Sexual function and pelvic floor activity in women:the role of traumatic events and PTSD symptoms

Background Traumatic sexual experiences can negatively affect sexual functioning and increase pelvic floor activity in women, especially when post-traumatic stress disorder (PTSD) is developed. However, little is known about the effect of other types of interpersonal and non-interpersonal, traumatic experiences on sexual function and pelvic floor overactivity. Objective The aim of this study was to examine the effects of lifetime traumatic experiences and subsequent PTSD symptoms on sexual function and pelvic floor activity and to investigate whether the effects differ for interpersonal and non-interpersonal trauma. Methods Women (N=82) with obesity and a history of infertility, participating in a follow-up study of an RCT investigating a lifestyle intervention programme, completed questionnaires on lifetime exposure to traumatic events (LEC-5), PTSD symptoms (PC-PTSD-5), sexual function (MFSQ) and pelvic floor activity (AOPFS-SV). Results A large majority of women (85%) reported exposure to at least one traumatic event during their lifetime. Sexual function and pelvic floor activity did not differ between women who experienced non-interpersonal or interpersonal (including sexual) trauma and those who did not experience traumatic events during their lifetime. Women who had developed PTSD symptoms, however, did have higher pelvic floor activity, but sexual function was not affected. Women with a positive screen for PTSD had the highest pelvic floor activity score, and individual PTSD symptoms nightmares and hypervigilance were associated with significantly higher pelvic floor activity scores. Conclusion Trauma exposure is associated with pelvic floor overactivity in women with a positive screen for PTSD, such that pelvic floor overactivity is more severe with greater PTSD severity. These findings suggest that the development of PTSD after interpersonal trauma is pivotal in this association. Sexual function was unrelated to trauma exposure and pelvic floor function, perhaps related to the fact that the interpersonal trauma events reported in this study were mainly non-sexual

Ganciclovir Therapeutic Drug Monitoring:A Case Series

This paper presents three cases of immunocompromised patients for whom therapeutic drug monitoring (TDM) of ganciclovir in combination with cytomegalovirus (CMV) viral load measurement was used to guide treatment. The first patient is diagnosed with Thymoma A, the second is a heart transplant recipient and the third is an HIV positive patient. These patients were all diagnosed with CMV and treated with ganciclovir. Our case studies illustrate how TDM guided dosing can be helpful in the management of these complex cases.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Employment Status and Work Functioning among Kidney Transplant Recipients

Background and objectives: To date, employment figures of kidney transplant recipients in Europe are inconsistent. Additionally, little is known about work functioning of employed kidney transplant recipients and work functioning trajectories before and after transplantation. Design, setting, participants, & measurements: Data from the ongoing TransplantLines Biobank and Cohort study and from community-dwelling employed adults were used. Health-related work functioning of kidney transplant recipients was assessed with the Work Role Functioning Questionnaire 2.0 and compared with potential kidney donors and community-dwelling employed adults. Results: We included 668 kidney transplant recipients of working age (59% men, age 51±11 years) at median 3 (interquartile range, 2–10) years after transplantation, 246 potential kidney donors of working age (43% men, age 53±9 years), and 553 community-dwelling employed adults (70% men, age 45±11 years). The proportion of employed kidney transplant recipients was lower compared with potential kidney donors (56% versus 79%). If employed, the work functioning score of kidney transplant recipients was slightly lower compared with employed potential kidney donors yet higher compared with community-dwelling employed adults (medians 91 [interquartile range, 76–98], 94 [interquartile range, 85–99], and 88 [interquartile range, 79–95], respectively). Backward linear regression analyses revealed that lower educational level, having a kidney from a deceased donor, presence of tingling or numbness of hands or feet, presence of concentration/memory problems, presence of anxiety, and presence of severe fatigue were independently associated with lower work functioning among kidney transplant recipients. Additional subgroup analyses showed that work functioning scores were lower before transplantation than at 12 months after transplantation (83 [interquartile range, 66–93] versus 92 [interquartile range, 88–98], respectively; P=0.002). Conclusions: Stable employed kidney transplant recipients report to function well at work. In addition, this study shows that self-reported work functioning is higher after successful kidney transplantation compared with before transplantation. Clinical Trial registry name and registration number: TransplantLines Biobank and Cohort study, NCT0327284

Employment and ability to work after kidney transplantation in the Netherlands:The impact of preemptive versus non-preemptive kidney transplantation

