Outbreaks of H5N1 High Pathogenicity Avian Influenza in South Africa in 2023 Were Caused by Two Distinct Sub-Genotypes of Clade 2.3.4.4b Viruses.

In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and ostriches in 2023, but that H5Nx was predominant. Genome sequencing and phylogenetic analysis of confirmed H5N1 HPAI cases determined that only two of the fifteen sub-genotypes that circulated in South Africa in 2021-2022 still persisted in 2023. Sub-genotype SA13 remained restricted to coastal seabirds, with accelerated mutations observed in the neuraminidase protein. SA15 caused the chicken outbreaks, but outbreaks in the Paardeberg and George areas, in the Western Cape province, and the Camperdown region of the KwaZulu-Natal province were unrelated to each other, implicating wild birds as the source. All SA15 viruses contained a truncation in the PB1-F2 gene, but in the Western Cape SA15 chicken viruses, PA-X was putatively expressed as a novel isoform with eight additional amino acids. South African clade 2.3.4.4b H5N1 viruses had comparatively fewer markers of virulence and pathogenicity compared to European strains, a possible reason why no spillover to mammals has occurred here yet.

Understanding Physician's Perspectives on AI in Health Care: Protocol for a Sequential Multiple Assignment Randomized Vignette Study.

BACKGROUND: As the availability and performance of artificial intelligence (AI)-based clinical decision support (CDS) systems improve, physicians and other care providers poised to be on the front lines will be increasingly tasked with using these tools in patient care and incorporating their outputs into clinical decision-making processes. Vignette studies provide a means to explore emerging hypotheses regarding how context-specific factors, such as clinical risk, the amount of information provided about the AI, and the AI result, may impact physician acceptance and use of AI-based CDS tools. To best anticipate how such factors influence the decision-making of frontline physicians in clinical scenarios involving AI decision-support tools, hypothesis-driven research is needed that enables scenario testing before the implementation and deployment of these tools. OBJECTIVE: This study's objectives are to (1) design an original, web-based vignette-based survey that features hypothetical scenarios based on emerging or real-world applications of AI-based CDS systems that will vary systematically by features related to clinical risk, the amount of information provided about the AI, and the AI result; and (2) test and determine causal effects of specific factors on the judgments and perceptions salient to physicians' clinical decision-making. METHODS: US-based physicians with specialties in family or internal medicine will be recruited through email and mail (target n=420). Through a web-based survey, participants will be randomized to a 3-part "sequential multiple assignment randomization trial (SMART) vignette" detailing a hypothetical clinical scenario involving an AI decision support tool. The SMART vignette design is similar to the SMART design but adapted to a survey design. Each respondent will be randomly assigned to 1 of the possible vignette variations of the factors we are testing at each stage, which include the level of clinical risk, the amount of information provided about the AI, and the certainty of the AI output. Respondents will be given questions regarding their hypothetical decision-making in response to the hypothetical scenarios. RESULTS: The study is currently in progress and data collection is anticipated to be completed in 2024. CONCLUSIONS: The web-based vignette study will provide information on how contextual factors such as clinical risk, the amount of information provided about an AI tool, and the AI result influence physicians' reactions to hypothetical scenarios that are based on emerging applications of AI in frontline health care settings. Our newly proposed "SMART vignette" design offers several benefits not afforded by the extensively used traditional vignette design, due to the 2 aforementioned features. These advantages are (1) increased validity of analyses targeted at understanding the impact of a factor on the decision outcome, given previous outcomes and other contextual factors; and (2) balanced sample sizes across groups. This study will generate a better understanding of physician decision-making within this context. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54787.

Academic machine learning researchers' ethical perspectives on algorithm development for health care: a qualitative study.

OBJECTIVES: We set out to describe academic machine learning (ML) researchers' ethical considerations regarding the development of ML tools intended for use in clinical care. MATERIALS AND METHODS: We conducted in-depth, semistructured interviews with a sample of ML researchers in medicine (N = 10) as part of a larger study investigating stakeholders' ethical considerations in the translation of ML tools in medicine. We used a qualitative descriptive design, applying conventional qualitative content analysis in order to allow participant perspectives to emerge directly from the data. RESULTS: Every participant viewed their algorithm development work as holding ethical significance. While participants shared positive attitudes toward continued ML innovation, they described concerns related to data sampling and labeling (eg, limitations to mitigating bias; ensuring the validity and integrity of data), and algorithm training and testing (eg, selecting quantitative targets; assessing reproducibility). Participants perceived a need to increase interdisciplinary training across stakeholders and to envision more coordinated and embedded approaches to addressing ethics issues. DISCUSSION AND CONCLUSION: Participants described key areas where increased support for ethics may be needed; technical challenges affecting clinical acceptability; and standards related to scientific integrity, beneficence, and justice that may be higher in medicine compared to other industries engaged in ML innovation. Our results help shed light on the perspectives of ML researchers in medicine regarding the range of ethical issues they encounter or anticipate in their work, including areas where more attention may be needed to support the successful development and integration of medical ML tools.

Vaccination of African penguins (Spheniscus demersus) against high-pathogenicity avian influenza.

BACKGROUND: High-pathogenicity avian influenza (HPAI) has become a conservation threat to wild birds. Therefore, suitable vaccine technology and practical application methods require investigation. METHODS: Twenty-four African penguins (Spheniscus demersus) were vaccinated with either a conventional inactivated clade 2.3.4.4b H5N8 HPAI whole virus or a tobacco leaf-produced H5 haemagglutinin-based virus-like particle (VLP). Six birds received a second dose of the inactivated vaccine. Antibody responses were assessed and compared by employing haemagglutination inhibition tests. RESULTS: A second dose of inactivated vaccine was required to induce antibody titres above the level required to suppress virus shedding, while a single dose of VLP vaccine produced these levels by day 14, and one bird still had antibodies on day 430. LIMITATIONS: Bacterial contamination of the VLP vaccine limited the monitoring period and sample size in that treatment group, and it was not possible to perform a challenge study with field virus. CONCLUSION: VLP vaccines offer a more practical option than inactivated whole viruses, especially in logistically challenging situations involving wild birds.

