Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines

Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS

Talking about sex after traumatic brain injury: perceptions and experiences of multidisciplinary rehabilitation professionals

Purpose: Research indicates that although 50–60% of people who have had a traumatic brain injury (TBI) experience changes in sexual functioning, sexuality issues remain largely unaddressed in rehabilitation. This study aimed to explore rehabilitation professionals’ perceptions and experiences of discussing sexuality with service-users who have had a TBI. Method: Purposeful sampling was used to recruit 24 participants from two local National Health Service trusts and from a national charity. Four focus groups were conducted with pre-existing groups of professionals, using a semi-structured interview schedule. Focus group data were transcribed verbatim and analysed using thematic analysis. Results: Six main themes were derived from the analysis: (1) sexuality after TBI is a specialist issue; (2) sexuality is a sensitive subject; (3) practicalities of discussing sexuality; (4) roles and responsibilities; (5) dilemmas about risk and vulnerabilities; and (6) organisational and structural issues. Conclusions: Our findings suggest that a more proactive approach to addressing sexuality issues be taken by incorporating sexuality into assessments and by having sexuality information available for service-users. Support for professionals is also needed in the form of the development of policy, on-going training and supervision

Disentangling the pollen signal from fen systems : modern and Holocene studies from southern and eastern England

Thick deposits of peat derived from fen environments accumulated in the coastal lowland areas adjacent to the North Sea during the middle and late Holocene. These sediments are frequently used in pollen-based reconstructions of in situ and more distant vegetation. However, discriminating between wetland and dry land originating pollen signals, and between the potential fen communities present in the wetland, is complex. In this study, a suite of analytical approaches are used to explore the pollen signal of modern fen communities and compare them against Holocene pollen assemblages. At two sites in eastern England, Woodwalton Fen and Upton Broad, vegetation composition was recorded around a series of moss polster sampling points. The communities investigated included herbaceous fen communities under different cutting regimes, a grazed area, glades, and woodland with canopies dominated by Alnus glutinosa and Betula. Cluster analysis is used to provide an overview of, and compare the structure within, the datasets consisting of the vegetation, the vegetation converted to palynological equivalents, and the pollen data. It is demonstrated that any loss of taxonomic precision in pollen identifications does not pose particular problems when attempting to identify fen communities, including tall-herbaceous vegetation, in the pollen record. Indices of Association imply pollen presence can be interpreted as indicating the local presence for some taxa, though few of these are confined to a particular community. Herbaceous fen vegetation subject to different management regimes are, however, shown to produce distinctive pollen signatures. Middle and late Holocene pollen assemblages from eastern (Fenland) and southern (Romney Marsh) England, interpreted as derived from fen vegetation, are compared against the modern pollen dataset using ordination. Most of the fossil samples plot out within or adjacent to the groupings produced by the modern samples in the ordinations. While these investigations demonstrate that modern pollen work can help improve the interpretation of Holocene assemblages they also call attention to a number of limitations including the restricted range of communities from which modern samples are currently available and the potential for non-analogous modern vegetation. The paper concludes with ideas to aid the interpretation of pollen data collected from fen peats and suggestions for future work

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

BACKGROUND: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. METHODS AND FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. CONCLUSIONS: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis

Background: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension.Methods and findings:Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (9June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (97,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (9sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (91,478 patients), which assessed selfmonitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (9clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (9dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies.Conclusions: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (9including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.</p

Individual patient data meta-analysis of self-monitoring of blood pressure (BP-SMART): a protocol.

INTRODUCTION: Self-monitoring of blood pressure is effective in reducing blood pressure in hypertension. However previous meta-analyses have shown a considerable amount of heterogeneity between studies, only part of which can be accounted for by meta-regression. This may be due to differences in design, recruited populations, intervention components or results among patient subgroups. To further investigate these differences, an individual patient data (IPD) meta-analysis of self-monitoring of blood pressure will be performed. METHODS AND ANALYSIS: We will identify randomised trials that have compared patients with hypertension who are self-monitoring blood pressure with those who are not and invite trialists to provide IPD including clinic and/or ambulatory systolic and diastolic blood pressure at baseline and all follow-up points where both intervention and control groups were measured. Other data requested will include measurement methodology, length of follow-up, cointerventions, baseline demographic (age, gender) and psychosocial factors (deprivation, quality of life), setting, intensity of self-monitoring, self-monitored blood pressure, comorbidities, lifestyle factors (weight, smoking) and presence or not of antihypertensive treatment. Data on all available patients will be included in order to take an intention-to-treat approach. A two-stage procedure for IPD meta-analysis, stratified by trial and taking into account age, sex, diabetes and baseline systolic BP will be used. Exploratory subgroup analyses will further investigate non-linear relationships between the prespecified variables. Sensitivity analyses will assess the impact of trials which have and have not provided IPD. ETHICS AND DISSEMINATION: This study does not include identifiable data. Results will be disseminated in a peer-reviewed publication and by international conference presentations. CONCLUSIONS: IPD analysis should help the understanding of which self-monitoring interventions for which patient groups are most effective in the control of blood pressure

Self-monitoring of blood pressure in patients with hypertension related multi-morbidity: Systematic review and individual patient data meta-analysis

BACKGROUND Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (−3.12 mm Hg, [95% confidence intervals −4.78, −1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.</div

Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial

Background: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. Methods: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. Findings: Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. Interpretation: Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. Funding: UK Vaccine Task Force and National Institute for Health Research