Managing nurse redeployment during the Covid-19 pandemic, lessons for future redeployment: A qualitative study.

BACKGROUND: The mass redeployment of nurses was critical across countries necessitated by the acute health impact of Covid-19. Knowledge was limited regarding how to manage nurse redeployment or the impact that redeployment might have. Redeployment continues, particularly in response to the current staffing crisis and surges such as winter pressures. This study aims to address these gaps in evidence to inform guidance on how best to manage nurse redeployment in practice. OBJECTIVES: First, to understand the processes and underpinning decisions made by managers when managing nurse redeployment prior to and during the Covid-19 pandemic. Second, to identify the lessons that can be learned to improve the management of on-going nurse redeployment. DESIGN: Qualitative study utilising semi-structured interviews and focus groups with nurse managers (ISRCTN: 18172749). SETTING(S): Three acute National Health Service (NHS) Trusts in England with geographical and ethnic diversity, and different Covid-19 contexts. PARTICIPANTS: Thirty-two nurse managers and four Human Resource advisors responsible for redeploying nurses or receiving and supporting redeployed nurses. METHODS: Participants took part in face-to-face or virtual semi-structured interviews from February 2021 to November 2021 and virtual focus groups from July to December 2021. Qualitative data were analysed using reflexive thematic analysis. RESULTS: Four themes were evident in the data, capturing four distinctive phases of the redeployment process. There was a fundamental mismatch between how different parts of the nursing and managerial workforce conceived of their decision-making responsibilities across different phases. This led to managers taking inconsistent and sometimes contradictory approaches when redeploying nurses, and a disconnect between nursing staff at all levels of the chain of command. Furthermore, in conjunction with limited guidance in operationalising redeployment and the distressing experiences vocalised by nurses, nurse managers found nurse redeployment logistically and emotionally challenging; and felt 'caught in the middle' of meeting both their managerial and mentoring responsibilities. This became increasingly challenging during subsequent phases of redeployment and remained challenging once the pandemic waned. CONCLUSIONS: The approach to nurse redeployment in response to the Covid-19 pandemic prioritised nurse staffing numbers over personal well-being. Key principles of good practice relating to nurse redeployment during the Covid-19 pandemic can be applied to improve future redeployment of nurses and support positive outcomes. Having a planned approach for staff redeployment during normal service delivery comprising operational guidance for those tasked with implementing redeployment, that is scalable in a crisis setting, would be beneficial for the nursing workforce.

Reboot coaching programme: a mixed-methods evaluation assessing resilience, confidence, burnout and depression in medical students.

BACKGROUND: Poor mental health in medical students is a global concern. Effective interventions are required, which are tailored towards the training-related stressors medical students experience. The Reboot coaching programme is an online, tailored intervention based on cognitive-behavioural principles. AIMS: To evaluate whether the Reboot coaching programme tailored for medical students was feasible and associated with improvements in mental health outcome indicators. METHODS: Medical students participated in two group online workshops and a one-to-one coaching call with a Reboot-trained licensed psychological therapist. Participants provided data at: baseline (T1), post-workshops (T2), post-coaching call (T3) and 4-month follow-up (T4). Outcome measures included resilience, confidence, burnout and depression. Feedback was provided regarding the workshops at T2. RESULTS: 115 participants (93/80.9% women; mage = 23.9; SD = 2.8) were recruited, 83 (72.2%) completed all intervention elements and 82 (71.3%) provided T4 data, surpassing recruitment and retention targets. There were significant improvements following baseline in resilience (ps < .001), confidence (ps < .001), burnout (ps < .001) and depression (ps ≤ .001). Most participants agreed the workshops imparted useful skills (n = 92; 99%) and would recommend Reboot to others (n = 89; 95.6%). CONCLUSIONS: Existing interventions have produced mixed results regarding their effectiveness in improving medical students' mental health. Reboot is a feasible intervention in this group which is associated with improvements in resilience, confidence, burnout and depression. Further controlled studies of Reboot are now needed.

Evaluation of the reboot coaching workshops among urology trainees: A mixed method approach.

