Health-related quality of life assessment in health economic analyses involving type 2 diabetes.

AIM: Incorporating health-related quality of life (HRQoL) measures into health economic analyses can help to provide evidence to inform decisions about how to improve patient outcomes in the most cost-effective manner. The aim of this narrative review was to assess which HRQoL instruments have been used in economic evaluations of type 2 diabetes management including in Indigenous communities. METHOD: MEDLINE (Ovid), Embase (Ovid) and Cochrane were searched from inception to June 2022. Studies included patients with type 2 diabetes; economic evaluations, derived scores from direct questioning of individuals; and were in English. Records were assessed for bias using the JBI critical appraisal tools. RESULTS: A total of 3737 records were identified, with 22 publications meeting the criteria for inclusion. Across those 22 articles, nine HRQoL instruments had been utilised. Generic tools were most frequently used to measure HRQoL, including EQ-5D (-3 L and -5 L) (n = 10, 38%); SF-12 (n = 5, 19%); and SF-36 (n = 4, 15%). Two tools addressing the specific stressors faced by people with type 2 diabetes were utilised: Problem Areas In Diabetes tool (n = 1, 4%) and Diabetes Distress Scale (n = 1, 4%). Two publications reported whether the study population included Indigenous peoples. CONCLUSION: A wide range of HRQoL instruments are used in economic evaluations of type 2 diabetes management, with the most frequent being varying forms of the EQ-5D. Few economic evaluations noted whether Indigenous peoples were featured in the study population. More research into HRQoL in people living with type 2 diabetes is urgently needed to improve evidence on effectiveness and cost-effectiveness of interventions.

Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom.

Background: Real-world data on the efficacy and safety of onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) are needed, especially to overcome uncertainties around its use in older and heavier children. This study evaluated the efficacy and safety of OA in patients with SMA type 1 in the UK, including patients ≥2 years old and weighing ≥13.5 kg. Methods: This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements. Findings: Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion: 10 [range, 0.6-89] months; median weight: 7.86 [range, 3.2-20.2] kg; duration of follow-up: 3-22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged <6 months had a 13.9 points higher gain in CHOP-INTEND score than patients ≥2 years (95% CI, 6.8-21.0; P < 0.001). Asymptomatic thrombocytopenia (71/99 patients; 71.7%), asymptomatic troponin-I elevation (30/89 patients; 33.7%) and transaminitis (87/99 patients; 87.9%) were reported. No thrombotic microangiopathy was observed. Median steroid treatment duration was 97 (range, 28-548) days with dose doubled in 35/99 patients (35.4%). There were 22.5-fold increased odds of having a transaminase peak >100 U/L (95% CI, 2.3-223.7; P = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2-209.2; P = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported. Interpretation: OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients. Funding: Novartis Innovative Therapies AG provided a grant for independent medical writing services.

Prevalence and distribution of antimicrobial resistance in effluent wastewater from animal slaughter facilities: A systematic review.

The extensive use of antibiotics in food animal production and disposal of untreated wastewater from food animal slaughter facilities may create a shift in microbiomes of different ecosystems by generating reservoirs of antimicrobial resistance along the human-animal-environmental interface. This epidemiological problem has been studied, but its magnitude and impact on a global scale is poorly characterised. A systematic review was done to determine global prevalence and distribution patterns of antimicrobial resistance in effluent wastewater from animal slaughter facilities. Extracted data were stratified into rational groups for secondary analyses and presented as percentages. Culture and sensitivity testing was the predominant method; Escherichia spp., Enterococcus spp., and Staphylococcus aureus were the most targeted isolates. Variable incidences of resistance were detected against all major antimicrobial classes including reserved drugs such as ceftazidime, piperacillin, gentamicin, ciprofloxacin, and chloramphenicol; the median frequency and range in resistant Gram-negative isolates were: 11 (0-100), 62 (0-100), 8 (0-100), 14 (0-93) and 12 (0-62) respectively. Ciprofloxacin was the most tested drug with the highest incidences of resistance in livestock slaughterhouses in Iran (93%), Nigeria (50%) and China (20%), and poultry slaughterhouses in Germany (21-81%) and Spain (56%). Spatial global distribution patterns for antimicrobial resistance were associated with previously reported magnitude of antibiotic use in livestock or poultry farming and, the implicit existence of jurisdictional policies to regulate antibiotic use. These data indicate that anthropogenic activities in farming systems are a major contributor to the cause and dissemination of antimicrobial resistance into the environment via slaughterhouse effluents.

A scoping methodological review of simulation studies comparing statistical and machine learning approaches to risk prediction for time-to-event data.

BACKGROUND: There is substantial interest in the adaptation and application of so-called machine learning approaches to prognostic modelling of censored time-to-event data. These methods must be compared and evaluated against existing methods in a variety of scenarios to determine their predictive performance. A scoping review of how machine learning methods have been compared to traditional survival models is important to identify the comparisons that have been made and issues where they are lacking, biased towards one approach or misleading. METHODS: We conducted a scoping review of research articles published between 1 January 2000 and 2 December 2020 using PubMed. Eligible articles were those that used simulation studies to compare statistical and machine learning methods for risk prediction with a time-to-event outcome in a medical/healthcare setting. We focus on data-generating mechanisms (DGMs), the methods that have been compared, the estimands of the simulation studies, and the performance measures used to evaluate them. RESULTS: A total of ten articles were identified as eligible for the review. Six of the articles evaluated a method that was developed by the authors, four of which were machine learning methods, and the results almost always stated that this developed method's performance was equivalent to or better than the other methods compared. Comparisons were often biased towards the novel approach, with the majority only comparing against a basic Cox proportional hazards model, and in scenarios where it is clear it would not perform well. In many of the articles reviewed, key information was unclear, such as the number of simulation repetitions and how performance measures were calculated. CONCLUSION: It is vital that method comparisons are unbiased and comprehensive, and this should be the goal even if realising it is difficult. Fully assessing how newly developed methods perform and how they compare to a variety of traditional statistical methods for prognostic modelling is imperative as these methods are already being applied in clinical contexts. Evaluations of the performance and usefulness of recently developed methods for risk prediction should be continued and reporting standards improved as these methods become increasingly popular.

Identifying the Impacts of Acne and the Use of Questionnaires to Detect These Impacts: A Systematic Literature Review.

BACKGROUND: Acne (syn: acne vulgaris) ranks as the most common inflammatory dermatosis treated worldwide. Acne typically affects adolescents at a time when they are undergoing maximum physical and social transitions, although prevalence studies suggest it is starting earlier and lasting longer, particularly in female patients. According to global burden of disease studies, acne causes significant psychosocial impact. Hence, identifying mechanisms to accurately measure the impact of the disease is important. Adopting an approach to harmonize and standardize measurements is now recognized as an essential part of any clinical evaluation and allows for better comparison across studies and meta-analyses. OBJECTIVE: The Acne Core Outcome Research Network (ACORN) has identified relevant domains as part of a core outcome set of measures for use in clinical studies. One of these is health-related quality of life (HRQoL). The aim of this systematic review was to provide information to inform the identification of the impacts most important to people with acne. METHODS: A synthesis of available evidence on acne impacts was constructed from a systematic review of the literature, with searches conducted in the MEDLINE, EMBASE and PsychInfo databases. RESULTS: We identified 408 studies from 58 countries using 138 different instruments to detect the impacts of acne. Four of the five most commonly used instruments (Dermatology Life Quality Index [DLQI], Cardiff Acne Disability Index [CADI], Acne Quality of Life scale [Acne-QoL], Hospital Anxiety and Depression Scale [HADS] and Skindex-29) do not identify specific impacts but rather quantify to what extent acne affects HRQoL. Other studies identified one or more impacts using open-ended questions or tailor-made questionnaires. CONCLUSION: This review serves as a rich data source for future efforts by groups such as ACORN (that include patients and health care providers) to develop a core set of outcome measurements for use in clinical trials.

Towards Improving the Outcomes of Assisted Reproductive Technologies of Cattle and Sheep, with Particular Focus on Recipient Management.

The Australian agricultural industry contributes AUD 47 billion to the Australian economy, and Australia is the world's largest exporter of sheep meat and the third largest for beef. Within Australia, sheep meat consumption continues to rise, with beef consumption being amongst the highest in the world; therefore, efficient strategies to increase herd/flock size are integral to the success of these industries. Reproductive management is crucial to increasing the efficiency of Australian breeding programs. The use of assisted reproductive technologies (ARTs) has the potential to increase efficiency significantly. The implementation of multiple ovulation and embryo transfer (MOET) and juvenile in vitro fertilization and embryo transfer (JIVET) in combination with genomic selection and natural mating and AI is the most efficient way to increase genetic gain, and thus increase reproductive efficiency within the Australian livestock industries. However, ARTs are costly, and high variation, particularly between embryo transfer recipients in their ability to maintain pregnancy, is a significant constraint to the widespread commercial adoption of ARTs. The use of a phenotypic marker for the selection of recipients, as well as the better management of recipient animals, may be an efficient and cost-effective means to increase the productivity of the Australian livestock industry.

Successful attentional set-shifting in 2-year-olds with and without Autism Spectrum Disorder.

The development of executive function is necessary for flexible and voluntary control of behavior. Deficits in executive function are purported to be a primary cause of behavioral inflexibility-a core clinical symptom-in Autism Spectrum Disorder (ASD). Attentional set-shifting has traditionally been measured with the Dimensional Change Card Sort, however, this task requires following verbal instructions. Here, we used a novel visual search task that does not require verbal instructions in conjunction with eye-tracking to test attentional set-shifting in 2-year-old toddlers diagnosed with ASD (N = 29) and chronological age-matched typically developing controls (N = 30). On each trial, a relevant and an irrelevant target were embedded in a set of feature-conjunction distractors, and toddlers were tasked with searching for the relevant target. Critically, after a set of trials the targets switched roles (i.e., the previously relevant target became irrelevant, and the previously relevant target became irrelevant). We measured visual search performance prior to and following a target switch. We found that both groups of toddlers could readily switch targets, and found strikingly similar performance between typically developing toddlers and toddlers with ASD. Our results challenge the centrality of deficits in attentional set-shifting to early behavioral inflexibility in ASD.

Extended dynamometry: reference values.

Grip strength is used as a measure of capacity in disability and personal injury claims. Although seemingly an objective measure, it is widely recognized that it is fallible to the effects of sub-maximal effort. We have developed an extended test protocol that uses the five positions of a Jamar dynamometer. The protocol mitigates the effect of inconsistency while retaining the ability to detect sub-maximal effort. Dynamometry was undertaken in 242 volunteers (male:female, 124:118) with a median age of 39 years (range 18-89, interquartile range 29-52). Normative values for consistency, curve deviation and variation from the expected curve pattern are provided. None of these measures were significantly affected by laterality, hand dominance, sex or age despite the effects of these variables on grip strength. The study defines the methodology and reference values to allow assessment of both the capacity of a patient and the reliability of the test for use in medicolegal practice. Level of evidence: II.

Don't ignore the green light: exploring diverse roles in plant processes.

The pleasant green appearance of plants, caused by their reflectance of wavelengths in the 500-600 nm range, might give the impression that green light is of minor importance in biology. This view persists to an extent. However, there is strong evidence that these wavelengths are not only absorbed but that they also drive and regulate physiological responses and anatomical traits in plants. This review details the existing evidence of essential roles for green wavelengths in plant biology. Absorption of green light is used to stimulate photosynthesis deep within the leaf and canopy profile, contributing to carbon gain and likely crop yield. In addition, green light also contributes to the array of signalling information available to leaves, resulting in developmental adaptation and immediate physiological responses. Within shaded canopies this enables optimization of resource-use efficiency and acclimation of photosynthesis to available irradiance. In this review, we suggest that plants may use these wavelengths not just to optimize stomatal aperture but also to fine-tune whole-canopy efficiency. We conclude that all roles for green light make a significant contribution to plant productivity and resource-use efficiency. We also outline the case for using green wavelengths in applied settings such as crop cultivation in LED-based agriculture and horticulture.

Off to a Good Start: The Early Development of the Neural Substrates Underlying Visual Working Memory.

