Background
In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 ...(HER2)-positive immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors.
Methods
HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed.
Results
The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %.
Conclusions
HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to.
Objective: Previous research has found that college students experience both positive and negative outcomes after a hookup. The present study examined the role that hookup motives and sex play in ...determining the overall positivity and negativity of the experience. Participants: College students (N = 156) completed an online survey about their most recent hookup. Method: The survey assessed hookup motivations and outcomes. Results: Lower coping motives and higher social-sexual, relationship-seeking, and enhancement motives predicted more positive outcomes. Higher coping motives and lower social-sexual, conformity, and enhancement motives predicted more negative outcomes. For men, positive outcomes were correlated with weaker enhancement motives, while negative outcomes were correlated with more enhancement motives. For women, higher levels of positive outcomes were positively correlated with enhancement, social-sexual, and relationship-seeking motives, while negative outcomes were negatively correlated with social-sexual, enhancement, and coping motives. Conclusions: The results of this study have implications for risk prevention and future research.
Summary Background Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), was investigated in combination with chemotherapy for first-line ...treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. Methods ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation. Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. Allocation was by block randomisation stratified by Eastern Cooperative Oncology Group performance status, chemotherapy regimen, extent of disease, primary cancer site, and measurability of disease, implemented with a central interactive voice recognition system. The primary endpoint was overall survival in all randomised patients who received study medication at least once. This trial is registered with ClinicalTrials.gov , number NCT01041404. Findings 594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290). Median follow-up was 18·6 months (IQR 11–25) in the trastuzumab plus chemotherapy group and 17·1 months (9–25) in the chemotherapy alone group. Median overall survival was 13·8 months (95% CI 12–16) in those assigned to trastuzumab plus chemotherapy compared with 11·1 months (10–13) in those assigned to chemotherapy alone (hazard ratio 0·74; 95% CI 0·60–0·91; p=0·0046). The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197 67% vs chemotherapy alone, 184 63%), vomiting (147 50% vs 134 46%), and neutropenia (157 53% vs 165 57%). Rates of overall grade 3 or 4 adverse events (201 68% vs 198 68%) and cardiac adverse events (17 6% vs 18 6%) did not differ between groups. Interpretation Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. Funding F Hoffmann-La Roche.
The revised 2023 Commission on Rehabilitation Counselor Certification (CRCC) Code of Ethics, adopted in September 2022, addresses changes in ethical standards related to the counseling relationship. ...To promote awareness and understanding of these changes, this article reviews the purpose of Section A (The Counseling Relationship) of the CRCC Code of Ethics and provides a summary of the key revisions that have been made to Section A in the new revised Code and how the changes in these sub-sections of Section A impact counselors/practice.
The Commission on Rehabilitation Counselor Certification (CRCC) certifies qualified candidates as certified rehabilitation counselors in the United States (CRCs) and as Canadian certified ...rehabilitation counselors (CCRCs) in Canada. Those professionals who are certified as CRCs/CCRCs are expected to adhere to the CRCC Code of Professional Ethics. The CRCC Code of Ethics is updated from time to time. With the completion of the recent revision process, a revised Code of Professional Ethics for CRCs/CCRCs is now being distributed and implemented by the CRCC. Given the changes and updates to the Code of Professional Ethics, this article and subsequent articles in this special issue help to outline the process and rationale that framed the recent revision process. Although some specific changes are highlighted through this special issue, practitioners are encouraged to familiarize themselves with the entire code.
Summary Background Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 ...receptor (AT2 R) is a new target for neuropathic pain. EMA401, a highly selective AT2 R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia. Methods In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22–89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22–28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987. Findings 92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores −2·29 SD 1·75 vs −1·60 1·66; difference of adjusted least square means −0·69 SE 0·25; 95% CI −1·19 to −0·20; p=0·0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo. Interpretation EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients. Funding Spinifex Pharmaceuticals.
