Recruitment and retention interventions in surgical and wound care trials: A systematic review.

BACKGROUND: Recruitment and retention to surgical trials has previously been reported to be problematic, resulting in research waste. Surgery often results in wounds, meaning these trials are likely to have similar populations. There is currently no systematic assessment of effective strategies for these populations and hence, systematic assessment of these was deemed to be of importance. METHODS: A systematic review was conducted. Studies were eligible if they were randomised controlled trials undertaken to test an intervention to improve recruitment or retention within a surgical or wound based host randomised controlled trial. MEDLINE, EMBASE, Cochrane Library, ORRCA Database and the Northern Ireland Hub for Trials Methodology Research SWAT Repository Store were searched. Two independent reviewers screened the search results and extracted data for eligible studies using a piloted extraction form. A narrative synthesis was used due to a lack of heterogeneity between strategies which prevented meta-analysis. RESULTS: A total of 2133 records were identified which resulted in 13 ultimately being included in the review; seven on recruitment and six on retention. All included studies were based within surgical host trials. Four of the seven recruitment studies focussed on the provision of consent information to participants, one focussed on study set up and one on staff training, with only one relating to consent information finding any significant effect. A range of retention strategies were assessed by the included studies, however only two found (pen vs no pen, mailing strategies) found any significant effect. CONCLUSION: The included studies within a trial were all conducted within surgical trials. There was significant variation in strategies used, and limited replications and therefore further assessment may be warranted. Given the lack of studies embedded within wound care trials, further studies in this area are recommended. TRIAL REGISTRATION: PROSPERO (CRD42020205475).

Reverse shoulder arthroplasty versus hemiarthroplasty versus non-surgical treatment for older adults with acute 3- or 4-part fractures of the proximal humerus: study protocol for a randomised controlled trial (PROFHER-2: PROximal Fracture of Humerus Evaluation by Randomisation - Trial Number 2).

BACKGROUND: Proximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF. METHODS: Adults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms. DISCUSSION: The PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal. TRIAL REGISTRATION: ISRCTN76296703. Prospectively registered on 5th April 2018.

Interventions for improving the design and conduct of scientific research: A scoping review protocol.

Background: Research waste is prevalent in many scientific fields despite a number of initiatives to improve research practices. Interventions to improve practice are often implemented without evaluating their effectiveness. It is therefore important to identify the interventions that have been evaluated, assess how they have been evaluated and to identify areas where further research is required. Objectives: A scoping review will be undertaken to assess what interventions, aimed at researchers or research teams, to improve research design and conduct have been evaluated. This review will also consider when in the research pathway these interventions are implemented; what aspects of research design or conduct are being targeted; and who is implementing these interventions. Methods: Interventions which aim to improve the design or conduct of research will be eligible for inclusion. The review will not include interventions aimed at hypothetical research projects or interventions implemented without evaluation.The following sources will be searched: MEDLINE, EMBASE, ERIC, HMIC, EconLit, Social Policy and Practice, ProQuest theses, and MetaArXiv. Hand searching of references and citations of included studies will also be undertaken. Searches will be limited to articles published in the last 10 years.Data extraction will be completed using a data extraction template developed for this review. Results will be tabulated by type of intervention, research stage, and outcome. A narrative review will also be provided addressing each of the objectives.

It has been shown that due to the poor way in which some research is done the results either cannot be trusted or are not useful. Examples of this include: not publishing research that is completed so the results cannot be used by others; using outdated or unreliable research methods; measuring outcomes that are not useful in the real world or not important to patients; having too small a sample of participants in a study to get a reliable answer to the research question. This means that the money that has been spent on the research and the time that any participants have given to that research has been wasted. There have been a number of initiatives to try and stop this happening. It is important to evaluate these to test whether they actually work. Some initiatives that have been evaluated include: reminders to publish research once it is complete, providing researchers with tools for better research design and public recognition for good research practices. We intend to search for and summarise all the initiatives that have already been tested. To do this we will do a comprehensive search for all studies that have tested these initiatives. By doing this we will be able to see what further initiatives could be developed and how we can better test them.

