Targeting BMI-1 in B cells restores effective humoral immune responses and controls chronic viral infection.

Ineffective antibody-mediated responses are a key characteristic of chronic viral infection. However, our understanding of the intrinsic mechanisms that drive this dysregulation are unclear. Here, we identify that targeting the epigenetic modifier BMI-1 in mice improves humoral responses to chronic lymphocytic choriomeningitis virus. BMI-1 was upregulated by germinal center B cells in chronic viral infection, correlating with changes to the accessible chromatin landscape, compared to acute infection. B cell-intrinsic deletion of Bmi1 accelerated viral clearance, reduced splenomegaly and restored splenic architecture. Deletion of Bmi1 restored c-Myc expression in B cells, concomitant with improved quality of antibody and coupled with reduced antibody-secreting cell numbers. Specifically, BMI-1-deficiency induced antibody with increased neutralizing capacity and enhanced antibody-dependent effector function. Using a small molecule inhibitor to murine BMI-1, we could deplete antibody-secreting cells and prohibit detrimental immune complex formation in vivo. This study defines BMI-1 as a crucial immune modifier that controls antibody-mediated responses in chronic infection.

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

B Cells Hit a Class Ceiling in the Germinal Center.

Class-switch recombination (CSR) provides diverse effector functions to B cells. In this issue of Immunity, Roco et al. (2019) refute long-standing dogma that germinal centers are the principal location for CSR; instead, CSR predominantly occurs early post immunization and declines during germinal center formation.

Pes cavovarus in Charcot-Marie-Tooth compared to the idiopathic cavovarus foot: A preliminary weightbearing CT analysis.

BACKGROUND: Pes cavovarus is a foot deformity that can be idiopathic (I-PC) or acquired secondary to other pathology. Charcot-Marie-Tooth disease (CMT) is the most common adult cause for acquired pes cavovarus deformity (CMT-PC). The foot morphology of these distinct patient groups has not been previously investigated. The aim of this study was to assess if morphological differences exist between CMT-PC, I-PC and normal feet (controls) using weightbearing computed tomography (WBCT). METHODS: A retrospective analysis of WBCT scans performed between May 2013 and June 2017 was undertaken. WBCT scans from 17 CMT-PC, 17 I-PC and 17 healthy normally-aligned control feet (age-, side-, sex- and body mass index-matched) identified from a prospectively collected database, were analysed. Eight 2-dimensional (2D) and three 3-dimensional (3D) measurements were undertaken for each foot and mean values in the three groups were compared using one-way ANOVA with the Bonferroni correction. RESULTS: Significant differences were observed between CMT-PC or I-PC and controls (p<0.05). Two-dimensional measurements were similar in CMT-PC and I-PC, except for forefoot arch angle (p=0.04). 3D measurements (foot and ankle offset, calcaneal offset and hindfoot alignment angle) demonstrated that CMT-PC exhibited more severe hindfoot varus malalignment than I-PC (p=0.03, 0.04 and 0.02 respectively). CONCLUSIONS: CMT-related cavovarus and idiopathic cavovarus feet are morphologically different from healthy feet, and CMT feet exhibit increased forefoot supination and hindfoot malalignment compared to idiopathic forms. The use of novel three-dimensional analysis may help highlight subtle structural differences in patients with similar foot morphology but aetiologically different pathology. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Dysregulation of humoral immunity in chronic infection.

Chronic viral infections disrupt the ability of the humoral immune response to produce neutralizing antibody or form effective immune memory, preventing viral clearance and making vaccine design difficult. Multiple components of the B-cell response are affected by pathogens that are not cleared from the host. Changes in the microenvironment shift production of B cells to short-lived plasma cells early in the response. Polyclonal B cells are recruited into both the plasma cell and germinal center compartments, inhibiting the formation of a targeted, high-affinity response. Finally, memory B cells shift toward an "atypical" phenotype, which may in turn result in changes to the functional properties of this population. While similar properties of B-cell dysregulation have been described across different types of persistent infections, key questions about the underlying mechanisms remain. This review will discuss the recent advances in this field, as well as highlight the critical questions about the interplay between viral load, microenvironment, the polyclonal response and atypical memory B cells that are yet to be answered. Design of new preventative treatments will rely on identifying the extrinsic and intrinsic modulators that push B cells toward an ineffective response, and thus identify new ways to guide them back onto the best path for clearance of virus and formation of effective immune memory.

