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.

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.