The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic was characterized by rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, affecting viral transmissibility, virulence, and response to vaccines/therapeutics. EMPATHY (NCT04828161), a phase 2 study, investigated the safety/efficacy of ensovibep, a multispecific designed ankyrin repeat protein (DARPin) with multivariant in vitro activity, in ambulatory patients with mild to moderate COVID-19. Methods: Nonhospitalized, symptomatic patients (N = 407) with COVID-19 were randomized to receive single-dose intravenous ensovibep (75, 225, or 600 mg) or placebo and followed until day 91. The primary endpoint was time-weighted change from baseline in log10 SARS-CoV-2 viral load through day 8. Secondary endpoints included proportion of patients with COVID-19-related hospitalizations, emergency room (ER) visits, and/or all-cause mortality to day 29; time to sustained clinical recovery to day 29; and safety to day 91. Results: Ensovibep showed superiority versus placebo in reducing log10 SARS-CoV-2 viral load; treatment differences versus placebo in time-weighted change from baseline were -0.42 (P = .002), -0.33 (P = .014), and -0.59 (P < .001) for 75, 225, and 600 mg, respectively. Ensovibep-treated patients had fewer COVID-19-related hospitalizations, ER visits, and all-cause mortality (relative risk reduction: 78% [95% confidence interval, 16%-95%]) and a shorter median time to sustained clinical recovery than placebo. Treatment-emergent adverse events occurred in 44.3% versus 54.0% of patients in the ensovibep and placebo arms; grade 3 events were consistent with COVID-19 morbidity. Two deaths were reported with placebo and none with ensovibep. Conclusions: All 3 doses of ensovibep showed antiviral efficacy and clinical benefits versus placebo and an acceptable safety profile in nonhospitalized patients with COVID-19.

Co-occurrence of chronic pain and anxiety/depression symptoms in U.S. adults: prevalence, functional impacts, and opportunities.

ABSTRACT: Co-occurrence of chronic pain and clinically significant symptoms of anxiety and/or depression is regularly noted in the literature. Yet, little is known empirically about population prevalence of co-occurring symptoms, nor whether people with co-occurring symptoms constitute a distinct subpopulation within US adults living with chronic pain or US adults living with anxiety and/or depression symptoms (A/D). To address this gap, this study analyzes data from the 2019 National Health Interview Survey, a representative annual survey of self-reported health status and treatment use in the United States (n = 31,997). Approximately 12 million US adults, or 4.9% of the adult population, have co-occurring chronic pain and A/D symptoms. Unremitted A/D symptoms co-occurred in 23.9% of US adults with chronic pain, compared with an A/D prevalence of 4.9% among those without chronic pain. Conversely, chronic pain co-occurred in the majority (55.6%) of US adults with unremitted A/D symptoms, compared with a chronic pain prevalence of 17.1% among those without A/D symptoms. The likelihood of experiencing functional limitations in daily life was highest among those experiencing co-occurring symptoms, compared with those experiencing chronic pain alone or A/D symptoms alone. Among those with co-occurring symptoms, 69.4% reported that work was limited due to a health problem, 43.7% reported difficulty doing errands alone, and 55.7% reported difficulty participating in social activities. These data point to the need for targeted investment in improving functional outcomes for the nearly 1 in 20 US adults living with co-occurring chronic pain and clinically significant A/D symptoms.

Prevalence and Characteristics of Chemsex: A Cross-Sectional Observational Study.

INTRODUCTION: Chemsex has been defined until now as the use of specific psychoactive substances during sexual activities in men who have sex with men (MSM) contexts to facilitate, enhance, and prolong the experience. Many studies have investigated this phenomenon in specific communities, such as MSM, or have explored the risk of sexually transmitted diseases (STDs). The objective of this study was to investigate the prevalence of chemsex in an Italian group and describe its main characteristics. Additionally, the study aimed to suggest prevention strategies addressing the risks associated with drug use. METHODS: We conducted a cross-sectional observational study. The survey was conducted among 1,828 individuals residing in Italy. Data were collected through a self-completed online survey consisting of 44 questions. RESULTS: 248 people (13.6%) disclosed that they had practiced chemsex, 89 of which (35.9%) were female. Moreover, 13 people (5%) defined themselves as addicted to chemsex; 173 people (69.8%) would like to have more information about the risks related to chemsex, and 79 people (31.8%) would like to talk about this to a professional working in the addiction field. DISCUSSION: The prevalence found in our Italian survey is consistent with findings from other studies. Notably, our survey reveals the presence of chemsex among women. Our results emphasize the necessity for a more comprehensive understanding of chemsex, highlighting the significance of engaging specialized services such as addiction units, STD outpatient clinics, and mental health services. These healthcare facilities can effectively share information and implement risk prevention campaigns focused on chemsex.

