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In 2013, shingles vaccination was introduced in Wales as a routine immunisation programme for older adults. Invitation for this vaccination has historically been recommended but not mandated by vaccination policy. We surveyed general practices to investigate if invitations and reminders are associated with higher uptake of shingles vaccine. Using data from general practices, we calculated practice-level shingles vaccine uptake between 01/07/2021 and 31/06/2022 for registered patients aged 70–84 years. We distributed an online survey via email to all general practices in Wales on their use of vaccination invitations and reminders, method of invitations, and characteristics of their vaccination delivery. We used linear regression to calculate coefficients and 95 %CI to measure associations between invitations and vaccine uptake, adjusting for key demographics, with a multi-level component to account for similarities between general practices within the same health board. Survey response rate was 37 % (143/384). Median vaccine uptake for responding general practices was 57 % (IQR 50–68 %) compared to 58 % (IQR 48–68 %) nationally. General practices inviting all eligible patients (n = 95) had a 9 % (95 %CI 6–13 %) higher vaccination uptake compared to those inviting none or some (n = 48, p < 0.001). Of practices sending invitations, those who reminded all patients (n = 42) had a 6 % (95 %CI 1–11 %, p = 0.02) higher uptake compared to those that reminded none (n = 30). Practice size was associated with higher uptake, with small practices (n = 11, p = 0.02) having coverage 9 % (95 %CI 2–16 %) higher compared to the reference population (medium-sized practices, n = 78). General practices inviting and reminding all eligible patients for shingles vaccination have a higher uptake compared to those inviting and reminding only some or none. From September 2023, shingles vaccination policy in Wales has been updated to explicitly mandate effective universal call and recall mechanisms in general practices.

•This study highlights an effective intervention to improve vaccine uptake and reduce inequities.•To our knowledge, it is the first intervention study to examine provision of live attenuated influenza vaccine in a nursery school setting.•The study utilises a novel data linkage approach for evaluation of a mixed service delivery model, in the absence of a central universal register.•This study led to a change evidence-based policy change in vaccination service delivery. The schools-based influenza vaccination programme has seen consistently high uptake in Wales, however coverage in pre-school two and three-year olds is lower. One health board area (Cwm Taf University Health Board (UHB)) developed an intervention to offer live attenuated influenza vaccine (LAIV) for three-year olds attending nursery schools alongside the existing general practice (GP) programme. During the pilot, sessions were delivered by health visitors, working with school nurses. The mixed delivery model led to vaccination data being recorded in two separate data systems. To evaluate the impact of the pilot on overall vaccine uptake, data linkage was carried out within the Secure Anonymised Information Linkage (SAIL) Databank. Overall influenza vaccine uptake was calculated for each health board in Wales for two and three-year olds for the 2015–16, 2016–17, and 2017–18 influenza programmes. Uptake in two-year olds in Cwm Taf UHB and also uptake in three-year olds in other health boards in Wales were the comparison groups. Uptake of influenza vaccine in the 2015–16 (pre-intervention) period was 41.0% for three-year olds in Cwm Taf UHB. Following the intervention, coverage increased to 70.7% and 71.5% for 2016–17 and 2017–18 respectively. The same increases in uptake were not seen in two-year olds in Cwm Taf UHB or in three-year olds in non-intervention health boards. In Cwm Taf UHB resident three-year olds in 2015–16 there was an inequality gap in the uptake of 17.4 percentage points between the most and least deprived areas. Uptake increased across all deprivation quintiles in 2016–17 and 2017–18; and the inequality gap decreased to 10.3 and 13.4 percentage points respectively. Influenza vaccination uptake and equality of uptake in three-year olds can be improved by adopting a mixed delivery model across nursery school based immunisation sessions with the additional option of influenza vaccination at GPs.