Background: Urology trainees experience high burnout, and there is an urgent need for acceptable and effective interventions. The current study evaluated Reboot coaching workshops (Reboot-C), a tailored intervention based on cognitive-behavioural principles, with urology trainees. Objective: Our primary objective was to evaluate the acceptability of Reboot-C among urology trainees. In addition, this study aimed to investigate whether there were changes in confidence, resilience, depression and burnout levels. Materials and method: A single-arm design was used, including pre- and post-online questionnaires and semi-structured interviews. Result: Twenty-one urology trainees replied to the survey, attended both Reboot-C workshops and responded to the post-intervention questionnaire. Thirteen of 21 (61%) urology trainees participated in the interview. Participating in Reboot-C was associated with significant improvements in resilience and confidence and a significant reduction in burnout. However, there was no significant reduction in depression. Qualitative data indicated that Reboot was acceptable and helped participants develop useful skills. Conclusion: These findings pave the way for more conclusive studies on the efficacy of Reboot-C for surgeons.

Critical care nursing workforce in crisis: A discussion paper examining contributing factors, the impact of the COVID-19 pandemic and potential solutions.

AIMS AND OBJECTIVES: The critical care nursing workforce is in crisis, with one-third of critical care nurses worldwide intending to leave their roles. This paper aimed to examine the problem from a wellbeing perspective, offering implications for research, and potential solutions for organisations. DESIGN: Discursive/Position paper. METHOD: The discussion is based on the nursing and wellbeing literature. It is guided by the authors' collaborative expertise as both clinicians and researchers. Data were drawn from nursing and wellbeing peer-reviewed literature, such as reviews and empirical studies, national surveys and government and thinktank publications/reports. RESULTS: Critical care nurses have been disproportionately affected by the COVID-19 pandemic with studies consistently showing critical care nurses to have the worst psychological outcomes on wellbeing measures, including depression, burnout and post-traumatic stress disorder (PTSD). These findings are not only concerning for the mental wellbeing of critical care nurses, they also raise significant issues for healthcare systems/organisations: poor wellbeing, increased burnout and PTSD are directly linked with critical care nurses intending to leave the profession. Thus, the wellbeing of critical care nurses must urgently be supported. Resilience has been identified as a protective mechanism against the development of PTSD and burnout, thus offering evidence-based interventions that address resilience and turnover have much to offer in tackling the workforce crisis. However, turnover data must be collected by studies evaluating resilience interventions, to further support their evidence base. Organisations cannot solely rely on the efficacy of these interventions to address their workforce crisis but must concomitantly engage in organisational change. CONCLUSIONS: We conclude that critical care nurses are in urgent need of preventative, evidence-based wellbeing interventions, and make suggestions for research and practice.

Patient and Family Involvement in Serious Incident Investigations From the Perspectives of Key Stakeholders: A Review of the Qualitative Evidence.

OBJECTIVES: Investigations of healthcare harm often overlook the valuable insights of patients and families. Our review aimed to explore the perspectives of key stakeholders when patients and families were involved in serious incident investigations. METHODS: The authors searched three databases (Medline, PsycInfo, and CINAHL) and Connected Papers software for qualitative studies in which patients and families were involved in serious incident investigations until no new articles were found. RESULTS: Twenty-seven papers were eligible. The perspectives of patients and families, healthcare professionals, nonclinical staff, and legal staff were sought across acute, mental health and maternity settings. Most patients and families valued being involved; however, it was important that investigations were flexible and sensitive to both clinical and emotional aspects of care to avoid compounding harm. This included the following: early active listening with empathy for trauma, sincere and timely apology, fostering trust and transparency, making realistic timelines clear, and establishing effective nonadversarial communication. Most staff perceived that patient and family involvement could improve investigation quality, promote an open culture, and help ensure future safety. However, it was made difficult when multidisciplinary input was absent, workload and staff turnover were high, training and support needs were unmet, and fears surrounded litigation. Potential solutions included enhancing the clarity of roles and responsibilities, adequately training staff, and providing long and short-term support to stakeholders. CONCLUSIONS: Our review provides insights to ensure patient and family involvement in serious incident investigations considers both clinical and emotional aspects of care, is meaningful for all key stakeholders, and avoids compounding harm. However, significant gaps in the literature remain.

Multiple meanings of resilience: Health professionals' experiences of a dual element training intervention designed to help them prepare for coping with error.

