Correlated charge noise and relaxation errors in superconducting qubits.

The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low1. Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.

Quasiparticle Poisoning of Superconducting Qubits from Resonant Absorption of Pair-Breaking Photons.

The ideal superconductor provides a pristine environment for the delicate states of a quantum computer: because there is an energy gap to excitations, there are no spurious modes with which the qubits can interact, causing irreversible decay of the quantum state. As a practical matter, however, there exists a high density of excitations out of the superconducting ground state even at ultralow temperature; these are known as quasiparticles. Observed quasiparticle densities are of order 1 µm^{-3}, tens of orders of magnitude greater than the equilibrium density expected from theory. Nonequilibrium quasiparticles extract energy from the qubit mode and can induce dephasing. Here we show that a dominant mechanism for quasiparticle poisoning is direct absorption of high-energy photons at the qubit junction. We use a Josephson junction-based photon source to controllably dose qubit circuits with millimeter-wave radiation, and we use an interferometric quantum gate sequence to reconstruct the charge parity of the qubit. We find that the structure of the qubit itself acts as a resonant antenna for millimeter-wave radiation, providing an efficient path for photons to generate quasiparticles. A deep understanding of this physics will pave the way to realization of next-generation superconducting qubits that are robust against quasiparticle poisoning.

A systematic review of whether Health Impact Assessment frameworks support best practice principles.

OBJECTIVES: Health Impact Assessment (HIA) is an evidence-based approach to assess the likely public health impacts of a policy or plan in any sector. Several HIA frameworks are available to guide practitioners doing a HIA. This systematic review sought to determine whether these support practitioners to meet best practice principles defined by the International Association for Impact Assessment. STUDY DESIGN: This was a systematic review. METHODS: Three complementary search strategies were used to identify frameworks in June 2022. We used three databases to find completed HIAs published in the last five years and hand-searched their reference lists for frameworks. We also searched 23 HIA repositories using Google's Advanced function and contacted HIA practitioners via two international mailing lists. We used a bespoke quality appraisal tool to assess frameworks against the principles. RESULTS: The search identified 24 HIA frameworks. None of the frameworks achieved a 'good' rating for all best practice principles. Many identified the principles but did not provide guidance on how to meet them at all HIA steps. The highest number of frameworks were rated 'good' for ethical use of evidence and comprehensive approach to health (n = 15). Eight frameworks were rated as 'good' for participation, and two for equity. The highest number of frameworks rated 'poor' for sustainability (n = 11). CONCLUSIONS: There is marked variation in the degree to which HIA frameworks support the best practice principles. HIA practitioners could select elements from different frameworks for practical guidance to meet all the best practice principles.

Hardware Implementation of Quantum Stabilizers in Superconducting Circuits.

Stabilizer operations are at the heart of quantum error correction and are typically implemented in software-controlled entangling gates and measurements of groups of qubits. Alternatively, qubits can be designed so that the Hamiltonian corresponds directly to a stabilizer for protecting quantum information. We demonstrate such a hardware implementation of stabilizers in a superconducting circuit composed of chains of π-periodic Josephson elements. With local on-chip flux and charge biasing, we observe a progressive softening of the energy band dispersion with respect to flux as the number of frustrated plaquette elements is increased, in close agreement with our numerical modeling.

Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142.

BACKGROUND: In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients. PATIENTS AND METHODS: Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). RESULTS: A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation. CONCLUSIONS: The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.

Tick-borne Encephalitis Identified in Ireland: Diagnosis and Outcome.

Presentation Tick borne encephalitis (TBE) is not endemic in Ireland and diagnostic tests are seldom requested. We describe the first notified case in Ireland. A 50-year-old female returned from Lithuania and presented with fever and new neurologic signs. Diagnosis TBE was diagnosed by detection of TBE virus specific antibodies in serum and cerebrospinal fluid (CSF). Treatment The patient was managed with observation and supportive care consisting of intravenous fluids and analgesia. Discussion The case highlights the importance of awareness of TBE among physicians and travellers to guide appropriate testing and vaccination. TBE is being recognised in non-endemic countries posing an emerging risk to public health.

