Acquired Brain Injury Among Adolescents and Young Adults: A Nationwide Study of Labor Market Attachment.

Purpose Young patients represent a particularly vulnerable group regarding vocational prognosis after an acquired brain injury (ABI). We aimed to investigate how sequelae and rehabilitation needs are associated with vocational prognosis up to 3 years after an ABI in 15-30-year-old patients. Methods An incidence cohort of 285 patients with ABI completed a questionnaire on sequelae and rehabilitation interventions and needs 3 months after the index hospital contact. They were followed-up for up to 3 years with respect to the primary outcome "stable return to education/work (sRTW)", which was defined using a national register of public transfer payments. Data were analyzed using cumulative incidence curves and cause-specific hazard ratios. Results Young individuals reported a high frequency of mainly pain-related (52%) and cognitive sequelae (46%) at 3 months. Motor problems were less frequent (18%), but negatively associated with sRTW within 3 years (adjusted HR 0.57, 95% CI 0.39-0.84). Rehabilitation interventions were received by 28% while 21% reported unmet rehabilitation needs, and both factors were negatively associated with sRTW (adjusted HR 0.66, 95% CI 0.48-0.91 and adjusted HR 0.72, 95% CI 0.51-1.01). Conclusions Young patients frequently experienced sequelae and rehabilitation needs 3 months post ABI, which was negatively associated with long-term labor market attachment. The low rate of sRTW among patients with sequelae and unmet rehabilitation needs indicates an untapped potential for ameliorated vocational and rehabilitating initiatives targeted at young patients.

Vocational/educational prognosis in adolescents and young adults with acquired brain injury: a nationwide cohort study.

OBJECTIVE: To determine prognostic factors for work ability and employment/educational status among young patients referred to outpatient neurorehabilitation clinics after an acquired brain injury. METHODS: A nationwide cohort study of 471 15-30-year-old patients who attended an interdisciplinary clinical assessment and provided questionnaire data at baseline and after one year. The outcomes were the Work Ability Score (WAS, 0-10 (best)) and employment/educational status after one year. Prognostic performance was analyzed using univariable regression and multivariable Ridge regression in a five-fold cross-validated procedure. RESULTS: Preinjury, 86% of the patients were employed, while the percentage had decreased to 55% at baseline and 52% at follow-up. The model, which included clinical measures of function, showed moderate prognostic performance with respect to WAS (R2=0.29) and employment/educational status (area under the curve (AUC)=0.77). Glasgow Outcome Scale Extended (R2=0.15, AUC=0.68) and the cognitive subscale of the Functional Independence Measure (R2=0.09, AUC=0.64), along with fatigue measured with the Multidimensional Fatigue Inventory (R2=0.15, AUC=0.60) were the single predictors with the highest predictive performance. CONCLUSION: Despite generally high scores in motor and cognitive tests, only about half of the patients were employed at baseline and this proportion remained stable. Global disability, cognitive sequelae and fatigue had the highest prognostic performance.

Predictors of disability in adolescents and young adults with acquired brain injury after the acute phase.

AIM: To develop and validate a prediction model for disability among young patients with acquired brain injury (ABI) after the acute phase. METHODS: Within a nationwide cohort of 446 15-30-year-old ABI-patients, we predicted disability in terms of Glasgow Outcome Scale - Extended (GOS-E) <7 12 months after baseline assessment in outpatient neurorehabilitation clinics. We studied 22 potential predictors covering demographic and medical factors, clinical tests, and self-reported fatigue and alcohol/drug consumption. The model was developed using multivariable logistic regression analysis and validated by 5-fold cross-validation and geographical validation. The model's performance was assessed by receiver operating characteristic curves and calibration plots. RESULTS: Baseline assessment took place a median of 12 months post-ABI. Low GOS-E (range 1-8 (best)) and Functional Independence Measure (range 18-126 (best)) along with high mental fatigue (range 4-20 (worst)) predicted disability. The model showed high validity and performance with an area under the curve of 0.82 (95% confidence interval (CI) 0.77, 0.87) in the cross-validation and 0.81 (95% CI 0.73, 0.88) in the geographical validation. CONCLUSION: We developed and validated a parsimonious model which effectively predicted disability. The model may be useful to guide decision-making in outpatient neurorehabilitation clinics treating young patients with ABI.

Segmentation, retardation and mass approximation of birefringent particles on a standard light microscope.

