Preclinical in vivo models of fracture-related infection: a systematic review and critical appraisal.

A fracture-related infection (FRI) is an important complication that can lead to an increase in morbidity, mortality and economic costs. Preclinical in vivo models are critical in the evaluation of novel prevention and treatment strategies, yet it is important that these studies recapitulate the features of an FRI that make it such a clinical challenge. The aim of this systematic review was to survey the available preclinical models of FRIs and assess which of the key FRI-specific parameters are incorporated in these models. A comprehensive search was performed on July 1st 2017 in PubMed, Embase and Web of Science. Overall, 75 preclinical studies were identified, 97.3 % (n = 73) of which use Staphylococcus aureus as the causative microorganism. The most common mode for creation of bone instability is an osteotomy (n = 30; 40 %), followed by the creation of a defect (n = 26; 34.7 %). An actual fracture is created in only 19 studies (25.3 %). 12 (16 %) of the models include a time gap between bacterial inoculation and fixation to mimic the time-to-treatment in clinical open fracture scenarios. This systematic review reveals that animal models used in translational research on prevention and treatment of FRIs rarely incorporate all key clinical features in one model and that there is an over-representation of S. aureus in comparison to actual clinical epidemiology. To improve the relevance of these studies, existing preclinical models should be adapted or new models developed that better recapitulate the clinical condition of FRI.

Children with PIMD in interaction with peers with PIMD or siblings.

BACKGROUND: The complex disabilities of children with profound intellectual and multiple disabilities (PIMD) impede their presentation of peer directed behaviours. Interactions with typically developing peers have been observed to be more frequent than those with peers with PIMD. The typically developing peers with whom people with PIMD have frequent contact are their siblings. In this study, the amount of peer directed behaviours was compared between an interaction with a sibling and an interaction with a peer with PIMD. In addition, the attention directing strategies of the siblings, and how these affect the presentation of peer directed behaviours, were examined. METHOD: Thirteen children and young people with PIMD, who had a typically developing sibling, were identified. For each of these thirteen children, a peer with PIMD and a sibling were selected. The child with PIMD was observed together with a peer with PIMD and together with a sibling. In both conditions, video observations were conducted. A coding scheme for the peer directed behaviours of the children and young people with PIMD and a coding scheme for the attention directing behaviours of the siblings were used. Descriptive, comparative and sequential analyses were conducted. RESULTS: Significantly, more peer directed behaviours of the children with PIMD were observed in the condition with the sibling (30.76%) compared with that of the condition with the peer with PIMD (13.73%). The siblings presented attention directing behaviours in 30% of the time; the most frequently used was nonverbal behaviour. When the siblings presented a combination of verbal and nonverbal attention directing behaviours, they elicited multiple peer directed behaviours in the children and young people with PIMD. CONCLUSIONS: Persons with PIMD interact more with their siblings compared with their peers with PIMD. Interacting with siblings may probably be more motivating and encouraging. Presenting a combination of verbal and nonverbal behaviours attracts more attention of the persons with PIMD.

The nature of peer-directed behaviours in children with profound intellectual and multiple disabilities and its relationship with social scaffolding behaviours of the direct support worker.

BACKGROUND: The multiple and complex disabilities of persons with profound intellectual and multiple disabilities (PIMD) form a barrier for peer interactions and peer-directed behaviours. In this study, we further explore the nature of peer-directed behaviours in persons with PIMD and its relationship with social scaffolding behaviour of direct support workers (DSWs). METHODS: Fourteen dyads of children with PIMD, who knew each other for at least 12 months, participated. They were sitting in close proximity while they were filmed with and without the presence of the DSW. Video recordings were coded continuously making use of observation schemes for the peer-directed behaviours of the children and the peer interaction influencing behaviours of the DSW. RESULTS: Significantly more singular peer-directed behaviour (without DSW: 18.00%; with DSW: 3.81%) was observed than multiple peer-directed behaviour (without DSW: 4.01%; with DSW: 0.52%). The amount of time the singular and multiple peer-directed behaviours were observed was significantly lower in the presence of a DSW. When the DSW shows peer interaction influencing behaviour, it was mostly social scaffolding behaviour (2.17%). The conditional probability of observing social scaffolding behaviour in the 10 s following on singular peer-directed behaviour was 0.02 with a Yule's Q of 0.04 and following on multiple peer-directed behaviour 0.04 with a Yule's Q of 0.33. CONCLUSION: The way in which peer interactions in children with PIMD are defined could have an impact on the amount of observed peer-directed behaviours and on the effect of the social scaffolding behaviours presented by DSW.

