Search

Lake desiccation is a global problem associated with increased human water use and climate change. Like other drying lakes, Utah’s Great Salt Lake (GSL) is producing health-harming dust. We estimate social disparities in dust fine particulate matter (PM2.5) exposures based on four policy-relevant water-level scenarios. Dust PM2.5exposures would increase as GSL levels drop (e.g., from 24.0 μg m−3to 32.0 μg m−3). People of color and those with no high school diploma would experience disproportionately higher exposures (e.g., 28.4 μg m−3for Pacific Islanders vs. 26.0 μg m−3for Whites under very low lake levels). Racial/ethnic disparities would be reduced if GSL water levels rose. If the GSL vanished, racial/ethnic disparities between the highest and lowest exposed groups would be moderate (16.3%). If the GSL stabilized at healthy levels, those disparities would be smaller (7.9%). While all nearby residents face unhealthy dust exposures, findings reveal exposure disparities for socially disadvantaged groups.

The purpose of this study is to investigate differences between women and men in chemistry, as reflected in their responses to a global gender gap survey. The survey was conducted in 2018; responses from 1,343 valid participants across the globe were collected and analyzed. The main results show that first, women were more likely to list their parents and themselves as important influences in their university studies than men. This result was consistent regardless of the Human Development Index (HDI, an index developed by the United Nations assessing the development of a country) and employment sectors. Also, men students reported more positive relationships and support from their advisors or supervisors than women. More women than men indicated that they had personally encountered sexual harassment at school or work. Also, in general, more men than women indicated that they had never experienced discrimination in the assessment or evaluation of their achievement across different HDI regions and in different employment sectors. Men reported having more research resources than women. More women than men indicated that their careers had influenced their decisions about their children, marriage, or long-term partnership across high and low HDI regions and employment sectors. Finally, women submitted fewer journal articles than men in the past five years, and this gender difference was also seen in respondents from both high and low HDI regions and working in industry. In contrast, by employment sector, the gender differences were relatively small.

Introduction: Cervical cancer screening (CCS) among East African immigrants (EAI) in the USA is under explored. This study aimed to investigate adherence to CCS and its correlates among EAI. Methods: We identified 1664 EAI women (25–65 years) with ≥ 1 primary care clinic visit(s) between 2017 and 2018, using University of Washington (UW) Medicine electronic health record data. CCS adherence was defined as Pap testing within 3 years or human papillomavirus/Pap co-testing within 5 years. We used Poisson regression with robust standard errors to cross-sectionally estimate associations with correlates of adherence. Twelve-month screening uptake was also evaluated among overdue women. Results: CCS adherence was 63%. Factors associated with higher adherence included older age (adjusted prevalence ratios [APRs]:1.47:95%CI:1.14–1.90, 1.38:95%CI:1.05–1.80, respectively, for ages 30–39 and 40–49 vs 25–29 years), longer duration of care at UW Medicine (APR:1.22:95%CI:1.03–1.45, comparing > 10 vs < 5 years), higher visit frequency (APR:1.23:95%CI:1.04–1.44, 1.46:95%CI:1.24–1.72, respectively, for 3–5 and ≥ 6 vs 1–2 visits), index visit in an obstetrics-gynecology clinic (APR:1.26:95%CI:1.03–1.55, vs family practice), having an assigned primary care provider (APR:1.35: 95%CI:1.02–1.79), breast cancer screening adherence (APR:1.66: 95%CI:1.27–2.17), and colorectal cancer screening adherence (APR:1.59:95%CI:1.24–2.03). Low BMI was associated with lower adherence (APR:0.50:95%CI:0.26–0.96, comparing < 18.5 kg/m2vs 18.5–24.9 kg/m2). Among 608 (37%) overdue women, 9% were screened in the subsequent 12 months. Having commercial health insurance vs Medicare/Medicaid was associated with higher uptake (adjusted risk ratio:2.44:95%CI:1.15–5.18). Conclusion: CCS adherence among EAI was lower than the national average of 80%. Interventions focused on increasing healthcare access/utilization or leveraging healthcare encounters to address barriers could increase CCS in EAIs.

