A Fever-Th17 Cell Immune Axis: Some SMADs Like It Hot.

Fever has beneficial effects on immune responses; however, its impact on T cell polarization is poorly understood. In this issue of Immunity, Wang et al. show that fever acts through a T cell-intrinsic SMAD4-dependent mechanism that selectively drives Th17 cell differentiation and pathogenicity in autoimmunity.

Evaluation of behavioral economic strategies to raise influenza vaccination rates across a health system: Results from a randomized clinical trial.

Influenza vaccination rates are low. Working with a large US health system, we evaluated three health system-wide interventions using the electronic health record's patient portal to improve influenza vaccination rates. We performed a two-arm RCT with a nested factorial design within the treatment arm, randomizing patients to usual-care control (no portal interventions) or to one or more portal interventions. We included all patients within this health system during the 2020-2021 influenza vaccination season, which overlapped with the COVID-19 pandemic. Through the patient portal, we simultaneously tested: pre-commitment messages (sent September 2020, asking patients to commit to a vaccination); monthly portal reminders (October - December 2020), direct appointment scheduling (patients could self-schedule influenza vaccination at multiple sites); and pre-appointment reminder messages (sent before scheduled primary care appointments, reminding patients about influenza vaccination). The main outcome measure was receipt of influenza vaccine (10/01/2020-03/31/2021). We randomized 213,773 patients (196,070 adults ≥18 years, 17,703 children). Influenza vaccination rates overall were low (39.0%). Vaccination rates for study arms did not differ: Control (38.9%), pre-commitment vs no pre-commitment (39.2%/38.9%), direct appointment scheduling yes/no (39.1%/39.1%), pre-appointment reminders yes/no (39.1%/39.1%); p > 0.017 for all comparisons (p value cut-off adjusted for multiple comparisons). After adjusting for age, gender, insurance, race, ethnicity, and prior influenza vaccination, none of the interventions increased vaccination rates. We conclude that patient portal interventions to remind patients to receive influenza vaccine during the COVID-19 pandemic did not raise influenza immunization rates. More intensive or tailored interventions are needed beyond portal innovations to increase influenza vaccination.

Student nurses as a future general practice nursing workforce. Implementing collaborative learning in practice: implications for placement learning and patient access. A mixed methods study.

BACKGROUND: There is a global shortage of nurses, with particularly acute shortfall in General Practice Nursing in the United Kingdom estimated at as high as 50% vacancy rate by 2031 by some sources. There has previously been reluctance for General Practices to host student nurses on placement, but it has become imperative to increase placement capacity if practices are to be able to recruit a future workforce. Collaborative Learning in Practice is a means of organising placement learning for student nurses using a coaching model, that allows for leadership development, peer support and earlier engagement in patient care, and increases placement capacity. METHODS: This was a mixed methods study using qualitative data from focus groups to evaluate the implementation of Collaborative Learning in Practice, and routinely collected audit data on numbers of clinic appointments to investigate the potential impact an increased capacity of student nurses might have on patient access to services. The aims of this study were: to implement and evaluate Collaborative Learning in Practice in General Practice Nursing settings; to explore issues of interprofessional learning; to explore patient access to services related to increased student nurse capacity. RESULTS: Our qualitative data indicated the following themes as important to students and staff: Peer Support; Interprofessional Learning; and the Importance of 'own clinics' for students to see patients. The audit data indicated that having students leading their own clinics increased the clinic numbers available by approximately 20% compared to when students were not in placement. CONCLUSIONS: This study shows that student nurses increased clinic capacity and improved access for patients. Students valued their placement, felt that they were more 'part of the team' than in other placements and consequently had a greater sense of belonging. This was multifaceted, coming in part from the welcoming practice staff, in part from the opportunities for peer support engendered by the collaborative learning in practice model, and in part from the interprofessional learning opportunities available. General Practice Nursing placements for students are important for future workforce recruitment and can help meet Quality and Outcomes Framework targets for General Practices.

Effect of Personalized Messages Sent by a Health System's Patient Portal on Influenza Vaccination Rates: a Randomized Clinical Trial.

