Standardising and simplifying the Global Leadership Initiative on Malnutrition (GLIM) for its more general application.

BACKGROUND: Malnutrition is present in 20-50% of hospital patients but its recognition is often neither timely nor complete. The Global Leadership Initiative on Malnutrition (GLIM) aims to improve this, but its successful implementation may be compromised by its dependence on (a choice of) prior screening tools and difficulties in consistent assessment of muscle mass. AIMS: To explore different approaches to screening and muscle assessment in GLIM and to offer simpler choices for its more widespread application. METHODS: (1) Data from 300 consenting in-patients provided Nutritional Risk Screening (NRS-2002), Malnutrition Universal Screening Tool (MUST), and Subjective Global Assessment (SGA) scores. GLIM scoring was preceded by NRS-2002 or MUST (using threshold scores of 1 or 2 for MUST), or no prior screening. The results of GLIM scoring preceded by different screening approaches were compared with those of SGA. (2) The literature on mid-upper arm circumference (MUAC) and calf circumference (CC) as simple, non-invasive, objective methods of muscle assessment methods was reviewed (3) The cumulative times taken to obtain GLIM scores were measured and corrected for the different screening strategies. RESULTS: (1) Participants' mean age was 60 years, 157 (52%) were female and mean BMI was 27.8 kg/m2. In comparison with SGA, GLIM with no prior screening had the highest sensitivity (65%) and negative predictive value (NPV) (76%), but the lowest specificity (90%) and positive predictive value (PPV) (84%). The equivalent figures for GLIM with prior MUST "1" were 62%, 75%, 93% and 88%; with prior NRS-2002, 55%∗, 73%, 98%∗ and 95%∗; and with prior MUST "2", 44%∗, 69%∗, 98%∗, 95%∗. The area under an ROC curve was the highest (0.78) when GLIM was performed without screening or with prior MUST "1". (2) Being less affected by oedema and gender differences than calf circumference, MUAC could serve as a standard globally accessible muscle mass assessment method which can be supplemented by technical approaches if available and deemed necessary. (3) The overall per-capita time requirement of GLIM was 240-245 s without prior screening, and was increased by 2-3% with prior MUST "1", by 27-29% with prior NRS-2002 and decreased by 8-9% with prior MUST "2". CONCLUSIONS: Preceding GLIM by screening can decrease its sensitivity and increase overall time utilisation; "gold standard" muscle assessment is not globally accessible. Our results therefore support considering using GLIM as a combined screening and assessment tool, with MUAC as the method of muscle assessment which can be supplemented by technical approaches if available and deemed necessary. This could potentially both simplify the use of GLIM and improve the early detection of malnutrition. ∗Indicates statistically significant difference from use of GLIM without prior screening.

A vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery.

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative Fi O2 was 0.30 (0.26-0.35 [0.20-0.59]) and 0.47 (0.44-0.51 [0.37-0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14-0.20), p < 0.001). Median time-weighted average intra-operative Fi O2 was 0.83 (0.80-0.85 [0.70-0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33-0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.

Postoperative systemic inflammation after major abdominal surgery: patient-centred outcomes.

