An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group

Evaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty‐one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty‐six of the joints were evaluated using two X‐ray scales. For all MRI scores, interreader agreement and correlations with X‐ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35–0.68) and with the X‐ray scores (Spearman correlation 0.40–0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X‐ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.     

Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes

Background

Minimal change disease (MCD) is the most common cause of nephrotic syndrome in children and is associated with the expression of CD80 in podocytes and the increased excretion of CD80 in urine. We hypothesized that serum from patients with MCD might stimulate CD80 expression in cultured podocytes.

Methods

Sera and peripheral blood mononuclear cells (PBMCs) were collected from subjects with MCD in relapse and remission and from normal controls. Immortalized human podocytes were incubated with culture media containing patient sera or supernatants from patient and control PBMC cultures. CD80 expression was measured by quantitative PCR and western blot analysis.

Results

Sera collected from patients with MCD in relapse, but not in remission, significantly increased CD80 expression (mean ± standard deviation: 1.8?±?0.7 vs. 0.8?±?0.2; p?<?0.004) and CD80 protein secretion by podocytes (p?<?0.05 between relapse and normal controls). No such CD80 increase was observed when podocytes were incubated with supernatants of PBMC cultures from patients in relapse.

Conclusions

Sera from MCD patients in relapse, but not in remission, stimulated CD80 expression in cultured podocytes. Identifying this factor in sera could provide insights into the pathogenesis of this disorder. No role in CD80 expression by podocytes was found for cytokines released by PBMCs.     

Supplement to the 2004 update of the AAPM Task Group No. 43 Report

Since publication of the 2004 update to the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report (TG-43U1), several new low-energy photon-emitting brachytherapy sources have become available. Many of these sources have satisfied the AAPM prerequisites for routine clinical use as of January 10, 2005, and are posted on the Joint AAPM/RPC Brachytherapy Seed Registry. Consequently, the AAPM has prepared this supplement to the 2004 AAPM TG-43 update. This paper presents the AAPM-approved consensus datasets for these sources, and includes the following 125I sources: Amersham model 6733, Draximage model LS-1, Implant Sciences model 3500, IBt model 1251L, IsoAid model IAI-125A, Mentor model SL-125/ SH-125, and SourceTech Medical model STM1251. The Best Medical model 2335 103Pd source is also included. While the methodology used to determine these data sets is identical to that published in the AAPM TG-43U1 report, additional information and discussion are presented here on some questions that arose since the publication of the TG-43U1 report. Specifically, details of interpolation and extrapolation methods are described further, new methodologies are recommended, and example calculations are provided. Despite these changes, additions, and clarifications, the overall methodology, the procedures for developing consensus data sets, and the dose calculation formalism largely remain the same as in the TG-43U1 report. Thus, the AAPM recommends that the consensus data sets and resultant source-specific dose-rate distributions included in this supplement be adopted by all end users for clinical treatment planning of low-energy photon-emitting brachytherapy sources. Adoption of these recommendations may result in changes to patient dose calculations, and these changes should be carefully evaluated and reviewed with the radiation oncologist prior to implementation of the current protocol.     

Brachytherapy dosimetry parameters calculated for a 131Cs source

A comprehensive analysis of the IsoRay Medical model CS-1 Rev2 131Cs brachytherapy source was performed. Dose distributions were simulated using Monte Carlo methods (MCNP5) in liquid water, Solid Water, and Virtual Water spherical phantoms. From these results, the in-water brachytherapy dosimetry parameters have been determined, and were compared with those of Murphy et al. [Med. Phys. 31, 1529-1538 (2004)] using measurements and simulations. Our results suggest that calculations obtained using erroneous cross-section libraries should be discarded as recommended by the 2004 AAPM TG-43U1 report. Our Mclambda value of 1.046+/-0.019 cGy h(-1) U(-1) is within 1.3% of that measured by Chen et al. [Med. Phys. 32, 3279-3285 (2005)] using TLDs and the calculated results of Wittman and Fisher [Med. Phys. 34, 49-54 (2007)] using MCNP5. Using the discretized energy approach of Rivard [Appl. Radiat. Isot. 55, 775-782 (2001)] to ascertain the impact of individual 131Cs photons on radial dose function and anisotropy functions, there was virtual equivalence of results for 29.461< or =Egamma< or = 34.419 keV and for a mono-energetic 30.384 keV photon source. Comparisons of radial dose function and 2D anisotropy function data are also included, and an analysis of material composition and cross-section libraries was performed.     

Patterns of arteriosclerotic lesions of the lower extremity in a West Indian population based on angiographic findings and ethnicity

Introduction

This study aimed to determine whether ethnic differences show different patterns of arterial disease in the lower limb.

Methods

A prospective analysis of 100 consecutive patients with 160 lower limb arteriograms was performed looking at the pattern of disease with relation to ethnicity in Trinidad and Tobago.