Negative pressure wound therapy versus usual care for surgical wounds healing by secondary intention (SWHSI-2 trial): study protocol for a pragmatic, multicentre, cross surgical specialty, randomised controlled trial.

BACKGROUND: The majority of surgical wounds are closed (for example with sutures or staples) and so heal by primary intention. Where closure is not possible, or the wound subsequently breaks down, wounds may be left to heal from the bottom up (healing by secondary intention). Surgical wound healing by secondary intention (SWHSI) frequently presents a significant management challenge. Additional treatments are often required during the course of healing, and thus a significant financial burden is associated with treating these wounds. Increasingly, negative pressure wound therapy (NPWT) is used in the management of SWHSI. This wound dressing system provides a negative pressure (vacuum) to the wound, removing fluid into a canister, which is believed to be conducive to wound healing. Despite the increasing use of NPWT, there is limited robust evidence for the effectiveness of this device. A well-designed and conducted randomised controlled trial is now required to ascertain if NPWT is a clinically and cost-effective treatment for SWHSI. METHODS: SWHSI-2 is a pragmatic, multi-centre, cross surgical specialty, two arm, parallel group, randomised controlled superiority trial. Adult patients with a SWHSI will be randomised to receive either NPWT or usual care (no NPWT) and will be followed up for 12 months. The primary outcome will be time to healing (defined as full epithelial cover in absence of a scab) in number of days since randomisation. Secondary outcomes will include key clinical events (hospital admission or discharge, treatment status, reoperation, amputation, antibiotic use and death), wound infection, wound pain, health-related quality of life, health utility and resource use. DISCUSSION: Given the increasing use of NPWT, despite limited high-quality supporting evidence, the SWHSI-2 Trial will provide robust evidence on the clinical and cost-effectiveness of NPWT in the management of SWHSI. The SWHSI-2 Trial opened to recruitment in May 2019 and is currently recruiting across 20 participating centres. TRIAL REGISTRATION: ISRCTN 26277546 . Prospectively registered on 25 March 2019.

Systematic review assessing the evidence for the use of stem cells in fracture healing.

AIMS: Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing. METHODS: The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series. RESULTS: In all, 94 eligible studies were identified. The clinical and methodological aspects of the studies were too heterogeneous for a meta-analysis to be undertaken. A narrative synthesis examined study characteristics, stem cell methods (source, aspiration, concentration, and application) and outcomes. CONCLUSION: Insufficient high-quality evidence is available to determine the efficacy of stem cells for fracture healing. The studies were heterogeneous in population, methods, and outcomes. Work to address these issues and establish standards for future research should be undertaken.Cite this article: Bone Joint Open 2020;1-10:628-638.

An assessment of the extent to which the contents of PROSPERO records meet the systematic review protocol reporting items in PRISMA-P.

Background: PROSPERO is an international prospective register for systematic review protocols. Many of the registrations are the only available source of information about planned methods. This study investigated the extent to which records in PROSPERO contained the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Methods: A random sample of 439 single entry PROSPERO records of reviews of health interventions registered in 2018 was identified. Using a piloted list of 19 PRISMA-P items, divided into 63 elements, two researchers independently assessed the registration records. Where the information was present or not applicable to the review, a score of 1 was assigned. Overall scores were calculated and comparisons made by stage of review at registration, whether or not a meta-analysis was planned and whether or not funding/sponsorship was reported. Results: Some key methodological details, such as eligibility criteria, were relatively frequently reported, but much of the information recommended in PRISMA-P was not stated in PROSPERO registrations. Considering the 19 items, the mean score was 4.8 (SD 1.8; median 4; range 2-11) and across all the assessed records only 25% (2081/8227) of the items were scored as reported. Considering the 63 elements, the mean score was 33.4 (SD 5.8; median 33; range 18-47) and overall, 53% (14,469/27,279) of the elements were assessed as reported. Reporting was more frequent for items required in PROSPERO than optional items. The planned comparisons showed no meaningful differences between groups. Conclusions: PROSPERO provides reviewers with the opportunity to be transparent in their planned methods and demonstrate efforts to reduce bias. However, where the PROSPERO record is the only available source of a priori reporting, there is a significant shortfall in the items reported, compared to those recommended. This presents challenges in interpretation for those wishing to assess the validity of the final review.

