Evidence-based circumcision policy for Australia.

The aim was (1) to perform an up-to-date systematic review of the male circumcision (MC) literature and (2) to determine the number of adverse medical conditions prevented by early MC in Australia. Searches of PubMed using "circumcision" with 39 keywords and bibliography searches yielded 278 publications meeting our inclusion criteria. Early MC provides immediate and lifetime benefits, including protection against: urinary tract infections, phimosis, inflammatory skin conditions, inferior penile hygiene, candidiasis, various STIs, and penile and prostate cancer. In female partners MC reduces risk of STIs and cervical cancer. A risk-benefit analysis found benefits exceeded procedural risks, which are predominantly minor, by approximately 200 to 1. It was estimated that more than 1 in 2 uncircumcised males will experience an adverse foreskin-related medical condition over their lifetime. An increase in early MC in Australia to mid-1950s prevalence of 85% from the current level of 18.75% would avoid 77,000 cases of infections and other adverse medical conditions over the lifetime for each annual birth cohort. Survey data, physiological measurements, and the anatomical location of penile sensory receptors responsible for sexual sensation indicate that MC has no detrimental effect on sexual function, sensitivity or pleasure. US studies found that early infant MC is cost saving. Evidence-based reviews by the AAP and CDC support early MC as a desirable public health measure. Although MC can be performed at any age, early MC maximizes benefits and minimises procedural risks. Parents should routinely be provided with accurate, up-to-date evidence-based information in an unbiased manner early in a pregnancy so that they have time to weigh benefits and risks of early MC and make an informed decision should they have a son. Parental choice should be respected. A well-trained competent practitioner is essential and local anaesthesia should be routinely used. Third party coverage of costs is advocated.

Musculoskeletal immune-related adverse events with the use of checkpoint inhibitors in malignancy.

BACKGROUND: Immunotherapy has revolutionised the treatment of many malignancies. Along with their success, there have been inflammatory and immune-related adverse events (irAE). There is a paucity of literature describing the Australian experience of rheumatic irAE. AIMS: To describe and characterise the Royal North Shore Hospital and Westmead Hospital cohort with rheumatic irAE. METHODS: This case series reports on 17 patients with advanced cancer treated at two sites in Sydney, Australia who were referred for rheumatological evaluation from 2013 to 2016. Data were collected retrospectively and inspected for clinical signs, duration of immunotherapy prior to onset of symptoms, management strategies and cancer outcomes. RESULTS: Patients presented with arthralgias, myalgias, periarticular and systemic symptoms. Onset of rheumatological symptoms was variable, with a median of 4 months (range 0.2-24) for monotherapy and 5.05 months (range 0.2-6.9) for combination. The predominant findings were of tenosynovitis (23%) and large joint involvement (65%). All patients were seronegative for RF and anti-CCP. Most patients responded well to non-steroidal anti-inflammatory drugs or low-dose prednisone (59%) and remained on immunotherapy (77%). The majority (76%) of patients experienced concomitant irAE in other organ systems. Sixty-five percent of patients had complete response of their malignancy to immunotherapy. CONCLUSION: Rheumatic irAE are heterogenous clinical entities, which require further evaluation into classification, patient susceptibility and response. From our study, there was no clear clinical pattern. The present case series supports that rheumatic irAE may be associated with tumour response. However, there is still limited experience in rheumatic irAE management and outcomes.

Cranial and large vessel activity on positron emission tomography scan at diagnosis and 6 months in giant cell arteritis.

