Complement and arthritis: another step in understanding

In a recent research article in Arthritis Research and Therapy ('Analysis of C204 and the C4 binding protein in the MRL/lpr mouse'), Wenderfer and colleagues report that deficiency in C4 binding protein, a down-regulator of the classic pathway of complement, does not affect the development of autoimmune disease. These data support the earlier finding that the alternative pathway, and not the classic pathway, drives disease progression. However, in a milder variant of the MRL/lpr model, the lpr/lpr mouse, classic pathway deficiency does contribute toward renal pathology and more severe disease. In this editorial we discuss the factors that may cause such a discrepancy

Patient-reported physical functioning and quality of life after pelvic ring injury:A systematic review of the literature

Background Pelvic ring injuries are one of the most serious traumatic injuries with large consequences for the patients' daily life. During recent years, the importance of the patients' perception of their functioning and quality of life following injury has increasingly received attention. This systematic review reports on self-reported physical functioning and quality of life after all types of pelvic ring injuries. Methods The online databases MEDLINE-PubMed and Ovid-EMBASE were searched for studies published between 2008 and 2019 to identify published evidence of patient-reported physical functioning and quality of life after which they were assessed for their methodological quality. Results Of the 2577 articles, 46 were reviewed in full-text, including 3049 patients. Most studies were heterogeneous, with small cohorts of patients, a variety of injury types, treatment methods and use of different, often non-validated, outcome measures. The overall methodological quality was moderate to poor. Nine different PROMs were used, of which the Majeed Pelvic Score (MPS), SF-36 and EQ-5D were the most widely used. Mean scores respectively ranged from 75-95 (MPS), 53-69 (SF-36, physical functioning) and 0.63-0.80 (EQ-5D). Conclusions Physical functioning and quality of life following pelvic ring injuries seem fair and tend to improve during follow-up. However, differences in patient numbers, injury definition, treatment strategy, follow-up duration and type of PROMs used between studies hampers to elucidate the actual effects of pelvic ring injuries on a patient's life. Implications of key findings Physicians and researchers should use valid and reliable patient-reported outcome instruments on large cohorts of patients with properly defined injuries to truly evaluate physical functioning and quality of life after pelvic ring injuries. Systematic review registration number PROSPERO International prospective register of systematic reviews; registration number CRD42019129176

Between-hospital variation in indicators of quality of care: a systematic review

Background: Efforts to mitigate unwarranted variation in the quality of care require insight into the 'level' (eg, patient, physician, ward, hospital) at which observed variation exists. This systematic literature review aims to synthesise the results of studies that quantify the extent to which hospitals contribute to variation in quality indicator scores. Methods: Embase, Medline, Web of Science, Cochrane and Google Scholar were systematically searched from 2010 to November 2023. We included studies that reported a measure of between-hospital variation in quality indicator scores relative to total variation, typically expressed as a variance partition coefficient (VPC). The results were analysed by disease category and quality indicator type. Results: In total, 8373 studies were reviewed, of which 44 met the inclusion criteria. Casemix adjusted variation was studied for multiple disease categories using 144 indicators, divided over 5 types: intermediate clinical outcomes (n=81), final clinical outcomes (n=35), processes (n=10), patient-reported experiences (n=15) and patient-reported outcomes (n=3). In addition to an analysis of between-hospital variation, eight studies also reported physician-level variation (n=54 estimates). In general, variation that could be attributed to hospitals was limited (median VPC=3%, IQR=1%-9%). Between-hospital variation was highest for process indicators (17.4%, 10.8%-33.5%) and lowest for final clinical outcomes (1.4%, 0.6%-4.2%) and patient-reported outcomes (1.0%, 0.9%-1.5%). No clear pattern could be identified in the degree of between-hospital variation by disease category. Furthermore, the studies exhibited limited attention to the reliability of observed differences in indicator scores. Conclusion: Hospital-level variation in quality indicator scores is generally small relative to residual variation. However, meaningful variation between hospitals does exist for multiple indicators, especially for care processes which can be directly influenced by hospital policy. Quality improvement strategies are likely to generate more impact if preceded by level-specific and indicator-specific analyses of variation, and when absolute variation is also considered. PROSPERO registration number: CRD42022315850.</p

BiomarCaRE: rationale and design of the European BiomarCaRE project including 300,000 participants from 13 European countries