BACKGROUND: Adult influenza vaccination rates are low. Tailored patient reminders might raise rates. OBJECTIVE: Evaluate impact of a health system's patient portal reminders: (1) tailored to patient characteristics and (2) incorporating behavioral science strategies, on influenza vaccination rates among adults. DESIGN: Pragmatic 6-arm randomized trial across a health system during the 2019-2020 influenza vaccination season. The setting was one large health system-53 adult primary care practices. PARTICIPANTS: All adult patients who used the patient portal within 12 months, stratified by the following: young adults (18-64 years, without diabetes), older adults (≥65 years, without diabetes), and those with diabetes (≥18 years). INTERVENTIONS: Patients were randomized within strata to either (1) pre-commitment reminder alone (1 message, mid-October), (2) pre-commitment + loss frame messages, (3) pre-commitment + gain frame messages, (4) loss frame messages alone, (5) gain frame messages alone, or (6) standard of care control. Patients in the pre-commitment group were sent a message in mid-October, asking if they planned on getting an influenza vaccination. Patients in loss or gain frame groups were sent up to 3 portal reminders (late October, November, and December, if no documented influenza vaccination in the EHR) about importance and safety of influenza vaccine. MAIN MEASURES: Receipt of 1 influenza vaccine from 10/01/2019 to 03/31/2020. KEY RESULTS: 196,486 patients (145,166 young adults, 29,795 older adults, 21,525 adults with diabetes) were randomized. Influenza vaccination rates were as follows: for young adults 36.8%, for older adults 55.6%, and for diabetics 60.6%. On unadjusted and adjusted (for age, gender, insurance, race, ethnicity, and prior influenza vaccine history) analyses, influenza vaccination rates were not statistically different for any study group versus control. CONCLUSIONS: Patient reminders sent by a health system's patient portal that were tailored to patient demographics (young adults, older adults, diabetes) and that incorporated two behavioral economic messaging strategies (pre-commitment and loss/gain framing) were not effective in raising influenza vaccination rates. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT04110314).

Genetic ancestry and population differences in levels of inflammatory cytokines in women: Role for evolutionary selection and environmental factors.

Selection pressure due to exposure to infectious pathogens endemic to Africa may explain distinct genetic variations in immune response genes. However, the impact of those genetic variations on human immunity remains understudied, especially within the context of modern lifestyles and living environments, which are drastically different from early humans in sub Saharan Africa. There are few data on population differences in constitutional immune environment, where genetic ancestry and environment are likely two primary sources of variation. In a study integrating genetic, molecular and epidemiologic data, we examined population differences in plasma levels of 14 cytokines involved in innate and adaptive immunity, including those implicated in chronic inflammation, and possible contributing factors to such differences, in 914 AA and 855 EA women. We observed significant differences in 7 cytokines, including higher plasma levels of CCL2, CCL11, IL4 and IL10 in EAs and higher levels of IL1RA and IFNα2 in AAs. Analyses of a wide range of demographic and lifestyle factors showed significant impact, with age, education level, obesity, smoking, and alcohol intake, accounting for some, but not all, observed population differences for the cytokines examined. Levels of two pro-inflammatory chemokines, CCL2 and CCL11, were strongly associated with percent of African ancestry among AAs. Through admixture mapping, the signal was pinpointed to local ancestry at 1q23, with fine-mapping analysis refined to the Duffy-null allele of rs2814778. In AA women, this variant was a major determinant of systemic levels of CCL2 (p = 1.1e-58) and CCL11 (p = 2.2e-110), accounting for 19% and 40% of the phenotypic variance, respectively. Our data reveal strong ancestral footprints in inflammatory chemokine regulation. The Duffy-null allele may indicate a loss of the buffering function for chemokine levels. The substantial immune differences by ancestry may have broad implications to health disparities between AA and EA populations.

Risk factors for renal disease and diabetes in remote Australia - findings from The Western Desert Kidney Health Project.

