Costs and Budget Impact of Collagen-Based Vascular Closure Device Versus Manual Compression Following Peripheral Endovascular Procedures.

BACKGROUND: The objective of this study was to evaluate the annual costs and budget impact of using a vascular closure device to achieve hemostasis following femoral access endovascular procedures in England, compared with manual compression. METHODS: A budget impact model was developed in Microsoft® Excel, based on the estimated number of peripheral endovascular procedures eligible for day-case management performed annually by the National Health Service in England. The clinical effectiveness of vascular closure devices was captured based on the requirement for inpatient stays and the incidence of complications. Data for endovascular procedures, time to hemostasis, length of hospital stay, and complications were collected from public sources and the published literature. There were no patients involved in this study. Model outcomes are reported as estimated number of bed days and annual costs to the National Health Service for all peripheral endovascular procedures in England, and the average cost per procedure. The robustness of the model was tested in a sensitivity analysis. RESULTS: The model estimated savings for the National Health Service of up to £4.5 million annually if vascular closure devices were used in every procedure instead of manual compression. The model estimated an average cost saving of £176 per procedure for vascular closure devices over manual compression, primarily due to fewer inpatient stays. The sensitivity analysis demonstrated that the proportion of day-case procedures for vascular closure devices and manual compression was a key driver of costs and savings. CONCLUSIONS: The use of vascular closure devices for achieving hemostasis after peripheral endovascular procedures may be associated with lower resource use and cost burden, compared with manual compression, based on shorter time to hemostasis and ambulation and an increased likelihood of a day-case procedure.

The Benefits of Promoting Junior Trainees in Vascular Surgery.

Introduction United Kingdom surgical training consists of a two-year core surgical training (CST) followed by a six-year higher speciality training (ST). There is a significant step up in responsibility and operative skills when transitioning from core to higher training. One-way trainees can bridge this gap is to "act up" to registrar level "CST-R." The CST "steps up" to the role of ST typically in the latter part of their core training and gains exposure at being the "reg of the week," primary assistant in theatre, managing MDTs, and taking speciality referrals. This can be an excellent training opportunity. This study aims to demonstrate a quantitative improvement in trainee operation as a result of stepping up. Methods This study compares the operative experience of one vascular surgery-themed trainee during six months as a CST and six months acting up as a CST-R. The trainee's eLogbook was searched for all operations between August 3, 2022, and January 31, 2023, and between February 1, 2023, and August 1, 2023. The number of cases performed and the role played in each were analyzed. The number of low complexity cases conducted in each block was used as a baseline to ensure the progression seen was because of increasingly complex ST operating rather than the increase in CST level operating expected throughout CST. An abscess incision and drainage were used as the reference low-complexity case. Results The number of cases the trainee performed independently increased from 13% to 25%, while the number where they were simply assisting decreased from 43% to 35%. The number of cases where the trainer remained scrubbed decreased nonsignificantly from 43% to 39%. The number of low-complexity cases performed remained unchanged for each six-month block. Conclusion As a CST-R, the trainee played a more prominent operative role in a greater number of cases. The CST-R does require a supportive department and consultant body. It also enables other STs to gain more surgical exposure because of their reduced frequency of being the "reg of the week." If a trainee can remain in a post for two six-month blocks, then there is much to be gained from a formalised acting-up program, and consideration should be given to formally incorporating this into core surgical programs.

The phenotype of HLA-binding B cells from sensitized kidney transplant recipients correlates with clinically prognostic patterns of interferon-γ production against purified HLA proteins.

B cells play crucial roles in cell-mediated alloimmune responses. In vitro, B cells can support or regulate indirect T-cell alloreactivity in response to donor antigens on ELISpot and these patterns associate with clinical outcome. Previous reports of associations between B-cell phenotype and function have examined global phenotypes and responses to polyclonal stimuli. We hypothesized that studying antigen-specific B cells, using samples from sensitized patients, would inform further study to identify novel targets for intervention. Using biotinylated HLA proteins, which bind HLA-specific B cells via the B-cell receptor in a dose-dependent fashion, we report the specific phenotype of HLA-binding B cells and define how they associated with patterns of anti-HLA response in interferon-γ ELISpot. HLA-binding class-switched and IgM+CD27+ memory cells associated strongly with B-dependent interferon-γ production and appeared not suppressible by endogenous Tregs. When the predominant HLA-binding phenotype was naïve B cells, the associated functional ELISpot phenotype was determined by other cells present. High numbers of non-HLA-binding transitional cells associated with B-suppressed interferon-γ production, especially if Tregs were present. However, high frequencies of HLA-binding marginal-zone precursors associated with B-dependent interferon-γ production that appeared suppressible by Tregs. Finally, non-HLA-binding marginal zone precursors may also suppress interferon-γ production, though this association only emerged when Tregs were absent from the ELISpot. Thus, our novel data provide a foundation on which to further define the complexities of interactions between HLA-specific T and B cells and identify new targets for intervention in new therapies for chronic rejection.

