A proposed methodology for uncertainty extraction and verification in priority setting partnerships with the James Lind Alliance: an example from the Common Conditions Affecting the Hand and Wrist Priority Setting Partnership.

BACKGROUND: To report our recommended methodology for extracting and then confirming research uncertainties - areas where research has failed to answer a research question - derived from previously published literature during a broad scope Priority Setting Partnership (PSP) with the James Lind Alliance (JLA). METHODS: This process was completed in the UK as part of the PSP for "Common Conditions Affecting the Hand and Wrist", comprising of health professionals, patients and carers and reports the data (uncertainty) extraction phase of this. The PSP followed the robust methodology dictated by the JLA and sought to identify knowledge gaps, termed "uncertainties" by the JLA. Published Cochrane Systematic Reviews, Guidelines and Protocols, NICE (National Institute for Health and Care Excellence) Guidelines, and SIGN (Scottish Intercollegiate Guidelines Network) Guidelines were screened for documented "uncertainties". A robust method of screening, internally verifying and then checking uncertainties was adopted. This included independent screening and data extraction by multiple researchers and use of a PRISMA flowchart, alongside steering group consensus processes. Selection of research uncertainties was guided by the scope of the Common Conditions Affecting the Hand and Wrist PSP which focused on "common" hand conditions routinely treated by hand specialists, including hand surgeons and hand therapists limited to identifying questions concerning the results of intervention, and not the basic science or epidemiology behind disease. RESULTS: Of the 2358 records identified (after removal of duplicates) which entered the screening process, 186 records were presented to the PSP steering group for eligibility assessment; 79 were deemed within scope and included for the purpose of research uncertainty extraction (45 full Cochrane Reviews, 18 Cochrane Review protocols, 16 Guidelines). These yielded 89 research uncertainties, which were compared to the stakeholder survey, and added to the longlist where necessary; before derived uncertainties were checked against non-Cochrane published systematic reviews. CONCLUSIONS: In carrying out this work, beyond reporting on output of the Common Conditions Affecting the Hand and Wrist PSP, we detail the methodology and processes we hope can inform and facilitate the work of future PSPs and other evidence reviews, especially those with a broader scope beyond a single disease or condition.

Combining bio-telemetry and underwater imagery to elucidate the reproductive behaviour of a large, long-lived Australian freshwater teleost.

Murray cod Maccullochella peelii (Mitchell) have a key ecological role in ensuring the health of Australia's largest inland waterway, but many aspects surrounding its reproductive strategies in the wild are unknown. From 2015 to 2019 within the Northern Murray-Darling Basin, Australia, we used a combination of bio-telemetry and underwater imagery to quantify the behaviour of Murray cod across their breeding cycle in a natural riverine environment. In most years, breeding behaviour including nest site selection was observed from early-August and spawning from late-August through to late-October, which is considerably earlier than previously reported. There was a positive correlation between the onset of breeding behaviour and week-of-year, and spawning was correlated with moon-phase. Whilst some nesting sites were amongst woody debris and in hollow logs, the majority were located in shallow water on hard substrate underneath undercuts along the riverbank edge. Nests were frequently established in isolated and disconnected pools with little or no measurable flow, suggesting that river hydraulics is not a key component driving spawning of Murray cod across at least some areas of its range. Larvae were observed actively swimming and controlling their position within and near nests and used a scatter tactic when dispersing. We also established that disturbing nesting Murray cod had a negative impact on egg and larval survival. We suggest a review of current regulations to safeguard the long-term conservation of the species across all sections of its range.

Climate refugia for kelp within an ocean warming hotspot revealed by stacked species distribution modelling.

