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Background: Using data from the COHERE collaboration, we investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count.
Methods: We implemented an established causal inference approach whereby observational data are used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/µL in line with existing recommendations. We compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/µL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio (HR) to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring.
Results: A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR, .8; 95% confidence interval, .6–1.1; P = .2).
Conclusions: This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count.
Background: This study investigated whether work ability is associated with the duration of unemployment, heart rate variability (HRV), and the level of physical activity. Methods: Thirty-four unemployed persons (mean 55.7 ± standard deviation 33.3 years, 22 female, 12 male, unemployed: range 1–22.5 years) participated in the cross-sectional study. The Work Ability Index (WAI) and International Physical Activity Questionnaire (IPAQ) were applied. Short-term (five minutes) resting HRV (Low Frequency (LF), High Frequency (HF), Total Power (TP)) was collected. Results: Work ability was positively associated with the HRV: LF (r = 0.383; p = 0.025), HF (r = 0.412; p = 0.015) and TP (r = 0.361; p = 0.036). The WAI showed a positive linear correlation with the amount of total physical activity (r = 0.461; p = 0.006) as well as with the amount of moderate to vigorous physical activity (r = 0.413; p = 0.015). No association between the WAI and the duration of unemployment occurred. Conclusions: the relation between self-perceived work ability, health-associated parameters, the HRV and the level of physical activity points out the relevance of health-care exercise and the need of stress-reducing interventions to improve perceived work ability. Our results point out the need for the further and more holistic development of healthcare for the unemployed.
Background & Aims: Elimination of chronic HBV/HDV infection remains a major global health challenge. Targeting excessive hepatitis B surface antigen (HBsAg) release may provide an interesting window of opportunity to break immune tolerance and to achieve a functional cure using additional antivirals.
Methods: We evaluated a HBsAg-specific human monoclonal antibody, as part of either a prophylactic or therapeutic strategy, against HBV/HDV infection in cell culture models and in human-liver chimeric mice. To assess prophylactic efficacy, mice were passively immunized prior to infection with HBV or HBV/HDV (coinfection and superinfection setting). Therapeutic efficacy was assessed in HBV and HBV/HDV-coinfected mice receiving 4 weeks of treatment. Viral parameters (HBV DNA, HDV RNA and HBsAg) were assessed in mouse plasma.
Results: The antibody could effectively prevent HBV/HDV infection in a dose-dependent manner with IC50 values of ∼3.5 ng/ml. Passive immunization showed complete protection of mice from both HBV and HBV/HDV coinfection. Moreover, HDV superinfection was either completely prevented or at least attenuated in HBV-infected mice. Finally, antibody treatment in mice with established HBV/HDV infection resulted in a significant decline in viremia and a concomitant drop in on-treatment HBsAg, with a moderate viral rebound following treatment cessation.
Conclusion: We present data on a valuable antibody candidate that could complement other antivirals in strategies aimed at achieving functional cure of chronic HBV and HDV infection.
Impact and implications: Patients chronically infected with HBV may eventually develop liver cancer and are at great risk of being superinfected with HDV, which worsens and accelerates disease progression. Unfortunately, current treatments can rarely eliminate both viruses from chronically infected patients. In this study, we present data on a novel antibody that is able to prevent chronic HBV/HDV infection in a mouse model with a humanized liver. Moreover, antibody treatment of HBV/HDV-infected mice strongly diminishes viral loads during therapy. This antibody is a valuable candidate for further clinical development.