Problem gambling among homeless clinic attenders.

OBJECTIVE: To examine the relationship between problem gambling and homelessness. METHOD: A consecutive sample of attenders at psychiatric clinics at three inner-city homeless hostels over 8.5 years. The demographic characteristics, comorbid conditions, pathway and pattern of homelessness of those identified to have problem gambling were compared with those who did not report problem gambling. RESULTS: A total of 2388 individuals were seen at the clinics in the 8 years of the study, of whom 289 (12.1%) reported problem gambling, mainly on poker machines. Those with problem gambling were more likely to be male, to have been married, employed for more than a year and to have a diagnosis of mood disorder. They were less likely to have a diagnosis of psychosis. However, the combination of psychosis and problem gambling was associated with the likelihood of having their financial affairs placed under the control of the Public Trustee. CONCLUSIONS: The findings suggest that earlier attention to problem gambling might reduce the likelihood of becoming homeless, as well as the need for routine enquiry about gambling behaviour, measures to reduce gambling, including expert counselling, restrictions on the availability of addictive forms of gambling and assisting vulnerable individuals with money management.

Intraobserver and interobserver reliability of cone beam weightbearing semi-automatic three-dimensional measurements in symptomatic pes cavovarus.

INTRODUCTION: Pes cavovarus is a three-dimensional (3D) foot deformity. New 3D semi-automatic measurements utilising weightbearing computerised topography (WBCT) images have recently been proposed to assess hindfoot alignment, but reliability in pes cavovarus has never been investigated. The aim of this study was to assess intraobserver and interobserver reliability of the foot ankle offset (FAO), calcaneal offset (CO) and hindfoot alignment angle (HAA) in pes cavovarus. METHODS: Anonymised WBCT datasets from 51 feet (17 Charcot-Marie-Tooth related cavovarus, 17 idiopathic cavovarus and 17 controls) were retrospectively reviewed. Three observers (two senior foot and ankle fellows and one orthopaedic resident) independently measured FAO, CO and HAA using dedicated software, with measurements repeated two weeks apart. Subgroup analysis was performed to assess whether aetiology or severity of varus deformity and level of seniority affected reliability. RESULTS: Mean values for intra and interobserver reliability for FAO (r=0.98; ICC: 0.99), CO (r=0.97; ICC: 0.98) and HAA measurements (r=0.97; ICC: 0.98) were excellent. Subgroup analyses showed that FAO, CO and HAA's intra (r/ρ range, 0.77-0.95) and interobserver (ICC range, 0.88-0.98) reliability remained excellent in patients with Charcot-Marie-Tooth related cavovarus, idiopathic pes cavovarus and normal feet, regardless of the severity of deformity. No difference was found in FAO, CO and HAA mean values from three observers (p>0.05 in all cases). DISCUSSION: This study demonstrates that 3D semi-automatic measurements of WBCT images have excellent intra and interobserver reliability in the assessment of hindfoot alignment in pes cavovarus. Aetiology and severity of deformity, and level of seniority do not affect reliability of these measurements. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Hepatitis C virus testing, liver disease assessment and direct-acting antiviral treatment uptake and outcomes in a service for people who are homeless in Sydney, Australia: The LiveRLife homelessness study.

People who are homeless have increased hepatitis C virus (HCV) infection risk, and are less likely to access primary healthcare. We aimed to evaluate HCV RNA prevalence, liver disease burden, linkage to care and treatment uptake and outcomes among people attending a homelessness service in Sydney. Participants were enrolled in an observational cohort study with recruitment at a homelessness service over eight liver health campaign days. Finger-stick whole-blood samples for Xpert® HCV Viral Load and venepuncture blood samples were collected. Participants completed a self-administered survey and received transient elastography and clinical assessment by a general practitioner or nurse. Clinical follow-up was recommended 2-12 weeks after enrolment. For participants initiating direct-acting antiviral (DAA) therapy, medical records were audited retrospectively and treatment outcome data were collected. Among 202 participants (mean age, 48 years), 82% were male (n = 165), 39% (n = 78) reported ever injecting drugs, of whom 63% (n = 49) injected in the previous month. Overall, 23% (n = 47) had detectable HCV RNA and 6% (n=12) had cirrhosis. HCV RNA prevalence among participants with either injecting or incarceration history was 35% (37/105), compared to 4% (3/73) among participants without these risk factors. Among those with detectable HCV RNA, 23 (49%) commenced therapy, of whom 65% (n = 15) achieved sustained virological response, while the remainder had no available treatment outcome. No participant had documented virological failure. HCV DAA treatment uptake among people attending a homelessness service was encouraging, but innovative models of HCV care are required to improve linkage to care and treatment uptake among this highly marginalized population.

