An introduction to realist evaluation and synthesis for kidney research.

Realist research describes a methodological approach that aims to explore how and why interventions work, for whom, and under what circumstances. Rather than quantifying how well an intervention works under specific conditions, realist theory explores the function of interventions in detail and specifically considers how the contexts in which interventional components are delivered influence the mechanisms that lead to outcomes. Realist methods can be applied to primary data (realist evaluation) or secondary data (realist synthesis). Although realist techniques are increasingly being used in the evaluation of complex interventions, there are relatively few published studies in the field of kidney care. In this review, we outline the theory and principles behind realist methods through discussion of a published realist synthesis describing complex interventions promoting delivery of optimal chronic kidney disease care. We discuss other kidney studies that have used realist methodology and situations where realist techniques could be applied to advance our understanding of how to best deliver care to patients with kidney disease.

Management and outcomes of myocardial infarction in people with impaired kidney function in England.

BACKGROUND: Acute myocardial infarction (AMI) causes significant mortality and morbidity in people with impaired kidney function. Previous observational research has demonstrated reduced use of invasive management strategies and inferior outcomes in this population. Studies from the USA have suggested that disparities in care have reduced over time. It is unclear whether these findings extend to Europe and the UK. METHODS: Linked data from four national healthcare datasets were used to investigate management and outcomes of AMI by estimated glomerular filtration rate (eGFR) category in England. Multivariable logistic and Cox regression models compared management strategies and outcomes by eGFR category among people with kidney impairment hospitalised for AMI between 2015-2017. RESULTS: In a cohort of 5 835 people, we found reduced odds of invasive management in people with eGFR < 60mls/min/1.73m2 compared with people with eGFR ≥ 60 when hospitalised for non-ST segment elevation MI (NSTEMI). The association between eGFR and odds of invasive management for ST-elevation MI (STEMI) varied depending on the availability of percutaneous coronary intervention. A graded association between mortality and eGFR category was demonstrated both in-hospital and after discharge for all people. CONCLUSIONS: In England, patients with reduced eGFR are less likely to receive invasive management compared to those with preserved eGFR. Disparities in care may however be decreasing over time, with the least difference seen in patients with STEMI managed via the primary percutaneous coronary intervention pathway. Reduced eGFR continues to be associated with worse outcomes after AMI.

Propensity Score and Instrumental Variable Techniques in Observational Transplantation Studies: An Overview and Worked Example Relating to Pre-Transplant Cardiac Screening.

Inferring causality from observational studies is difficult due to inherent differences in patient characteristics between treated and untreated groups. The randomised controlled trial is the gold standard study design as the random allocation of individuals to treatment and control arms should result in an equal distribution of known and unknown prognostic factors at baseline. However, it is not always ethically or practically possible to perform such a study in the field of transplantation. Propensity score and instrumental variable techniques have theoretical advantages over conventional multivariable regression methods and are increasingly being used within observational studies to reduce the risk of confounding bias. An understanding of these techniques is required to critically appraise the literature. We provide an overview of propensity score and instrumental variable techniques for transplant clinicians, describing their principles, assumptions, strengths, and weaknesses. We discuss the different patient populations included in analyses and how to interpret results. We illustrate these points using data from the Access to Transplant and Transplant Outcome Measures study examining the association between pre-transplant cardiac screening in kidney transplant recipients and post-transplant cardiac events.

Preoperative planning of total knee arthroplasty: reliability of axial alignment using a three-dimensional planning approach.

BACKGROUND: Preoperative templating of total knee arthroplasty (TKA) can nowadays be performed three-dimensionally with software solutions using computed tomography (CT) datasets. Currently there is no consensus concerning the axial orientation of TKA components in three-dimensional (3D) planning. PURPOSE: To assess intra-/inter-observer reliability of detection of different bony landmarks in planning axial component alignment using axial CT images and 3D reconstructions. MATERIAL AND METHODS: Intra- and inter-observer reliability of determination of four predefined axial femoral and tibial axes was calculated using data from CT scans. Axes determination was performed on the axial slices and on the 3D reconstruction using preoperative planning software. In summary, 61 datasets were analyzed by one medical student (intra-observer reliability) and 15 datasets were analyzed by four different observers independently (inter-observer reliability). RESULTS: For the femur, clinical epicondylar axis and posterior condylar axis showed the best reliability with an inter-observer variability of 0.7° and 0.5°, respectively. For the tibia, posterior condylar axis provided best reliability (inter-observer variability: 1.7°). Overall variability was greater for tibial than for femoral axes. Reliability of axis determination was more accurate using axial CT slices rather than 3D reconstructions. CONCLUSION: The femoral clinical epicondylar axis is highly reliable. Landmarks for the tibia are not as easily identifiable as for the femur. The tibial posterior condylar axis presents the axis with highest reliability. Based on these results, clinical epicondylar axis for orientation of the femoral TKA component and posterior condylar axis for the tibial implant, both defined on axial slices can be recommended.