Aims The aim of this study was to provide guidance to improve the completeness and clarity of meta-ethnography reporting. Background Evidence-based policy and practice require robust evidence syntheses which can further understanding of people’s experiences and associated social processes. Meta-ethnography is a rigorous seven-phase qualitative evidence synthesis methodology, developed by Noblit and Hare. Meta-ethnography is used widely in health research, but reporting is often poor quality and this discourages trust in and use of its findings. Meta-ethnography reporting guidance is needed to improve reporting quality. Design The eMERGe study used a rigorous mixed-methods design and evidence-based methods to develop the novel reporting guidance and explanatory notes. Methods The study, conducted from 2015 to 2017, comprised of: (1) a methodological systematic review of guidance for meta-ethnography conduct and reporting; (2) a review and audit of published meta-ethnographies to identify good practice principles; (3) international, multidisciplinary consensus-building processes to agree guidance content; (4) innovative development of the guidance and explanatory notes. Findings Recommendations and good practice for all seven phases of meta-ethnography conduct and reporting were newly identified leading to 19 reporting criteria and accompanying detailed guidance. Conclusion The bespoke eMERGe Reporting Guidance, which incorporates new methodological developments and advances the methodology, can help researchers to report the important aspects of meta-ethnography. Use of the guidance should raise reporting quality. Better reporting could make assessments of confidence in the findings more robust and increase use of meta-ethnography outputs to improve practice, policy, and service user outcomes in health and other fields. This is the first tailored reporting guideline for meta-ethnography. This article is being simultaneously published in the following journals: Journal of Advanced Nursing, Psycho-oncology, Review of Education, and BMC Medical Research Methodology.

We conducted a mixed methods evaluation to assess whether implementing a primary care quality improvement (QI) programme utilising a digital call-and-recall tool improved timely receipt and equity of first measles, mumps and rubella (MMR) and diphtheria tetanus, pertussis and polio-containing (DTaP /IPV) vaccinations. 138,133 and 136,952 children were eligible to receive first MMR and DTaP/IPV respectively between 1st January 2019 and 31st January 2024 in North East London. We compared proportions with timely first MMR or DTaP/IPV receipt (by ages 18 and six months respectively) pre- and post-implementation using an interrupted time series analysis. We calculated change in the Slope Index of Inequality (SII) by an area-level deprivation measure. We conducted ‘Think Aloud’ exercises and semi-structured interviews with users. The proportion of children with timely first MMR receipt increased by 5·3 % (Rate Ratio [RR]:1·053, 95 % confidence interval [CI]:1·033–1·073), equating to an absolute increase in timely MMR receipt of 4·1 % - from 77·7 % to 81·8 % - and for first DTaP/IPV by 0·9 % (RR:1·009, 95 % CI:1·003–1·015). There was no significant change in SII for either vaccine. Users reported improved recall with tool use, but identified practice-level and systemic barriers, including staff dynamics and unachievable national targets, limiting its consistent use. In a real-world setting, a call-and-recall tool within a primary care QI programme improved timely first MMR receipt. Sustained improvement requires additional support including by incentivising achievable targets and improving staff capacity and training. National Institute of Health and Care Research; Barts Charity.

Synthetic CpG oligonucleotides (ODN) have potent immunostimulatory properties exploited in clinical vaccine trials. How CpG ODN are captured and delivered to the intracellular receptor TLR9, however, has been elusive. Here we show that DEC-205, a multilectin receptor expressed by a variety of cells, is a receptor for CpG ODN. When CpG ODN are used as an adjuvant, mice deficient in DEC-205 have impaired dendritic cell (DC) and B-cell maturation, are unable to make some cytokines such as IL-12, and display suboptimal cytotoxic T-cell responses. We reveal that DEC-205 directly binds class B CpG ODN and enhances their uptake. The CpG-ODN binding function of DEC-205 is conserved between mouse and man, although human DEC-205 preferentially binds a specific class B CpG ODN that has been selected for human clinical trials. Our findings identify an important receptor for class B CpG ODN and reveal a unique function for DEC-205.

