Benjamin R. Fletcher

Amphiphilic Surface Active Triblock Copolymers with Mixed Hydrophobic and Hydrophilic Side Chains for Tuned Marine Fouling-Release Properties

Two series of amphiphilic triblock surface active block copolymers (SABCs) were prepared through chemical modification of two polystyrene-block-poly(ethylene-ran-butylene)-block-polyisoprene ABC triblock copolymer precursors. The methyl ether of poly(ethylene glycol) [M(n) approximately 550 g/mol (PEG550)] and a semifluorinated alcohol (CF(3)(CF(2))(9)(CH(2))(10)OH) [F10H10] were attached at different molar ratios to impart both hydrophobic and hydrophilic groups to the isoprene segment. Coatings on glass slides consisting of a thin layer of the amphiphilic SABC deposited on a thicker layer of an ABA polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene thermoplastic elastomer were prepared for biofouling assays with algae. Dynamic water contact angle analysis, X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) measurements were utilized to characterize the surfaces. Clear differences in surface structure were realized as the composition of attached side chains was varied. In biofouling assays, the settlement (attachment) of zoospores of the green alga Ulva was higher for surfaces incorporating a large proportion of the hydrophobic F10H10 side chains, while surfaces with a large proportion of the PEG550 side chains inhibited settlement. The trend in attachment strength of sporelings (young plants) of Ulva did not show such an obvious pattern. However, amphiphilic SABCs incorporating a mixture of PEG550 and F10H10 side chains performed the best. The number of cells of the diatom Navicula attached after exposure to flow decreased as the content of PEG550 to F10H10 side chains increased.

Effect of background colour on growth and adhesion strength of Ulva sporelings

This study examined the effects of a range of black, grey and white substrata on the growth and attachment strength of Ulva sporelings on glass and polydimethylsiloxane (Silastic®-T2) surfaces. The rate of development of sporelings was strongly influenced by the colour of the substratum on which they grew. On black backgrounds, sporelings grew slowly and germination was delayed. Laboratory screening methods for antifouling and fouling-release coatings that rely on the growth of Ulva sporelings can be compromised if samples are of different colours. Hydrodynamic removal of sporelings from coatings may also be affected by substratum colour, since smaller plants generate lower hydrodynamic forces making them more difficult to remove.

Fatigue, psychological and cognitive impairment following transient ischaemic attack and minor stroke: a systematic review

Transient ischaemic attack (TIA) and minor stroke are characterized by short‐lasting symptoms; however, anecdotal and empirical evidence suggests that these patients experience ongoing cognitive/psychological impairment for which they are not routinely treated. The aims were (i) to investigate the prevalence and time course of fatigue, anxiety, depression, post‐traumatic stress disorder(PTSD) and cognitive impairment following TIA/minor stroke; (ii) to explore the impact on quality of life (QoL), change in emotions and return to work; and (iii) to identify where further research is required and potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the Cochrane libraries and the grey literature between January 1993 and April 2013 was undertaken. Literature was screened and data were extracted by two independent reviewers. Studies were included of adult TIA/minor stroke participants with any of the outcomes of interest: fatigue, anxiety, depression, PTSD, cognitive impairment, QoL, change in emotions and return to work. Random‐effects meta‐analysis pooled outcomes by measurement tool. Searches identified 5976 records, 289 were assessed for eligibility and 31 studies were included. Results suggest high levels of cognitive impairment and depression post‐TIA/minor stroke which decreased over time. However, frequencies varied between studies. Limited information was available on anxiety, PTSD and fatigue. Meta‐analysis revealed that the measurement tool administered influenced the prevalence of cognitive impairment: Mini‐Mental State Examination 17% [95% confidence interval (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that TIA/minor stroke patients may experience residual impairments; however, results should be interpreted with caution because of the few high quality studies. Notwithstanding, it is important to raise awareness of potential subtle but meaningful residual impairments.