Current neuroscientific models describe the functional neural architecture of visual working memory (VWM) as an interaction of the frontal-parietal control network and more posterior areas in the ventral visual stream (Jonides et al., 2008; D'Esposito and Postle, 2015; Eriksson et al., 2015). These models are primarily based on adult neuroimaging studies. However, VWM undergoes significant development in infancy and early childhood, and the goal of this mini-review is to examine how recent findings from neuroscientific studies of early VWM development can be reconciled with this model. We surveyed 29 recent empirical reports that present neuroimaging findings in infants, toddlers, and preschoolers (using EEG, fNIRS, rs-fMRI) and neonatal lesion studies in non-human primates. We conclude that (1) both the frontal-parietal control network and the posterior cortical storage areas are active from early infancy; (2) this system undergoes focalization and some reorganization during early development; (3) and the MTL plays a significant role in this process as well. Motivated by both theoretical and methodological considerations, we offer some recommendations for future directions for the field.

Spread of the newly emerging infectious laryngotracheitis viruses in Australia.

Infectious laryngotracheitis (ILT) is a significant viral disease of chickens in many countries around the globe. In this report the status of ILT in Australia has been used as a model to evaluate the evolution of the ILT viruses (ILTVs). Due to its geographical isolation, Australia harbored a distinct lineage of ILT viruses (ILTV) up to 2007. However examination of the ILT viruses (ILTV) involved in outbreaks between 2007 and 2009 has revealed that many of the outbreaks were caused by two new viral genotypes, class 8 and class 9. These two recombinant viruses were found to emerge as a result of recombination between previously existing live vaccine strains (SA2 and A20), and another live vaccine strain (Serva) introduced into the country in 2007. The new recombinant ILTVs were also shown to possess significantly higher virulence and replication capacity compared with a previously predominant ILTV, class 2. In the current study, examination of a large number of ILTVs isolated from outbreaks between 2009 and 2015 revealed the emergence of yet another recombinant virus (class 10) that appears to have become a predominant genotype in New South Wales. In Victoria however, the recombinant class 9 gradually became the predominant virus, replacing class 2. Therefore, there was an unusual pattern in geographical spread of the newly emerged viruses in different states of the country. These results suggest that ILTV is fast evolving towards a greater transmissibility and therefore greater capacity to spread into ILTV-free areas.

Unimpaired attentional disengagement in toddlers with autism spectrum disorder.

A prominent hypothesis holds that 'sticky' attention early in life in children with autism spectrum disorder (ASD) limits their ability to explore and learn about the world. Under this hypothesis, the core clinical symptoms of ASD - restricted interests, repetitive behaviors and impaired social/communication abilities - could all result from impaired attentional disengagement during development. However, the existence of disengagement deficits in children with ASD is controversial, and a recent study found no deficit in 5- to 12-year-olds with ASD. Nonetheless, the possibility remains that disengagement is impaired earlier in development in children with ASD, altering their developmental trajectory even if the attentional deficit itself is remediated or compensated for by the time children with ASD reach school age. Here, we tested this possibility by characterizing attentional disengagement in a group of toddlers just diagnosed with ASD (age 21 to 37 months). We found strikingly similar performance between the ASD and age-matched typically developing (TD) toddlers, and no evidence of impaired attentional disengagement. These results show that even at a young age when the clinical symptoms of ASD are first emerging, disengagement abilities are intact. Sticky attention is not a fundamental characteristic of ASD, and probably does not play a causal role in its etiology.

The personal experience of partners of individuals with motor neuron disease.

Most research on partners' experiences of living with a person with MND is questionnaire-based with no qualitative study focusing on the period between diagnosis and end-of-life care. This study aimed to provide an in-depth qualitative exploration of the experience of living with, and caring for, a partner with MND. Semi-structured interviews were conducted with eight individuals, and transcripts analysed from an interpretative phenomenological perspective. Two main themes were derived. 'Impact on life' included having concern for partner's safety, having social restrictions, being continually tired, struggling with anger and frustration, loss of intimacy and uncertainty around the future; while 'Adjusting to the situation' included trying to be strong, retaining a sense of normality, appreciation of specialist services, adopting a problem-solving approach, living day to day and ability to remain positive. In conclusion, experiences of stress and loss are illustrated in this sample of partners of those with MND, and it is suggested both these aspects should be integrated into understanding of carers' experiences. Carers appear to inhibit their grief in order to appear strong. Greater understanding of the consequences of this would help in providing appropriate emotional support.

Whole grain intakes in the diets of Irish children and teenagers.

A growing body of evidence supports the inclusion of whole grain foods in the diet to help prevent certain chronic diseases. Although much of the research has been conducted in adult cohorts, it is thought that younger populations may also benefit from whole-grain-rich diets. The aim of the present study was to quantify the intake of whole grain in Irish children and teenagers, and assess the major sources of intake. Data used in the present study were from the National Children's Food Survey and the National Teens' Food Survey, which used 7 d food diaries to collect data on habitual food and beverage consumption in representative samples of Irish children and teenagers. Results showed that over 90 % of children (5-12 years) and over 86 % of teenagers (13-17 years) are consumers of whole grain, with mean daily intakes of 18·5 and 23·2 g/d, respectively. Ready-to-eat breakfast cereals made the greatest contribution to whole grain intakes for both children and teenagers (59·3 and 44·3 %), followed by bread (14·4 and 26·5 %), with wheat being the major source of intake, accounting for over 65 % of all whole grains consumed. Whole grain consumers had significantly higher intakes of fibre, P and Mg in comparison with non-consumers of whole grain, even though whole grain intakes in this sample were well below the recommendation of three servings or 48 g/d. The present study characterises, for the first time, the patterns of whole grain consumption in Irish children and teenagers and shows whole grain intake to be low.

Increasing prevalence of domiciliary ventilation: changes in service demand and provision in the South West of the UK.

We examine the incidence and prevalence of domiciliary ventilation in the South West region of the UK, assess trends over 15 years, and describe patient outcome. We conducted a retrospective review of all patients below 18 years receiving domiciliary ventilation in the South West region of the UK between January 1994 and August 2009. Children who received long-term ventilation solely in hospital were excluded from the study. Information was obtained from a locally held database, medical notes, and hospital administration systems. One hundred-six patients were identified. Prevalence has increased since 1994 from 0.2 to 6.7 per 100,000 children. The incidence of both invasive and non-invasive ventilations has increased with a trend towards more non-invasive therapy. The commonest underlying disorders were airway pathology (37 patients), neuromuscular disease (34 patients), and central congenital hypoventilation disorder (17 patients). Sixty-seven patients had significant co-morbidities. Of 38 non-current patients, 19 were transferred to adult ventilation services, 11 died, and 6 were successfully weaned from ventilatory support. In conclusion, there has been a 30-fold increase in the prevalence of paediatric domiciliary ventilation, in the South West region of the UK, since 1994. Co-morbidities are common. Very few children discontinue long-term ventilation, and increasing numbers of ventilated children are transferred to adult services.

Wet powder suspensions as an additional technique for the enhancement of bloodied marks.

The enhancement of marks in blood on dark surfaces poses significant challenges to the forensic scientist. Current methods of enhancement include the sequential use of acid dyes (acid yellow, acid violet and acid black). Acid yellow is used to greatest effect on lighter deposits of blood on a non-porous background, and is visualised using a light source which causes it to fluoresce [1]. However, further enhancement with acid violet and acid black produces a dark product which may fail to improve the contrast of the mark against a dark background. The use of wet powder suspensions (WPSs) has been proposed as a complementary procedure for use in fingermark enhancement, beyond its typical use in the enhancement of marks on adhesive surfaces. In this investigation, the use of WPS was tested in conjunction with conventional acid dye treatments on marks in blood deposited on a selection of substrates. The results demonstrated that white WPS alone or together with acid dyes results in an overall enhancement of mark quality (p<0.005) on marks deposited on smooth non-porous surfaces. The technique was shown to not interfere with subsequent presumptive tests on blood. However WPS treatments were shown to reduce the amount of DNA recoverable from the marks, resulting on an average decrease of 91% compared to untreated controls. The decline in DNA yields was shown to result in a decrease in the quality of the DNA profiles obtained. The enhancement properties of WPS were evaluated by electron microscopy. It was shown that the titanium dioxide particles in the WPS primarily interact with the non-bloodied part of the mark, thus producing a contrasting effect with the background and acid dyes.