Longitudinal assessment of real-world patient adherence: a 12-month electronic patient-reported outcomes follow-up of women with early breast cancer undergoing treatment.

BACKGROUND: Electronic patient-reported outcomes (ePROs) assess patients' health status and quality of life, improving patient care and treatment effects, yet little is known about their use and adherence in routine patient care. AIMS: We evaluated the adherence of invasive breast cancer and ductal carcinoma in situ (DCIS) patients to ePROs follow-up and whether specific patient characteristics are related to longitudinal non-adherence. METHODS: Since November 2016, the Breast Center at Charité - Universitätsmedizin Berlin has implemented an ongoing prospective PRO routine program, requiring patients to complete ePROs assessments and consent to email-based follow-up in the first 12 months after therapy starts. Frequencies and summary statistics are presented. Multiple logistic regression models were performed to determine an association between patient characteristics and non-adherence. RESULTS: Out of 578 patients, 239 patients (41.3%, 95%CI: 37.3-45.5%) completed baseline assessment and all five ePROs follow-up during the first 12 months after therapy. On average, above 70% of those patients responded to the ePROs follow-up assessment. Adherence to the ePROs follow-up was higher during the COVID-19 pandemic than in the time periods before (47.4% (111/234) vs. 33.6% (71/211)). Factors associated with longitudinal non-adherence were younger age, a higher number of comorbidities, no chemotherapy, and a low physical functioning score in the EORTC QLQ-C30 at baseline. CONCLUSIONS: The study reveals moderate adherence to 12-month ePROs follow-up assessments in invasive early breast cancer and DCIS patients, with response rates ranging from 60 to 80%. Emphasizing the benefits for young patients and those with high disease burdens might further increase adherence.

How breast cancer therapies impact body image - real-world data from a prospective cohort study collecting patient-reported outcomes.

BACKGROUND: In breast cancer patients body image (BI) is a crucial aspect of quality of life (QoL). This study examined the postoperative impact of different surgical approaches on long-term BI analyzing real-world data to guide pre- and postoperative patient care and preserve QoL. METHODS: EORTC QLQ-BR23 BI scores were collected electronically in 325 breast cancer patients within routine clinical care for a duration of 41.5 months (11/17/2016 - 4/30/2020) at predefined time points preoperatively and repeatedly up to two years after breast-conserving surgery (BCS) (n = 212), mastectomy alone (M) (n = 27) or mastectomy with immediate breast reconstruction (MIBR) (n = 86). Higher scores indicated better BI. A linear mixed regression model was used to analyze the impact of BCS, M and MIBR, as well as non-surgical therapies on BI at treatment initiation and over time. RESULTS: BI scores deteriorated by 5 points (95%-confidence interval (CI) -8.94 to -1.57, p≈0.005) immediately after BCS, by 7 points (95%-CI -12.13 to -1.80, p≈0.008) after MIBR and by 19 points (95%-CI -27.34 to -10.34, p < 0.001) after M. The change over time after BCS (+ 0.10 points per week, 95%-CI -0.17 to 0.38), MIBR (-0.07 points per week, 95%-CI -0.35 to 0.20) and M (+ 0.14 points per week, 95%-CI -0.19 to 0.48) were not statistically significant (each p > 0.05). At treatment initiation chemotherapy was associated with a 22-point decline (95%-CI -25.39 to -17.87, p < 0.001) in BI score, while radiotherapy was associated with a 5-point increase (95%-CI 1.74 to 9.02, p≈0.004). However, over time chemotherapy was associated with a score recovery (+ 0.28 points per week, 95%-CI 0.19 to 0.37, p < 0.001), whereas for radiotherapy a trend towards BI deterioration was observed (-0.11 points per week, 95%-CI -0.23 to 0.02, p≈0.101). CONCLUSIONS: Breast cancer surgery negatively affects BI. BCS and MIBR presumably harm BI less than M in the early postoperative period. Our data suggests BI to be deteriorating in the long term after MIBR while improving after BCS or M. Radiotherapy seems to have an additional negative long-term impact on BI. These findings should be confirmed in further studies to enable evidence-based patient information as part of preoperative shared decision-making and postoperative patient care.