Canopy forming macroalgae are declining globally due to climate change and the identification of refuges for these habitats is crucial for their conservation. This is particularly pertinent in ocean warming hotspots where significant range contractions of kelp have occurred and are projected to continue. We developed a stacked urchin-kelp species distribution model (SDM) to predict climate refugia for kelp (Ecklonia radiata) in an ocean warming hotspot, south-eastern Australia. The optimal stacked-SDM incorporated biotic and abiotic explanatory covariates and was validated using an independent dataset. Density of the urchin Centrostephanus rodgersii, summer bottom temperature and photosynthetically available radiation at the seabed were significant predictors of kelp cover, highlighting the physiological and ecological influence of these variables on the distribution of kelp. Our optimal stacked-SDM predicted three spatially distinct refuge areas, where kelp occurs in deeper waters than surrounding seascapes. The presence of kelp at two of these refuge areas was confirmed using independent data. The identification of these refuge areas is crucial for conservation, as they are likely to facilitate the persistence of ecologically and economically important kelp forests as waters warm in shallow areas and kelp retreat to depth under climate change. Furthermore, identification of refugia will enable proactive spatial planning that prioritises new locations for protection to ensure that key kelp habitats can persist in a future of increasing stress.

A randomised feasibility trial comparing needle fasciotomy with limited fasciectomy treatment for Dupuytren's contractures.

PURPOSE: The purpose of this study is to assess the feasibility of conducting a large, multicentre randomised controlled trial (RCT) comparing needle fasciotomy with limited fasciectomy for treatment of Dupuytren's contractures. DESIGN: The design of this study is a parallel, two-arm, multicentre, randomised feasibility trial with embedded QuinteT Recruitment Intervention. PARTICIPANTS: Patients aged 18 years or over who were referred from primary to secondary care for treatment of a hand with Dupuytren's contractures of one or more fingers of more than 30° at the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints and well-defined cord(s). Patients were excluded if they had undergone previous Dupuytren's contracture surgery on the same hand. METHODS: Potential participants were screened for eligibility. Recruited participants randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy and followed-up for up to 6 months after treatment. Data on recruitment rates, completion of follow-up, and procedure costs were collected. Four patient reported outcome measures (PROMs) and objective outcome measures were collected before intervention and 6 weeks and 6 months afterwards. RESULTS: One hundred and fifty-three of 267 (57%) primary-care referrals for Dupuytren's contractures met the eligibility criteria for the study. Seventy-one of the 153 (46%) agreed to participate and were randomly allocated to treatment with needle fasciotomy or limited fasciectomy. Sixty-seven of these underwent their allocated treatment, two were crossovers from limited fasciectomy to needle fasciotomy, and two (both allocated limited fasciectomy) received no treatment. Fifty-nine participants (85%) completed 6-month follow-up PROMs. Participants felt the MYMOP, PEM and URAM PROMs allowed them to better describe how their treatment affected their hand function than the DASH PROM. The estimated costs of limited fasciectomy (in an operating theatre) and needle fasciotomy (in a clinic room) were £777 and £111 respectively. CONCLUSION: A large RCT comparing treatment of Dupuytren's contractures by needle fasciotomy and limited fasciectomy is feasible. Data from this study will help determine the number of sites and duration of recruitment required to complete an adequately powered RCT and will assist the selection of PROMs in future studies on the treatment of Dupuytren's contractures. (Level 1 feasibility study). TRIAL REGISTRATION: Trial registered with ISRCTN (registration number: ISRCTN11164292), date assigned - 28/08/2015.

Outcome of cardiac arrests attended by emergency medical services staff at community outpatient dialysis centers.