Results

There were 53 male and 47 female patients with an age range of 43–90 years (mean: 66 years). Of the 100 patients, 45 were of East Indian descent, 36 of Afro-Caribbean descent, 14 of mixed descent and 5 had other backgrounds. There were 32 smokers and 69 diabetics.The most commonly affected artery in East Indians was the anterior tibial artery (ATA, 70%) followed by the peroneal artery (60%), superficial femoral artery (SFA, 60%), posterior tibial artery (PTA, 57%) and tibioperoneal trunk (TPT, 39%). In Afro-Caribbeans, the most commonly affected artery was the ATA (79%) followed by the PTA (74%), peroneal artery (66%) and TPT (55%). The mixed group showed the PTA (85%) to be most diseased followed by the peroneal artery (75%), ATA (70%), SFA (70%), dorsalis pedis artery (DPA, 60%) and TPT (50%). Overall, the most diseased vessel in all groups was the ATA (73%) followed by the PTA (66%), peroneal artery (64%), SFA (59%), TPT (46%), DPA (38%), popliteal artery (31%) and medial plantar artery (MPA, 29%), with the proximal vessels not being affected severely.

Conclusions

Ethnic divisions were only statistically significant (p<0.05) with East Indians showing worse disease in the profunda femoris artery and Afro-Caribbeans showing worse disease in the PTA, DPA and MPA. This suggests that environmental factors may play a significant role in the disease process including smoking and dietary factors rather than purely genetics.     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Genomic insights into abdominal aortic aneurysms

Introduction

An individual’s genetic background plays a significant role in his or her chances of developing an abdominal aortic aneurysm (AAA). This risk is likely to be due to a combination of multiple small effect genetic factors acting together, resulting in considerable difficulty in the identification of these factors.

Methods

Methods for the identification of genetic factors associated with disease are usually based on the analysis of genetic variants in case-control studies. Over the last decade, owing to advances in bioinformatics and laboratory technology, these studies have progressed from focusing on the examination of a single genetic variant in each study to the examination of many millions of variants in a single experiment. We have conducted a series of such experiments using these methods.

Results

Our original methods using candidate gene approaches led to the initial identification of a genetic variant in the interleukin-10 gene associated with AAA. However, further studies failed to confirm this association and highlighted the necessity for adequately powered studies to be conducted, as well as the need for confirmatory studies to be performed, prior to the acceptance of a variant as a risk for disease. The subsequent application of genomic techniques to our sample set, in a global collaboration, has led to the identification of three robustly verified risk loci for AAA in the LRP1, LDLR and SORT1 genes.

Conclusions

Genomic studies of AAA have led to the identification of new pathways involved in the pathogenesis of AAA. The exploration of these pathways has the potential to unlock new avenues for therapeutic intervention to prevent the development and progression of AAA.     

Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

Workplace Incivility Among Nationally Certified EMS Professionals and Associations with Workforce-Reducing Factors and Organizational Culture

Background: Incivility, defined as negative interpersonal acts that violate workplace and social norms, has been linked to negative outcomes in healthcare settings. A minimal amount is known regarding workplace incivility among emergency medical services (EMS) professionals. Our objectives were to (1) evaluate the prevalence of incivility and factors associated with experiencing workplace incivility; (2) describe the association between incivility and workforce-reducing factors (stress, career satisfaction, turnover intentions, and workplace absences); and (3) quantify the association between incivility and the organizational culture of an EMS agency. Methods: A random sample of 38,000 nationally-certified EMS professionals received an electronic questionnaire with an EMS-adapted Workplace Incivility Scale, the Competing Values Framework organizational culture scale, and factors that may negatively impact the EMS workforce. All completed surveys from nonmilitary EMS professionals currently providing patient care at the EMT level or higher were included in these analyses. We constructed multivariable logistic regression models (OR, 95% CI) to identify factors associated with experiencing workplace incivility and to examine the associations between experiencing incivility and workforce-reducing factors. We calculated univariable odds ratios to assess the association between organizational culture type and incivility. Results: A total of 3,741 EMS professionals responded to the survey (response rate =10.3%), with 2,815 (75.2%) meeting inclusion criteria. Incivility from supervisors or coworkers was experienced at least once a week by 47.4% of respondents. Factors associated with increased odds of experiencing incivility included female sex, AEMT/paramedic certification level, increasing years of EMS experience, service types other than 9-1-1 response, and higher weekly call volumes. Exposure to regular incivility was associated with increased odds of dissatisfaction with EMS, a main EMS job or a main supervisor; moderate or higher stress levels; intent to leave one’s job and EMS in the next 12 months; and 10 or more workplace absences in the past 12 months. The organizational culture type “market” was associated with the greatest odds of incivility. Conclusions: Nearly half of respondents experienced incivility once a week or more, and incivility was associated with potential workforce-reducing factors. Further research is needed to understand how organizational climate and interpersonal behaviors in the workplace affect the EMS workforce.