Periprocedural imaging compared to endometrial biopsy: is biopsy required prior to uterine artery embolisation?

AIM: To compare the detection rate of magnetic resonance imaging (MRI) and ultrasound relative to endometrial biopsy for endometrial abnormalities in both pre- and post-menopausal women. MATERIALS AND METHODS: The present study was an institutional review board-approved, single-institution retrospective analysis of patients who underwent pelvic MRI within 1 year of diagnostic-quality biopsies from 2008-2018 (n=668). There were 303 patients who received uterine artery embolisation (UAE) and 478 patients who received pelvic ultrasound within the study period. Medical records were evaluated for radiological-histopathological correlation, demographics, laboratory studies, and clinical follow-up. RESULTS: In this cohort of 668 patients, there were 37 biopsies positive for malignancy; women with malignancy were older (58 versus 47 years, p<0.0001) and more likely to be post-menopausal (66% versus 12%, p<0.0001). There were 303 patients who underwent UAE and underwent a diagnostic-quality endometrial biopsy during the pre-procedural evaluation, none of whom were post-menopausal and had a mean age of 45 years. In women with abnormal uterine bleeding (AUB) or post-menopausal bleeding (PMB), the sensitivity of MRI for detecting endometrial cancer was 96.2%, with a negative predictive value (NPV) of 99.8%, compared to 68% and 97% for ultrasound, respectively. The receiver operating characteristic (ROC) curve of pre-biopsy MRI in identifying pre-malignant and malignant endometrial pathology demonstrated an AUC of 0.8920 (p<0.0001). CONCLUSION: In women with AUB or PMB, MRI has a 99.8% NPV in ruling out endometrial cancer. Further consideration should be made towards optimising pre-procedural evaluation for UAE.

High burden of invasive group A streptococcal disease in the Northern Territory of Australia.

Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response.

Melioidosis in New Caledonia: a dominant strain in a transmission hotspot.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia. In New Caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. To improve our understanding of melioidosis epidemiology in New Caledonia, we compared the local cases and B. pseudomallei isolates with those from endemic areas. Nineteen melioidosis cases have been diagnosed in New Caledonia since 1999, mostly severe and with frequent bacteraemia, leading to three (16%) fatalities. All but one occurred in the North Province. Besides sporadic cases caused by non-clonal strains, we also identified a hotspot of transmission related to a clonal group of B. pseudomallei that is phylogenetically related to Australian strains.

The melioidosis agent Burkholderia pseudomallei and related opportunistic pathogens detected in faecal matter of wildlife and livestock in northern Australia.

The Darwin region in northern Australia has experienced rapid population growth in recent years, and with it, an increased incidence of melioidosis. Previous studies in Darwin have associated the environmental presence of Burkholderia pseudomallei, the causative agent of melioidosis, with anthropogenic land usage and proximity to animals. In our study, we estimated the occurrence of B. pseudomallei and Burkholderia spp. relatives in faecal matter of wildlife, livestock and domestic animals in the Darwin region. A total of 357 faecal samples were collected and bacteria isolated through culture and direct DNA extraction after enrichment in selective media. Identification of B. pseudomallei, B. ubonensis, and other Burkholderia spp. was carried out using TTS1, Bu550, and recA BUR3-BUR4 quantitative PCR assays, respectively. B. pseudomallei was detected in seven faecal samples from wallabies and a chicken. B. cepacia complex spp. and Pandoraea spp. were cultured from wallaby faecal samples, and B. cenocepacia and B. cepacia were also isolated from livestock animals. Various bacteria isolated in this study represent opportunistic human pathogens, raising the possibility that faecal shedding contributes to the expanding geographical distribution of not just B. pseudomallei but other Burkholderiaceae that can cause human disease.

Crusted scabies is associated with increased IL-17 secretion by skin T cells.

Scabies is an ectoparasitic infestation by the mite Sarcoptes scabiei. Although commonly self-limiting, a fraction of patients develop severely debilitating crusted scabies. The immune mechanisms underlying the development of crusted scabies are unclear, and undertaking longitudinal infection studies in humans is difficult. We utilized a porcine model to compare cellular immune responses in peripheral blood and skin of pigs with different clinical manifestations of scabies (n = 12), and in uninfected controls (n = 6). Although clinical symptoms were not evident until at least 4 weeks post-infestation, the numbers of peripheral IFNγ-secreting CD4(+) T cells and γδ T cells increased in infected pigs from week 1 post-infestation. γδ T cells remained increased in the blood at week 15 post-infestation. At week 15, skin cell infiltrates from pigs with crusted scabies had significantly higher CD8(+) T cell, γδ T cell and IL-17(+) cell numbers than those with ordinary scabies. Peripheral IL-17 levels were not increased, suggesting that localized skin IL-17-secreting T cells may play a critical role in the pathogenesis of crusted scabies development. Given the potential of anti-IL-17 immunotherapy demonstrated for other inflammatory skin diseases, this study may provide a novel therapeutic avenue for patients with recurrent crusted scabies.

Melioidosis in a patient on monoclonal antibody therapy for psoriatic arthritis.

