Effect of EVAR on International Ruptured AAA Mortality-Sex and Geographic Disparities.

Background: We sought to investigate the differential impact of EVAR (endovascular aneurysm repair) vis-à-vis OSR (open surgical repair) on ruptured AAA (abdominal aortic aneurysm) mortality by sex and geographically. Methods: We performed a retrospective study of administrative data on EVAR from state statistical agencies, vascular registries, and academic publications, as well as ruptured AAA mortality rates from the World Health Organization for 14 14 states across Australasia, East Asia, Europe, and North America. Results: Between 2011-2016, the proportion of treatment of ruptured AAAs by EVAR increased from 26.1 to 43.8 percent among females, and from 25.7 to 41.2 percent among males, and age-adjusted ruptured AAA mortality rates fell from 12.62 to 9.50 per million among females, and from 34.14 to 26.54 per million among males. The association of EVAR with reduced mortality was more than three times larger (2.2 vis-à-vis 0.6 percent of prevalence per 10 percentage point increase in EVAR) among females than males. The association of EVAR with reduced mortality was substantially larger (1.7 vis-à-vis 1.1 percent of prevalence per 10 percentage point increase in EVAR) among East Asian states than European+ states. Conclusions: The increasing adoption of EVAR coincided with a decrease in ruptured AAA mortality. The relationship between EVAR and mortality was more pronounced among females than males, and in East Asian than European+ states. Sex and ethnic heterogeneity should be further investigated.

Outcomes of symptomatic penetrating aortic ulcer and intramural hematoma in the endovascular era.

BACKGROUND: Although endovascular technology has resulted in a paradigm shift in treatment, medical management remains the standard of care for penetrating aortic ulcer (PAU) and intramural hematoma (IMH). This study aimed to detail the short- and long-term outcomes of symptomatic PAU/IMH. METHODS: Institutional data on symptomatic PAU/IMH were gathered (2005-2020). The primary outcome was the composite of recurrent symptoms, radiographic progression, intervention, rupture, and death from related or unknown cause. Factors associated with the primary outcome were determined using a Fine-Gray model with death from an unrelated cause as a competing risk. RESULTS: A total of 83 symptomatic patients treated with medical management aside from ruptures and type A dissections: 21 isolated PAU, 30 isolated IMH, and 32 IMH and PAU. Adverse outcomes included symptom recurrence in 14 (16.9%), radiographic progression to dissection or saccular aneurysm in 17 (20.5%), surgery in 20 (24.1%) (17 thoracic endovascular aortic repair, 1 endovascular aortic repair, 1 frozen elephant trunk, and 1 open repair), and rupture in 4 (4.8%). Twenty-seven patients (32.5%) died during follow-up: 6 from IMH treatment complications, 8 from an unknown cause, and 13 from other causes. The 30-day, 1-year, and 5-year cumulative incidences of the primary outcome was 26.5% (95% confidence interval [CI], 16.9%-37.0%), 44.9% (95% CI, 32.8%-56.2%), and 57.5% (95% CI, 42.4%-69.9%), respectively. IMH with PAU was associated with a significantly higher risk of the primary outcome compared with isolated IMH (subdistribution hazard ratio, 2.21; 95% CI, 1.09-4.50; P = .027) and isolated PAU (subdistribution hazard ratio, 3.58; 95% CI, 1.44-8.88; P = .006). CONCLUSIONS: Complications from symptomatic PAU and IMH are frequent, with intervention, recurrent symptoms, radiographic progression, rupture, or death affecting 25% of patients at 30 days after diagnosis and almost one-half of patients 1 year after diagnosis. Given the high rate of adverse events in this population, investigation into a more aggressive interventional strategy may warranted, especially in patients with a combined IMH and PAU.

Linkage to care following community-based mobile HIV testing compared with clinic-based testing in Umlazi Township, Durban, South Africa.