AIM: Positron emission tomography/computed tomography (PET/CT) can detect cranial and large vessel inflammation in giant cell arteritis (GCA). We aimed to determine the change and significance of vascular activity at diagnosis and 6 months. METHOD: Newly diagnosed GCA patients underwent time-of-flight fluorine-18-fluoro-2-deoxyglucose PET/CT from vertex to diaphragm within 72 hours of commencing corticosteroids and were followed for 12 months. A 6 months scan was performed in patients with inflammatory features on biopsy or CT aortitis. Vascular uptake was visually graded by 2 blinded readers across 18 artery segments from 0 (no increased uptake) to 3 (very marked uptake). Scores were summed to give a total vascular score (TVS). RESULTS: We enrolled 21 GCA patients and 15 underwent the serial scan. Twelve (57%) patients experienced a relapse and 5 of these had ischemic features of vision disturbance, jaw or limb claudication. The median TVS fell from 14 (interquartile range [IQR] 4-24) at baseline to 5 (IQR 0-10) at 6 months (P < .01) with reduction in both cranial and large artery scores. While the overall relapse rate was similar between patients with a high (≥10) and low baseline TVS, patients with high scores were numerically more likely to experience an ischemic relapse (33% vs 11%, P = .34). Five out of 15 patients had persistent uptake in at least 1 vessel on the serial PET/CT but none experienced a subsequent relapse. CONCLUSION: Vascular activity decreased in cranial and large arteries between diagnosis and 6 months. Persistent activity did not predict subsequent relapse.

Diagnostic Accuracy of Positron Emission Tomography/Computed Tomography of the Head, Neck, and Chest for Giant Cell Arteritis: A Prospective, Double-Blind, Cross-Sectional Study.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) has not been well studied as a first-line test for giant cell arteritis (GCA), due, in part, to historical limitations in visualizing the cranial arteries. The Giant Cell Arteritis and PET Scan (GAPS) study was therefore carried out to assess the accuracy of a newer generation PET/CT of the head, neck, and chest for determining a diagnosis of GCA. METHODS: In the GAPS study cohort, 64 patients with newly suspected GCA underwent time-of-flight PET/CT (1-mm slice thickness from the vertex to diaphragm) within 72 hours of starting glucocorticoids and before undergoing temporal artery biopsy (TAB). Two physicians with experience in PET reviewed the patients' scans in a blinded manner and reported the scans as globally positive or negative for GCA. Tracer uptake was graded across 18 artery segments. The clinical diagnosis was confirmed at 6 months' follow-up. RESULTS: In total, 58 of 64 patients underwent TAB, and 12 (21%) of the biopsies were considered positive for GCA. Twenty-one patients had a clinical diagnosis of GCA. Compared to TAB, the sensitivity of PET/CT for a diagnosis of GCA was 92% (95% confidence interval [95% CI] 62-100%) and specificity was 85% (95% CI 71-94%). The negative predictive value (NPV) was 98% (95% CI 87-100%). Compared to clinical diagnosis, PET/CT had a sensitivity of 71% (95% CI 48-89%) and specificity of 91% (95% CI 78-97%). Interobserver reliability was moderate (κ = 0.65). Among the enrolled patients, 20% had a clinically relevant incidental finding, including 7 with an infection and 5 with a malignancy. Furthermore, 5 (42%) of 12 TAB-positive GCA patients had moderate or marked aortitis. CONCLUSION: The high diagnostic accuracy of this PET/CT protocol would support its use as a first-line test for GCA. The NPV of 98% indicates the particular utility of this test in ruling out the condition in patients considered to be at lower risk of GCA. PET/CT had benefit over TAB in detecting vasculitis mimics and aortitis.

Comparison of physical examination performance of medical students trained by musculoskeletal versus non-musculoskeletal specialists.