Assessing the impact of retraction on the citation of randomized controlled trial reports: an interrupted time-series analysis.

OBJECTIVES: To assess the impact of retraction on the citation of randomized controlled trials. METHODS: We used an interrupted time-series with matched controls. PubMed, CINHAL, Google and the Retraction Watch Database were searched. We identified retracted publications reporting the results of randomized controlled trials involving human participants with two years of available data before and after retraction. We obtained monthly citation counts across all articles for the 24 months before and after retraction, from Web of Science. We used a Poisson segmented regression to detect changes in the level and trend of citation following retraction. We also undertook a matched control analysis of unretracted randomized controlled trials and a sensitivity analysis to account for cases of large-scale, well-advertised fraud. RESULTS: We identified 387 retracted randomized controlled trial reports, of which 218 (56.3%) were included in the interrupted time-series analysis. A reduction of 22.9% (95% CI 4.0% to 38.2%, p = 0.02) was observed in the number of citations in the month after retraction, and a further reduction of 1.9% (95% CI 0.4% to 3.5%, p = 0.02) per month in the following 24 months, relative to the expected trend. There was no evidence of a statistically significant reduction among the matched controls. Authors with a large number of retractions saw a 48.2% reduction at the time of retraction (95% CI 17.7% to 67.3%, p = 0.01). Other cases had a more gradual reduction with no change at the time of retraction and a 1.8% reduction per month in the following 24 months (95% CI 0.2% to 3.4%, p = 0.03). CONCLUSIONS: Retractions of randomized controlled trial reports can be effective in reducing citations. Other factors, such as the scale of the retractions and media attention, may play a role in the effectiveness of the reduction.

Fluence-induced reversal of saturable absorption in a ruthenium-based porphyrin.

Experimental nonlinear absorption data obtained using the open-aperture Z-scan technique are presented for 2, 3, 7, 8, 12, 17, 18-octaethyl-21H, 23H-porphine ruthenium (II) carbonyl in tetrahydrofuran. These data show saturation of nonlinear absorption dominating at low fluence but being overcome by induced absorption (reverse saturable absorption) at high fluence. Large-angle scattering measurements demonstrate that the induced absorption is real and not merely the result of scattering of light outside of the collection aperture of the detector by scattering centers induced at high fluence. A possible mechanism based on a four-band effective rate equation model is proposed. The model is used to accurately predict the results of Z scans taken at different pulse energies and to extract values for excited-state lifetimes and absorption cross sections from the experimental data.

Strong triplet excited-state absorption in a phenanthrolinyl iridium(III) complex with benzothiazolylfluorenyl-substituted ligands.

Femtosecond transient difference absorption (fs TA) measurements, together with a series of open-aperture Z scans at picosecond and nanosecond pulse widths and a variety of pulse energies, were performed on a 1,10-phenanthrolinyl iridium(III) complex bearing ligands containing a benzothiazolylfluorenyl motif. An analysis of decay data from the fs TA experiment yields a value of 1.24±0.26 ns for the singlet excited-state lifetime τ(S) of the complex. By fitting the Z scans to a five-level dynamic model incorporating the independently measured value of τ(S) and previously reported values of the complex's triplet quantum yield (0.13) and triplet excited-state lifetime (230 ns), we obtain values of 3.5×10(-17) cm(2) (singlet) and 5.0×10(-16) cm(2) (triplet) for the excited-state absorption cross-sections of the complex in toluene solution at 532 nm; the latter value represents one of the largest triplet excited-state absorption cross-sections ever reported at this wavelength. The ratio of the triplet excited-state cross-section to the ground-state absorption cross-section exceeds 3800.

Giant electro-optic effect in nanodisordered KTN crystals.

