Weight loss with subcutaneous semaglutide versus other glucagon-like peptide 1 receptor agonists in type 2 diabetes: a systematic review.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce elevated blood glucose levels and induce weight loss. Multiple GLP-1 RAs and one combined GLP-1/glucose-dependent insulinotropic polypeptide agonist are currently available. This review was conducted with the aim of summarising direct comparisons between subcutaneous semaglutide and other GLP-1 RAs in individuals with type 2 diabetes (T2D), particularly with respect to efficacy for inducing weight loss and improving other markers of metabolic health. This systematic review of PubMed and Embase from inception to early 2022 was registered on PROSPERO and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Of the 740 records identified in the search, five studies fulfilled the inclusion criteria. Comparators included liraglutide, exenatide, dulaglutide and tirzepatide. In the identified studies, multiple dosing regimens were utilised for semaglutide. Randomised trials support the superior efficacy of semaglutide over other GLP-1 RAs with respect to weight loss in T2D, but tirzepatide is more effective than semaglutide.

A novel likely pathogenic CLCN5 variant in Dent's disease.

BACKGROUND: The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity. CASE PRESENTATION: A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant. CONCLUSIONS: The identification of this novel variant in four individuals with features of Dent's disease, has led to the re-classification of the variant to one of likely pathogenicity. As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

Sampling implications of variation in daily activity of the sheep tick, Ixodes ricinus at a coastal grassland site in the U.K.

The sheep tick, Ixodes ricinus L. (Acari: Ixodidae), is an important vector of many pathogens of medical and veterinary significance. Determining vector abundance is a requisite of assessing potential vector-borne disease risk. Estimation of tick abundance is often conducted by blanket drag sampling a site, conducted at one time point during the day. The time of day chosen for sampling can vary, is not widely standardized and is often unreported by the investigator. This study investigated whether the time of day chosen for sampling had an effect on tick collection at an open grassland coastal site in North Devon, U.K., during May 2019 to July 2019. Tick abundance for both adults and nymphs in the evening period was more than twice that found in the mid-day sampling period. Overall abundance differed with site aspect, ground temperature and relative humidity. This study shows that for this open grassland recreational site, the time of day chosen for sampling has important implications for tick collection and the assessment of the relative risk of human exposure to ticks and tick-borne infections.

Designing the ultimate general medicine model.

The ideal model of care in general medicine remains elusive, perhaps because of interhospital heterogeneity in patient population and resource allocation to both general medicine and the medical subspecialties. We explain why successful interventions at one site are not easily applied in another and recommend a nationally coordinated examination of the best general medicine departments' methods of clinical practice improvement.

Modular structures and the delivery of inpatient care in hospitals: a Network Science perspective on healthcare function and dysfunction.

BACKGROUND: Reinforced by the COVID-19 pandemic, the capacity of health systems to cope with increasing healthcare demands has been an abiding concern of both governments and the public. Health systems are made up from non-identical human and physical components interacting in diverse ways in varying locations. It is challenging to represent the function and dysfunction of such systems in a scientific manner. We describe a Network Science approach to that dilemma. General hospitals with large emergency caseloads are the resource intensive components of health systems. We propose that the care-delivery services in such entities are modular, and that their structure and function can be usefully analysed by contemporary Network Science. We explore that possibility in a study of Australian hospitals during 2019 and 2020. METHODS: We accessed monthly snapshots of whole of hospital administrative patient level data in two general hospitals during 2019 and 2020. We represented the organisations inpatient services as network graphs and explored their graph structural characteristics using the Louvain algorithm and other methods. We related graph topological features to aspects of observable function and dysfunction in the delivery of care. RESULTS: We constructed a series of whole of institution bipartite hospital graphs with clinical unit and labelled wards as nodes, and patients treated by units in particular wards as edges. Examples of the graphs are provided. Algorithmic identification of community structures confirmed the modular structure of the graphs. Their functional implications were readily identified by domain experts. Topological graph features could be related to functional and dysfunctional issues such as COVID-19 related service changes and levels of hospital congestion. DISCUSSION AND CONCLUSIONS: Contemporary Network Science is one of the fastest growing areas of current scientific and technical advance. Network Science confirms the modular nature of healthcare service structures. It holds considerable promise for understanding function and dysfunction in healthcare systems, and for reconceptualising issues such as hospital capacity in new and interesting ways.