Impact of arteriovenous fistulas versus arteriovenous grafts on vascular access performance in haemodialysis patients: A systematic review and meta-analysis.

BACKGROUND: Controversy exists regarding the best-performing vascular access type for patients undergoing haemodialysis. We aimed to compare outcomes of starting dialysis on arteriovenous fistulas (AVFs) versus arteriovenous grafts (AVGs) in haemodialysis patients. METHODS: We conducted a systematic search of multiple electronic information sources and bibliographic reference lists. The following outcome parameters were evaluated at 1, 2 and 5 years: primary failure, defined as access never used for dialysis; primary patency, defined as intervention-free access survival; primary-assisted patency, defined as uninterrupted access survival with interventions; and secondary patency, defined as cumulative access survival. RESULTS: We identified 15 comparative studies reporting a total of 118,434 patients who initiated haemodialysis with AVF (n = 95,143) or AVG (n = 23,291). Our analysis demonstrated that AVF was associated with significantly higher primary failure rate (OR: 2.05, p = .0005) but significantly higher rate of primary patency at 1 year (OR: 1.91, p < .00001), at 2 years (OR: 2.52, p < .00001) and at 5 years (OR: 2.59, p < .00001); and primary-assisted patency at 1 year (OR: 1.71, p < .00001), at 2 years (OR: 2.13, p < .00001) and 5 years (OR: 2.79, p < .00001). There was no significant difference in secondary patency at 1 year (OR: 1.08, p < .00001) but AVF had better secondary patency at 2 years (OR: 1.26, p < .00001) and 5 years (OR: 1.60, p < .00001) than AVG. CONCLUSIONS: The meta-analysis of best available comparative evidence (Level 2) demonstrated that AVFs may be associated with significantly higher primary failure rate but higher primary patency, primary-assisted patency and secondary patency at 1, 2 and 5 years compared to AVGs. However, the available evidence is subject to significant selection bias and confounding by indication.

Barriers and facilitators to implementing measurement-based care for depression in Shanghai, China: a situational analysis.

BACKGROUND: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. OBJECTIVE: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. METHODS: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. RESULTS: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. CONCLUSIONS: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.

Proprioception After Multiligament Knee Injury: Does Ligament Repair Lead to Better Proprioceptive Acuity Than Ligament Reconstruction?

Introduction Multiligament knee injuries are uncommon but serious injuries. There is ongoing debate on the optimal treatment of these injuries. We designed a study to establish the effects of repair or reconstruction on proprioceptive outcomes following multiligament injury to the knee. Materials and Methods A total of 34 patients were analysed by independent researchers who had no conflict of interest in the cases (23 in the repair group and 11 in the reconstruction group). Proprioception of the knee was measured using a previously validated tool to assess the reproduction of passive positioning. Functional outcome was measured using the Lysholm score. Sub-group analysis was performed. The mean time from injury to review was 83 months (range: 25-193 months). Results There were no significant differences in proprioceptive acuity between the injured (5.9±4.2°; range: 1.0-18.3°) and uninjured contralateral (control) knees (5.2±3.8°; range: 1.0-15.0°; p=0.35). Similarly, there was no significant difference in proprioceptive acuity identified between the injured knees that underwent repair (6.0±4.3°; range: 1.0-18.3°) or reconstruction (5.0±3.6°; range: 1.3-14°; p=0.53). Overall knee outcomes were good; the mean Lysholm score at final follow-up was 75.5±16.8 (range: 36-100). No significant differences were identified in any of the sub-groups. Conclusions We were unable to identify any differences in knee proprioceptive acuity between injured knees and controls nor between the types of surgical treatment, demonstrating equivocal recovery for both methods of treatment.

Network Meta-Analysis of Tofacitinib, Biologic Disease-Modifying Antirheumatic Drugs, and Apremilast for the Treatment of Psoriatic Arthritis.