Postoperative systemic inflammation is strongly associated with surgical outcomes, but its relationship with patient-centred outcomes is largely unknown. Detection of excessive inflammation and patient and surgical factors associated with adverse patient-centred outcomes should inform preventative treatment options to be evaluated in clinical trials and current clinical care. This retrospective cohort study analysed prospectively collected data from 3000 high-risk, elective, major abdominal surgery patients in the restrictive vs. liberal fluid therapy for major abdominal surgery (RELIEF) trial from 47 centres in seven countries from May 2013 to September 2016. The co-primary endpoints were persistent disability or death up to 90 days after surgery, and quality of recovery using a 15-item quality of recovery score at days 3 and 30. Secondary endpoints included: 90-day and 1-year all-cause mortality; septic complications; acute kidney injury; unplanned admission to intensive care/high dependency unit; and total intensive care unit and hospital stays. Patients were assigned into quartiles of maximum postoperative C-reactive protein concentration up to day 3, after multiple imputations of missing values. The lowest (reference) group, quartile 1, C-reactive protein ≤ 85 mg.l-1 , was compared with three inflammation groups: quartile 2 > 85 mg.l-1 to 140 mg.l-1 ; quartile 3 > 140 mg.l-1 to 200 mg.l-1 ; and quartile 4 > 200 mg.l-1 to 587 mg.l-1 . Greater postoperative systemic inflammation had a higher adjusted risk ratio (95%CI) of persistent disability or death up to 90 days after surgery, quartile 4 vs. quartile 1 being 1.76 (1.31-2.36), p < 0.001. Increased inflammation was associated with increasing decline in risk-adjusted estimated medians (95%CI) for quality of recovery, the quartile 4 to quartile 1 difference being -14.4 (-17.38 to -10.71), p < 0.001 on day 3, and -5.94 (-8.92 to -2.95), p < 0.001 on day 30. Marked postoperative systemic inflammation was associated with increased risk of complications, poor quality of recovery and persistent disability or death up to 90 days after surgery.

Enhancing diabetes care for the most vulnerable in the 21st century: Interim findings of the National Advisory Panel on Care Home Diabetes (NAPCHD).

Older adults with diabetes may carry a substantial health burden in Western ageing societies, occupy more than one in four beds in care homes, and are a highly vulnerable group who often require complex nursing and medical care. The global pandemic (COVID-19) had its epicentre in care homes and revealed many shortfalls in diabetes care resulting in hospital admissions and considerable mortality and comorbid illness. The purpose of this work was to develop a national Strategic Document of Diabetes Care for Care Homes which would bring about worthwhile, sustainable and effective quality diabetes care improvements, and address the shortfalls in care provided. A large diverse and multidisciplinary group of stakeholders (NAPCHD) defined 11 areas of interest where recommendations were needed and using a subgroup allocation approach were set tasks to produce a set of primary recommendations. Each subgroup was given 5 starter questions to begin their work and a format to provide responses. During the initial phase, 16 key findings were identified. Overall, after a period of 18 months, 49 primary recommendations were made, and 7 major conclusions were drawn from these. A model of community and integrated diabetes care for care home residents with diabetes was proposed, and a series of 5 'quick-wins' were created to begin implementation of some of the recommendations that would not require significant funding. The work of the NAPCHD is ongoing but we hope that this current resource will help leaders to make these required changes happen.

Musculoskeletal ultrasound for 3D bone modeling: A preliminary study applied to lumbar vertebra.

BACKGROUND: There is no non-invasive in vivo method to assess intervertebral kinematics. Current kinematics models are based on in vitro bone reconstructions from computed tomography (CT)-scan imaging, fluoroscopy and MRIs, which are either expensive or deleterious for human tissues. Musculoskeletal ultrasound is an accessible, easy to use and cost-effective device that allows high-resolution, real-time imaging of bone structure. OBJECTIVE: The aim of this preliminary study was to compare the concordance of 3D bone modeling of lumbar vertebrae between CT-scan and ultrasound imaging and to study the intra and inter-reliability of distances measured on 3D ultrasound bone models. METHODS: CT-scan, ultrasound, and in situ data of five lumbar vertebrae from the same human specimen were used. All vertebrae were scanned by tomography and a new musculoskeletal ultrasound procedure. Then, 3D bone modeling was created from both CT-scan and ultrasound image data set. Distances between anatomical bones landmarks were measured on the 3D models and compared to in situ measurements.

Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.

Comparison of small-sample standard-error corrections for generalised estimating equations in stepped wedge cluster randomised trials with a binary outcome: A simulation study.