IMPORTANCE: Intraoperative identification of tissues through gross inspection during thyroid and parathyroid surgery is challenging yet essential for preserving healthy tissue and improving outcomes for patients. OBJECTIVE: To evaluate the performance and clinical applicability of the MasSpec Pen (MSPen) technology for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively. DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic/prognostic study, the MSPen was used to analyze 184 fresh-frozen thyroid, parathyroid, and lymph node tissues in the laboratory and translated to the operating room to enable in vivo and ex vivo tissue analysis by endocrine surgeons in 102 patients undergoing thyroidectomy and parathyroidectomy procedures. This diagnostic study was conducted between August 2017 and March 2020. Fresh-frozen tissues were analyzed in a laboratory. Clinical analyses occurred in an operating room at an academic medical center. Of the analyses performed on 184 fresh-frozen tissues, 131 were included based on sufficient signal and postanalysis pathologic diagnosis. From clinical tests, 102 patients undergoing surgery were included. A total of 1015 intraoperative analyses were performed, with 269 analyses subject to statistical classification. Statistical classifiers for discriminating thyroid, parathyroid, and lymph node tissues were generated using training sets comprising both laboratory and intraoperative data and evaluated on an independent test set of intraoperative data. Data were analyzed from July to December 2022. MAIN OUTCOMES AND MEASURES: Accuracy for each tissue type was measured for classification models discriminating thyroid, parathyroid, and lymph node tissues using MSPen data compared to gross analysis and final pathology results. RESULTS: Of the 102 patients in the intraoperative study, 80 were female (78%) and the median (IQR) age was 52 (42-66) years. For discriminating thyroid and parathyroid tissues, an overall accuracy, defined as agreement with pathology, of 92.4% (95% CI, 87.7-95.4) was achieved using MSPen data, with 82.6% (95% CI, 76.5-87.4) accuracy achieved for the independent test set. For distinguishing thyroid from lymph node and parathyroid from lymph node, overall training set accuracies of 97.5% (95% CI, 92.8-99.1) and 96.1% (95% CI, 91.2-98.3), respectively, were achieved. CONCLUSIONS AND RELEVANCE: In this study, the MSPen showed high performance for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively, suggesting this technology may be useful for providing near real-time feedback on tissue type to aid in surgical decision-making.

ABSTRACTThere is a dearth of literature on factors associated with citation of publications in ophthalmology. We investigated predictors of citations for original ophthalmologic research articles based on author, study, and journal characteristics. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), we extracted articles that studied the leading cause of vision impairment in the United States (cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma) and were published in the top fifteen ophthalmology journals with the highest impact factors that accepted original research. Descriptive statistics, one-way analysis of variance (ANOVA) tests, and negative binomial regression were used to compare citation counts based on author, study, and journal characteristics. In this study, author research productivity, journal impact factor, study funding, and location in high-income countries were predictors of increased citation in ophthalmology.

We report aircraft observations of extreme levels of HCl and the dihalogens Cl2, Br2, and BrCl in an industrial plume near the Great Salt Lake, Utah. Complete depletion of O3was observed concurrently with halogen enhancements as a direct result of photochemically produced halogen radicals. Observed fluxes for Cl2, HCl, and NOxagreed with facility-reported emissions inventories. Bromine emissions are not required to be reported in the inventory, but are estimated as 173 Mg year–1Br2and 949 Mg year–1BrCl, representing a major uncounted oxidant source. A zero-dimensional photochemical box model reproduced the observed O3depletions and demonstrated that bromine radical cycling was principally responsible for the rapid O3depletion. Inclusion of observed halogen emissions in both the box model and a 3D chemical model showed significant increases in oxidants and particulate matter (PM2.5) in the populated regions of the Great Salt Lake Basin, where winter PM2.5is among the most severe air quality issues in the U.S. The model shows regional PM2.5increases of 10%–25% attributable to this single industrial halogen source, demonstrating the impact of underreported industrial bromine emissions on oxidation sources and air quality within a major urban area of the western U.S.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy. A “non-α” IL-2 mutein induces systemic expansion of CD8+T cells and natural killer (NK) cells over Tregs but exhibits limited anti-tumor efficacy. We develop a programmed cell death protein 1 (PD-1)-targeted, receptor-masked IL-2 immunocytokine, PD1-IL2Ra-IL2, which attenuates systemic IL-2 activity while maintaining the capacity to engage IL-2Rα on PD-1+T cells. Mice treated with PD1-IL2Ra-IL2 show no systemic toxicities observed with unmasked IL-2 treatment yet achieve robust tumor growth control. Furthermore, PD1-IL2Ra-IL2 can be effectively combined with other T cell-mediated immunotherapies to enhance anti-tumor responses. These findings highlight the therapeutic potential of PD1-IL2Ra-IL2 as a targeted, receptor-masked, and “α-maintained” IL-2 therapy for cancer.