The electro-optic (EO) effect in nanodisordered potassium tantalate niobate (KTN) crystal is quantitatively investigated. It is found out that the EO coefficient of nanodisordered KTN crystal depends not only on the cooling temperature but also on the cooling rate. A larger EO coefficient can be obtained by employing a faster cooling rate. A Kerr EO efficient (s(11) - s(12) = 6.94 × 10(-14) m(2)/V(2)) is obtained at a cooling rate of 0.45 °C/s. The enhanced EO efficient by employing a faster cooling rate will be greatly beneficial for a variety of applications such as laser Q switches, laser pulse shaping, high-speed optical shutters, and modulating retroreflectors.

Kovacs effect enhanced broadband large field of view electro-optic modulators in nanodisordered KTN crystals.

The unique physical effect-Kovacs effect is explored to enhance the performance of EO modulators by employing the non-thermal equilibrium state nanodisordered KTN crystals created by super-cooling process, which can have a significant 3.5 fold increase in quadratic electro-optic coefficient. This enables to reduce the switching half wave voltage (almost by half) so that a broadband (~GHz range) and large field of view (+/-30 deg) electro-optic modulator can be realized with much lowered driving power, which can be very useful for a variety of applications: laser Q-switches, laser pulse shaping, high speed optical shutters and modulating retro reflectors.

Excited-state absorption of a bipyridyl platinum(II) complex with alkynyl-benzothiazolylfluorene units.

The singlet excited-state lifetime of a bipyridyl platinum(II) complex containing two alkynyl-benzothiazolylfluorene units was determined to be 145+/-105 ps by fitting femtosecond transient difference absorption data, and the triplet quantum yield was measured to be 0.14. A ground-state absorption cross section of 6.1 x 10(-19) cm(2) at 532 nm was deduced from UV-visible absorption data. Excited-state absorption cross sections of (6.7+/-0.1) x 10(-17) cm(2) (singlet) and (4.6+/-0.1) x 10(-16) cm(2) (triplet) were obtained by using a five-level dynamic model to fit open-aperture Z scans at picosecond and nanosecond pulse widths and a variety of pulse energies. For this complex, the ratio of the triplet excited-state absorption cross section to the ground-state absorption cross section--long used as a figure of merit for reverse saturable absorbers--thus stands at 754, to our knowledge the largest ever reported at 532 nm wavelength.

Photophysical properties of C60 colloids suspended in water with Triton X-100 surfactant: excited-state properties with femtosecond resolution.

We examine the photophysics of a colloidal suspension of C(60) particles in a micellar solution of Triton X-100 and water, prepared via a new synthesis which allows high-concentration suspensions. The particle sizes are characterized by transmission electron microscopy and dynamic light scattering and found to be somewhat polydisperse in the range of 10-100 nm. The suspension is characterized optically by UV-vis spectroscopy, femtosecond transient absorption spectroscopy, laser flash photolysis, and z-scan. The ground-state absorbance spectrum shows a broad absorbance feature centered near 450 nm which is indicative of colloidal C(60). The transient absorption dynamics, presented for the first time with femtosecond resolution, are very similar to that of thin films of C(60) and indicate a strong quenching of the singlet excited state on short time scales and evidence of little intersystem crossing to a triplet excited state. Laser flash photolysis reveals that a triplet excited-state absorption spectrum, which is essentially identical in shape to that of molecular C(60) solutions, does indeed arise, but with much lower magnitude and somewhat shorter lifetime. Z-scan analysis confirms that the optical response of this material is dominated by nonlinear scattering.

Excited-state absorption in a terpyridyl platinum(II) pentynyl complex.

The singlet excited-state lifetime of a terpyridyl platinum(II) pentynyl complex was determined to be 268+/-87 ps by fitting femtosecond transient absorption data, the triplet excited-state lifetime was found to be 62 ns by fitting nanosecond transient absorption decay data, and the triplet quantum yield was measured to be 0.16. A ground-state absorption cross section of 2.5 x 10(-19) cm(2) at 532 nm was deduced from UV-vis absorption data. Excited-state absorption cross sections of 3.5 x 10(-17) cm(2) (singlet) and 4.5 x 10(-17) cm(2) (triplet) were obtained by using a five-level dynamic model to fit open-aperture Z scans at picosecond and nanosecond pulse widths and a variety of pulse energies.