Extraterritorial Application of Canadian Foreign Investment Review

The ICA, which purportedly liberalized review of foreign investment, in fact reaffirmed the Foreign Investment Review Agency\u27s role in reviewing extraterritorial transactions indirectly affecting control of Canadian business.\u27 This Comment examines the policy implications of FIRA\u27s and ICA\u27s extraterritorial application, and concludes that it is unnecessary and counterproductive when direct control of Canadian business is unchanged, or when contractual liability follows a direct change of control

A Theory of Relativity: Kinship Foster Care May Be the Key to Stopping the Pendulum of Terminations vs. Reunification

The foster care system in the United States is universally regarded as a disaster: too many children languishing for too many years, bouncing from foster home to foster home, or worse yet, returning to the abusive or neglectful home only to face more danger. The failures of the federal foster care system have spurred members of Congress to advocate reform. Answering the call for reform, Congress overwhelmingly passed and, on November 19, 1997, President Clinton signed into law the Adoption and Safe Families Act of 1997 ( ASFA ). One of the primary purposes of the ASFA is to correct many of the perceived deficiencies of its predecessor, the Adoption Assistance and Child Welfare Act of 1980 ( AACWA ). The AACWA\u27s requirement that states use reasonable efforts to reunite foster children with their biological parents drew the sharpest criticism as going too far to ensure family preservation. The ASFA clarifies the reasonable efforts requirement, providing that the child\u27s safety shall be the paramount concern in all foster care decisions. Although this statute remedies some of the AACWA\u27s deficiencies, the ASFA also creates new problems. Of particular concern is the provision that requires states to seek the termination of parental rights, with few exceptions, in the case of any child who has been in foster care for fifteen of the most recent twenty-two months. While this provision intends to create permanency for children in foster care, it may instead terminate rights of parents who with assistance could provide a stable home, without guaranteeing that the child will be placed in a permanent home. Indeed, just as the pendulum swung too far towards reunification in 1980, in 1998 the pendulum is swinging too far towards termination. This Note argues that the swing of the pendulum in either direction is inconsistent with a child\u27s best interests. Part II examines the failures of the AACWA and the solution embodied in the ASFA. Part III discusses the shortcomings of the ASFA and argues that its strong endorsement of adoption is both short-sighted and inconsistent with a best interests of the child analysis. Part IV discusses kinship foster care, in which extended family members of the child serve as foster parents, as a solution to the swinging pendulum. Finally, Part V makes suggestions for a federal kinship care policy

PROmotion of COvid-19 VA(X)ccination in the Emergency Department-PROCOVAXED: study protocol for a cluster randomized controlled trial.

Background: We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial, we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients. Methods: This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 1-week periods to the intervention and 30 1-week periods to the control. Adult patients who have not received a COVID-19 vaccine are eligible with these exclusions: (1) major trauma, intoxication, altered mental status, or critical illness; (2) incarceration; (3) psychiatric chief complaint; and (4) suspicion of acute COVID-19 illness. Participants receive an orally administered Intake survey. During intervention weeks, participants then receive three COVID-19 vaccine messaging platforms (4-min video, one-page informational flyer and a brief, scripted face-to-face message delivered by an ED physician or nurse); patients enrolled during non-intervention weeks do not receive these platforms. Approximately, an hour after intake surveys, participants receive a Vaccine Acceptance survey during which the primary outcome of acceptance of the COVID-19 vaccine in the ED is ascertained. The other primary outcome of receipt of a COVID-19 vaccine within 32 days is ascertained by electronic health record review and phone follow-up. To determine whether provision of vaccine messaging platforms is associated with a 7% increase in vaccine acceptance and uptake, we will need to enroll 1290 patients. Discussion: Highlighting the difficulties of trial implementation during the COVID-19 pandemic in acute care settings, our novel trial will lay the groundwork for delivery of public health interventions to vulnerable populations whose only health care access occurs in EDs. Conclusions: Toward addressing vaccine hesitancy in vulnerable populations who seek care in EDs, our cluster-RCT will determine whether implementation of vaccine messaging platforms is associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients. Trial status: We began enrollment in December 2021 and expect to continue through 2022. Trial registration: ClinicalTrials.gov NCT05142332 . Registered 02 December 2021

Immunosuppression and outcomes in adult patients with de novo acute myeloid leukemia with normal karyotypes

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; \u3e5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with \u3e5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European LeukemiaNet [ELN] 2017 criteria) was not sufficient to explain the outcomes of many SFR cases. Single-cell RNA-sequencing studies of 15 AML samples showed that SFR AML cells differentially expressed many genes associated with immune suppression. The bone marrow of SFR cases had significantly fewer CD

Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms

BACKGROUND: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. METHODS: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. RESULTS: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. CONCLUSIONS: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized

Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022.

Background: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. Results: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; Conclusions: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. Trial Registration: NCT04610515

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. EXPOSURES: SARS-CoV-2 status (positive or negative test result) at enrollment. MAIN OUTCOMES AND MEASURES: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. RESULTS: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (β = 3.32; 95% CI, 1.84-4.80; P \u3c .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: β = 3.90; 95% CI, 1.75-6.05; P \u3c .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: β = 4.16; 95% CI, 2.12-6.20; P \u3c .001). CONCLUSIONS AND RELEVANCE: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19

Internalized Stigma, Depressive Symptoms, and the Modifying Role of Antiretroviral Therapy: A Cohort Study in Rural Uganda

Depression affects over 40% of people with HIV (PHIV) in low- and middle-income countries, and over half of PHIV report HIV-related internalized stigma. However, few longitudinal studies of PHIV have examined the relationship between HIV-related stigma and depression. Data were analyzed from the 2007-15 Uganda AIDS Rural Treatment Outcomes (UARTO) Study, a cohort of 454 antiretroviral therapy (ART)-naïve PHIV (68% women) starting ART. Our primary outcome was depression symptom severity over the first two years of ART, measured using a locally adapted version of the Hopkins Symptom Checklist; our primary exposure was the 6-item Internalized AIDS-Related Stigma Scale. Both scores were measured at enrollment and at quarterly follow-up visits. We fit linear generalized estimating equations (GEE) regression models to estimate the association between stigma and depression symptom severity, adjusting for potential confounders. We included a stigma × time product term to assess the modifying effect of ART on the association between internalized stigma and depression symptom severity. UARTO participants had a median age of 32 years and median enrollment CD4 count of 217 cells/mm3. Both depression symptom severity and internalized stigma declined on ART, particularly during the first treatment year. In multivariable regression models, depression symptom severity was positively associated with internalized stigma (b = 0.03; 95% confidence interval [CI], 0.02 to 0.04) and negatively associated with ART duration \u3e6 months (b = −0.16; 95% CI, −0.19 to −0.13). The estimated product term coefficient was negative and statistically significant (P = 0.004), suggesting that the association between internalized stigma and depression symptom severity weakened over time on ART. Thus, in this large cohort of PHIV initiating ART in rural Uganda, depression symptom severity was associated with internalized stigma but the association declined with time on ART. These findings underscore the potential value of ART as a stigma reduction intervention for PHIV, particularly during early treatment