Effects of very low-carbohydrate vs. high-carbohydrate weight loss diets on psychological health in adults with obesity and type 2 diabetes: a 2-year randomized controlled trial.

AIMS: Very low-carbohydrate (LC) diets are popular for type 2 diabetes (T2DM) management; however, long-term effects on psychological health remain largely unknown. This study reports the effects of a LC diet on mood and cognitive function after 2 years and explores the potential predictors of changes in psychological health. METHODS: 115 adults (57% males; age: 58.5 ± 7.1 years) with obesity and T2DM were randomized to consume an energy reduced (~ 500 to 1000 kcal/day deficit), LC diet [14% energy as carbohydrate, 28% protein, 58% fat (< 10% saturated fat)] or an isocaloric high unrefined carbohydrate, low-fat diet [HC: 53% carbohydrate, 17% protein, 30% fat (< 10% saturated fat)] for 2 years. Both diets were combined with aerobic/resistance exercise (1 h, 3 days/week). Mood/well-being [Beck Depression Inventory (BDI), Spielberger State Anxiety Inventory (SAI), Profile of Mood States (POMS)], diabetes-related quality of life [Diabetes-39 (D-39)] and distress [Problem Areas in Diabetes (PAID) Questionnaire], and cognitive function were assessed during and post-intervention. RESULTS: 61 (LC: 33, HC: 28) participants completed the study. Weight loss was 9.1% after 12 months and 6.7% after 2 years with no difference between diet groups. There were no differences between the groups for the changes in any psychological health outcome (smallest p ≥ 0.19 for all time x diet interactions). Overtime, improvements in BDI, POMS [Total Mood Disturbance (TMD); four subscales], PAID, and D-39 (three subscales) scores occurred (p ≤ 0.05, time). Stepwise regression analysis showed improvements in BDI, POMS (TMD; two subscales), D-39, SAI, and PAID scores were significantly (p < 0.05) correlated with reductions in body weight and glycated hemoglobin. CONCLUSION: In adults with obesity and T2DM, energy-restricted LC and HC diets produced comparable long-term improvements on a comprehensive range of psychological health outcomes. The findings suggest both diets can be used as a diabetes management strategy as part of a holistic lifestyle modification program without concern of negative effects on mental well-being or cognition. TRIAL REGISTRATION: ACTRN12612000369820, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362168&isReview=true . Data described in the manuscript, code book, and analytic code will not be made available because approval has not been granted by participants.

Cardiopulmonary exercise testing in severe osteoarthritis: a crossover comparison of four exercise modalities.

Cardiopulmonary exercise testing is performed increasingly for cardiorespiratory fitness assessment and pre-operative risk stratification. Lower limb osteoarthritis is a common comorbidity in surgical patients, meaning traditional cycle ergometry-based cardiopulmonary exercise testing is difficult. The purpose of this study was to compare cardiopulmonary exercise testing variables and subjective responses in four different exercise modalities. In this crossover study, 15 patients with osteoarthritis scheduled for total hip or knee arthroplasty (mean (SD) age 68 (7) years; body mass index 31.4 (4.1) kg.m-2 ) completed cardiopulmonary exercise testing on a treadmill, elliptical cross-trainer, cycle and arm ergometer. Mean (SD) peak oxygen consumption was 20-30% greater on the lower limb modalities (treadmill 21.5 (4.6) (p < 0.001); elliptical cross-trainer (21.2 (4.1) (p < 0.001); and cycle ergometer (19.4 (4.2) ml.min-1 .kg-1 (p = 0.001), respectively) than on the arm ergometer (15.7 (3.7) ml.min-1 .kg-1 ). Anaerobic threshold was 25-50% greater on the lower limb modalities (treadmill 13.5 (3.1) (p < 0.001); elliptical cross-trainer 14.6 (3.0) (p < 0.001); and cycle ergometer 10.7 (2.9) (p = 0.003)) compared with the arm ergometer (8.4 (1.7) ml.min-1 .kg-1 ). The median (95%CI) difference between pre-exercise and peak-exercise pain scores was greater for tests on the treadmill (2.0 (0.0-5.0) (p = 0.001); elliptical cross-trainer (3.0 (2.0-4.0) (p = 0.001); and cycle ergometer (3.0 (1.0-5.0) (p = 0.001)), compared with the arm ergometer (0.0 (0.0-1.0) (p = 0.406)). Despite greater peak exercise pain, cardiopulmonary exercise testing modalities utilising the lower limbs affected by osteoarthritis elicited higher peak oxygen consumption and anaerobic threshold values compared with arm ergometry.

Quantifying movement of multiple threatened species to inform adaptive management of environmental flows.

There is a growing need for water managers to refine and optimise environmental flow strategies (e-flows) to balance water requirements for humans and nature. With increasing demands for freshwater and consequent declines in biodiversity, managers are faced with the problem of how to adaptively manage e-flows for multiple stakeholders and species whose flow requirements may overlap or vary. This study assessed the effectiveness of a regulated e-flow release strategy from a dam, aimed at providing movement opportunities and facilitating reproductive processes for multiple threatened species. Movements of 24 Mary River cod (Maccullochella mariensis), 20 Australian lungfish (Neoceratodus forsteri) and 13 Mary River turtle (Elusor macrurus) were quantified using acoustic telemetry over a three-year period. The influence of regulated e-flow releases, season, river depth, water temperature and rainfall on animal movements was assessed using Generalised linear mixed models (GLMMs). Models showed that hydraulic connectivity provided by both natural flows and regulated e-flow releases facilitated movement of all three species between pool habitats, throughout the year. Mary River turtles made extensive use of regulated e-flow releases when moving between habitats, whereas Mary River cod and Australian lungfish required additional natural rises in river height above the regulated e-flows to trigger movements. Significant movement activity was also recorded for cod and turtles during the dry season (winter and spring), broadly coinciding with breeding periods for these species. The effectiveness of, and potential improvements to, current e-flow strategies to sustain key life-history requirements of these species is discussed. Findings suggest a revised e-flow strategy with relatively minor increases in the magnitude of e-flow releases throughout winter and spring, would be effective in providing movement opportunities and supporting reproductive success for all three species. This study demonstrates that by quantifying movement behaviour in an e-flow context, ecological risk assessment frameworks can then be used to assess and provide for critical life-history requirements of multiple species within the context of a highly regulated system under increasing water use demands.

Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.

Very Low and Higher Carbohydrate Diets Promote Differential Appetite Responses in Adults with Type 2 Diabetes: A Randomized Trial.

BACKGROUND: Effects of very low carbohydrate (VLC) diets on appetite response in individuals with type 2 diabetes remain unclear. OBJECTIVE: A secondary analysis was conducted to determine appetite responses to an energy-restricted [30% of energy (%E) deficit] very low carbohydrate (VLC) diet compared with a higher carbohydrate (HC) diet in adults who were overweight or obese with type 2 diabetes. METHODS: Forty-four men and 40 women (mean ± SD, age: 58.7 ± 6.6 y; weight: 100.4 ± 15.5 kg; BMI: 34.5 ± 4.1 kg/m2; glycated hemoglobin: 7.3 ± 1.0%; duration of diabetes: 6.7 ± 5.6 y) were randomly assigned to diets categorized as VLC [14%E carbohydrate (<50 g/d), 28%E protein, 58%E fat (<10%E saturated fat)], or energy-matched HC [53%E carbohydrate, 17%E protein, 30%E fat (<10%E saturated fat)] combined with progressive multicomponent exercise (60 min; 3 d/wk). Body weight, average weekly "daily fasting" and "daily overall" appetite perceptions (hunger, fullness, prospective consumption, and desire to eat-visual analog scales) were assessed at baseline and after 4 and 16 wk. Changes between diets over time were assessed using repeated measures ANOVA. RESULTS: Significant decreases in body weight did not differ between groups (VLC: -11.0 ± 5.4 kg/16 wk compared with HC: -10.1 ± 4.3 kg/16 wk, P = 0.40). Compared with HC, VLC had greater decreases in "daily overall" ratings of fullness (P time × diet < 0.01), such that scores were higher in HC at Week 4 (VLC:48 ± 3 vs HC:56 ± 3 mm, P = 0.001) and 16 (VLC:51 ± 2 vs HC:57 ± 3 mm, P = 0.019). Compared with HC, VLC had greater increases in prospective consumption ratings (P time × diet = 0.03), such that scores were lower in HC at Week 4 (VLC:33 ± 2 vs HC:28 ± 2 mm, P = 0.008), but not at Week 16 (VLC:33 ± 2 vs HC 31 ± 2 mm, P = 0.289). CONCLUSIONS: In the context of energy restriction, both HC and VLC energy-matched diets promoted comparable effects on fasting perceptions of appetite, but the HC diet resulted in greater "daily overall" fullness and reduced prospective consumption. Further research is required to evaluate the effects of ad libitum diets differing in amounts of carbohydrate on appetite response in populations with type 2 diabetes. This trial was registered at www.anzctr.org.au as ACTRN12612000369820.

Optimising the response to acute clinical deterioration: the role of observation and response charts.

We sought the role of the hospital inpatient observation and response chart (ORC) in reducing adverse outcomes. We sourced articles written in English and published in PubMed. Track, trigger and response systems can be tiered and use single parameter or aggregate scoring systems; the latter being more prone to error. The documentation and detection of abnormal vital signs can be affected by choice of trigger and response and by ORC design. There is considerable variation in the design of ORC and of rapid response systems (RRS) in general, and this impairs assessment of their efficacy. A high rate of modification of pre-determined triggers and poor sensitivity of measured outcomes further compromise systematic review. The best-designed ORC and RRS should optimise the frequency of response team activation to minimise adverse patient outcomes without excess resource utilisation. The role and the risks of electronic data recording are under-explored. Detecting and responding to deteriorating patients relies upon accurate and clear documentation of vital signs. ORC design and staff education on ORC implementation and usage are integral to minimising ALF and optimising patient outcomes. Standardisation of the design of both the ORC and the hospital RRS are overdue.

Peanut Yield Loss in the Presence of Defoliation Caused by Late or Early Leaf Spot.

Late and early leaf spot, respectively caused by Nothopassalora personata and Passalora arachidicola, are damaging diseases of peanut (Arachis hypogaea) capable of defoliating canopies and reducing yield. Although one of these diseases may be more predominant in a given area, both are important on a global scale. To assist informed management decisions and quantify relationships between end-of-season defoliation and yield loss, meta-analyses were conducted over 140 datasets meeting established criteria. Slopes of proportion yield loss with increasing defoliation were estimated separately for Virginia and runner market type cultivars. Yield loss for Virginia types was described by an exponential function over the range of defoliation levels, with a loss increase of 1.2 to 2.2% relative to current loss levels per additional percent defoliation. Results for runner market type cultivars showed yield loss to linearly increase 2.2 to 2.8% per 10% increase in defoliation for levels up to approximately 95% defoliation, after which the rate of yield loss was exponential. Defoliation thresholds to prevent economic yield loss for Virginia and runner types were estimated at 40 and 50%, respectively. Although numerous factors remain important in mitigating overall yield losses, the integration of these findings should aid recommendations about digging under varying defoliation intensities and peanut maturities to assist in minimizing yield losses.

Unmet supportive care needs of haematological cancer survivors: rural versus urban residents.

Due to fewer cancer services in rural locations, rural survivors may have unique unmet needs compared to urban survivors. This study compared among rural and urban haematological cancer survivors the most common "high/very high" unmet supportive care needs and the unmet need scores for five domains (information, financial concerns, access and continuity of care, relationships and emotional health). Survivors' socio-demographics, rurality, cancer history and psychological factors associated with each unmet need domain were also explored. A total of 1511 haematological cancer survivors were recruited from five Australian state cancer registries and 1417 (1145 urban, 272 rural) allowed extraction of their residential postcode from registry records. A questionnaire that contained the Survivor Unmet Needs Survey was mailed to survivors. Dealing with feeling tired was the most common "high/very high" unmet need for rural (15.2%) and urban (15.5%) survivors. The emotional health domain had the highest mean unmet need score for rural and urban survivors. Rurality was associated with a decreased unmet emotional health domain score whereas travelling for more than 1 h to treatment was associated with increased unmet financial concerns and unmet access and continuity of care. Depression, anxiety and stress were associated with increased unmet need scores for all five domains. Unmet need domain scores generally did not differ by rurality. Travelling for more than 1 h to treatment was associated with increased unmet need scores on two domains. Telemedicine and increased financial assistance with travel and accommodation may help those travelling long distances for treatment.

Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial.

AIM: To examine whether a low-carbohydrate, high-unsaturated/low-saturated fat diet (LC) improves glycaemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D). METHODS: A total of 115 adults with T2D (mean [SD]; BMI, 34.6 [4.3] kg/m2 ; age, 58 [7] years; HbA1c, 7.3 [1.1]%) were randomized to 1 of 2 planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1 hour, 3 days/week) for 2 years: LC: 14% energy as carbohydrate, 28% as protein, 58% as fat (<10% saturated fat); or low-fat, high-carbohydrate, low-glycaemic index diet (HC): 53% as CHO, 17% as protein, 30% as fat (<10% saturated fat). HbA1c, glycaemic variability (GV), anti-glycaemic medication effect score (MES, calculated based on the potency and dosage of diabetes medication), weight, body composition, CVD and renal risk markers were assessed before and after intervention. RESULTS: A total of 61 (LC = 33, HC = 28) participants completed the study (trial registration: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820). Reductions in weight (estimated marginal mean [95% CI]; LC, -6.8 [-8.8,-4.7], HC, -6.6 [-8.8, -4.5] kg), body fat (LC, -4.3 [-6.2, -2.4], HC, -4.6 [-6.6, -2.7] kg), blood pressure (LC, -2.0 [-5.9, 1.8]/ -1.2 [-3.6, 1.2], HC, -3.2 [-7.3, 0.9]/ -2.0 [-4.5, 0.5] mmHg), HbA1c (LC, -0.6 [-0.9, -0.3], HC, -0.9 [-1.2, -0.5] %) and fasting glucose (LC, 0.3 [-0.4, 1.0], HC, -0.4 [-1.1, 0.4] mmol/L) were similar between groups (P ≥ 0.09). Compared to HC, the LC achieved greater reductions in diabetes medication use (MES; LC, -0.5 [-0.6, -0.3], HC, -0.2 [-0.4, -0.02] units; P = 0.03), GV (Continuous Overall Net Glycemic Action calculated every 1 hour (LC, -0.4 [-0.6, -0.3], HC, -0.1 [-0.1, 0.2] mmol/L; P = 0.001), and 4 hours (LC, -0.9 [-1.3, -0.6], HC, -0.2 [-0.6, 0.1] mmol/L; P = 0.02)); triglycerides (LC, -0.1 [-0.3, 0.2], HC, 0.1 [-0.2, 0.3] mmol/L; P = 0.001), and maintained HDL-C levels (LC, 0.02 [-0.05, 0.1], HC, -0.1 [-0.1, 0.01] mmol/L; P = 0.004), but had similar changes in LDL-C (LC, 0.2 [-0.1, 0.5], HC, 0.1 [-0.2, 0.4] mmol/L; P = 0.85), brachial artery flow mediated dilatation (LC, -0.5 [-1.5, 0.5], HC, -0.4 [-1.4, 0.7] %; P = 0.73), eGFR and albuminuria. CONCLUSIONS: Both diets achieved comparable weight loss and HbA1c reductions. The LC sustained greater reductions in diabetes medication requirements, and in improvements in diurnal blood glucose stability and blood lipid profile, with no adverse renal effects, suggesting greater optimization of T2D management.

Healthcare and wider societal implications of stillbirth: a population-based cost-of-illness study.

OBJECTIVE: To extend previous work and estimate health and social care costs, litigation costs, funeral-related costs, and productivity losses associated with stillbirth in the UK. DESIGN: A population-based cost-of-illness study using a synthesis of secondary data. SETTING: The National Health Service (NHS) and wider society in the UK. POPULATION: Stillbirths occurring within a 12-month period and subsequent events occurring over the following 2 years. METHODS: Costs were estimated using published data on events, resource use, and unit costs. MAIN OUTCOME MEASURES: Mean health and social care costs, litigation costs, funeral-related costs, and productivity costs for 2 years, reported for a single stillbirth and at a national level. RESULTS: Mean health and social care costs per stillbirth were £4191. Additionally, funeral-related costs were £559, and workplace absence (parents and healthcare professionals) was estimated to cost £3829 per stillbirth. For the UK, the annual health and social care costs were estimated at £13.6 million, and total productivity losses amounted to £706.1 million (98% of this cost was attributable to the loss of the life of the baby). The figures for total productivity losses were sensitive to the perspective adopted about the loss of life of the baby. CONCLUSION: This work expands the current intelligence on the costs of stillbirth beyond the health service to costs for parents and society, and yet these additional findings must still be regarded as conservative estimates of the true economic costs. TWEETABLE ABSTRACT: The costs of stillbirth are significant, affecting the health service, parents, professionals, and society. PLAIN LANGUAGE SUMMARY: Why and how was the study carried out? The personal, social, and emotional consequences of stillbirth are profound. Placing a monetary value on such consequences is emotive, yet necessary, when deciding how best to invest limited healthcare resources. We estimated the average costs associated with a single stillbirth and the costs for all stillbirths occurring in the UK over a 1-year period. What were the main findings? The average cost to the National Health Service (NHS) of care related to the stillbirth and a first subsequent pregnancy was £4191 for each stillbirth. For the UK, this cost was £13.6 million annually. Clinical negligence payments to bereaved parents were estimated at £2.5 million per year. Parents were estimated to spend £1.8 million per year on funerals. The cost of workplace absence as parents cope with the effects of grief was estimated at £2476 per stillbirth. For the UK, this cost was £8.1 million annually. The loss of a baby is also the loss of an individual with the potential to become a valued and productive member of society. The expected value of an adult's lifetime working hours was taken as an estimate of this productivity loss, and was £213,304 for each stillbirth. The annual cost for all stillbirths was £694 million. We know from parents that the birth of a subsequent child in no way replaces a stillborn baby. We found that 52% of women fall pregnant within 12 months of a stillbirth. From a purely economic perspective concerned only with the number of individuals in society, babies born during this period could potentially replace the productivity losses of the stillborn baby. Adopting this approach, which we understand is controversial and difficult for bereaved parents, the expected productivity losses would be lower, at £333 million. What are the limitations of the work? For some categories, existing data were unavailable and we used clinical opinion to estimate costs. Furthermore, we were unable to quantify some indirect consequences, for example the psychological distress experienced by wider family members. What is the implication for parents? Placing a monetary value on what is for parents a profound personal tragedy may seem unkind. It is, however, unavoidable if we are to provide policy makers with vital information on the wide-ranging consequences that could be prevented through future investments in initiatives to reduce stillbirth.

The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis.

BACKGROUND: Vitamin D has been linked with improved cancer outcome. This systematic review and meta-analysis investigates the relationship between cancer outcomes and both vitamin D-related genetic variation and circulating 25-hydroxyvitamin D (25OHD) concentration. METHODS: A systematic review and meta-analysis of papers until November 2016 on PubMed, EMBASE and Web of Science pertaining to association between circulating vitamin D level, functionally relevant vitamin D receptor genetic variants and variants within vitamin D pathway genes and cancer survival or disease progression was performed. RESULTS: A total of 44 165 cases from 64 studies were included in meta-analyses. Higher 25OHD was associated with better overall survival (hazard ratio (HR=0.74, 95% CI: 0.66-0.82) and progression-free survival (HR=0.84, 95% CI: 0.77-0.91). The rs1544410 (BsmI) variant was associated with overall survival (HR=1.40, 95% CI: 1.05-1.75) and rs7975232 (ApaI) with progression-free survival (HR=1.29, 95% CI: 1.02-1.56). The rs2228570 (FokI) variant was associated with overall survival in lung cancer patients (HR=1.29, 95% CI: 1.0-1.57), with a suggestive association across all cancers (HR=1.26, 95% CI: 0.96-1.56). CONCLUSIONS: Higher 25OHD concentration is associated with better cancer outcome, and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link. This analysis provides powerful background rationale to instigate clinical trials to investigate the potential beneficial effect of vitamin D in the context of stratification by genotype.

Psychological morbidity among Australian rural and urban support persons of haematological cancer survivors: Results of a national study.

OBJECTIVE: To compare the prevalence of anxiety, depression, and stress among rural and urban support persons of haematological cancer survivors and explore factors associated with having one or more of these outcomes. METHODS: Haematological cancer survivors were identified via 1 of 5 state-based cancer registries and invited to take part in a survey. Those who agreed were asked to pass on a questionnaire package to their support person. Measures included the Depression, Anxiety, and Stress Scale, Support Persons' Unmet Need Survey, and sociodemographic questions. RESULTS: Nine-hundred and eighty-nine (66%) participating survivors had a participating support person. There were no significant differences in the proportion of urban versus rural support persons who reported elevated levels of depression (21% vs 23%), anxiety (16% vs 17%), or stress (16% vs 20%), P > .05. Odds of reporting at least 1 indicator of psychological morbidity increased by 10% to 17% for each additional high or very high unmet need and by 2% for those who had relocated from their usual place of residence for the survivor to receive treatment and was decreased by 5% to 54% for those support persons who reported that they had no chronic health conditions. CONCLUSIONS: Psychological outcomes for rural and urban support persons are similar. Those who have poor health, have had to relocate, and who have multiple unmet needs are particularly vulnerable to poor psychological outcomes. These factors should be assessed to enable early intervention for those at risk of poor outcomes.

Treatment of prednisolone-induced hyperglycaemia in hospitalized patients: Insights from a randomized, controlled study.

AIM: Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients. MATERIALS AND METHODS: Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system. RESULTS: On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P = .02) and the insulin dose was increased over time ( P = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P = .45) or between groups ( P = .24). CONCLUSIONS: There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.

Risk factors for pertussis in adults and teenagers in England.

Pertussis is a vaccine-preventable respiratory infection caused by Bordetella pertussis which can be fatal in infants. Although high vaccine coverage led to prolonged disease control in England, a national outbreak of pertussis in 2011 led to the largest increase in over two decades, including a marked increase in cases aged ⩾15 years. A case-control study in four regions of England was undertaken to investigate risk factors for pertussis in adolescents and adults, specifically employment type and professional and household contact with children. Pertussis cases were laboratory-confirmed and aged ⩾15 years. Controls were recruited through general practitioner nomination. Demographic and risk factor information were collected using an online survey. Multivariable logistic regression was used to estimate independent associations with outcome. Two hundred and thirty-one cases and 190 controls were recruited. None of the four employment variables (social care, education, health sector, patient contact) were significantly associated with pertussis. Professional contact with children aged < 1 year was associated with a significantly reduced odds of pertussis [odds ratio (OR) 0·25, 95% confidence interval (CI) 0·08-0·78, P = 0·017]. Household contact with ⩾1 child aged 10-14 years was associated with significantly increased odds of pertussis (OR 2·61, 95% CI 1·47-4·64, P = 0·001). Occupational contact with very young children was associated with reduced odds of pertussis, probably due to immune boosting by low-level exposures to B. pertussis. Sharing a household with a young adolescent was a significant risk factor for pertussis in adults and older teenagers. The primary focus of the childhood pertussis vaccination programmes is to prevent infant disease. Although evidence is emerging that adolescent vaccination does not provide indirect protection to infants, our results highlight the importance of children aged 10-14 years in pertussis transmission to older adolescents and adults.

Validation of Molecular Markers for Use With Adapted Sources of Fusarium Head Blight Resistance in Wheat.

Genetic control of resistance to Fusarium head blight (FHB) is quantitative, making phenotypic selection difficult. Genetic markers to resistance are helpful to select favorable genotypes. This study was conducted to determine if Fhb1 and Fhb5 present in the Sumai 3 source of FHB resistance occur in Sumai 3-derived North American spring wheat cultivars and to understand the appropriateness of using markers to select for the favorable alleles at these loci in breeding. Sumai 3-derived parents Alsen, ND3085, ND744, Carberry, and Glenn were used in crosses to generate 14 doubled haploid breeding populations. The parents and progeny were genotyped with five Fhb1 and three Fhb5 microsatellite markers. Progeny were selected based on performance relative to parents and other control cultivars in FHB nurseries near Portage la Prairie and Carman, MB. χ2 and t test analyses were performed on marker and FHB data. The χ2 test frequently determined the proportion of lines carrying molecular variants associated with FHB resistance increased following nursery selection for FHB. Similarly, the t test regularly demonstrated that selection for FHB resistance lowered the mean level of disease associated with resistant marker haplotypes. The study affirmed FHB resistance sources Alsen, Carberry, ND3085, and ND744 have Fhb1 and Fhb5 loci like Sumai 3, but no evidence was found that Glenn carries Fhb1 and Fhb5 resistance alleles. The results justified use of Fhb1 and Fhb5 markers for marker assisted selection in populations derived from Alsen, Carberry, ND3085, and ND744, but not Glenn. Combined or individual application of Xgwm493 and Xgwm533 in selection of genotypes carrying Fhb1, and Xgwm150, Xgwm304, and Xgwm595 for Fhb5 will enhance FHB resistance in wheat.