BACKGROUND: Tofacitinib and other new treatments approved for use in psoriatic arthritis have only recently been included in psoriatic arthritis treatment guidelines, and studies evaluating the relative efficacy of available therapies are important to inform treatment decisions by healthcare professionals. OBJECTIVE: To perform a network meta-analysis to evaluate the efficacy and safety profiles of tofacitinib, biologic disease-modifying antirheumatic drugs (bDMARDs), and apremilast in patients with psoriatic arthritis naïve to tumor necrosis factor inhibitor therapy (TNFi-naïve) or with an inadequate response (TNFi-IR). METHODS: A systematic literature review used searches of MEDLINE, Embase, and The Cochrane Library on October 9, 2017. Randomized controlled trials including adult patients with psoriatic arthritis receiving treatment administered as monotherapy or with conventional synthetic DMARDs were selected. Efficacy outcomes included American College of Rheumatology 20 response, change from baseline in Health Assessment Questionnaire-Disability Index, ≥75% improvement in Psoriasis Area and Severity Index, and change from baseline in Dactylitis Severity Score and Leeds Enthesitis Index. Treatment effects were evaluated during placebo-controlled phases, using a binomial logit model for binary outcomes and a normal identify link model for other outcomes. Discontinuations due to adverse events and serious infection events were assessed as safety outcomes. RESULTS: The network meta-analysis included 24 published randomized controlled trials, of which 13 enrolled TNFi-naïve patients only, 3 enrolled TNFi-IR patients only, and 8 enrolled both TNFi-naïve and TNFi-IR patients. Placebo-controlled treatment durations ranged from 12 to 24 weeks. Indirect comparisons showed tofacitinib 5 and 10 mg BID to have similar efficacy compared with most bDMARDs and apremilast in improving joint symptoms (based on American College of Rheumatology 20 response), and with some bDMARDs in improving skin symptoms (based on Psoriasis Area and Severity Index) (tofacitinib 10 mg BID only in TNFi-IR) in patients with psoriatic arthritis who were TNFi-naïve or TNFi-IR. Results also showed that, compared with placebo, the improvement in physical functioning (based on Health Assessment Questionnaire-Disability Index) with tofacitinib 5 and 10 mg BID was similar to that observed with most bDMARDs and apremilast in TNFi-naïve patients, and similar to that observed with all bDMARDs with available data in the TNFi-IR population. Improvements in Dactylitis Severity Score and Leeds Enthesitis Index scores were comparable between treatments. Tofacitinib 5 and 10 mg BID were median-ranked 8 and 15, respectively, for discontinuation due to any adverse events, and 5 and 16, respectively, for a serious infection event out of a total of 20 treatments in the network (lower numbers are more favorable). CONCLUSIONS: Tofacitinib provides an additional treatment option for patients with psoriatic arthritis, both in patients naïve to TNFi and in those with TNFi-IR. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Effect of Optimized Immunosuppression (Including Rituximab) on Anti-Donor Alloresponses in Patients With Chronically Rejecting Renal Allografts.

RituxiCAN-C4 combined an open-labeled randomized controlled trial (RCT) in 7 UK centers to assess whether rituximab could stabilize kidney function in patients with chronic rejection, with an exploratory analysis of how B cell-depletion influenced T cell anti-donor responses relative to outcome. Between January 2007 and March 2015, 59 recruits were enrolled after screening, 23 of whom consented to the embedded RCT. Recruitment was halted when in a pre-specified per protocol interim analysis, the RCT was discovered to be significantly underpowered. This report therefore focuses on the exploratory analysis, in which we confirmed that when B cells promoted CD4+ anti-donor IFNγ production assessed by ELISPOT, this associated with inferior clinical outcome; these patterns were inhibited by optimized immunosuppression but not rituximab. B cell suppression of IFNγ production, which associated with number of transitional B cells and correlated with slower declines in kidney function was abolished by rituximab, which depleted transitional B cells for prolonged periods. We conclude that in this patient population, optimized immunosuppression but not rituximab promotes anti-donor alloresponses associated with favorable outcomes. Clinical Trial Registration: Registered with EudraCT (2006-002330-38) and www.ClinicalTrials.gov, identifier: NCT00476164.

Urgent Arthroplasty Interventions During the COVID-19 Pandemic: Operating Risks in Low-Prevalence Areas.