A propensity score-matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients.

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

Do routine hospital data accurately record comorbidity in advanced kidney disease populations? A record linkage cohort study.

BACKGROUND: Routine healthcare datasets capturing clinical and administrative information are increasingly being used to examine health outcomes. The accuracy of such data is not clearly defined. We examine the accuracy of diagnosis recording in individuals with advanced chronic kidney disease using a routine healthcare dataset in England with comparison to information collected by trained research nurses. METHODS: We linked records from the Access to Transplant and Transplant Outcome Measures study to the Hospital Episode Statistics dataset. International Classification of Diseases (ICD-10) and Office for Population Censuses and Surveys Classification of Interventions and Procedures (OPCS-4) codes were used to identify medical conditions from hospital data. The sensitivity, specificity, positive and negative predictive values were calculated for a range of diagnoses. RESULTS: Comorbidity information was available in 96% of individuals prior to starting kidney replacement therapy. There was variation in the accuracy of individual medical conditions identified from the routine healthcare dataset. Sensitivity and positive predictive values ranged from 97.7 and 90.4% for diabetes and 82.6 and 82.9% for ischaemic heart disease to 44.2 and 28.4% for liver disease. CONCLUSIONS: Routine healthcare datasets accurately capture certain conditions in an advanced chronic kidney disease population. They have potential for use within clinical and epidemiological research studies but are unlikely to be sufficient as a single resource for identifying a full spectrum of comorbidities.

Conjugated porous polymers: incredibly versatile materials with far-reaching applications.

Conjugated porous polymers (CPPs) are a class of amorphous polymer networks that are, in their design, fully cross-linked and fully π-conjugated. The cross-linked nature of CPPs means that they have permanent intrinsic porosity (on the nanometer scale), which, in combination with the fully π-conjugated framework, makes these materials unique among the wider class of porous polymeric materials. In recent years, the need for new and efficient functional materials has driven the development of CPPs as versatile platforms for applications including (photo)catalysis, light harvesting, gas separation and storage, chemosensing, environmental remediation and energy storage. The efficiency of these materials towards these described applications is heavily influenced by the choice of molecular building blocks and synthetic conditions, allowing for facile tailoring and optimisation of the structure and properties. The aim of this review is to highlight select works on CPPs, including basic structural design principles, various synthetic protocols and topical applications of these versatile materials.

Limited health literacy is associated with reduced access to kidney transplantation.

Limited health literacy is common in patients with chronic kidney disease (CKD) and has been variably associated with adverse clinical outcomes. The prevalence of limited health literacy is lower in kidney transplant recipients than in individuals starting dialysis, suggesting selection of patients with higher health literacy for transplantation. We investigated the relationship between limited health literacy and clinical outcomes, including access to kidney transplantation, in a prospective UK cohort study of 2,274 incident dialysis patients aged 18-75 years. Limited health literacy was defined by a validated Single Item Literacy Screener (SILS). Multivariable regression was used to test for association with outcomes after adjusting for age, sex, socioeconomic status (educational level and car ownership), ethnicity, first language, primary renal diagnosis, and comorbidity. In fully adjusted analyses, limited health literacy was not associated with mortality, late presentation to nephrology, dialysis modality, haemodialysis vascular access, or pre-emptive kidney transplant listing, but was associated with reduced likelihood of listing for a deceased-donor transplant (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.51-0.90), receiving a living-donor transplant (HR 0.41; 95% CI 0.19-0.88), or receiving a transplant from any donor type (HR 0.65; 95% CI 0.44-0.96). Limited health literacy is associated with reduced access to kidney transplantation, independent of patient demographics, socioeconomic status, and comorbidity. Interventions to ameliorate the effects of low health literacy may improve access to kidney transplantation.

Health literacy and patient outcomes in chronic kidney disease: a systematic review.