Background: Work can have a major positive impact on health and wellbeing. Employment of kidney transplant recipients (KTR) of working age is much lower than in the general population. The first aim of this study was to examine the impact of a preemptive kidney transplantation (PKT) on employment, in addition to other possible influencing factors. The second aim was to explore differences in work ability, absenteeism and work performance among employed KTR with different types of transplantations. Methods: A cross-sectional survey study was conducted between 2018 and 2019 in nine Dutch hospitals. PKT as potential predictor of employment was examined. Furthermore, work ability, absenteeism and loss of work performance were compared between employed preemptive recipients with a living donor (L-PKT) and non-preemptive recipients with a living donor (L-nPKT) and with a deceased donor (D-nPKT). Results: Two hundred and twenty four KTR participated; 71% reported having paid work. Paid work was more common among PKT recipients (82% vs. 65% in L-nPKT and 55% in D-nPKT) and recipients who were younger (OR .950, 95%CI .913-.989), had no comorbidities (1 comorbidity: OR .397, 95%CI .167-.942; 2 comorbidities: OR .347, 95%CI .142-.844), had less fatigue (OR .974, 95%CI .962-.987) and had mentally demanding work tasks (only in comparison with physically demanding tasks, OR .342, 95%CI .145-.806). If recipients were employed, D-nPKT recipients worked fewer hours (mean 24.6 +/- 11.3 vs. PKT 31.1 +/- 9.6, L-nPKT 30.1 +/- 9.5) and D-nPKT and L-nPKT recipients received more often supplemental disability benefits (32 and 33.3%, respectively) compared to PKT recipients (9.9%). No differences were found for self-reported ability to work, sick leave (absenteeism) and loss of work performance with the exception of limitations in functioning at work. Conclusions: Preemptive kidney transplantation recipients with a kidney from a living donor are employed more often, work more hours per week (only in comparison with D-nPKT) and have a partial disability benefit less often than nPKT recipients. More knowledge regarding treatments supporting sustainable participation in the labor force is needed as work has a positive impact on recipients' health and wellbeing and is also beneficial for society as a whole

Barriers to and Facilitators of Sustained Employment:A Qualitative Study of Experiences in Dutch Patients With CKD

Rationale & Objective: Although patients with chronic kidney disease (CKD) are at risk for work disability and loss of employment, not all experience work disruption. We aimed to describe the barriers to and facilitators of sustained employment experienced by Dutch patients with CKD. Study Design: Qualitative study using semi-structured interviews. Setting & Participants: 27 patients with CKD glomerular filtration rate categories 3b-5 (G3b-G5) from 4 nephrology outpatient clinics in The Netherlands. Analytical Approach: Content analyses with constant comparison of interview data based on the International Classification of Functioning, Disability and Health framework. Results: Participants were 6 patients with CKD G3b-G4, 8 patients receiving maintenance dialysis, and 13 patients with functioning kidney transplants. We identified health-related barriers (symptoms, physical toll of dialysis/transplantation, limited work capacity) and facilitators (few physical symptoms, successful posttransplantation recovery, absence of comorbidities, good physical condition), personal barriers (psychological impact, limited work experience) and facilitators (positive disposition, job satisfaction, work attitude, person-job fit), and environmental barriers and facilitators. Environmental barriers were related to nephrology care (waiting time, use of a hemodialysis catheter) and work context (reorganization, temporary contract, working hours, physical demands); environmental facilitators were related to nephrology care (personalized dialysis, preemptive transplant), work context (large employer, social climate, job requiring mental rather than physical labor, flexible working hours, adjustment of work tasks, reduced hours, remote working, support at work, peritoneal dialysis exchange facility), and support at home. Occupational health services and social security could be barriers or facilitators. Limitations: The study sample of Dutch patients may limit the transferability of these findings to other countries. Conclusions: The wide range of barriers and facilitators in all International Classification of Functioning, Disability and Health components suggests great diversity among patients and their circumstances. These findings underline the importance of personalized nephrology and occupational health care as well as the importance of individually tailored workplace accommodations to promote sustained employment for patients with CKD

Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region

Context. Leri–Weill dyschondrosteosis is a clinically variable skeletal dysplasia, caused by SHOX deletion or mutations, or a deletion of enhancer sequences in the 3’-flanking region. Recently, a 47.5 kb recurrent PAR1 deletion downstream of SHOX was reported, but its frequency and clinical importance are still unknown.Objective. This study aims to compare the clinical features of different sizes of deletions in the 3’-flanking SHOX region in order to determine the relevance of the regulatory sequences in this region.Design. We collected DNA from 28 families with deletions in the 3’-PAR1 region. Clinical data were available from 23 index patients and 21 relatives.Results. In 9 families (20 individuals) a large deletion ( ∼ 200–900 kb) was found and in 19 families (35 individuals) a small deletion was demonstrated, equal to the recently described 47.5 kb PAR1 deletion. Median height SDS, sitting height/height ratio SDS and the presence of Madelung deformity in patients with the 47.5 kb deletion were not significantly different from patients with larger deletions. The index patients had a median height SDS which was slightly lower than in their affected family members (p = 0.08). No significant differences were observed between male and female patients.Conclusions. The phenotype of patients with deletions in the 3’-PAR1 region is remarkably variable. Height, sitting height/height ratio and the presence of Madelung deformity were not significantly different between patients with the 47.5 kb recurrent PAR1 deletion and those with larger deletions, suggesting that this enhancer plays an important role in SHOX expression

Liver function tests and risk prediction of incident type 2 diabetes:evaluation in two independent cohorts

BACKGROUND: Liver function tests might predict the risk of type 2 diabetes. An independent study evaluating utility of these markers compared with an existing prediction model is yet lacking. METHODS AND FINDINGS: We performed a case-cohort study, including random subcohort (6.5%) from 38,379 participants with 924 incident diabetes cases (the Dutch contribution to the European Prospective Investigation Into Cancer and Nutrition, EPIC-NL, the Netherlands), and another population-based cohort study including 7,952 participants with 503 incident cases (the Prevention of Renal and Vascular End-stage Disease, PREVEND, Groningen, the Netherlands). We examined predictive value of combination of the Liver function tests (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase and albumin) above validated models for 7.5-year risk of diabetes (the Cooperative Health Research in the Region of Augsburg, the KORA study). Basic model includes age, sex, BMI, smoking, hypertension and parental diabetes. Clinical models additionally include glucose and uric acid (model1) and HbA1c (model2). In both studies, addition of Liver function tests to the basic model improved the prediction (C-statistic by~0.020; NRI by~9.0%; P<0.001). In the EPIC-NL case-cohort study, addition to clinical model1 resulted in statistically significant improvement in the overall population (C-statistic = +0.009; P<0.001; NRI = 8.8%; P<0.001), while addition to clinical model 2 yielded marginal improvement limited to men (C-statistic = +0.007; P = 0.06; NRI = 3.3%; P = 0.04). In the PREVEND cohort study, addition to clinical model 1 resulted in significant improvement in the overall population (C-statistic change = 0.008; P = 0.003; NRI = 3.6%; P = 0.03), with largest improvement in men (C-statistic change = 0.013; P = 0.01; NRI = 5.4%; P = 0.04). In PREVEND, improvement compared to clinical model 2 could not be tested because of lack of HbA1c data. CONCLUSIONS: Liver function tests modestly improve prediction for medium-term risk of incident diabetes above basic and extended clinical prediction models, only if no HbA1c is incorporated. If data on HbA1c are available, Liver function tests have little incremental predictive value, although a small benefit may be present in men

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice:52-Week results from the Dutch BioDay registry

Background Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited. Objective To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis. Methods Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated. Results Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was –70.0% (standard deviation 33.2%) and further decreased to –76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment. Limitations Because of the lack of a control group and observational design, factors of bias may have been induced. Conclusion Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period

Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective stud

Plasma Transfusion and Procoagulant Product Administration in Extracorporeal Membrane Oxygenation:A Secondary Analysis of an International Observational Study on Current Practices

OBJECTIVES: To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO.DESIGN: A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications. SETTING: Sixteen international ICUs.PATIENTS: Adult patients on VA-ECMO or VV-ECMO.INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 420 VA-ECMO patients, 59% (n = 247) received plasma, 20% (n = 82) received fibrinogen concentrate, 17% (n = 70) received TXA, and 7% of patients (n = 28) received PCC. Fifty percent of patients (n = 208) suffered bleeding complications and 27% (n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p &lt; 0.001), fibrinogen concentrate (28% vs 11%, p &lt; 0.001), and TXA (23% vs 10%, p &lt; 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% (n = 81) received plasma, 6% (n = 12) fibrinogen concentrate, 7% (n = 14) TXA, and 5% (n = 10) PCC. Thirty-nine percent (n = 80) of VV-ECMO patients suffered bleeding complications and 23% (n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p &lt; 0.001), fibrinogen concentrate (13% vs 2%, p &lt; 0.01), and TXA (11% vs 2%, p &lt; 0.01). CONCLUSIONS: The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided.</p