Patient-reported outcome measures for patients with hand-specific impairments-A scoping review.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used to provide evidence for treatment effects and to guide rehabilitation. To our knowledge, no disease-specific PROM exists for the assessment of patients with flexor tendon lesions of the hand. We believe that PROMs used to assess hand function, regardless of diagnosis, contain relevant items for patients with flexor tendon lesions of the hand. PURPOSE: The aim of our study was to identify and collect items from pre-existing PROMs used by clinical experts to assess the health status and function in patients with reduced hand function. STUDY DESIGN: A scoping review searching for PROMs with hand-specific content was conducted to ensure face validity. As these items are assumed to have been through an evaluation process by the clinical specialists, they have the advantage and likelihood of being useful. METHODS: We searched five bibliographic databases. All PROMs with hand-specific content used to assess hand function were considered for inclusion. Questionnaires written in English, Danish, Swedish, and Norwegian were included. An analysis of content redundancy was conducted, and items were grouped according to The World Health Organization's International Classification of Functioning, Disability and Health. RESULTS: Seventy-three PROMs were included with a total of 1,582 items. The majority of the items were redundant across measurement instruments, and redundant items were consolidated, resulting in 179 nonredundant items. All nonredundant items were classified according to the International Classification of Functioning, Disability and Health components. CONCLUSIONS: This review presents a collection of 179 items ensuring face validity for patients with hand-related disease/injury.

Complications after surgical management of proximal humeral fractures: a systematic review of event terms and definitions.

BACKGROUND: The most frequently used surgical procedures for treating a proximal humeral fracture (PHF) are plate osteosynthesis, nail osteosynthesis and arthroplasty. Evidence-based recommendations for an appropriate surgical procedure after PHF requires transparent and valid safety data. We performed a systematic review to examine reported terms and definitions of complications after surgically-treated PHFs. METHODS: A literature search was conducted on PubMed, Cochrane Library, EMBASE, Scopus and WorldCat to identify clinical articles and book chapters on complications of PHF published from 2010 to 2017. Complication terms and definitions were extracted from each selected article independently by two reviewers and grouped according to a predefined scheme. RESULTS: From 1376 initial references, we selected 470 articles, of which 103 were reviewed in reverse chronological order until no further information was gained. Twelve book chapters were reviewed. We found 667 local event terms associated with complications after surgical treatment of PHFs. The most frequently used event terms were infection (52 references), nonunion (n = 42), malunion (n = 35), avascular necrosis (n = 27) and pain (n = 25). Overall, 345, 177, 257 and 102 local event terms were related to plating, nailing, arthroplasty and other surgical techniques, respectively. Radiological assessment was the basis for the majority of event terms and complication definitions. Thirty-six event definitions were extracted, mostly defining the terms "secondary fracture displacement", "screw perforation/cutout", "malunion", "delayed healing" and "notching". CONCLUSION: Scientific literature on surgically-managed PHF uses different terms to describe complications and without approved definitions, which highlights a lack of agreement on adverse event terminology for PHFs. Defined event terms are mostly based on radiological observations. Consensus among shoulder surgeons on a core event set is indispensable to support the standardization of safety reporting for surgically-treated PHFs.

Reverse shoulder arthroplasty has a higher risk of revision due to infection than anatomical shoulder arthroplasty: 17 730 primary shoulder arthroplasties from the Nordic Arthroplasty Register Association.

AIMS: The aim of this study was to use national registry database information to estimate cumulative rates and relative risk of revision due to infection after reverse shoulder arthroplasty. PATIENTS AND METHODS: We included 17 730 primary shoulder arthroplasties recorded between 2004 and 2013 in The Nordic Arthroplasty Register Association (NARA) data set. With the Kaplan-Meier method, we illustrated the ten-year cumulative rates of revision due to infection and with the Cox regression model, we reported the hazard ratios as a measure of the relative risk of revision due to infection. RESULTS: In all, 188 revisions were reported due to infection during a mean follow-up of three years and nine months. The ten-year cumulative rate of revision due to infection was 1.4% overall, but 3.1% for reverse shoulder arthroplasties and 8.0% for reverse shoulder arthroplasties in men. Reverse shoulder arthroplasties were associated with an increased risk of revision due to infection also when adjusted for sex, age, primary diagnosis, and year of surgery (relative risk 2.41 (95% confidence interval 1.26 to 5.59); p = 0.001). CONCLUSION: The overall incidence of revision due to infection was low. The increased risk in reverse shoulder arthroplasty must be borne in mind, especially when offering it to men. Cite this article: Bone Joint J 2019;101-B:702-707.

