Recruitment and retention of participants in UK surgical trials: survey of key issues reported by trial staff.

BACKGROUND: Recruitment and retention of participants in surgical trials is challenging. Knowledge of the most common and problematic issues will aid future trial design. This study aimed to identify trial staff perspectives on the main issues affecting participant recruitment and retention in UK surgical trials. METHODS: An online survey of UK surgical trial staff was performed. Respondents were asked whether or not they had experienced a range of recruitment and retention issues, and, if yes, how relatively problematic these were (no, mild, moderate or serious problem). RESULTS: The survey was completed by 155 respondents including 60 trial managers, 53 research nurses, 20 trial methodologists and 19 chief investigators. The three most common recruitment issues were: patients preferring one treatment over another (81·5 per cent of respondents); clinicians' time constraints (78·1 per cent); and clinicians preferring one treatment over another (76·8 per cent). Seven recruitment issues were rated moderate or serious problems by a majority of respondents, the most problematic being a lack of eligible patients (60·3 per cent). The three most common retention issues were: participants forgetting to return questionnaires (81·4 per cent); participants found to be ineligible for the trial (74·3 per cent); and long follow-up period (70·7 per cent). The most problematic retention issues, rated moderate or serious by the majority of respondents, were participants forgetting to return questionnaires (56·4 per cent) and insufficient research nurse time/funding (53·6 per cent). CONCLUSION: The survey identified a variety of common recruitment and retention issues, several of which were rated moderate or serious problems by the majority of participating UK surgical trial staff. Mitigation of these problems may help boost recruitment and retention in surgical trials.

ANTECEDENTES: El reclutamiento y la retención de participantes en los ensayos quirúrgicos es un desafío. Conocer los problemas más habituales y conflictivos ayudará al diseño de futuros ensayos. Este estudio tuvo como objetivo identificar la percepción de los participantes sobre cuáles son los principales problemas que afectan el reclutamiento y la retención de participantes en los ensayos quirúrgicos del Reino Unido. MÉTODOS: Encuesta electrónica a profesionales de la salud que habían participado en ensayos quirúrgicos del Reino Unido. Se preguntó a los encuestados si habían experimentado o no algún problema en temas de reclutamiento o retención y, en caso afirmativo, qué tan conflictivos fueron (ningún problema/problema leve/moderado/grave). RESULTADOS: Completaron la encuesta 155 participantes, de los que 60 eran directores del ensayo, 53 enfermeras de investigación, 20 metodólogos de ensayos y 19 investigadores principales. Los tres problemas más comunes en el reclutamiento fueron: pacientes que prefieren un tratamiento sobre otro (81,5% de los encuestados), escaso tiempo de dedicación de los médicos (78,1%) y médicos que prefieren un tratamiento sobre otro (76,8%). La mayoría de los encuestados calificaron siete problemas de reclutamiento como "moderados" o "graves", siendo el más conflictivo la falta de pacientes elegibles (60,3%). Los tres problemas de retención más habituales fueron: participantes que olvidaron devolver los cuestionarios (81,4%), participantes que no fueron elegibles para el ensayo (74,3%) y el largo período de seguimiento (70,7%). Los problemas de retención más conflictivos, calificados como "moderados" o "graves" por la mayoría de los encuestados, fueron el olvido de los participantes para devolver los cuestionarios (56,4%) y el escaso tiempo/financiación para la enfermera investigadora (53,6%). CONCLUSIÓN: La encuesta identificó una serie de problemas habituales en el reclutamiento y la retención de los pacientes, muchos ellos calificados como "moderados" o "graves" por la mayoría del personal involucrado en los ensayos quirúrgicos del Reino Unido. Mitigar estos problemas puede ayudar a impulsar el reclutamiento y la retención en los ensayos quirúrgicos.

Snapping Biceps Femoris: clinical demonstration and operative technique.

Snapping biceps femoris syndrome has been reported in the literature in a handful of case reports but not yet with a demonstration of clinical examination and intraoperative findings. We present an educational clinical video of snapping biceps femoris with intraoperative demonstration of findings and surgical repair.

Randomized feasibility trial of replacing or discarding the nail plate after nail-bed repair in children.