RATIONALE, AIMS AND OBJECTIVES: Consistent data demonstrates negative psychological effects of caregiving on front-line health professionals. Evidence that psychological resilience factors can help minimize distress and the potential for low-cost interventions have created interest in resilience-based development programmes; yet evidence of perceived value amongst health professionals is lacking. This study explored health professionals' experiences and perceptions of a novel, resilience-based intervention designed to pro-actively prepare staff for coping with error; to investigate their perceptions of what resilience meant to them, the relevance of the intervention, and impact of participation on ability to cope with error. METHODS: Semi-structured interviews 4-6 weeks post intervention with 23 randomly selected participants from seven cohorts (midwives, paediatricians, obstetricians/gynaecologists, paramedics) and trainees (physician associates, mammographers, sonographers). Thematic analysis of interview data. FINDINGS: Participants reported various interpretations of, and a shift in perception regarding what the concept of psychological resilience meant to them and their practice. These included for example, resilience as a positive or negative concept and their awareness and response to a range of personal, organizational and system factors influencing personal resilience. They valued the prophylactic, clinically relevant, interactive and applied nature of the intervention; having developed and applied valuable skills beyond the context of involvement in error, noting that individuals needed to be willing to explore their own coping mechanisms and human fallibility to gain maximum benefit. There was also consensus that whilst proactively developing individual level psychological resilience is important, so too is addressing the organizational and system factors that affect staff resilience which are outside individual staff control. CONCLUSION: Enhancing resilience appears to be considered useful in supporting staff to prepare for coping with error and the wider emotional burden of clinical work, but such interventions require integration into wider system approaches to reduce the burden of clinical work for health professionals.

Association between age at first reported e-cigarette use and subsequent regular e-cigarette, ever cigarette and regular cigarette use.

BACKGROUND AND AIMS: Association of electronic cigarette use and subsequent smoking has received considerable attention, although age of first use has not. This study tested differences in regular (e-cigarettes, cigarettes) and ever (cigarettes) use between e-cigarette user groups: early versus never users, late versus never users, early versus late users and effects of controlling for covariates. DESIGN: Prospective study with 12- and 24-month follow-up of e-cigarette/cigarette ever/regular use with data from an intervention. SETTING: Forty-five schools in England (Staffordshire and Yorkshire). PARTICIPANTS: Never smokers (3289 13-14-year-olds) who were part of a cluster randomized controlled trial. MEASUREMENTS: The sample was divided into groups of e-cigarette users: early users (at 13-14 years), late users (at 14-15 years) and never users (at 13-14 and 14-15 years). Dependent variables were self-reported regular e-cigarette and cigarette use and ever cigarette use at 15-16 years. Covariates were assessed. FINDINGS: Early and late users compared with never users were significantly more likely to be regular e-cigarette users [early: odds ratio (OR) = 9.42, 95% confidence interval (CI) = 5.38, 16.49, P < 0.001; late: OR = 6.89, 95% CI = 4.11, 11.54, P < 0.001], ever cigarette users (early: OR = 7.96, 95% CI = 6.02, 10.53, P < 0.001; late: OR = 5.13, 95% CI = 3.85, 6.84, P < 0.001) and regular cigarette users (early: OR = 7.80, 95% CI = 3.99, 15.27, P < 0.001; late: OR = 4.34, 95% CI = 1.93, 9.77, P < 0.001) at age 15-16 years. Late users compared with early users had significantly lower rates of ever use of cigarettes at 15-16 years (OR = 0.48, 95% CI = 0.35, 0.66, P < 0.001), although this difference was non-significant at 12 months after first use of e-cigarettes (OR = 0.89, 95% CI = 0.64, 1.25, P = 0.498). Controlling for covariates did not change the findings. CONCLUSIONS: Adolescents in England who report using e-cigarettes at age 13-14 years have higher rates of subsequently initiating cigarette use than adolescents who report using e-cigarettes at age 14-15 years, a difference that may be attributable to a longer period of time to initiate cigarette use in former group.

Can we prepare healthcare professionals and students for involvement in stressful healthcare events? A mixed-methods evaluation of a resilience training intervention.