A Diagram of the Social-Ecological Conditions of Opioid Misuse and Overdose.

The United States is experiencing a crisis of opioid misuse and overdose. To understand the underlying factors, researchers have begun looking upstream to identify social and structural determinants. However, no study has yet aggregated these into a comprehensive ecology of opioid overdose. We scoped 68 literature sources and compiled a master list of opioid misuse and overdose conditions. We grouped the conditions and used the Social Ecological Model to organize them into a diagram. We reviewed the diagram with nine subject matter experts (SMEs) who provided feedback on its content, design, and usefulness. From a literature search and SME interviews, we identified 80 unique conditions of opioid overdose and grouped them into 16 categories. In the final diagram, we incorporated 40 SME-recommended changes. In commenting on the diagram's usefulness, SMEs explained that the diagram could improve intervention planning by demonstrating the complexity of opioid overdose and highlighting structural factors. However, care is required to strike a balance between comprehensiveness and legibility. Multiple design formats may be useful, depending on the communication purpose and audience. This ecological diagram offers a visual perspective of the conditions of opioid overdose.

Reclaiming Indigenous Health in the US: Moving beyond the Social Determinants of Health.

The lack of literature on Indigenous conceptions of health and the social determinants of health (SDH) for US Indigenous communities limits available information for Indigenous nations as they set policy and allocate resources to improve the health of their citizens. In 2015, eight scholars from tribal communities and mainstream educational institutions convened to examine: the limitations of applying the World Health Organization's (WHO) SDH framework in Indigenous communities; Indigenizing the WHO SDH framework; and Indigenous conceptions of a healthy community. Participants critiqued the assumptions within the WHO SDH framework that did not cohere with Indigenous knowledges and epistemologies and created a schematic for conceptualizing health and categorizing its determinants. As Indigenous nations pursue a policy role in health and seek to improve the health and wellness of their nations' citizens, definitions of Indigenous health and well-being should be community-driven and Indigenous-nation based. Policies and practices for Indigenous nations and Indigenous communities should reflect and arise from sovereignty and a comprehensive understanding of the nations and communities' conceptions of health and its determinants beyond the SDH.

Adult ADHD and sleep disorders: Prevalence, severity and predictors of sleep disorders in a sample of Italian psychiatric outpatients.

OBJECTIVE: Sleep disorders are frequent in adult subjects diagnosed with ADHD. The aims of the present study were to assess the prevalence and the severity of sleep disorders in a sample of Italian psychiatric outpatients, to compare the prevalence and severity of sleep disorders in patients with and without diagnosis of adult ADHD, and to evaluate the role of ADHD as an individual predictor of sleep disturbances severity. METHOD: 634 outpatients accessing psychiatric services were assessed with the Mini-International Neuropsychiatric Interview (MINI) Plus V. 5.0.0 interview and the Adult ADHD self-report Scale Symptoms Checklist (ASRS)-V 1.1 Short Form. Patients positive to the ASRS-V 1.1 were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Sleep disorders and sleep disturbances' severity were assessed with the PROMIS Adult Sleep Disturbance Scale. RESULTS: Sleep disorders were more frequent (p < 0.001) and sleep disturbances were more severe (d = 1.26, p < 0.001) in subjects diagnosed with adult ADHD compared to other outpatients. Among the 44 subjects diagnosed with ADHD, 15 (34.1%) reported no or slight sleep disturbances, 9 (20.5%) a mild sleep disorder, 17 (38.6%) a moderate sleep disorder and 3 (6.8%) a severe sleep disorder. ADHD diagnosis, multiple psychiatric comorbidity and history of suicide attempts emerged as individual predictors of worse sleep disturbances. CONCLUSION: Sleep disorders are more frequent and severe in subjects diagnosed with ADHD compared to other adult outpatients. Sleep disturbances might represent an intrinsic feature in adult ADHD subjects, presenting important clinical repercussions, and should be routinely evaluated and monitored in this population.

Gender, psychiatric disability, and dropout from peer support specialist training.