This study aimed to elicit preferences for psoriasis treatment features and to test for preference heterogeneity across groups of respondents.
A discrete-choice experiment was employed to elicit ...preferences of patients with plaque psoriasis in multiple countries. The survey instrument included a series of choice questions between three hypothetical treatments, each characterized by varying levels of six attributes (namely, lesion reduction, risk of impairing side effects, time to reach results, mode and frequency of administration, itching reduction, and side effects). Random parameters logit was used to model the data. Results were compared across a total of 18 subgroup sets.
The data analysis from 1,123 respondents showed that, on average, respondents receive more utility gain from higher levels of lesion reduction and lower risks of impairing side effects than changes in other attributes included in the study. Systematic differences were detected for 13 sets; the most pronounced differences were observed based on disease severity, nail psoriasis, biologic experience, and quality-of-life scores.
These many sources of preference heterogeneity identified by our analysis suggest that to improve patient satisfaction and, probably, adherence and persistence, clinicians should discuss options with patients when prescribing their treatment.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Supervision is a key element to the development of ethical skills and awareness in rehabilitation counselors. Ethical standards specific to rehabilitation counselor educators and supervisors were ...first introduced in 2002 and updated in 2010 and 2017. This article discusses supervision and professional dispositions as constructs that were used to help frame the revision process and outlines some of the key change to Section I. (Supervision, Teaching, and Training) of the Code of Professional Ethics for certified rehabilitation counselors. In conjunction with the revision process, special considerations for multicultural competencies have been strengthened throughout Section I, as well as specific requirements for the measurement and assessment of professional dispositions in educational settings. The article helps to inform and guide supervisors, trainers, and educators as they review Section I and consider their role in the development of ethical skills in those they supervise and their own respective practice.
The use of technology in rehabilitation counseling including the delivery of rehabilitation services via virtual counseling is occurring at greater rates than ever before. At the same time, views ...about the utility of social media have evolved, necessitating increased consideration of social media benefits while at the same time highlighting a need for more detailed guidance regarding its usage and risks. As a standard of ethical practice, certified rehabilitation counselors (CRCs) are required to be aware of guidelines that govern the ethical use of technology in the provision of rehabilitation services, including revisions to the Code of Professional Ethics for CRCs. The 2023 revisions to the Technology, Social Media, and Virtual Counseling section of the Code of Professional Ethics for CRCs specify expanded guidance for CRCs integrating apps, relevant social media, and the provision of virtual counseling. To assist CRCs to meet their standard of ethical practice, this article reviews the historical evolution of technology within the Code, the changes and expansions to Section K of the Code and discusses ethical consideration and revised guidance in the critical technology areas of virtual counseling and social media.
Scanning electron micrographs of microtomed surface shows pristine surface free of corrosion related ‘mud cracking’ inset for an inhibited AA7050 specimen when only 150
ppm Ce(dpp)3 is present in 0.1
...M NaCl solution.
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▶ The thin film of hydrolysis products of Ce(dpp)3 and aluminium oxide is proposed to cause the inhibition. ▶ The film consists of discrete Ce rich particles and a thin film over the matrix of Ce, P and Al oxides. ▶ Discrete deposition of Ce is specifically influenced by Cu rich intermetallics.
Cerium diphenyl phosphate (Ce(dpp)
3) has previously been shown to be a strong corrosion inhibitor for aluminium–copper magnesium alloy AA2024-T3 and AA7075 in chloride solutions. Surface characterisation including SEM and ToF-SIMS coupled with electrochemical impedance spectroscopy (EIS) measurements are used to propose a mechanism of corrosion inhibition which appears to involve the formation of a complex oxide film of aluminium and cerium also incorporating the organophosphate component. The formation of a thin complex film consisting of hydrolysis products of the Ce(dpp)
3 compound and aluminium oxide is proposed to lead to the observed inhibition. SEM analysis shows that some intermetallics favour the creation of thicker deposits predominantly containing cerium oxide compounds.
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