Splints, with or without wrist immobilization, following surgical repair of flexor tendon lesions of the hand: A systematic review.

Splints with or without wrist immobilization can be used during the rehabilitation of flexor tendon lesions of the hand. The evidence base for these techniques has not previously been studied in a systematic review. We sought to thoroughly review patient-reported functional outcomes and pain to compare splinting with or without wrist immobilization. Five bibliographic databases were searched. Studies were considered for inclusion if they were randomized controlled trials or observational comparative studies reporting the difference in outcome among patients treated with or without wrist immobilization. No limits were set on publication date or language. Study selection was performed independently by two authors, and disagreements were resolved by consensus. The review protocol was preregistered in PROSPERO. There were no randomized controlled trials. No studies could be included based on our inclusion criteria. We decided to qualitatively summarize the most relevant studies although they did not meet our inclusion criteria. This resulted in a narrative review of the studies we found relevant. Based on the current literature, it is impossible to provide evidence-based recommendations for or against wrist immobilization during the rehabilitation period following flexor tendon repair. The lack of high-quality evidence points to a need for randomized clinical trials to guide rehabilitation decisions.

Anatomical total shoulder arthroplasty used for glenohumeral osteoarthritis has higher survival rates than hemiarthroplasty: a Nordic registry-based study.

OBJECTIVE: To report the10-year survival rates of different shoulder arthroplasty types used for glenohumeral osteoarthritis. DESIGN: Data from 2004 to 2013 was prospectively collected by the national shoulder arthroplasty registers in Denmark, Norway and Sweden and merged into a harmonized dataset under the umbrella of the Nordic Arthroplasty Register Association. The common dataset included data that all three registers could deliver and where consensus regarding definitions could be made. Revision was defined as removal or exchange of any component or the addition of a glenoid component. RESULTS: The cumulative survival rates at 10 years after resurfacing hemiarthroplasty (RHA) (n = 1,923), stemmed hemiarthroplasty (SHA) (n = 1,587) and anatomical total shoulder arthroplasty (TSA) (n = 2,340) were 0.85, 0.93 and 0.96 respectively (P < 0.001, Log rank test). RHA (HR: 2.5; CI 1.9-3.4, P < 0.001) and SHA (HR: 1.4; CI 1.0-2.0, P < 0.04) had an increased risk of revision compared to TSA. Gender, age and period of surgery were included in the Cox regression model. For patients below 55 years, the 10-year cumulative survival rates were 0.75 (RHA, n = 354), 0.81 (SHA, n = 146), and 0.87 (TSA, n = 201). CONCLUSIONS: Anatomical TSA had the highest implant-survival rate. Young patients had, independently of the arthroplasty type, lower implant-survival rates. The treatment of young patients with end-stage osteoarthritis remains a challenge.

The impact of lifestyle risk factors on the rate of infection after surgery for a fracture of the ankle.

AIMS: Lifestyle risk factors are thought to increase the risk of infection after acute orthopaedic surgery but the evidence is scarce. We aimed to investigate whether smoking, obesity and alcohol overuse are risk factors for the development of infections after surgery for a fracture of the ankle. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent internal fixation of a fracture of the ankle between 2008 and 2013. The primary outcome was the rate of deep infection and the secondary outcome was any surgical site infection (SSI). Associations with the risk factors and possible confounding variables were analysed univariably and multivariably with backwards elimination. RESULTS: A total of 1043 patients were included; 64 (6.1%) had a deep infection and 146 (14.0%) had SSI. Obesity was strongly associated with both outcomes (odds ratio (OR) 2.21, p = 0.017 and OR 1.68, p = 0.032) in all analyses. Alcohol overuse was similarly associated, though significant only in unadjusted analyses. Surprisingly, smoking did not yield statistically significant associations with infections. CONCLUSION: These findings suggest that obesity and possibly alcohol overuse are independent risk factors for the development of infection following surgery for a fracture of the ankle. This large study brings new evidence concerning these common risk factors; although prospective studies are needed to confirm causality. Cite this article: Bone Joint J 2017;99-B:225-30.

Tartrate-resistant acid phosphatase (TRAP) co-localizes with receptor activator of NF-KB ligand (RANKL) and osteoprotegerin (OPG) in lysosomal-associated membrane protein 1 (LAMP1)-positive vesicles in rat osteoblasts and osteocytes.

Tartrate-resistant acid phosphatase (TRAP) is well known as an osteoclast marker; however, a recent study from our group demonstrated enhanced number of TRAP + osteocytes as well as enhanced levels of TRAP located to intracellular vesicles in osteoblasts and osteocytes in experimental osteoporosis in rats. Such vesicles were especially abundant in osteoblasts and osteocytes in cancellous bone as well as close to bone surface and intracortical remodeling sites. To further investigate TRAP in osteoblasts and osteocytes, long bones from young, growing rats were examined. Immunofluorescence confocal microscopy displayed co-localization of TRAP with receptor activator of NF-KB ligand (RANKL) and osteoprotegerin (OPG) in hypertrophic chondrocytes and diaphyseal osteocytes with Pearson's correlation coefficient ≥0.8. Transmission electron microscopy showed co-localization of TRAP and RANKL in lysosomal-associated membrane protein 1 (LAMP1) + vesicles in osteoblasts and osteocytes supporting the results obtained by confocal microscopy. Recent in vitro data have demonstrated OPG as a traffic regulator for RANKL to LAMP1 + secretory lysosomes in osteoblasts and osteocytes, which seem to serve as temporary storage compartments for RANKL. Our in situ observations indicate that TRAP is located to RANKL-/OPG-positive secretory lysosomes in osteoblasts and osteocytes, which may have implications for osteocyte regulation of osteoclastogenesis.

Outcome, revision rate and indication for revision following resurfacing hemiarthroplasty for osteoarthritis of the shoulder: 837 operations reported to the Danish Shoulder Arthroplasty Registry.

In this study, we evaluated patient-reported outcomes, the rate of revision and the indications for revision following resurfacing hemiarthroplasty of the shoulder in patients with osteoarthritis. All patients with osteoarthritis who underwent primary resurfacing hemiarthroplasty and reported to the Danish Shoulder Arthroplasty Registry (DSR), between January 2006 and December 2010 were included. There were 772 patients (837 arthroplasties) in the study. The Western Ontario Osteoarthritis of the Shoulder (WOOS) index was used to evaluate patient-reported outcome 12 months (10 to 14) post-operatively. The rates of revision were calculated from the revisions reported to the DSR up to December 2011 and by checking deaths with the Danish National Register of Persons. A complete questionnaire was returned by 688 patients (82.2%). The mean WOOS was 67 (0 to 100). A total of 63 hemiarthroplasties (7.5%) required revision; the cumulative five-year rate of revision was 9.9%. Patients aged < 55 years had a statistically significant inferior WOOS score, which exceeded the minimal clinically important difference, compared with older patients (mean difference 14.2 (8.8; 95% CI 19.6; p < 0.001), but with no increased risk of revision. There was no significant difference in the mean WOOS or the risk of revision between designs of resurfacing hemiarthroplasty.

Gene expression and distribution of key bone turnover markers in the callus of estrogen-deficient, vitamin D-depleted rats.

An experimental rat model was used to test the hypothesis that in osteoporosis (OP) the molecular composition of the extracellular matrix in the fracture callus is disturbed. OP was induced at 10 weeks of age by ovariectomy and a vitamin D(3)-deficient diet, and sham-operated animals fed normal diet served as controls. Three months later a closed tibial fracture was made and stabilized with an intramedullary nail. After 3 and 6 weeks of healing, the animals were killed and the fracture calluses examined with global gene expression, in situ mRNA expression, and ultrastructural protein distribution of four bone turnover markers: osteopontin, bone sialoprotein, tartrate-resistant acid phosphatase, and cathepsin K. Global gene expression showed a relatively small number of differently regulated genes, mostly upregulated and at 3 weeks. The four chosen markers were not differently regulated, and only minor differences in the in situ mRNA expression and ultrastructural protein distribution were detected. Gene expression and composition of fracture calluses are not generally disturbed in experimental OP.

Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding.

BACKGROUND: Blinding can reduce bias in randomized clinical trials, but blinding procedures may be unsuccessful. Our aim was to assess how often randomized clinical trials test the success of blinding, the methods involved and how often blinding is reported as being successful. METHODS: We analysed a random sample of blinded randomized clinical trials indexed in the The Cochrane Central Register of Controlled Trials and published in 2001. We identified 1599 blinded trials, and noted if they had conducted any test for the success of blinding. We also selected 200 trials randomly that did not report any such test, and sent a questionnaire to the corresponding authors asking them if they had conducted any tests. RESULTS: Thirty-one out of 1599 trials (2%) reported tests for the success of blinding. Test methods varied, and reporting was generally incomplete. Blinding was considered successful in 14 out of the 31 trials (45%) and unclear in 10 (32%). Of the seven trials (23%) reporting unsuccessful blinding the risk of a biased trial result was either not addressed or was discounted in six cases. We received 130 questionnaires from trial authors (65%) of which 15 (12%) informed that they had conducted, but not published, tests. CONCLUSIONS: Blinding is rarely tested. Test methods vary, and the reporting of tests, and test results, is incomplete. There is a considerable methodological uncertainty how best to assess blinding, and an urgent need for improved methodology and improved reporting.

An in vitro study of the activity of telithromycin against mobile and cystic forms of Borrelia afzelii.

In this study the new ketolide telithromycin was tested in vitro against motile and cystic forms of Borrelia afzelii, one of the species of Borrelia burgdorferi sensu lato. Acridine orange staining, dark field microscopy, and transmission electron microscopy were the techniques used to study the influence of telithromycin on the bacteria. The activity was unexpectedly high, 0.0003 microg/ml < MBC < or = 0.0006 microg/ml for the mobile forms after 7 days of incubation at 34 degrees C. MIC was < 0.00015 microg/ml. It is likely that the agent works bacteriostatically and kills in a time-dependent and concentration-independent way, by binding tightly to the ribosomes. The agent was not able to prevent cyst formation, and the cysts were not affect ed at an in vivo achievable concentration. Electron microscopy also supports the hypothesis of telithromycin being an effective agent against the mobile bacteria.

[Lupus nephritis with crystal structures in glomerulopathy ]. / Lupusnephritis mit Kristallstrukturen in glomerulären Ablagerungen.

Lupus nephritis is a common phenomenon in Systemic Lupus Erythematosus (SLE). We analyzed a renal biopsy of a 30-year-old woman with SLE. The clinical history showed a typical SLE with generalized symptoms without demonstrable lupus coagulant, positive for anti-nuclear antibodies and anti-ds-DNA antibodies but negative for rheumatoid factor, cryoglobulins and antiphospholipid antibodies. A paraproteinemia for IgA, IgG and IgM was not detectable. Using light, electron and immunoelectron microscopy electron-dense deposits were noted in subepithelial, subendothelial and mesangial position. Most remarkably, the electron-dense deposits and mesangial areas in the vicinity of deposits contained an electron-dense crystalline material. The crystalline structures were composed of IgG and kappa light chains, while they were negative for IgM, IgA and lambda light chains, as demonstrated by immunoelectron microscopy. As far as we know, this is the first case of lupus nephritis with crystalline structures. Since we could not detect cryoglobulinemia or paraproteinemia, other mechanisms possibly favor organization of macromolecular structures.

Improved interobserver variation after training of doctors in the Neer system. A randomised trial.

We investigated whether training doctors to classify proximal fractures of the humerus according to the Neer system could improve interobserver agreement. Fourteen doctors were randomised to two training sessions, or to no training, and asked to categorise 42 unselected pairs of plain radiographs of fractures of the proximal humerus according to the Neer system. The mean kappa difference between the training and control groups was 0.30 (95% CI 0.10 to 0.50, p = 0.006). In the training group the mean kappa value for interobserver variation improved from 0.27 (95% CI 0.24 to 0.31) to 0.62 (95% CI 0.57 to 0.67). The improvement was particularly notable for specialists in whom kappa increased from 0.30 (95% CI 0.23 to 0.37) to 0.79 (95% CI 0.70 to 0.88). These results suggest that formal training in the Neer system is a prerequisite for its use in clinical practice and research.

Low agreement among 24 doctors using the Neer-classification; only moderate agreement on displacement, even between specialists.

Twenty-four orthopaedic surgeons classified 42 pairs of radiographs according to the Neer system for proximal humeral fractures. Mean kappa value for inter-observer agreement was 0.27 (95% CI 0.26-0.28) with no clinically significant difference between orthopaedic residents ( n=9), fellows ( n=6) and specialists ( n=9). Mean kappa for agreement of displacement versus non-displacement was 0.41 (95% CI 0.39-0.43) overall, and 0.50 (95% CI 0.45-0.56) within the specialist group. The agreement found in our study is unsatisfactory from a clinical perspective.

An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine.

In this work the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine (HCQ) was studied. The minimal bactericidal concentration (MBC) of HCQ against the mobile spirochetes was > 32 microg/ml at 37 degrees C, and > 128 microg/ml at 30 degrees C. Incubation with HCQ significantly reduced the conversion of mobile spirochetes to cystic forms. When incubated at 37 degrees C, the MBC for young biologically active cysts (1-day old) was > 8 microg/ml, but it was > 32 microg/ml for old cysts (1-week old). Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that the contents of the cysts were partly degraded when the concentration of HCQ was > or = MBC. At high concentrations of HCQ (256 microg/ml) about 95% of the cysts were ruptured. When the concentration of HCQ was > or = MBC, core structures did not develop inside the cysts, and the amount of RNA in these cysts decreased significantly. Spirochetal structures inside the cysts dissolved in the presence of high concentrations of HCQ. When the concentration of HCQ was > or = MBC, the core structures inside the cysts were eliminated. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of HCQ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi.

pH-dependent effect of heat-induced antigen retrieval of epoxy section for electron microscopy.

The aim was to examine how the pH in the antigen retrieval medium (citrate) affects the yield of immunogold labeling of epoxy sections. Renal swine tissue with glomerular immune complex deposits with reactivity against IgG was embedded in epoxy resin. Prior to immunogold labeling with anti-IgG, ultrathin sections from these blocks were exposed to antigen retrieval by heating in citrate solution (pH 6, 9 or 12) at 95 degrees C in a PCR-machine or at 121 or 135 degrees C min in an autoclave. The level of immunogold labeling was significantly higher for pH 12 than for pH 6 when heated at 95 degrees C (50% more intense), but at the cost of the ultrastructural preservation of the tissue. At pH 12 and temperature 135 degrees C the epoxy sections were completely destroyed. The sections which had been heated at 135 degrees C, pH 6 appeared significantly better both with respect to intensity of immunogold labeling (85% more intense) and to ultrastructural preservation than those which were heated at 95 degrees C, pH 12. Therefore, our results indicate that relatively low pH (pH 6) and high temperature is the method of choice, but low temperature and high pH can be used when an autoclave is not available.

Heat-induced antigen retrieval of epoxy sections for electron microscopy.

The purpose of this manuscript is to review the literature on the use of heat-induced antigen retrieval methods to enhance the immunolabeling of epoxy sections at the electron microscopical level. The history of the development of antigen retrieval by heating formaldehyde fixed paraffin sections in a buffer solution is given in short, and how this technique has been extended to resin sections and in particular epoxy sections is explained. Theories for the mechanism of enhancement of the immunolabeling of epoxy sections by the heat-retrieval method are discussed, and it is finally speculated whether most of the mechanisms for antigen retrieval on epoxy sections in heated buffer solution are essentially the same as for conventional immunoenhancing by deplastizing and etching. The more accelerator used in the processing of the tissue the more intense the immunolabeling of the heated epoxy sections becomes. The intensity of immunolabeling of the epoxy sections increases with the temperature in the heated buffer solution, and the intensity is significantly higher at high autoclave temperatures than at 95 degrees C, Heat-induced antigen retrieval is also compared with other, conventional techniques for enhancing the immunolabeling of epoxy sections.