This study presents a simple technique for the approximation of retardation, thickness and mass of birefringent particles with a retardation from 8 to 231 nm retardation. Tuning of the imaging system (standard light microscope equipped with a left and a right circular polarizer) to match grey values of polymer retarder films of known retardation with rendered grey values allows for a robust calibration and accurate approximation of retardation. In addition, a technique for accurate particle segmentation using a Canny-Deriche algorithm was used to minimize the bias on mass estimated from different thresholding techniques. The technique was tested using microscopic calcitic plates called coccoliths produced by the marine algal group coccolithophores, and the results compare well with published coccolith mass estimates obtained from volumetric analysis. LAY DESCRIPTION: Material with certain optical properties display interference colours when observed in a light microscope under circular polarized light. This study presents a simple technique for measuring the thickness and retardation of small particles within the 8 to 231 nm retardation range based on the grey values of their interference colours. Retardation is a measure of the distance between waves of two mutually perpendicular polarized light waves after passing through material. The technique involves the tuning of a standard light microscope system equipped with a left and a right circular polarizer and a digital camera to match grey values of polymer retarder films with a known retardation with grey values of a digitially rendered Michel-Lévy chart. A technique for accurate isolation of particles from the image background using a Canny-Deriche algorithm is also described, which avoids possible biased results from thresholding. The techniques were tested using microscopic calcitic plates called coccoliths produced by the marine algal group coccolithophores, and the results compare well with published estimates obtained from volumetric analysis.

Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response.

BACKGROUND: The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems' decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. DISCUSSION: A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. CONCLUSION: Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

Preoperative antithrombotic therapy and risk of blood transfusion and mortality following hip fracture surgery: a Danish nationwide cohort study.

Hip fracture surgery is associated with high risk of bleeding and mortality. The patients often have cardiovascular comorbidity, which requires antithrombotic treatment. This study found that preoperative use of oral anticoagulants was not associated with transfusion or mortality following hip fracture surgery, whereas increased risk may exist for antiplatelet drugs. INTRODUCTION: Hip fracture surgery is associated with high bleeding risk and mortality; however, data on operative outcomes of hip fracture patients admitted while on antithrombotic therapy is sparse. We examined if preoperative antithrombotic treatment was associated with increased use of blood transfusion and 30-day mortality following hip fracture surgery. METHODS: Using data from the Danish Multidisciplinary Hip Fracture Registry, we identified 74,791 hip fracture surgery patients aged ≥ 65 years during 2005-2016. Exposure was treatment with non-vitamin K antagonist oral anticoagulant (NOAC), vitamin K antagonists (VKA), or antiplatelet drugs at admission for hip fracture. Outcome was blood transfusion within 7 days postsurgery and death within 30 days. RESULTS: A 45.3% of patients received blood transfusion and 10.6% died. Current NOAC use was associated with slightly increased risk of transfusion (adjusted relative risk (aRR) 1.07, 95% confidence interval (CI) 1.01-1.14), but similar mortality risk (adjusted hazard ratio (aHR) 0.88, 95% CI 0.75-1.03) compared with non-users. The pattern remained when restricting to patients with short surgical delay (< 24 h). VKA users did not have increased risk of transfusion or mortality. The risks of transfusion (aRR 1.15 95% CI 1.12-1.18) and 30-day mortality (aHR 1.18 95% CI 1.14-1.23) were increased among antiplatelet users compared with non-users. CONCLUSIONS: In an observational setting, neither preoperative NOAC nor VKA treatments were associated with increased risk of 30-day postoperative mortality among hip fracture patients. NOAC was associated with slightly increased risk of transfusion. Preoperative use of antiplatelet drugs was associated with increased risk of transfusion and mortality.

Acute endovascular reperfusion treatment in patients with ischaemic stroke and large-vessel occlusion (Denmark 2011-2017).

BACKGROUND AND PURPOSE: Acute endovascular reperfusion treatment (aERT) of stroke patients with large-vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of aERT in daily clinical routine are warranted and, in this study, we present national data from Denmark during 2011-2017. METHODS: National data for Denmark from 2011 to 2017 on all aERT procedures in patients with acute ischaemic stroke and computed tomography angiography/magnetic resonance angiography-verified large-vessel occlusion were derived from the Danish Stroke Registry, a national clinical quality registry to which reporting is mandatory for all hospitals treating stroke patients. Outcome (modified Rankin Scale score) after 3 months, including time of death, was assessed prospectively based on clinical examination or the Danish Civil Registration System. RESULTS: During the 7 years of observation, a total of 1720 patients were treated with aERT. The annual number of procedures increased from 128 in 2011 to 409 in 2017. The median age was 70 years, 58% were males and median National Institutes of Health Stroke Scale score at baseline was 16. Median time from symptom onset to groin puncture was 238 min with a decreasing trend during the years. Successful recanalization was reported in 1306 (76%) patients. At 3-month follow-up, an modified Rankin Scale score of 0-2 was reported in 46% of patients, whereas 14% of patients had died. CONCLUSION: Routine data on aERT in acute ischaemic stroke in Denmark from 2011 to 2017 suggest that the procedure is safe and efficacious.

Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation. RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

Accurate representation of interference colours (Michel-Lévy chart): from rendering to image colour correction.

Here a work flow towards an accurate representation of interference colours (Michel-Lévy chart) digitally captured on a polarised light microscope using dry and oil immersion objectives is presented. The work flow includes accurate rendering of interference colours considering the colour temperature of the light source of the microscope and chromatic adaptation to white points of RGB colour spaces as well as the colour correction of the camera using readily available colour targets. The quality of different colour correction profiles was tested independently on an IT8.7/1 target. The best performing profile was using the XYZ cLUT algorithm and it revealed a ΔE00 of 1.9 (6.4 no profile) at 5× and 1.1 (8.4 no profile) at 100× magnification, respectively. The overall performance of the workflow was tested by comparing rendered interference colours with colour-corrected images of a quartz wedge captured over a retardation range from 80-2500 nm at 5× magnification. Uncorrected images of the quartz wedge in sRGB colour space revealed a mean ΔE00 of 12.3, which could be reduced to a mean of 4.9 by applying a camera correction profile based on an IT8.7/1 target and the Matrix only algorithm (ΔE00 < 1.0 signifies colour differences imperceptible by the human eye). ΔE00 varied significantly over the retardation range of 80-2500 nm of the quartz wedge, but the reasons for this variation is not well understood and the quality of colour correction might be further improved in future by using custom made colour targets specifically designed for the analysis of high-order interference colours.

Prescription and predictors of post-stroke antidepressant treatment: A population-based study.

OBJECTIVES: Post-stroke depression and pathological crying are common and potentially serious complications after stroke and should be diagnosed and treated accordingly. Diagnosis and treatment probably rely on clinical experience and may pose certain challenges. We aimed to examine prescription and predictors of antidepressant treatment after ischemic stroke in a clinical setting. MATERIALS AND METHODS: In this registry-based follow-up study, consecutive ischemic stroke patients were identified from the Danish Stroke Registry, holding information on antidepressant treatment during admission in Aarhus County from 2003 to 2010. Information on prescription after discharge was obtained from the Danish Prescription Database. Treatment initiation was analyzed using the cumulative incidence method including death as a competing risk. Multiple logistic regression was used to identify potential predictors of treatment. RESULTS: Among 5070 consecutive first-ever ischemic stroke patients without prior antidepressant treatment, the cumulative incidence of antidepressant treatment and prescription over 6 months was 35.2% (95% CI: 33.8-36.6). Overall 16.5% (95% CI: 15.5-17.6) started treatment within 14 days corresponding to 48.1% (95% CI: 45.8-50.5) of all treated patients, and the most widely prescribed group of antidepressants was selective serotonin reuptake inhibitors (86%). Increasing stroke severity was associated with higher odds of initiating treatment. CONCLUSION: Antidepressant treatment in this real-life clinical setting was common and initiated early, in almost half the treated patients within 14 days. Our results suggest that special focus should be given to the severe strokes as they may have a greater risk of requiring treatment.

Return to work predictors after traumatic brain injury in a welfare state.

OBJECTIVE: To identify predictors of return to work (RTW) and stable labour market attachment (LMA) after severe traumatic brain injury (TBI) in Denmark. MATERIALS & METHODS: Patients aged 18-64 years, admitted to highly specialized neurorehabilitation after severe TBI 2004-2012 were included and followed up for ≤6 years. Weekly LMA data were retrieved from a national register of public assistance benefits. Weeks without or with supplemental public assistance benefits were defined as LMA weeks. Time of RTW was defined as first week with LMA. Stable LMA was defined as weeks with LMA ≥75% first year after RTW. Multivariable regressions were used to identify predictors of RTW and stable LMA among preinjury characteristics, injury severity, functional ability and rehabilitation trajectories. RESULTS: For the analyses of RTW and stable LMA, 651 and 336 patients were included, respectively. RTW was significantly associated with age (adjusted subhazard ratio 0.98, 95% CI 0.97-0.99), education (1.83, 95% CI 1.16-2.89), supplemental benefits (3.97, 95% CI 2.04-7.71), no benefits (4.86, 95% CI 2.90-8.17), length of stay in acute care (0.77, 95% CI 0.60-0.99) and time period of injury (1.56, 95% CI 1.15-2.10). The only significant predictor of stable LMA was age (adjusted odds ratio 0.97, 95% CI 0.95-0.99). CONCLUSION: RTW after severe TBI was associated with several socio-economic factors, whereas maintaining LMA depended on age only. We suggest that RTW rates could be improved by extensive rehabilitation targeting people that are older and low-educated, as these were less likely to RTW.

