Patient-reported Quality of Life and Survival Outcomes in Prostate Cancer: Analysis of the ECOG-ACRIN E3805 Chemohormonal Androgen Ablation Randomized Trial (CHAARTED).

BACKGROUND: Chemohormonal therapy with androgen deprivation therapy and docetaxel (ADT + D) improves overall survival (OS) and quality of life (QOL) at 12 mo versus androgen deprivation therapy (ADT) alone in men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the prognostic role of QOL is unknown in this population. OBJECTIVE: To study the relationship between QOL, disease characteristics, and OS in men with mHSPC. DESIGN, SETTING, AND PARTICIPANTS: In this exploratory post hoc analysis, 790 patients with mHSPC completed the QOL instruments Functional Assessment of Cancer Therapy-Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Brief Pain Inventory (BPI). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Log-rank test and Cox proportional hazard models tested the association between QOL and OS by clinical and disease characteristics. RESULTS AND LIMITATIONS: Baseline higher FACT-P trended toward improved survival after accounting for clinical variables (hazard ratio [HR] 0.80 [0.62, 1.04], p = 0.09), while higher 3-mo FACT-P was independently associated with better survival (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the poorest QOL (bottom quartile) at baseline and 3 mo had longer survival if they received ADT + D rather than ADT alone (median OS 45.2 vs 34.4 mo, HR 0.75 [0.53, 1.05], p = 0.09, and 48.3 vs 29.3 mo, HR 0.69 [0.48, 0.99], p = 0.05 respectively). In contrast, patients with the best QOL (top quartile) at baseline and 3 mo had comparable survival irrespective of whether or not docetaxel was added (median OS 72.1 vs 51.7 mo, HR 0.92 [0.63, 1.36], p = 0.69, and 69.9 vs 68.9 mo, HR 1.11 [0.73, 1.67], p = 0.63, respectively). Survival was linked with baseline FACIT-F (HR 0.76 [0.57, 1.0], p = 0.05), but not BPI (HR 0.98 [0.75, 1.28], p = 0.90). CONCLUSIONS: Three-month QOL had a stronger independent association with survival. The most symptomatic patients had longer survival with the addition of docetaxel; conversely, the least symptomatic patients did not appear to benefit. Consideration of QOL may enhance decision-making and patient selection when choosing chemohormonal treatment in mHSPC. PATIENT SUMMARY: Quality of life independently forecasted the survival of men with metastatic hormone-sensitive prostate cancer in the CHAARTED study. Close tracking of quality of life could help patients and clinicians make decisions about the appropriate treatment in this setting.

Pharmacokinetics and pharmacodynamics of five distinct commercially available hemp-derived topical cannabidiol products.

Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9-tetrahydrocannabinol (Δ9-THC)). CBD-containing topical products have surged in popularity, but controlled clinical studies on them are limited. This study characterized the effects of five commercially available hemp-derived high CBD/low Δ9-THC topical products. Healthy adults (N = 46) received one of six study drugs: a CBD-containing cream (N = 8), lotion (N = 8), patch (N = 7), balm (N = 8), gel (N = 6) or placebo (N = 9; matched to an active formulation). The protocol included three phases conducted over 17 days: (i) an acute drug application laboratory session, (ii) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7 and 10) (iii) a 1-week washout phase. In each phase, whole blood, oral fluid and urine specimens were collected and analyzed via liquid chromatography with tandem mass spectrometry (LC-MS-MS) for CBD, Δ9-THC and primary metabolites of each and pharmacodynamic outcomes (subjective, cognitive/psychomotor and physiological effects) were assessed. Transdermal absorption of CBD was observed for three active products. On average, CBD/metabolite concentrations peaked after 7-10 days of product use and were highest for the lotion, which contained the most CBD and a permeation enhancer (vitamin E). Δ9-THC/metabolites were below the limit of detection in blood for all products, and no urine samples tested "positive" for cannabis using current US federal workplace drug testing criteria (immunoassay cut-off of 50 ng/mL and confirmatory LC-MS-MS cut-off of 15 ng/mL). Unexpectedly, nine participants (seven lotions, one patch and one gel) exhibited Δ9-THC oral fluid concentrations ≥2 ng/mL (current US federal workplace threshold for a "positive" test). Products did not produce discernable pharmacodynamic effects and were well-tolerated. This study provides important initial data on the acute/chronic effects of hemp-derived topical CBD products, but more research is needed given the diversity of products in this market.

How public catering accelerates sustainability: a German case study.

