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.

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.

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.

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.

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.

Superprotonic conduction of intrinsically zwitterionic microporous polymers based on easy-to-make squaraine, croconaine and rhodizaine dyes.

Porous organic polymers (POPs) have been prepared via a novel metal free polycondensation between a tritopic indole-based monomer and squaric, croconic and rhodizonic acids. Each of the three POPs exhibited high BET surface areas (331-667 m2 g-1) and zwitterionic structures. Impedance measurements revealed that the intrinsic POPs were relatively weak proton conductors, with a positive correlation between the density of oxo-groups and the proton conduction. Doping the materials with LiCl vastly improved the proton conductivity up to a value of 0.54 S cm-1 at 90 °C and 90% relative humidity.

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.

Impact of chronic kidney disease on case ascertainment for hospitalised acute myocardial infarction: an English cohort study.

OBJECTIVES: Acute myocardial infarction (AMI) case ascertainment improves for the UK general population using linked health data sets. Because care pathways for people with chronic kidney disease (CKD) change based on disease severity, AMI case ascertainment for these people may differ compared with the general population. We aimed to determine the association between CKD severity and AMI case ascertainment in two secondary care data sets, and the agreement in estimated glomerular filtration rate (eGFR) between the same data sets. METHODS: We used a cohort study design. Primary care records for people with CKD or risk factors for CKD, identified using the National CKD Audit (2015-2017), were linked to the Myocardial Ischaemia National Audit Project (MINAP, 2007-2017) and Hospital Episode Statistics (HES, 2007-2017) secondary care registries. People with an AMI recorded in either MINAP, HES or both were included in the study cohort. CKD status was defined using eGFR, derived from the most recent serum creatinine value recorded in primary care. Moderate-severe CKD was defined as eGFR <60 mL/min/1.73 m2, and mild CKD or at risk of CKD was defined as eGFR ≥60 mL/min/1.73 m2 or eGFR missing. CKD stages were grouped as (1) At risk of CKD and Stages 1-2 (eGFR missing or ≥60 mL/min/1.73 m2), (2) Stage 3a (eGFR 45-59 mL/min/1.73 m2), (3) Stage 3b (eGFR 30-44 mL/min/1.73 m2) and (4) Stages 4-5 (eGFR <30 mL/min/1.73 m2). RESULTS: We identified 6748 AMIs: 23% were recorded in both MINAP and HES, 66% in HES only and 11% in MINAP only. Compared with people at risk of CKD or with mild CKD, AMIs in people with moderate-severe CKD were more likely to be recorded in both MINAP and HES (42% vs 11%, respectively), or MINAP only (22% vs 5%), and less likely to be recorded in HES only (36% vs 84%). People with AMIs recorded in HES only or MINAP only had increased odds of death during hospitalisation compared with those recorded in both (adjusted OR 1.61, 95% CI 1.32 to 1.96 and OR 1.60, 95% CI 1.26 to 2.04, respectively). Agreement between eGFR at AMI admission (MINAP) and in primary care was poor (kappa (K) 0.42, SE 0.012). CONCLUSIONS: AMI case ascertainment is incomplete in both MINAP and HES, and is associated with CKD severity.

Femoral Stem Fracture in Hip Revision Arthroplasty: A Systematic Literature Review of the Real-World Evidence.

