Obstructing colorectal cancer: a population-based review of colonic stenting in Queensland, Australia.

PURPOSE: Stenting is a useful treatment option for malignant colonic obstruction, but its role remains unclear. This study was designed to establish how stents have been used in Queensland, Australia, and to review outcomes. METHODS: Patients diagnosed with colorectal cancer in Queensland from January 1, 2008, to December 31, 2014, who underwent colonic stent insertion were reviewed. Primary outcomes of 5-year survival, 30-day mortality, and overall length of survival were calculated. The secondary outcomes included patient and tumor factors, and stoma rates. RESULTS: In total, 319 patients were included, and distant metastases were identified in 183 patients (57.4%). The 30-day mortality rate was 6.6% (n=21), and the 5-year survival was 11.9% (n=38). Median survival was 11 months (interquartile range, 4-27 months). A further operation (hazard ratio [HR], 0.19; P<0.001) and chemotherapy and/or radiotherapy (HR, 0.718; P=0.046) reduced the risk of 5-year mortality. The presence of distant metastases (HR, 2.052; P<0.001) and a comorbidity score of 3 or more (HR, 1.572; P=0.20) increased mortality. Surgery was associated with a reduced risk of mortality even in patients with metastatic disease (HR, 0.14; P<0.001). Twenty-two patients (6.9%) ended the study period with a stoma. CONCLUSION: Colorectal stenting was used in Queensland in several diverse scenarios, in both localized and metastatic disease. Surgery had a survival advantage, even in patients with metastatic disease. There was no survival difference according to whether patients were socioeconomically disadvantaged, diagnosed in a major city or not, or treated at private or public hospitals. Stenting proved a valid treatment option with low stoma rates.

Effects of improved amino acid balance diet on lysine mammary utilization, whole body protein turnover and muscle protein breakdown on lactating sows.

BACKGROUND: The study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.24% CP) and reduced CP with "optimal" AA profile (OPT; 14.00% CP). Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1, 14, 18, and 21 of lactation. Between d 14 and 18, a subset of 9 sows (CON = 4, OPT = 5) was infused with a mixed solution of 3-[methyl-2H3]histidine (bolus injection) and [13C]bicarbonate (priming dose) first, then a constant 2-h [13C]bicarbonate infusion followed by a 6-h primed constant [1-13C]lysine infusion. Serial blood and milk sampling were performed to determine plasma and milk Lys enrichment, Lys oxidation rate, whole body protein turnover, and muscle protein breakdown. RESULTS: Over the 21-d lactation period, compared to CON, sows fed OPT had greater litter growth rate (P < 0.05). Compared to CON, sows fed OPT had greater efficiency of Lys (P < 0.05), Lys mammary flux (P < 0.01) and whole-body protein turnover efficiency (P < 0.05). Compared to CON, sows fed OPT tended to have lower whole body protein breakdown rate (P = 0.069). Muscle protein breakdown rate did not differ between OPT and CON (P = 0.197). CONCLUSION: Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein breakdown. These results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.

Association between Patient Race and Ethnicity and Use of Invasive Ventilation in the United States.

