Role for a Web-Based Intervention to Alleviate Distress in People With Newly Diagnosed Testicular Cancer: Mixed Methods Study.

BACKGROUND: Distress is common immediately after diagnosis of testicular cancer. It has historically been difficult to engage people in care models to alleviate distress because of complex factors, including differential coping strategies and influences of social gender norms. Existing support specifically focuses on long-term survivors of testicular cancer, leaving an unmet need for age-appropriate and sex-sensitized support for individuals with distress shortly after diagnosis. OBJECTIVE: We evaluated a web-based intervention, Nuts & Bolts, designed to provide support and alleviate distress after diagnosis of testicular cancer. METHODS: Using a mixed methods design to evaluate the acceptability, feasibility, and impact of Nuts & Bolts on distress, we randomly assigned participants with recently diagnosed testicular cancer (1:1) access to Nuts & Bolts at the time of consent (early) or alternatively, 1 week later (day 8; delayed). Participants completed serial questionnaires across a 4- to 5-week period to evaluate levels of distress (measured by the National Comprehensive Cancer Network Distress Thermometer [DT]; scored 0-10), anxiety, and depression (Hospital Anxiety and Depression Score [HADS]-Anxiety and HADS-Depression; each scored 0-21). The primary end point was change in distress between consent and day 8. Secondary end points of distress, anxiety, and depression were assessed at defined intervals during follow-up. Optional, semistructured interviews occurring after completion of quantitative assessments were thematically analyzed. RESULTS: Overall, 39 participants were enrolled in this study. The median time from orchidectomy to study consent was 14.8 (range 3-62) days. Moderate or high levels of distress evaluated using DT were reported in 58% (23/39) of participants at consent and reduced to 13% (5/38) after 1 week of observation. Early intervention with Nuts & Bolts did not significantly decrease the mean DT score by day 8 compared with delayed intervention (early: 4.56-2.74 vs delayed: 4.47-2.74; P=.85), who did not yet have access to the website. A higher baseline DT score was significantly predictive of reduction in DT score during this period (P<.001). Median DT, HADS-Anxiety, and HADS-Depression scores reduced between orchidectomy and 3 weeks postoperatively and then remained stable throughout the observation period. Thematic analysis of 16 semistructured interviews revealed 4 key themes, "Nuts & Bolts is a helpful tool," "Maximizing benefits of the website," "Whirlwind of diagnosis and readiness for treatment," and "Primary stressors and worries," as well as multiple subthemes. CONCLUSIONS: Distress is common following the diagnosis of testicular cancer; however, it decreases over time. Nuts & Bolts was considered useful, acceptable, and relevant by individuals diagnosed with testicular cancer, with strong support for the intervention rendered by thematic analyses of semistructured interviews. The best time to introduce support, such as Nuts & Bolts, is yet to be determined; however, it may be most beneficial as soon as testicular cancer is strongly suspected or diagnosed.

End of life care pathways in the Emergency Department and their effects on patient and health service outcomes: An integrative review.

INTRODUCTION: End of life (EOL) care in the Emergency Department (ED) requires focused, person-centred care to meet the needs of this vulnerable cohort of patients. METHODS: An integrative review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was conducted. Studies were included if they were primary research relating to patients in the ED at the EOL, and/or evaluated EOL care pathways in the ED. Databases OVID Emcare, OVID Medline, and Scopus were searched from 1966-September 2021; followed by screening and appraisal. Articles were compared and data grouped into categories. RESULTS: Eleven research articles were included generating three categories for EOL care in ED. 1) tools/criteria to identify patients who may require EOL care in ED; 2) processes for providing EOL care, and 3) implementation methods/frameworks to support the uptake of EOL care processes. CONCLUSION: There were some commonalities in the criteria used to identify patients who may be at their EOL and the interventions implemented thereafter. There was no standardised process for screening for or treating EOL care needs in the ED. Further research is required to determine the impact that EOL care pathways have on patient and health service outcomes to inform strategies for future policy development.

Clinician and Patient Experience of Internet-Mediated Eye Movement Desensitisation and Reprocessing Therapy.