Child sexual abuse has been discussed thoroughly; however, marginalized groups of victims such as victims of child sexual abuse in early childhood and victims of maternal sexual abuse have rarely been considered. This essay combines these two relevant perspectives in child protection and aims to pin out future directions in the field of child abuse and specifically maternal sexual abuse and its early prevention. In the course of the 7th Haruv International PhD Workshop on Child Maltreatment at the Hebrew University, Jerusalem, in 2019 the topics of maternal sexual abuse and early prevention of child maltreatment in Germany were discussed and intertwined. Problems concerning the specific research of maternal sexual abuse in early childhood and prevention were identified. Both, maternal sexual abuse as well as sexual abuse in early childhood, i.e. before the age of three, are underreported topics. Society still follows a “friendly mother illusion” while recent cases in German media as well as research findings indicate that the mother can be a perpetrator of child sexual abuse. Similarly, sexual abuse in early childhood, namely abuse before the age of three, is existent; although the recognition of it is difficult and young children are, in regards to their age and development especially vulnerable. They need protective adults in their environment, who are aware of sexual abuse in the first years of life. Raising awareness on marginalized or tabooed topics can be a form of prevention. An open dialog in research and practice about the so far marginalized topics of maternal sexual abuse and sexual abuse in early childhood is crucial.
Mitochondria are involved in the aging processes that ultimately lead to neurodegeneration and the development of Alzheimer’s disease (AD). A healthy lifestyle, including a diet rich in antioxidants and polyphenols, represents one strategy to protect the brain and to prevent neurodegeneration. We recently reported that a stabilized hexanic rice bran extract (RBE) rich in vitamin E and polyphenols (but unsuitable for human consumption) has beneficial effects on mitochondrial function in vitro and in vivo (doi:10.1016/j.phrs.2013.06.008, 10.3233/JAD-132084). To enable the use of RBE as food additive, a stabilized ethanolic extract has been produced. Here, we compare the vitamin E profiles of both extracts and their effects on mitochondrial function (ATP concentrations, mitochondrial membrane potential, mitochondrial respiration and mitochondrial biogenesis) in PC12 cells. We found that vitamin E contents and the effects of both RBE on mitochondrial function were similar. Furthermore, we aimed to identify components responsible for the mitochondria-protective effects of RBE, but could not achieve a conclusive result. α-Tocotrienol and possibly also γ-tocotrienol, α-tocopherol and δ-tocopherol might be involved, but hitherto unknown components of RBE or a synergistic effect of various components might also play a role in mediating RBE’s beneficial effects on mitochondrial function.
In der Prävention und Behandlung des frühen Mammakarzinoms sind über die Jahre immer wieder kleine, aber bedeutsame Fortschritte gemacht worden. In der Prävention gewinnen die sogenannten Panel-Gen-Analysen immer mehr an Bedeutung, da das durch die getesteten Gene bedingte Risiko immer besser verstanden wird und somit Konzepte für die Integration in die Krankenversorgung erarbeitet werden können. In der adjuvanten Situation konnte die erste Studie in der sogenannten postneoadjuvanten Situation bei fehlender pathologischer Komplettremission nach Trastuzumab oder Pertuzumab + Trastuzumab eine deutliche Verbesserung der Prognose zeigen. Weitere Studien mit diesem postneoadjuvanten Therapiekonzept werden zurzeit noch durchgeführt. Die CDK4/6-Inhibitoren, die in der metastasierten Situation eine deutliche Verbesserung des progressionsfreien Überlebens gezeigt hatten, werden zurzeit in der adjuvanten Situation in großen Therapiestudien getestet. Diese und weitere neue Daten zur Behandlung oder Prävention des primären Mammakarzinoms werden in dieser Übersichtsarbeit vor dem Hintergrund aktueller Studien vorgestellt.
For many years, small but significant advancements have been made time and again in the prevention and treatment of early breast cancer. The so-called panel gene analyses are becoming more and more important in prevention, since the risk due to the tested genes is better understood and as a result, concepts for integration in health care can be developed. In the adjuvant situation, the first study in the so-called post-neoadjuvant situation was able to demonstrate a clear improvement in the prognosis with an absent pathological complete remission following trastuzumab or pertuzumab + trastuzumab. Additional studies with this post-neoadjuvant therapeutic concept are still being conducted at present. The CDK4/6 inhibitors which had shown a significant improvement in progression-free survival in a metastatic situation are currently being tested in the adjuvant situation in large therapeutic studies. These and other new data for the treatment or prevention of primary breast cancer are presented in this review against the backdrop of current studies.