Melioidosis is caused by the environmental bacterium Burkholderia pseudomallei and can present with severe sepsis. Predisposing risk factors are present in 80% of cases. Monoclonal antibodies are increasingly prescribed for varied medical conditions. This report describes the first known case of melioidosis in a patient whose only risk factor for disease is treatment with a monoclonal antibody. Prescribers of monoclonal antibodies and other immunosuppressants should ensure that their patients are aware of the potential risk of melioidosis prior to travel and the precautions that should be taken.

First records of reproductive behaviour and early development of the bearded goby Sufflogobius bibarbatus.

Data on developmental characteristics from fertilization to 2 days post-hatching during captivity of the anoxia tolerant bearded goby Sufflogobius bibarbatus, one of the keystone prey species for many of the commercial fish populations, sea mammals and birds in south-west Africa, are presented.

Comparison of percutaneous endoscopic, laparoscopic and open gastrostomy insertion in children.

PURPOSE: To compare the outcomes and complications between percutaneous endoscopic gastrostomy (PEG), laparoscopic gastrostomy (LAPG) and open gastrostomy (OG) in children. METHODS: Retrospective review of 369 patients from July 1998 to December 2010 who had their gastrostomies inserted at a single tertiary paediatric institution. Patients who were lost in follow-up (59) and had insufficient data (23) were excluded from this study. Results were analysed using descriptive statistics. RESULTS: Of the 369 included in our study, 260 patients underwent LAPG, 86 PEG and 23 open gastrostomy (OG) procedures. The early complication rate for PEGs was 10.5 %, and for LAPGS 2.7 % (p = 0.006). The late complication rate was 41.9 % for PEGs and 43.1 % for LAPGs (p = NS). The overall complication rate for PEG was 54.7 % and it was 44.6 % for LAPG (p = NS). Major complications occurred only in the PEG group: gastro-colonic fistula (1), peritonitis (1), and "buried bumper syndrome" (1). The overall complication rate for OG was 78.3 % (p = 0.01, when this was compared to LAPGs and PEGs together), although there were no early complications in the OG group. CONCLUSION: PEGs had a significantly higher early complication rate than LAPGs and the only major complications occurred in the PEG group. PEGs also had a higher overall complication rate than LAPGs, although the difference was not statistically significant. Both PEGs and LAPGs were significantly superior to OG in terms of overall complication rates.

Key lessons from the COVID-19 public health response in Australia.

Australia avoided the worst effects of the COVID-19 pandemic, but still experienced many negative impacts. Reflecting on lessons from Australia's public health response, an Australian expert panel composed of relevant discipline experts identified the following key lessons: 1) movement restrictions were effective, but their implementation requires careful consideration of adverse impacts, 2) disease modelling was valuable, but its limitations should be acknowledged, 3) the absence of timely national data requires re-assessment of national surveillance structures, 4) the utility of advanced pathogen genomics and novel vaccine technology was clearly demonstrated, 5) decision-making that is evidence informed and consultative is essential to maintain trust, 6) major system weaknesses in the residential aged-care sector require fixing, 7) adequate infection prevention and control frameworks are critically important, 8) the interests and needs of young people should not be compromised, 9) epidemics should be recognised as a 'standing threat', 10) regional and global solidarity is important. It should be acknowledged that we were unable to capture all relevant nuances and context specific differences. However, the intent of this review of Australia's public health response is to critically reflect on key lessons learnt and to encourage constructive national discussion in countries across the Western Pacific Region.

Outpatient parenteral antimicrobial therapy-treated bone and joint infections in a tropical setting.

BACKGROUND: Osteoarticular infections are a primary indication for outpatient parenteral antimicrobial therapy (OPAT). The climate and geographical diversity of tropical Australia, together with the prevalence of melioidosis, disseminated gonococcal disease and community-acquired methicillin-resistant Staphylococcus aureus renders this a challenging environment in which to manage such infections. We evaluated patients managed by the Royal Darwin Hospital Hospital in the Home service for bone and joint infections. METHODS: A retrospective analysis of the therapeutic outcomes at the end of intravenous therapy was carried out for patients treated between 1 January 2006 and 15 September 2007. RESULTS: Fifty-five patients were treated, including 21 (38%) indigenous Australians and 18 (33%) from remote communities. Baseline characteristics were similar to other published data, but there were two cases each of gonococcal septic arthritis and melioidosis. During treatment, 39 (71%) lived at home, with five (9%) of these receiving treatment at community clinics. Thirteen (24%) resided in self-care units in the hospital grounds. Three (5%) were managed at hostels or in prison. Median duration of parenteral therapy was 42 days, with a median of 22 days outside hospital, providing a total saving of 1307 bed-days. Clinical success at end of therapy was 84%, with no significant difference between indigenous and non-indigenous cohorts. CONCLUSION: OPAT for osteoarticular infections is both feasible and effective in a tropical environment, including for indigenous patients. Extension of treatment to remote-dwelling patients is facilitated by the innovative use of self-care units and administration of treatment at remote clinics.