Many eye movement desensitization and reprocessing (EMDR) therapists moved their practice online during COVID-19. We conducted surveys and interviews to understand the implementation and acceptability of online EMDR therapy. From 17 June to 2nd August 2021 an online survey was open to EMDR therapists from the EMDR Association UK & Ireland and EMDR International Association email lists, and, through them, their clients. Questions related to determinants of implementation (for therapists) and acceptability (for clients) of online EMDR. Semi-structured interviews were conducted with a sample of therapist respondents to provide a deeper understanding of survey responses. Survey responses were received from therapists (n = 562) from five continents, and their clients (n = 148). 88% of clients responded as being extremely or very comfortable receiving EMDR therapy online. At the initial point of 'social distancing', 54% of therapists indicated strong or partial reluctance to deliver online EMDR therapy compared to 11% just over one year later. Four fifths of therapists intended to continue offering online therapy after restrictions were lifted. Free-text responses and interview data showed that deprivation and clinical severity could lead to exclusion from online EMDR. Internet connectivity could disrupt sessions, lead to cancellations, or affect the therapy process. Therapists benefited from training in online working. Online EMDR is generally acceptable to therapists and clients, with reservations about digital exclusion, case severity, poor internet connectivity and the need for training. Further research is needed to confirm that online EMDR is clinically non-inferior to in-person working. Supplementary Information: The online version contains supplementary material available at 10.1007/s40737-022-00260-0.

The EU Green Deal's ambition for a toxic-free environment: Filling the gap for science-based policymaking.

Around the world, many ambitious environmental conventions and regulations have been implemented over recent decades. Despite this, the environment is still deteriorating. An increase in the volume and diversity of chemicals is one of the main drivers of this deterioration, of which biodiversity loss is a telling indicator. In response to this situation, in October 2020, a chemicals strategy for sustainability (CSS) was published in the EU. The CSS is the first regional framework aiming to address chemical pollution in a holistic manner. The CSS covers the complete lifecycle of a chemical, including the design of better substances and remediation options, to remove chemicals from the environment. The strategy contains terms, such as a "toxic-free environment," for which no clear definition exists, potentially hampering the implementation of the CSS. In this paper, a definition for a "toxic-free environment" is proposed on the basis of a survey and a discussion held at the 2020 SETAC Europe Annual Meeting. In addition, key issues that are absent from the CSS but are considered to be key for the realization of a toxic-free environment are identified. To achieve the policy goals, it is recommended to align the definition of risk across the different chemical legislations, to establish a platform for open data and data sharing, and to increase the utility and use of novel scientific findings in policymaking, through the development of a strong science to regulation feedback mechanism and vice versa. The paper concludes that environmental scientists have the tools to address the key challenges presented in the CSS. However, an extra step is needed by both policymakers and scientists to develop methods, processes and tools, to increase the robustness and transparency of deliberation processes, and the utility of science. Integr Environ Assess Manag 2021;17:1105-1113. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Comparative toxicity assessment of in situ burn residues to initial and dispersed heavy fuel oil using zebrafish embryos as test organisms.

In situ burning (ISB) is discussed to be one of the most suitable response strategies to combat oil spills in extreme conditions. After burning, a highly viscous and sticky residue is left and may over time pose a risk of exposing aquatic biota to toxic oil compounds. Scientific information about the impact of burn residues on the environment is scarce. In this context, a comprehensive ISB field experiment with approx. 1000L IFO 180 was conducted in a fjord in Greenland. The present study investigated the toxicity of collected ISB residues to early life stages of zebrafish (Danio rerio) as a model for potentially exposed pelagic organisms. The toxicity of ISB residues on zebrafish embryos was compared with the toxicity of the initial (unweathered) IFO 180 and chemically dispersed IFO 180. Morphological malformations, hatching success, swimming behavior, and biomarkers for exposure (CYP1A activity, AChE inhibition) were evaluated in order to cover the toxic response on different biological organization levels. Across all endpoints, ISB residues did not induce greater toxicity in zebrafish embryos compared with the initial oil. The application of a chemical dispersant increased the acute toxicity most likely due to a higher bioavailability of dissolved and particulate oil components. The results provide insight into the adverse effects of ISB residues on sensitive life stages of fish in comparison with chemical dispersant application.

Receptor-mediated estrogenicity of native and chemically dispersed crude oil determined using adapted microscale reporter gene assays.