Public catering has become increasingly important in recent years. With increasing annual customers, the sector's impact on the environment is also growing continuously. At the same time, public catering offers a lever to promote sustainable nutrition that has rarely been used so far. Small changes in kitchen practices and food offers can thus be multiplied into a significant positive impact on environmental challenges, such as climate change or loss of biodiversity due to the large number of servings. In contrast to private households, management decisions in public catering can influence the food-related environmental impact of thousands of customers. This article deals with the nationwide level of greenhouse gas (GHG) emissions and resource use in the German public catering segment "business" and its saving potentials by different scenarios of unsupported and supported recipe revision. In this paper, we define "unsupported" as the intuitive optimization of recipes by employees of public catering businesses. In contrast, "supported" approaches had to meet specific target goals, for example of the Deutsche Gesellschaft für Ernährung; engl. German Nutrition Society or the sustainable level. Specifically, we will test how (A) an unsupported recipe revision, (B) a recipe revision based on dietary recommendations and (C) a recipe revision using scientific guidance affect the environmental impact of a dish. As a methodological framework, an online survey of public catering companies was conducted as well as a scenario analysis at menu level and at nationwide level. The results are based on empirical data on the one hand, and on extrapolations on the other. The results show that the nationwide implementation of recipe revision according to scientific guidance-such as concrete target goals for the GHG emissions per serving-can save up to 44% of resource use in the German business catering sector (which corresponds to 3.4 million tons of resources per year) and as much as 40% of GHG emissions (0.6 million tons GHG emissions per year). Even in the scenario of unsupported recipe revision, GHG and resource savings of up to 20% can be realized. The results show that public catering can reduce its material and carbon footprint by 20% overnight. Moreover, the findings show indications for the sustainable transformation of public catering. Nevertheless, it must be noted that these are some first steps of the transformation, which will require further changes with even greater impacts and political activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01183-2.

Evaluation of an individualized, tablet-based physiotherapy training programme for patients with Parkinson's disease: the ParkProTrain study, a quasi-randomised controlled trial.

BACKGROUND: Regular physical activity is of great relevance in Parkinson's disease (PD). It is part of the inpatient multimodal Parkinson's complex treatment (MKP) in Germany. However, there is often a lack of human resources in outpatient settings to continue an interprofessional approach. A large proportion of PD patients live a predominantly sedentary lifestyle and do not get enough exercise. METHODS: The intervention group (IG) used a tablet-based physiotherapy training programme at home for a period of nine months. We conducted a quasi-randomised longitudinal study with three measurement times (at the beginning (t0) and end of MKP (t1) and at 9 months after MKP (t2)). The primary outcome measured was PD-specific quality of life using the PDQ-8. The secondary outcome focused on participation restrictions, falling anxiety, sleep disorder, anxiety and depression as well as comorbidity, pain, performance capability and physical activity. RESULTS: For n = 93 IG and n = 137 control group (CG) patients, evaluable cases were available for all measurement times. Both groups achieved significant improvements in all parameters at the end of MKP. These parameters deteriorated again at nine months after MKP for most parameters and were even below the baseline levels. However, this deterioration was less pronounced in the IG than in the CG. For general health and social participation, a significant slightly positive effect was observed in the IG nine months after MKP when compared with the baseline level. Paying attention to physical activity slightly increased in the IG for the catamnesis survey compared to baseline. Nearly all IG patients were satisfied with the intervention, especially with the consultations with the physiotherapist. CONCLUSIONS: Although the expected extent of effects could not be determined for the IG, stabilisation effects could be demonstrated. These stabilisation effects shown for the IG might be attributed to the intervention. The effects might have been greater without the COVID-19 pandemic. TRIAL REGISTRATION: German Register of Clinical Trials, drks.de. Identifier: DRKS00014952. Registered 20/06/2018. Date and version identifier 25/04/2019; version 1.

[Implementation of an individualized tablet-based training program in the domestic setting following complex treatment of Parkinson's disease-Success factors and barriers]. / Implementierung eines individualisierbaren tabletbasierten Trainingsprogramms im Anschluss an eine Parkinson-Komplexbehandlung in der Häuslichkeit ­ Erfolgsfaktoren und Barrieren.

BACKGROUND: Regular physical activity is of great relevance in Parkinson's disease. As part of the project "Individualized training program for Parkinson's disease patients" (ParkProTrain), a tablet-based program was developed to support individual self-training. It has been tested over a period of 9 months in domestic settings. Patients were asked about the feasibility of use and satisfaction. METHODS: Patients who used the program at home following inpatient Parkinson's complex treatment (PCT) were interviewed twice (9 and 36 weeks after PCT). RESULTS: The program helped patients to stay motivated throughout the interventional period. It provided them with both structure and flexibility to develop their own training routine. The following were named as positive aspects (success factors), including: the introductory seminars in the clinic, the close supervision during the interventional period, the soundness and Parkinson's specificity, the feasibility and manageability of the program and the individualized training plans; however, patients also provided information on how the program could still be optimized (barriers). DISCUSSION: The program has already successfully implemented a number of aspects that promote activity. Further recommendations were derived for future use, to which more attention should be paid: Parkinson's specificity and individualization of the program, flexible training in terms of location and time, close and personal support throughout the study period and the technique should be designed to be easy to learn and manage.