INTRODUCTION: The Western Desert Kidney Health Project (WDKHP) aimed to determine the prevalence of type 2 diabetes (T2DM), kidney disease and associated risk factors in Aboriginal and non-Aboriginal people in a remote area of Western Australia. METHODS: The project, featuring whole-of-community cross-sectional surveys and health assessments using point-of-care testing, was conducted in five small towns and six remote Aboriginal communities in the Goldfields of Western Australia between 2010 and 2014. Initial health assessments were completed by 597 adults (424 Aboriginal) and 502 children (393 Aboriginal). This included almost 80% of the Aboriginal population. All non-Aboriginal people residing in the six remote Aboriginal communities participated. RESULTS: Risk factors for renal disease and T2DM were present in participants of all ages, including children as young as 2 years. There was no significant difference between Aboriginal and non-Aboriginal children. Aboriginal and non-Aboriginal adult participants had twice the burden of T2DM than the standard Australian population. More than 12% of all children had elevated albumin-creatinine ratio (ACR). Adults had markers of kidney disease at higher rates than expected: 51% of Aboriginal adults and 27% of non-Aboriginal adults had at least one marker of kidney disease (haematuria, proteinuria or elevated ACR). Aboriginal women were the highest risk group (32% T2DM, 40% elevated ACR). Haematuria and low urine pH were common findings, 21% of people had haematuria (greater than trace) and 71% had urine pH of 6 or less; there was no difference in this finding between Aboriginal and non-Aboriginal people. CONCLUSION: The WDKHP found higher than expected rates of risk factors for T2DM and renal disease compared with Australian Bureau of Statistics rates for Australian Aboriginal and non-Aboriginal adults and children, with Aboriginal women the highest risk group. The rates for non-Aboriginal participants were higher than expected, suggesting exposures in common might be more important than ethnicity.The high prevalence of aciduria and haematuria found in both Aboriginal and non-Aboriginal participants in this study suggests that factors contributing to a chronic metabolic acidosis and inflammation or irritation of the urinary tract need to be explored. Drinking water quality in this remote area is known to be poor and may be an important contributing factor. Many of the contributing factors are potentially modifiable - such as water quality, food supply, exercise opportunities and living conditions - offering scope for interventions to reduce the risk and burden of these diseases.

In situ thermal ablation augments antitumor efficacy of adoptive T cell therapy.

Purpose: The aim of this study is to investigate whether radiofrequency ablation (RFA) improves the efficacy of adoptive T cell immunotherapy in preclinical mouse cancer models.Method: Mice implanted subcutaneously (sc) with syngeneic colon adenocarcinoma or melanoma were treated with sub-curative in situ RFA (90 °C, 1 min). Trafficking of T cells to lymph nodes (LN) or tumors was quantified by homing assays and intravital microscopy (IVM) after sham procedure or RFA. Expression of trafficking molecules (CCL21 and intercellular adhesion molecule-1 [ICAM-1]) on high endothelial venules (HEV) in LN and tumor vessels was evaluated by immunofluorescence microscopy. Tumor-bearing mice were pretreated with RFA to investigate the therapeutic benefit when combined with adoptive transfer of in vitro-activated tumor-specific CD8+ T cells.Results: RFA increased trafficking of naïve CD8+ T cells to tumor-draining LN (TdLN). A corresponding increase in expression of ICAM-1 and CCL21 was detected on HEV in TdLN but not in contralateral (c)LN. IVM revealed that RFA substantially enhanced secondary firm arrest of lymphocytes selectively in HEV in TdLN. Furthermore, strong induction of ICAM-1 in tumor vessels was associated with significantly augmented trafficking of adoptively transferred in vitro-activated CD8+ T cells to tumors after RFA. Finally, preconditioning tumors with RFA augmented CD8+ T cell-mediated apoptosis of tumor targets and delayed growth of established tumors when combined with adoptive T cell transfer immunotherapy.Conclusions: These studies suggest that in addition to its role as a palliative therapeutic modality, RFA may have clinical potential as an immune-adjuvant therapy by augmenting the efficacy of adoptive T cell therapy.

Feedback learning opportunities from medical student logs of paediatric patients.