Improving systems of care during and after a pregnancy complicated by hyperglycaemia: A protocol for a complex health systems intervention.

BACKGROUND: Many women with hyperglycaemia in pregnancy do not receive care during and after pregnancy according to standards recommended in international guidelines. The burden of hyperglycaemia in pregnancy falls disproportionately upon Indigenous peoples worldwide, including Aboriginal and Torres Strait Islander women in Australia. The remote and regional Australian context poses additional barriers to delivering healthcare, including high staff turnover and a socially disadvantaged population with a high prevalence of diabetes. METHODS: A complex health systems intervention to improve care for women during and after a pregnancy complicated by hyperglycaemia will be implemented in remote and regional Australia (the Northern Territory and Far North Queensland). The Theoretical Domains Framework was used during formative work with stakeholders to identify intervention components: (1) increasing workforce capacity, skills and knowledge and improving health literacy of health professionals and women; (2) improving access to healthcare through culturally and clinically appropriate pathways; (3) improving information management and communication; (4) enhancing policies and guidelines; (5) embedding use of a clinical register as a quality improvement tool. The intervention will be evaluated utilising the RE-AIM framework at two timepoints: firstly, a qualitative interim evaluation involving interviews with stakeholders (health professionals, champions and project implementers); and subsequently a mixed-methods final evaluation of outcomes and processes: interviews with stakeholders; survey of health professionals; an audit of electronic health records and clinical register; and a review of operational documents. Outcome measures include changes between pre- and post-intervention in: proportion of high risk women receiving recommended glucose screening in early pregnancy; diabetes-related birth outcomes; proportion of women receiving recommended postpartum care including glucose testing; health practitioner confidence in providing care, knowledge and use of relevant guidelines and referral pathways, and perception of care coordination and communication systems; changes to health systems including referral pathways and clinical guidelines. DISCUSSION: This study will provide insights into the impact of health systems changes in improving care for women with hyperglycaemia during and after pregnancy in a challenging setting. It will also provide detailed information on process measures in the implementation of such health system changes.

Staff Attitudes towards Patient Safety Culture and Working Conditions in an Irish Tertiary Neonatal Unit

Introduction There is little published research evaluating attitudes towards patient safety culture and working conditions in neonatal units. This study aimed to explore this within a Level III Irish neonatal unit setting. Methods This was a quantitative, cross-sectional study performed in the Rotunda Hospital, Dublin. A 30-item safety attitudes questionnaire (SAQ) was utilized to analyze staff perceptions in areas including job satisfaction, working conditions and stress recognition. Results The 'Stress Recognition' domain received the highest score (75.3) followed by 'Job Satisfaction' domain with a mean score of 74.4. The lowest mean scale score in the neonatal unit was for 'Perceptions of Management', with a mean score of 50.7. Collaboration and Communication scores were high across all disciplines. Conclusion This SAQ has highlighted a number of important areas for quality improvement and staff satisfaction in our neonatal unit.

Proceedings of the First Workshop Organized by the IAFSS Working Group on Measurement and Computation of Fire Phenomena (MaCFP).

This paper provides a report of the discussions held at the first workshop on Measurement and Computation of Fire Phenomena (MaCFP) on June 10-11 2017. The first MaCFP work-shop was both a technical meeting for the gas phase subgroup and a planning meeting for the condensed phase subgroup. The gas phase subgroup reported on a first suite of experimental- computational comparisons corresponding to an initial list of target experiments. The initial list of target experiments identifies a series of benchmark configurations with databases deemed suitable for validation of fire models based on a Computational Fluid Dynamics approach. The simulations presented at the first MaCFP workshop feature fine grid resolution at the millimeter- or centimeter- scale: these simulations allow an evaluation of the performance of fire models under high-resolution conditions in which the impact of numerical errors is reduced and many of the discrepancies between experimental data and computational results may be attributed to modeling errors. The experimental-computational comparisons are archived on the MaCFP repository [1]. Furthermore, the condensed phase subgroup presented a review of the main issues associated with measurements and modeling of pyrolysis phenomena. Overall, the first workshop provided an illustration of the potential of MaCFP in providing a response to the general need for greater levels of integration and coordination in fire research, and specifically to the particular needs of model validation.

Modeling flame extinction and reignition in large eddy simulations with fast chemistry.

This work seeks to support the validation of large eddy simulation models used to simulate fire suppression. The emphasis in the present study is on the prediction of flame extinction and the prevention of spurious reignition using a fast chemistry, mixing-controlled combustion model applicable to realistic fire scenarios of engineering interest. The configuration provides a buoyant, turbulent methane diffusion flame within a controlled co-flowing oxidizer. The oxidizer allows for the supply of a mixture of air and nitrogen, including conditions for which oxygen-dilution in the oxidizer leads to flame extinction. Measurements to support model validation include local profiles of thermocouple temperature and oxygen mole fraction, global combustion efficiency, and the limiting oxygen index. The present study evaluates the performance of critical-flame-temperature-based extinction and reignition models using the Fire Dynamics Simulator, an open-source fire dynamics solver. Alternate model cases are explored, each offering a unique treatment of extinction and reignition. Comparisons between simulated results and experimental measurements are used to evaluate the capability of these models to accurately describe flame extinction. Of the considered cases, those that include provisions to prevent spurious reignition show excellent agreement with measured data, whereas a baseline case lacking explicit reignition treatment fails to predict extinction.

Understanding patient access patterns for primary health-care services for Aboriginal and Islander people in Queensland: a geospatial mapping approach.

This paperexplores the patterns ofpatients'accessingsix Aboriginal and Islander CommunityControlled Health Services (AICCHSs) in Queensland. Between August 2011 and February 2014, 26199 patients made at least one visit over a 2-year period prior to at least one of six Queensland AICCHS - one urban service (RA 1) in south-east Queensland, and five services in regional towns (RA 3) in Far North Queensland. Geospatial mapping of addresses for these registered patients was undertaken. The outcomes analysed included travel times to, the proportion of catchment populations using each AICCHS and an assessment of alternative mainstream general practice availability to these patients was made. In brief, the use of AICCHS was higher than Australian Bureau of Statistics census data would suggest. Approximately 20% of clients travel more than 30min to seek Aboriginal Health services, but only 8% of patients travelled longer than 60min. In the major city site, many other general practitioner (GP) services were bypassed. The data suggest Aboriginal and Islander patients in Queensland appear to value community-controlled primary care services. The number of Indigenous clients in regional locations in the Far North Queensland registered with services is often higher than the estimated resident population numbers.

Management of Indigenous patients presenting with non ST-segment elevation acute coronary syndrome in South Australia: a retrospective cohort study.

AIM: Using Australian guidelines for management of acute coronary syndromes, we assessed the probability of an Indigenous patient receiving interventional and therapeutic care after presenting in two metropolitan hospitals. METHODS: A retrospective case note review of patients admitted through two Adelaide public tertiary hospital emergency departments from December 2007 to December 2009. The study cohort was 488 patients with high-risk clinical features without ST-segment elevation. RESULTS: Indigenous patients were significantly younger, present later in the disease process and have a higher burden of cardiovascular risk factors when compared with non-Indigenous patients. Indigenous patients were 54% more likely to receive angiography (Risk ratios (RR) = 1.54; 95% CI 1.31; 1.81) than non-Indigenous patients, however, this difference disappeared after adjustment for age, sex and propensity score. Indigenous patients were 20% more likely to receive the recommended medications (RR = 1.19, 95% CI 1.01; 1.40) compared with non-Indigenous patients. Patients over 65 years were 53% less likely to receive an angiogram (RR = 0.47, 95% CI 0.38; 0.56) and were 35% less likely to receive the recommended medications (RR = 0.65, 95% CI 0.54; 0.78) than a patient at the ages of 18-49. Women were almost 20% less likely to receive an angiogram (RR = 0.81, 95% CI 0.66; 0.99) and 20% less likely to receive the recommended medications (RR = 0.80, 95% CI 0.71; 0.91) when compared with men. The likelihood of receiving medications on discharge was significantly influenced by age, gender, ethnicity, comorbid burden and revascularisation. CONCLUSIONS: The younger age and significantly higher-risk profile of Indigenous adults presenting to SA hospitals with acute coronary syndromes appears to lead to different management decisions, which may well be led by patient factors. Many of these risk conditions can be better managed in the primary care setting.

Effect of a general practitioner management plan on health outcomes and hospitalisations in older patients with diabetes.

BACKGROUND: Little is known about the impact of a general practitioner management plan (GPMP) on health outcomes of patients with diabetes. AIM: To examine the impact of a GPMP on the risk of hospitalisation for diabetes. METHODS: A retrospective study using administrative data from the Australian Government Department of Veterans' Affairs was conducted (1 July 2006 to 30 June 2014) of diabetes patients either exposed or unexposed to a GPMP. The primary end-point was the risk of first hospitalisation for a diabetes-related complication and was assessed using Cox proportional hazard regression models with death as a competing risk. Secondary end-points included rates of receiving guideline care for diabetes, with differences assessed using Poisson regression analyses. RESULTS: A total of 16 214 patients with diabetes were included; 8091 had a GPMP, and 8123 did not. After 1 year, 545 (6.7%) patients with a GPMP and 634 (7.8%) of patients without a GPMP were hospitalised for a diabetes complication. There was a 22% reduction in the risk of being hospitalised for a diabetes complication (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.87, P < 0.0001) for those who received a GPMP by comparison to those who did not. Increased rates of diabetes guideline care, HbA1c claims (adjusted HR 1.29, 95% CI 1.25-1.33) and microalbuminura claims (adjusted HR 1.65, 95% CI 1.58-1.72) were observed after a GPMP. CONCLUSION: Provision of a GPMP in older patients with diabetes resulted in improved health outcomes, delaying the risk of hospitalisation at 12 months for diabetes complications. GPMP should be included as part of routine primary care for older patients with diabetes.

A prolonged outbreak of invasive meningococcal disease in an extended Irish Traveller family across three Health Service Executive (HSE) areas in Ireland, 2010 to 2013.

Between March 2010 and November 2013 eight laboratory-confirmed cases of serogroup B, invasive meningococcal disease (IMD) were identified in an extended Irish Traveller family across three Health Service Executive (HSE) areas of Ireland. Cases were aged between 5 and 46 months, and were either a cousin or sibling of another case. All eight cases survived. Chemoprophylaxis was given to relevant nuclear family members and close contacts on each occasion, but failed to prevent further cases. Neisseria meningitidis isolates from six cases were highly related, belonging to the ST-41/44 clonal complex, and shared the porA designation 7­2,4. In November 2013, the outbreak control team recommended that directly observed ciprofloxacin chemoprophylaxis be administered simultaneously to the extended family, and that the four component meningococcal B (4CMenB) vaccine be administered to family members aged 2 months to 23 years inclusive and relevant close contacts of the eighth case. Subsequently these recommendations were implemented at three regional clinics. Additionally pharyngeal swabs (n=112) were collected to assess carriage rates of N. meningitidis in this extended family. Pharyngeal carriage of N. meningitidis was detected in 15 (13%) family members. From the epidemiological investigation and carriage study overcrowding was the most likely risk factor identified in this outbreak. To date, the combination of directly observed ciprofloxacin chemoprophylaxis and use of 4CMenB vaccine have controlled the outbreak with no further cases diagnosed.

General practitioner management plans delaying time to next potentially preventable hospitalisation for patients with heart failure.

BACKGROUND: Several studies have shown that the Australian Medicare-funded chronic disease management programme can lead to improvements in care processes. No study has examined the impact on long-term health outcomes. AIMS: This retrospective cohort study assessed the association between provision of a general practitioner management plan and time to next potentially preventable hospitalisation for older patients with heart failure. METHODS: We used the Australian Government Department of Veterans' Affairs (DVA) claims database and compared patients exposed to a general practitioner management plan with those who did not receive the service. Kaplan-Meier analysis and Cox proportional hazards models were used to compare time until next potentially preventable hospitalisation for heart failure between the exposed and unexposed groups. RESULTS: There were 1993 patients exposed to a general practitioner management plan and 3986 unexposed patients. Adjusted results showed a 23% reduction in the rate of potentially preventable hospitalisation for heart failure at any time (adjusted hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.92; P = 0.0051) among those with a general practitioner management plan compared with the unexposed patients. Within one year, 8.6% of the exposed group compared with 10.7% of the unexposed group had a potentially preventable hospitalisation for heart failure. CONCLUSIONS: A general practitioner management plan is associated with delayed time to next potentially preventable hospitalisation for heart failure.

Unscheduled undergraduate teaching in surgery: a multi-institutional analysis.

A significant amount of valuable undergraduate medical teaching may be informal, unscheduled and delivered by non-consultant hospital doctors (NCHDs). 800 Questionnaires were distributed to consultants, NCHDs and medical students in Irish teaching hospitals. The aim was to quantify the level of unscheduled teaching carried out in these hospitals and the manner in which it was performed. The response rate was 46% (364/800). 71% of doctors who replied are independently teaching undergraduate medical students (77/109), including 71% of interns and senior house officers (48/68). Students tend to prefer small group teaching. Fifty-six percent of students suggest they would benefit from more surgical teaching time (144/255). No interns surveyed were scheduled to teach as part of a formal curriculum. A significant amount of unscheduled teaching by interns and senior house officers takes place in Irish hospitals. It may prove beneficial to incorporate interns into scheduled surgical teaching curricula.

Impact of age, gender and indigenous status on access to diagnostic coronary angiography for patients presenting with non-ST segment elevation acute coronary syndromes in Australia.

Using Australian guidelines for management of acute coronary syndromes, we investigated the proportion of high-risk patients enrolled in the Acute Coronary Syndromes Prospective Audit registry who received a coronary angiogram. A prospective nationwide multicentre registry involving 39 Australian hospitals was used. The study cohort were patients with high-risk clinical features without ST segment elevation (n = 1948) admitted from emergency departments between 1 November 2005 and 31 July 2007. Eighty nine per cent of patients with ST segment elevation myocardial infarction and only 53% of eligible patients with high-risk acute coronary syndromes with no ST elevation received a diagnostic angiogram. Increasing age was associated with lower rates of angiography; a high-risk patient at the age of ≥ 70 years was 19% less likely to receive an angiogram than one at the age of <70 years (risk ratio (RR) = 0.81 95% confidence interval (CI) 0.76, 0.76). Women were 26% less likely than men to receive an angiogram (RR = 0.74; 95% CI = 0.65, 0.83). The adjusted RR from the multivariate analysis suggests that a patient at the age of ≥ 70 years was 35% less likely to receive an angiogram than one at the age of <70 years (RR = 0.65, 95% CI = 0.60, 0.73), and that women were 13% less likely than men to receive an angiogram (RR = 0.87, 95% CI = 0.80, 0.96). Indigenous patients were as likely to access angiography as eligible non-indigenous patients (RR = 1.03, 95% CI 0.85, 1.25). There is underinvestigation of high-risk patients without ST segment elevation in Australian hospitals, particularly for women and older patients. Indigenous patients are younger and have poorer risk profiles, and represent a group that would benefit from greater investment in prevention strategies.

Hypertriglyceridemic waist and newly-diagnosed diabetes among remote-dwelling Indigenous Australians.

AIMS: Hypertriglyceridemic waist (HTgW) is predictive of cardiovascular disease. The HTgW relationship with diabetes is little studied. METHODS: This study analysed data from diabetes and cardiovascular risk factor screening programmes in remote Indigenous Australian settlements. Elevated waist girth (EW) was defined as ≥90 cm for men (n = 1134) or ≥80 cm for women (n = 1313). Hypertriglyceridemia (ETg) was defined as ≥1.7 mmol/L. Diabetes was defined as fasting plasma glucose ≥7.0 mmol/L. Body mass index (BMI) was categorised as <22, 22-24.9 and >25.0 kg/m(2). Logistic regression was used to analyse the odds of newly-diagnosed diabetes for individuals with either HTgW, ETg or EW, relative to individuals with values below cut-offs. RESULTS: The prevalence of HTgW was 33.2% for men and 34.8% for women. Accounting for age-group and gender, newly-diagnosed diabetes was associated (odds ratio (OR) (95% confidence interval)) with HTgW: 9.6 (6.6, 13.8). The relationship remained strong after accounting for the covariates BMI and smoking (OR = 4.9 (2.7, 8.8)). In BMI-stratified analyses the strongest odds were observed for the lowest category (<22 kg/m(2): OR = 12.9 (4.0, 41.7)). CONCLUSIONS: HTgW has a high prevalence and is associated with newly-diagnosed diabetes in Indigenous people, particularly those with BMI <22 kg/m(2), whom clinicians might not normally consider for screening.

Fluoropyrimidine-induced hand-foot syndrome and cardiotoxicity: recommendations for the use of the oral fluoropyrimidine S-1 in metastatic colorectal cancer.

BACKGROUND: Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has been approved by the European Medicines Agency as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic CRC in whom it is not possible to continue treatment with another FP due to hand-foot syndrome (HFS) or cardiovascular toxicity (CVT). Subsequently, this indication has been included in the 2022 ESMO guidelines for metastatic CRC. Recommendations for use in daily practice are not available. PATIENTS AND METHODS: Based on peer-reviewed published data on the use of S-1 in Western patients with metastatic CRC who switched from infusional 5-fluorouracil (5-FU) or capecitabine to S-1 for reasons of HFS or CVT, recommendations for its use were formulated by an international group of medical oncologists with expertise in the treatment of metastatic CRC and a cardio-oncologist. RESULTS: In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU. S-1 should preferably be initiated at full dose when HFS has decreased to grade ≤1. In patients with cardiac complaints, in whom an association with capecitabine or infusional 5-FU treatment cannot be excluded, capecitabine/5-FU should be discontinued and a switch to S-1 is recommended. CONCLUSIONS: These recommendations should guide clinicians in daily practice in the treatment of patients with metastatic CRC with FP-containing regimens.

Does an early childhood intervention affect cardiometabolic risk in adulthood? Evidence from a longitudinal study of preschool attendance in South Australia.

OBJECTIVES: There is an expectation that a positive social, cognitive and behavioural trajectory from early childhood developmental interventions will lead to improved population health and reduced health inequalities. However, there is limited direct evidence for this. The aim of this study was to assess the effect of participation in the South Australian Kindergarten Union preschool programme on adult cardiovascular biomedical risk factors. Kindergarten Union preschools delivered high-quality, comprehensive services to children aged 2-4 years and their families, including education, parenting and health services. STUDY DESIGN: Retrospective population-based cohort study. METHODS: The effect of attendance at a Kindergarten Union preschool on a range of cardiometabolic risk factors was assessed using data from the North West Adelaide Health Study 1999-2007. The study sample was taken from participants in the 2007 survey (n = 1064, 44.8% attended preschool) who lived in South Australia as children and were born during the years 1937-1969. RESULTS: Preschool attendance had a beneficial effect on hypertension in adulthood [prevalence ratio 0.82, 95% confidence interval (CI) 0.69-0.97] and an indication of benefit on hypercholesterolaemia (prevalence ratio 0.86, 95% CI 0.71-1.05), but had no effect on dyslipidaemia, central obesity, high fasting blood glucose or metabolic syndrome. CONCLUSIONS: This study found that preschool attendance was associated with reduced risk of hypertension in adulthood, but no effect was seen for the other cardiometabolic factors. These findings may reflect differing causal pathways and trajectories of these risk factors from childhood to adulthood, but confirmation from other studies is required.