Background: Limited health literacy affects 25% of people with chronic kidney disease (CKD), and may reduce self-management skills resulting in poorer clinical outcomes. By disproportionately affecting people with low socio-economic status and non-white ethnicity, limited health literacy may promote health inequity. Methods: We performed a systematic review of quantitative studies of health literacy and clinical outcomes among adults with CKD. Results: A total of 29 studies (13 articles; 16 conference abstracts) were included. One included non-USA patients. Of the 29 studies, 5 were cohort studies and 24 were cross-sectional. In all, 18 300 patients were studied: 4367 non-dialysis CKD; 13 202 dialysis; 390 transplant; 341 unspecified. Median study size was 127 [interquartile range (IQR) 92-238)], but 480 (IQR 260-2392) for cohort studies. Median proportion of non-white participants was 48% (IQR 17-70%). Six health literacy measures were used. Outcomes included patient attributes, care processes, clinical/laboratory parameters and 'hard' clinical outcomes. Limited health literacy was significantly, independently associated with hospitalizations, emergency department use, missed dialysis sessions, cardiovascular events and mortality (in cohort studies). Study quality was high (1 study), moderate (3 studies) and poor (25 studies), limited by sampling methods, variable adjustment for confounders and reduced methodological detail given in conference abstracts. Conclusions: There is limited robust evidence of the causal effects of health literacy on patient outcomes in CKD. Available evidence suggests associations with adverse clinical events, increased healthcare use and mortality. Prospective studies are required to determine the causal effects of health literacy on outcomes in CKD patients, and examine the relationships between socio-economic status, comorbidity, health literacy and CKD outcomes. Intervention development and evaluation will determine whether health literacy is a modifiable determinant of poor outcomes in CKD.

Concomitant Sternal Fracture in Flail Chest: An Analysis of 21,741 Polytrauma Patients from the TraumaRegister DGU®.

Background Isolated sternal fractures (SFs) rarely show complications, but their influence in a thorax trauma of the seriously injured still remains unclear. Methods A retrospective analysis of the TraumaRegister DGU® was performed involving the years 2009 to 2013 (Injury Severity Score [ISS] ≥ 16, primary admission to a trauma center). Cohort formation: Unilateral and bilateral flail chest (FC) injuries with and without a concomitant SF, respectively. Results In total, 21,741 patients (25% female) met the inclusion criteria, with 3,492 (16.1%) showing SF. Unilateral FC patients were on average 53.6 ± 18.4 years old, and bilateral FC patients were on average 55.2 ± 17.7 years old. The ISS in unilateral FC and bilateral FC amounted to 31.2 ± 13.0 and 43.4 ± 13.1 points, respectively. FC with an SF occurred more frequently as an injury to car occupants and less frequently as an injury to motorcyclists or in injuries due to falls. Conclusion Patients with an SF additional to an FC had longer hospital and intensive care unit stays and were longer artificially respirated than those patients without an SF. SF indicates possible cardiac and thoracic spine injuries.

Antibacterial Effect of a 4x Cu-TiO2 Coating Simulating Acute Periprosthetic Infection-An Animal Model.

The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO2 in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the femoral condyle of rabbits (n = 36) divided into 3 groups. After one week in group 1 (control) the bolts were removed without any replacement. In group2 Ti6Al4V bolts with a 4x Cu-TiO2 coating and in group 3 beads of a gentamicin-PMMA chain were imbedded into the borehole. Microbiological investigation was performed at the primary surgery, at the revision surgery and after scarification of the rabbits 3 weeks after the first surgery. Blood tests were conducted weekly. The initial overall infection rate was 88.9%. In group 2 and 3 a significant decrease of the infection rate was shown in contrast to the control group. The C-reactive protein (CRP) levels declined one week after the first surgery except in the control group where the CRP level even increased. This is the first in vivo study that demonstrated the antibacterial effects of a fourfold Cu-TiO2 coating. For the future, the coating investigated could be a promising option in the treatment of implant-associated infections.

Limited health literacy in advanced kidney disease.

Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

The oblique fracture of the manubrium sterni caused by a seatbelt--a rare injury? Treatment options based on the experiences gained in a level I trauma centre.

INTRODUCTION: Sternal fractures are rare with 3-8 % out of the total number of trauma cases mostly caused by direct impact to the anterior chest wall. Most cases described are due to motor vehicle crash either caused by direct impact to the steering wheel or by the seat belt. Fractures mainly occur to the sternal body. Only rarely are cases of manubrium fractures described in literature, for example, in relationship with a direct impact to the shoulder which caused an oblique fracture near to the sternoclavicular joint. Three patients with profoundly dislocated oblique manubrium fracture were admitted to our Level I Trauma Center in 2012 and 2013. Those patients suffered from instability of the upper sternum and the shoulder girdle. MATERIAL AND METHODS: Between January 2012 and October 2013, a total of 538 trauma patients were admitted to the emergency room and received whole body CT-scan. They were analysed retrospectively for sternal fractures. In cases of instability and dislocation, fracture stabilisation was performed by anterior plating through a medial approach using low profile titanium plates (MatrixRib®). RESULTS: Seventy-nine (14.7 %) patients showed sternal fracture, out of which 13 (2.4 %) patients showed a fracture of manubrium, ten caused by seatbelt. In three cases stabilization was performed. Follow up showed sufficient consolidation without complications. DISCUSSION: A total of 16.5 % of sternal fractures were localized at the manubrium, mostly caused by seat belt. Fractures without significant dislocation seemed to be stable and healed well under conservative treatment. Dislocation in this region leads to unstable shoulder girdle. Anterior plating provides sufficient stabilisation and allowed consolidation.