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.

BACKGROUND: Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. OBJECTIVES: Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. METHODS: The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). RESULTS: In the external validation cohort, ROC AUC for blood eosinophils was 89% (p<0.001) and for FE(NO) level 78% (p<0.001) to detect sputum eosinophilia ≥3%. Serum periostin was not able to distinguish eosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, p<0.001). CONCLUSIONS: In patients with mild to moderate asthma, as well as patients with more severe asthma, blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. TRIAL REGISTRATION: NTR1846 and NTR2364.

Efficacy of etravirine combined with darunavir or other ritonavir-boosted protease inhibitors in HIV-1-infected patients: an observational study using pooled European cohort data.

OBJECTIVES: This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data. METHODS: Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012). Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived. RESULTS: Baseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small. CONCLUSIONS: These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir.

Intramedullary nailing of humeral shaft fractures: failure analysis of a single centre series.

INTRODUCTION: Intramedullary nailing (IMN) is an accepted technique for the treatment of humeral shaft fractures. Previous studies published concerns over whether this technique had higher complication rates such as nonunion and technical failures compared to plate osteosynthesis. We, therefore, conducted a single centre failure analysis to critically evaluate our results regarding IMN of humeral shaft fractures. MATERIALS AND METHODS: Between January 2000 and January 2013, 246 consecutive patients with humeral shaft fractures were enrolled. Inclusion criteria were skeletal maturity and humeral shaft fractures treated with IMN. Exclusion criteria were skeletal immaturity, primary treatment by plate osteosynthesis, primary treatment outside the University Hospitals Leuven, presence of metaphyseal fractures and the presence of pathological fractures. Negative outcome measures such as infection, nonunion and early technical failure were retrospectively assessed. RESULTS: During the study period, 149 patients with 149 fractures met the inclusion criteria. Of these, 14 patients were lost to follow-up, two died from trauma-related causes within the first 30 days after the accident, and eight died from other causes (cardiovascular disease and cancer) leaving 125 patients with 125 fractures for a minimum follow-up period of 12 months. Failure analysis showed that six (4.8 %) patients developed a nonunion. One (0.8 %) patient was diagnosed with a deep infection. In total, five (5 %) patients underwent surgical revision due to early technical failures. CONCLUSIONS: IMN is a valid therapeutic option for humeral shaft fractures. Good surgical technique and soft tissue handling are important for good outcome. Currently, patient demands are receiving greater consideration. In an era where early full range of motion and rapid return to work with minimal scarring is mandatory for most patients, the use of IMN will most likely increase in popularity in the future.

Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study.

OBJECTIVES: PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥ 6 to < 12 years) and adolescents (≥ 12 to < 18 years) over 48 weeks. METHODS: In a phase II, open-label, single-arm study, 101 treatment-experienced patients (41 children; 60 adolescents) with screening viral load (VL) ≥ 500 HIV-1 RNA copies/mL received etravirine 5.2 mg/kg (maximum dose 200 mg) twice a day (bid) plus OBR. RESULTS: Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At week 48, the most common treatment-related grade ≥ 2 adverse event (AE) was rash (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68% children; 48% adolescents) achieved a virological response (VL<50 copies/mL; intent-to-treat, noncompleter=failure). Factors predictive of response were adherence > 95%, male sex, low baseline etravirine weighted genotypic score and high etravirine trough concentration (C0h ). Seventy-six patients (75%) completed the trial; most discontinuations occurred because of protocol noncompliance or AEs (8% each). Sixty-five per cent of patients were > 95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration-time curve over 12 h (AUC0-12h ; 5216 ng h/mL) and C0h (346 ng/mL) were comparable to adult target values. CONCLUSIONS: Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200 mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients.

The interference of distal humeral plating with the medial and lateral collateral ligaments of the elbow.

INTRODUCTION: The aim of the present study was to determine the anatomical relationship and evaluate the potential interference of today's common distal humerus plates with the medial and lateral collateral ligaments of the elbow. MATERIALS AND METHODS: The elbow joints of 23 embalmed upper extremities were dissected. Three different brands of distal humerus double-plating systems were applied in a standardized fashion. We used a caliper to measure the amount of absolute overlap of the plates on the corresponding collateral ligaments. RESULTS: The data show contact and overlap with the medial and lateral collateral ligaments in all tested medial and lateral plates. The posterolateral and posteromedial plates showed no contact with the ligaments, yet they did contact the posterior joint capsules. The medial plates showed less contact/overlap when compared with the lateral and extended medial plates. CONCLUSION: Based on the present data, we conclude that distal humerus plating using the perpendicular technique with standard-sized medial plates shows the least amount of overlap over the medial and lateral collateral ligaments. The extent of the overlap of the ligaments by the humeral plates is clearly shown in the present study.