Cardiac arrest is the leading cause of death among dialysis patients in the United States. We measured the outcome of cardiac arrests attended by Emergency Medical Services (EMS) staff at hemodialysis facilities in a 14-year population-based retrospective study to identify cardiac arrest cases at a dialysis unit. Associated factors were determined using unconditional logistic regression. Of the 102 cardiac arrests identified around the time of dialysis, 10 occurred before, 72 during, and 20 after hemodialysis. The initial measured abnormality was ventricular fibrillation or tachycardia in 72 cases. Of those who survived transportation to a hospital, survival to discharge was 24 with 15% survival at 1 year. Compared to arrests that occurred prior to dialysis, the odds of ventricular fibrillation were 5-fold greater in patients on dialysis but 14-fold greater in those arresting after dialysis. One-third of cases occurred after the introduction of automated external defibrillators, and in half of the cases these devices were attached prior to EMS arrival. Once these devices were attached, most were used for defibrillation. We conclude that ventricular arrhythmias are the predominant features among arrested in-center dialysis patients with most occurrences during dialysis. The role of these devices in dialysis units will need a larger study to evaluate their efficacy.

Evidence-based management of adult trigger digits.

The aim of this systematic review was to develop an evidence-based guideline to assist clinicians in the treatment of adult trigger digits. There is moderate evidence to suggest that local corticosteroid injection is a safe and effective short-term treatment and it may, therefore, be recommended as an initial treatment for this condition. However, when compared with surgery, there is strong evidence that corticosteroid injection is associated with increased rates of ongoing or recurrent symptoms at 6 months after intervention. There is strong evidence suggesting that trigger digit can be managed safely by surgical release. There is weak evidence to support the use of splinting or other non-operative modalities. Hence a single corticosteroid injection may be offered as the first line in treatment of adult trigger digits, but percutaneous release is a safe alternative. Surgery should be the next line if the injection fails, symptoms recur or the patient chooses. LEVEL OF EVIDENCE: I.

Recovery, responsiveness and interpretability of patient-reported outcome measures after surgery for Dupuytren's disease.

This prospective cohort study investigated the responsiveness and interpretability of the Disabilities of the Arm, Shoulder and Hand (DASH) and Unité Rhumatologique des Affections de la Main (URAM) outcome measures for assessing recovery after fasciectomy and dermofasciectomy for Dupuytren's disease. DASH outcome scores at 1 year were significantly better than at 6 weeks, suggesting that recovery is not complete by 6 weeks. Of the 101 patients recruited to the DASH cohort, 71 completed preoperative, 6 week and 1 year postoperative DASH scores; 68 of them completed preoperative and 1 year postoperative DASH scores and an external anchor question. In the URAM cohort, 30/44 completed the preoperative and the 1 year postoperative URAM scores and the anchor question. The DASH score exhibited moderate responsiveness but poor interpretability on receiver operating characteristic curve analysis, such that a minimal important change could not be estimated. The URAM score showed acceptable responsiveness, and an MIC of 10.5 on receiver operating characteristic analysis. LEVEL OF EVIDENCE: II.

Functional outcome and complications following surgery for Dupuytren's disease: a multi-centre cross-sectional study.

Variables associated with recurrent Dupuytren's disease, or a 'diathesis', have been investigated, but those associated with functional outcome and complications are less well studied. Outcomes 1 or 5 years after an aponeurotomy, fasciectomy or dermofasciectomy were assessed by patient interview and examination at five UK centres. A total of 432 procedures were studied. The reoperation rate did not differ at 1 year ( p = 0.396, Chi-square test with Monte Carlo simulation), but was higher after aponeurotomy in the 5-year group (30%, versus 6% after fasciectomy and 0% after dermofasciectomy, p = 0.003, Chi square test with Monte Carlo simulation). Loss of function (DASH>15) did not differ between procedures at 5 years, even when reoperation and other variables were controlled. Diabetes, female gender and previous ipsilateral surgery were associated with poorer function in logistic regression analysis. The variables associated with poor function after treatments differ from diathesis variables. Aponeurotomy had lower complication rates than fasciectomy and dermofasciectomy. This may counterbalance the former's higher recurrence rate and explain why aponeurotomy demonstrated similar long-term functional outcome compared with excisional surgery in this study. LEVEL OF EVIDENCE: III.

Preservation of the ulnar bursa within the carpal tunnel: does it improve the outcome of carpal tunnel surgery? A randomized, controlled trial.