Generalised estimating equations with the sandwich standard-error estimator provide a promising method of analysis for stepped wedge cluster randomised trials. However, they have inflated type-one error when used with a small number of clusters, which is common for stepped wedge cluster randomised trials. We present a large simulation study of binary outcomes comparing bias-corrected standard errors from Fay and Graubard; Mancl and DeRouen; Kauermann and Carroll; Morel, Bokossa, and Neerchal; and Mackinnon and White with an independent and exchangeable working correlation matrix. We constructed 95% confidence intervals using a t-distribution with degrees of freedom including clusters minus parameters (DFC-P), cluster periods minus parameters, and estimators from Fay and Graubard (DFFG), and Pan and Wall. Fay and Graubard and an approximation to Kauermann and Carroll (with simpler matrix inversion) were unbiased in a wide range of scenarios with an independent working correlation matrix and more than 12 clusters. They gave confidence intervals with close to 95% coverage with DFFG with 12 or more clusters, and DFC-P with 18 or more clusters. Both standard errors were conservative with fewer clusters. With an exchangeable working correlation matrix, approximated Kauermann and Carroll and Fay and Graubard had a small degree of under-coverage.

A qualitative study exploring the factors that influence the uptake of pre-pregnancy care among women with Type 2 diabetes.

AIM: To elicit the views and experiences of women with Type 2 diabetes and healthcare professionals relating to the pregnancy and pre-pregnancy care they have received or provided. METHODS: A qualitative study using in-depth semi-structured interviews with women with Type 2 diabetes (n=30) and healthcare professionals (n=22) from primary and specialist care. Women were purposively sampled to include different experiences of pregnancy and pre-pregnancy care. Data were transcribed verbatim and analysed thematically using Framework Analysis. RESULTS: The median age of the women was 37 years, and most were obese (median BMI 34.9 kg/m2 ), of black or Asian ethnicity (n=24, 80%) and from areas of high deprivation (n=21, 70%). Participating healthcare professionals were from primary (n=14), intermediate (n=4) and secondary (n=4) care. Seven themes expressing factors that mediate reproductive behaviour and care in women with Type 2 diabetes were identified at the patient, professional and system levels. Type 2 diabetes was generally perceived negatively by the women and the healthcare professionals. There was a lack of awareness about the pre-pregnancy care needs for this population, and communication between both groups was unhelpful in eliciting the reproductive intentions of these women. The themes also reveal a lack of systemic processes to incorporate pre-pregnancy care into the care of women with Type 2 diabetes, and consequently, health professionals in primary care have limited capacity to provide such support. CONCLUSION: If the current high levels of unprepared pregnancies in women with Type 2 diabetes are to be reduced, the reproductive healthcare needs of this group need to be embedded into their mainstream diabetes management.

Generation of structured light by multilevel orbital angular momentum holograms.

Structured light has been created by a myriad of near-and far-field techniques and has found both classical and quantum applications. In the case of orbital angular momentum (OAM), continuous spiral phase patterns in dynamic or geometric phase are often employed with the phase patterns existing across the entire transverse plane. Here, we exploit the uncertain relationship between OAM and angle in order to create structured OAM fields by using multilevel OAM holograms. We show theoretically and experimentally that only a multilevel angular phase contour in the near-field is needed to create structured OAM light in the far-field, exploiting the reciprocal nature of angular momentum and angle. We use this approach to demonstrate exotic 3D structured light control to show the Poynting vector's evolution in such fields and to highlight the physics underlying this phenomenon.

Impact of non-uniform correlation structure on sample size and power in multiple-period cluster randomised trials.