AIM: To compare the musculoskeletal (MSK) physical examination skills, knowledge acquisition and performance of first-year medical students trained by MSK specialist tutors to students trained by non-MSK specialist tutors, after a 6-week MSK physical examination tutorial program. METHODS: Twenty-first year medical students took part in the study. They were recruited into two groups, according to their exposure to either an MSK specialist or a non-MSK specialist tutor during their 6-week MSK training block. Knowledge acquisition was measured via a pre- and post-training objective structured clinical examination (OSCE). We assessed students' self-belief and confidence levels regarding their newly acquired skills via a questionnaire. Independent t tests were used to examine mean group differences of OSCE scores and perceived level of confidence. RESULTS: Both groups demonstrated a significant improvement (3.9 and 3.8 points, respectively, on an eight-point scale for shoulder assessment, P < 0.01, 3.3 and 3.5, respectively, on a five-point scale for spine assessment, P < 0.01) in OSCE scores compared to baseline after completing the 6-week MSK physical examination tutorial program. There was no between-group difference in the OSCE scores from pre- to post-training (P = 0.92 for shoulder, P = 0.66 for spine) or for perceived level of confidence in performing a basic MSK examination after training (P = 0.91). CONCLUSION: Students exposed to MSK specialist tutors did not demonstrate increased skill levels or knowledge in the area of MSK physical examination compared to those receiving the same training under the supervision of non-MSK specialist tutors. Both student groups demonstrated improvement.

Early infant male circumcision: Systematic review, risk-benefit analysis, and progress in policy.

AIM: To determine whether recent evidence-based United States policies on male circumcision (MC) apply to comparable Anglophone countries, Australia and New Zealand. METHODS: Articles in 2005 through 2015 were retrieved from PubMed using the keyword "circumcision" together with 36 relevant subtopics. A further PubMed search was performed for articles published in 2016. Searches of the EMBASE and Cochrane databases did not yield additional citable articles. Articles were assessed for quality and those rated 2+ and above according to the Scottish Intercollegiate Grading System were studied further. The most relevant and representative of the topic were included. Bibliographies were examined to retrieve further key references. Randomized controlled trials, recent high quality systematic reviews or meta-analyses (level 1++ or 1+ evidence) were prioritized for inclusion. A risk-benefit analysis of articles rated for quality was performed. For efficiency and reliability, recent randomized controlled trials, meta-analyses, high quality systematic reviews and large well-designed studies were used if available. Internet searches were conducted for other relevant information, including policies and Australian data on claims under Medicare for MC. RESULTS: Evidence-based policy statements by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) support infant and later age male circumcision (MC) as a desirable public health measure. Our systematic review of relevant literature over the past decade yielded 140 journal articles that met our inclusion criteria. Together, these showed that early infant MC confers immediate and lifelong benefits by protecting against urinary tract infections having potential adverse long-term renal effects, phimosis that causes difficult and painful erections and "ballooning" during urination, inflammatory skin conditions, inferior penile hygiene, candidiasis, various sexually transmissible infections in both sexes, genital ulcers, and penile, prostate and cervical cancer. Our risk-benefit analysis showed that benefits exceeded procedural risks, which are predominantly minor, by up to 200 to 1. We estimated that more than 1 in 2 uncircumcised males will experience an adverse foreskin-related medical condition over their lifetime. Wide-ranging evidence from surveys, physiological measurements, and the anatomical location of penile sensory receptors responsible for sexual sensation strongly and consistently suggested that MC has no detrimental effect on sexual function, sensitivity or pleasure. United States studies showed that early infant MC is cost saving. The evidence supporting early infant MC has further strengthened since the positive AAP and CDC reviews. CONCLUSION: Affirmative MC policies are needed in Australia and New Zealand. Routine provision of accurate, unbiased education, and access in public hospitals, will maximize health and financial benefits.

A blind randomized controlled trial of cognitive versus behavioral versus cognitive-behavioral therapy for patients with rheumatoid arthritis.