Justice and Negotiation.

This review article examines the literature regarding the role played by principles of justice in negotiation. Laboratory experiments and high-stakes negotiations reveal that justice is a complex concept, both in relation to attaining just outcomes and to establishing just processes. We focus on how justice preferences guide the process and outcome of negotiated exchanges. Focusing primarily on the two types of principles that have received the most attention, distributive justice (outcomes of negotiation) and procedural justice (process of negotiation), we introduce the topic by reviewing the most relevant experimental and field or archival research on the roles played by these justice principles in negotiation. A discussion of the methods used in these studies precedes a review organized in terms of a framework that highlights the concept of negotiating stages. We also develop hypotheses based on the existing literature to point the way forward for further research on this topic.

Effectiveness of rapid prescreening and 10% rescreening in liquid-based Papanicolaou testing.

Although rapid prescreening (RPS) has been shown to be an effective quality control procedure for detecting false-negative conventional Papanicolaou (Pap) tests, RPS has not been widely implemented in the United States. In our laboratory, cytotechnologists performed RPS in 3,567 liquid-based Pap tests: 1,911 SurePath (BD Diagnostics-TriPath, Burlington, NC) preparations that were manually screened and 1,656 ThinPrep Pap tests (Hologic, Bedford, MA) that were imaged using the ThinPrep Imaging System (Hologic). We compared the sensitivity of RPS, 10% rescreening (R-10%), and routine screening (RS). In contrast with previously published findings, we found that RS + RPS did not improve screening sensitivity compared with RS + R-10%. These results support the following hypotheses: (1) Higher baseline RS sensitivity as a result of Pap test diagnoses standardization implemented for quality improvement purposes decreases the performance impact of RPS. (2) R-10% and RPS quality assurance methods detect diagnostic failures caused by different types of cognitive errors.

Domain V peptides inhibit beta2-glycoprotein I-mediated mesenteric ischemia/reperfusion-induced tissue damage and inflammation.

Reperfusion of ischemic tissue induces significant tissue damage in multiple conditions, including myocardial infarctions, stroke, and transplantation. Although not as common, the mortality rate of mesenteric ischemia/reperfusion (IR) remains >70%. Although complement and naturally occurring Abs are known to mediate significant damage during IR, the target Ags are intracellular molecules. We investigated the role of the serum protein, ß2-glycoprotein I as an initiating Ag for Ab recognition and ß2-glycoprotein I (ß2-GPI) peptides as a therapeutic for mesenteric IR. The time course of ß2-GPI binding to the tissue indicated binding and complement activation within 15 min postreperfusion. Treatment of wild-type mice with peptides corresponding to the lipid binding domain V of ß2-GPI blocked intestinal injury and inflammation, including cellular influx and cytokine and eicosanoid production. The optimal therapeutic peptide (peptide 296) contained the lysine-rich region of domain V. In addition, damage and most inflammation were also blocked by peptide 305, which overlaps with peptide 296 but does not contain the lysine-rich, phospholipid-binding region. Importantly, peptide 296 retained efficacy after replacement of cysteine residues with serine. In addition, infusion of wild-type serum containing reduced levels of anti-ß2-GPI Abs into Rag-1(-/-) mice prevented IR-induced intestinal damage and inflammation. Taken together, these data suggest that the serum protein ß2-GPI initiates the IR-induced intestinal damage and inflammatory response and as such is a critical therapeutic target for IR-induced damage and inflammation.

TLR4-mediated Cox-2 expression increases intestinal ischemia/reperfusion-induced damage.

Mesenteric IR induces significant inflammation and immune-mediated mucosal damage. TLR4 is a critical receptor in the induction of the inflammatory response and plays a role in intestinal homeostasis. To determine the role of TLR4 in IR-induced epithelial damage, we performed IR studies using TLR4(lps-def) and TLR4(lps-n) mice and analyzed mucosal damage and inflammation. We found that the absence of TLR4 or TLR4-induced signaling attenuated local mucosal damage with significantly decreased cytokine and eicosanoid secretion including PGE2 production. Similar results were seen in MyD88-/- mice. Wild-type mice treated with NS-398 (a Cox-2 inhibitor) not only decreased PGE2 production but also attenuated tissue damage. In contrast, PGE2 was not sufficient to induce damage in the TLR4(lps-def) mice. Together, these data indicate that TLR4 stimulation of Cox-2 activation of PGE2 production is necessary but not sufficient for intestinal IR-induced damage and inflammation.