Stepped wedge and cluster randomised crossover trials are examples of cluster randomised designs conducted over multiple time periods that are being used with increasing frequency in health research. Recent systematic reviews of both of these designs indicate that the within-cluster correlation is typically taken account of in the analysis of data using a random intercept mixed model, implying a constant correlation between any two individuals in the same cluster no matter how far apart in time they are measured: within-period and between-period intra-cluster correlations are assumed to be identical. Recently proposed extensions allow the within- and between-period intra-cluster correlations to differ, although these methods require that all between-period intra-cluster correlations are identical, which may not be appropriate in all situations. Motivated by a proposed intensive care cluster randomised trial, we propose an alternative correlation structure for repeated cross-sectional multiple-period cluster randomised trials in which the between-period intra-cluster correlation is allowed to decay depending on the distance between measurements. We present results for the variance of treatment effect estimators for varying amounts of decay, investigating the consequences of the variation in decay on sample size planning for stepped wedge, cluster crossover and multiple-period parallel-arm cluster randomised trials. We also investigate the impact of assuming constant between-period intra-cluster correlations instead of decaying between-period intra-cluster correlations. Our results indicate that in certain design configurations, including the one corresponding to the proposed trial, a correlation decay can have an important impact on variances of treatment effect estimators, and hence on sample size and power. An R Shiny app allows readers to interactively explore the impact of correlation decay.

A qualitative study exploring women's health behaviours after a pregnancy with gestational diabetes to inform the development of a diabetes prevention strategy.

AIM: To inform targeted interventions for women with gestational diabetes mellitus (GDM) by exploring the factors that influence their health behaviours and their preferences for lifestyle support. METHODS: Participants were women with previous GDM taken from a diverse inner-city UK population. Data collection involved focus groups (n = 35 women in six groups) and semi-structured interviews (n = 15 women). The transcribed data were analysed using framework analysis. RESULTS: Eight themes relating to factors influencing health behaviour were identified: psychological legacy of pregnancy, relationships with healthcare professionals, physical impacts of pregnancy, social support and cultural norms, life-scheduling, understanding and risk perception, appetite regulation, and prioritization of the baby. The women's recommendations for intervention components included addressing the emotional stress of pregnancy; conveying personalized risk in a motivational way, adopting a family-centered approach, focusing on women's health rather than just the infant's, and developing flexible interventions. These recommendations were used to construct a model integrating the behaviour-regulating factors with a suggested framework for intervention. CONCLUSIONS: This study identified some common drivers that may regulate the health behaviours of women following GDM, and recognized some ways to improve care to impact on this. Interventions for diabetes prevention in this population need to address factors at both the individual and systemic levels.

Learning about Type 1 diabetes and learning to live with it when diagnosed in adulthood: two distinct but inter-related psychological processes of adaptation A qualitative longitudinal study.

AIM: To explore the experiences of adults with newly diagnosed Type 1 diabetes in order to understand the adaptive processes that occur in the early phase of the condition. METHODS: We conducted longitudinal semi-structured interviews with 30 adults newly diagnosed with Type 1 diabetes (age range 20-67 years; 16 men; median diabetes duration 23.5 months), recruited from hospitals in Denmark and the UK. The data were analysed using a narrative approach. RESULTS: The narratives could be grouped into three thematic areas: the diagnosis; learning about diabetes; and learning to live with diabetes. Diabetes was characterized as a major disruptor to the established and future life plans of participants, causing significant emotional distress. The narratives showed how early experiences triggered the development of ongoing psychological problems (fear of complications or hypoglycaemia) and diabetes distress, and that navigating different social scenarios (relationships and employment) could be challenging, leading to suboptimal self-management behaviours. The narratives also showed that health professionals often did not attend effectively to participants' emotional needs after diagnosis, and that the language used frequently triggered negative feelings, such as fear or a sense of failure. CONCLUSIONS: Many of the common psychosocial problems associated with Type 1 diabetes seem to gestate in the early phase of life with the condition. There appear to be opportunities to enhance the support provided in this phase to minimize these problems.

Bioelectrical impedance analysis (BIA)-derived phase angle (PA) is a practical aid to nutritional assessment in hospital in-patients.