Rationale: Outcomes for people with respiratory failure in the United States vary by patient race and ethnicity. Invasive ventilation is an important treatment initiated based on expert opinion. It is unknown whether the use of invasive ventilation varies by patient race and ethnicity. Objectives: To measure 1) the association between patient race and ethnicity and the use of invasive ventilation; and 2) the change in 28-day mortality mediated by any association. Methods: We performed a multicenter cohort study of nonintubated adults receiving oxygen within 24 hours of intensive care admission using the Medical Information Mart for Intensive Care IV (MIMIC-IV, 2008-2019) and Phillips eICU (eICU, 2014-2015) databases from the United States. We modeled the association between patient race and ethnicity (Asian, Black, Hispanic, White) and invasive ventilation rate using a Bayesian multistate model that adjusted for baseline and time-varying covariates, calculated hazard ratios (HRs), and estimated 28-day hospital mortality changes mediated by differential invasive ventilation use. We reported posterior means and 95% credible intervals (CrIs). Results: We studied 38,258 patients, 52% (20,032) from MIMIC-IV and 48% (18,226) from eICU: 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% White (31,113). Invasive ventilation occurred in 9.2% (3,511), and 7.5% (2,869) died. The adjusted rate of invasive ventilation was lower in Asian (HR, 0.82; CrI, 0.70-0.95), Black (HR, 0.78; CrI, 0.71-0.86), and Hispanic (HR, 0.70; CrI, 0.61-0.79) patients compared with White patients. For the average patient, lower rates of invasive ventilation did not mediate differences in 28-day mortality. For a patient on high-flow nasal cannula with inspired oxygen fraction of 1.0, the odds ratios for mortality if invasive ventilation rates were equal to the rate for White patients were 0.97 (CrI, 0.91-1.03) for Asian patients, 0.96 (CrI, 0.91-1.03) for Black patients, and 0.94 (CrI, 0.89-1.01) for Hispanic patients. Conclusions: Asian, Black, and Hispanic patients had lower rates of invasive ventilation than White patients. These decreases did not mediate harm for the average patient, but we could not rule out harm for patients with more severe hypoxemia.

Opportunities and Challenges: Hepatitis C Testing and Treatment Access Experiences Among People in Methadone and Buprenorphine Treatment During COVID-19, Arizona, 2021.

Introduction: The purpose of this study was to characterize hepatitis C virus screening and treatment access experiences among people in treatment for opioid use disorder in Arizona during COVID-19. Methods: Arizonans receiving treatment for opioid use disorder from methadone clinics and buprenorphine providers during COVID-19 were interviewed about hepatitis C virus testing, curative treatment, and knowledge about screening recommendations. Interviews were conducted with 121 people from August 4, 2021 to October 10, 2021. Qualitative data were coded using the categories of hepatitis C virus testing, knowledge of screening recommendations, diagnosis, and experiences seeking curative treatment. Data were also quantitated for bivariate testing with outcome variables of last hepatitis C virus test, diagnosis, and curative treatment process. Findings were arrayed along an adapted hepatitis C virus cascade framework to inform program and policy improvements. Results: Just over half of the sample reported ever having tested for hepatitis C virus (51.2%, n=62) and of this group, 58.1% were tested in the past 12 months. Among those who were ever tested, 54.8% reported a hepatitis C virus diagnosis and 16.1% reported either being in treatment or having been declared cured of the hepatitis C virus. Among those who were diagnosed with hepatitis C, 14.7% indicated that they unsuccessfully tried to access curative treatment and would not attempt to again. Reasons cited for not accessing or receiving curative treatment included beliefs about treatment safety, barriers created by access requirements, natural resolution of the infection, and issues with healthcare coverage and authorization. Conclusions: Structural barriers continue to prevent curative hepatitis C virus treatment access. Given that methadone and buprenorphine treatment providers serve patients who are largely undiagnosed or treated for hepatitis C virus, opportunities exist for them to screen their patients regularly and provide support for and/or navigation to hepatitis C virus curative treatment.

Survival outcomes of head and neck melanoma patients in Queensland, Australia from 2009 to 2018.

BACKGROUND/OBJECTIVES: To compare survival outcomes for patients with cutaneous invasive head and neck melanoma (HNM) with those of patients with melanoma on other anatomical sites. METHODS: Retrospective cohort study using patient data extracted from the Cancer Alliance Queensland's Oncology Analysis System (OASYS) over a 10-year period from 2009 to 2018. Melanoma-specific survival was compared between patients with HNM and non-HNM. Kaplan-Meier survival estimates were calculated at 5 and 10 years. Univariable and multivariable Cox proportional hazards regression analysis determined factors associated with survival. RESULTS: The 5- and 10-year survival probabilities were 90.7% and 89.1%, respectively for HNM, compared with 94.7% and 93.0%, respectively, for non-HNM melanoma. The 5- and 10-year survival probabilities for scalp melanoma were 77.8% and 75.5%, respectively. Patients with HNM died of melanoma at 1.22 times (HR 1.22, 95% CI 1.09-1.37) the rate of those with non-HNM, controlling for sex, age, socioeconomic status, remoteness, Breslow thickness, the presence of multiple invasion melanoma and ulceration. Patients with scalp melanoma died of melanoma at 1.57 times (HR 1.57, 95% CI 1.26-1.95) the rate of those with non-scalp HNM. CONCLUSIONS: There is a statistically significant survival difference between patients with HNM and non-HNM, and between patients with scalp melanoma and non-scalp HNM, even after adjusting for prognostic factors.