BACKGROUND: Healthcare professionals are experiencing unprecedented levels of occupational stress and burnout. Higher stress and burnout in health professionals is linked with the delivery of poorer quality, less safe patient care across healthcare settings. In order to understand how we can better support healthcare professionals in the workplace, this study evaluated a tailored resilience coaching intervention comprising a workshop and one-to-one coaching session addressing the intrinsic challenges of healthcare work in health professionals and students. METHODS: The evaluation used an uncontrolled before-and-after design with four data-collection time points: baseline (T1); after the workshop (T2); after the coaching session (T3) and four-to-six weeks post-baseline (T4). Quantitative outcome measures were Confidence in Coping with Adverse Events ('Confidence'), a Knowledge assessment ('Knowledge') and Resilience. At T4, qualitative interviews were also conducted with a subset of participants exploring participant experiences and perceptions of the intervention. RESULTS: We recruited 66 participants, retaining 62 (93.9%) at T2, 47 (71.2%) at T3, and 33 (50%) at T4. Compared with baseline, Confidence was significantly higher post-intervention: T2 (unadj. ß = 2.43, 95% CI 2.08-2.79, d = 1.55, p < .001), T3 (unadj. ß = 2.81, 95% CI 2.42-3.21, d = 1.71, p < .001) and T4 (unadj. ß = 2.75, 95% CI 2.31-3.19, d = 1.52, p < .001). Knowledge increased significantly post-intervention (T2 unadj. ß = 1.14, 95% CI 0.82-1.46, d = 0.86, p < .001). Compared with baseline, resilience was also higher post-intervention (T3 unadj. ß = 2.77, 95% CI 1.82-3.73, d = 0.90, p < .001 and T4 unadj. ß = 2.54, 95% CI 1.45-3.62, d = 0.65, p < .001). The qualitative findings identified four themes. The first addressed the 'tension between mandatory and voluntary delivery', suggesting that resilience is a mandatory skillset but it may not be effective to make the training a mandatory requirement. The second, the 'importance of experience and reference points for learning', suggested the intervention was more appropriate for qualified staff than students. The third suggested participants valued the 'peer learning and engagement' they gained in the interactive group workshop. The fourth, 'opportunities to tailor learning', suggested the coaching session was an opportunity to personalise the workshop material. CONCLUSIONS: We found preliminary evidence that the intervention was well received and effective, but further research using a randomised controlled design will be necessary to confirm this.

Evaluating a Strategy for Implementation and Sustainability of School-Based Health Centers in 3 Disparate Communities.

BACKGROUND: School-based health centers (SBHCs) increase access to health care and improve academic achievement for underserved students. We report on the test of a strategy to take SBHCs to scale by addressing the issues of community need and support and financial sustainability. METHODS: Using mixed methods, we collected data on student enrollment, utilization, health outcomes, seat time, patient revenues, surveys and key informant interviews from SBHCs located in 3 geographically and demographically different communities over a 2-year period. RESULTS: The 3 health centers were comparable in their capacity to implement their operations and achieve quality outcomes but varied considerably in their abilities to achieve sustainability after 2 years of operation. All participated in a planning phase and were able to achieve community buy in and support which impacted their implementation. Only one of the SBHCs which had the highest patient utilization was able to generate enough revenue from patient billings to become sustainable after the second year. CONCLUSION: Expanding SBHCs requires a period of planning to generate community buy in and support which is required for successful implementation. Sustainability requires sustained high clinic utilization and is enhanced by health centers that are able to receive high Medicaid reimbursements.

Evidence that an intervention weakens the relationship between adolescent electronic cigarette use and tobacco smoking: a 24-month prospective study.