Endocrine disrupting compounds (EDCs) emerged as a major concern for water quality in the last decade and have been studied extensively since. Besides typical natural and synthetic estrogens also petroleum product compounds such as some PAHs have been identified as potential EDCs, revealing endocrine disruption to be a relevant mode of action for crude oil toxicity. Hence, in the context of a comprehensive retro- or prospective risk assessment of oil spills the implementation of mechanism-specific toxicity such as endocrine disruption is of high importance. To evaluate the exposure risk for the aquatic biota, research focuses on water-soluble fractions underlying an oil slick that could be simulated via water-accommodated fractions (WAF). Against this background human (ERα-CALUX®) and yeast based (A-YES®) reporter gene bioassays were successfully optimized for the application in estrogenicity evaluation of the water-accommodated fraction (WAF) from a crude oil. Combining different approaches, the estrogenicity of the WAFs from a naphthenic North Sea crude oil was tested with and without the addition of a chemical dispersant addressing specific aspects of estrogenicity including the influence of biotransformation capacities and different salinity conditions. Both the WAF free from droplets (LEWAF) as well as the chemically dispersed WAF (CEWAF) gave indications of an ER-mediated estrogenicity with much stronger ERα agonists in the CEWAF treatment. Resulting estradiol equivalents of the WAFs were above the established effect-based trigger values for both bioassays. Results indicate that the dispersant rather increased the fraction of ER-activating crude oil compounds instead of interacting with the receptor itself. Only slight changes in estrogenic responses were observed when cells capable of active metabolism (T47D) were used instead of cells without endogenous metabolism (U2-OS) in the recombinant ER transactivation CALUX assay. With the yeast cells a higher estrogenic activity was observed in the experiments under elevated salinity conditions (6‰), which was in contrast to previous expectations due to typical decrease in dissolved PAH fraction with increasing salinity (salting-out effect) but might be related to increased cell sensitivity.

Differences in biomarker and behavioral responses to native and chemically dispersed crude and refined fossil oils in zebrafish early life stages.

Petroleum products including crude oils and refined distillates are unique environmental pollutants consisting of thousands of compounds with varying physical-chemical properties and resulting toxicity for aquatic biota. Hence, for a reliable risk assessment individual petroleum product toxicity profiles are needed. Furthermore, the influence of oil spill response strategies like the application of chemical dispersants has to be implemented. The present study addressed the toxicity of water-accommodated fractions (WAFs) of two different oil types on fish early life stages on different biological organization levels in the laboratory model species Danio rerio. Experiments with a 3rd generation dispersant used in loading rated resembling the exposure in experiments with chemically dispersed oils were included, enabling a direct comparability of results. This approach is of high importance as especially the investigation of dispersant toxicity in relevant exposure concentrations is rather scarce. Zebrafish embryos were exposed to different WAFs shortly after and up to 120 hour post fertilization (hpf). Besides phenotypic effects including edema and spine deformations, reduced responses to dark stimuli, increased CYP1A activity and marginal AChE inhibition were observed in sublethal effect concentrations. Both oil types had varying strength of toxicity, which did not correlate with corresponding chemical analysis of target PAHs. Chemically dispersed oils induced stronger acute toxicity in zebrafish embryos compared to native (initial) oil exposure, which was further reflected by very low exposure concentrations for biomarker endpoints. Based on a comparison to the dispersant alone, a higher toxicity of dispersed oils was related to a combination of dispersant toxicity and an elevated crude oil compound bioavailability, due to dispersion-related partitioning kinetics. In contrast to LEWAF and CEWAF neither typical morphological effects nor mechanism-specific toxicity were observed for the dispersant alone, indicating narcosis as the responsible cause of effects.

Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry.

BACKGROUND: Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. OBJECTIVE: Early-medium-term cancer control and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8mo [interquartile range (IQR) 19.5-36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies. INTERVENTION: Focal cryoablation of MR-visible tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes. RESULTS AND LIMITATIONS: A total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7yr (IQR 64.9-73.8) and preoperative PSA 10.8ng/ml (IQR 7.8-15.6). Overall FFS at 3yr was 90.5% [95% confidence interval (CI) 84.2-97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4-100) in high risk and 93.3% (95% CI 86.8-100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes. CONCLUSIONS: Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. PATIENT SUMMARY: In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems.

European demonstration program on the effect-based and chemical identification and monitoring of organic pollutants in European surface waters.

