Evaluation of short-term hair follicle storage conditions for maintenance of RNA integrity.

Hair follicles provide an easily accessible tissue for interrogating gene expression for multiple purposes in mammals. RNAlater® is a liquid storage solution that stabilises and preserves cellular RNA, eliminating the need to immediately process or freeze tissue specimens. The manufacturer advises storage of samples at 2-8°C overnight before transfer to -20°C. This study aimed to evaluate RNA integrity in hair follicle samples collected from horses, stabilized in RNAlater®, and stored under three short-term storage conditions. Mane hair samples complete with follicles were collected from four horses at a single time point. Approximately 15 hairs were placed in each of three 2 mL tubes containing 0.75ml RNAlater® solution. Test group A was stored at 4°C for 24-h, then decanted and stored at -20°C. Test groups B and C were stored at 4°C and 19°C (room temperature) respectively for 7 days, then decanted and stored at -20°C. RNA was isolated from all samples and RNA quantity and quality were measured. One-way ANOVA revealed no difference in RNA concentration (A:516 +/-125 ng/ml, B:273+/-93 ng/ml, C:476+/-176 ng/ml;P = 0.2) or quality (A:9.5 +/-0.19, B:9.8+/-0.09, C:9.2+/-0.35 RIN; P = 0.46) between the test groups. There were no group differences in mean Cycle Threshold values from qPCR validation assays confirming high-quality template cDNA. The results suggest that storage of hair follicles for one week in RNAlater® at cool or room temperature conditions will not compromise RNA integrity and will permit extended transport times from remote sampling locations without the need for freezing.

Genomic insights into the population history and adaptive traits of Latin American Criollo cattle.

Criollo cattle, the descendants of animals brought by Iberian colonists to the Americas, have been the subject of natural and human-mediated selection in novel tropical agroecological zones for centuries. Consequently, these breeds have evolved distinct characteristics such as resistance to diseases and exceptional heat tolerance. In addition to European taurine (Bos taurus) ancestry, it has been proposed that gene flow from African taurine and Asian indicine (Bos indicus) cattle has shaped the ancestry of Criollo cattle. In this study, we analysed Criollo breeds from Colombia and Venezuela using whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) array data to examine population structure and admixture at high resolution. Analysis of genetic structure and ancestry components provided evidence for African taurine and Asian indicine admixture in Criollo cattle. In addition, using WGS data, we detected selection signatures associated with a myriad of adaptive traits, revealing genes linked to thermotolerance, reproduction, fertility, immunity and distinct coat and skin coloration traits. This study underscores the remarkable adaptability of Criollo cattle and highlights the genetic richness and potential of these breeds in the face of climate change, habitat flux and disease challenges. Further research is warranted to leverage these findings for more effective and sustainable cattle breeding programmes.

An economic evaluation and incremental analysis of the cost effectiveness of three universal childhood varicella vaccination strategies for Ireland.

BACKGROUND: The cost effectiveness of childhood varicella vaccination is uncertain, as evidenced by variation in national health policies. Within the European Economic Area (EEA), only 10 of 30 countries offer universally funded childhood varicella vaccination. This study estimates the cost effectiveness of universal childhood varicella vaccination for one EEA country (Ireland), highlighting the difference in cost effectiveness between alternative vaccination strategies. METHODS: An age-structured dynamic transmission model, simulating varicella zoster virus transmission, was developed to analyse the impact of three vaccination strategies; one-dose at 12 months old, two-dose at 12 and 15 months old (short-interval), and two-dose at 12 months and five years old (long-interval). The analysis adopted an 80-year time horizon and considered payer and societal perspectives. Clinical effectiveness was based on cases of varicella and subsequently herpes zoster and post-herpetic neuralgia avoided, and outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented in 2022 Irish Euro and cost effectiveness was interpreted with reference to a willingness-to-pay threshold of €20,000 per QALY gained. RESULTS: From the payer perspective, the incremental cost-effectiveness ratio (ICER) for a one-dose strategy, compared with no vaccination, was estimated at €8,712 per QALY gained. The ICER for the next least expensive strategy, two-dose long-interval, compared with one-dose, was estimated at €45,090 per QALY gained. From a societal perspective, all three strategies were cost-saving compared with no vaccination; the two-dose short-interval strategy dominated, yielding the largest cost savings and health benefits. Results were stable across a range of sensitivity and scenario analyses. CONCLUSION: A one-dose strategy was highly cost effective from the payer perspective, driven by a reduction in hospitalisations. Two-dose strategies were cost saving from the societal perspective. These results should be considered alongside other factors such as acceptability of a new vaccine within the overall childhood immunisation schedule, programme objectives and budget impact.