Characteristics of people attending psychiatric clinics in inner Sydney homeless hostels.

OBJECTIVE: To describe the characteristics of people attending mental health clinics at shelters for the homeless in inner city Sydney. DESIGN: Retrospective review of medical records of homeless hostel clinic attenders. SETTING: Mental health clinics located in three inner city homeless hostels. PARTICIPANTS: Consecutive series of clinic attenders, 21 July 2008 - 31 December 2016. MAIN OUTCOME MEASURES: Demographic characteristics; social, medical and mental health histories of homeless people. RESULTS: 2388 individual patients were seen at the clinics during the 8.5-year study period. Their mean age was 42 years (standard deviation, 13 years), 93% were men, and 56% were receiving disability support pensions. 59% of attenders had been homeless for more than a year, and 34% of all attenders reported sleeping in the open. The most common diagnoses were substance use disorder (66%), psychotic illness (51%), acquired brain injury (14%), and intellectual disability (5%). Most patients had more than one diagnosis. Early life and recent trauma was reported by 42% of patients. Pathways to homelessness included release from prison (28% of the homeless), discharge from a psychiatric hospital (21%), loss of public housing tenancy (21%), and inability to pay rent because of problem gambling. CONCLUSIONS: The high rates of substance use and mental disorder among homeless people in inner Sydney confirms the need for increased access to treatment for these conditions in this setting. Homelessness among those with mental illness might be reduced by developing alternative housing models, and supporting people with multiple problems to retain tenancy.

Wrist denervation of the posterior interosseous nerve through a volar approach: a new technique with anatomical considerations.

PURPOSE: Full or selective wrist denervation is an effective treatment for chronic wrist pain. In this cadaveric study, a volar approach for prophylactic denervation of the posterior interosseous nerve (PIN) and the anterior interosseous nerve (AIN) was assessed, which can simultaneously be performed during volar approaches for distal radius fracture fixation or in combination with metalwork removal. MATERIALS AND METHODS: In total 40 adult upper limbs, embalmed using Thiel's method, were investigated. Group 1 included 20 limbs of which the distances between AIN and PIN to the ulnar margin of radius were measured at levels 6, 8 and 10 cm proximal to the styloid process and the distance radial styloid process to proximal border of pronator quadratus which might be useful as an intraoperative landmark. Subsequently further additional 20 adult limbs (group 2) were used. Transection of the PIN via this volar approach at the evaluated best level of step 1 was performed and evaluated by dissection via a dorsal approach. RESULTS: In group 1, the PIN runs within the interosseous membrane, from the ulnar border of the radius, 6.4 mm (SD 2.66) at 6 cm, 8.4 mm (SD 2.28) at 8 cm and 3.75 mm (SD 5.46) at 10 cm proximal to the radial styloid. The AIN runs within the interosseous membrane, from the ulna edge of the radius, 7.5 mm (SD 2.4) at 6 cm, 7.3 mm (SD 1.95) at 8 cm and 2.35 mm (3.42) at 10 cm proximal to the radial styloid. AIN and PIN were in close proximity at the 8-cm level which equals a 1-cm distance proximal to the pronator quadratus border. Group 2 showed a successful transection of the PIN through a single volar surgical approach in additional 18 out of 20 adult upper limbs. CONCLUSIONS: This study shows the local anatomy of the PIN, allowing denervation via a volar approach.

Results of a metabolic health clinic at a hostel for homeless men.

