communication with health care providers is pivotal in supporting patients to adapt to having HIV and adhering to treatment, in order to maintain health and quality of life. Previous research indicates that communication is optimal when it matches patient preferences for information exchange, relationship establishment, and involvement in treatment decisions. The aim of the present study is to explore HIV patient communication preferences as well as patient experiences with their providers (not) matching their preferences. A second aim is to explore provider beliefs about patient preferences and provider views on optimal communication. Data were collected through interviews with 28 patients and 11 providers from two academic hospitals. Results indicate that patient preferences reflect their cognitive, emotional, and practical needs such that patients look to increase their sense of control over their HIV. Patients aim to further increase their sense of control (by proxy) through their relationship with their providers and through their decisional involvement preferences. Providers are well aware of patient communication preferences but do not explicate underlying control needs. Implications for clinical practice are discussed.     

Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

The effect of smoking on survival in lung carcinoma patients with brain metastasis: a systematic review and meta-analysis

The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to analyse the effects of cigarette smoking on overall survival (OS) and progression-free survival (PFS) in lung cancer BM patients. PubMed, Embase, Web of Science, Cochrane and Google Scholar were searched for comparative studies regarding the effects of smoking on incidence and survival in brain metastases patients up to December 2020. Three independent reviewers extracted overall survival (OS) and progression-free survival data (PFS). Random-effects models were used to pool multivariate-adjusted hazard ratios (HR). Out of 1890 studies, fifteen studies with a total of 2915 patients met our inclusion criteria. Amongst lung carcinoma BM patients, those who were smokers (ever or yes) had a worse overall survival (HR: 1.34, 95% CI 1.13, 1.60, I2: 72.1%, p-heterogeneity?<?0.001) than those who were non-smokers (never or no). A subgroup analysis showed the association to remain significant in the ever/never subgroup (HR: 1.34, 95% CI 1.11, 1.63) but not in the yes/no smoking subgroup (HR: 1.30, 95% CI 0.44, 3.88). This difference between the two subgroups was not statistically significant (p?=?0.91). Amongst lung carcinoma BM patients, smoking was associated with a worse OS and PFS. Future studies examining BMs should report survival data stratified by uniform smoking status definitions.

     

Lack of effectiveness of a multidisciplinary fall-prevention program in elderly people at risk: a randomized, controlled trial

OBJECTIVES: To assess whether a pragmatic multidisciplinary fall‐prevention program was more effective than usual care in preventing new falls and functional decline in elderly people. DESIGN: A two‐group, randomized, controlled trial with 12 months of follow‐up. SETTING: University hospital and home‐based intervention, the Netherlands. PARTICIPANTS: Three hundred thirty‐three community‐dwelling Dutch people aged 65 and over who were seen in an emergency department after a fall. INTERVENTION: Participants in the intervention group underwent a detailed medical and occupational‐therapy assessment to evaluate and address risk factors for recurrent falls, followed by recommendations and referral if indicated. People in the control group received usual care. MEASUREMENTS: Number of people sustaining a fall (fall calendar) and daily functioning (Frenchay Activity Index). RESULTS: Results showed no statistically significantly favorable effects on falls (odds ratio=0.86, 95% confidence interval (CI)=0.50–1.49) or daily functioning (regression coefficient=0.37, CI=?0.90 to 1.63) after 12 months of follow‐up. CONCLUSION: The multidisciplinary fall‐prevention program was not effective in preventing falls and functional decline in this Dutch healthcare setting. Implementing the program in its present form in the Netherlands is not recommended. This trial shows that there can be considerable discrepancy between the “ideal” (experimental) version of a program and the implemented version of the same program. The importance of implementation research in assessing feasibility and effectiveness of such a program in a specific healthcare setting is therefore stressed.     