Appraisal of Cardiovascular Risk Factors, Biomarkers, and Ocular Imaging in Cardiovascular Risk Prediction.

Cardiovascular disease remains a leading cause of death worldwide despite the use of available cardiovascular disease risk prediction tools. Identification of high-risk individuals via risk stratification and screening at sub-clinical stages, which may be offered by ocular screening, is important to prevent major adverse cardiac events. Retinal microvasculature has been widely researched for potential application in both diabetes and cardiovascular disease risk prediction. However, the conjunctival microvasculature as a tool for cardiovascular disease risk prediction remains largely unexplored. The purpose of this review is to evaluate the current cardiovascular risk assessment methods, identifying gaps in the literature that imaging of the ocular microcirculation may have the potential to fill. This review also explores the themes of machine learning, risk scores, biomarkers, medical imaging, and clinical risk factors. Cardiovascular risk classification varies based on the population assessed, the risk factors included, and the assessment methods. A more tailored, standardised and feasible approach to cardiovascular risk prediction that utilises technological and medical imaging advances, which may be offered by ocular imaging, is required to support cardiovascular disease prevention strategies and clinical guidelines.

Maternal Psychosocial Stress Is Associated with Reduced Diversity in the Early Infant Gut Microbiome.

The developing infant gut microbiome is highly sensitive to environmental exposures, enabling its evolution into an organ that supports the immune system, confers protection from infection, and facilitates optimal gut and central nervous system function. In this study, we focus on the impact of maternal psychosocial stress on the infant gut microbiome. Forty-seven mother-infant dyads were recruited at the HEAL Africa Hospital in Goma, Democratic Republic of Congo. Extensive medical, demographic, and psychosocial stress data were collected at birth, and infant stool samples were collected at six weeks, three months, and six months. A composite maternal psychosocial stress score was created, based on eight questionnaires to capture a diverse range of stress exposures. Full-length 16S rRNA gene sequences were generated. Infants of mothers with high composite stress scores showed lower levels of gut microbiome beta diversity at six weeks and three months, as well as higher levels of alpha diversity at six months compared to infants of low stress mothers. Longitudinal analyses showed that infants of high stress mothers had lower levels of health-promoting Lactobacillus gasseri and Bifidobacterium pseudocatenulatum at six weeks compared to infants of low stress mothers, but the differences largely disappeared by three to six months. Previous research has shown that L. gasseri can be used as a probiotic to reduce inflammation, stress, and fatigue, as well as to improve mental state, while B. pseudocatenulatum is important in modulating the gut-brain axis in early development and in preventing mood disorders. Our finding of reduced levels of these health-promoting bacteria in infants of high stress mothers suggests that the infant gut microbiome may help mediate the effect of maternal stress on infant health and development.

Trends and patterns of care of sentinel node biopsy in cutaneous melanoma: a population-based study in Queensland.