Variation in care and outcome for fragile hip fracture patients: a European multicentre study benchmarking fulfilment of established quality indicators.

PURPOSE: Despite the availability of clinical guidelines for hip fracture patients, adherence to these guidelines is challenging, potentially resulting in suboptimal patient care. The goal of this study was (1) to evaluate and benchmark the adherence to recently established quality indicators (QIs), and (2) to study clinical outcomes, in fragile hip fracture patients from different European countries. METHODS: This observational, cross-sectional multicenter study was performed in 10 hospitals from 9 European countries including data of 298 consecutive patients. RESULTS: A large variation both within and between hospitals were seen regarding adherence to the individual QIs. QIs with the lowest overall adherence rates were the administration of systemic steroids (5.4%) and tranexamic acid (20.1%). Indicators with the highest adherence rates (above 95%) were pre-operative (99.3%) and post-operative haemoglobin level assessment (100%). The overall median time to surgery was 22.6 h (range 15.7-42.5 h). The median LOS was 9.0 days (range 5.0-19.0 days). The most common complications were delirium (23.2%) and postsurgical constipation (25.2%). CONCLUSION: The present study shows large variation in the care for fragile patients with hip fractures indicating room for improvement. Therefore, hospitals should invest in benchmarking and knowledge-sharing. Large quality improvement initiatives with longitudinal follow up of both process and outcome indicators should be initiated.

Three phenotypes of adult-onset asthma.

RATIONALE: Adult-onset asthma differs from childhood-onset asthma in many respects. It is more heterogeneous, often severe and frequently associated with loss of lung function. To identify underlying mechanisms of adult-onset asthma and to capture predictors of disease progression, detailed characterization and phenotyping is necessary. OBJECTIVES: To characterize adult-onset asthma and identify subphenotypes of adult-onset asthma. METHODS: A cohort of 200 patients with adult-onset (>18 year) asthma (age 54 (26-75) year) was recruited from one academic and three nonacademic pulmonary outpatient clinics in Amsterdam, the Netherlands. These patients were fully characterized with respect to clinical, functional and inflammatory markers. After data reduction, K-means nonhierarchical cluster analysis was performed to identify clusters of adult-onset asthma. MEASUREMENTS AND MAIN RESULTS: Patients with adult-onset asthma were predominately female (61%) and nonatopic (55%). Within this group of patients were identified three clusters of adult-onset asthma. Cluster 1 (n = 69) consisted of patients with severe eosinophilic inflammation-predominant asthma and persistent airflow limitation despite high-intensity anti-inflammatory treatment, with relatively low symptom scores. The second cluster was characterized by obese women with frequent symptoms, high healthcare utilization and low sputum eosinophils. The third cluster consisted of patients with mild-to-moderate, well-controlled asthma with normal lung function and low inflammatory markers. Repeatability accuracy was 98.2%. CONCLUSIONS: Amongst patients with adult-onset asthma, three subphenotypes can be identified with distinct clinical and inflammatory characteristics. These subphenotypes help to understand the underlying pathobiology and provide clinicians with directions for personalized management.

Non-atopic males with adult onset asthma are at risk of persistent airflow limitation.

BACKGROUND: Patients with asthma have on average a more rapid decline in FEV (1) as compared with the general population. Recent cluster analysis has revealed different asthma phenotypes that can be distinguished by age of onset and reversibility of airflow limitation. OBJECTIVE: This study aimed at detecting risk factors associated with persistent airflow limitation in patients with the adult onset asthma phenotype. METHODS: We recruited 88 patients with adult onset (≥ 18 years) asthma from an academic pulmonary outpatient clinic in the Netherlands. The associations of age, age of asthma onset, asthma duration, gender, race, atopy, smoking pack-years, BMI, use of oral corticosteroids with post-bronchodilator FEV (1) /FVC were investigated. RESULTS: Multiple linear regression analysis showed an association of absence of atopy (r = -0.27, B = -0.26, P = 0.01) and male gender (r = 0.31, B = 0.30, P = 0.004) with post-bronchodilator FEV (1) /FVC. Multiple logistic regression analysis showed that male patients were 10.8 (CI: 2.6-45.2) times the odds than women to have an FEV (1) /FVC < 0.7, and non-atopic patients were 5.2 (CI: 1.3-20.3) times the odds to have an FEV (1) /FVC < 0.7 than atopic patients. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that in patients with adult onset asthma, male gender and absence of atopy are associated with persistent airflow limitation. This might suggest that amongst patients with adult onset asthma, non-atopic male patients are at increased risk of accelerated decline in lung function.