Build observation hides around Lake Pape in southwest Latvia, one of the last refuges for European bison.

Rub shoulders with royalty when you book a tropical beach holiday to Hua Hin, in southern Thailand. It's unashamedly laid-back and traditional, which is why the Thai royal family still come here each year to relax in their Klai Kang Won palace (which translates as 'Far From Worries'). The beach is the sort of white sandy stretch that delights holiday brochure designers and you can enjoy watersports, from noisy and nasty jetskis to wind-surfing and sailing. Beach touts are friendly and have a soft- sell approach, offering everything from massages to cold drinks. Fancy a late breakfast on the beach beneath your own personal 'sala' while watching the local elephants taking a bath in the sea before their afternoon polo game? Check out the Anantara Spa and Resort, which combines exotic traditional architecture with fab modern facilities. Spend a leisurely day in and out of the beautiful landscaped pools or in the fragrant flower- filled spa area. The treatments all tend toward the blissed-out with plenty of aromatherapy and relaxing options, although you can opt for a traditional Thai massage if you prefer. There's a wide choice of restaurants within the resort, such as Ba'an Thalia, where you can enjoy innovative Italian cuisine with a Thai slant (which tastes a lot better than it sounds). You'll stay in luxurious 'lagoon rooms' - huge, high-ceilinged spaces decorated with a jaw-dropping modern take on traditional local style. I loved the freestanding stone bath in the centre of my room, filled daily with floating flowers. Lazing on the spacious cushion-filled balcony watching the sun set is a tempting option, before setting off for the comparative hustle and bustle of the nearby town.

IntroductionCall and recall systems provide actionable intelligence to improve equity and timeliness of childhood vaccinations, which have been disrupted during the COVID-19 pandemic. We will evaluate the effectiveness, fidelity and sustainability of a data-enabled quality improvement programme delivered in primary care using an Active Patient Link Immunisation (APL-Imms) call and recall system to improve timeliness and equity of uptake in a multiethnic disadvantaged urban population. We will use qualitative methods to evaluate programme delivery, focusing on uptake and use, implementation barriers and service improvements for clinical and non-clinical primary care staff, its fidelity and sustainability.Methods and analysisThis is a mixed-methods observational study in 284 general practices in north east London (NEL). The target population will be preschool-aged children eligible to receive diphtheria, tetanus and pertussis (DTaP) or measles, mumps and rubella (MMR) vaccinations and registered with an NEL general practice. The intervention comprises an in-practice call and recall tool, facilitation and training, and financial incentives. The quantitative evaluation will include interrupted time Series analyses and Slope Index of Inequality. The primary outcomes will be the proportion of children receiving at least one dose of a DTaP-containing or MMR vaccination defined, respectively, as administered between age 6 weeks and 6 months or between 12 and 18 months of age. The qualitative evaluation will involve a ‘Think Aloud’ method and semistructured interviews of stakeholders to assess impact, fidelity and sustainability of the APL-Imms tool, and fidelity of the implementation by facilitators.Ethics and disseminationThe research team has been granted permission from data controllers in participating practices to use deidentified data for audit purposes. As findings will be specific to the local context, research ethics approval is not required. Results will be disseminated in a peer-reviewed journal and to stakeholders, including parents, health providers and commissioners.