OBJECTIVES: People who are homeless have high mortality and morbidity, including from metabolic disorder. The aim of this study was to report on the characteristics and progress of the metabolic health of people attending a metabolic clinic at a homeless men's shelter. METHODS: Homeless men attending the clinic were assessed by measuring their weight, height, body mass index (BMI), waist circumference, blood pressure, blood lipids, fasting blood glucose and, if indicated, HbA1c. The sample characteristics of people who attended once (one-off clients) were compared to those who attended on more than one occasion (returning clients). Changes in health status were examined among returning clients by comparing baseline results to those at their last clinic visit. RESULTS: Baseline data were recorded on a total of 136 men, of whom 126 had a consultation with a general practitioner and at least one blood test. The 136 clients had a median BMI of 27.4 kg/m2. Forty-three were obese (BMI ≥30 kg/m2), 18 had class II obesity (BMI >35 kg/m2) and seven were underweight (BMI <20 kg/m2). Sixty-five had an intervention for either a newly diagnosed condition or a change to existing medical treatment. Seventy-six returning clients were seen on an average of 2.3 further occasions. Returning clients had significant improvements in measures of metabolic health. CONCLUSIONS: Homeless people in Sydney appear to be at a high risk of metabolic disease. The feasibility of a metabolic health clinic was demonstrated, and an encouraging improvement in some health indicators was found.

Developing, delivering and evaluating primary mental health care: the co-production of a new complex intervention.

BACKGROUND: Health services face the challenges created by complex problems, and so need complex intervention solutions. However they also experience ongoing difficulties in translating findings from research in this area in to quality improvement changes on the ground. BounceBack was a service development innovation project which sought to examine this issue through the implementation and evaluation in a primary care setting of a novel complex intervention. METHODS: The project was a collaboration between a local mental health charity, an academic unit, and GP practices. The aim was to translate the charity's model of care into practice-based evidence describing delivery and impact. Normalisation Process Theory (NPT) was used to support the implementation of the new model of primary mental health care into six GP practices. An integrated process evaluation evaluated the process and impact of care. RESULTS: Implementation quickly stalled as we identified problems with the described model of care when applied in a changing and variable primary care context. The team therefore switched to using the NPT framework to support the systematic identification and modification of the components of the complex intervention: including the core components that made it distinct (the consultation approach) and the variable components (organisational issues) that made it work in practice. The extra work significantly reduced the time available for outcome evaluation. However findings demonstrated moderately successful implementation of the model and a suggestion of hypothesised changes in outcomes. CONCLUSIONS: The BounceBack project demonstrates the development of a complex intervention from practice. It highlights the use of Normalisation Process Theory to support development, and not just implementation, of a complex intervention; and describes the use of the research process in the generation of practice-based evidence. Implications for future translational complex intervention research supporting practice change through scholarship are discussed.

A Robust Infinite Zirconium Phenolate Building Unit to Enhance the Chemical Stability of Zr MOFs.

A novel Zr-chain based MOF, namely MIL-163, was designed and successfully synthesized using a bis-1,2,3-trioxobenzene ligand. Endowed with large square-shaped channels of 12 Šwidth, it shows remarkable water uptake (ca. 0.6 cm(3) g(-1) at saturating vapor pressure) and a remarkable stability in simulated physiological media, where archetypical Zr carboxylate MOFs readily degrade.

Trust, openness and continuity of care influence acceptance of antibiotics for children with respiratory tract infections: a four country qualitative study.

BACKGROUND: Clinician-parent interaction and health system influences on parental acceptance of prescribing decisions for children with respiratory tract infections (RTIs) may be important determinants of antibiotic use. OBJECTIVE: To achieve a deeper understanding of parents' acceptance, or otherwise, of clinicians' antibiotic prescribing decisions for children with RTIs. METHODS: Qualitative interviews with parents of child patients who had recently consulted in primary care with a RTI in four European countries, with a five-stage analytic framework approach (familiarization, developing a thematic framework from interview questions and emerging themes, indexing, charting and interpretation). RESULTS: Fifty of 63 parents accepted clinicians' management decisions, irrespective of antibiotic prescription. There were no notable differences between networks. Parents ascribed their acceptance to a trusting and open clinician-patient relationship, enhanced through continuity of care, in which parents felt able to express their views. There was a lack of congruence about antibiotics between parents and clinicians in 13 instances, mostly when parents disagreed about clinicians' decision to prescribe (10 accounts) rather than objecting to withholding antibiotics (three accounts). All but one parent adhered to the prescribing decision, although some modified how the antibiotic was administered. CONCLUSIONS: Parents from contrasting countries indicated that continuity of care, open communication in consultations and clinician-patient trust was important in acceptance of management of RTI in their children and in motivating adherence. Interventions to promote appropriate antibiotic use in children should consider a focus on eliciting parents' perspectives and promoting and building on continuity of care within a trusting clinician-patient relationship.