BACKGROUND: Nail-bed injuries are the most common hand injury in children. Surgical dogma is to replace the nail plate after repairing the nail bed. Recent evidence suggests this might increase infection rates and returns to clinic. The aim of this feasibility trial was to inform the design and conduct of a definitive trial comparing replacing or discarding the nail plate after nail-bed repair. METHODS: This study recruited participants from four hand units in the UK between April and July 2015. Participants were children under the age of 16 years with a nail-bed injury requiring surgery. They were randomized to either having the nail plate replaced or discarded after nail-bed repair. The follow-up method was also allocated randomly (postal versus clinic). Information was collected on complications at 2 weeks and 30 days, and on nail-plate appearance at 4 months using the Zook classification. Two possible approaches to follow-up were also piloted and compared. RESULTS: During the recruitment phase, there were 156 potentially eligible children. Sixty were randomized in just over 3 months using remote web-based allocation. By 2 weeks, there were two infections, both in children with replaced nail plates. The nail-replaced group also experienced more complications. There was no evidence of a difference in return rates between postal and clinic follow-up. CONCLUSION: Recruitment was rapid and nail-bed repair appeared to have low complication and infection rates in this pilot trial. The findings have led to revision of the definitive trial protocol, including the mode and timing of follow-up, and modification of the Zook classification.

Scarf osteotomy in the management of symptomatic adolescent hallux valgus.

PURPOSE: This study was designed to assess the utility of the scarf osteotomy in the management of symptomatic adolescent hallux valgus. MATERIALS AND METHODS: This is a case series of 29 patients (39 feet) with a mean follow up of 38.6 months (range 6-60 months). The mean age at the time of surgery was 14.1 years (range 10-17 years). American Orthopaedic Foot and Ankle Society (AOFAS) scores were collected at final follow up, along with a rating of the overall satisfaction. Any complications were recorded. Pre- and post-surgical radiographic angles were measured and analysed using the Student's t-test. The angles measured were the hallux valgus angle (HVA), the inter-metatarsal angle (IMA) and the distal metatarsal articular angle (DMAA). A second surgeon independently reviewed the angles in order to assess the inter-rater reliability using the Pearson product moment correlation. RESULTS: The mean AOFAS score at final follow up was 94.2 (range 54-100). Of all patients, 93 % were either satisfied or very satisfied with their final outcome. One patient has been listed for revision surgery after symptomatic recurrence at 3 years follow up. The pre-operative HVA, IMA and DMAA were 34.8°, 15.9° and 16.0°, respectively. The post-operative values were 16.3°, 8.8° and 9.2°, respectively (p < 0.001 for each). Pearson's r coefficient values demonstrated good inter-rater reliability of measurement. CONCLUSION: We have presented the results of the largest case series of scarf osteotomies for adolescent hallux valgus reported in the literature up to now, as far as we are aware. AOFAS scores at final follow up are comparable to the smaller studies previously reported and provide evidence that good outcomes and high levels of patient satisfaction can be achieved. Early follow up demonstrates a low level of symptomatic recurrence, but longer term data are still required.

Role of the juncturae tendinum in preventing radial subluxation of the extensor communis tendons after ulnar sagittal band rupture: a cadaveric study.

Background. Radial subluxation of the extensor communis tendons at the metacarpophalangeal (MCP) joints is a rarely reportedvinjury. These injuries have proved difficult to reproduce in cadaveric studies and have a low biomechanical likelihood of occurrence due to the ulnar direction of pull of the extensor communis tendons. It has been suggested that the juncturae tendinum may have a stabilising role, preventing radial subluxation after ulnar sagittal band rupture; however this has not been established. Methods. 40 cadaveric digits were dissected to reveal the extensor mechanism around the MCP joints. The ulnar sagittal bands were released and then the juncturae tendinum divided, in stages, before observing for radial subluxation or dislocation during finger flexion. Results. Radial subluxation of the extensor tendon was observed in only one digit after complete ulnar sagisttal band release. When all the fingers were flexed, after the juncturae tendinorum were divided, four additional tendons subluxed radially and a fifth tendon dislocated in this direction. When the digits were then flexed individually, there were eight unstable tendons in total. Conclusions. The juncturae tendinum appear to have a role in stabilising the extensor communis tendons at the MCP joints and preventing radial subluxation after ulnar sagittal band rupture.

Development of the vagal innervation of the gut: steering the wandering nerve.

BACKGROUND: The vagus nerve is the major neural connection between the gastrointestinal tract and the central nervous system. During fetal development, axons from the cell bodies of the nodose ganglia and the dorsal motor nucleus grow into the gut to find their enteric targets, providing the vagal sensory and motor innervations respectively. Vagal sensory and motor axons innervate selective targets, suggesting a role for guidance cues in the establishment of the normal pattern of enteric vagal innervation. PURPOSE: This review explores known molecular mechanisms that guide vagal innervation in the gastrointestinal tract. Guidance and growth factors, such as netrin-1 and its receptor, deleted in colorectal cancer, extracellular matrix molecules, such as laminin-111, and members of the neurotrophin family of molecules, such as brain-derived neurotrophic factor have been identified as mediating the guidance of vagal axons to the fetal mouse gut. In addition to increasing our understanding of the development of enteric innervation, studies of vagal development may also reveal clinically relevant insights into the underlying mechanisms of vago-vagal communication with the gastrointestinal tract.