BACKGROUND: Despite evidence that cognitive-behavioral therapy (CBT) is effective for rheumatoid arthritis (RA), little is known about which components of therapy are most efficacious. The present study compared the efficacy of CBT with cognitive therapy (CT) and behavioral therapy (BT) for patients with RA. We hypothesized that CBT would be more efficacious on a broader range of outcomes. METHODS: Participants (n = 104) with classic or definite RA were randomized to receive one of three active treatments (CBT, CT or BT) or a wait-list control (WLC). Participants were assessed at baseline, post-treatment and 6 months on a range of outcomes. Measures of disease activity, joint function, disability and psychological functioning were included. RESULTS: The results showed that participants who received cognitive components had greater improvements in tender joint counts and C-reactive protein at post-treatment. Those receiving either BT or CT alone improved more on anxiety than CBT or WLC. At 6 months, the three active treatment groups could only be distinguished on tender joints, which favored CT and CBT. CONCLUSIONS: CBT did not demonstrate the broader benefits to patients that we expected, nor was there evidence that BT produced effects that were superior to CT alone. CT was superior to at least one of the other two active treatment components on 3 of the 7 outcome measures at post-treatment. Effect sizes for the interventions that included cognitive components were similar to those reported in the literature. These results suggest that CT is an effective treatment for RA and need not necessarily include behavioral strategies.

Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti-apolipoprotein A-I (anti-Apo A-I), anti-high-density lipoprotein (anti-HDL), and anti-C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. METHODS: IgG anti-Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. RESULTS: Serum levels of IgG anti-Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti-Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti-Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti-Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti-double-stranded DNA. CONCLUSION: Persistent disease activity is associated with a significant increase in IgG anti-Apo A-I and anti-HDL in patients with SLE.

Attentional biases in chronic pain associated with rheumatoid arthritis: hypervigilance or difficulties disengaging?

UNLABELLED: There is evidence that pain patients demonstrate attentional biases toward some pain-related stimuli (eg, sensory words) and not others (eg, affective words). However, whether individuals in chronic pain caused by rheumatoid arthritis (RA) also demonstrate this bias has not been investigated. Further, within the pain literature, whether these biases reflect hypervigilance or difficulty disengaging from stimuli remains contentious. The present study aimed to determine (a) whether RA patients demonstrate an attentional bias to sensory pain words; and (b) whether this bias is a result of hypervigilance or failure to disengage from the stimuli. RA patients showed a bias toward sensory words and away from threat-related words. The effect for sensory words resulted from slowed performance on incongruent trials (ie, difficulty disengaging), whereas the bias away from threat words resulted from faster responses on incongruent trials (ie, avoidance of threat). The pattern of attention biases in RA patients is very similar to those found in patients with chronic pain. At least in RA, attentional biases appear to be related to a failure to disengage from pain-related words rather than hypervigilance. PERSPECTIVE: There is continued debate about whether these biases are caused by hypervigilance toward pain stimuli or difficulty disengaging from pain stimuli. This study shows that in a group of RA patients, attentional biases toward pain are caused by difficulty disengaging rather than hypervigilance.

Relationship between appearance and psychological distress in rheumatic diseases.

OBJECTIVE: To examine the relationship between physical appearance concerns and psychological distress in patients with rheumatic diseases. METHODS: A total of 60 patients with systemic lupus erythematosus (SLE), 44 with chronic rheumatoid arthritis (RA), and 53 with recent-onset RA were evaluated for levels of appearance concern and a range of illness-specific measures to determine how these demographic and clinical variables were related to the dependent variable psychological distress. RESULTS: Using hierarchical multiple regression analyses, we found that both appearance concerns and levels of disability were predictive of depression in patients with RA. In the SLE sample, physical disability was predictive of depression when appearance concerns were not included in the analysis. However, disability did not predict depression when appearance concerns were entered into the analysis. This indicates that appearance concerns mediated the relationship between disability and depression in SLE. There was no association between appearance concerns and anxiety in either sample. CONCLUSION: The results suggest that appearance concerns are strongly related to depression in patients with rheumatic diseases and should be routinely assessed.

Immunotherapy of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a remarkably heterogeneous multisystem autoimmune disease. Improved understanding of the immunopathogenesis of this disorder over the past two decades is now being applied to therapy, with treatment being directed at specific immunological targets. This review will focus on both new uses for established therapies as well as on the introduction of novel agents. It is premature to claim that any one agent has superior efficacy to current therapies. However, the willingness of investigators supported by the pharmaceutical and biotechnology industries to evaluate the efficacy and safety of new products in controlled clinical trials may provide answers.