The developmental profile: Validation of a theory-driven instrument for personality assessment

Abstract

The Developmental Profile is an instrument for personality assessment. It covers both maladaptive and adaptive characteristics. The current study examined its internal consistency and construct validity in a Dutch sample of 763 participants from various clinical and nonclinical settings. The internal consistency reliability estimates were good for the clusters of levels (adaptive, neurotic, and primitive), although not for all separate levels. Confirmatory factor analysis showed an overall good fit, with the exception of the level of primary narcissism. Furthermore, empirical evidence was found for the interpretation of a patient's Developmental Profile according to increasing levels of aggregation, with as a highest level a single maladaptivity–adaptivity scale score. This scale significantly distinguished among different patient groups.     

Dyspnea severity, changes in dyspnea status and mortality in the general population: the Vlagtwedde/Vlaardingen study

Dyspnea is a predictor of mortality. The effects of dyspnea severity and changes in dyspnea status on all-cause and cause-specific mortality remain unclear. The Vlagtwedde/Vlaardingen study started in 1965 and subjects were re-examined every 3?years until 1989/1990. Vital status of all 8,465 subjects on December 31st, 2008 was assessed. Associations between mortality and dyspnea severity and changes in dyspnea status were investigated using Cox regression adjusted for gender, age, FEV₁ %predicted, place of residence, smoking and BMI. After 43?years of follow-up, 2,883 (39?%) of 7,360 subjects examined for dyspnea severity had died, 1,386 (19?%) due to cardiovascular disease, 267 (4?%) due to chronic obstructive pulmonary disease (COPD). Subjects with moderate and severe dyspnea had increased all-cause and cardiovascular mortality [moderate: HR?=?1.3 (95?% CI 1.2–1.5) and 1.4 (1.1–1.6), severe: 1.5 (1.1–2.0) and 1.9 (1.3–2.6) respectively] compared to asymptomatics. Severe dyspnea was significantly associated with COPD mortality [3.3 (2.0–5.2)]. Subjects who lost dyspnea had hazard ratios for all-cause and cause-specific mortality comparable to asymptomatics. Persistent dyspnea and dyspnea development were risk factors for all-cause, cardiovascular and COPD mortality [persistent: 2.0 (1.4–2.8), 1.9 (1.2–3.3) and 3.3 (1.2–8.9), development: 1.5 (1.2–1.8), 2.0 (1.5–2.6) and 3.8 (2.3–6.3) respectively]. Additionally, dyspnea effects on mortality were more pronounced in overweight/obese and older subjects and in subjects with better lung function. These results show that dyspnea is associated with mortality in a severity-dependent manner. Furthermore this study is the first showing that dyspnea remission normalizes mortality risk. Having or developing dyspnea is a risk factor for mortality.     

Value of Scintigraphy for Assessing Delayed Gastric Emptying After Pancreatic Surgery

Background

Delayed gastric emptying (DGE) occurs frequently after pancreatic surgery. Recently a consensus definition of DGE was introduced, and this grading system is currently widely used. The aim of this study was to compare results of gastric emptying scintigraphy with the grade of DGE after pancreatic surgery.

Methods

In 44 patients undergoing exploration for a pancreatic head or periampullary tumor, 28 pancreatoduodenectomies (PDs) and 16 double-bypass procedures were performed. All patients underwent preoperative and postoperative gastric emptying scintigraphy. We investigated whether the incidence of DGE was correlated with the results of gastric emptying scintigraphy.

Results

DGE occurred in 19 (43 %) patients. Clinically relevant DGE (grades B and C) prevailed in the PD group. Median postoperative residual activity at t = 2 h (%RA120) in these groups was 36 % (no DGE), 75 % (grade A), 93 % (grade B), and 95 % (grade C). DGE grade B or C was found in 7 of 10 patients with %RA120 of ≥94 % on postoperative day (POD) 7.

Conclusions

Postoperative %RA120 on scintigraphy is positively associated with severity of DGE. Gastric emptying scintigraphy on POD 7 can predict the severity of DGE. When postoperative gastric emptying scintigraphy shows high residual radioactivity, the likelihood of further progression to grade B or C DGE is high and warrants investigation for underlying causes.