BACKGROUND: Feedback can alter medical student logging practices, although most learners feel feedback is inadequate. A varied case mix in rural and urban contexts offers diverse clinical encounters. Logs are an indicator of these clinical experiences, and contain opportunities for feedback, which can greatly influence learning: we labelled these 'feedback learning opportunities' (FLOs). We asked: How often do FLOs occur? What are the case complexities of rural compared to urban paediatric logs? Do more complex cases result in more FLOs? METHODS: In Western Australia, 25% of medical students are dispersed in a Rural Clinical School (RCSWA) up to 2175 miles (3500 km) from the city. Urban students logged 20 written cases; rural students logged a minimum of 25 paediatric cases electronically. These were reviewed to identify FLOs, using a coding convention. FLO categories provided a structure for feedback: medical, professionalism, insufficient, clinical reasoning, student wellbeing, quality and safety, and sociocultural. Each log was assigned an overall primary, secondary or tertiary case complexity. RESULTS: There were 76 consenting students in each urban and rural group, providing 3034 logs for analysis after exclusions. FLOs occurred in more than half the logs, with significantly more rural (OR 1.35 95% CI 1.17, 1.56; p < 0.0001). Major FLOs occurred in over a third of logs, but with no significant difference between rural and urban (OR 1.10 95% CI 0.94, 1.28; p = 0.24). Medical FLOs were the most common, accounting for 64.0% of rural and 75.2% of urban FLOs (OR 1.71 95% CI 1.37, 2.12; p < 0.0001). Students logged cases with a variety of complexities. Most cases logged by urban students in a tertiary healthcare setting were of primary and secondary complexity. Major medical FLOs increased with increasing patient complexity, occurring in 32.1% of tertiary complexity cases logged by urban students (p < 0.001). CONCLUSIONS: Case logs are a valuable resource for medical educators to enhance students' learning by providing meaningful feedback. FLOs occurred often, particularly in paediatric cases with multiple medical problems. This study strengthens recommendations for regular review and timely feedback on student logs. We recommend the FLOs categories as a framework for medical educators to identify FLOs.

The two faces of IL-6 in the tumor microenvironment.

Within the tumor microenvironment, IL-6 signaling is generally considered a malevolent player, assuming a dark visage that promotes tumor progression. Chronic IL-6 signaling is linked to tumorigenesis in numerous mouse models as well as in human disease. IL-6 acts intrinsically on tumor cells through numerous downstream mediators to support cancer cell proliferation, survival, and metastatic dissemination. Moreover, IL-6 can act extrinsically on other cells within the complex tumor microenvironment to sustain a pro-tumor milieu by supporting angiogenesis and tumor evasion of immune surveillance. A lesser known role for IL-6 signaling has recently emerged in which it plays a beneficial role, presenting a fairer face that opposes tumor growth by mobilizing anti-tumor T cell immune responses to attain tumor control. Accumulating evidence establishes IL-6 as a key player in the activation, proliferation and survival of lymphocytes during active immune responses. IL-6 signaling can also resculpt the T cell immune response, shifting it from a suppressive to a responsive state that can effectively act against tumors. Finally, IL-6 plays an indispensable role in boosting T cell trafficking to lymph nodes and to tumor sites, where they have the opportunity to become activated and execute their cytotoxic effector functions, respectively. Here, we discuss the dual faces of IL-6 signaling in the tumor microenvironment; the dark face that drives malignancy, and the fairer aspect that promotes anti-tumor adaptive immunity.

Paediatric case mix in a rural clinical school is relevant to future practice.

BACKGROUND: Exposure to a representative case mix is essential for clinical learning, with logbooks established as a way of demonstrating patient contacts. Few studies have reported the paediatric case mix available to geographically distributed students within the same medical school. Given international interest in expanding medical teaching locations to rural contexts, equitable case exposure in rural relative to urban settings is topical. The Rural Clinical School of Western Australia locates students up to 3500 km from the urban university for an academic year. There is particular need to examine paediatric case mix as a study reported Australian graduates felt unprepared for paediatric rotations. We asked: Does a rural clinical school provide a paediatric case mix relevant to future practice? How does the paediatric case mix as logged by rural students compare with that by urban students? METHODS: The 3745 logs of 76 urban and 76 rural consenting medical students were categorised by presenting symptoms and compared to the Australian Institute of Health and Welfare (AIHW) database Major Diagnostic Categories (MDCs). RESULTS: Rural and urban students logged core paediatric cases, in similar order, despite the striking difference in geographic locations. The pattern of overall presenting problems closely corresponded to Australian paediatric hospital admissions. Rural students logged 91% of cases in secondary healthcare settings; urban students logged 90% of cases in tertiary settings. The top four presenting problems were ENT/respiratory, gastrointestinal/urogenital, neurodevelopmental and musculoskeletal; these made up 60% of all cases. Rural and urban students logged similar proportions of infants, children and adolescents, with a variety of case morbidity. CONCLUSIONS: Rural clinical school students logged a mix of core paediatric cases relevant to illnesses of Australian children admitted to public hospitals, with similar order and pattern by age group to urban students, despite major differences in clinical settings. Logged cases met the curriculum learning outcomes of graduates. Minor variations were readily addressed via recommendations about logging. This paper provides evidence of the legitimacy of student logs as useful tools in affirming appropriate paediatric case mix. It validates the rural clinical school context as appropriate for medical students to prepare for future clinical paediatric practice.