BACKGROUND: The electronic cigarette (e-cigarette) use to subsequent smoking relationship in adolescents has received much attention. Whether an intervention to reduce smoking initiation attenuated this relationship was assessed. METHOD: Data were from 3994 adolescent never smokers (aged 13-14 years at baseline) as part of a cluster randomised controlled trial. Self-report measures of smoking, e-cigarette use and covariates were assessed and used to predict ever smoked cigarettes, any recent tobacco smoking and regularly smoked cigarettes at 24-month follow-up. RESULTS: Baseline ever use of e-cigarettes was associated with ever smoked cigarettes (OR=4.03, 95% CI 3.33 to 4.88; controlling for covariates, OR=2.78, 95% CI 2.20 to 3.51), any recent tobacco smoking (OR=3.38, 95% CI 2.72 to 4.21; controlling for covariates, OR=2.17, 95% CI 1.76 to 2.69) and regularly smoked cigarettes (OR=3.60, 95% CI 2.35 to 5.51; controlling for covariates, OR=1.27, 95% CI 1.17 to 1.39) at follow-up. For ever smoked cigarettes only, the impact of e-cigarette use was attenuated in the intervention (OR=1.83) compared with control (OR=4.53) condition. For ever smoked cigarettes and any recent tobacco smoking, the impact of e-cigarette use was attenuated among those with friends who smoked (OR=2.05 (ever smoked); 1·53 (any tobacco use)) compared with those without friends who smoked (OR=3.32 (ever smoked); 2·17 (any tobacco use)). CONCLUSIONS: This is one of the first studies to show that e-cigarette use was robustly associated with measures of smoking over 24 months and the first to show an intervention to attenuate the relationship. Further research with a broader age range of adolescents is required.

Patterns and predictors of e-cigarette, cigarette and dual use uptake in UK adolescents: evidence from a 24-month prospective study.

BACKGROUND AND AIMS: To assess prevalence and predictors of e-cigarettes/cigarettes patterns of use in adolescents in England. DESIGN: Prospective study with 24-month follow-up of e-cigarette/cigarette ever/regular use with data from an intervention evaluation. SETTING: Forty-five schools in England (Staffordshire and Yorkshire). PARTICIPANTS: A total of 3210 adolescents who, at baseline, were aged 13-14 years and had never used e-cigarettes/cigarettes. MEASUREMENTS: Based on e-cigarette/cigarette ever use at follow-up, six groups were created: (a) never user, (b) e-cigarette only, (c) cigarette only, (d) dual use-order of use unclear, (e) dual use-e-cigarettes used first and (f) dual use-cigarettes used first. Baseline measures were: gender, ethnicity, socio-economic status, impulsivity, family plus friend smoking and smoking-related beliefs (attitude and perceived behavioural control). FINDINGS: In groups (a) to (f), there were 71.5, 13.3, 3.3, 5.7, 2.9 and 3.4% adolescents, respectively. Among groups using cigarettes, regular smoking was more prevalent in group (f) (dual use-cigarettes used first) [17.6%, 95% confidence interval (CI) = 10.4, 24.8] than in groups (c), (d) and (e) combined (7.3%, 95% CI = 4.7, 9.9). Among groups using e-cigarettes, regular use was less prevalent in group (b) (e-cigarette only) (1.9%, 95% CI = 0.6, 3.2) than in groups (d), (e) and (f) combined (12.2%, 95% CI = 8.9, 15.5). Higher impulsivity plus friends and family smoking were predictive of being in groups (b) to (f) compared with group (a) (never users). Males were more likely to be in group (b) compared to group (a); females were more likely to be in groups (c) to (f) compared to group (a). CONCLUSIONS: Regular use of e-cigarettes/cigarettes varies across groups defined by ever use of e-cigarettes/cigarettes. Interventions targeted at tackling impulsivity or adolescents whose friends and family members smoke may represent fruitful avenues for future research.

Effectiveness and cost-effectiveness of repeated implementation intention formation on adolescent smoking initiation: A cluster randomized controlled trial.