Growing concern about the adverse environmental and human health effects of a wide range of micropollutants requires the development of novel tools and approaches to enable holistic monitoring of their occurrence, fate and effects in the aquatic environment. A European-wide demonstration program (EDP) for effect-based monitoring of micropollutants in surface waters was carried out within the Marie Curie Initial Training Network EDA-EMERGE. The main objectives of the EDP were to apply a simplified protocol for effect-directed analysis, to link biological effects to target compounds and to estimate their risk to aquatic biota. Onsite large volume solid phase extraction of 50 L of surface water was performed at 18 sampling sites in four European river basins. Extracts were subjected to effect-based analysis (toxicity to algae, fish embryo toxicity, neurotoxicity, (anti-)estrogenicity, (anti-)androgenicity, glucocorticoid activity and thyroid activity), to target analysis (151 organic micropollutants) and to nontarget screening. The most pronounced effects were estrogenicity, toxicity to algae and fish embryo toxicity. In most bioassays, major portions of the observed effects could not be explained by target compounds, especially in case of androgenicity, glucocorticoid activity and fish embryo toxicity. Estrone and nonylphenoxyacetic acid were identified as the strongest contributors to estrogenicity, while herbicides, with a minor contribution from other micropollutants, were linked to the observed toxicity to algae. Fipronil and nonylphenol were partially responsible for the fish embryo toxicity. Within the EDP, 21 target compounds were prioritized on the basis of their frequency and extent of exceedance of predicted no effect concentrations. The EDP priority list included 6 compounds, which are already addressed by European legislation, and 15 micropollutants that may be important for future monitoring of surface waters. The study presents a novel simplified protocol for effect-based monitoring and draws a comprehensive picture of the surface water status across Europe.

Analysis of Pelagia noctiluca proteome Reveals a Red Fluorescent Protein, a Zinc Metalloproteinase and a Peroxiredoxin.

Pelagia noctiluca is the most venomous jellyfish in the Mediterranean Sea where it forms dense blooms. Although there is several published research on this species, until now none of the works has been focused on a complete protein profile of the all body constituents of this organism. Here, we have performed a detailed proteomics characterization of the major protein components expressed by P. noctiluca. With that aim, we have considered the study of jellyfish proteins involved in defense, body constituents and metabolism, and furthered explore the significance and potential application of such bioactive molecules. P. noctiluca body proteins were separated by1D SDS-PAGE and 2DE followed by characterization by nanoLC-MS/MS and MALDI-TOF/TOF techniques. Altogether, both methods revealed 68 different proteins, including a Zinc Metalloproteinase, a Red Fluorescent Protein (RFP) and a Peroxiredoxin. These three proteins were identified for the first time in P. noctiluca. Zinc Metalloproteinase was previously reported in the venom of other jellyfish species. Besides the proteins described above, the other 65 proteins found in P. noctiluca body content were identified and associated with its clinical significance. Among all the proteins identified in this work we highlight: Zinc metalloproteinase, which has a ShK toxin domain and therefore should be implicated in the sting toxicity of P. noctiluca.; the RFP which are a very important family of proteins due to its possible application as molecular markers; and last but not least the discovery of a Peroxiredoxin in this organism makes it a new natural resource of antioxidant and anti-UV radiation agents.

Galbulimima bark and ethnomedicine in Papua New Guinea.

This article reviews the literature and current information on the use of Galbulimima bark in traditional medicine in Papua New Guinea. Galbulimima bark is used in Papua New Guinea as an analgesic, to treat fever or to get rid of head lice. It is used in divination to produce trance-like states for counteracting malevolent power that is thought to be the cause of a variety of illnesses. Galbulimima bark has also been chewed, or drunk as a decoction, to induce visions and a dream-like state. It is also chewed and then rubbed on the legs before fighting.

Psychoactive properties of Galbulimima bark.

There are several reports that the bark of the rainforest tree Galbulimima belgraveana (F. Muell.) Sprague has been chewed for its psychoactive properties in Papua New Guinea. Twenty-eight alkaloids have been isolated from Galbulimima bark. There is no direct pharmacological evidence that any of these alkaloids are psychoactive. Two different pharmacological explanations for the reported psychoactive properties of Galbulimima bark are offered.

Life-threatening hyperkalaemia following therapeutic barbiturate coma.

OBJECTIVE: To report the occurrence of life-threatening hyperkalaemia following treatment with therapeutic thiopentone coma. SETTING: The neurosurgical intensive care units of Royal North Shore Hospital and Liverpool Hospital, Sydney, Australia. PATIENTS: Three patients treated with theraputic thiopentone coma. One patient with raised intracranial pressure secondary to a severe traumatic brain injury and two patients with refractory vasospasm secondary to subarachnoid haemorrhage. Two of the three patients developed hypokalaemia on starting thiopentone, which was resistant to potassium supplementation. All three patients developed severe hyperkalaemia during the recovery phase of coma. This was life-threatening in all three patients and fatal in one. CONCLUSIONS: Severe hypokalaemia refractory to potassium therapy may occur during therapeutic thiopentone coma. Severe rebound hyperkalaemia may occur after cessation of thiopentone infusion. Protocols for the management of patients with therapeutic barbiturate coma should recognise this potentially serious complication.