BACKGROUND: Total hip arthroplasty (THA) presents as an excellent treatment for the osteoarthritic hip, demonstrating good survival rates. However, aseptic loosening and infection are the main causes of operative revision. The methods used in revision surgery are non-modular or modular THA implants. In addition to the abovementioned revision reasons for THA, this treatment could be associated with the possibility of femoral stem fracture, especially in the modular system. The topic of material failure has been focused on in the public media. The question arises as to how such media reports correlate with the published literature. The observed mentioned number of cases concerning a femoral stem fracture vary between one single case and up to 18.5% within a clinical study, thus presenting an inhomogeneous data situation with a large span. The specific aim of this systematic review is to establish facts and clarify the number of unforeseen events of a femoral stem fracture based on peer review articles and registry data. This clarification is important to us, as these media reports have led to uncertainty among patients. METHODS: A systematic review was performed in accordance with the PRISMA statement. Peer review articles in English and German, presenting original articles, meta-analyses, or case reports, were searched from the turn of the millennium up to December 2019. Only articles that reported a femoral stem component fracture, with content of clinical data as well as register data, were included. Relevant papers published after the defined research time frame were taken into account within the discussion. RESULTS: In total, 218 fractures of a femoral stem (141 primary and 77 revision THA) component could be identified within the selected literature. Most cases of a femoral stem fracture occurred in the modular THA implants compared to the non-modular stems. Regarding revision THA, in summary, 77 implants, presenting 23 non-modular and 54 modular implants, failed by means of femoral stem fracture. A review of 11 National Joint Registries shows a revision rate between 0.04 and 0.05% in only 2 registers according to the specific subject of a femoral stem fracture. For the remaining 9 registers, however, detailed information is lacking and only nonspecific information such as a generic "implant failure" or "other reason" (which can cover a multitude of causes) is supplied. CONCLUSION: A femoral stem fracture presents a devastating complication for the patient, the surgeon as well as for the manufacturer of the implant. Modular THA implants play an increasingly valuable role concerning restoration of individual anatomy in modern THA revision surgery, especially within complex cases. Regarding revision procedures, data suggests a lower risk of femoral stem fracture for modular implants compared to primary procedures, while the risk of fracture for non-modular implants seems to increase during revision. Ultimately, it cannot be proven whether this is actually applicable, since the absolute number of implanted prosthesis systems is not known. Various implant-, patient-, and surgeon-related factors may lead to these reported femoral stem fractures. However, this systematic review suggests that this is, in general, a rare complication.

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.

Ethical Duties of Nephrologists: When Patients Are Nonadherent to Treatment.

When providing care, nephrologists are subject to various ethical duties. Beyond the Hippocratic notion of doing no harm, nephrologists also have duties to respect their patients' autonomy and dignity, to meet their patients' care goals in the least invasive way, to act impartially, and, ultimately, to do what is (clinically) beneficial for their patients. Juggling these often-conflicting duties can be challenging at the best of times, but can prove especially difficult when patients are not fully adherent to treatment. When a patient's nonadherence begins to cause harm to themselves and/or others, it may be questioned whether discontinuation of care is appropriate. We discuss how nephrologists can meet their ethical duties when faced with nonadherence in patients undergoing hemodialysis, including episodic extreme agitation, poor renal diet, missed hemodialysis sessions, and emergency presentations brought on by nonadherence. Furthermore, we consider the impact of cognitive impairment and provider-family conflict when making care decisions in a nonadherence context, as well as how the coronavirus disease 2019 pandemic might affect responses to nonadherence. Suggestions are provided for ethically informed responses, prioritizing a patient-narrative approach that is attentive to patients' values and preferences, multidisciplinarity, and the use of behavioral contracts and/or technology where appropriate.

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.

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.

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.

Model-Based Roentgen Stereophotogrammetric Analysis to Monitor the Head-Taper Junction in Total Hip Arthroplasty in Vivo-And They Do Move.

Model-based Roentgen stereophotogrammetric analysis (RSA) using elementary geometrical shape (EGS) models allows migration measurement of implants without the necessity of additional attached implant markers. The aims of this study were: (i) to assess the possibility of measuring potential head-taper movement in THA in vivo using model-based RSA and (ii) to prove the validity of measured head-taper migration data in vitro and in vivo. From a previous RSA study with a 10 years follow-up, retrospectively for n = 45 patients head-taper migration was calculated as the relative migration between femoral ball head and taper of the femoral stem using model-based RSA. A head-taper migration of 0.026 mm/year can be detected with available RSA technology. In vitro validation showed a total migration of 268 ± 11 µm along the taper axis in a similar range to what has been reported using the RSA method. In vivo, a proof for interchangeable applicability of model-based RSA (EGS) and standard marker-based RSA methods was indicated by a significant deviation within the migration result after 12-month follow-up for all translation measurements, which was significantly correlated to the measured head-taper migration (r from 0.40 to 0.67; p < 0.05). The results identified that model-based RSA (EGS) could be used to detect head-taper migration in vivo and the measured movement could be validated in vitro and in vivo as well. Those findings supported the possibility of applying RSA for helping evaluate the head-taper corrosion related failure (trunnionosis).