OBJECTIVES: The aim of the study was to assess HIV prevalence, disease stage and linkage to HIV care following diagnosis at a mobile HIV testing unit, compared with results for clinic-based testing, in a Durban township. METHODS: This was a prospective cohort study. We enrolled adults presenting for HIV testing at a community-based mobile testing unit (mobile testers) and at an HIV clinic (clinic testers) serving the same area. Testers diagnosed with HIV infection, regardless of testing site, were offered immediate CD4 testing and instructed to retrieve results at the clinic. We assessed rates of linkage to care, defined as CD4 result retrieval within 90 days of HIV diagnosis and/or completion of antiretroviral therapy (ART) literacy training, for mobile vs. clinic testers. RESULTS: From July to November 2011, 6957 subjects were HIV tested (4703 mobile and 2254 clinic); 55% were female. Mobile testers had a lower HIV prevalence than clinic testers (10% vs. 36%, respectively), were younger (median 23 vs. 27 years, respectively) and were more likely to live >5 km or >30 min from the clinic (64% vs. 40%, respectively; all P < 0.001). Mobile testers were less likely to undergo CD4 testing (33% vs. 83%, respectively) but more likely to have higher CD4 counts [median (interquartile range) 416 (287-587) cells/µL vs. 285 (136-482) cells/µL, respectively] than clinic testers (both P < 0.001). Of those who tested HIV positive, 10% of mobile testers linked to care, vs. 72% of clinic testers (P < 0.001). CONCLUSIONS: Mobile HIV testing reaches people who are younger, who are more geographically remote, and who have earlier disease compared with clinic-based testing. Fewer mobile testers underwent CD4 testing and linked to HIV care. Enhancing linkage efforts may improve the impact of mobile testing for those with early HIV disease.

The development of a preliminary ultrasonographic scoring system for features of hand osteoarthritis.

OBJECTIVES: Painful osteoarthritis (OA) of the hand is common and a validated ultrasound (US) scoring system would be valuable for epidemiological and therapeutic outcome studies. US is increasingly used to assess peripheral joints, though most of the US focus in rheumatic diseases has been on rheumatoid arthritis. We aimed to develop a preliminary US hand OA scoring system, initially focusing on relevant pathological features with potentially high reliability. METHODS: A group of experts in the fields of OA, US and novel tool development agreed on domains and suggested scaling of the items to be used in US hand OA scoring systems. A multi-observer reliability exercise was then performed to evaluate the draft items. RESULTS: Synovitis (grey scale and Power Doppler) and osteophytes (representing activity and damage domains) were included and evaluated as the initial components of the scoring system. All three features were evaluated for their presence/absence and if present were scored using a 1-3 scale. The reliability exercise demonstrated intra-reader kappa values of 0.444-1.0, 0.211-1.0 and 0.087-1.0 for grey scale synovitis, power Doppler and osteophytes respectively. Inter-reader reliability kappa values were 0.398, 0.327 and 0.530 grey-scale synovitis, power Doppler and osteophytes respectively. Without extensive standardisation, both intra- and inter-reader reliability were moderately good. CONCLUSIONS: The draft scoring system demonstrated substantive to almost perfect percentage exact agreement on the presence/absence of the selected OA features and moderate to substantive percentage exact agreement on semi-quantitative grading. This preliminary process provides a good basis from which to further develop an US outcome tool for hand OA that has the potential to be utilised in multicentre clinical trials.

Musculoskeletal ultrasound training in rheumatology: the Belfast experience.

OBJECTIVES: Despite the increasing use of musculoskeletal ultrasound (MSUS) as a clinical tool in rheumatology, there is no consensus yet regarding the standards required to achieve a basic level of competence in the use of this imaging technique. A number of sonographers worldwide are developing curricula and standardizing teaching methods in order to improve training in MSUS for rheumatologists. In the meantime, clinicians are devising informal means of training in order to acquire these new skills. Here we describe the informal team approach to MSUS training adopted by a group of rheumatologists from the Regional Rheumatology Centre in Belfast, UK. METHODS: Over a 5-yr period, eight rheumatologists from Musgrave Park Hospital in Belfast used a variety of means to learn the basic skills of MSUS. RESULTS: Seven of the team underwent a formal assessment of their competency in a practical examination devised by an experienced sonographer. All were judged to have attained a basic competency in MSU. CONCLUSIONS: This Belfast experience shows what can be achieved despite the absence of formal MSUS training. Nevertheless, the development of recognized training programmes and international standards of competency are important goals on the way to achieving more widespread acceptance of MSUS as a useful tool in everyday clinical practice.

Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee--the MOVE consensus.

OBJECTIVES: Exercise is an effective and commonly prescribed intervention for lower limb osteoarthritis (OA). Many unanswered questions remain, however, concerning the practical delivery of exercise therapy. We have produced evidence-based recommendations to guide health-care practitioners. METHODS: A multidisciplinary guideline development group was formed from representatives of professional bodies to which OA is of relevance and other interested parties. Each participant contributed up to 10 propositions describing key clinical points regarding exercise therapy for OA of the hip or knee. Ten final recommendations were agreed by the Delphi technique. The research evidence for each was determined. A literature search was undertaken in the Medline, PubMed, EMBASE, PEDro, CINAHL and Cochrane databases. The methodological quality of each retrieved publication was assessed. Outcome data were abstracted and effect sizes calculated. The evidence for each recommendation was assessed and expert consensus highlighted by the allocation of two categories: (1) strength of evidence and (2) strength of recommendation. RESULTS: The first round of the Delphi process produced 123 propositions. This was reduced to 10 after four rounds. These related to aerobic and strengthening exercise, group versus home exercise, adherence, contraindications and predictors of response. The literature search identified 910 articles; 57 intervention trials relating to knee OA, 9 to hip OA and 73 to adherence. The evidence to support each proposition is presented. CONCLUSION: These are the first recommendations for exercise in hip and knee OA to clearly differentiate research evidence and expert opinion. Gaps in the literature are identified and issues requiring further study highlighted.

EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the management of hip osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation was assessed using the traditional A-D grading scale and a visual analogue scale. RESULTS: Ten key treatment propositions were generated through three Delphi rounds. They included 21 interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids, intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two general propositions. 461 studies were identified from the literature search for the proposed interventions of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation varied according to category of research evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of hip OA were developed based on research evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were evaluated and the strength of recommendation was scored.

EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVES: To update the EULAR recommendations for management of knee osteoarthritis (OA) by an evidence based medicine and expert opinion approach. METHODS: The literature search and guidelines were restricted to treatments for knee OA pertaining to clinical and/or radiological OA of any compartment of the knee. Papers for combined treatment of knee and other types of OA were excluded. Medline and Embase were searched using a combination of subject headings and key words. Searches for those treatments previously investigated were conducted for January 1999 to February 2002 and for those treatments not previously investigated for 1966 to February 2002. The level of evidence found for each treatment was documented. Quality scores were determined for each paper, an effect size comparing the treatment with placebo was calculated, where possible, and a toxicity profile was determined for each treatment modality. RESULTS: 497 new publications were identified by the search. Of these, 103 were intervention trials and included in the overall analysis, and 33 treatment modalities were identified. Previously identified publications which were not exclusively knee OA in the initial analysis were rejected. In total, 545 publications were included. Based on the results of the literature search and expert opinion, 10 recommendations for the treatment of knee OA were devised using a five stage Delphi technique. Based on expert opinion, a further set of 10 items was identified by a five stage Delphi technique as important for future research. CONCLUSION: The updated recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions. Although a large number of treatment options for knee OA exist, the evidence based format of the EULAR Recommendations continues to identify key clinical questions that currently are unanswered.

A randomised study of two training programmes for general practitioners in the techniques of shoulder injection.

OBJECTIVES: To evaluate the impact of two different modes of shoulder injection training on the level of confidence and number of injections performed by general practitioners (GPs) METHODS: Demographic details, and information on referrals for shoulder problems, shoulder joint injection activity, and confidence in the six months before training were obtained for 40 GP principals at baseline. Standardised training in the techniques of shoulder joint injection using rubber mannequins was given to all GPs. Twenty of these GPs were randomly allocated to receive additional training on patients in hospital joint injection clinics. Six months after both forms of training the shoulder injection and referral activities of all GPs were reassessed. RESULTS: Both training groups had comparable demographic characteristics and baseline clinical activity. GPs who had additional training with patients reported a marked increase in their level of confidence in performing shoulder injections and the number performed. The number of shoulder referrals did not differ between the groups CONCLUSION: Training on patients in addition to conventional training on mannequins increased GPs' shoulder injection activity and their level of confidence. Hospital injection clinics may provide a suitable setting in which to train GPs interested in developing their shoulder joint injection skills.