The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.

BACKGROUND: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. METHODS: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. RESULTS: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. CONCLUSION: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. CLINICAL TRIAL REGISTRATION: NCT 02317237.

Socioeconomic inequality in clinical outcome among hip fracture patients: a nationwide cohort study.

The evidence is limited regarding the association between socioeconomic status and the clinical outcome among patients with hip fracture. In this nationwide, population-based cohort study, higher education and higher family income were associated with a substantially lower 30-day mortality and risk of unplanned readmission after hip fracture. INTRODUCTION: We examined the association between socioeconomic status and 30-day mortality, acute readmission, quality of in-hospital care, time to surgery and length of hospital stay among patients with hip fracture. METHODS: This is a nationwide, population-based cohort study using prospectively collected data from the Danish Multidisciplinary Hip Fracture Registry. We identified 25,354 patients ≥65 years admitted with a hip fracture between 2010 and 2013 at Danish hospitals. Individual-level socioeconomic status included highest obtained education, family mean income, cohabiting status and migrant status. We performed multilevel regression analysis, controlling for potential confounders. RESULTS: Hip fracture patients with higher education had a lower 30-day mortality risk compared to patients with low education (7.3 vs 10.0% adjusted odds ratio (OR) = 0.74 (95% confidence interval (CI) (0.63-0.88)). The highest level of family income was also associated with lower 30-day mortality (11.9 vs 13.0% adjusted OR = 0.77, 95% CI 0.69-0.85). Cohabiting status and migrant status were not associated with 30-day mortality in the adjusted analysis. Furthermore, patients with both high education and high income had a lower risk of acute readmission (14.5 vs 16.9% adjusted OR = 0.94, 95% CI 0.91-0.97). Socioeconomic status was, however, not associated with quality of in-hospital care, time to surgery and length of hospital stay. CONCLUSIONS: Higher education and higher family income were associated with substantially lower 30-day mortality and risk of readmission after hip fracture.

Effectiveness of intensification therapies in Danes with Type 2 diabetes who use basal insulin: a population-based study.

AIMS: To examine the usage and real-life effectiveness of intensification therapies in people with Type 2 diabetes treated with basal insulin. METHODS: We used population-based healthcare databases in Denmark during 2000-2012 to identify all individuals with a first basal insulin prescription (with or without oral drugs), and evaluated subsequent intensification therapy with bolus insulin, premixed insulin or glucagon-like peptide-1 (GLP-1) receptor agonists. Poisson regression was used to compute the adjusted relative risks of reaching glycaemic control targets. RESULTS: We included 7034 initiators of basal insulin (median age 64 years, diabetes duration 5.3 years, 84% with oral co-medication and median (interquartile range) pre-insulin HbA1c level 77 (65-92) mmol/mol [9.2% (8.1-10.6%)]. Of these, 3076 (43.7%) received intensification therapy after a median of 11 months: 58.5% with premixed insulin, 29.0% with bolus insulin, 10.6% with GLP-1 receptor agonists, and 1.9% with more than one add-on. Overall, 22% had attained an HbA1c level of < 53 mmol/mol (< 7%) by 3-6 months after intensification, while 38% attained an HbA1c < 58 mmol/mol (< 7.5%). Compared with premixed insulin intensification, attainment of HbA1c < 53 and < 58 mmol/mol was similar with bolus insulin add-on [adjusted relative risk 1.03 (95% CI 0.86-1.24) and 1.02 (95% CI 0.91-1.15), and higher for GLP-1 receptor agonist add-on [adjusted relative risk 1.56 (95% CI 1.27-1.92) and 1.27 (1.10-1.47)]. CONCLUSIONS: Among people with Type 2 diabetes, 22 and 38% reached a target HbA1c < 53 mmol/mol (< 7%) or < 58 mmol/mol (< 7.5%), respectively, after intensification of their basal insulin therapy. Compared with premixed insulin, target attainment was similar with bolus insulin and higher with GLP-1 receptor agonists.