This position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth.
Hintergrund: Das Kindesalter wurde bei der Entwicklung von wirksamen Präventions- und Interventionsprogrammen bei Computerspiel- und Internetabhängigkeit bisher kaum berücksichtigt. PROTECTdissonanz wurde daher als 1-stündiges dissonanzbasiertes universelles Primärpräventionsprogramm für die Klassenstufe 5 konzipiert. Die vorliegende Pilotstudie überprüft die unmittelbaren Effekte der Dissonanzinduktion auf die Einstellung zum Gaming. Methodik: In einem einarmigen A+B-Design mit drei Messzeitpunkten (T0, T1, T2) wurde die Einstellung zum Gaming anhand des Gaming Attitude Test (GAT) erfasst. In die Baselinesequenz (Sequenz A, T0 bis T1, Teilstichprobe) wurden N = 83 Schüler_innen eingeschlossen (Alter: M = 10.27; SD = 0.48) und in die Interventionssequenz (Sequenz B, T1 bis T2, Gesamtstichprobe) N = 200 Schüler_innen (Alter: M = 10.24; SD = 0.47). Akzeptanz und Zufriedenheit wurden nach der Intervention erfasst. Ergebnisse: Hierarchisch lineare Wachstumsmodelle zeigten eine signifikante Reduktion der GAT-Symptome durch die Intervention, sowohl im Gesamtwert des GAT als auch auf der Subskala „Bagatellisierung negativer Konsequenzen“. Im natürlichen Verlauf (Baselinesequenz A) zeigten sich keine Veränderungen. Die Schüler_innen bewerteten PROTECTdissonanz zudem mit einer hohen Zufriedenheit. Schlussfolgerungen: Eine kurze, gezielte übung zur Dissonanzinduktion zeigt unmittelbare Effekte auf ein Einstellungsmaß zum Gaming. Zur Weiterverfolgung dieses vielversprechenden Ansatzes sollte in künftigen Studien untersucht werden, ob sich eine verringerte Bagatellisierung negativer Konsequenzen von Gaming im Sinne der kognitiven Dissonanztheorie auch tatsächlich in einer Verhaltensänderung widerspiegelt.
Background: Surgical complications are associated with a significant burden to patients and hospitals and are increasingly discussed in recent literature. This cohort study reviewed surgery-related complications in a Level I trauma center. The effect of a complication avoidance care bundle on the rate of surgical complications was analyzed. Methods: All complications (surgical and nonsurgical) that occur in our trauma department are prospectively captured using a standardized documentation form and are discussed and analyzed in a weekly trauma Morbidity and Mortality (M&M) conference. Surgical complication rates are calculated using the annual surgical procedure numbers. Based on discussions in the M&M conference, a complication avoidance care bundle consisting of five measures was established: (1) Improving team situational awareness; (2) reducing operating room traffic by staff members and limiting door-opening events; (3) preoperative screening for infectious foci; (4) adapted preoperative antibiotic prophylaxis in anatomic regions with a high risk of infectious complications; and (5) use of iodine-impregnated adhesive drape. Results: The number of surgical procedures steadily increased over the study years, from 3587 in 2015 to 3962 in 2019 (an increase of 10.5%). Within this 5-year study period, the overall rate of surgical complications was 0.8%. Surgical site infections were the most frequently found complications (n = 40, 24.8% of all surgical complications), followed by screw malposition (n = 20, 12.4%), postoperative dislocations of arthroplasties (n = 18, 11.2%), and suboptimal fracture reduction (n = 18, 11.2%). Following implementation of the complication avoidance care bundle, the overall rate of surgical complications significantly decreased, from 1.14% in the year 2016 to 0.56% in the study year 2019, which represents a reduction of 51% within a 3-year time period. Conclusions: A multimodal strategy targeted at reducing the surgical complication rate can be successfully established based on a transparent discussion of adverse surgical outcomes. The combination of the different preventive measures was associated with reducing the overall complication rate by half within a 3-year time period.