Detection of Lymphocytic Choriomeningitis Virus-Specific Memory B Cells Using Antigen Tetramers.

Memory B cells are central to the establishment of immunological memory, providing long-term protection against specific pathogens and playing a vital role in the efficacy of vaccines. Understanding how memory B cell formation is disrupted during persistent infection is essential for new therapeutics. Lymphocytic choriomeningitis virus (LCMV) is an ideal model for investigating memory B cells in acute versus chronic infection. This protocol details techniques to isolate, enrich, and examine LCMV-specific memory B cells in both acute and chronic LCMV infection. Using an antigen tetramer enrichment system and flow cytometry, this method assesses low-frequency, polyclonal antigen-specific memory B cells.

What is different about living alone with cancer in older age? A qualitative study of experiences and preferences for care.

BACKGROUND: Increasing numbers of older patients with advanced cancer live alone but there is little research on how well health services meet their needs. The aim of this study was to compare the experiences and future preferences for care between two groups of older people with cancer in their last year of life; those who live alone, and those who live with co-resident carers. METHODS: In-depth qualitative interviews were conducted with 32 people aged between 70 and 95 years who were living with cancer. They were recruited from general practices and hospice day care, when the responsible health professional answered no to the question, of whether they would be surprised if the patient died within twelve months. Twenty participants lived alone. Interviews were recorded and transcribed and the data analysed using a Framework approach, focussing on the differences and commonalities between the two groups. RESULTS: Many experiences were common to all participants, but had broader consequences for people who lived alone. Five themes are presented from the data: a perception that it is a disadvantage to live alone as a patient, the importance of relational continuity with health professionals, informal appraisal of care, place of care and future plans. People who lived alone perceived emotional and practical barriers to accessing care, and many shared an anxiety that they would have to move into a care home. Participants were concerned with remaining life, and all who lived alone had made plans for death but not for dying. Uncertainty of timescales and a desire to wait until they knew that death was imminent were some of the reasons given for not planning for future care needs. CONCLUSIONS: Older people who live alone with cancer have emotional and practical concerns that are overlooked by their professional carers. Discussion and planning for the future, along with continuity in primary care may hold the key to enhancing end-of-life care for this group of patients.

Elevated BMI reduces the humoral response to SARS-CoV-2 infection.

Objective: Class III obesity (body mass index [BMI] ≥ 40 kg m-2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m-2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear. Methods: We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m-2. Results: Here, we show that an increased BMI (≥ 25 kg m-2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m-2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination. Conclusions: Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m-2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.

'The body gets used to them': patients' interpretations of antibiotic resistance and the implications for containment strategies.

BACKGROUND: Interventions promoting evidence based antibiotic prescribing and use frequently build on the concept of antibiotic resistance but patients and clinicians may not share the same assumptions about its meaning. OBJECTIVE: To explore patients' interpretations of 'antibiotic resistance' and to consider the implications for strategies to contain antibiotic resistance. DESIGN: Multi country qualitative interview study. PARTICIPANTS: One hundred and twenty-one adult patients from primary care research networks based in nine European countries who had recently consulted a primary care clinician with symptoms of Lower Respiratory Tract Infection (LRTI). APPROACH: Semi-structured interviews with patients following their consultation and subjected to a five-stage analytic framework approach (familiarization, developing a thematic framework from the interview questions and the themes emerging from the data, indexing, charting, and mapping to search for interpretations in the data), with local network facilitators commenting on preliminary reports. RESULTS: The dominant theme was antibiotic resistance as a property of a 'resistant human body', where the barrier to antibiotic effectiveness was individual loss of responsiveness. Less commonly, patients correctly conceptualized antibiotic resistance as a property of bacteria. Nevertheless, the over-use of antibiotics was a strong central concept in almost all patients' explanations, whether they viewed resistance as located in either the body or in bacteria. CONCLUSIONS: Most patients were aware of the link between antibiotic use and antibiotic resistance. The identification of the misinterpretation of antibiotic resistance as a property of the human body rather than bacterial cells could inform clearer clinician-patient discussions and public health interventions through emphasising the transferability of resistance, and the societal contribution individuals can make through more appropriate antibiotic prescribing and use.