Ischemic stroke subtype is associated with outcome in thrombolyzed patients.

OBJECTIVES: The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients treated with IV-tPA. MATERIAL AND METHODS: We conducted a single-center retrospective analysis of MRI-selected stroke patients treated with IV-tPA between 2004 and 2010. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish the stroke subtype by 3 months. The outcomes of interest were a 3-month modified Rankin Scale score of 0-1 (favorable outcome), and early neurological improvement defined as complete remission of neurological deficit or improvement of ≥4 on the National Institute of Health Stroke Scale at 24 h. The outcomes among stroke subtypes were compared with multivariable logistic regression. RESULTS: Among 557 patients, 202 (36%) had large vessel disease (LVD), 153 (27%) cardioembolic stroke (CE), 109 (20%) small vessel disease, and 93 (17%) were of other or undetermined etiology. Early neurological improvement was present in 313 (56.4%) patients, and 361 (64.8%) patients achieved a favorable outcome. Early neurological improvement and favorable outcome were more likely in CE patients compared with LVD patients (odds ratio (OR), 2.1 (95% confidence interval, 1.4-3.3), and 2.0 (95% confidence interval, 1.2-3.3), respectively). CONCLUSIONS: Cardioembolic stroke patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV-tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes.

How can the research potential of the clinical quality databases be maximized? The Danish experience.

In Denmark, the need for monitoring of clinical quality and patient safety with feedback to the clinical, administrative and political systems has resulted in the establishment of a network of more than 60 publicly financed nationwide clinical quality databases. Although primarily devoted to monitoring and improving quality of care, the potential of these databases as data sources in clinical research is increasingly being recognized. In this review, we describe these databases focusing on their use as data sources for clinical research, including their strengths and weaknesses as well as future concerns and opportunities. The research potential of the clinical quality databases is substantial but has so far only been explored to a limited extent. Efforts related to technical, legal and financial challenges are needed in order to take full advantage of this potential.

Low Protein A20 in Minor Salivary Glands is Associated with Lymphoma in Primary Sjögren's Syndrome.

Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing lymphomas, particularly the subtype mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic antigen stimulation and increased activation of nuclear factor-κB (NF-κB) are important factors for the pathogenesis of MALT lymphomas. Protein A20 is an inhibitor of NF-κB. A recent study of pSS-associated MALT lymphomas identified potential functional abnormalities in the TNFAIP3 gene, which encodes protein A20. The present study aimed to assess protein A20 by immunohistochemistry (IHC) in minor salivary glands (MSGs) and lymphoma tissue sections of patients with pSS and investigate a potential association with lymphoma development. Protein A20 staining in lymphocytes was scored in four categories (0 = negative, 1 = weak, 2 = moderate and 3 = strong). For statistical purposes, these scores were simplified into negative (scores 0-1) and positive (scores 2-3). We investigated associations between protein A20-staining, focus scores, germinal centre (GC)-like structures and monoclonal B-cell infiltration in MSGs. MSG protein A20 staining was weaker in pSS patients with lymphomas than in those without lymphomas (P = 0.01). Weak protein A20 staining was also highly associated with a lack of GC formation (P < 0.01). Finally, weaker A20 staining was observed in the majority of pSS-associated MALT lymphoma tissues. In conclusion, we found absent or weak protein A20 immunoreactivity in MSGs of patients with pSS with lymphomas. This finding indicates that protein A20 downregulation in lymphocytes might be a mechanism underlying lymphoma genesis in patients with pSS.

Patient-level predictors of achieving early glycaemic control in Type 2 diabetes mellitus: a population-based study.