BACKGROUND: It was hypothesized that preserving a layer of gliding tissue, the parietal layer of the ulnar bursa, between the contents of the carpal tunnel and the soft tissues incised during carpal tunnel surgery might reduce scar pain and improve grip strength and function following open carpal tunnel decompression. METHODS: Patients consented to randomization to treatment with either preservation of the parietal layer of the ulnar bursa beneath the flexor retinaculum at the time of open carpal tunnel decompression (fifty-seven patients) or division of this gliding layer as part of a standard open carpal tunnel decompression (sixty-one patients). Grip strength was measured, scar pain was rated, and the validated Patient Evaluation Measure questionnaire was used to assess symptoms and disability preoperatively and at eight to nine weeks following the surgery in seventy-seven women and thirty-four men; the remaining seven patients were lost to follow-up. RESULTS: There was no difference between the groups with respect to age, sex, hand dominance, or side of surgery. Grip strength, scar pain, and the Patient Evaluation Measure score were not significantly different between the two groups, although there was a trend toward a poorer subjective outcome as demonstrated by the questionnaire in the group in which the ulnar bursa within the carpal tunnel had been preserved. Preserving the ulnar bursa within the carpal tunnel did, however, result in a lower prevalence of suspected wound infection or inflammation (p = 0.04). CONCLUSIONS: In this group of patients, preservation of the ulnar bursa around the median nerve during open carpal tunnel release produced no significant difference in grip strength or self-rated symptoms. We recommend incision of the ulnar bursa during open carpal tunnel decompression to allow complete visualization of the median nerve and carpal tunnel contents.

The effect of short-term dependency and immobility on skin temperature and colour in the hand.

The effects of short-term dependency and immobility on skin temperature were assessed in two experiments. In the first study, ten volunteers hung their left arm dependent and motionless while using their right hand for light office work. After 30 minutes, the dependent left hands were cooler (mean=0.9 degrees C: 95% CI=0.7-1.1) than the active right hands and exhibited a deeper colour with significantly increased green intensity (P=0.03) as assessed on digital images. In the second study, seven volunteers submerged both their hands in water at 15 degrees C for 15 minutes. The left arm was then left dependent and motionless while the right hand was placed on the table and its fingers were flexed and extended every 10 seconds. The left hands remained cooler than the right and were a median of 3.6 (range 2.9-4.5) degrees C cooler after 60 minutes. These studies demonstrate that skin temperature and colour differences between the hands, which are sometimes used to support the diagnosis of CRPS-1, can be produced and maintained by short-term immobility and dependency of the hand.

Changes in scaphoid bone density after acute fracture.

The radiographic density of the proximal fragments of 16 scaphoid fractures was assessed on scaphoid series radiographs taken at 6 to 12 weeks. In addition, dual energy X-ray absorptiometry measurements of bone mineral density in the distal radius and proximal and distal fracture fragments were performed at 1 to 2 weeks and 6 to 12 weeks. Median reductions of 9% and 10% were observed in bone mineral density in the proximal fracture fragment and the distal radius respectively, but these did not correlate with the radiographic density of the proximal fragment. A greater median reduction in bone mineral density (27%) was observed in the distal fracture fragment and more bone loss occurred at this site when there was an apparent increase in the radiographic density of the proximal fragment (median fall of 0.23 g/cm2 versus 0.14 g/cm2). Thus, apparent increased radiographic density of the proximal fragment may be due to increased bone loss from the distal fragment.

Intramedullary fixation of unstable metacarpal fractures.

Intramedullary stabilization of metacarpal shaft and neck fractures is a relatively simple, cost-effective, and safe technique with good published outcomes (Fig. 9); however definite advantages over other techniques of fracture stabilization, or indeed simple early mobilization in some instances, have not been clearly demonstrated. A recent publication does suggest that the technique is comparable to percutaneous transverse fixation in the context of fifth metacarpal neck fractures.