Cognitive bias in systemic lupus erythematosus.

Evidence of cognitive bias in depression and anxiety has sparked an increasing interest in the potential for pain-related bias in patients suffering from chronic pain and/or illness. Research to date has been somewhat inconsistent, and the vast majority has been conducted on just two patient populations: rheumatoid arthritis (RA) and chronic pain patients. The present study investigates cognitive bias in Systemic Lupus Erythematosus (SLE) patients, particularly in relation to disease activity and depression. Forty-three SLE patients are compared to RA patients and healthy controls on their endorsement and recall of pain/illness words relative to depression and control words. Patients are first divided according to their disease activity, and secondly according to depression. SLE and RA patients self-endorsed more negative illness words and fewer positive illness words than did healthy controls, regardless of disease activity or depression status. Groups did not differ in their recall patterns, although all groups demonstrated a recall bias for positive words and illness words. Post-hoc analyses revealed a significant recall bias for disability-related illness words compared to sensory pain words in ill, depressed patients compared to ill, non-depressed patients and healthy controls. Consistent with the most recent research, it appears to be both the nature of the illness stimuli and the depression status of the patient that determines cognitive bias in chronically ill populations.

Patient education.

There are a wide range of opportunities for arthritis patient education including individual or group counselling, printed notes and the Internet. Over the past 20 years efforts have been made to evaluate patient education programmes and determine if they are effective and, more recently, whether they are cost-effective. In the short term (up to 6-12 months) structured educational programmes have been demonstrated to increase patient knowledge and improve desirable behaviours such as relaxation, exercise and compliance with medications. More controversial has been the long term outcome (>12 months) of these programmes. Some studies indicate continuing benefit, albeit at reduced levels, compared to earlier evaluation points. Other studies, including a recent Cochrane report suggest that the beneficial effects are not sustained. In conclusion, patient education programmes have a modest, but significant, benefit on patient knowledge and behaviour, at least in the short term.

PRISM: Enmeshment of illness and self-schema.

BACKGROUND: The Pictorial Representation of Illness and Self Measure (PRISM) is a recently developed tool purported to assess burden of suffering due to illness. The nature of the PRISM task suggests a conceptual link to the illness self-schema construct hypothesised to be present in some individuals with chronic illness. This study investigates the relationship between PRISM and schema as measured by cognitive bias. METHODS: 43 patients with systemic lupus erythematosus (SLE) completed an information-processing task involving endorsement of positive and negative illness words as descriptors of themselves, followed by free recall of the words. The outcome measures were endorsement and recall bias for negative illness words. Patients also completed the PRISM task and were assessed on other physical and psychological variables. RESULTS: PRISM did not correlate significantly with age, depression, functional impairment or disease activity. In a multiple regression analysis, only recall bias made an independent contribution to PRISM. CONCLUSIONS: Illness self-schema appears to play a significant role in determining the way in which SLE patients complete the PRISM task. This is discussed in light of a schema enmeshment model recently proposed in the cognitive bias literature.

Isolated fascicular oculomotor nerve palsy as the initial presentation of the antiphospholipid syndrome.

This case report describes a 24-year-old female who presented with sudden onset of painless diplopia and ptosis in her left eye. Examination identified an isolated incomplete pupil-sparing left oculomotor nerve palsy. Magnetic resonance imaging demonstrated focal hyperintensity in the left midbrain with infarction suggested by diffusion-weighted imaging. A diagnosis of primary antiphospholipid syndrome was made with the demonstration of a positive lupus anticoagulant. Other autoimmune markers were present on initial assessment, but did not fulfil diagnostic criteria for systemic lupus erythematosus. Anticoagulation with warfarin was commenced, with gradual resolution of neurological deficits. This case illustrates an unusual initial manifestation of primary antiphospholipid syndrome causing midbrain stroke in a young woman.