Field deployment of thin film passive air samplers for persistent organic pollutants: a study in the urban atmospheric boundary layer.

This paper reports on the first field deployment of rapidly equilibrating thin-film passive air samplers under ambient conditions. The POlymer-coated Glass (POG) samplers have a coating of ethylene vinyl acetate (EVA) less than 1 microm thick applied to a glass surface. This can be dissolved off after exposure and prepared for the quantification of persistent organic pollutants (POPs) that have partitioned into the film during field exposure. In this study, POGs were deployed at various heights on the CN Tower in Toronto, Canada, to investigate the vertical distribution of selected compounds (PCBs, PAHs, organochlorine pesticides) in the atmospheric boundary layer of an urban area. The feasibility of the method to detect POPs from a few cubic meters of air was demonstrated, indicating the potential for rapid, low-volume sampling of air for ambient levels of POPs. PAH levels declined sharply with height, confirming ground-level emissions in urban areas as sources of these compounds; PCBs did the same, although less strongly. Different sampling events detected different vertical distributions of OC pesticides which could be related to local or distantsources, and variations in POPs on the samplers in these different events/heights demonstrate the dynamic nature of sources and atmospheric mixing of POPs.

Field calibration of rapidly equilibrating thin-film passive air samplers and their potential application for low-volume air sampling studies.

This paper reports on a field calibration and ambient deployment study with rapidly equilibrating thin-film passive air samplers. POlymer-coated Glass (POG) samplers have a coating of ethylene vinyl acetate (EVA) less than 1 microm thick coated on to glass, which can be dissolved off after exposure and prepared for quantification of persistent organic pollutants (POPs) that have partitioned into the film during field exposure. In this study, POGs were exposed for up to 18 d, in a study to assess compound uptake rates and their time to approach equilibrium. Results confirmed theoretical predictions, with time to equilibrium varying between a few hours to ca. 20 d for PCB-18 and PCB-138, respectively. Performance reference compounds and contaminated POGs were used to investigate depuration kinetics, confirming that lighter congeners behave extremely dynamically with substantial losses from the films over periods of a few hours. Repeated deployments of the samplers for different3-d periods yielded detectable levels of a range of PCB congeners, which had partitioned from as little as approximately 2 to 10 m3 air. This highlights the potential utility of POGs for extremely sensitive and dynamic passive air sampling in the future to help improve understanding of sources, environmental fate, and behavior of POPs. Recommendations are made for future improvements/refinements in POG sampling and handling procedures.

Atmospheric emissions of polybrominated diphenyl ethers and other persistent organic pollutants during a major anthropogenic combustion event.

Air samples were taken for the analysis of persistent organic pollutants before, during, and after the national U.K. "Bonfire Festival" in November 2000. As expected, ambient levels of polynuclear aromatic hydrocarbons (PAHs) increased sharply in response to the widespread diffusive combustion processes that occurred at the time. Polybrominated diphenyl ethers (PBDEs) also increased at the suburban sampling location, to a greater extent than the PAHs. The rise and fall in PBDE concentrations was rapid, coinciding closely with the PAH "combustion markers". These data provide evidence for a novel mechanism responsible for dissipation of PBDEs into the environment. It is hypothesized that products treated with the penta-BDE product--notably household furnishing foams and textiles--have been subject to (unsanctioned) burning on private bonfires; even if the majority of the PBDE burden of such products is debrominated/broken down in the fires, it is shown that only small amounts of the total "stock" of penta product need be emitted to generate the concentrations detected. The mixture of PBDEs in the air during the Bonfire Festival was enriched in higher brominated congeners (e.g., BDE-99, -153, and -154) compared to that in background air. Estimates are made of the masses of compound classes that may have been emitted to the atmosphere during the festival.

Pulverulent cataract with variably associated microcornea and iris coloboma in a MAF mutation family.