Scaphoid fracture non-union: a systematic review of surgical treatment using bone graft.

UNLABELLED: This systematic review assesses the quality and outcomes of published articles concerning bone graft surgery for scaphoid fracture non-union. Searches of the CENTRAL, MEDLINE, EMBASE, CINAHL and AMED databases captured 2710 articles. Each article was screened and 144 met our inclusion criteria. Data regarding source, study design, population, intervention, comparator and outcomes were extracted. There were 5464 scaphoid non-union outcomes within the 144 studies. Mean reported union rates for vascularized and non-vascularized bone graft were 84% and 80%, respectively. Avascular necrosis was diagnosed in several ways and, when present, the vascularized bone graft union rate was 74% compared with 62% with non-vascularized bone graft. Reported union rates vary considerably. These differences may be due to patient factors, fracture factors, treatment factors or study design failures or bias. We recommend that future researchers take into account the deficiencies of previous studies and use the suggested minimum data set in future studies. LEVEL OF EVIDENCE: II.

Basic fibroblast growth factor induces 3T3 fibroblasts to synthesize and secrete a cyclophilin-like protein and beta 2-microglobulin.

When stimulated by fibroblast growth factor (FGF) BALB/c 3T3 cells synthesize and secrete elevated amounts of five proteins called the 'superinducible proteins', or SIPs. The expression of these proteins is greatly enhanced if the cells are treated with cycloheximide during induction. The 24 kDa protein (SIP24) has been purified and antiserum raised against it. This protein is N-glycosylated and probably structurally constrained by one or more intramolecular disulfide bonds. The amino acid sequences of three of four peptides show significant identity with cyclophilin, an abundant cytoplasmic protein believed to mediate the immunosuppressive effects of cyclosporin A. Several members of the cyclophilin family have been identified, and cDNA clones of two cyclophilin-like proteins with signal sequences have been reported. Here we show that at least one cyclophilin-like protein is secreted and that its expression is regulated by growth factors. The 12.5 kDa protein (SIP12.5) was found to be immunoprecipitated by an antiserum raised to human beta 2-microglobulin. This protein is strongly induced by interferon, which is a characteristic of the beta 2-microglobulin gene. Thus, FGF stimulates mouse embryo 3T3 cells to produce two proteins related to immune regulatory molecules. This may reflect an interaction between immune cells and nonimmune cells that occurs in vivo during processes such as wound healing when growth factors are released locally.

Dorsal fracture-dislocation of the proximal interphalangeal joint: a comparative study of percutaneous Kirschner wire fixation versus open reduction and internal fixation.

Nineteen patients with a dorsal fracture-dislocation of the proximal interphalangeal joint of a finger were treated with either closed reduction and transarticular Kirschner wire fixation (eight cases) or open reduction and internal fixation, using either one or two lag screws (six cases) or a cerclage wire (five cases). At a mean follow-up of 7 (range 6-9) years, most patients reported satisfactory finger function, even though some of the injuries healed with proximal interphalangeal joint incongruency (seven cases) or subluxation (four cases). Those treated by open reduction complained of more "loss of feeling" in the affected finger and those specifically treated by cerclage wire fixation reported more cold intolerance and had a significantly larger fixed flexion deformity (median, 30 degrees : range 18-38 degrees ) and a smaller arc of motion (median, 48 degrees : range 45-60 degrees ) at the proximal interphalangeal joint, despite having the best radiological outcomes. Closed reduction and transarticular Kirschner wire fixation produced satisfactory results, with none of the eight patients experiencing significant persistent symptoms despite a reduced arc of proximal interphalangeal joint flexion (median=75 degrees ; range 60-108 degrees ). The results of this relatively simple treatment appear at least as satisfactory as those obtained by the two techniques of open reduction and internal fixation, both of which were technically demanding.