IL-17 promotes neutrophil entry into tumor-draining lymph nodes following induction of sterile inflammation.

Blood-borne neutrophils are excluded from entering lymph nodes across vascular portals termed high endothelial venules (HEVs) because of lack of expression of the CCR7 homeostatic chemokine receptor. Induction of sterile inflammation increases neutrophil entry into tumor-draining lymph nodes (TDLNs), which is critical for induction of antitumor adaptive immunity following treatments such as photodynamic therapy (PDT). However, the mechanisms controlling neutrophil entry into TDLNs remain unclear. Prior evidence that IL-17 promotes neutrophil emigration to sites of infection via induction of CXCL2 and CXCL1 inflammatory chemokines raised the question of whether IL-17 contributes to chemokine-dependent trafficking in TDLNs. In this article, we demonstrate rapid accumulation of IL-17-producing Th17 cells in the TDLNs following induction of sterile inflammation by PDT. We further report that nonhematopoietic expression of IL-17RA regulates neutrophil accumulation in TDLNs following induction of sterile inflammation by PDT. We show that HEVs are the major route of entry of blood-borne neutrophils into TDLNs through interactions of l-selectin with HEV-expressed peripheral lymph node addressin and by preferential interactions between CXCR2 and CXCL2 but not CXCL1. CXCL2 induction in TDLNs was mapped in a linear pathway downstream of IL-17RA-dependent induction of IL-1ß. These results define a novel IL-17-dependent mechanism promoting neutrophil delivery across HEVs in TDLNs during acute inflammatory responses.

Advance care planning and end-of-life care in a network of rural Western Australian hospitals.

OBJECTIVE: To provide a current perspective on end-of-life (EOL) care in regional Western Australia, with a particular focus on the final admission prior to death and the presence of documented advance care planning (ACP). DESIGN: Retrospective medical notes audit. SETTING: One regional hospital (including colocated hospice) and four small rural hospitals in the Great Southern region of Western Australia. PARTICIPANTS: Ninety recently deceased patients, who died in hospitals in the region. Fifty consecutive patients from the regional hospital and 10 consecutive patients from each of the four rural hospitals were included in the audit. INTERVENTIONS: A retrospective medical notes audit was undertaken. MAIN OUTCOME MEASURES: A 94-item audit tool assessed patient demographics, primary diagnosis, family support, status on admission and presence of documented ACP. Detailed items described the clinical care delivered during the final admission, including communication with family, referral to palliative care, transfers, medical investigations, medical treatments and use of EOL care pathways. RESULTS: Fifty-two per cent were women; median age was 82 years old. Forty per cent died of malignancy. Median length of stay was 7 days. Thirty-nine per cent had formal or informal ACP documented. Rural hospitals performed comparably with the regional hospital on all measures. CONCLUSIONS: This study provides benchmarking information that can assist other rural hospitals and suggests ongoing work on optimal methods of measuring quality in EOL care.

A comparison of vitamin D levels in two antenatal populations in regional Western Australia--'Tjindoo Ba Thonee Thurra': sunshine for the pregnant belly.

BACKGROUND: There is a known increased risk of vitamin D deficiency in darker skinned people living in in temperate latitudes, but there is limited literature specifically on Australian Aboriginal women and their vitamin D status in pregnancy. METHODS: This paper reports the findings of a prospective cohort study comparing vitamin D levels in a group of pregnant Aboriginal women with a group of pregnant non-Aboriginal women living in the same town in Western Australia. RESULTS: Aboriginal patients from the Aboriginal Community Controlled Health Service (ACCHS) had lower serum vitamin D levels (mean 46.7, SD 21.7 nmol/L), compared with their non-Aboriginal women (mean 65.4, SD 18.4 nmol/L, P CONCLUSION: We believe this is the first study to compare vitamin D levels in pregnant Aboriginal women with non-Aboriginal women living in the same community at temperate latitude.