Pooled week 96 results of the phase III DUET-1 and DUET-2 trials of etravirine: further analysis of adverse events and laboratory abnormalities of special interest.

OBJECTIVES: The aim of the study was to investigate the frequency and severity of adverse events (AEs) and laboratory abnormalities of interest over 96 weeks of treatment with etravirine or placebo in the pooled TMC125 DUET (Demonstrate Undetectable viral load in patients Experienced with ARV Therapy) trials. METHODS: Treatment-experienced, HIV-1-infected patients randomly received etravirine 200 mg twice a day (bid) or placebo, plus a background regimen. The frequency and severity of neuropsychiatric, rash, hepatic and lipid AEs were analysed; frequencies were also adjusted for total patient-years of exposure (PYE). RESULTS: A total of 599 and 604 patients received etravirine and placebo, respectively (median treatment duration 96.0 and 69.6 weeks, respectively). There was no significant difference between the treatment groups in the frequency of neuropsychiatric AEs. However, a significant difference in the frequency of rash was observed (20.5% vs. 11.8%, respectively; P < 0.0001); rash was generally mild to moderate in severity; the rate of discontinuation because of rash was low (2.2% vs. 0% in the etravirine and placebo groups, respectively). The frequency of hepatic AEs was low and similar between the treatment groups (8.7% vs. 7.1%, respectively; P = 0.3370); hepatic enzyme levels did not increase over time. Lipid-related laboratory abnormalities and changes over time in lipid levels were generally comparable between treatment groups. Adjusting for treatment exposure, the frequency of AEs remained similar between treatment groups, with the exception of rash [13.7 vs. 9.3 per 100 PYE; relative risk (95% confidence interval) 1.48 (1.02-1.95)]. CONCLUSIONS: The frequency of AEs of interest was generally similar between the treatment groups, both overall and when adjusted for treatment exposure, with the exception of rash which was more frequent in the etravirine group.

Stakeholders' perspectives on how to improve the support for persons with an intellectual disability and challenging behaviors: a concept mapping study.

INTRODUCTION: People with an intellectual disability (ID) are at risk of developing challenging behavior. Although previous research provided important insights into how to support people with an ID and challenging behavior, it remains unclear what various stakeholders consider to be the most essential aspects to further improve their support. METHOD: Statements regarding aspects perceived necessary to improve the support to people with an ID and challenging behavior were collected in focus groups. Afterwards participants individually prioritized and clustered these statements, resulting in concept maps for people with an ID, direct support workers, and psychologists. Since only three relatives participated in the entire concept mapping procedure, no concept map could be composed based on their input. RESULTS: Participants generated 200 statements. In the concept map of clients, statements were mentioned regarding relational aspects, providing clarity and structure, characteristics of support staff, and professional attitude of direct support workers. Direct support workers provided statements related to their own personal competencies, the necessity of feeling supported and appreciated, and a physical safe environment. Psychologists provided statements regarding their support for direct support workers, the support for the clients, the perspective on the client, and their role as psychologists. CONCLUSION: The results of this study may be a starting point to foster increased evidence based practice for the support for persons with an ID and challenging behavior. Moreover, it provides opportunities to create care founded on mutual attunement, based on listening to each other's ideas and insight into perspectives and needs of various stakeholders.

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD.

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics. Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed. Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p < 0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p < 0.01; eNose breathprint r = 0.84, p = 0.002) (MPO: four compounds, p < 0.01; eNose r = 0.72, p = 0.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD. Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.

Value of three-dimensional computed tomography reconstruction in the treatment of posterior tibial plateau fractures.

BACKGROUND: Indication for surgical treatment of posterior tibial plateau fractures (TPFs) remains up for debate. Three-dimensional computed tomography (3D-CT) reconstruction can provide insight into fracture morphology and could improve treatment strategy and surgical planning. In this study, we investigated the value of 3D-CT reconstruction in the treatment of posterior TPF and evaluated the influence on surgical decision-making. METHODS: CT images of 34 cases with a TPF involving the posterior column were included and digitally presented to a panel of five international observers at two intervals. At the first evaluation, only coronal, axial and sagittal images were shown. After an interval of at least three weeks, 3D-CT reconstruction images were added. During both surveys, observers were asked to classify the TPF according to the revised three-column classification (rTCC), as well as to define operative strategy. RESULTS: When using 2D images, overall multirated kappa value was 0.48, with an average pairwise agreement of 68%. After adding 3D images, overall multirated kappa value was 0.43, with average pairwise agreement of 67%. Hierarchical logistic regression of decision to operate on image condition (3D vs. 2D) shows an odds ratio of 2.01 (95% confidence interval, 1.11-3.67), P = .022. Increase in operative indication was seen mainly in posterolateral fractures. CONCLUSION: This study investigated the value of 3D classification in the treatment of posterior column TPF. Contrary to expectations, the addition of 3D images to the assessment did not reduce but rather appeared to increase operative indications, especially in fractures involving the posterolateral region.

Effectiveness of pulmonary rehabilitation at high-altitude compared to sea-level in adults with severe refractory asthma.

BACKGROUND: Beneficial effects of pulmonary rehabilitation at high-altitude (HAPR) in patients with severe refractory asthma have been reported earlier, but evidence for the effectiveness is limited. AIM: To investigate the effectiveness of high-altitude pulmonary rehabilitation to comparable treatment at sea-level (LAPR) on patient outcome parameters. METHODS: Adults with severe refractory asthma living in The Netherlands were included. Treatment consisted of a 12-week personalized multidisciplinary rehabilitation program either at high-altitude (Davos Switzerland) (n = 93) or in a tertiary lung center at sea-level in The Netherlands (n = 45). At baseline, after treatment, and during 12 months follow-up asthma related quality of life (AQLQ), asthma control (ACQ), pulmonary function and OCS-dose were assessed. Patients could not be randomized resulting in different asthma populations. Groups were compared using linear regression analysis (ANCOVA) adjusted for baseline values, in addition to age, atopy, smoking history, BMI and gender. RESULTS: After treatment, and at 12 months follow-up, improved AQLQ(0.92,p < 0.001 and 0.82,p = 0.001, respectively), ACQ(-0.87,p < 0.001 and -0.69,p = 0.008, respectively) and lower maintenance OCS dose (Unadjusted linear regression analysis-5.29 mg, p = 0.003 and Crude Odds Ratio-1.67, p = 0.003, respectively) were observed in the HAPR-group compared to the LAPR group. Patients receiving HAPR also had less asthma exacerbations (≥1 exacerbation: 20% vs 60%,p < 0.001) and showed improvement in lung function (%predFEV1 3.4%,p = 0.014) compared to the LAPR group, but at 12 months no differences between groups were observed. CONCLUSION: HAPR resulted in a larger improvement in patient outcome parameters compared to LAPR, on the long run the improvement in patient reported symptoms and lower maintenance OCS-dose persists. Underlying factors that explain this observed effect need to be investigated.

Reamer-Irrigator-Aspirator bone graft harvesting for treatment of segmental bone loss: analysis of defect volume as independent risk factor for failure.

INTRODUCTION: The management of segmental bone loss poses a significant clinical challenge. The purpose of this study was to conduct a retrospective evaluation of our experience in treating segmental bone loss, using Reamer-Irrigator-Aspirator (RIA)-harvested autologous bone graft. MATERIALS AND METHODS: Between June 2008 and March 2015, 81 patients were treated with the RIA technique for multiple purposes. Inclusion criteria for this study were skeletal mature patients with segmental bone loss, due to acute trauma or non-union, who were treated with RIA-harvested bone graft. Exclusion criteria were skeletal immaturity, pathological fractures and indications for the RIA system other than bone graft harvesting. The primary outcome parameter was clinical and radiographical bone healing. RESULTS: During the study period, 72 patients met the inclusion criteria. In total, 39 patients (54.2%) were classified as having clinical and radiographical bone healing. Although univariate analysis could not reveal any significant influence of specific risk factors to predict the outcome, there was a trend towards statistical significance for defect volume. Further analysis indeed revealed that smaller defect volumes (< 8 cm3) had a lower risk of non-union. CONCLUSIONS: In approximately half of our study population, the use of the RIA technique for autologous bone graft harvesting in cases of segmental bone loss resulted in a successful outcome with bone healing. Defect size seems to be a critical issue regarding the outcome. Although our results are less promising than previously published, the RIA technique has its place in the treatment algorithm of segmental bone defects.