Thymidine kinase 1 immunoassay: a potential marker for breast cancer.

Previous research indicates that thymidine kinase I (TKI) possesses value as a tool for both prognosis and diagnosis in breast cancer. However, drawbacks to the existing radioassay for thymidine kinase have frustrated its clinical use. To overcome these drawbacks, we developed a monoclonal antibody to TK1. We have assessed this antibody for a linear antibody-antigen response and for reproducibility using ELISA techniques. We also have evaluated this antibody for TKI specificity as determined by Western blot. To test the accuracy of this monoclonal antibody further, we treated human MCF-7 breast cancer cells with tamoxifen and measured decreasing TKI activity and protein levels with the radioassay and with our monoclonal antibody in an ELISA, respectively. We then used the radioassay and our monoclonal antibody to measure TK1 activity and protein levels, respectively, in 218 serum samples of postoperative breast cancer patients and found a correlation between the two assays. Our results demonstrated that the TK1 immunoassay not only had a linear, reproducible, and specific response but accurately measured TK1 levels in both MCF-7 breast cancer cells and serum. Thus, our monoclonal antibody may demonstrate potential for practical use in a clinical setting for the management of breast cancer.

Effects of latrunculin reveal requirements for the actin cytoskeleton during secretion from mast cells.

To investigate the role of the actin cytoskeleton in exocytosis, we have tested the effects of latrunculin B, a microfilament-disrupting drug, on secretion from intact and permeabilised rat peritoneal mast cells. The toxin strongly inhibited secretion from intact cells (attached or in suspension) responding to a polybasic agonist, compound 48/80. However, this effect was revealed only after a profound depletion of actin filaments. This was achieved by a long (1 h) exposure of cells to the drug before activation, together with its presence during activation. Maximal inhibition of secretion by such treatment was 85% at 40 microgram/ml latrunculin B. These results indicate that minimal actin structures are essential for the exocytotic response. In contrast, stimulus-induced cell spreading was prevented by latrunculin (5 microgram/ml) applied either before or after activation. The effects of the toxin on intact cells were fully reversible. The responses of permeabilised cells were affected differentially: secretion induced by calcium was more sensitive to latrunculin than that induced by GTP-gamma-S. The calcium response, therefore, is more dependent upon the integrity of the actin cytoskeleton than the response induced by GTP-gamma-S. Again, maximal inhibitory effects (approximately 65 and 25% at 40 microgram/ml) were observed only when cells were exposed to the toxin both before and after permeabilisation. Since the permeabilised cells system focuses on the final steps of exocytosis, the incomplete inhibition suggests that actin plays a modulatory rather than a central role at this stage.

EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).

BACKGROUND: Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. METHODS: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, meta-analyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. RESULTS: Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS: These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities. It is apparent that certain clinical propositions are supported by substantial research based evidence, while others are not. There is thus an urgent need for future well designed trials to consider key clinical questions.

Loss of NADPH during assays of HMG-CoA reductase: implications and approaches to minimize errors.

In assays of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, preincubation of isolated washed microsomes with NADPH led to a time- and protein concentration-dependent loss of enzyme activity. This occurred despite the presence of an NADPH regenerating system. Addition of fresh NADP, glucose 6-phosphate and glucose 6-phosphate dehydrogenase restored activity. Of the individual components, only NADP was effective. Errors due to loss of NADPH are most pronounced in assays using high microsomal protein, low NADPH levels and preincubation with NADPH and when glutathione rather than dithiothreitol is present. To minimize the effects of NADPH depletion, it is recommended that (i) NADP and NADPH not be present during the preincubation period; (ii) incubation periods be relatively short; (iii) microsomal protein concentrations be less than 1 mg; and (iv) NADPH concentrations be 1 to 2 mM.