Background and objective Orthopaedic services have reorganised their delivery of care in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we aimed to share our operating experience during the coronavirus disease 2019 (COVID-19) pandemic and analyse its effect on urgent hip and knee arthroplasty. Our study involved a comparative analysis between a cohort of patients from 2019 (pre-COVID) and another from 2020. Methods Tha data relating to patients undergoing urgent operations requiring arthroplasty interventions such as for infection, periprosthetic fracture (PPF) and neck of femur fracture (NOF) between April and July of 2020 and 2019 were reviewed prospectively and retrospectively. Patients were categorised according to the Royal College of Surgeons (RCS) case prioritisation and the COVID-19 risk assessment. Data were collected on 30-day mortality, readmissions, reoperations, complications, length of hospital stay and theatre efficiency. This was analysed, matched and compared. Statistical analysis was performed on categorical variables including the time to the theatre as well as dual consultant operating. Results A total of 46 consecutive patients were included in the 2020 cohort with a mean age of 78 years (range: 58-108 years). The median length of stay was 6.5 days (range: 3-35 days) and the median time to theatre for NOF patients was 23.8 hours (range: 16.2-87.7 hours). There were six complications and two deaths; one of the deaths was COVID-19-related. A total of 56 patients were included from 2019 with a mean age of 74.6 years (range: 45-88 years). The median length of stay was five days (range: 1-18 days) and the median time to theatre for NOF patients was 40.8 hours (range: 18.9-167 hours). There were four complications and one death. Conclusion Based on our findings, it is safe to perform complex surgery in a region of low community prevalence of COVID-19, and the outcomes were comparable to those from a pre-COVID-19 cohort.

Developing a theory-driven framework for a football intervention for men with severe, moderate or enduring mental health problems: a participatory realist synthesis.

Background: Physical activity interventions are an important adjunct therapy for people with severe to moderate and/or enduring mental health problems. Football is particularly popular for men in this group. Several interventions have emerged over the past decade and there is a need to clearly articulate how they are intended to work, for whom and in what circumstances.Aims: To develop a theory-driven framework for a football intervention for men with severe, moderate and/or enduring mental health problems using a participatory realist approach.Methods: A participatory literature review on playing football as a means of promoting mental health recovery with a realist synthesis. It included the accounts and input of 12 mental health service users and the contributions of other stakeholders including football coaches and occupational therapists.Results: Fourteen papers were included in the review. Analysis revealed that interventional mechanisms were social connectedness, identity security, normalising experiences and positive affectivity. These supported mental health recovery. Outcomes were moderated by social stigma and several interventional factors such as over-competitiveness.Conclusions: The context mechanism outcome configuration framework for these interventions map well onto social models of mental health recovery and provide insight into how they work. This now requires testing.

Regulatory B cells: Development, phenotypes, functions, and role in transplantation.

The interest in regulatory B cells (Bregs) began in the 1970s with the evidence that B cells could downregulate the immune system by the production of "inhibitory" antibodies. Subsequently, a series of results from different studies have emphasized that B cells have antibody-independent immunoregulatory functions. Since then, different subsets of B cells with regulatory functions and their development and mechanisms of action have been identified both in human and in animal models of inflammation, transplantation, and autoimmunity. The present review outlines the suggested pathways by which Bregs develop, describes the different subsets of Bregs with their phenotypes and function as well as their role in transplantation, highlighting the differences between human and animal studies throughout.

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study.

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2-11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan-Meier analysis, the presence of DGF was associated with lower graft survival (log-rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617-11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.

Causes of renal allograft failure in the UK: trends in UK Renal Registry and National Health Service Blood and Transplant data from 2000 to 2013.

Background: Improvement in long-term renal allograft survival is impeded by incomplete or erroneous coding of causes of allograft loss. This study reports 13-year trends in causes of graft failure across the UK. Methods: National Health Service Blood and Transplant (NHSBT) and UK Renal Registry data were linked to describe UK kidney patients transplanted in 2000-13. NHSBT graft failure categories were used, with 'other' recoded when free text was available. Adjusted analyses examined the influence of age, ethnicity and donor type on causes of graft failure. Results: In 22 730 recipients, 5389 (23.7%) grafts failed within a median follow-up of 5 years. The two most frequent causes were death with a functioning graft (40.8%) and alloimmune pathology (25.0%). Graft survival was higher in recipients who were younger (mean 47.3 versus 50.7 years), received a pre-emptive transplant (20.2% versus 10.4%), spent less time on dialysis (median 1.6 versus 2.4 years) and received a living donor transplant (36.3% versus 22.2%), with no differences by sex, ethnicity or human leucocyte antigen mismatch. Allograft failure within 2 years of transplantation fell from 12.5% (2000-4) to 9.8% (2009-13). Surgical- and alloimmune-related failures decreased over time while death with a functioning graft became more common. Age, ethnicity and donor type were factors in recurrent primary disease and alloimmune pathology. Conclusions: Since 2000 there have been reductions in surgical and alloimmune graft failures in the UK. However, graft failure codes need to be revised if they are to remain useful and effective in epidemiological and quality improvement trials.