Transcriptomics analysis of the bovine endometrium during the perioestrus period.

During the oestrous cycle, the bovine endometrium undergoes morphological and functional changes, which are regulated by alterations in the levels of oestrogen and progesterone and consequent changes in gene expression. To clarify these changes before and after oestrus, RNA-seq was used to profile the transcriptome of oestrus-synchronized beef heifers. Endometrial samples were collected from 29 animals, which were slaughtered in six groups beginning 12 h after the withdrawal of intravaginal progesterone releasing devices until seven days post-oestrus onset (luteal phase). The groups represented proestrus, early oestrus, metoestrus and early dioestrus (luteal phase). Changes in gene expression were estimated relative to gene expression at oestrus. Ingenuity Pathway Analysis (IPA) was used to identify canonical pathways and functional processes of biological importance. A total of 5,845 differentially expressed genes (DEGs) were identified. The lowest number of DEGs was observed at the 12 h post-oestrus time point, whereas the greatest number was observed at Day 7 post-oestrus onset (luteal phase). A total of 2,748 DEGs at this time point did not overlap with any other time points. Prior to oestrus, Neurological disease and Organismal injury and abnormalities appeared among the top IPA diseases and functions categories, with upregulation of genes involved in neurogenesis. Lipid metabolism was upregulated before oestrus and downregulated at 48h post-oestrus, at which point an upregulation of immune-related pathways was observed. In contrast, in the luteal phase the Lipid metabolism and Small molecule biochemistry pathways were upregulated.

Enablers and barriers to accessing self-management support services for those living with and beyond cancer: A qualitative study using the theoretical domains framework.

BACKGROUND: Supporting those living with and beyond cancer to self-manage their health can optimise health-related quality of life and reduce symptom burden. Self-management support (SMS) programmes have been shown to be effective, but uptake is often low. This qualitative study aimed to identify experienced and perceived enablers and barriers to accessing SMS services among those who had completed primary cancer treatment and were living with and beyond cancer. METHODS: Participants were recruited through social media and cancer advocacy groups. Semi-structured telephone and online interviews were conducted. Transcripts were coded inductively based on participants' reported experiences. Statements related to factors that enable or inhibit access to SMS were then mapped to the Theoretical Domains Framework (TDF). RESULTS: Twenty-six people participated. Six themes explain the factors that act as barriers and enablers which mapped to 11 TDF domains. Lack of knowledge of available SMS was a prominent barrier, as well as inaccessible services due to timing and place of delivery. Lack of confidence and emotional factors including fear were barriers to seeking SMS. Social influences shaped knowledge, attitudes and readiness to access SMS. Perceptions of SMS service goals and if in alignment with self-identity, intentions and goals also shaped decisions around accessing support. CONCLUSIONS: While lack of knowledge and provider signposting were common barriers, findings suggest that other psychosocial and emotional factors may be barriers, even if SMS services are accessible. Findings are relevant for oncology healthcare services developing strategies to increase reach of SMS for those living with and beyond cancer.

Integrative and comparative genomic analyses of mammalian macrophage responses to intracellular mycobacterial pathogens.