John Lin and Sony Devabhaktuni (University of Hong Kong) received the RIBA President’s Medal for Research 2021 for their research and book on As Found Houses: Experiments from Self-builders in Rural China. They were interviewed by Deane Simpson on 28 April 2022 at the Royal Danish Academy.

In the United States, adherence for cervical cancer screening decreased from 86% to 77% between 2005 and 2019. Over 50% of cervical cancers are diagnosed in individuals overdue for screening, and promoting access and adherence is essential. Unlike traditional Papanicolaou testing, human papillomavirus (HPV) screening can use self-collected samples, which have comparable sensitivity and specificity to clinician-collected samples. Self-collecting has been shown to increase screening adherence, possibly by circumventing important barriers such as scheduling clinic appointments and negativity about pelvic examinations. Despite this, most individuals in prior studies remained unscreened with low follow-up of HPV-positive results, and kit uptake among populations that are screening adherent or have unknown screening history is unknown.The STEP trial (self-testing options in the era for primary HPV screening for cervical cancer) was a parallel, single-blind, randomized clinical trial comparing cervical cancer screening completion across groups of individuals with due (screening-adherent), overdue, or unknown screening history. Participants were randomized to traditional care (patient reminders and clinician electronic health record [HER] alerts), education (usual care plus educational materials about screening), direct mail (traditional care plus educational materials plus a mailed HPV self-collection kit), or to opt in (traditional care plus educational materials plus the option to request a self-collection kit). Patients were identified using the Kaiser Permanente Washington HER and administrative claims. Eligible participants were females aged 30 to 64 years with current Kaiser Permanente Washington insurance and primary care, intact cervix, who were either due or overdue for screening. The primary study outcome was screening completion within 6 months after randomization, which could be done either in clinic or using the self-collection kit. Modified Poisson regression was used to estimate relative risk (RR) of screening completion for the direct-mail and opt-in groups, relative to the education group.A total of 32,771 participants were randomized between November 2020 and January 2022, of which 13,356 were due for screening, 8682 were overdue, and 10,733 had unknown screening history. Of those due for screening, the RR for screening completion was 1.30 (95% confidence interval [CI], 1.23–1.36; absolute difference, 14.1% [95% CI, 11.2%–16.9%]) for direct mail and 1.07 (95% CI, 1.02–1.12; absolute difference, 3.5% [95% CI, 1.2%–5.7%]) for the opt-in group compared with education. Of those overdue for screening, the RR for screening completion was 1.90 (95% CI, 1.68–2.16; absolute difference 16.9% [95% CI, 13.8%–20.0%]) for direct mail compared with education. Of those with unknown screening history, the RR for screening completion was 1.14 (95% CI, 1.03–1.25; absolute difference 2.2% [95% CI, 0.5%–3.9%]) for the opt-in group compared with education.The results of this randomized controlled trial showed that directly mailing HPV self-collection kits increased cervical cancer screening by over 14% compared with education alone. The effect was similar between participants that were due or overdue for screening, and an opt-in approach was found to minimally increase screening.

A half-decade of clinical experience using Kymriah for children and young adults (CAYA) with B-cell acute lymphoblastic leukemia (B-ALL) has amassed since commercialization, yet financial analyses remain sparse. Kymriah's list price is $475,000, not accounting for costs related to delivery of care, inpatient hospitalization, toxicity management or follow-up. We conduct the first multi-centered financial analysis of commercial CAR in CAYA B-ALL.

IMPORTANCE: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. OBJECTIVE: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children’s Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. EXPOSURES: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). MAIN OUTCOMES AND MEASURES: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line–associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. RESULTS: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. CONCLUSIONS AND RELEVANCE: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

ABSTRACTPurposeTo investigate the characteristics of first-year ophthalmology residents associated with high research productivity in twelve years.MethodsAll first-year ophthalmology residents in the United States (US) in 2009 listed by institutional websites were identified. Publications were obtained from Scopus and Google Scholar, h-indices were calculated, and medical school characteristics such as research productivity, region, rank, and average USMLE Steps 1 and 2 scores were obtained from National Institutes of Health, US Census Bureau, and US News.ResultsData were obtained on 70% (316/453) of residents; most were male, had Doctor of Medicine (MD) degrees, and graduated from medical schools in the US or Canada. Having an additional graduate degree [OR: 3.05, 95% CI: 1.07–8.67], between 1 and 3 publications [OR: 4.16, 95% CI: 2.22–7.79], or 4 or more publications [OR: 14.27, 95% CI: 3.13–64.94] were associated with higher future research productivity.ConclusionGraduate degrees and publication count were key predictors of future research productivity among ophthalmology residents in the US.