Intensive care unit (ICU)-acquired weakness often develops in patients who are undergoing invasive mechanical ventilation. Early active mobilization may mitigate ICU-acquired weakness, increase survival, and reduce disability. We randomly assigned 750 adult patients in the ICU who were undergoing invasive mechanical ventilation to receive increased early mobilization (sedation minimization and daily physiotherapy) or usual care (the level of mobilization that was normally provided in each ICU). The primary outcome was the number of days that the patients were alive and out of the hospital at 180 days after randomization. The median number of days that patients were alive and out of the hospital was 143 (interquartile range, 21 to 161) in the early-mobilization group and 145 days (interquartile range, 51 to 164) in the usual-care group (absolute difference, -2.0 days; 95% confidence interval [CI], -10 to 6; P = 0.62). The mean (±SD) daily duration of active mobilization was 20.8±14.6 minutes and 8.8±9.0 minutes in the two groups, respectively (difference, 12.0 minutes per day; 95% CI, 10.4 to 13.6). A total of 77% of the patients in both groups were able to stand by a median interval of 3 days and 5 days, respectively (difference, -2 days; 95% CI, -3.4 to -0.6). By day 180, death had occurred in 22.5% of the patients in the early-mobilization group and in 19.5% of those in the usual-care group (odds ratio, 1.15; 95% CI, 0.81 to 1.65). Among survivors, quality of life, activities of daily living, disability, cognitive function, and psychological function were similar in the two groups. Serious adverse events were reported in 7 patients in the early-mobilization group and in 1 patient in the usual-care group. Adverse events that were potentially due to mobilization (arrhythmias, altered blood pressure, and desaturation) were reported in 34 of 371 patients (9.2%) in the early-mobilization group and in 15 of 370 patients (4.1%) in the usual-care group (P = 0.005). Among adults undergoing mechanical ventilation in the ICU, an increase in early active mobilization did not result in a significantly greater number of days that patients were alive and out of the hospital than did the usual level of mobilization in the ICU. The intervention was associated with increased adverse events. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; TEAM ClinicalTrials.gov number, NCT03133377.).

Bacterial two-component regulatory systems, comprising a membrane-bound sensor kinase and cytosolic response regulator, are critical in coordinating the bacterial response to changing environmental conditions. More recently, auxiliary regulators which act to modulate the activity of two-component systems, allowing integration of multiple signals and fine-tuning of bacterial responses, have been identified. RocA is a regulatory protein encoded by all serotypes of the important human pathogen group A Streptococcus . Although RocA is known to exert its regulatory activity via the streptococcal two-component regulatory system CsrRS, the mechanism by which it functions was unknown. Based on new experimental evidence, we propose a model whereby RocA interacts with CsrS in the streptococcal cell membrane to enhance CsrS autokinase activity and subsequent phosphotransfer to the response regulator CsrR, which mediates transcriptional repression of target genes. The orphan regulator RocA plays a critical role in the colonization and pathogenesis of the obligate human pathogen group A Streptococcus . Despite multiple lines of evidence supporting a role for RocA as an auxiliary regulator of the control of virulence two-component regulatory system CsrRS (or CovRS), the mechanism of action of RocA remains unknown. Using a combination of in vitro and in vivo techniques, we now find that RocA interacts with CsrS in the streptococcal membrane via its N-terminal region, which contains seven transmembrane domains. This interaction is essential for RocA-mediated regulation of CsrRS function. Furthermore, we demonstrate that RocA forms homodimers via its cytoplasmic domain. The serotype-specific RocA truncation in M3 isolates alters this homotypic interaction, resulting in protein aggregation and impairment of RocA-mediated regulation. Taken together, our findings provide insight into the molecular requirements for functional interaction of RocA with CsrS to modulate CsrRS-mediated gene regulation. IMPORTANCE Bacterial two-component regulatory systems, comprising a membrane-bound sensor kinase and cytosolic response regulator, are critical in coordinating the bacterial response to changing environmental conditions. More recently, auxiliary regulators which act to modulate the activity of two-component systems, allowing integration of multiple signals and fine-tuning of bacterial responses, have been identified. RocA is a regulatory protein encoded by all serotypes of the important human pathogen group A Streptococcus . Although RocA is known to exert its regulatory activity via the streptococcal two-component regulatory system CsrRS, the mechanism by which it functions was unknown. Based on new experimental evidence, we propose a model whereby RocA interacts with CsrS in the streptococcal cell membrane to enhance CsrS autokinase activity and subsequent phosphotransfer to the response regulator CsrR, which mediates transcriptional repression of target genes.