Mycobacterium tuberculosis, the causative agent of human tuberculosis (hTB), is a close evolutionary relative of Mycobacterium bovis, which causes bovine tuberculosis (bTB), one of the most damaging infectious diseases to livestock agriculture. Previous studies have shown that the pathogenesis of bTB disease is comparable to hTB disease, and that the bovine and human alveolar macrophage (bAM and hAM, respectively) transcriptomes are extensively reprogrammed in response to infection with these intracellular mycobacterial pathogens. In this study, a multi-omics integrative approach was applied with functional genomics and GWAS data sets across the two primary hosts (Bos taurus and Homo sapiens) and both pathogens (M. bovis and M. tuberculosis). Four different experimental infection groups were used: 1) bAM infected with M. bovis, 2) bAM infected with M. tuberculosis, 3) hAM infected with M. tuberculosis, and 4) human monocyte-derived macrophages (hMDM) infected with M. tuberculosis. RNA-seq data from these experiments 24 h post-infection (24 hpi) was analysed using three computational pipelines: 1) differentially expressed genes, 2) differential gene expression interaction networks, and 3) combined pathway analysis. The results were integrated with high-resolution bovine and human GWAS data sets to detect novel quantitative trait loci (QTLs) for resistance to mycobacterial infection and resilience to disease. This revealed common and unique response macrophage pathways for both pathogens and identified 32 genes (12 bovine and 20 human) significantly enriched for SNPs associated with disease resistance, the majority of which encode key components of the NF-κB signalling pathway and that also drive formation of the granuloma.

Long-term patient-reported outcomes of immediate breast reconstruction after mastectomy for breast cancer: population-based cohort study.

BACKGROUND: Breast reconstruction is offered to improve quality of life for women after mastectomy for breast cancer, but information regarding the long-term patient-reported outcomes of different reconstruction procedures is currently lacking. The Brighter study aimed to evaluate long-term patient-reported outcomes after immediate breast reconstruction (IBR) in a population-based cohort. METHODS: Women who underwent mastectomy with IBR for breast cancer in England between 1 January 2008 and 31 March 2009 were identified from National Health Service Hospital Episode Statistics. Surviving women were invited to complete the BREAST-Q, EQ-5D-5L™, and ICECAP-A at least 12 years after the index procedure. Questionnaires were scored according to developers' instructions and compared by IBR type. RESULTS: Some 1236 women underwent IBR; 343 (27.8 per cent) had 2-stage expander/implant, 630 (51.0 per cent) latissimus dorsi, and 263 (21.3 per cent) abdominal flap reconstructions, with a mean(s.d.) follow-up of 13.3(0.5) years. Women who underwent abdominal flap reconstruction reported higher scores in all BREAST-Q domains than those who had other procedures. These differences remained statistically significant and clinically meaningful after adjusting for age, ethnicity, geographical region, socioeconomic status, smoking, BMI, and complications. The greatest difference was seen in scores for satisfaction with breasts; women who had abdominal flap reconstructions reported scores that were 13.17 (95 per cent c.i. 9.48 to 16.87) points; P < 0.001) higher than those among women who had two-stage expander/implant procedures. Women who underwent latissimus dorsi reconstruction reported significantly more pain/discomfort on the EQ-5D-5L™, but no other differences between procedures were seen. CONCLUSION: Long-term patient-reported outcomes are significantly better following abdominal flap reconstruction than other traditional procedure types. These findings should be shared with women considering IBR to help them make informed decisions about their surgical options.

Optimised Stable Lighting Strengthens Circadian Clock Gene Rhythmicity in Equine Hair Follicles.

Hair follicles (HF) represent a useful tissue for monitoring the circadian clock in mammals. Irregular light exposure causes circadian disruption and represents a welfare concern for stabled horses. We aimed to evaluate the impact of two stable lighting regimes on circadian clock gene rhythmicity in HF from racehorses. Two groups of five Thoroughbred racehorses in training at a commercial racehorse yard were exposed to standard incandescent light or a customized LED lighting system. The control group received light from incandescent bulbs used according to standard yard practice. The treatment group received timed, blue-enriched white LED light by day and dim red LED light at night. On weeks 0 and 20, mane hairs were collected at 4 h intervals for 24 h. Samples were stored in RNAlater at -20 °C. RNA was isolated and samples interrogated by quantitative PCR for the core clock genes: ARNTL, CRY1, PER1, PER2, NR1D2, and the clock-controlled gene DBP. Cosinor analyses revealed 24 h rhythmicity for NR1D2 and PER2 and approached significance for CRY1 (p = 0.013, p = 0.013, and p = 0.051, respectively) in week 20 in the treatment group only. No rhythmicity was detected in week 0 or in week 20 in the HF of control horses. Results suggest that lighting practices in racehorse stables may be improved to better stimulate optimum functioning of the circadian system.

Experiences of and preferences for self-management among low grade non-Hodgkin's lymphoma survivors: A qualitative interview study.

PURPOSE: Supporting self-management is one strategy to help cancer survivors optimise their quality of life. Low grade non-Hodgkin's lymphoma is often incurable with a chronic disease trajectory requiring lifelong self-management. This study explored the views on self-management and preferences for self-management support among survivors of low grade non-Hodgkin's lymphoma and their informal caregivers more than 6 months after completion of systemic anti-cancer therapy. METHOD: In-depth semi-structured telephone interviews were conducted. Key themes and subthemes were determined using inductive and deductive thematic analysis. RESULTS: The sample included eight survivors of low grade non-Hodgkin's lymphoma and two family caregivers. There were four themes. 1) The chronic nature of low grade non-Hodgkin's lymphoma shapes perceptions of self-management; participants described their cancer as a chronic condition and self-management strategies reflected this. 2) Social networks enable self-management; participants emphasised the importance of making low grade non-Hodgkin's lymphoma survivors aware of social networks. 3) Support and monitoring are needed immediately after the initial treatment phase ends. 4) Preferred components of self-management support; this included regular review with monitoring, advice on diet, and strategies to manage the psychosocial consequences of low grade non-Hodgkin's lymphoma. CONCLUSIONS: Providing self-management support to those diagnosed with low grade non-Hodgkin's lymphoma is relevant given the chronic trajectory of the disease. Findings suggest that necessary components of a self-management support programme for those with low grade non-Hodgkin's lymphoma should include regular review with monitoring and practical support around facilitating engagement with social networks.

The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls.

Feline mammary adenocarcinomas (FMA) are aggressive tumours with metastatic capability and limited treatment options. This study aims to investigate whether miRNAs associated with FMA tumours are secreted in extracellular vesicles (EVs) and whether they can potentially be used as a cancer biomarker in EVs from feline plasma. Tumours and matched tumour free margins from 10 felines with FMA were selected. Following a detailed literature search, RT-qPCR analyses of 90 miRNAs identified 8 miRNAs of interest for further investigation. Tumour tissue, margins and plasma were subsequently collected from a further 10 felines with FMA. EVs were isolated from the plasma. RT-qPCR expression analyses of the 8 miRNAs of interest were carried out in tumour tissue, margins, FMA EVs and control EVs. Additionally, proteomic analysis of both control and FMA plasma derived EVs was undertaken. RT-qPCR revealed significantly increased miR-20a and miR-15b in tumours compared to margins. A significant decrease in miR-15b and miR-20a was detected in EVs from FMAs compared to healthy feline EVs. The proteomic content of EVs distinguished FMAs from controls, with the protein targets of miR-20a and miR-15b also displaying lower levels in the EVs from patients with FMA. This study has demonstrated that miRNAs are readily detectable in both the tissue and plasma derived EVs from patients with FMA. These miRNAs and their protein targets are a detectable panel of markers in circulating plasma EVs that may inform future diagnostic tests for FMA in a non-invasive manner. Moreover, the clinical relevance of miR-20a and miR-15b warrants further investigation.

Gene expression analysis of Canine Demodicosis; A milieu promoting immune tolerance.

Canine demodicosis is a common skin disease seen in companion animal practice that results from an overpopulation of the commensal Demodex mite species. Common predisposing factors to the development of canine demodicosis include immunosuppressive diseases, such as neoplasia and hypothyroidism, and administration of immunosuppressive therapies, such as corticosteroids. Despite this, the pathogenesis of development of canine demodicosis remains unclear. Previous studies have implicated a role for increased expression of toll like receptor 2 (TLR2), increased production of interleukin (IL)-10) and T cell exhaustion. Here, we investigate gene expression of formalin fixed paraffin embedded skin samples from twelve cases of canine demodicosis in comparison to twelve healthy controls, using a 770 gene panel (NanoString Canine IO Panel). Results show an increase in the T cell population, specifically Th1 and Treg cells in dogs with demodicosis. In addition, while there is an upregulation of immunosuppressive cytokines such as IL-10 and IL-13, there is also an upregulation of immune check point molecules including PD-1/PD-L1 and CTLA-4. These findings suggest that Demodex spp. mites are modulating the host immune system to their advantage through upregulation of several immune tolerance promoting pathways.