Quality of life after risk-reducing salpingo-oophorectomy in women with a pathogenic BRCA variant.

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is recommended to women with a pathogenic BRCA variant, but as a main side effect, RRSO could lead to an early onset of menopause. AIM: To evaluate the impact of RRSO and preoperative menopausal status on menopausal symptoms, sexual functioning, and quality of life (QOL). METHODS: The study was conducted between November 2019 and April 2020. Women were included who tested positive for a pathogenic BRCA1/2 variant between 2015 and 2018. Depression levels, QOL, and global health status were measured and compared with those of women who opted against RRSO. Furthermore, women who underwent RRSO treatment were asked to report menopausal complaints that they experienced at 1 month postsurgery and any current complaints. OUTCOMES: RRSO had no significant impact on QOL, but women who were premenopausal at the time of surgery reported more sexual complaints than postmenopausal women. RESULTS: In total, 134 carriers of a BRCA mutation were included: 90 (67%) underwent RRSO and 44 (33%) did not. At the time of the survey, neither the control nor experimental group experienced significant changes in QOL (b = -0.18, P = .59). Women who underwent RRSO reported a significantly lower global health status (b = -0.66, P = .05). Women who were premenopausal at the time of surgery were bothered more by sexual symptoms (b = 0.91, P = .19) but experienced fewer vasomotor complaints (b = -1.09, P = .13) than women who were postmenopausal at the time of RRSO. CLINICAL IMPLICATIONS: The decrease of sexual functioning after RRSO should be an integral part of preoperative counseling because it is important for BRCA carriers, especially for premenopausal women. STRENGTHS AND LIMITATIONS: Some strengths of the present study were the long follow-up, a high response rate, and the existence of a control group, whereas defining menopausal status by last menstrual bleeding and self-report of data (eg, breast cancer history) increased the risk of errors. CONCLUSION: Our study indicated that women who underwent RRSO experienced no difference in QOL when compared with women without RRSO and that patients with premenopausal status seemed to be at higher risk to experience sexual complaints after surgery.

Statistical review of animal trials-A guideline.

Any experiment involving living organisms requires justification of the need and moral defensibleness of the study. Statistical planning, design, and sample size calculation of the experiment are no less important review criteria than general medical and ethical points to consider. Errors made in the statistical planning and data evaluation phase can have severe consequences on both results and conclusions. They might proliferate and thus impact future trials-an unintended outcome of fundamental research with profound ethical consequences. Unified statistical standards are currently missing for animal review boards in Germany. In order to accompany, we developed a biometric form to be filled and handed in with the proposal at the concerned local authority on animal welfare. It addresses relevant points to consider for biostatistical planning of animal experiments and can help both the applicants and the reviewers in overseeing the entire experiment(s) planned. Furthermore, the form might also aid in meeting the current standards set by the 3+3R's principle of animal experimentation: Replacement, Reduction, Refinement as well as Robustness, Registration, and Reporting. The form has already been in use by the concerned local authority of animal welfare in Berlin, Germany. In addition, we provide reference to our user guide giving more detailed explanation and examples for each section of the biometric form. Unifying the set of biostatistical aspects will help both the applicants and the reviewers to equal standards and increase quality of preclinical research projects, also for translational, multicenter, or international studies.

Prospective, double-blind diagnostic multicentre study of confocal laser endomicroscopy for wheat sensitivity in patients with irritable bowel syndrome.