A Systematic Literature Review of Economic Evaluations of Antibiotic Treatments for Clostridium difficile Infection.

BACKGROUND AND OBJECTIVE: Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI. METHODS: Electronic databases (MEDLINE®, Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality. RESULTS: Overall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation. CONCLUSIONS: In most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets. OTHER: This analysis was initiated and funded by Astellas Pharma Inc.

Transitional B cell subsets-a convincing predictive biomarker for allograft loss?

In this issue, Cherukuri and colleagues describe a convincing association between the proportion of transitional B lymphocyte subsets in kidney transplant recipients and long-term outcomes, and present a biologically plausible mechanism, based on differential ability of T1 and T2 cells to regulate in vitro T cell responses to explain the link. Further work is clearly needed to validate their claim that measurement of T1/T2 ratios may represent a reliable and reproducible predictive biomarker of transplant outcomes.

Graft dysfunction in chronic antibody-mediated rejection correlates with B-cell-dependent indirect antidonor alloresponses and autocrine regulation of interferon-γ production by Th1 cells.

Chronic antibody-mediated rejection, a common cause of renal transplant failure, has a variable clinical phenotype. Understanding why some with chronic antibody-mediated rejection progress slowly may help develop more effective therapies. B lymphocytes act as antigen-presenting cells for in vitro indirect antidonor interferon-γ production in chronic antibody-mediated rejection, but many patients retain the ability to regulate these responses. Here we test whether particular patterns of T and B cell antidonor response associate with the variability of graft dysfunction in chronic antibody-mediated rejection. Our results confirm that dynamic changes in indirect antidonor CD4+ T-cell responses correlate with changes in estimated glomerular filtration rates, independent of other factors. Graft dysfunction progressed rapidly in patients who developed unregulated B-cell-driven interferon-γ production. However, conversion to a regulated or nonreactive pattern, which could be achieved by optimization of immunosuppression, associated with stabilization of graft function. Functional regulation by B cells appeared to activate an interleukin-10 autocrine pathway in CD4+ T cells that, in turn, impacted on antigen-specific responses. Thus, our data significantly enhance the understanding of graft dysfunction associated with chronic antibody-mediated rejection and provide the foundation for strategies to prolong renal allograft survival, based on regulation of interferon-γ production.

Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient.

Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a "full house" immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting "past resolved" infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

A Systematic Review of Methods for Handling Missing Variance Data in Meta-Analyses of Interventions in Type 2 Diabetes Mellitus.

AIMS: Meta-analysis is of critical importance to decision makers to assess the comparative efficacy and safety of interventions and is integral to health technology assessment. A major problem for the meta-analysis of continuous outcomes is that associated variance data are not consistently reported in trial publications. The omission of studies from a meta-analysis due to incomplete reporting may introduce bias. The objectives of this study are to summarise and describe the methods used for handling missing variance data in meta-analyses in populations with type 2 diabetes mellitus (T2DM). METHODS: Electronic databases, Embase, MEDLINE, and the Cochrane Library (accessed June 2015), were systematically searched to identify meta-analyses of interventions in patients with T2DM. Eligible studies included those which analysed the change in HbA1c from baseline. RESULTS: Sixty-seven publications reporting on meta-analyses of change in HbA1c from baseline in T2DM were identified. Approaches for dealing with missing variance data were reported in 41% of publications and included algebraic calculation, trial-level imputation, and no imputation. CONCLUSIONS: Meta-analysis publications typically fail to report standardised approaches for dealing with missing variance data. While no particular imputation method is favoured, authors are discouraged from using a no-imputation approach. Instead, authors are encouraged to explore different approaches using sensitivity analyses and to improve the quality of reporting by documenting the methods used to deal with missing variance data.

Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans.

Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation-induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes.