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Aboriginal and Torres Strait Islander (Aboriginal) people in South Australia are overburdened by cardiovascular disease, diabetes and cancer. The South Australian Aboriginal Chronic Disease Consortium (Consortium) was established in June 2017 as a collaborative partnership to lead the implementation of three state‐wide chronic disease plans using a strategic approach to identifying key priority areas for action. In 2017–2018, the Consortium Coordinating Centre facilitated a priority setting process, which involved extensive consultation, including a prioritisation survey and stakeholder workshops. The Consortium's Aboriginal Community Reference Group was instrumental in leading the identification of priorities for action. The Consortium RoadMap for Action identified seven across‐plan priorities and six condition‐specific priorities. It acknowledged that: strengthening social and emotional well‐being is central to improving health outcomes; prevention and early detection, acute management and ongoing management are all components of the continuum of care; and improving access to services, strengthening the workforce, and monitoring and evaluation are required across the continuum of care. Widespread implementation failure in the past across the health system and health services implementation and research translation highlights the value of the Consortium approach and its commitment to implementing the state‐wide chronic disease plans in a collaborative manner. The Consortium relies on and fosters cross‐sectoral alignment, with all key players including all public, private and Aboriginal Community Controlled health services, to progress its priorities and aspirations to improve health outcomes for Aboriginal people using evidence‐based strategies. Rigorous and transparent priority setting processes that bring together research, clinical practice, health services operations, policy and community perspectives can foster intersectoral collaboration and partnership and support the implementation of shared priorities.

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy.

BackgroundCardiovascular disease (CVD) risk increases with age. Statins reduce cardiovascular risk but their effects are less certain at older ages. We assessed the long-term effects and cost-effectiveness of statin therapy for older people in the contemporary UK population using a recent meta-analysis of randomised evidence of statin effects in older people and a new validated CVD model.MethodsThe performance of the CVD microsimulation model, developed using the Cholesterol Treatment Trialists’ Collaboration (CTTC) and UK Biobank cohort, was assessed among participants ≥70 years old at (re)surveys in UK Biobank and the Whitehall II studies. The model projected participants’ cardiovascular risks, survival, quality-adjusted life years (QALYs) and healthcare costs (2021 UK£) with and without lifetime standard (35%–45% low-density lipoprotein cholesterol reduction) or higher intensity (≥45% reduction) statin therapy. CTTC individual participant data and other meta-analyses informed statins’ effects on cardiovascular risks, incident diabetes, myopathy and rhabdomyolysis. Sensitivity of findings to smaller CVD risk reductions and to hypothetical further adverse effects with statins were assessed.ResultsIn categories of men and women ≥70 years old without (15,019) and with (5,103) prior CVD, lifetime use of a standard statin increased QALYs by 0.24–0.70 and a higher intensity statin by a further 0.04–0.13 QALYs per person. Statin therapies were cost-effective with an incremental cost per QALY gained below £3502/QALY for standard and below £11778/QALY for higher intensity therapy and with high probability of being cost-effective. In sensitivity analyses, statins remained cost-effective although with larger uncertainty in cost-effectiveness among older people without prior CVD.ConclusionsBased on current evidence for the effects of statin therapy and modelling analysis, statin therapy improved health outcomes cost-effectively for men and women ≥70 years old.

BackgroundDespite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic burden; however, contemporary studies have produced conflicting outcomes.ObjectivesThis meta-analysis aims to evaluate the efficacy and safety of adjunctive IC thrombolytic therapy at the time of primary percutaneous coronary intervention (PCI) among patients with STEMI.MethodsComprehensive literature search of six electronic databases identified relevant randomised controlled trials. The primary outcome was major adverse cardiac events (MACE). The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated.Results12 studies with 1915 patients were included. IC thrombolysis was associated with a significantly lower incidence of MACE (RR=0.65, 95% CI 0.51 to 0.82, I2=0%, p<0.0004) and improved left ventricular ejection fraction (WMD=1.87; 95% CI 1.07 to 2.67; I2=25%; p<0.0001). Subgroup analysis demonstrated a significant reduction in MACE for trials using non-fibrin (RR=0.39, 95% CI 0.20 to 0.78, I2=0%, p=0.007) and moderately fibrin-specific thrombolytic agents (RR=0.62, 95% CI 0.47 to 0.83, I2=0%, p=0.001). No significant reduction was observed in studies using highly fibrin-specific thrombolytic agents (RR=1.10, 95% CI 0.62 to 1.96, I2=0%, p=0.75). Furthermore, there were no significant differences in mortality (RR=0.91; 95% CI 0.48 to 1.71; I2=0%; p=0.77) or bleeding events (major bleeding, RR=1.24; 95% CI 0.47 to 3.28; I2=0%; p=0.67; minor bleeding, RR=1.47; 95% CI 0.90 to 2.40; I2=0%; p=0.12).ConclusionAdjunctive IC thrombolysis at the time of primary PCI in patients with STEMI improves clinical and myocardial perfusion parameters without an increased rate of bleeding. Further research is needed to optimise the selection of thrombolytic agents and treatment protocols.

Inflammation has a direct role in the development of atherosclerotic vascular disease, and oral colchicine displays broad anti-inflammatory properties. Several large, randomised controlled trials (RCTs) have evaluated colchicine’s impact on cardiovascular outcomes. Results from a meta-analysis of these trials demonstrate that colchicine reduces the risk of recurrent major adverse cardiovascular events (MACEs) by 25%, leading to its recent approval by the Food and Drug Administration for the treatment and prevention of cardiovascular disease. Despite this, colchicine has not been shown to confer any survival benefit in these trials. The non-significant reduction in cardiovascular death of 18% (95% CI: 45% decrease to 23% increase) is outweighed by a more prominent, borderline non-significant increase in the risk of non-cardiovascular death by 38% (95% CI: 1% decrease to 92% increase). Key populations including those with heart failure, those undergoing surgical revascularisation, women, elderly individuals and non-Caucasians are under-represented in completed trials, which limits generalisability. C reactive protein has been proposed as a biomarker for colchicine response and shows promise for identifying a high-risk population where the benefit on MACE reduction and specifically reduced cardiovascular death might outweigh any real increased risk of non-cardiovascular death; however, this approach is still to be validated in ongoing RCTs. In conclusion, while colchicine shows promise in reducing MACE, its net risk–benefit profile requires further elucidation before its widespread adoption into clinical practice for the secondary prevention of atherosclerotic cardiovascular disease. Much more large-scale, long-term trial data are still needed in this space.

The Wellbeing Economy, which places human and ecological wellbeing at the centre of policy making, aligns with holistic Aboriginal and Torres Strait Islander conceptualisations of health and wellbeing. In order to address chronic diseases in South Australian Aboriginal and Torres Strait Islander populations, the South Australian Aboriginal Chronic Disease Consortium (Consortium) is fostering action in ways that align both with the Wellbeing Economy and with Health in All Policies (HiAP) approaches. In June 2017, the Consortium was established as a collaborative partnership between government and non‐government organisations, researchers, Aboriginal organisations and communities to lead the effective implementation of three state‐wide chronic disease plans. A coordinating centre was funded to support and progress the work of the Consortium. During its first 5 years, the Consortium has developed a foundation for sustained system reform through partnering with stakeholders, leading projects and initiatives, advocating for key priorities, leveraging existing infrastructure and funding, supporting services, and coordinating delivery of priority actions using innovative approaches. Through the Consortium governance structure, Aboriginal and Torres Strait Islander community members, policy actors, service providers and researchers oversee, drive, influence and support the implementation of priority action initiatives. Sustained funding, competing priorities of partner organisations and project evaluation are constant challenges. A consortium approach provides direction and shared priorities, which foster collaboration across and between organisations, service providers and the Aboriginal community. Aligning with HiAP approaches and the Wellbeing Economy, it harnesses knowledge, networks and partnerships that support project implementation and reduce duplication.

Bordetella pertussisepidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent B pertussisinfection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus–diphtheria–acellular pertussis vaccine (Tdap).

Physical activity can have a transformational positive impact on both individual and public health outcomes. It can be used to positively and proactively manage many common chronic conditions, as well as reducing the risk of developing them. However, in the UK, over one-in-four adults is physically inactive, and one-in-three children do less than half the physical activity recommended for their age. This article looks at the benefits of physical activity, UK government recommendations for physical activity in different age groups, and how to support patients in primary care to become more active.

Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy.

Very preterm infants are at increased risk of adverse outcomes in early childhood. We assessed whether delayed clamping of the umbilical cord reduces mortality or major disability at 2 years in the APTS Childhood Follow Up Study.

IMPORTANCE: Hybrid closed-loop (HCL) therapy has improved glycemic control in children and adolescents with type 1 diabetes; however, the efficacy of HCL on glycemic and psychosocial outcomes has not yet been established in a long-term randomized clinical trial. OBJECTIVE: To determine the percentage of time spent in the target glucose range using HCL vs current conventional therapies of continuous subcutaneous insulin infusion or multiple daily insulin injections with or without continuous glucose monitoring (CGM). DESIGN, SETTING, AND PARTICIPANTS: This 6-month, multicenter, randomized clinical trial included 172 children and adolescents with type 1 diabetes; patients were recruited between April 18, 2017, and October 4, 2019, in Australia. Data were analyzed from July 25, 2020, to February 26, 2021. INTERVENTIONS: Eligible participants were randomly assigned to either the control group for conventional therapy (continuous subcutaneous insulin infusion or multiple daily insulin injections with or without CGM) or the intervention group for HCL therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of time in range (TIR) within a glucose range of 70 to 180 mg/dL, measured by 3-week masked CGM collected at the end of the study in both groups. Secondary outcomes included CGM metrics for hypoglycemia, hyperglycemia, and glycemic variability and psychosocial measures collected by validated questionnaires. RESULTS: A total of 135 patients (mean [SD] age, 15.3 [3.1] years; 76 girls [56%]) were included, with 68 randomized to the control group and 67 to the HCL group. Patients had a mean (SD) diabetes duration of 7.7 (4.3) years and mean hemoglobin A1c of 64 (11) mmol/mol, with 110 participants (81%) receiving continuous subcutaneous insulin infusion and 72 (53%) receiving CGM. In the intention-to-treat analyses, TIR increased from a mean (SD) of 53.1% (13.0%) at baseline to 62.5% (12.0%) at the end of the study in the HCL group and from 54.6% (12.5%) to 56.1% (12.2%) in the control group, with a mean adjusted difference between the 2 groups of 6.7% (95% CI, 2.7%-10.8%; P = .002). Hybrid closed-loop therapy also reduced the time that patients spent in a hypoglycemic (&lt;70 mg/dL) range (difference, −1.9%; 95% CI, −2.5% to −1.3%) and improved glycemic variability (coefficient of variation difference, −5.7%; 95% CI, −10.2% to −0.9%). Hybrid closed-loop therapy was associated with improved diabetes-specific quality of life (difference, 4.4 points; 95% CI, 0.4-8.4 points), with no change in diabetes distress. There were no episodes of severe hypoglycemia or diabetic ketoacidosis in either group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, 6 months of HCL therapy significantly improved glycemic control and quality of life compared with conventional therapy in children and adolescents with type 1 diabetes. TRIAL REGISTRATION: ANZCTR identifier: ACTRN12616000753459

Reductions in blood pressure (BP) induced by exercise training may be associated with the acute reduction in BP observed minutes to hours following an exercise session, termed post-exercise hypotension (PEH). However, the magnitude and time-course of PEH, including the optimal exercise characteristics to maximise it, are still unclear. Using a randomised crossover design, 16 normotensive participants (median age (range) 22 (19–31) years; 50% female) undertook three different exercise sessions: sprint interval exercise (SIE, 30 × 8-s sprints with 32 s recovery), high-intensity interval exercise (HIIE, 15 × 1-min intervals at 90% peak heart rate (HR) with 1-min recovery), and moderate-intensity continuous exercise (MICE, 48 min at 65% peak HR). BP and HR were monitored before and up to 90 min following each session. The three exercise sessions each showed distinct PEH and of similar overall magnitude up to 90 min post exercise; however, there were distinct differences in the time-course. Systolic BP was lower 40 min after MICE compared to HIIE (−7.7 (−13.9 to −2.4) mmHg) and diastolic BP was higher 5 min after HIIE compared to SIE (8.5 (2.3–14.7) mmHg). MICE induced lower HR up to 40 min after exercise compared to HIIE and SIE. HIIE and SIE induced PEH of similar magnitude to MICE. A phasic or ‘W-shaped’ time-course of PEH observed following HIIE and SIE contrasted to a distinct ‘V-shaped’ PEH following MICE, indicating the physiological mechanisms driving BP regulation after exercise are influenced by exercise intensity.

Purpose: Black British minority ethnics (BME) students are nationally underachieving in comparison to their Ethnic Chinese and White peers, showing typically a 16 per cent graduate attainment gap in the UK. Previous research has suggested that the attainment gap could be explained by BME student disengagement, as the students typically commute from family home to University, and they work part time. However, peer-assisted learning (PAL) has been shown to have a positive impact on addressing and resolving student alienation and disengagement. However, a question still remains regarding whether student perceptions hold up to statistical analysis when scrutinised in comparison to similar cohorts without PAL interventions. The paper aims to discuss these issues. Design/methodology/approach: This paper presents the results of a statistical study for two cohorts of students on engineering courses with a disproportionately high representation of BME students. The research method involved a statistical analysis of student records for the two cohorts to ascertain any effect of correlation between: PAL; student ethnicity; and student parental employment on student academic performance and placement attainment. Findings: The results indicate that PAL has no significant impact on the academic performance; however, PAL has a positive impact on the placement/internship attainment for BME students and students from parental households with parents in non-managerial/professional employment. Research limitations/implications: The research limitations are that the cohorts are small, but more equal diverse mix of different social categories than any other courses. However, as the cohorts are less than 30 students, comparing social categories the data sets are small to have absolute confidence in the statistical results of academic performance. Even the t-test has its limitations as the subjects are human, and there are multiple personal factors that can impact an individual academic performance; therefore, the data sets are heterostatic. Practical implications: The results highlight that there is need for pedagogy interventions to support: ideally all BME students from all social categery to secure placements; BME students who are unable to go on placement to gain supplementary learning that has the same impact on their personal development and learning as placement/internship experience; and White students from managerial/professional family households to engage more in their studies. Social implications: Not addressing and providing appropriate pedagogy interventions, in the wider context not addressing/resolving the BME academic and placement attainment gap, a set of students are being disadvantaged to their peers through no fault of their own, and compounding their academic attainment. As academics we have a duty to provide every opportunity to develop our student attainment, and as student entry is generally homogeneous, all students should attain it. Originality/value: Previous research evaluation of PAL programmes has focused on quantitative students surveys and qualitative semi-structured research interviews with students on their student engagement and learning experience. On the other hand, this paper evaluates the intervention through conducting a quantitative statistical analysis of the student records to evaluate the impact of PAL on a cohort’s performance on different social categories (classifications) and compares the results to a cohort of another group with a similar student profile, but without PAL intervention implementation.

IMPORTANCE: The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Patients with metabolic syndrome (MetS) are at increased cardiovascular risk. OBJECTIVE: To investigate outcomes with evolocumab in patients with and without MetS. DESIGN, SETTING, AND PARTICIPANTS: The FOURIER trial randomized patients worldwide with stable atherosclerotic cardiovascular disease receiving statin to evolocumab vs placebo with follow-up for a median of 2.2 years. Data were collected February 2013 to November 2016. For this prespecified analysis, patients with the requisite data were stratified based on the National Cholesterol Education Program Adult Treatment Panel III MetS criteria; in secondary analyses, patients were further substratified by diabetes at baseline. Analysis was intention to treat. Analysis began March 2018 and ended April 2020. INTERVENTIONS: Patients were randomized to evolocumab or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point was cardiovascular death, myocardial infarction, or stroke. RESULTS: Of 27 342 patients (mean [SD] age, 63 [9] years; 20 623 men [75.4%]) included in this analysis, 16 361 (59.8%) with baseline MetS were, when compared with patients without MetS, at higher risk of cardiovascular events (adjusted hazard ratio [95% CI], 1.31 [1.18-1.46]; P &lt; .001 for the primary and 1.38 [1.20-1.57]; P &lt; .001 for the key secondary end point). Evolocumab reduced low-density lipoprotein cholesterol similarly in patients with MetS (median [interquartile range], 92 [79-109] mg/dL vs 30 [19-48] mg/dL; P &lt; .001) and without MetS (median [interquartile range], 92 [81-108] mg/dL vs 29 [18-44] mg/dl; P &lt; .001). For the primary end point, the hazard ratios (95% CI) with evolocumab vs placebo were 0.83 (0.76-0.91) and 0.89 (0.79-1.01) in patients with and without MetS (P for interaction = .39). For the key secondary end point, the corresponding hazard ratios (95% CIs) were 0.76 (0.68-0.86) and 0.86 (0.74-1.01) (P for interaction = .23), respectively. Evolocumab did not increase the risk of new-onset diabetes or other major safety outcomes including worsening glycemic control, compared with placebo in patients with MetS. CONCLUSIONS AND RELEVANCE: Patients with atherosclerotic cardiovascular disease and MetS have substantial residual risk of cardiovascular events despite statin therapy. Evolocumab significantly reduced low-density lipoprotein cholesterol and cardiovascular risk in patients with MetS without increasing new-onset diabetes, worsening glycemic control, or other major safety events. These data suggest the addition of evolocumab to statin therapy in patients with atherosclerotic cardiovascular disease and MetS is safe and efficacious to reduce residual cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01764633

Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes. We aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle programme.

The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients.

IMPORTANCE: The 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol identified patients with recent (past 12 months) myocardial infarction (MI) as very high risk, in whom a PCSK9 inhibitor is reasonable to add to maximally tolerated statin combined with ezetimibe if their low-density lipoprotein cholesterol level is 70 mg/dL or greater or non–high-density lipoprotein cholesterol level is 100 mg/dL or greater. OBJECTIVE: To examine the clinical efficacy of evolocumab in patients with recent MI. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, in which 27 564 patients with atherosclerotic cardiovascular disease treated with a statin were randomized to evolocumab vs placebo. Patients with prior MI with a known date (n = 22 320) were stratified as having a recent MI (within 12 months of randomization) or a remote MI (more than 12 months prior to randomization). Per protocol, patients with MI within 4 weeks prior to randomization were excluded from the FOURIER trial. Data were collected from February 2013 to November 2016, and data were analyzed from May 2019 to February 2020. MAIN OUTCOMES AND MEASURES: The primary composite end point was cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary composite end point was cardiovascular death, MI, or stroke. RESULTS: Of 22 320 included patients, 17 516 (78.5%) were male, and the mean (SD) age was 62.2 (9.0) years. Compared with 16 609 patients with a remote MI, 5711 patients with a recent MI were younger and more likely to be treated with high-intensity statin (77.3% [4415] vs 69.3% [11 506]). In the placebo arm, the 3-year Kaplan-Meier rate for the primary end point was 17.2% in patients with recent MI compared with 14.4% in those with remote MI (adjusted HR, 1.45; 95% CI, 1.29-1.64; P &lt; .001). Similarly, the 3-year Kaplan-Meier rates for the key secondary end point was also higher in those with recent MI (10.9% vs 9.5%; adjusted HR, 1.45; 95% CI, 1.24-1.69; P &lt; .001). In patients with a recent MI, evolocumab reduced the risk of the primary and key secondary end points by 19% (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93) and 25% (HR, 0.75; 95% CI, 0.62-0.91), respectively. In patients with a remote MI, evolocumab reduced the risk of the primary and key secondary end points by 8% (HR, 0.92; 95% CI, 0.84-1.01; P for interaction = .13) and 15% (HR, 0.85; 95% CI, 0.76-0.96; P for interaction = .24), respectively. Given the higher event rates in patients with a recent MI, the absolute risk reductions over 3 years with evolocumab were 3.7% in those with recent MI vs 1.1% in those with remote MI for the primary end point and 3.2% vs 1.3%, respectively, for the key secondary end point. CONCLUSIONS AND RELEVANCE: Patients with a recent MI were at higher risk of cardiovascular events and tended to experience greater absolute risk reductions with evolocumab than those with remote MIs. These findings support the concept in US and European guidelines to aggressively lower low-density lipoprotein cholesterol levels in very high-risk patients, such as those with a recent MI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01764633

IMPORTANCE: The PCSK9 inhibitor evolocumab reduced major vascular events in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, yet the types and sizes of myocardial outcomes in FOURIER have not been previously explored. OBJECTIVE: To assess the types and sizes of myocardial infarction (MI) and the effect of evolocumab on MI by subtype. DESIGN, SETTING, AND PARTICIPANTS: A prespecified analysis of a multicenter double-blind randomized clinical trial. Patients were randomized to evolocumab or placebo and followed up for a median of 2.2 years. The study included 27 564 patients with stable atherosclerotic disease receiving statin therapy. Clinical end points were evaluated by the Thrombolysis in Myocardial Infarction clinical events committee. Rates presented are 3-year Kaplan-Meier estimates. Data were collected from 2013 to 2016 and analyzed from June 2017 to December 2019. MAIN OUTCOMES AND MEASURES: Myocardial infarction was defined based on the third universal MI definition, and further classified according to MI type (universal MI subclass, ST-segment elevation myocardial infarction [STEMI] vs non–STEMI) and by MI size (determined by peak troponin level). RESULTS: A total of 27 564 patients were randomized, with a mean (SD) age of 62.5 (9.0) years, and 20 795 (75%) were male. Of these, 1107 patients experienced a total of 1288 MIs. Most MIs (68%) were atherothrombotic (type 1), with 15% from myocardial oxygen supply-demand mismatch (type 2) and 15% percutaneous coronary intervention–related (type 4). Sudden death (type 3) and coronary artery bypass grafting–related (type 5) accounted for a total of 21 MIs (&lt;2%). Evolocumab significantly reduced the risk of first MI by 27% (4.4% vs 6.3%; hazard ratio [HR], 0.73; 95% CI, 0.65-0.82; P &lt; .001), type 1 by 32% (2.9% vs 4.5%; HR, 0.68; 95% CI, 0.59-0.79; P &lt; .001), and type 4 by 35% (0.8% vs 1.1%; HR, 0.65; 95% CI, 0.48-0.87; P = .004), with no effect on type 2 (0.9% vs 0.8%; HR, 1.09; 95% CI, 0.82-1.45; P = .56). Most MIs (688 [59.8%]) had troponin levels greater than or equal to 10 times the upper limit of normal. The benefit was highly significant and consistent regardless of the size of MI with a 34% reduction in MIs with troponin level greater than or equal to 10 times the upper limit of normal (2.6% vs 3.7%; HR, 0.66; 95% CI, 0.56-0.77; P &lt; .001) and a 36% reduction in the risk of STEMI (1.0% vs 1.5%; HR, 0.64; 95% CI, 0.49-0.84; P &lt; .001). CONCLUSIONS AND RELEVANCE: Low-density lipoprotein cholesterol lowering with evolocumab was highly effective in reducing the risk of MI. This reduction with evolocumab included benefit across multiple subtypes of MI related to plaque rupture, smaller and larger MIs, and both STEMI and non–STEMI. These data are consistent with the known benefit of low-density lipoprotein cholesterol lowering and underscore the reduction in clinically meaningful events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01764633

AbstractLifetime predictions of used nuclear fuel containers (UFCs) destined for permanent storage in deep geological repositories are challenged by the uncertainty surrounding the environment and resultant performance of both the containers and the balance of engineered barriers over repository timescales. Much of the work to characterize the response of engineered barriers to postulated evolving environmental conditions and degradation mechanisms is limited to very short-term laboratory tests or at best in situ large-scale experiments spanning less than a few decades. While much is learned from these test programs, the fact remains that long-term performance of many tens of thousands of UFCs across a timescale of 100 000 years or more cannot be estimated with a significant degree of confidence by extrapolating single-point results of short-term experiments. This is particularly true when there is a desire to understand the progression of container failures and the timing of contaminants subsequently released into the geosphere. Lifetime predictions for UFCs require a probabilistic approach to address uncertainty. In the present work, a recently developed probabilistic corrosion model to estimate the life expectancy of copper-coated UFCs destined for a Canadian geological repository is expanded by modeling the impact of latent copper-coating defects and repository temperature on the key container life-limiting mechanism: sulfide-induced corrosion.

Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Approximately 1 of every 300 children in the United States has type 1 diabetes mellitus (T1D), and these patients may require anesthetics for a variety of procedures. Perioperative coordination is complex, and attention to perioperative fasting, appropriate insulin administration, and management of hypo- and hyperglycemia, as well as other metabolic abnormalities, is required. Management decisions may be impacted by the patient’s baseline glycemic control and home insulin regimen, the type of procedure being performed, and expected postoperative recovery. If possible, preoperative planning with input from the patient’s endocrinologist is considered best practice. A multi-institutional working group was formed by the Society for Pediatric Anesthesia Quality and Safety Committee to review current guidelines in the endocrinology and anesthesia literature and provide recommendations to anesthesiologists caring for pediatric patients with T1D in the perioperative setting. Recommendations for preoperative evaluation, glucose monitoring, insulin administration, fluid management, and postoperative management are discussed, with particular attention to increasingly prevalent insulin pumps and continuous glucose monitoring (CGM).

Supplemental Digital Content is available in the text.

AbstractAutoimmune encephalitis is a rapidly evolving area of study in pediatric populations, and functional neurological symptom disorders are under-studied in children. Differential diagnosis among these disorders is challenging, but pediatric neuropsychologists are uniquely qualified to assist a multidisciplinary team. This case illustrates a young girl with suspected autoimmune encephalitis, whose symptoms were revealed to be primarily functional in nature. She was followed over the course of two years with neuropsychological evaluation and consultation. Immunomodulatory treatments were tried, but psychosocial interventions eventually had the greatest impact. The implications for careful monitoring and assessment of pediatric patients with suspected autoimmune encephalitis by a pediatric neuropsychologist are illuminated by the case of this interesting girl and her family.

The benefits of LDL cholesterol-lowering treatment for the prevention of atherosclerotic cardiovascular disease are well established. However, the extent to which these effects differ by baseline LDL cholesterol, atherosclerotic cardiovascular disease risk, and the presence of comorbidities remains uncertain.

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.