Dual energy X-ray absorptiometry (DXA): can it detect acute scaphoid fractures?

This prospective study investigated whether dual energy X-ray absorptiometry (DXA) could detect acute scaphoid fractures. We blindly compared 10 normal and 10 fractured scaphoid images produced with a new technique of DXA scan analysis. This measured and plotted the density of the scaphoid throughout its length, producing a linear graph of the scaphoids' density instead of a single area (g/cm2) measurement of bone density. These new plots only detected six of the 10 fractures and suggested that four of the normal controls were fractured. Thus, this technique of DXA scan analysis is neither sensitive nor specific for the detection of acute scaphoid fractures.

An assessment of the tensile properties and technical difficulties of two- and four-strand flexor tendon repairs.

This study compares the mechanical properties of locking Kessler and four-strand flexor tendon repairs and examines for difficulties related to technical ability. Two trainee surgeons each carried out 10 locking Kessler and 10 four-strand single-cross flexor tendon repairs on an in vitro porcine model. Outcome measures included gap formation and ultimate forces, operative time and repair bulk. Ultimate force was 81% greater for the four-strand repair compared to the Kessler (52 N, SD 5, versus 29 N, SD 6). Operating times were similar between the two techniques (Kessler 10.0 minutes, four strand 10.1 minutes). Rupture force and operating times improved slightly during the study for the Kessler repairs, but in the four strand repairs results remained stable throughout the study. We conclude that the single-cross four-strand repair tolerates superior loads yet is no more technically demanding than the modified Kessler, and can be reliably performed without additional operating time.

Partial union of acute scaphoid fractures.

Sixty-six patients with acute scaphoid fractures were treated non-operatively in a below elbow plaster for 8 to 12 weeks and underwent CT scans along the longitudinal axis of the scaphoid at 12 to 18 weeks. These scans showed that 14 fractures had not united and that 30 had united throughout the whole cross-section of the scaphoid. The other 22 had partially united with bridging trabeculae in some areas of the cross-section. These 22 partial unions were graded as 0% to 24% union (0 cases), 25% to 49% union (5 cases), 50% to 74% union (7 cases), and 75% to 99% union (10 cases). The 12 patients who had less than 75% fracture union were followed-up further and nine underwent another CT scan at 23 to 40 weeks after the initial injury. These showed union across the whole of the cross-section of the fracture in seven cases and 75% to 99% union in the other two cases, who had full and painless wrist function. We conclude that partial union of the scaphoid is a common occurrence but, in most cases, it progresses to full union without the need for prolonged plaster immobilization.

Cost-effectiveness of volar locking plate versus percutaneous fixation for distal radial fractures: Economic evaluation alongside a randomised clinical trial.

This study compares the cost-effectiveness of treating dorsally displaced distal radial fractures with a volar locking plate and percutaneous fixation. It was performed from the perspective of the National Health Service (NHS) using data from a single-centre randomised controlled trial. In total 130 patients (18 to 73 years of age) with a dorsally displaced distal radial fracture were randomised to treatment with either a volar locking plate (n = 66) or percutaneous fixation (n = 64). The methodology was according to National Institute for Health and Care Excellence guidance for technology appraisals. . There were no significant differences in quality of life scores between groups at any time point in the study. Both groups returned to baseline one year post-operatively. NHS costs for the plate group were significantly higher (p < 0.001, 95% confidence interval 497 to 930). For an additional £713, fixation with a volar locking plate offered 0.0178 additional quality-adjusted life years in the year after surgery. The incremental cost-effectiveness ratio (ICER) for plate fixation relative to percutaneous fixation at list price was £40 068. When adjusting the prices of the implants for a 20% hospital discount, the ICER was £31 898. Patients who underwent plate fixation did not return to work earlier. We found no evidence to support the cost-effectiveness, from the perspective of the NHS, of fixation using a volar locking plate over percutaneous fixation for the operative treatment of a dorsally displaced radial fracture.