AIMS: To identify individual predictors of early glycaemic control in people with Type 2 diabetes mellitus after initiation of first glucose-lowering drug treatment in everyday clinical practice. METHODS: Using medical registries, we identified a population-based cohort of people with a first-time glucose-lowering drug prescription in Northern Denmark in the period 2000-2012. We used Poisson regression analysis to examine patient-level predictors of success in reaching early glycaemic control [HbA1c target of < 53 mmol/mol (7%)] < 6 months after treatment start. RESULTS: Among the 38 418 people (median age 63 years), 27 545 (72%) achieved early glycaemic control. The strongest predictor of achieving early control was pre-treatment HbA1c level; compared with a pre-treatment HbA1c level of ≤ 58 mmol/mol (7.5%), the adjusted relative risks of attaining early control were 0.63 (95% CI 0.61-0.64) for baseline HbA1c levels of > 58 and ≤ 75 mmol/mol (> 7.5 and ≤ 9%), and 0.58 (95% CI 0.57-0.59) for a baseline HbA1c level of > 9% (> 75 mmol/mol). All other examined predictors were only weakly associated with the chance of achieving early control. After adjustment, the only characteristics that remained independently associated with early control (in addition to high baseline HbA1c ) were being widowed (adjusted relative risk 0.95; 95% CI 0.93-0.97) and having a high Charlson comorbidity index score (score ≥ 3; adjusted relative risk 0.94; 95% CI 0.90-0.97). CONCLUSIONS: In a real-world clinical setting, people with Type 2 diabetes mellitus initiating glucose-lowering medication had a similar likelihood of achieving glycaemic control, regardless of sex, age, comorbidities and other individual factors; the only strong and potentially modifiable predictor was HbA1c before therapy start.

The influence of ERAP1 gene variants on clinical phenotype in ankylosing spondylitis.

OBJECTIVES: Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene variants diminish the risk of developing ankylosing spondylitis (AS) through a reduction in ERAP1 activity. We investigated whether disease expression was altered in patients who developed AS despite the presence of two protective ERAP1 variants. METHOD: We conducted a cross-sectional and longitudinal cohort study of patients with established AS (n = 334, 90% B27+, mean age at study 45 years) for whom clinical data and biological samples were collected during a research visit. Genotyping for the single nucleotide polymorphisms (SNPs) rs27044 and rs30187 was performed on genomic DNA by reverse transcription polymerase chain reaction (RT-PCR) with interleukin (IL)-6 and tumour necrosis factor (TNF) levels determined by a sandwich enzyme-linked immunosorbent assay (ELISA). Associations between genotypes and haplotypes, clinical and serological findings were analysed using SNPstats. RESULTS: Both SNPs were in strong linkage disequilibrium and formed three common haplotypes (C/C 0.65, G/T 0.30, and C/T 0.04). Haplotype C/T carried a lower risk for uveitis [odds ratio (OR) 0.32, p = 0.03] and elevated C-reactive protein (CRP) levels (OR 0.26, p = 0.04). There was no effect of ERAP1 haplotypes on cytokine levels or major outcomes after 8 years of follow-up. CONCLUSIONS: The ERAP1 rs27044/rs30187 haplotype C/T is associated with lower risk of extraspinal disease and systemic inflammation in Nordic AS patients but has no impact on IL-6 or TNF levels.

Prediction of adverse perinatal outcome of small-for-gestational-age pregnancy using size centiles and conditional growth centiles.

OBJECTIVE: To test whether adding conditional growth centiles to size centiles of estimated fetal weight (EFW) improves prediction of adverse perinatal outcome in pregnancies with or at risk of having a small-for-gestational-age (SGA) fetus. METHODS: This prospective longitudinal study included pregnant women at risk of or diagnosed with an SGA (≤ 5(th) centile) fetus. They underwent serial ultrasound measurements and the final two were included in the analyses for this study. The EFW was categorized into normal (> 5(th) or 10(th) centile) and abnormal (≤ 5(th) or 10(th) centile) for size and conditional growth before entering the variables into log-binomial regression analyses. Adverse outcomes were delivery < 37 weeks, operative delivery due to fetal distress, 5-min Apgar score < 7, newborn hypoglycemia (glucose < 2.0 mmol/L), admission to the neonatal intensive care unit and perinatal mortality. A combined outcome variable ('any adverse outcome') included one or more adverse outcomes. RESULTS: Complete biometric data were obtained for 211 women. Conditional growth and size centiles contributed independently to the prediction of adverse outcome. Combining conditional growth and size centiles significantly improved the prediction of outcomes compared with size centiles alone (e.g. for 5(th) centile cut-off for any adverse outcome, P = 0.023, log-likelihood test). Using a 5(th) centile threshold, for any adverse outcome, the specificity of 78% (95% CI, 70-84%) using size centile as a predictor was improved to 94% (95% CI, 89-97%) when conditional growth centile was added to the model, whereas the sensitivity was not significantly changed (60% (95% CI, 49-69%) vs 39% (95% CI, 30-50%)). CONCLUSIONS: Size centiles and conditional growth centiles contribute independently to the prediction of adverse perinatal outcome, and their combination further improves the prediction model. The results support an increased use of conditional growth centiles in the monitoring of fetuses at risk. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.