Impact of the Rural Clinical School of Western Australia on work location of medical graduates.

OBJECTIVE: To determine whether completing a year of the Rural Clinical School of Western Australia (RCSWA) program is associated with entering the rural medical workforce. DESIGN AND SETTING: Cohort study of graduates from the University of Western Australia who completed Year 5 of medical school between 2002 and 2009, comparing work location (identified from the Australian Health Practitioner Regulation Agency database in March-June 2013) between those who participated in the RCSWA (RCSWA graduates) and those who did not (controls). MAIN OUTCOME MEASURE: Rural or urban work location of graduates. RESULTS: Of 1116 eligible graduates, 1017 (91.1%) could be traced and were included in the study. Of 258 RCSWA graduates, 42 (16.3%) were working rurally compared with 36 of 759 controls (4.7%). Of 195 RCSWA graduates from urban backgrounds, 29 (14.9%) were working rurally compared with 26 of 691 urban-background controls (3.8%). Of 63 rural-background RCSWA graduates, 13 (20.6%) were working rurally, compared with 10 of 68 rural-background controls (14.7%). Using logistic regression, RCSWA participation had a strong relationship with working rurally (rural-background RCSWA graduates: odds ratio [OR], 7.5; 95% CI, 3.5-15.8; urban-background RCSWA graduates: OR, 5.1; 95% CI, 2.9-9.1). Rural background without RCSWA participation (OR, 4.2; 95% CI, 1.8-9.2) and older age (age in 2012, 30-39 years: OR, 2.2; 95% CI, 1.3-3.7 v ≥ 40 years: OR, 6.6; 95% CI, 2.8-15.0) were also significant factors for working rurally. CONCLUSIONS: Participation in the RCSWA is strongly associated with greater likelihood of working rurally. Graduates from urban backgrounds who participated in the RCSWA were much more likely to work in rural areas than those who did not. These data substantiate the RCSWA as an effective rural workforce strategy.

The micronutrient status of patients with phenylketonuria on dietary treatment: an ongoing challenge.

BACKGROUND: In phenylketonuria (PKU), phenylalanine-free L-amino acid supplements are the major source of dietary micronutrients. METHODS: Four hundred fifty-two retrospective annual/bi-annual non-fasting blood samples for nutritional markers (plasma zinc, selenium, and serum folate) from 78 subjects aged 1-16 years (median number of blood samples: 6, range 1-14) were analysed over 12 years. Longitudinal blood result data were available for 51 subjects (65%). The dietary intake from supplements was calculated. RESULTS: The median intakes of all of the micronutrients studied were >200% of the reference nutrient intakes (RNI). There was no statistical correlation between dietary intake and nutritional markers outside of the normal reference range (RR) except for selenium, but there was a correlation between a lower plasma zinc, plasma selenium and haemoglobin status and better blood phenylalanine control in 1- to 4-year-old children. On at least one occasion, the individual plasma concentrations of zinc (71%, n = 54/76) and selenium (21%, n = 16/75) were below the RR; however, the concentrations of selenium (41%, n = 31/75) and serum folate (83%, n = 34/41) were also above the RR. Dietary intakes exceeded the upper tolerable intakes for zinc and copper (32%, n = 25) and folate (65%, n = 51). Individual longitudinal data demonstrated little change in micronutrient status over time. CONCLUSIONS: In PKU, biochemical micronutrient deficiencies are common despite micronutrient intakes above the RNI. Further study of the nutritional profiling of L-amino acid supplements in PKU is needed.

Brugada-type patterns are easily observed in high precordial lead ECGs in collegiate athletes.