BACKGROUND: Sentinel node biopsy (SNB) has evolved from offering staging and prognostication to a procedure that guides therapeutic management. The aim was to evaluate the rate of SNB for patients with high-risk melanoma and assess factors that may have impacted on the procedure being performed. METHODS: Data of patients with primary invasive cutaneous melanoma from 01 January 2009 to 31 December 2019 were obtained from the Queensland Oncology Repository. High-risk melanoma was defined as ≥0.8 mm thick or < 0.8 mm with ulceration present (AJCC eighth edition pT1b -pT4 ). RESULTS: 14 006 (33.8%) of 41 412 patients diagnosed with cutaneous invasive melanoma were in the high-risk group. 2923(20.9%) patients had SNB, with the rate increasing from 14.2% (2009) to 36.8% (2019) (P = 0.002), and an increasing proportion being performed in public hospitals over the 11 year period (P = 0.02). Older age (OR0.96 (0.959-0.964) (P < 0.001)), female (OR0.91 (0.830-0.998) (P = 0.03)), head and neck primary (OR0.38 (0.33-0.45) (P < 0.001)), and pT1b (OR0.22 (0.19-0.25) (P < 0.001)) were factors associated with SNB not being performed. Travel out of the Hospital and Health Services of residence for SNB occurred in 26.2%. Although the travel rate decreased from 24.7% (2009) to 23.0% (2019) (P = 0.04), the absolute number increased due to the increase in SNB rate. Those most likely to travel were younger, from remote areas, or from affluent backgrounds. CONCLUSION: In this first Australian population-based study, there was an increased adherence to SNB guideline, although overall SLNB rates remain low, with nearly 2/3 of eligible cases not having the procedure in 2019. Although travel rates decreased marginally, the overall number increased. This study highlights the crucial need to further improve access to SNB for melanoma surgery for the Queensland population.

Assessment of Indices of Conjunctival Microvascular Function in Patients With and Without Obstructive Coronary Artery Disease.

BACKGROUND: Atherosclerotic heart disease often remains asymptomatic until presentation with a major adverse cardiovascular event. Primary preventive therapies improve outcomes, but conventional screening often misattributes risk. Vascular imaging can be utilised to detect atherosclerosis, but often involves ionising radiation. The conjunctiva is a readily accessible vascular network allowing non-invasive hemodynamic evaluation. AIM: To compare conjunctival microcirculatory function in patients with and without obstructive coronary artery disease. METHODS: We compared the conjunctival microcirculation of myocardial infarction patients (MI-cohort) to controls with no obstructive coronary artery disease (NO-CAD cohort). Conjunctival imaging was performed using a smartphone and slit-lamp biomicroscope combination. Microvascular indices of axial (Va) and cross-sectional (Vcs) velocity; blood flow rate (Q); and wall shear rate (WSR) were compared in all conjunctival vessels between 5 and 45 µm in diameter. RESULTS: A total of 127 patients were recruited (66 MI vs 61 NO-CAD) and 3602 conjunctival vessels analysed (2414 MI vs 1188 NO-CAD). Mean Va, Vcs and Q were significantly lower in the MI vs NO-CAD cohort (Va 0.50 ± 0.17 mm/s vs 0.55 ± 0.15 mm/s, p < 0.001; Vcs 0.35 ± 0.12 mm/s vs 0.38 ± 0.10 mm/s, p < 0.001; Q 154 ± 116 pl/s vs 198 ± 130 pl/s, p < 0.001). To correct for differences in mean vessel diameter, WSR was compared in 10-36 µm vessels (3268/3602 vessels) and was lower in the MI-cohort (134 ± 64 s-1 vs 140 ± 63 s-1, p = 0.002). CONCLUSIONS: Conjunctival microcirculatory alterations can be observed in patients with obstructive coronary artery disease. The conjunctival microvasculature merits further evaluation in cardiovascular risk screening.

Assessment of hemodynamic indices of conjunctival microvascular function in patients with coronary microvascular dysfunction.

OBJECTIVE: Coronary microvascular dysfunction (CMD) is a cause of ischaemia with non-obstructive coronary arteries (INOCA). It is notoriously underdiagnosed due to the need for invasive microvascular function testing. We hypothesized that systemic microvascular dysfunction could be demonstrated non-invasively in the microcirculation of the bulbar conjunctiva in patients with CMD. METHODS: Patients undergoing coronary angiography for the investigation of chest pain or dyspnoea, with physiologically insignificant epicardial disease (fractional flow reserve ≥0.80) were recruited. All patients underwent invasive coronary microvascular function testing. We compared a cohort of patients with evidence of CMD (IMR ≥25 or CFR <2.0); to a group of controls (IMR <25 and CFR ≥2.0). Conjunctival imaging was performed using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allows measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. RESULTS: A total of 111 patients were included (43 CMD and 68 controls). There were no differences in baseline demographics, co-morbidities or epicardial coronary disease severity. The mean number of vessel segments analysed per patient was 21.0 ± 12.8 (3.2 ± 3.5 arterioles and 14.8 ± 10.8 venules). In the CMD cohort, significant reductions were observed in axial/cross-sectional velocity, blood flow, wall shear rate and stress. CONCLUSION: The changes in microvascular function linked to CMD can be observed non-invasively in the bulbar conjunctiva. Conjunctival vascular imaging may have utility as a non-invasive tool to both diagnose CMD and augment conventional cardiovascular risk assessment.