Cryopreservation of Growth Factor-Mobilized Peripheral Blood Stem Cells Does Not Compromise Major Outcomes after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience.

During the Coronavirus disease 2019 pandemic, cryopreservation of allogeneic donor stem cell products ensured the availability of products at the start of conditioning for hematopoietic cell transplantation (HCT). Following recommendations from unrelated donor registries, including the National Marrow Donor Program, many centers began to cryopreserve related donor peripheral blood stem cell (PBSC) products. Throughout this process, several centers have published outcomes with cryopreserved versus fresh products, some with conflicting results. Even though cryopreservation was initially considered only a temporary measure driven by the pandemic, potential advantages include greater flexibility of transplantation timing. However, concerns about detrimental effects of cryopreservation, including increased risk of graft rejection, relapse, and consequent mortality, remained. The primary objective of the present study was to describe our center's experience comparing outcomes following PBSC transplantation with cryopreserved versus fresh grafts. This was an observational case study with a retrospective review comparing cryopreserved grafts (n = 213) to a recent historical cohort (controls) using fresh grafts (n = 167). In multivariable analyses, the adjusted hazard ratio (HR) for fresh versus cryopreserved grafts was 1.20 (95% confidence interval [CI], .79 to 1.82; P = .40) for overall mortality, .99 (95% CI, .55 to 1.77; P = .98) for nonrelapse mortality, and .94 (95% CI, .60 to 1.48; P = .80) for relapse. The adjusted HR for platelet engraftment was 1.31 (95% CI, 1.05 to 1.63; P = .02) and the odds ratio of grade III-IV acute GVHD was 1.75 (95% CI, 1.01 to 3.04; P = .05) with fresh grafts compared to cryopreserved grafts. There was no demonstrable difference in the risk of chronic GHVD. Although longer-term follow-up is needed, these data provide preliminary reassurance that in the event of another pandemic or should the logistical need arise in individual patients, cryopreservation of PBSC products is a reasonably safe alternative.

COVID-19 related change in breast cancer diagnosis, stage, treatment, and case volume: 2019-2021.

PURPOSE: Evaluate the COVID-19 pandemic impact on breast cancer detection method, stage and treatment before, during and after health care restrictions. METHODS: In a retrospective tertiary cancer care center cohort, first primary breast cancer (BC) patients, years 2019-2021, were reviewed (n = 1787). Chi-square statistical comparisons of detection method (patient (PtD)/mammography (MamD), Stage (0-IV) and treatment by pre-pandemic time 1: 2019 + Q1 2020; peak-pandemic time 2: Q2-Q4 2020; pandemic time 3: Q1-Q4 2021 (Q = quarter) periods and logistic regression for odds ratios were used. RESULTS: BC case volume decreased 22% in 2020 (N = 533) (p = .001). MamD declined from 64% pre-pandemic to 58% peak-pandemic, and increased to 71% in 2021 (p < .001). PtD increased from 30 to 36% peak-pandemic and declined to 25% in 2021 (p < .001). Diagnosis of Stage 0/I BC declined peak-pandemic when screening mammography was curtailed due to lock-down mandates but rebounded above pre-pandemic levels in 2021. In adjusted regression, peak-pandemic stage 0/I BC diagnosis decreased 24% (OR = 0.76, 95% CI: 0.60, 0.96, p = .021) and increased 34% in 2021 (OR = 1.34, 95% CI: 1.06, 1.70, p = .014). Peak-pandemic neoadjuvant therapy increased from 33 to 38% (p < .001), primarily for surgical delay cases. CONCLUSIONS: The COVID-19 pandemic restricted health-care access, reduced mammography screening and created surgical delays. During the peak-pandemic time, due to restricted or no access to mammography screening, we observed a decrease in stage 0/I BC by number and proportion. Continued low case numbers represent a need to re-establish screening behavior and staffing.

Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients.

Introduction: Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT. Methods: Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the cause-specific hazard of AKI. Results: We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%) were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model . Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overall mortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01). Discussion: AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT.

The Molecular Epidemiology of Clade 2.3.4.4B H5N1 High Pathogenicity Avian Influenza in Southern Africa, 2021-2022.

In southern Africa, clade 2.3.4.4B H5N1 high pathogenicity avian influenza (HPAI) was first detected in South African (SA) poultry in April 2021, followed by outbreaks in poultry or wild birds in Lesotho and Botswana. In this study, the complete or partial genomes of 117 viruses from the SA outbreaks in 2021-2022 were analyzed to decipher the sub-regional spread of the disease. Our analysis showed that seven H5N1 sub-genotypes were associated with the initial outbreaks, but by late 2022 only two sub-genotypes still circulated. Furthermore, SA poultry was not the source of Lesotho's outbreaks, and the latter was most likely an introduction from wild birds. Similarly, SA and Botswana's outbreaks in 2021 were unrelated, but viruses of Botswana's unique sub-genotype were introduced into SA later in 2022 causing an outbreak in ostriches. At least 83% of SA's commercial poultry cases in 2021-2022 were point introductions from wild birds. Like H5N8 HPAI in 2017-2018, a coastal seabird-restricted sub-lineage of H5N1 viruses emerged in the Western Cape province in 2021 and spread to Namibia, causing mortalities in Cape Cormorants. In SA ~24,000 of this endangered species died, and the loss of >300 endangered African penguins further threatens biodiversity.