OBJECTIVE: Forming implementation intentions (if-then plans) about how to refuse cigarette offers plus antismoking messages was tested for reducing adolescent smoking. METHOD: Cluster randomized controlled trial with schools randomized (1:1) to receive implementation intention intervention and messages targeting not smoking (intervention) or completing homework (control). Adolescents (11-12 years at baseline) formed implementation intentions and read messages on 8 occasions over 4 years meaning masking treatment allocation was not possible. Outcomes were: follow-up (48 months) ever smoking, any smoking in last 30 days, regular smoking, and breath carbon monoxide levels. Analyses excluded baseline ever smokers, controlled for clustering by schools and examined effects of controlling for demographic variables. Economic evaluation (incremental cost effectiveness ratio; ICER) was conducted. Trial is registered (ISRCTN27596806). RESULTS: Schools were randomly allocated (September-October 2012) to intervention (n = 25) or control (n = 23). At follow-up, among 6,155 baseline never smokers from 45 retained schools, ever smoking was significantly lower (RR = 0.83, 95% CI [0.71, 0.97], p = .016) in intervention (29.3%) compared with control (35.8%) and remained so controlling for demographics. Similar patterns observed for any smoking in last 30 days. Less consistent effects were observed for regular smoking and breath carbon monoxide levels. Economic analysis yielded an ICER of $134 per ever smoker avoided at age 15-16 years. CONCLUSIONS: This pragmatic trial supports the use of repeated implementation intentions about how to refuse the offer of a cigarette plus antismoking messages as an effective and cost-effective intervention to reduce smoking initiation in adolescents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Diagnostic Accuracy of Early Secretory Antigenic Target-6-Free Interferon-gamma Release Assay Compared to QuantiFERON-TB Gold In-tube.

BACKGROUND: Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6-containing vaccines. We aimed to qualify a recently developed ESAT-6-free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT). METHODS: Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes. RESULTS: ESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability. CONCLUSIONS: The novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.

The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: first-in-human trial.

Tuberculosis (TB) is the leading cause of infectious death worldwide. Development of improved TB vaccines that boost or replace BCG is a major global health goal. ID93 + GLA-SE is a fusion protein TB vaccine candidate combined with the Toll-like Receptor 4 agonist adjuvant, GLA-SE. We conducted a phase 1, randomized, double-blind, dose-escalation clinical trial to evaluate two dose levels of the ID93 antigen, administered intramuscularly alone or in combination with two dose levels of the GLA-SE adjuvant, in 60 BCG-naive, QuantiFERON-negative, healthy adults in the US (ClinicalTrials.gov identifier: NCT01599897). When administered as 3 injections, 28 days apart, all dose levels of ID93 alone and ID93 + GLA-SE demonstrated an acceptable safety profile. All regimens elicited vaccine-specific humoral and cellular responses. Compared with ID93 alone, vaccination with ID93 + GLA-SE elicited higher titers of ID93-specific antibodies, a preferential increase in IgG1 and IgG3 subclasses, and a multifaceted Fc-mediated effector function response. The addition of GLA-SE also enhanced the magnitude and polyfunctional cytokine profile of CD4+ T cells. The data demonstrate an acceptable safety profile and indicate that the GLA-SE adjuvant drives a functional humoral and T-helper 1 type cellular response.

Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination.

BACKGROUND: Recent Mycobacterium tuberculosis infection confers a predisposition to the development of tuberculosis disease, the leading killer among global infectious diseases. H4:IC31, a candidate subunit vaccine, has shown protection against tuberculosis disease in preclinical models, and observational studies have indicated that primary bacille Calmette-Guérin (BCG) vaccination may offer partial protection against infection. METHODS: In this phase 2 trial, we randomly assigned 990 adolescents in a high-risk setting who had undergone neonatal BCG vaccination to receive the H4:IC31 vaccine, BCG revaccination, or placebo. All the participants had negative results on testing for M. tuberculosis infection on the QuantiFERON-TB Gold In-tube assay (QFT) and for the human immunodeficiency virus. The primary outcomes were safety and acquisition of M. tuberculosis infection, as defined by initial conversion on QFT that was performed every 6 months during a 2-year period. Secondary outcomes were immunogenicity and sustained QFT conversion to a positive test without reversion to negative status at 3 months and 6 months after conversion. Estimates of vaccine efficacy are based on hazard ratios from Cox regression models and compare each vaccine with placebo. RESULTS: Both the BCG and H4:IC31 vaccines were immunogenic. QFT conversion occurred in 44 of 308 participants (14.3%) in the H4:IC31 group and in 41 of 312 participants (13.1%) in the BCG group, as compared with 49 of 310 participants (15.8%) in the placebo group; the rate of sustained conversion was 8.1% in the H4:IC31 group and 6.7% in the BCG group, as compared with 11.6% in the placebo group. Neither the H4:IC31 vaccine nor the BCG vaccine prevented initial QFT conversion, with efficacy point estimates of 9.4% (P=0.63) and 20.1% (P=0.29), respectively. However, the BCG vaccine reduced the rate of sustained QFT conversion, with an efficacy of 45.4% (P=0.03); the efficacy of the H4:IC31 vaccine was 30.5% (P=0.16). There were no clinically significant between-group differences in the rates of serious adverse events, although mild-to-moderate injection-site reactions were more common with BCG revaccination. CONCLUSIONS: In this trial, the rate of sustained QFT conversion, which may reflect sustained M. tuberculosis infection, was reduced by vaccination in a high-transmission setting. This finding may inform clinical development of new vaccine candidates. (Funded by Aeras and others; C-040-404 ClinicalTrials.gov number, NCT02075203 .).

Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial.

BACKGROUND: A vaccine that prevents pulmonary tuberculosis in adults is needed to halt transmission in endemic regions. This trial aimed to assess the safety and immunogenicity of three administrations at varying doses of antigen and adjuvant of an investigational vaccine (ID93 + GLA-SE) compared with placebo in previously BCG-vaccinated healthy adults in a tuberculosis endemic country. METHODS: In this randomised, double-blind, placebo-controlled phase 1 trial, we enrolled HIV-negative, previously BCG-vaccinated adults (aged 18-50 years), with no evidence of previous or current tuberculosis disease, from among community volunteers in the Worcester region of Western Cape, South Africa. Participants were randomly assigned to receive varying doses of ID93 + GLA-SE or saline placebo at day 0, day 28, and day 112. Enrolment into each cohort was sequential. Cohort 1 participants were Mycobacterium tuberculosis uninfected (as defined by negative QuantiFERON [QFT] status), and received 10 µg ID93 plus 2 µg GLA-SE, or placebo; in cohorts 2-4, QFT-negative or positive participants received escalating doses of vaccine or placebo. Cohort 2 received 2 µg ID93 plus 2 µg GLA-SE; cohort 3 received 10 µg ID93 plus 2 µg GLA-SE; and cohort 4 received 10 µg ID93 plus 5 µg GLA-SE. Dose cohort allocation was sequential; randomisation within a cohort was according to a randomly-generated sequence (3 to 1 in cohort 1, 5 to 1 in cohorts 2-4). The primary endpoint was safety of ID93 + GLA-SE as defined by solicited and unsolicited adverse events up to 28 days after each study injection and serious adverse events for the duration of the study. Specific immune responses were measured by intracellular cytokine staining, flow cytometry, and ELISA. All analyses were done according to intention to treat, with additional per-protocol analyses for immunogenicity outcomes. This trial is registered with ClinicalTrials.gov, number NCT01927159. FINDINGS: Between Aug 30, 2013, and Sept 4, 2014, 227 individuals consented to participate; 213 were screened (three participants were not included as study number was already met and 11 withdrew consent before screening occurred, mostly due to relocation or demands of employment). 66 healthy, HIV-negative adults were randomly allocated to receive the vaccine (n=54) or placebo (n=12). All study participants received day 0 and day 28 study injections; five participants did not receive an injection on day 112. ID93 + GLA-SE was well tolerated; no severe or serious vaccine-related adverse events were recorded. Vaccine dose did not affect frequency or severity of adverse events, but mild injection site adverse events and flu-like symptoms were common in M tuberculosis-infected participants compared with uninfected participants. Vaccination induced durable antigen-specific IgG and Th1 cellular responses, which peaked after two administrations. Vaccine dose did not affect magnitude, kinetics, or profile of antibody and cellular responses. Earlier boosting and greater T-cell differentiation and effector-like profiles were seen in M tuberculosis-infected than in uninfected vaccinees. INTERPRETATION: Escalating doses of ID93 + GLA-SE induced similar antigen-specific CD4-positive T cell and humoral responses, with an acceptable safety profile in BCG-immunised, M tuberculosis-infected individuals. The T-cell differentiation profiles in M tuberculosis-infected vaccinees suggest priming through natural infection. While cohort sample sizes in this phase 1 trial were small and results should be interpreted in context, these data support efficacy testing of two administrations of the lowest (2 µg) ID93 vaccine dose in tuberculosis endemic populations. FUNDING: Aeras and the Paul G Allen Family Foundation.