Development of a key performance indicator for breast cancer in Queensland, Australia.

PURPOSE: Using population-based data for women diagnosed with stage I-III breast cancer, our aim was to examine the impact of time to treatment completion on survival and to identify factors associated with treatment delay. METHODS: This retrospective study used clinical and treatment data from the Queensland Oncology Repository. Time from diagnosis to completing surgery, chemotherapy and radiation therapy identified a cut-off of 37 weeks as the optimal threshold for completing treatment. Logistic regression was used to identify factors associated with the likelihood of completing treatment > 37 weeks. Overall (OS) and breast cancer-specific survival (BCSS) were examined using Cox proportional hazards models. RESULTS: Of 8279 women with stage I-III breast cancer, 31.9% completed treatment > 37 weeks. Apart from several clinical factors, being Indigenous (p = 0.002), living in a disadvantaged area (p = 0.003) and receiving ≥ two treatment modalities within the public sector (p < 0.001) were associated with an increased likelihood of completing treatment > 37 weeks. The risk of death from any cause was about 40% higher for women whose treatment went beyond 37 weeks (HR 1.37, 95%CI 1.16-1.61), a similar result was observed for BCSS. Using the surgery + chemotherapy + radiation pathway, a delay of > 6.9 weeks from surgery to starting chemotherapy was significantly associated with poorer survival (p = 0.001). CONCLUSIONS: Several sociodemographic and system-related factors were associated with a greater likelihood of treatment completion > 37 weeks. We are proposing a key performance indicator for the management of early breast cancer where a facility should have > 90% of patients with a time from surgery to adjuvant chemotherapy < 6.9 weeks.

Polymorphic Molecular Signatures in Variable Regions of the Plasmodium falciparum var2csa DBL3x Domain Are Associated with Virulence in Placental Malaria.

The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic diversity contributes to immune evasion and virulence remains poorly understood. The deep sequencing of the var2csa DBL3X domain in placental blood from forty-nine primigravid and multigravid women living in malaria-endemic western Kenya revealed numerous unique sequences within individuals in association with chronic PM but not gravidity. Additional analysis unveiled four distinct sequence types that were variably present in mixed proportions amongst the study population. An analysis of the abundance of each of these sequence types revealed that one was inversely related to infant gestational age, another was inversely related to placental parasitemia, and a third was associated with chronic PM. The categorization of women according to the type to which their dominant sequence belonged resulted in the segregation of types as a function of gravidity: two types predominated in multigravidae whereas the other two predominated in primigravidae. The univariate logistic regression analysis of sequence type dominance further revealed that gravidity, maternal age, placental parasitemia, and hemozoin burden (within maternal leukocytes), reported a lack of antimalarial drug use, and infant gestational age and birth weight influenced the odds of membership in one or more of these sequence predominance groups. Cumulatively, these results show that unique var2csa sequences differentially appear in women with different PM exposure histories and segregate to types independently associated with maternal factors, infection parameters, and birth outcomes. The association of some var2csa sequence types with indicators of pathogenesis should motivate vaccine efforts to further identify and target VAR2CSA epitopes associated with maternal morbidity and poor birth outcomes.

A novel algorithm for cardiovascular screening using conjunctival microcirculatory parameters and blood biomarkers.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case-control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

Trends in surgery and adjuvant treatment for early-stage breast cancer: a population-based study in Queensland, Australia.