Medication-related osteonecrosis of the jaw in a paediatric patient taking denosumab: a case report.

Medication-related osteonecrosis of the jaw (MRONJ) is a known complication of antiresorptive and anti-angiogenic therapies in adults. Increasingly, these drugs are being prescribed for children with a variety of conditions, such as osteogenesis imperfecta and cancers of the bone. Review of the literature, however, reveals no reported paediatric MRONJ cases to date. We present such a case in a nine-year-old female patient with a vertebral aneurysmal bone cyst, who received dental extractions subsequent to denosumab therapy.

Regioselective electrophilic aromatic borylation as a method for synthesising sterically hindered benzothiadiazole fluorophores.

Regioselective stepwise phenylation of 4,7-diarylbenzo[c][1,2,5]thiadiazole fluorophores has been achieved through a facile one-pot, three-step synthetic strategy involving sequential borylation, hydroxydechlorination and Suzuki-Miyaura cross-coupling reactions. Crucial to the selectivity was the use of BCl3 to regioselectively install a boronic acid group in the ortho-position of only one of the diaryl groups. The subsequent introduction of ortho-phenyl groups through Suzuki-Miyaura cross-coupling gave rise to twisted structures with hindered intramolecular rotation, providing a structural lever with which the fluorophore absorption and emission properties could be adjusted.

Complex Interventions Across Primary and Secondary Care to Optimize Population Kidney Health: A Systematic Review and Realist Synthesis to Understand Contexts, Mechanisms, and Outcomes.

BACKGROUND: CKD affects 850 million people worldwide and is associated with high risk of kidney failure and death. Existing, evidence-based treatments are not implemented in at least a third of eligible patients, and there is socioeconomic inequity in access to care. While interventions aiming to improve delivery of evidence-based care exist, these are often complex, with intervention mechanisms acting and interacting in specific contexts to achieve desired outcomes. METHODS: We undertook realist synthesis to develop a model of these context-mechanism-outcome interactions. We included references from two existing systematic reviews and from database searches. Six reviewers produced a long list of study context-mechanism-outcome configurations based on review of individual studies. During group sessions, these were synthesized to produce an integrated model of intervention mechanisms, how they act and interact to deliver desired outcomes, and in which contexts these mechanisms work. RESULTS: Searches identified 3371 relevant studies, of which 60 were included, most from North America and Europe. Key intervention components included automated detection of higher-risk cases in primary care with management advice to general practitioners, educational support, and non-patient-facing nephrologist review. Where successful, these components promote clinician learning during the process of managing patients with CKD, promote clinician motivation to take steps toward evidence-based CKD management, and integrate dynamically with existing workflows. These mechanisms have the potential to result in improved population kidney disease outcomes and cardiovascular outcomes in supportive contexts (organizational buy-in, compatibility of interventions, geographical considerations). However, patient perspectives were unavailable and therefore did not contribute to our findings. CONCLUSIONS: This systematic review and realist synthesis describes how complex interventions work to improve delivery of CKD care, providing a framework within which future interventions can be developed. Included studies provided insight into the functioning of these interventions, but patient perspectives were lacking in available literature.

Persistent renal replacement requirement following fulminant psittacosis infection in pregnancy.

Chlamydia psittaci is a zoonotic bacterial infection that most commonly causes mild flu-like symptoms in humans. However, in pregnancy, it can present as fulminant psittacosis associated with systemic illness, disseminated intravascular coagulation, renal and hepatic failure. We describe a case of a veterinary nurse in her 30s who presented at 32 weeks' gestation with rapidly progressive multiorgan failure, with positive, C. psittaci serology. Further history revealed that she had delivered a number of dead lambs in the preceding weeks to her illness, highlighting the importance of a thorough social history. C. psittaci should be suspected in the differential as a causative organism for severe pneumonia with multiorgan failure particularly in pregnant women with animal or bird contacts.