BACKGROUND: Displacement of ECG leads can result in unwarranted findings. We assessed the frequency of Brugada-type patterns in athletes when precordial leads were purposely placed upward. METHODS: Four hundred ninety-one collegiate athletes underwent two ECGs: one with standard leads, one with V1 and V2 along the 2nd intercostal space. A positive Brugada-type pattern was defined as ST elevation in V1 or V2 consistent with a Type 1, 2, or 3 pattern in the high-lead ECG. A control group was comprised of 181 outpatients. RESULTS: No Type 1 patterns were seen. In 58 athletes (11.8%), a Brugada-type 2 or 3 pattern was observed. Those with Brugada-type 2 or 3 patterns were more likely male, taller, and heavier. In the control group, 18 (9.9%) had Brugada-type 2 or 3 patterns and were more likely male. CONCLUSIONS: Proper lead positioning is essential to avoid unwarranted diagnosis of a Brugada-type ECG, especially in taller, heavier male athletes.

Gestational diabetes in a rural, regional centre in south Western Australia: predictors of risk.

INTRODUCTION: Gestational diabetes mellitus (GDM) is the most common antenatal complication in Western Australia. Rural areas may be at greater risk due to poorer socioeconomic status, reduced healthcare access, increased obesity and greater Aboriginal population. This paper reviews the prevalence and risk factors of GDM and outcomes for pregnancies in a regional rural centre, with a view to predicting the risk of GDM in this population, given factors identified early in the pregnancy. METHODS: Retrospective logistic regression analysis of all deliveries at Bunbury Regional Hospital (BRH) from February 2009 to March 2011 was used to produce a risk score for development of GDM. RESULTS: Of 1645 women delivered at BRH in the study period, nine had pre-existing diabetes and were excluded. A further 73 (4.46%) developed GDM in the current pregnancy. Logistic regression showed GDM to be strongly associated with maternal obesity (adjusted odds ratio 2.48; 95% CI 1.62-3.82), age (2.21; 1.57-3.09) lowest socioeconomic quintile (2.34; 1.23-4.22) and Asian ethnicity (3.47; 1.25-8.26). A cut-off value of 0.4 for the scoring system predicted the absence of GDM in 97.75% of women with a sensitivity of 69.9% and a predicted risk of 20.7% for GDM. Maternal outcomes showed that GDM was associated with an increased caesarean section rate (48.0% vs 30.8%; p=0.0066), lower spontaneous vaginal birth rate (37.7% vs 56.6%; p=0.048), postpartum haemorrhage (28.8% vs 17.7%; p=0.028) and longer median hospital stay (3 vs 2 days; p=0.0001). Neonatal outcomes showed a threefold increase in shoulder dystocia (10.5% vs 3.5%; p=0.025). CONCLUSIONS: These results confirm the known association of GDM with age; obesity, lower socioeconomic quintile and Asian ethnicity are also present in the rural population. The absence of association with Aboriginal ethnicity was not expected and is discussed.

Text vs Patient Portal Messaging to Improve Influenza Vaccination Coverage: A Health System-Wide Randomized Clinical Trial.

Importance: Increasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated. Objective: To evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system. Design, Setting, and Participants: This 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system. Interventions: Arm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated. Main Outcomes and Measures: The primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources. Results: A total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders. Conclusions and Relevance: At the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels. Trial Registration: ClinicalTrials.gov Identifier: NCT05525494.

Downregulation of IRF8 in alveolar macrophages by G-CSF promotes metastatic tumor progression.

Tissue-resident macrophages (TRMs) are abundant immune cells within pre-metastatic sites, yet their functional contributions to metastasis remain incompletely understood. Here, we show that alveolar macrophages (AMs), the main TRMs of the lung, are susceptible to downregulation of the immune stimulatory transcription factor IRF8, impairing anti-metastatic activity in models of metastatic breast cancer. G-CSF is a key tumor-associated factor (TAF) that acts upon AMs to reduce IRF8 levels and facilitate metastasis. Translational relevance of IRF8 downregulation was observed among macrophage precursors in breast cancer and a CD68hiIRF8loG-CSFhi gene signature suggests poorer prognosis in triple-negative breast cancer (TNBC), a G-CSF-expressing subtype. Our data highlight the underappreciated, pro-metastatic roles of AMs in response to G-CSF and identify the contribution of IRF8-deficient AMs to metastatic burden. AMs are an attractive target of local neoadjuvant G-CSF blockade to recover anti-metastatic activity.