PURPOSE: Our aim was to describe variations in the treatment of early-stage breast cancer and to examine factors associated with disease-specific survival (DSS). METHODS: The study used linked data for 24,190 women with a T1 (≤ 20 mm) breast cancer who underwent surgery from 2005 to 2019. Multivariate logistic regression was used to model predictors of receiving breast-conserving surgery (BCS) compared to mastectomy and a multinomial model was used to examine factors associated with type(s) of treatment received. RESULTS: Overall, 70.3% had BCS, with a reduced likelihood of BCS observed for younger women (p < 0.001), rural residence, (p < 0.001), socioeconomic disadvantage (p = 0.004), higher tumour grade (p < 0.001) and surgery in a public versus private hospital (p < 0.001). Compared to women who received BCS and radiation therapy (RT), those having mastectomy alone or mastectomy plus RT were more likely to be younger (p < 0.001), live in a rural area (p < 0.001), have higher-grade tumours (p < 0.001) and positive lymph nodes (p < 0.001). Overall 5-year survival was 95.3% and breast cancer-specific survival was 98.3%. Highest survival was observed for women having BCS and RT and lowest for those having mastectomy and RT (p < 0.001). CONCLUSION: Our results indicate some variation in the management of early-stage breast cancer. Lower rates of BCS were observed for rural and disadvantaged women and for those treated in a public or low-volume hospital. Whilst survival was high for this cohort, differences in tumour biology likely explain the differences in survival according to treatment type.

A novel murine model of post-implantation malaria-induced preterm birth.

Despite major advances made in malaria treatment and control over recent decades, the development of new models for studying disease pathogenesis remains a vital part of malaria research efforts. The study of malaria infection during pregnancy is particularly reliant on mouse models, as a means of circumventing many challenges and costs associated with pregnancy studies in endemic human populations. Here, we introduce a novel murine model that will further our understanding of how malaria infection affects pregnancy outcome. When C57BL/6J (B6) mice are infected with Plasmodium chabaudi chabaudi AS on either embryonic day (E) 6.5, 8.5, or 10.5, preterm birth occurs in all animals by E16.5, E17.5, or E18.5 respectively, with no evidence of intrauterine growth restriction. Despite having the same outcome, we found that the time to delivery, placental inflammatory and antioxidant transcript upregulation, and the relationships between parasitemia and transcript expression prior to preterm birth differed based on the embryonic day of infection. On the day before preterm delivery, E6.5 infected mice did not experience significant upregulation of the inflammatory or antioxidant gene transcripts examined; however, peripheral and placental parasitemia correlated positively with Il1ß, Cox1, Cat, and Hmox1 placental transcript abundance. E8.5 infected mice had elevated transcripts for Ifnγ, Tnf, Il10, Cox1, Cox2, Sod1, Sod2, Cat, and Nrf2, while Sod3 was the only transcript that correlated with parasitemia. Finally, E10.5 infected mice had elevated transcripts for Ifnγ only, with a tendency for Tnf transcripts to correlate with peripheral parasitemia. Tumor necrosis factor deficient (TNF-/-) and TNF receptor 1 deficient (TNFR1-/-) mice infected on E8.5 experienced preterm birth at the same time as B6 controls. Further characterization of this model is necessary to discover the mechanism(s) and/or trigger(s) responsible for malaria-driven preterm birth caused by maternal infection during early pregnancy.

IgG antibody production and persistence to 6 months following SARS-CoV-2 vaccination: A Northern Ireland observational study.

BACKGROUND: This study evaluates spike protein IgG antibody response following Oxford-AstraZeneca COVID-19 vaccination using the AbC-19™ lateral flow device. METHODS: Plasma samples were collected from n = 111 individuals from Northern Ireland. The majority were >50 years old and/or clinically vulnerable. Samples were taken at five timepoints from pre-vaccination until 6-months post-first dose. RESULTS: 20.3% of participants had detectable IgG responses pre-vaccination, indicating prior COVID-19. Antibodies were detected in 86.9% of participants three weeks after the first vaccine dose, falling to 74.7% immediately prior to the second dose, and rising to 99% three weeks post-second vaccine. At 6-months post-first dose, this decreased to 90.5%. At all timepoints, previously infected participants had significantly higher antibody levels than those not previously infected. CONCLUSION: This study demonstrates that strong anti-spike protein antibody responses are evoked in almost all individuals that receive two doses of Oxford-AstraZeneca vaccine, and which largely persist beyond six months after first vaccination.