Biomarkers are considered as tools to enhance cardiovascular risk estimation. However, the value of biomarkers on risk estimation beyond European risk scores, their comparative impact among different European regions and their role towards personalised medicine remains uncertain. Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) is an European collaborative research project with the primary objective to assess the value of established and emerging biomarkers for cardiovascular risk prediction. BiomarCaRE integrates clinical and epidemiological biomarker research and commercial enterprises throughout Europe to combine innovation in biomarker discovery for cardiovascular disease prediction with consecutive validation of biomarker effectiveness in large, well-defined primary and secondary prevention cohorts including over 300,000 participants from 13 European countries. Results from this study will contribute to improved cardiovascular risk prediction across different European populations. The present publication describes the rationale and design of the BiomarCaRE project. Electronic supplementary material The online version of this article (doi:10.1007/s10654-014-9952-x) contains supplementary material, which is available to authorized users

Does 3D-Assisted Operative Treatment of Pelvic Ring Injuries Improve Patient Outcome?:A Systematic Review of the Literature

Background: There has been an exponential growth in the use of advanced technologies for three-dimensional (3D) virtual pre- and intra-operative planning of pelvic ring injury surgery but potential benefits remain unclear. The purpose of this study was to evaluate differences in intra- and post-operative results between 3D and conventional (2D) surgery. Methods: A systematic review was performed including published studies between 1 January 2010 and 22 May 2020 on all available 3D techniques in pelvic ring injury surgery. Studies were assessed for their methodological quality according to the Modified McMaster Critical Review form. Differences in operation time, blood loss, fluoroscopy time, screw malposition rate, fracture reduction and functional outcome between 3D-assisted and conventional (2D) pelvic injury treatment were evaluated and a best-evidence synthesis was performed. Results: Eighteen studies fulfilled the inclusion criteria, evaluating a total of 988 patients. Overall quality was moderate. Regarding intra-operative results of 3D-assisted versus conventional surgery: The weighted mean operation time per screw was 43 min versus 52 min; for overall operation time 126 min versus 141 min; blood loss 275 ± 197 mL versus 549 ± 404 mL; fluoroscopy time 74 s versus 125 s and fluoroscopy frequency 29 ± 4 versus 63 ± 3. In terms of post-operative outcomes of 3D-assisted versus conventional surgery: weighted mean screw malposition rate was 8% versus 18%; quality of fracture reduction measured by the total excellent/good rate by Matta was 86% versus 82% and Majeed excellent/good rate 88% versus 83%. Conclusion: The 3D-assisted surgery technologies seem to have a positive effect on operation time, blood loss, fluoroscopy dose, time and frequency as well as accuracy of screw placement. No improvement in clinical outcome in terms of fracture reduction and functional outcome has been established so far. Due to a wide range of methodological quality and heterogeneity between the included studies, results should be interpreted with caution

Are sarcopenia and myosteatosis in elderly patients with pelvic ring injury related to mortality, physical functioning and quality of life?

The purpose of this study was to evaluate the prevalence of sarcopenia and/or myosteatosis in elderly patients with pelvic ring injuries and their influence on mortality, patient-perceived physical functioning and quality of life (QoL). A multicenter retrospective cohort study was conducted including elderly patients aged ≥ 65 treated for a pelvic ring injury. Cross-sectional computed tomography (CT) muscle measurements were obtained to determine the presence of sarcopenia and/or myosteatosis. Kaplan–Meier analysis was used for survival analysis, and Cox proportional hazards regression analysis was used to determine risk factors for mortality. Patient-reported outcome measures for physical functioning (SMFA) and QoL (EQ-5D) were used. Multivariable linear regression analyses were used to determine the effect of sarcopenia and myosteatosis on patient-perceived physical functioning and QoL. Data to determine sarcopenia and myosteatosis were available for 199 patients, with a mean follow-up of 2.4 ± 2.2 years: 66 patients (33%) were diagnosed with sarcopenia and 65 (32%) with myosteatosis, while 30 of them (15%) had both. Mortality rates in patients at 1 and 3 years without sarcopenia and myosteatosis were 13% and 21%, compared to 11% and 36% in patients with sarcopenia, 17% and 31% in patients with myosteatosis and 27% and 43% in patients with both. Higher age at the time of injury and a higher Charlson Comorbidity Index (CCI) were independent risk factors for mortality. Patient-reported mental and emotional problems were significantly increased in patients with sarcopenia

The effects of pelvic ring injuries on quality of life, physical, and mental health:results of a 2-year prospective cohort study

PURPOSE: Pelvic ring injuries are known to affect the patients' daily life in terms of physical functioning and quality of life (QoL). Still, prospective studies on the patient's perception over the first 2 years of rehabilitation are lacking. Therefore, patients cannot be properly informed about whether or when they will return to their pre-existing level of physical functioning and QoL. METHODS: A prospective longitudinal cohort study was performed over a 4-year period including all consecutive patients above 18 years who sustained a pelvic ring injury in a level 1 trauma center. Validated patient-reported outcome measures (PROMs) were used to assess physical functioning (SMFA) and QoL (EQ-5D) at baseline (recalled pre-injury score), 6 weeks, 3 months, 6 months, 1 year and 2 years after the injury. It was assessed whether patients had fully recovered by comparing follow-up scores to baseline PROMs. Binary logistic regression analysis was used to identify independent predictors for patients who did not fully recover. Most experienced difficulties at 3 months and 1 year were identified by analyzing the highest reported scores on individual items of the SMFA. RESULTS: A total of 297 patients with a pelvic ring injury were identified of which 189 were eligible for follow-up and 154 (82%) responded. Median SMFA function score at 3 months, 1 and 2 years was 70, 78 and 88, respectively, compared to 96 out of 100 before the injury. Median SMFA bother score was 67, 79 and 88, respectively. Median EQ-5D score at 3 months, 1 and 2 years was 0.61, 0.81 and 0.85, respectively, compared to 1 (maximum achievable) before the injury. After 1 and 2 years of follow-up, 61% and 75% of the patients fully "recovered" in physical functioning and 52% and 71% fully recovered in terms of QoL. Female gender and high-energy trauma were independent predictors for not fully recovering after 1 year. After 3 months of follow-up, 54% of patients reported severe difficulties with recreational activities, whereas after 1 year, most experienced difficulties (31% of patients) concerned heavy house or yard work. Moreover, after 3 months and 1 year, 44% and 27% of patients reported feeling physically disabled. CONCLUSION: Pelvic ring injuries have a large impact on the patients' daily life in the first 2 years of rehabilitation. Directly after the injury, physical functioning and QoL decrease strongly but then gradually improve over a 2-year period with about 75% of patients fully recovering. Female gender and high-energy trauma are shown to be independent predictors for not fully recovering. After 3 months, patients experience difficulties with both the physical and mental effects of the injury which continue to be present after 1 year

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis : a record linkage analysis of Scottish healthcare databases

This study was commissioned by GSK through the Farr Institute/SHIP/eDRIS single portal. DJM is a Clinician Scientist Fellow funded by the Health Foundation/Academy of Medical Sciences.Objectives: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. Setting: Health boards in Scotland (n=4). Participants: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. Methods: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. Results: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. Conclusions: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high.Publisher PDFPeer reviewe

Triggering Collapse of the Presolar Dense Cloud Core and Injecting Short-Lived Radioisotopes with a Shock Wave. I. Varied Shock Speeds

The discovery of decay products of a short-lived radioisotope (SLRI) in the Allende meteorite led to the hypothesis that a supernova shock wave transported freshly synthesized SLRI to the presolar dense cloud core, triggered its self-gravitational collapse, and injected the SLRI into the core. Previous multidimensional numerical calculations of the shock-cloud collision process showed that this hypothesis is plausible when the shock wave and dense cloud core are assumed to remain isothermal at ~10 K, but not when compressional heating to ~1000 K is assumed. Our two-dimensional models (Boss et al. 2008) with the FLASH2.5 adaptive mesh refinement (AMR) hydrodynamics code have shown that a 20 km/sec shock front can simultaneously trigger collapse of a 1 solar mass core and inject shock wave material, provided that cooling by molecular species such as H2O, CO, and H2 is included. Here we present the results for similar calculations with shock speeds ranging from 1 km/sec to 100 km/sec. We find that shock speeds in the range from 5 km/sec to 70 km/sec are able to trigger the collapse of a 2.2 solar mass cloud while simultaneously injecting shock wave material: lower speed shocks do not achieve injection, while higher speed shocks do not trigger sustained collapse. The calculations continue to support the shock-wave trigger hypothesis for the formation of the solar system, though the injection efficiencies in the present models are lower than desired.Comment: 39 pages, 14 figures. in press, Ap