OBJECTIVE: A considerable proportion of patients with irritable bowel syndrome (IBS) may be wheat-sensitive and respond to a gluten-free diet (GFD) although they do not have coeliac disease. However, a diagnostic test for wheat sensitivity (WS) is missing. Our study evaluated the diagnostic accuracy (sensitivity and specificity) of confocal laser endomicroscopy (CLE) for the identification of WS as primary outcome. DESIGN: In this prospective, double-blind diagnostic study 147 non-coeliac patients fulfilling the Rome III criteria for IBS were tested by CLE for duodenal changes after wheat (index test), soy, yeast or milk exposure. Patients with IBS responding to 2 months of GFD were classified as having WS (reference test) using response criteria recommended by regulatory bodies for pharmaceutical trials of patients with IBS. After 2 months, CLE results were unblinded and patients were advised to exclude those food components that had led to a positive CLE reaction. The clinical response was assessed at follow-up after 6 and 12 months. RESULTS: Of 130 patients who completed the study per protocol, 74 (56.9%) responded to GFD and were classified as WS after 2 months, and 38 of these 74 patients were correctly identified by CLE (sensitivity 51.4%; 97.5% CI: 38.7% to 63.9%). A total of 38 of 56 patients without WS were correctly identified by CLE (specificity 67.9%; 97.5% CI: 52.9% to 79.9%). At 6 months follow-up, CLE correctly identified 49 of 59 food-sensitive patients (sensitivity 83.1%; 97.5% CI: 69.9% to 91.3%) but specificity was only 32% (97.5% CI: 15.7% to 54.3%). CONCLUSION: In light of the high proportion of patients with IBS responding to GFD, the diagnostic accuracy of CLE is too low to recommend widespread use of this invasive procedure. TRAIL REGISTRATION NUMBER: This study was registered as clinical trial in the German Registry for Clinical Studies (DRKS00010123).

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study.

PURPOSE: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. METHODS: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. RESULTS: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. CONCLUSIONS: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19.

Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd-LIFE study.

BACKGROUND: In patients with congenital adrenal hyperplasia (CAH) type and doses of glucocorticoids used as well as sex hormone secretion during puberty have important actions on bone mineral density (BMD) in adulthood. AIM: To evaluate BMD in adult CAH patients depending on current glucocorticoid therapy and on androgen levels in adulthood and at age 16 years. METHODS: We included 244 CAH patients from the dsd-LIFE cohort (women n = 147, men n = 97; salt-wasting n = 148, simple-virilizing n = 71, nonclassical n = 25) in which BMD and bloods were available. Clinical and hormonal data at age 16years were retrieved from patients' files. RESULTS: Simple-virilizing women showed lower BMD compared to salt-wasting women at trochanter (0.65 ± 0.12 vs 0.75 ± 0.15 g/cm2 ; P < .050), whole femur T-score (-0.87 ± 1.08 vs -0.16 ± 1.24; P < .05) and lumbar T-score (-0.81 ± 1.34 vs 0.09 ± 1.3; P < .050). Fracture prevalence did not differ significantly between the CAH groups. Prednisolone vs. hydrocortisone only therapy caused worse trochanter Z-score (-1.38 ± 1.46 vs -0.47 ± 1.16; P < .050). In women lumbar spine, BMD correlated negatively with hydrocortisone-equivalent dose per body surface (r2  = 0.695, P < .001). Furthermore, BMI at age 16years correlated positively with lumbar spine T-score (r2  = 0.439, P = .003) and BMD (r2  = 0.420, P = .002) in women. The androstenedione/testosterone ratio at age 16years correlated positively with lumbar spine Z-score in women (r2  = 0.284, P = .024) and trochanter Z-score in men (r2  = 0.600, P = .025). CONCLUSION: Higher glucocorticoid doses seemed to cause lower BMD especially in women. Prednisolone appeared to have more detrimental effects on BMD than hydrocortisone. Higher glucocorticoid doses (lower androstenedione/testosterone ratio) during adolescence may cause lower BMD in adulthood.

Mental Health of a Large Group of Adults With Disorders of Sex Development in Six European Countries.

OBJECTIVE: The aim of the study was to evaluate psychiatric symptoms among 1022 persons with various disorders of sex development (DSDs). METHODS: The study was a European multicenter cross-sectional clinical evaluation in six countries. The mean (SD) age of participants was 32.1 (13.4) years. The cohort consisted of 325 individuals with Turner syndrome, 219 individuals with Klinefelter syndrome (KS), female individuals with various XY-DSD conditions (107 with and 67 without androgenization), 87 male individuals with XY-DSD conditions, and 221 female individuals with congenital adrenal hyperplasia. The Hospital Anxiety and Depression Scale, the Short Autism Spectrum Quotient, the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Scale, and self-reported mental health history were used to assess psychiatric symptoms. RESULTS: Across the six DSD diagnostic groups, clinical cutoff symptom scores were reached in 19.5% of participants for anxiety, in 7.1% for depression, in 4.1% for attention-deficit/hyperactivity disorder, and in 9.1% for autism. The mean depression and anxiety scores were higher compared with population norms in men with KS and men with XY-DSD. Compared with participants with other DSD conditions, men with KS reported significantly more mental health symptoms. Self-esteem, satisfaction with care, body dissatisfaction, and experiences of shame were associated with psychiatric symptoms in many DSD conditions. CONCLUSIONS: A substantial minority of adults with DSD, with KS in particular, experience psychiatric morbidity. Across DSD conditions, adults may share feelings of shame. Developing a positive self-esteem and body image may be challenging. Multidisciplinary DSD care that involves specialized mental health support can be of important value. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006072.

Sexuality in Adults with Differences/Disorders of Sex Development (DSD): Findings from the dsd-LIFE Study.

For various reasons, sexuality of individuals with differences/disorders of sex development (DSD) may be affected. The aim of the study was to describe sexual activity, satisfaction with sex life, satisfaction with genital function, and sexual problems in people with different DSD conditions. Data were collected from 1,040 participants in Europe. Many people with a variety of DSD conditions do not appear to be satisfied with their sex life, experience a variety of sexual problems, and are less sexually active than the general population; therefore sexuality should be explicitly addressed in the care of people with DSD.

Gender Dysphoria and Gender Change in Disorders of Sex Development/Intersex Conditions: Results From the dsd-LIFE Study.

BACKGROUND: Information on the psychosexual outcome of individuals with disorders of sex development (DSDs) and intersex conditions is of great importance for sex assignment at birth of newborns with DSD. AIM: To assess gender change and gender dysphoria in a large sample of individuals with different DSDs. METHODS: A cross-sectional study was conducted in 14 European centers with 1,040 participants (717 female-identifying and 311 male-identifying persons and 12 persons identifying with another gender) with different forms of DSD. The cohort (mean age = 32.36 years, SD = 13.57) was divided into 6 major subgroups: women with 45,X DSD and variants (Turner syndrome; n = 325), men with 47,XXY DSD and variants (Klinefelter syndrome; n = 219), women with XY DSD without androgen effects (n = 107) and with androgen effects (n = 63), men with XY DSD (n = 87), and women with 46,XX congenital adrenal hyperplasia (n = 221). Data on psychosexual outcome were gathered by medical interviews and questionnaires. OUTCOMES: Gender change and gender dysphoria. RESULTS: Although gender changes were reported by 5% of participants, only in 1% (3% if those with Klinefelter and Turner syndromes-conditions in which gender issues are not prominent-are excluded) did the gender change take place after puberty and was likely initiated by the patient. 39 participants (4%) reported gender variance: between male and female, a gender other than male or female, or gender queer, alternating gender roles, or a gender expression that differed from the reported gender. This group had lower self-esteem and more anxiety and depression than the other participants. CLINICAL IMPLICATIONS: Clinicians should be aware of and sensitive to the possibility that their patients with DSD not only might have transgender feelings and a desire to change gender, but also identify as different from male or female. The complexity of their feelings might require counseling for some patients. STRENGTHS AND LIMITATIONS: The study is unique in the large number of participants from many different clinics, with sizable numbers in most subgroups, and in the large number of aspects that were measured. However, the very broadness of the study made it impossible to focus in detail on gender issues. Also, there is a need for instruments specifically measuring gender dysphoria in individuals with DSD that take non-binary genders into account. CONCLUSION: To make appropriate gender care possible for people with DSD, the gender-normative and gender-variant development of children with DSD should be studied in longitudinal studies. Kreukels BPC, Köhler B, Nordenström A, et al. Gender Dysphoria and Gender Change in Disorders of Sex Development/Intersex Conditions: Results From the dsd-LIFE Study. J Sex Med 2018;15:777-785.

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Correction to: Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Multicentre cross-sectional clinical evaluation study about quality of life in adults with disorders/differences of sex development (DSD) compared to country specific reference populations (dsd-LIFE).

BACKGROUND: Previous studies in quality of life (QOL) in individuals with disorders/differences of sex development (DSD) have been restricted to subpopulations of the condition. We describe QOL in adult persons with DSD compared to country specific references and assess the impact of diagnosis. METHODS: The multicentre cross-sectional clinical evaluation (dsd-LIFE) took place in 14 specialized clinics in six European countries. Adolescents (≥16 years) and adults having a DSD condition were included from 02/2014 to 09/2015. The main outcome QOL was measured by the WHOQOL-BREF (domains of physical health, psychological, social relationships, and environment). QOL was compared to country specific reference populations by using unpaired t-tests. Linear regression models explained the additional variance of the diagnosis on QOL. RESULTS: Three hundred one individuals with Turner Syndrome, 219 with Klinefelter Syndrome (including XYY), 226 with 46,XX CAH and 294 with rare DSD conditions (gonadal dysgenesis, androgen insensitivity syndrome, severe hypospadias, and androgen synthesis errors or other diagnosis) took part. Compared to healthy European populations, QOL was similar in psychological, slightly worse in physical health, and slightly better in environment. In social relationships, QOL was significantly poorer compared to healthy and non-healthy reference populations. In linear regression models health status was the most important predictor of QOL; additional variance was explained by feelings about household's income in all domains, and the relationship status in social relationships. Diagnosis explained nearly no additional variance. CONCLUSIONS: Except for social relationships, most people with DSD adapt well to their life circumstances and report a good QOL. Not diagnosis, but the individual's health status is much more important than previously thought. Therefore care for people with DSD should focus more on chronic physical or mental health problems both related and unrelated to the diagnosis itself. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006072 .

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.

OBJECTIVE: A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. METHODS: In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. RESULTS: A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. CONCLUSIONS: All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

Quality of health care in adolescents and adults with disorders/differences of sex development (DSD) in six European countries (dsd-LIFE).

BACKGROUND: To investigate the association between the structural quality of care and patient satisfaction with care in individuals with disorders/ differences of sex development (DSD). METHODS: A multicenter cross-sectional comparative study was conducted in 14 clinics in six European countries. We assessed the level of structural quality of care in each center using a self-constructed measure (Center Score) and the level of participant satisfaction with care using the customer satisfaction questionnaire (CSQ-4) and an adopted version of the Youth Health Care - Satisfaction, Utilization & Needs (YHC-SUN-SF). Data were obtained from individuals with Turner Syndrome (261), Klinefelter Syndrome (173), 46, XX congenital adrenal hyperplasia (190) and XY-DSD (257). RESULTS: We found large variations between the scores for structural quality of care both within a diagnostic group and within a country; the overall association between participant satisfaction with the center score was significant. CONCLUSIONS: Comparative effectiveness research across Europe can lead to more insight on beneficial structures and processes and the overall strategy to care for people with rare diseases in general and specific conditions such as disorders/ differences of sex development. Appreciation of higher levels of structural quality of the centers in this study supports the concept of comprehensive care. TRIAL REGISTRATION: German Clinical Trials Register: Registration identification number: DRKS00006072 , date of registration April 17th, 2014. DRKS00006072 (German Clinical Trials Register).

Analysis and Prediction of Claustrophobia during MR Imaging with the Claustrophobia Questionnaire: An Observational Prospective 18-month Single-Center Study of 6500 Patients.

Purpose To analyze claustrophobia during magnetic resonance (MR) imaging and to explore the potential of the 26-item claustrophobia questionnaire (CLQ) (range, 0-4) as a screening tool in patients scheduled for MR imaging. Materials and Methods The study received institutional review board approval, and patients in the CLQ cohort provided informed consent. A total of 6520 consecutive patients were included. Overall, 4288 patients completed the CLQ before MR imaging (CLQ cohort), and 2232 patients underwent MR imaging without having completed the CLQ (non-CLQ cohort). Claustrophobic events were recorded by the staff. Results The CLQ mean score in patients with claustrophobic events (1.48 ± 0.93) was significantly higher (P < .01) than in the group without claustrophobic events (0.60 ± 0.5). The CLQ cutoff value was 0.16 for men and 0.56 for women. Because of the low prevalence, negative predictive values of CLQ cutoff values (men, 0.99 [573 of 582]; women, 0.97 [745 of 766]) were higher than positive predictive values (men, 0.01 [88 of 582]; women, 0.16 [192 of 1186]). The overall claustrophobic event rate was 9.8% (640 of 6520; 95% confidence interval [CI]: 9.1, 10.6). The CLQ did not induce claustrophobic events because the event rate in the CLQ cohort was significantly lower than that in the non-CLQ cohort, as shown by the adjusted odds ratio of 0.81 (95% CI: 0.68, 0.96). Conclusion The CLQ is a suitable screening tool for the absence of a subsequent claustrophobic event. Furthermore, while it is possible to identify patients with a considerable risk of claustrophobia, prediction in individual patients is not possible. © RSNA, 2016 Online supplemental material is available for this article.

Impact of elevated lipoprotein(a) on coronary artery disease phenotype and severity.

AIMS: A thorough characterization of the relationship between elevated lipoprotein(a) [Lp(a)] and coronary artery disease (CAD) is lacking. This study aimed to quantitatively assess the association of increasing Lp(a) levels and CAD severity in a real-world population. METHODS AND RESULTS: This non-interventional, cross-sectional, LipidCardio study included patients aged ≥21 years undergoing angiography (October 2016-March 2018) at a tertiary cardiology centre, who have at least one Lp(a) measurement. The association between Lp(a) and CAD severity was determined by synergy between PCI with taxus and cardiac surgery (SYNTAX)-I and Gensini scores and angiographic characteristics. Overall, 975 patients (mean age: 69.5 years) were included; 70.1% were male, 97.5% had Caucasian ancestry, and 33.2% had a family history of premature atherosclerotic cardiovascular disease. Median baseline Lp(a) level was 19.3 nmol/L. Patients were stratified by baseline Lp(a): 72.9% had < 65 nmol/L, 21.0% had ≥100 nmol/L, 17.2% had ≥125 nmol/L, and 12.9% had ≥150 nmol/L. Compared with the normal (Lp(a) < 65 nmol/L) group, elevated Lp(a) groups (e.g. ≥ 150 nmol/L) had a higher proportion of patients with prior CAD (48.4% vs. 62.7%; P < 0.01), prior coronary revascularization (39.1% vs. 51.6%; P = 0.01), prior coronary artery bypass graft (6.0% vs. 15.1%; P < 0.01), vessel(s) with lesions (68.5% vs. 81.3%; P = 0.03), diffusely narrowed vessels (10.9% vs. 16.5%; P = 0.01) or chronic total occlusion lesions (14.3% vs. 25.2%; P < 0.01), and higher median SYNTAX-I (3.0 vs. 5.5; P = 0.01) and Gensini (10.0 vs. 16.0; P < 0.01) scores. CONCLUSION: Elevated Lp(a) was associated with a more severe presentation of CAD. Awareness of Lp(a) levels in patients with CAD may have implications in their clinical management.

Patients with coronary artery disease (CAD) suffer with progressive plaque buildup in the walls of coronary blood vessels, which restricts blood flow and may result in serious cardiovascular outcomes such as chest pain (angina) and heart attacks (myocardial infarction). In this study, we assessed whether elevated levels of lipoprotein(a) [Lp(a)­a lipoprotein found in blood] are associated with more severe illness. We observed that elevated Lp(a) was associated with a higher proportion of patients with prior CAD, prior interventions on coronary blood vessels, and more diseased blood vessels. These collectively form what is considered a 'severe' clinical presentation of CAD, meaning a greater likelihood of adverse clinical outcomes.

Correction: Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0216790.].

Long-term indoor gunshot exposure of special police forces induces bronchitic reactions and elevated blood lead levels-The Berlin shooting range study.

BACKGROUND: Gunshot emissions contain toxic elements that can harm those frequently exposed, such as police officers. Several years ago, police indoor firing ranges were closed by the Berlin municipality in response to police officer health complaints, and an investigation was launched into the possible respiratory health risks of frequent gunshot emission exposure. We, therefore, conducted an exploratory cross-sectional study to investigate clinical and functional parameters of respiratory health as well as the burden of trace elements in policemen with long-term high exposure to indoor gunshot emissions, compared to low-exposure and control groups. METHODS: We conducted lung function tests and collected blood and urine samples from Berlin police officers and government employees who were divided into three subject groups based on exposure to gunshot emissions: high exposure (n = 53), low exposure (n = 94) and no exposure (n = 76). Lung function was examined using body plethysmography. Blood and urine samples were tested via inductively coupled plasma mass spectrometry for the presence of common gunshot powder elements (antimony, lead and manganese). Exposure and symptoms were assessed using records as well as questionnaires. RESULTS: Higher exposure was associated with more respiratory symptoms during gun shooting practice (64% vs. 21%, P < 0.001) compared to the low-exposure group. Headache, cough, discoloured mucous and shortness of breath were also more common as were some other symptoms. The cough symptomatology of the high-exposure group also persisted significantly longer (median: 0.67 vs. 0.01 days, range: 0 to 5 days, P = 0.029) compared to the low-exposure group. They also showed a lower forced expiratory volume in 1 s/forced vital capacity quotient (Tiffeneau index), P = 0.018 between the three groups and P = 0.005 for the high-exposure group, a possible marker of early, subclinical bronchial obstruction. We observed increased blood lead concentrations depending on subject's age (+1.2% per year, 95% confidence interval: 0.5-1.9%, P < 0.001) and cumulative gunshot exposure (+0.34% per 100 000 shots, 0.02-0.66%, P = 0.037). CONCLUSIONS: These first results suggest that long-term exposure to indoor gunshot emissions induces bronchitic reactions due to repeated irritation of the airways. Higher levels of exposure lead to more negatively impacted lung function and higher blood lead levels with the possible reason that more frequent exposure may mean shorter regeneration phases for the respiratory mucous membrane. We recommend a reduction of exposure to gunshot emissions in order to decrease symptoms and avoid any-even small-deterioration in spirometry.

Data of real-world reference scores for EORTC QLQ-C30 and QLQ-BR23 at baseline in women with early breast cancer and other breast diseases.

Patient-reported outcomes are information about health status and health-related quality of life collected directly from patients. The data in this publication contain the first assessment of patient-reported outcomes (PROs) from real-life measurements in the breast cancer center at Charité - Universitätsmedizin Berlin between November 2016 and March 2021. At baseline (before the start of treatment), 1727 ambulatory patients with early breast cancer, ductal carcinoma in situ (DCIS), fibroadenoma, and other breast diseases were registered in the digital PRO-system as part of clinical routine. Patients' sociodemographic data, medical history, clinical variables, and raw scores of the EORTC QLQ-C30 and EORTC QLQ-BR23 are provided in this publication. This dataset can be used as a reference for PROs in a clinical care setting or in clinical studies with breast diseases and contribute to the discussion about the interpretation of score values. Furthermore, the association between patients' sociodemographic data, clinical variables, and PRO data at baseline can be analysed further.