Symptom experiences of critically-ill hematologic malignancy patients: A scoping review.

CONTEXT: Critically-ill patients with hematologic malignancies are increasingly admitted to intensive care units globally. Unrelieved symptoms during intensive care treatment may contribute to poor outcomes. OBJECTIVE: To better understand the symptom experience(s) for critically-ill patients with hematologic malignancies. METHODS: A scoping review was conducted searching Medline, CINAHL, PychInfo, Embase, and ProQuest databases, the Cochrane Library, and the grey literature between January 1st, 1990 and July 15th, 2020. Two authors independently reviewed articles for inclusion and verified abstracted data. RESULTS: Seventeen articles met inclusion criteria, including 11 cohort studies, 1 case-control study, and five review articles. No qualitative or mixed-method studies were retrieved. Symptoms were reported as the primary outcome across two studies (17%). Reported hematologic malignancy subtypes included leukemia and/or myelodysplastic syndrome (9, 53%), lymphoma (8, 47%), multiple myeloma (7, 41%), and aplastic anemia (2, 12%). The principal indication for ICU admission was respiratory failure, followed by cardiogenic shock/cardiac failure, endocrine disturbances, sepsis, and neurological failure. Only one study used validated tools for evaluating symptoms. Thirty-four symptoms were reported: altered level of consciousness/coma (35%); diarrhea (35%); nausea (35%); dyspnea (35%); vomiting (29%); and pain (29%). Two articles (13%) identified symptom clusters. CONCLUSION: There is minimal research that measures and explores the symptom experiences of critically-ill patients with hematologic malignancies. New research in this domain is needed to inform targeted symptom care for this vulnerable patient population.

User experience of home-based AbC-19 SARS-CoV-2 antibody rapid lateral flow immunoassay test.

The urgent need to scale up testing capacity during the COVID-19 pandemic has prompted the rapid development of point-of-care diagnostic tools such as lateral flow immunoassays (LFIA) for large-scale community-based rapid testing. However, studies of how the general public perform when using LFIA tests in different environmental settings are scarce. This user experience (UX) study of 264 participants in Northern Ireland aimed to gather a better understanding of how self-administered LFIA tests were performed by the general public at home. The UX performance was assessed via analysis of a post-test questionnaire including 30 polar questions and 11 7-point Likert scale questions, which covers the multidimensional aspects of UX in terms of ease of use, effectiveness, efficiency, accuracy and satisfaction. Results show that 96.6% of participants completed the test with an overall average UX score of 95.27% [95% confidence interval (CI) 92.71-97.83%], which suggests a good degree of user experience and effectiveness. Efficiency was assessed based on the use of physical resources and human support received, together with the mental effort of self-administering the test measured via NASA Task Load Index (TLX). The results for six TLX subscales show that the participants scored the test highest for mental demand and lowest for physical demand, but the average TLX score suggests that the general public have a relatively low level of mental workload when using LFIA self-testing at home. Five printed LFIA testing results (i.e. the 'simulated' results) were used as the ground truth to assess the participant's performance in interpreting the test results. The overall agreement (accuracy) was 80.63% [95% CI 75.21-86.05%] with a Kappa score 0.67 [95% CI 0.58-0.75] indicating substantial agreement. The users scored lower in confidence when interpreting test results that were weak positive cases (due to the relatively low signal intensity in the test-line) compared to strong positive cases. The end-users also found that the kit was easier to use than they expected (p < 0.001) and 231 of 264 (87.5%) reported that the test kit would meet their requirements if they needed an antibody testing kit. The overall findings provide an insight into the opportunities for improving the design of self-administered SARS-CoV-2 antibody testing kits for the general public and to inform protocols for future UX studies of LFIA rapid test kits.