Addressing smoking in sheltered homelessness with intensive smoking treatment (ASSIST project): A pilot feasibility study of varenicline, combination nicotine replacement therapy and motivational interviewing.

BACKGROUND: This pilot study aimed to test the feasibility of providing varenicline in combination with nicotine replacement therapy (NRT) and motivational interviewing (MI) to adult male smokers attending a clinic in a hostel for homeless people. METHODS: A single group pre- and post-treatment (12 weeks following intervention commencement) design with embedded process evaluation (at weekly counselling and fortnightly safety check-ins). Participants were 20 male smokers attending a health clinic within a homelessness service in Sydney, Australia, between December 2019 and March 2020. Participants set a target quit date 7-days post intervention commencement. Adverse events, self-reported abstinence, cigarettes per day, treatment adherence and acceptability of the study interventions were assessed 12 weeks post intervention commencement. Abstinence was biochemically verified. Results are complete cases. RESULTS: Retention was 65% at 12-weeks post-intervention commencement (n = 13). No related adverse events were reported. Three participants (15%) reported continuous abstinence. Two participants self-reported 30-day point prevalence abstinence (10%), confirmed by CO level. Participants who did not quit smoking (n = 10), reported a significant reduction in the number of cigarettes smoked per day (19.4 vs 4.7, p < .01). Cravings, withdrawal symptoms, and psychological distress significantly decreased from baseline to 12-week follow-up (all < 0.01). Adherence to the pharmacological interventions was good, most used combination NRT and varenicline. Adherence to the counselling sessions was low, attending three of 12 sessions. Both NRT and MI were rated as highly acceptable. Some participants expressed concerns about the safety of varenicline. CONCLUSIONS: The intervention was feasible and acceptable and associated with short-term smoking cessation and significant reductions in the number of cigarettes smoked-per-day.

Enhancing the health of NHS staff: eTHOS - protocol for a randomised controlled pilot trial of an employee health screening clinic for NHS staff to reduce absenteeism and presenteeism, compared with usual care.

BACKGROUND: Staff absenteeism and presenteeism incur high costs to the NHS and are associated with adverse health outcomes. The main causes are musculoskeletal complaints and mental ill-health, which are potentially modifiable, and cardiovascular risk factors are also common. We will test the feasibility of an RCT to evaluate the clinical and cost-effectiveness of an employee health screening clinic on reducing sickness absenteeism and presenteeism. METHODS: This is an individually randomised controlled pilot trial aiming to recruit 480 participants. All previously unscreened employees from four hospitals within three UK NHS hospital Trusts will be eligible. Those randomised to the intervention arm will be invited to attend an employee health screening clinic consisting of a screening assessment for musculoskeletal (STarT MSK and STarT Back), mental (PHQ-9 and GAD-7) and cardiovascular (NHS Health Check if aged ≥ 40, lifestyle check if < 40 years) health. Screen positives will be given advice and/or referral to recommended services. Those randomised to the control arm will receive usual care. Participants will complete a questionnaire at baseline and 26 weeks; anonymised absenteeism and staff demographics will also be collected from personnel records. The co-primary outcomes are as follows: recruitment, referrals and uptake of recommended services in the intervention arm. Secondary outcomes include the following: results of screening assessments, uptake of individual referrals, reported changes in health behaviours, acceptability and feasibility of intervention, indication of contamination and costs. Outcomes related to the definitive trial include self-reported and employee records of absenteeism with reasons. Process evaluation to inform a future trial includes interviews with participants, intervention delivery staff and service providers receiving referrals. Analyses will include presentation of descriptive statistics, framework analysis for qualitative data and costs and consequences presented for health economics. DISCUSSION: The study will provide data to inform the design of a definitive RCT which aims to find an effective and cost-effective method of reducing absenteeism and presenteeism amongst NHS staff. The feasibility study will test trial procedures, and process outcomes, including the success of strategies for including underserved groups, and provide information and data to help inform the design and sample size for a definitive trial. TRIAL REGISTRATION: ISRCTN reference number 10237475 .