Systematic review of the clinical effectiveness of wound-edge protection devices in reducing surgical site infection in patients undergoing open abdominal surgery

Objective:Assess the existing evidence on the clinical effectiveness of wound-edge protection devices (WEPDs) in reducing the surgical site infection (SSI) rate in patients undergoing open abdominal surgery. Background:Surgical site infections are a common postoperative complication associated with considerable morbidity, extended hospital stay, increased health care costs, and reduced quality of life. Wound-edge protection devices have been used in surgery to reduce SSI rates for more than 40 years; however, they are yet to be cited in major clinical guidelines addressing SSI management. Methods:A review protocol was prespecified. A variety of sources were searched in November 2010 for studies containing primary data on the use of WEPDs in reducing SSI compared with standard care in patients undergoing open abdominal surgery. The outcome of interest was a well-specified, clinically based definition of an SSI. No language or time restrictions were applied. The quality assessment of the studies and the quantitative analyses were performed in line with the principles of the Cochrane Collaboration. Results:Twelve studies reporting primary data from 1933 patients were included in the review. The quality assessment found all of them to be at considerable risk of bias. An exploratory meta-analysis was performed to provide a quantitative indication on the effect of WEPDs. The pooled risk ratio under a random effects model was 0.60 (95% confidence interval, 0.41–0.86), indicating a potentially significant benefit from the use of WEPDs. No indications of significant between-study heterogeneity or publication bias, respectively, were identified. Conclusions:Evidence to date suggests that WEPDs may be efficient in reducing SSI rates in patients undergoing open abdominal surgery. However, the poor quality of the existing studies and their small sample sizes raise the need for a large, good quality randomized controlled trial to validate this indication.

The views of stakeholders on the role of the primary school in preventing childhood obesity: a qualitative systematic review

Schools are increasingly recognized as an ideal setting for interventions to tackle childhood obesity. A better understanding of the views of key stakeholders would help to engage schools and inform the feasibility of such interventions in practice. This meta‐synthesis of 18 qualitative studies explores the views of parents, school staff, school governors, school nurses and students on the role of the primary school in preventing childhood obesity. Six categories emerged: ‘School as a key setting’; ‘What schools should be doing to promote healthy eating (HE)’; ‘What schools should be doing to promote physical activity (PA)’; ‘General barriers’; ‘Barriers to promoting HE at school’; and ‘Barriers to promoting PA at school’. Thirty‐seven finer‐level themes emerged within these categories. Stakeholders agreed on the key role of the primary school as a setting for obesity prevention, the importance of schools providing and promoting opportunities for HE and PA, and the need for schools to work with parents. Some perceived barriers could be overcome at school level, e.g. using unhealthy foods as rewards/fundraisers or withholding PA for bad behaviour. Leadership and guidance from government were considered to be needed to counteract other observed barriers, particularly regarding school canteens, support for parents and time for PA.

The Effect of Self-Monitoring of Blood Pressure on Medication Adherence and Lifestyle Factors: A Systematic Review and Meta-Analysis

BACKGROUND Self-monitoring of blood pressure (SMBP) can contribute to reduced blood pressure in people with hypertension. Potential mediators include increased medication, improved adherence, and changes in lifestyle factors including dietary change and increased physical activity. The objective of this review was to determine the effect of SMBP on medication adherence, medication persistence, and lifestyle factors in people with hypertension. METHODS Electronic bibliographic databases were searched through February 2014 to identify randomized controlled trials that compared SMBP to control/usual care in ambulatory hypertensive patients and reported medication or nonpharmacologic treatment adherence measures. RESULTS Twenty-eight trials with 7,021 participants fulfilled the inclusion criteria. Medication adherence was assessed in 25 trials (89%), dietary outcomes in 8 (29%), physical activity in 6 (21%), and medication persistence in 1 (4%). Blood pressure was assessed in 26 studies (93%). Follow-up ranged from 2 weeks to 12 months. Pooled results of 13 studies demonstrated a small but significant overall effect on medication adherence in favor of SMBP interventions (standardized mean difference 0.21, 95% CI 0.08, 0.34), with moderate heterogeneity (I2 = 43%). Standardized mean difference was used to express the size of intervention effect in each study relative to the variability observed, and was used to combine the results of studies where different measures of medication adherence were used. Where SMBP interventions had a significant effect on lifestyle factor change, the effect was unlikely to be clinically significant. Pooled results of 11 studies demonstrate a significant overall effect on diastolic blood pressure in favor of SMBP (weighted mean difference -2.02, 95% CI -2.93, -1.11), with low heterogeneity (I2 = 0%). A test for subgroup differences showed no difference when studies were grouped according to whether medication adherence was significantly improved or not. CONCLUSIONS SMBP may contribute to improvements in medication adherence in hypertensives. However, evidence for the effect of SMBP on lifestyle change and medication persistence is scarce, of poor quality, and suggests little clinically relevant benefit.