Variation of the clavicle's muscle insertion footprints - a cadaveric study.

The muscle footprint anatomy of the clavicle is described in various anatomical textbooks but research on the footprint variation is rare. Our goal was to assess the variation and to create a probabilistic atlas of the muscle footprint anatomy. 14 right and left clavicles of anatomical specimens were dissected until only muscle fibers remained. 3D models with muscle footprints were made through CT scanning, laser scanning and photogrammetry. Then, for each side, the mean clavicle was calculated and non-rigidly registered to all other cadaveric bones. Muscle footprints were indicated on the mean left and right clavicle through the 1-to-1 mesh correspondence which is achieved by non-rigid registration. Lastly, 2 probabilistic atlases from the clavicle muscle footprints were generated. There was no statistical significant difference between the surface area (absolute and relative), of the originally dissected muscle footprints, of male and female, and left and right anatomical specimens. Visualization of all muscle footprints on the mean clavicle resulted in 72% (right) and 82% (left) coverage of the surface. The Muscle Insertion Footprint of each specimen covered on average 36.9% of the average right and 37.0% of the average left clavicle. The difference between surface coverage by all MIF and the mean surface coverage, shows that the MIF location varies strongly. From the probabilistic atlas we can conclude that no universal clavicle exists. Therefore, patient-specific clavicle fracture fixation plates should be considered to minimally interfere with the MIF. Therefore, patient-specific clavicle fracture fixation plates which minimally interfere with the footprints should be considered.

Epidemiology of clavicle fractures in a level 1 trauma center in Belgium.

PURPOSE: In the last 10 years, there has been an increasing tendency toward operative fixation of clavicle fractures. In this retrospective analysis, we will demographically assess all patients who sustained a clavicle fracture and were treated in our university hospital between 2004 and 2014. METHODS: We retrospectively updated our database and analyzed all adult patients who were diagnosed with a clavicle fracture in our hospital. The following parameters were included in the database: age, gender, Robinson classification, date of trauma, injury mechanism, time until surgery, and reason for delayed surgery. Descriptive statistics were used to describe differences between patient groups and linear regression was performed to identify trends over time. RESULTS: 667 patients were included for analysis. The mean age was 43 ± 17.7 years. The majority of clavicle fractures occurred due to bicycle injuries (35.3%) and these increased from 2004 until 2014 (r = 0.738, R² = 0.545, p = 0.009). Patients with a midshaft clavicle fracture were increasingly treated primarily surgically (r = 0.928, R² = 0.861, p < 0.0001). There was an increased ratio of delayed surgery in relation to age from the age of 16 (9.1%) until the age of 70 years (37.2%). CONCLUSIONS: There is an increasing number of fractures sustained by bicycle accidents and an increasing number of patients undergoing operative treatment. Middle-aged patients more often had delayed surgery compared with young adult patients. This could be due to an increased activity level of the elder population and the concomitant demand for a faster return to activities. LEVEL OF EVIDENCE: III, retrospective comparative study.

Functional outcome and economic burden of operative management of patellar fractures: the pivotal role of onerous implants.

OBJECTIVES: The complication rate following operative treatment of patellar fractures remains high and is associated with a poor functional outcome. The primary goal of this study was to evaluate our functional outcome of patellar fracture osteosynthesis and define strategies to improve the outcome. The healthcare costs and utilization were calculated. METHODS: All demographic, clinical, radiographic variables and hospital-related costs of 111 patients with 113 surgically treated patellar fractures between January 2005 and December 2014 were analyzed. Fractures were grouped as either simple or complex. Functional outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: There were 67 simple fractures (59.3%) and 46 complex fractures (40.7%). The overall complication rate was 48.7%, including 19.5% implant-related complications. In 69 patients (61.1%), implants were removed. The outcome was rather poor, with considerable impairment in all KOOS subscales with the knee-related quality of life rated worst (median 62.5, IQR 37.5-81.25). Poor outcome correlated significantly with complex patellar fractures and extensive tension-band constructs. CONCLUSIONS: The operative treatment of patellar fractures was associated with a high complication rate, functional impairment and reduced quality of life. Complex patellar fractures and extensive tension-band constructs were identified as the main determinants of poor outcome and increased economic burden due to higher reinterventions rates. Strategies to reduce complications and improve outcome should focus on less onerous implants.