Introduction: Interviews are commonly used to select applicants for medical school, residency, and fellowship. However, interview techniques vary in acceptability, feasibility, reliability, and validity. This systematic review investigated the effectiveness of different interview methods in selecting the best qualified applicants for admission to medical school and developed a logic model to implement best practices for interviewing. Methods: Five electronic literature databases were searched for comparative studies related to interviewing in medical schools from inception through February 1, 2021. Inclusion criteria included publications in English that compared different methods of conducting a selection interview in medical schools with a controlled trial design. General study characteristics, measurement methodologies, and outcomes were reviewed. Quality appraisal was performed using the Medical Education Research Study Quality Instrument (MERSQI) and the Oxford Risk of Bias Scale. Based on these findings, a logic model was constructed using content analysis. Results: Thirteen studies were included. The multiple mini-interview (MMI) was reliable, unbiased, and predicted clinical and academic performance; the virtual MMI increased reliability and lowered costs. For unstructured interviews, blinding interviewers to academic scores reduced bias towards higher scorers; student and faculty interviewers rated applicants similarly. Applicants preferred structured over unstructured interviews. Study quality was above average per the MERSQI, risk of bias was high per the Oxford scale, and between-study heterogeneity was substantial. Discussion: There were few high-quality studies on interviewing applicants for admission to medical school; the MMI appears to offer a reliable method of interviewing. A logic model can provide a conceptual framework for conducting evidence-based admissions interviews.

Supplemental Digital Content is available in the text

ABSTRACTGay, bisexual, and other men who have sex with men (MSM) and transgender women are disproportionately affected by human papillomavirus (HPV). HPV vaccination is routinely recommended for U.S. adolescents at age 11–12 years, with catch-up vaccination through age 26 years. We assessed HPV vaccination coverage and associated factors among young MSM and transgender women. The Vaccine Impact in Men study enrolled MSM aged 18–26 years from clinics in Seattle, Chicago, and Los Angeles, during February 2016–September 2018. Participants self-reported socio-demographic information and HPV vaccination status. Among 1416 participants, 673 (47.5%) reported ≥1 HPV vaccine dose. Among vaccinated participants, median age at first dose was 19 years and median age at first sex was 17 years; 493 (73.3%) reported that their age at first dose was older than their age at first sex. There were significant differences in HPV vaccination coverage by city (range 33%–62%), age, race/ethnicity, and gender identity. Coverage was highest in Seattle, where younger age was the only factor associated with vaccination. Differences in coverage by city may be due to variation in vaccination practices or enrollment at study sites. Increasing both routine and catch-up vaccination will improve coverage among MSM and transgender women.

Food authenticity and safety are major public concerns due to the increasing number of food fraud cases. Meat fraud is an economically motivated practice of covertly replacing one type of meat with a cheaper alternative raising health, safety, and ethical concerns for consumers. In this study, we implement the MasSpec Pen technology for rapid and direct meat analysis and authentication. The MasSpec Pen is an easy-to-use handheld device connected to a mass spectrometer that employs a solvent droplet for gentle chemical analysis of samples. Here, MasSpec Pen analysis was performed directly on several meat and fish types including grain-fed beef, grass-fed beef, venison, cod, halibut, Atlantic salmon, sockeye salmon, and steelhead trout, with a total analysis time of 15 s per sample. Statistical models developed with the Lasso method using a training set of samples yielded per-sample accuracies of 95% for the beef model, 100% for the beef versus venison model, and 84% for the multiclass fish model. Predictors of meat type selected included several molecules previously reported in the skeletal muscles of animals, including carnosine, anserine, succinic acid, xanthine, and taurine. When testing the models on independent test sets of samples, per-sample accuracies of 100% were achieved for all models, demonstrating the robustness of our method for unadulterated meat authentication. MasSpec Pen feasibility testing for classifying venison and grass-fed beef samples adulterated with grain-fed beef achieved per-sample prediction accuracies of 100% for both classifiers using test sets of samples. Altogether, the results obtained in this study provide compelling evidence that the MasSpec Pen technology is a powerful alternative analytical method for meat analysis and investigation of meat fraud.

CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. In vitro, BCMAxCD3 bsAb efficiently induced polyclonal T-cell killing of primary human plasma cells and multiple myeloma (MM) cell lines expressing a range of BCMA cell surface densities. In vivo, BCMAxCD3 bsAb suppressed the growth of human MM tumors in murine xenogeneic models and showed potent combinatorial efficacy with programmed cell death protein 1 blockade. BCMAxCD3 bsAb administration to cynomolgus monkeys was well tolerated, resulting in the depletion of BCMA+ cells and mild inflammatory responses characterized by transient increases in C-reactive protein and serum cytokines. The antitumor efficacy of BCMAxCD3 bsAb was compared with BCMA-specific CAR T cells containing a BCMA-binding single-chain variable fragment derived from REGN5458. Both BCMAxCD3 bsAb and anti-BCMA CAR T cells showed similar targeted cytotoxicity of MM cell lines and primary MM cells in vitro. In head-to-head in vivo studies, BCMAxCD3 bsAb rapidly cleared established systemic MM tumors, whereas CAR T cells cleared tumors with slower kinetics. Thus, using the same BCMA-binding domain, these results suggest that BCMAxCD3 bsAb rapidly exerts its therapeutic effects by engaging T cells already in place at the tumor site, whereas anti-BCMA CAR T cells require time to traffic to the tumor site, activate, and numerically expand before exerting antitumor effects.

CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. In vitro, BCMAxCD3 bsAb efficiently induced polyclonal T-cell killing of primary human plasma cells and multiple myeloma (MM) cell lines expressing a range of BCMA cell surface densities. In vivo, BCMAxCD3 bsAb suppressed the growth of human MM tumors in murine xenogeneic models and showed potent combinatorial efficacy with programmed cell death protein 1 blockade. BCMAxCD3 bsAb administration to cynomolgus monkeys was well tolerated, resulting in the depletion of BCMA+cells and mild inflammatory responses characterized by transient increases in C-reactive protein and serum cytokines. The antitumor efficacy of BCMAxCD3 bsAb was compared with BCMA-specific CAR T cells containing a BCMA-binding single-chain variable fragment derived from REGN5458. Both BCMAxCD3 bsAb and anti-BCMA CAR T cells showed similar targeted cytotoxicity of MM cell lines and primary MM cells in vitro. In head-to-head in vivo studies, BCMAxCD3 bsAb rapidly cleared established systemic MM tumors, whereas CAR T cells cleared tumors with slower kinetics. Thus, using the same BCMA-binding domain, these results suggest that BCMAxCD3 bsAb rapidly exerts its therapeutic effects by engaging T cells already in place at the tumor site, whereas anti-BCMA CAR T cells require time to traffic to the tumor site, activate, and numerically expand before exerting antitumor effects.

Urban environments are characterized by pronounced spatiotemporal heterogeneity, which can present sampling challenges when utilizing conventional greenhouse gas (GHG) measurement systems. In Salt Lake City, Utah, a GHG instrument was deployed on a light rail train car that continuously traverses the Salt Lake Valley (SLV) through a range of urban typologies. CO2measurements from a light rail train car were used within a Bayesian inverse modeling framework to constrain urban emissions across the SLV during the fall of 2015. The primary objectives of this study were to (1) evaluate whether ground-based mobile measurements could be used to constrain urban emissions using an inverse modeling framework and (2) quantify the information that mobile observations provided relative to conventional GHG monitoring networks. Preliminary results suggest that ingesting mobile measurements into an inverse modeling framework generated a posterior emission estimate that more closely aligned with observations, reduced posterior emission uncertainties, and extends the geographical extent of emission adjustments.

•Mental skills training improves resident surgical performance.•Mental practice, relaxation exercises, and mindfulness are effective mental skills.•More studies linking mental skills training to operating room performance are needed.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Infection with influenza virus causes substantial morbidity and mortality globally, although antiviral treatments are available. Previous studies have suggested that anti-influenza immune plasma could be beneficial as treatment, but they were not designed as randomised, blinded, placebo-controlled trials. Therefore, we aimed to prospectively evaluate the clinical efficacy of high-titre immune plasma compared with standard low-titre plasma to improve outcomes in patients with severe influenza A infection.