BACKGROUND: Nutritional status can be difficult to assess. Bioelectrical impedance analysis (BIA)-derived phase angle (PA), and the plasma markers citrulline and transthyretin (pre-albumin) have the potential to assist, but the protocol of fasting and resting for BIA renders the investigation impractical for routine use, especially so in populations at high risk of malnutrition. AIMS: 1 To clarify whether starving and resting are necessary for reliable measurement of PA. 2 To identify whether PA, citrulline and transthyretin correlate with nutritional status. METHODS: Eighty consenting adult in-patients were recruited. Nutritional status was determined by subjective global assessment (SGA) used as gold standard. The Malnutrition Universal Screening Tool (MUST) was used and anthropometric measurements were performed. Serum was analysed for citrulline and transthyretin. PA was measured using Bodystat 4000. The PA was considered to define malnutrition when lower than reference ranges for sex and age, and severe malnutrition if more than 2 integers below the lower limit. Anthropometric measurements were categorised according to WHO reference centiles. Ordinal logistic regression estimated the strength of association of PA, citrulline and transthyretin with SGA. PA values in the different metabolic states were compared using paired t tests. RESULTS: All 80 subjects completed the BIA and the nutritional assessments in the 3 different states; 14 declined to provide blood samples for the biochemical assays. Malnutrition was identified in 32 cases, severe malnutrition in 14 cases, the remaining 34 cases were deemed not to be malnourished. PA was strongly inversely associated with SGA (Odds Ratio [OR] per unit increase = 0.21, CI 0.12-0.37, p < 0.001). PA was not influenced by exercise (p = 0.134) or food intake (p = 0.184). Transthyretin was inversely associated with malnourished/severely malnourished states (OR = 0.98, 95% CI 0.97-0.99, p = 0.001), but had poorer predictive values than PA. There was no significant association between citrulline concentration and SGA (OR = 1.01, 95% CI 0.99-1.04, p = 0.348). CONCLUSIONS: The BIA-derived PA reliably identifies malnutrition. It is strongly associated with SGA but requires less skill and experience, and out-performs circulating transthyretin, rendering it a promising and less operator-dependent tool for assessing nutritional status in hospital patients. Our novel demonstration that fasting and bed-rest are unnecessary consolidates that position.

Evidence-based diabetes care for older people with Type 2 diabetes: a critical review.

In our ageing society diabetes imposes a significant burden in terms of the numbers of people with the condition, diabetes-related complications including disability, and health and social care expenditure. Older people with diabetes can represent some of the more complex and difficult challenges facing the clinician working in different settings, and the recognition that we have only a relatively small (but increasing) evidence base to guide us in diabetes management is a limitation of our current approaches. Nevertheless, in this review we attempt to explore what evidence there is to guide us in a comprehensive scheme of treatment for older adults, often in a high-risk clinical state, in terms of glucose lowering, blood pressure and lipid management, frailty care and lifestyle interventions. We strive towards individualized care and make a call for action for more high-quality research using different trial designs.

Correction to: Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY.

After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study.

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.

Healthcare professionals' views of group structured education for people with newly diagnosed Type 2 diabetes.

AIM: To determine healthcare professionals' (HCP) views of group structured education for people with newly diagnosed Type 2 diabetes. METHODS: This was a qualitative study using semi-structured interviews to ascertain primary care HCPs' views and experiences of education for people with newly diagnosed Type 2 diabetes. A thematic framework method was applied to analyse the data. Participants were HCPs (N = 22) from 15 general practices in three south London boroughs. RESULTS: All but one HCP viewed diabetes education favourably and all identified that low attendance was a problem. Three key themes emerged from the qualitative data: (1) benefits of diabetes education, including the group mode of delivery, improved patient interactions, saving HCPs' time and improved patient outcomes; (2) factors limiting uptake of education, including patient-level problems such as access and the appropriateness of the programme for certain groups, and difficulties communicating the benefits to patients and integration of education management plans into ongoing diabetes care; and (3) suggestions for improvement, including strategies to improve attendance at education with more localized and targeted marketing and enhanced programme content including follow-up sessions and support for people with pre-existing psychological issues. CONCLUSIONS: Most HCPs valued diabetes education and all highlighted the lack of provision for people with different levels of health literacy. Because there was wide variation in terms of the level of knowledge regarding the education on offer, future studies may want to focus on how to help HCPs encourage their patients to attend.