AIMS: To report the detailed clinical findings in a three generation pedigree with autosomal dominant cataract, microcornea, and coloboma resulting from mutation of the lens development gene, MAF. METHODS: Five members of a three generation pedigree with progressive cataracts underwent detailed ophthalmic examination to characterise associated ocular phenotypic features. RESULTS: The cataracts present in all affected individuals were cortical, and/or nuclear, pulverulent opacities. Corneal diameters of 10-10.25 mm were present in two family members. Axial lengths were in the normal range. Bilateral iris coloboma in the 6 o'clock position was present in one patient. Uveal melanoma was present in one patient, with uveal naevi in this and one other patient. CONCLUSION: The bZIP transcription factor MAF is a key lens development gene that regulates the expression of the crystallins. Individuals with a mutation in MAF may have pulverulent cataract alone or cataract in association with microcornea or iris coloboma.

Effect of a series of novel sulphonylthioureas on glucose tolerance in the obese fa/fa Zucker rat.

1. The recent development of a series of novel KATP channel modulators, namely sulphonylthioureas and sulphonylureas, is thought to make improvements in potency and tissue selectivity compared with current sulphonylureas, such as glibenclamide, which shares a similar structure to the novel compounds. 2. These novel compounds were first examined for their effect on hyperglycaemia and glucose tolerance during an oral glucose tolerance test following 5 days administration in the lean fa/- and obese fa/fa Zucker rat (a model of insulin resistance). Comparisons with present antidiabetic agents, metformin and glibenclamide were performed. 3. Several compounds showed improvements in glucose tolerance compared with control and the primary structural prerequisites for the maintenance of this activity were investigated. Of most interest was compound 3-15 ((N-[(4-methylphenylsulphonyl]-N'-(2-ethoxypyrid-4-yl)thiourea; 0.1 mg/kg per day), which significantly improved glucose tolerance following 5 days administration in the fa/fa Zucker rat. This paralleled the improvement seen in metformin (300 mg/kg per day)-treated fa/fa rats, but compound 3-15 was up to 3000-fold more potent than metformin. 4. Obese fa/fa Zucker rats were then treated with compound 3-15 for 28 days to determine whether glycaemic control could be maintained over the longer term. 5. Compound 3-15 showed a significant improvement in glucose clearance and reduction in insulin concentration following 28 days treatment during an intravenous glucose tolerance test compared with untreated rats, without any change in the rate of weight gain. 6. The novel sulphonylthiourea 3-15 appears to improve glucose clearance during acute and chronic treatment in the fa/fa Zucker rat with no effect on the rate of weight gain. It is thought that compound 3-15 may be eliciting its actions by improving insulin sensitivity, but its effects on insulin secretion are still to be elucidated.

Vacuolar H(+)-ATPase and weak base action in Dictyostelium.

Amoebae of Dictyostelium discoideum release ammonia during development, and the accumulation of this weak base is believed to be responsible for inhibiting fruiting-body formation and switching aggregates into migrating slugs. Exposure to weak bases can also inhibit aggregation and cell-type specific gene expression. The pathway by which weak bases influence development is not understood. We show here that the development of a set of mutants defective in acidification of intracellular acidic compartments is abnormally sensitive to inhibition by weak bases. Moreover even in the absence of added weak bases these mutants are delayed in aggregation and have a protracted migratory phase. The same behaviour is observed in transformants harbouring an antisense construct for one of the vacuolar H(+)-ATPase subunits. These results support the idea that weak bases exert their effects by inhibiting acidification of an intracellular acidic compartment.

Nucleotide sequence of Ddp1, a high copy number nuclear plasmid of Dictyostelium discoideum.

The complete nucleotide sequence of Ddp1, a high copy number 13.7-kbp endogenous nuclear plasmid of Dictyostelium discoideum is presented. Previous studies have shown nine transcripts which map to five different regions of Ddp1, suggesting alternative transcription initiation sites and/or post-transcriptional processing. The sequence presented here shows five long open reading frames corresponding to previously known transcribed regions, as well as an additional reading frame, in the region of the presumed origin of replication. Two of the predicted proteins from the Ddp1 reading frames have potential leader sequences and transmembrane domains, while the rest, if translated, would encode soluble proteins. One of these has both leucine zipper and zinc finger-like motifs. Sequences upstream of the reading frames show strong similarities to chromosomal promoter elements, suggesting that transcription of at least some of the plasmid-encoded genes is regulated by factors which regulate chromosomal transcription in this organism. The region containing the presumptive origin of replication contains the promoters of the major growth-specific gene, as well as a second gene; thus, the processes of transcription and replication of Ddp1 may be intimately linked. The origin-encompassing region has a long homopurine/homopyrimidine stretch, which is similar to sequences shown in vitro to be capable of forming a triple helix structure through Hoogsteen base pairing. Possible roles for these sequences and the products of the ORFs in plasmid maintenance are discussed.