Although research indicates that the prevalence of psychiatric disability differs depending on gender, a paucity of information exists as to whether men and women with psychiatric disability also differ regarding service program outcomes. For a United States Southwest peer support specialist training program, this study examines whether gender moderates the association between psychiatric disability and a key outcome-training dropout. Data were collected for 78 men and 157 women with psychiatric disability and 137 men and 203 women with mental illness only. Logistic regression was used to examine the association between psychiatric disability and dropout, with gender as a moderator variable, and age, education, race/ethnicity, and substance use disorder as control variables. Of trainees with psychiatric disability, dropout was greater among men than women (34.6% and 20.4%, respectively; p < .05). Dropout was also greater among men with psychiatric disability than among men with mental illness only (34.6% and 15.3%; p < .01). In contrast, dropout was similar for women with psychiatric disability and mental illness only (20.4% and 18.7%; p > .05), and dropout was comparable among men and women with mental illness only (15.3% and 18.7%; p > .05). In summary, risk of dropout was substantially higher among men with psychiatric disability than women with psychiatric disability. Gender tailoring of the program's services should be considered to better support training completion. This study's findings also raise questions as to possible underrepresentation of men with psychiatric disability in the peer support workforce training pipeline. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pediatric hematology/oncology healthcare professional emotional health during COVID-19.

OBJECTIVES: Little is known about the impact of coronavirus disease 2019 (COVID-19) on healthcare professional emotional health in pediatric hematology/oncology. Primary objective was to describe anxiety, depression, positive affect, and perceived stress among pediatric hematology/oncology healthcare professionals following a COVID-19 outbreak. Secondary objectives were to compare these outcomes based on contact with a positive person, and to identify risk factors for worse outcomes. MATERIALS AND METHODS: We included 272 healthcare professionals working with pediatric hematology/oncology patients. We determined whether respondents had direct or indirect contact with a COVID-19-positive individual and then measured outcomes using the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, and positive affect measures, and the Perceived Stress Scale. RESULTS: Among eligible respondents, 205 agreed to participate (response rate 75%). Sixty-nine (33.7%) had contact with a COVID-19-positive person. PROMIS anxiety, depression, and positive affect scores were similar to the general United States population. Those who had contact with a COVID-19-positive individual did not have significantly different outcomes. In multiple regression, non-physicians had significantly increased anxiety (nurses: p = 0.013), depression (nurses: p = 0.002, pharmacists: p = 0.038, and other profession: p = 0.021), and perceived stress (nurses: p = 0.002 and other profession: p = 0.011) when compared to physicians. CONCLUSIONS: Pediatric hematology/oncology healthcare professionals had similar levels of anxiety, depression, and positive affect as the general population. Contact with a COVID-19-positive individual was not significantly associated with outcomes. Non-physician healthcare professionals had more anxiety, depression, and perceived stress when compared to physicians. These findings may help to develop programs to support healthcare professional resilience.

Adult ADHD: Prevalence and Clinical Correlates in a Sample of Italian Psychiatric Outpatients.

Objective: ADHD remains a largely underdiagnosed disorder in Europe and especially in Italy. Aims of the present study were to assess the prevalence of ADHD and its clinical and demographic correlates in a large sample of Italian outpatients. Method: 634 outpatients accessing psychiatric services were assessed with the Mini-International Neuropsychiatric Interview (MINI) Plus V. 5.0.0 interview and the Adult ADHD self-report Scale Symptoms Checklist (ASRS)-V 1.1 Short Form. Patients positive to the ASRS-V 1.1 were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Results: Of the total patients' sample, 81 (12.8%) were positive on the ASRS-V 1.1. After performing the DIVA 2.0, 44 patients (6.9%) met the criteria for Adult ADHD. Significant clinical and demographic differences between ADHD positive and negative groups were found. Conclusion: The prevalence and correlates of ADHD comorbidity in our outpatient psychiatric population were comparable to those found in other high-income countries. Considering the prevalence of ADHD and its impact on functioning, implementing specific knowledge on this subject is needed.

Electronic Cigarette Policy Recommendations: A Scoping Review.