Focusing anomalies with binary diffractive optical elements.

Binary diffractive optics have been extensively studied to date as tools for arbitrary laser beam shaping and experimentally implemented with etched transparent optics and spatial light modulators. Here we demonstrate that a simple one-step binary optic is able to enhance the intensity of a focused beam, displaying some counterintuitive focusing anomalies. We explain these effects by considering the optical aberrations in binary diffractive optics and outline how this may be exploited for further improvements in refractive/diffractive combinations for super-resolution microscopy.

Targeted anthelmintic treatment of parasitic gastroenteritis in first grazing season dairy calves using daily live weight gain as an indicator.

Control of parasitic gastroenteritis in cattle is typically based on group treatments with anthelmintics, complemented by grazing management, where feasible. However, the almost inevitable evolution of resistance in parasitic nematodes to anthelmintics over time necessitates a reappraisal of their use in order to reduce selection pressure. One such approach is targeted selective treatment (TST), in which only individual animals that will most benefit are treated, rather than whole groups of at-risk cattle. This study was designed to assess the feasibility of implementing TST on three commercial farms, two of which were organic. A total of 104 first-grazing season (FGS), weaned dairy calves were enrolled in the study; each was weighed at monthly intervals from the start of the grazing season using scales or weigh-bands. At the same time dung and blood samples were collected in order to measure faecal egg counts (FEC) and plasma pepsinogen, respectively. A pre-determined threshhold weight gain of 0.75kg/day was used to determine those animals that would be treated; the anthelmintic used was eprinomectin. No individual animal received more than one treatment during the grazing season and all treatments were given in July or August; five animals were not treated at all because their growth rates consistently exceeded the threshold. Mean daily live weight gain over the entire grazing season ranged between 0.69 and 0.82kg/day on the three farms. Neither FEC nor pepsinogen values were significantly associated with live weight gain. Implementation of TST at farm level requires regular (monthly) handling of the animals and the use of weigh scales or tape, but can be integrated into farm management practices. This study has shown that acceptable growth rates can be achieved in FGS cattle with modest levels of treatment and correspondingly less exposure of their nematode populations to anthelmintics, which should mitigate selection pressure for resistance by increasing the size of the refugia in both hosts and pasture.

Stepped wedge designs: insights from a design of experiments perspective.

Stepped wedge designs (SWDs) have received considerable attention recently, as they are potentially a useful way to assess new treatments in areas such as health services implementation. Because allocation is usually by cluster, SWDs are often viewed as a form of cluster-randomized trial. However, since the treatment within a cluster changes during the course of the study, they can also be viewed as a form of crossover design. This article explores SWDs from the perspective of crossover trials and designed experiments more generally. We show that the treatment effect estimator in a linear mixed effects model can be decomposed into a weighted mean of the estimators obtained from (1) regarding an SWD as a conventional row-column design and (2) a so-called vertical analysis, which is a row-column design with row effects omitted. This provides a precise representation of "horizontal" and "vertical" comparisons, respectively, which to date have appeared without formal description in the literature. This decomposition displays a sometimes surprising way the analysis corrects for the partial confounding between time and treatment effects. The approach also permits the quantification of the loss of efficiency caused by mis-specifying the correlation parameter in the mixed-effects model. Optimal extensions of the vertical analysis are obtained, and these are shown to be highly inefficient for values of the within-cluster dependence that are likely to be encountered in practice. Some recently described extensions to the classic SWD incorporating multiple treatments are also compared using the experimental design framework.