The comparative performance of a custom Canine NanoString® panel on FFPE and snap frozen liver biopsies.

Formalin-Fixed Paraffin Embedded (FFPE) biopsies would provide a critical mass of cases to allow investigation of canine liver disease, however their use is often limited by challenges typically associated with transcriptomic analysis. This study evaluates the capability of NanoString® to measure the expression of a broad panel of genes in FFPE liver samples. RNA was isolated from matched histopathologically normal liver samples using FFPE (n = 6) and snap frozen in liquid nitrogen (n = 6) and measured using a custom NanoString® panel. Out of the 40 targets on the panel, 27 and 23 targets were above threshold for non-diseased snap frozen and FFPE tissue respectively. The binding density and total counts were significantly reduced in the FFPE samples relative to the snap frozen samples (p = 0.005, p = 0.01, respectively), confirming a reduction in sensitivity. The concordance between the snap frozen and FFPE samples was high, with correlations (R) ranging between 0.88 and 0.99 between the paired samples. An additional 14 immune-related targets, undetectable the non-diseased FFPE liver, were above threshold when the technique was applied to a series of diseased samples, further supporting their inclusion on this panel. This use of NanoString® based analysis opens up huge opportunity for retrospective evaluation of gene signatures in larger caseloads through harnessing the capacity of archived FFPE samples This information used alongside clinical and histological data will not only afford a way to explore disease etiopathogenesis, it may also offer insight into sub-types of liver disease in dogs, which cannot be discerned using more traditional diagnostic methods.

Variation in salivary cortisol responses in yearling Thoroughbred racehorses during their first year of training.

Thoroughbred horses are bred for competitive racing and undergo intense training regimes. The maintenance of physical soundness and desirable behavioural characteristics are critical to the longevity of a racing career. Horses intended for Flat racing generally enter training as yearlings and undergo introductory training prior to exercise conditioning for racing. This period requires rapid adjustment to a novel environment. As a prey animal, a horse's 'fight-or-flight' response is highly adapted, in which a well-understood component of this response, the hypothalamic-pituitary-axis, is activated in response to a stress stimulus, releasing cortisol. In the Thoroughbred, a significant difference in salivary cortisol concentrations between pre- and post-first time ridden (i.e., first backing) by a jockey have previously been identified. Here, to test the hypothesis that salivary cortisol concentrations may be used to objectively detect individual variations in the acute physiological stress response we investigate individual variation in cortisol response to training milestones. Saliva samples were collected from a cohort of n = 96 yearling Flat racehorses, at the same training yard, across three timepoints at rest: before entering the training yard (n = 66), within three days of entry to the training yard (n = 67) and following 2-3 weeks in the training yard (n = 50). Salivary cortisol concentration was measured using an ELISA. There was no significant difference in cortisol concentration (ANOVA, P > 0.05) across the samples collected at timepoints at rest. Samples were also collected before and 30 minutes after exposure to three novel training events: first time long-reined (n = 6), first time backed by a jockey (n = 34), and first time ridden on the gallops (n = 10). Mean salivary cortisol concentration after all three novel training events was significantly higher than prior to the training event (Paired t-test, P <0.005). The ranges of post-event salivary cortisol concentration across all timepoints suggest individual variation in the measured stress response, reflecting individual differences in stress response to the early training environment. This measure may be used as an objective assessment of the stress response of Thoroughbred racehorses during training.

Determinants of regulatory compliance in health and social care services: A systematic review using the Consolidated Framework for Implementation Research.

BACKGROUND: The delivery of high quality care is a fundamental goal for health systems worldwide. One policy tool to ensure quality is the regulation of services by an independent public authority. This systematic review seeks to identify determinants of compliance with such regulation in health and social care services. METHODS: Searches were carried out on five electronic databases and grey literature sources. Quantitative, qualitative and mixed methods studies were eligible for inclusion. Titles and abstracts were screened by two reviewers independently. Determinants were identified from the included studies, extracted and allocated to constructs in the Consolidated Framework for Implementation Research (CFIR). The quality of included studies was appraised by two reviewers independently. The results were synthesised in a narrative review using the constructs of the CFIR as grouping themes. RESULTS: The search yielded 7,500 articles for screening, of which 157 were included. Most studies were quantitative designs in nursing home settings and were conducted in the United States. Determinants were largely structural in nature and allocated most frequently to the inner and outer setting domains of the CFIR. The following structural characteristics and compliance were found to be positively associated: smaller facilities (measured by bed capacity); higher nurse-staffing levels; and lower staff turnover. A facility's geographic location and compliance was also associated. It was difficult to make findings in respect of process determinants as qualitative studies were sparse, limiting investigation of the processes underlying regulatory compliance. CONCLUSION: The literature in this field has focused to date on structural attributes of compliant providers, perhaps because these are easier to measure, and has neglected more complex processes around the implementation of regulatory standards. A number of gaps, particularly in terms of qualitative work, are evident in the literature and further research in this area is needed to provide a clearer picture.

Impact of procedure type on revisional surgery and secondary reconstruction after immediate breast reconstruction in a population-based cohort.

BACKGROUND: Women considering immediate breast reconstruction require high-quality information about the likely need for secondary reconstruction and the long-term risk of revisional surgery to make fully informed decisions about different reconstructive options. Such data are currently lacking. This study aimed to explore the impact of reconstruction type on the number of revisions and secondary reconstructions performed 3, 5, and 8 years after immediate breast reconstruction in a large population-based cohort. METHODS: Women undergoing unilateral mastectomy and immediate breast reconstruction for breast cancer or ductal carcinoma in situ in England between 1 April 2009 and 31 March 2015 were identified from National Health Service Hospital Episode Statistics. Numbers of revisions and secondary reconstructions in women undergoing primary definitive immediate breast reconstruction were compared by procedure type at 3, 5, and 8 years after index surgery. RESULTS: Some 16 897 women underwent immediate breast reconstruction with at least 3 years' follow-up. Of these, 14 069 had a definitive reconstruction with an implant only (5193), latissimus dorsi flap with (3110) or without (2373) an implant, or abdominal free flap (3393). Women undergoing implant-only reconstruction were more likely to require revision, with 69.5 per cent (747 of 1075) undergoing at least one revision by 8 years compared with 49.3 per cent (1568 of 3180) in other reconstruction groups. They were also more likely to undergo secondary reconstruction, with the proportion of women having further reconstructive procedures increasing over time: 12.8 per cent (663 of 5193) at 3 years, 14.3 per cent (535 of 3752) at 5 years, and 17.6 per cent (189 of 1075) at 8 years. CONCLUSION: Long-term rates of revisions and secondary reconstructions were considerably higher after primary implant-based reconstruction than autologous procedures. These results should be shared with patients to support informed decision-making.

BACKGROUND: Breast reconstruction is performed to improve well-being for women who need mastectomy (removal of the breast) as part of breast cancer treatment. There are many different types of breast reconstruction operation, and it can be difficult for women to decide which operation, if any, is right for them. Information about the number of extra operations that a woman is likely to need after breast reconstruction surgery is an important factor in helping them make this decision. This study aimed to investigate the number of extra operations that women who had breast reconstruction needed by 3, 5, and 8 years after surgery, and how this differed by the type of breast reconstruction surgery they had. Routinely collected hospital record data were used to identify women having breast reconstruction at the time of mastectomy for breast cancer, and identify any extra operations performed for problems related to the reconstruction in the 8 years after the first operation. The number of extra operations performed after different types of breast reconstructions was compared at 3, 5, and 8 years after the mastectomy. Women who had implant-based reconstruction required more extra operations than those having reconstruction using their own tissue. They were also more likely to have the implant replaced with another type of breast reconstruction than women undergoing tissue-based reconstruction at 3, 5, and 8 years after the first surgery. This information should be discussed with women thinking about breast reconstruction to help them decide what type of operation would be best for them.

Safety of varicella vaccination strategies: An overview of reviews.

The safety of new vaccines under development as well as existing vaccines is a key priority for national and international public health agencies. A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of the number of doses, type of vaccine(s) recommended, age at vaccination and interval between doses for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the safety of varicella vaccination strategies. The review was restricted to immunocompetent children aged 9 months to 6 years inclusive. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. Overlap of included reviews was also assessed. A total of 17 reviews, incorporating both the monovalent varicella only and quadrivalent measles-mumps-rubella-varicella (MMRV) vaccines were included in the overview; six assessed the safety of one-dose strategies, four assessed the safety of two-dose strategies and 14 reviews did not specify the dosing strategy. The evidence suggests that mild local and systemic reactions are relatively common with varicella vaccination. Febrile seizures are also possible adverse effects of both the monovalent and quadrivalent MMRV vaccine, but serious adverse reactions are rare. While most reviews contained methodological flaws, and analysis by vaccine type and dosing strategy was restricted due to lack of detail in reporting of the reviews, there was clear and consistent evidence from a substantial evidence base, comprising 34 randomised controlled trials and 62 other primary studies/reviews, that varicella vaccination is safe.

Clinical efficacy and effectiveness of alternative varicella vaccination strategies: An overview of reviews.

A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of dosing schedule (one- or two-dose), type of vaccine(s) recommended (monovalent, quadrivalent measles-mumps-rubella-varicella, or both), age at vaccination, and dosing interval for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the clinical efficacy/effectiveness of alternative varicella vaccination strategies. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. A total of 20 reviews were included in the overview; 17 assessed the efficacy/effectiveness of one-dose strategies and 10 assessed the efficacy/effectiveness of two-dose strategies. Although the quality of most reviews was deemed 'critically low', there was clear and consistent evidence that vaccination is very effective at reducing varicella. While the analysis was restricted due to lack of detail in reporting of the reviews, the evidence suggests that two-dose strategies are more efficacious/effective than one-dose strategies in preventing varicella of any severity, but that both strategies have similar high efficacy/effectiveness in preventing moderate or severe varicella. Based on this evidence in this overview of reviews, a key consideration for policymakers on the possible introduction of a childhood varicella vaccination programme and the choice between a one- or two-dose strategy, will be whether the objective of a programme is to prevent varicella of any severity or to prevent moderate to severe varicella.

Rationalising Antipsychotic Prescribing in Dementia (RAPID) complex intervention: A mixed-methods feasibility intervention study.

Background: To help address the issue of inappropriate antipsychotic prescribing to nursing home residents with dementia, the 'Rationalising Antipsychotic Prescribing in Dementia' (RAPID) complex intervention was developed, comprising staff education and training, academic detailing and a novel resident assessment tool. Objectives: The primary objective was to assess the feasibility and acceptability of the RAPID complex intervention in a nursing home setting. The secondary objective was to describe associated trends in psychotropic prescribing, falls, and behavioural symptoms. Methods: A mixed-methods feasibility intervention study in one large nursing home in Ireland was undertaken between 07/2017 and 01/2018. Focus groups and semi-structured interviews were conducted with nursing home staff and GPs at the end of the 3-month follow up period to assess participants' experience of the intervention. Quantitative measurements included pre- and post-course evaluation and psychotropic prescribing rates. Results: Sixteen nursing home staff members attended the two education and training days (21% attendance rate), and four GPs participated in the academic detailing sessions (100% attendance rate). Participants of the focus groups and interviews (n = 18) found the education and training beneficial for their work and expressed a desire to continue educating new staff after the study's completion. However, there was limited usage of the resident assessment tool. Participants also offered recommendations to enhance the intervention.The proportion of dementia residents prescribed at least one regular antipsychotic was stable over the 3-months pre-intervention at 45% (n = 18), and at baseline at 44% (n = 19) but decreased slightly to 36% (n = 14) at 3-months post-intervention. At the same time the absolute number of 'PRN' psychotropics administered monthly to dementia residents decreased substantially from 90 at baseline to 69 at 3-months post-intervention. Conclusion: The RAPID complex intervention was broadly feasible to conduct and may be acceptable to stakeholders. However, before it can be evaluated in larger scale studies, certain protocol modifications and further exploratory work are required to improve implementation.