How Is Stress Reduced by a Workplace Mindfulness Intervention? A Qualitative Study Conceptualising Experiences of Change.

Mindfulness-based interventions are effective as curative and preventative approaches to psychological health. However, the mechanisms by which outcomes are secured from such interventions when delivered in the workplace, and to a stressed workforce, are not well understood. The aim of the present study was to elicit and analyse accounts from past participants of a workplace mindfulness intervention in order to generate a preliminary model of how positive benefits appear to be secured. In-depth, semi-structured interviews were completed with 21 employees of a higher education institution who had completed an eight-week intervention based on Mindfulness-Based Stress Reduction, adapted for the workplace. Interviews invited participants to recount their experiences of the intervention and its impact, if any, on their work life. Aspects of the interview data that pertained to intervention experience and positive benefits were analysed using a version of grounded theory, leading to the generation of a provisional model of how positive change occurred. The model suggests that discrete, temporal experiences build on each other to generate multiple, positive benefits. As anticipated in mindfulness-based interventions, enhanced attentional capacity was important, but our provisional model also suggests that resonance, self-care, detection of stress markers, perceiving choice, recovering self-agency and upward spiralling may be central mechanisms that lead to positive outcomes. Understanding mechanisms of change may help support participant engagement and trust in work-based mindfulness programmes, and enhance participants' ability to apply mindfulness in their work life.

Hemoglobin variants shape the distribution of malaria parasites in human populations and their transmission potential.

Hemoglobin variants C and S protect against severe malaria but their influence on parameters not directly linked to disease severity such as gametocyte carriage and infection chronicity is less well understood. To assess whether these infection-related phenotypes depend on the host hemoglobin genotype, we followed 500 Malian individuals over 1-2 years and determined their parasitological status during monthly visits and incidental clinical episodes. While adults heterozygous for hemoglobin S mutation were less often parasitemic compared to AA adults (odds ratio [OR] 0.50 95% confidence interval [CI] 0.31-0.79, P = 0.003), schoolchildren (but not toddlers or adults) with AC genotype carried parasites, including gametocytes, more often than their AA counterparts (OR 3.01 95% CI 1.38-6.57, P = 0.006). AC children were also likelier to be parasite-positive during the dry season, suggesting longer infections, and were more infectious in mosquito skin feeding assays than AA children. Notably, AC school-aged children, who comprise ~5% of the population, harbor a third of infections with patent gametocytes between May and August, when transmission transitions from very low to intense. These findings indicate that schoolchildren with hemoglobin C mutation might contribute disproportionately to the seasonal malaria resurgence in parts of West Africa where the HbC variant is common.

Do electronic cigarettes increase cigarette smoking in UK adolescents? Evidence from a 12-month prospective study.

BACKGROUND: In cross-sectional surveys, increasing numbers of adolescents report using both electronic cigarettes (e-cigarettes) and cigarettes. This study assessed whether adolescent e-cigarette use was associated prospectively with initiation or escalation of cigarette use. METHODS: Data were from 2836 adolescents (aged 13-14 years at baseline) in 20 schools in England. At baseline, breath carbon monoxide levels, self-reported e-cigarette and cigarette use, sex, age, friends and family smoking, beliefs about cigarette use and percentage receiving free school meals (measure of socioeconomic status) were assessed. At 12-month follow-up, self-reported cigarette use was assessed and validated by breath carbon monoxide levels. RESULTS: At baseline, 34.2% of adolescents reported ever using e-cigarettes (16.0% used only e-cigarettes). Baseline ever use of e-cigarettes was strongly associated with subsequent initiation (n=1726; OR 5.38, 95% CI 4.02 to 7.22; controlling for covariates, OR 4.06, 95% CI 2.94 to 5.60) and escalation (n=318; OR 1.91, 95% CI 1.14 to 3.21; controlling for covariates, this effect became non-significant, OR 1.39, 95% CI 0.97 to 1.82) of cigarette use. CONCLUSIONS: This is the first study to report prospective relationships between ever use of e-cigarettes and initiation and escalation of cigarette use among UK adolescents. Ever use of e-cigarettes was robustly associated with initiation but more modestly related to escalation of cigarette use. Further research with longer follow-up in a broader age range of adolescents is required.