Systematic evaluation of the patient-reported outcome (PRO) content of clinical trial protocols

Background Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols. Methods and Findings We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the ‘Standard Protocol Items: Recommendations for Interventional Trials’ (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16–41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4–18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively ‘complete’ using SPIRIT were still likely to have omitted a large proportion of PRO checklist items. Conclusions The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully addressed by the current SPIRIT statement. We therefore advocate the development of consensus-based supplementary guidelines, aimed at improving the completeness and quality of PRO content in clinical trial protocols.

Stakeholder views on secondary findings in whole-genome and whole-exome sequencing: a systematic review of quantitative and qualitative studies.

Purpose:As whole-exome sequencing (WES) and whole-genome sequencing (WGS) move into routine clinical practice, it is timely to review data that might inform the debate regarding secondary findings (SF) and the development of policies that maximize participant benefit.Methods:We systematically searched for qualitative and quantitative studies that explored stakeholder views on SF in WES/WGS. Framework analysis was undertaken to identify major themes.Results:Forty-four articles reporting the views of 11,566 stakeholders were included. Stakeholders were broadly supportive of returning “actionable” findings, but definitions of actionability varied. Stakeholder views on SF disclosure exist along a spectrum: potential WES/WGS recipients’ views were largely influenced by a sense of rights, whereas views of genomics professionals were informed by a sense of professional responsibility. Experience with genetic illness and testing resulted in greater caution about SF, suggesting that truly informed decisions require an understanding of the implications and limitations of WES/WGS and possible findings.Conclusion:This review suggests that bidirectional interaction during consent might best facilitate informed decision making about SF and that dynamic forms of consent, allowing for changing preferences, should be considered. Research exploring views from wider perspectives and from recipients who have received SF is critical if evidence-based policies are to be achieved.Genet Med 19 3, 283–293.

Centre selection for clinical trials and the generalisability of results: a mixed methods study.

Background The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. Methods and Findings Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists’ views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. Conclusions Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize ‘generalisability’ and incorporate it at the design stage of RCTs so that results are readily transferable to ‘real world’ practice.

Self-monitoring blood pressure in hypertension, patient and provider perspectives: A systematic review and thematic synthesis.

OBJECTIVE To systematically review the qualitative evidence for patient and clinician perspectives on self-measurement of blood pressure (SMBP) in the management of hypertension focussing on: how SMBP was discussed in consultations; the motivation for patients to start self-monitoring; how both patients and clinicians used SMBP to promote behaviour change; perceived barriers and facilitators to SMBP use by patients and clinicians. METHODS Medline, Embase, PsycINFO, Cinahl, Web of Science, SocAbs were searched for empirical qualitative studies that met the review objectives. Reporting of included studies was assessed using the COREQ framework. All relevant data from results/findings sections of included reports were extracted, coded inductively using thematic analysis, and overarching themes across studies were abstracted. RESULTS Twelve studies were included in the synthesis involving 358 patients and 91 clinicians. Three major themes are presented: interpretation, attribution and action; convenience and reassurance v anxiety and uncertainty; and patient autonomy and empowerment improve patient-clinician alliance. CONCLUSIONS SMBP was successful facilitating the interaction in consultations about hypertension, bridging a potential gap in the traditional patient-clinician relationship. PRACTICE IMPLICATIONS Uncertainty could be reduced by providing information specifically about how to interpret SMBP, what variation is acceptable, adjustment for home-clinic difference, and for patients what they should be concerned about and how to act.