Objective: There is a lack of consensus on whether e-cigarettes facilitate or threaten existing tobacco prevention strategies. This uncertainty is reflected in organizations' conflicting e-cigarette position statements. We conducted a scoping review of position statements in published and gray literature to map the range and frequency of e-cigarette use recommendations. Methods: We collected 81 statements from international health organizations. Two coders independently performed qualitative content analysis to categorize e-cigarette recommendations. We explored differences based on organization type, geography, and the year recommendations were published. Results: We identified 5 recommendation types: encourage smokers to use ecigarettes as a cessation aid or as an alternative source of nicotine (N = 5); support individuals who use e-cigarettes to quit smoking (N = 20); avoid using until more research is available (N = 19); restrict access based on available evidence (N = 30); and prohibit e-cigarette marketing and sale (N = 7). Conclusion: Organizations presented diverse e-cigarette use recommendations. The variation related to organizations' differing tobacco prevention priorities and level of confidence in current e-cigarette research. These differences may create confusion. Additional research can examine whether this variability influences stakeholders' attitudes or behavior.

Monitoring the implementation of the WHO Global Code of Practice on the International Recruitment of Health Personnel.

OBJECTIVE: To present the findings of the first round of monitoring of the global implementation of the WHO Global Code of Practice on the International Recruitment of Health Personnel ("the Code"), a voluntary code adopted in 2010 by all 193 Member States of the World Health Organization (WHO). METHODS: WHO requested that its Member States designate a national authority for facilitating information exchange on health personnel migration and the implementation of the Code. Each designated authority was then sent a cross-sectional survey with 15 questions on a range of topics pertaining to the 10 articles included in the Code. FINDINGS: A national authority was designated by 85 countries. Only 56 countries reported on the status of Code implementation. Of these, 37 had taken steps towards implementing the Code, primarily by engaging relevant stakeholders. In 90% of countries, migrant health professionals reportedly enjoy the same legal rights and responsibilities as domestically trained health personnel. In the context of the Code, cooperation in the area of health workforce development goes beyond migration-related issues. An international comparative information base on health workforce mobility is needed but can only be developed through a collaborative, multi-partnered approach. CONCLUSION: Reporting on the implementation of the Code has been suboptimal in all but one WHO region. Greater collaboration among state and non-state actors is needed to raise awareness of the Code and reinforce its relevance as a potent framework for policy dialogue on ways to address the health workforce crisis.

Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas.

BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK. RESULTS: In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the ALK gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of ALK rearrangements and hybridization patterns in a large unselected cohort of 1387 patients with a referred diagnosis of non-small cell lung cancer (1011 of these patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal patterns varied from a single split signal to complex patterns. Among 49 abnormal samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had deletions of the green 5' end of the ALK signal, and 1 of these 15 samples showed amplification of the orange 3' end of the ALK signal. Two patients showed a deletion of the 3'ALK signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions by multiplex RT-PCR. Among the 45 ALK-rearranged samples tested, only 1 EGFR mutation (T790M) was detected. Two KRAS mutations were detected among 24 ALK-rearranged samples tested. CONCLUSIONS: In a large unselected series, the frequency of ALK gene rearrangement detected by FISH was approximately 3.5% of lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant signal patterns frequently detected. Rare cases with coexisting KRAS and EGFR mutations were seen.

Human resources for health in southeast Asia: shortages, distributional challenges, and international trade in health services.

In this paper, we address the issues of shortage and maldistribution of health personnel in southeast Asia in the context of the international trade in health services. Although there is no shortage of health workers in the region overall, when analysed separately, five low-income countries have some deficit. All countries in southeast Asia face problems of maldistribution of health workers, and rural areas are often understaffed. Despite a high capacity for medical and nursing training in both public and private facilities, there is weak coordination between production of health workers and capacity for employment. Regional experiences and policy responses to address these challenges can be used to inform future policy in the region and elsewhere. A distinctive feature of southeast Asia is its engagement in international trade in health services. Singapore and Malaysia import health workers to meet domestic demand and to provide services to international patients. Thailand attracts many foreign patients for health services. This situation has resulted in the so-called brain drain of highly specialised staff from public medical schools to the private hospitals. The Philippines and Indonesia are the main exporters of doctors and nurses in the region. Agreements about mutual recognition of professional qualifications for three groups of health workers under the Association of Southeast Asian Nations Framework Agreement on Services could result in increased movement within the region in the future. To ensure that vital human resources for health are available to meet the needs of the populations that they serve, migration management and retention strategies need to be integrated into ongoing efforts to strengthen health systems in southeast Asia. There is also a need for improved dialogue between the health and trade sectors on how to balance economic opportunities associated with trade in health services with domestic health needs and equity issues.