Association of the melioidosis agent Burkholderia pseudomallei with water parameters in rural water supplies in Northern Australia.

We analyzed water parameters and the occurrence of the melioidosis agent Burkholderia pseudomallei in 47 water bores in Northern Australia. B. pseudomallei was associated with soft, acidic bore water of low salinity but high iron levels. This finding aids in identifying water supplies at risk of contamination with this pathogenic bacterium.

Geospatial epidemiology of Staphylococcus aureus in a tropical setting: an enabling digital surveillance platform.

Delivery of information to clinicians on evolving antimicrobial susceptibility needs to be accurate for the local needs, up-to-date and readily available at point of care. In northern Australia, bacterial infection rates are high but resistance to first- and second-line antibiotics is poorly described and currently-available datasets exclude primary healthcare data. We aimed to develop an online geospatial and interactive platform for aggregating, analysing and disseminating data on regional bacterial pathogen susceptibility. We report the epidemiology of Staphylococcus aureus as an example of the power of digital platforms to tackle the growing spread of antimicrobial resistance in a high-burden, geographically-sparse region and beyond. We developed an online geospatial platform called HOTspots that visualises antimicrobial susceptibility patterns and temporal trends. Data on clinically-important bacteria and their antibiotic susceptibility profiles were sought from retrospectively identified clinical specimens submitted to three participating pathology providers (96 unique tertiary and primary healthcare centres, n = 1,006,238 tests) between January 2008 and December 2017. Here we present data on S. aureus only. Data were available on specimen type, date and location of collection. Regions from the Australian Bureau of Statistics were used to provide spatial localisation. The online platform provides an engaging visual representation of spatial heterogeneity, demonstrating striking geographical variation in S. aureus susceptibility across northern Australia. Methicillin resistance rates vary from 46% in the west to 26% in the east. Plots generated by the platform show temporal trends in proportions of S. aureus resistant to methicillin and other antimicrobials across the three jurisdictions of northern Australia. A quarter of all, and up to 35% of methicillin-resistant S. aureus (MRSA) blood isolates in parts of the northern Australia were resistant to inducible-clindamycin. Clindamycin resistance rates in MRSA are worryingly high in regions of northern Australia and are a local impediment to empirical use of this agent for community MRSA. Visualising routinely collected laboratory data with digital platforms, allows clinicians, public health physicians and guideline developers to monitor and respond to antimicrobial resistance in a timely manner. Deployment of this platform into clinical practice supports national and global efforts to innovate traditional disease surveillance systems with the use of digital technology and to provide practical solutions to reducing the threat of antimicrobial resistance.

Determining superficial dosimetry for the internal canthus from the Monte Carlo simulation of kV photon and MeV electron beams.

This paper presents the findings of an investigation into the Monte Carlo simulation of superficial cancer treatments of an internal canthus site using both kilovoltage photons and megavoltage electrons. The EGSnrc system of codes for the Monte Carlo simulation of the transport of electrons and photons through a phantom representative of either a water phantom or treatment site in a patient is utilised. Two clinical treatment units are simulated: the Varian Medical Systems Clinac 2100C accelerator for 6 MeV electron fields and the Pantak Therapax SXT 150 X-ray unit for 100 kVp photon fields. Depth dose, profile and isodose curves for these simulated units are compared against those measured by ion chamber in a PTW Freiburg MP3 water phantom. Good agreement was achieved away from the surface of the phantom between simulated and measured data. Dose distributions are determined for both kV photon and MeV electron fields in the internal canthus site containing lead and tungsten shielding, rapidly sloping surfaces and different density interfaces. There is a relatively high level of deposition of dose in tissue-bone and tissue-cartilage interfaces in the kV photon fields in contrast to the MeV electron fields. This is reflected in the maximum doses in the PTV of the internal canthus field being 12 Gy for kV photons and 4.8 Gy for MeV electrons. From the dose distributions, DVH and dose comparators are used to assess the simulated treatment fields. Any indication as to which modality is preferable to treat the internal canthus requires careful consideration of many different factors, this investigation provides further perspective in being able to assess which modality is appropriate.

Oral eradication therapy for melioidosis: Important but not without risks.

OBJECTIVES: The purpose of this study was to quantify the adverse effects from oral eradication therapy for melioidosis, which is usually with high dose trimethoprim-sulfamethoxazole for 3-6 months. METHODS: This retrospective cohort study reviewed side effects from oral eradication therapy in patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory between 1st October 2012 and 1st January 2017. RESULTS: 234 patients presented for the first time with culture-confirmed melioidosis. Of these, 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital. Of the remaining 212 patients, 203 (95.8%) were initially prescribed trimethoprim-sulfamethoxazole as oral eradication therapy, 6 (2.8%) were prescribed doxycycline and 3 (1.4%) had no eradication therapy. Of the 203 prescribed trimethoprim-sulfamethoxazole, 61 (30.0%) experienced adverse effects, which necessitated a cessation, a change in antibiotic or reduction in dose. CONCLUSIONS: In patients treated for melioidosis in northern Australia there are high rates of adverse effects from oral trimethoprim-sulfamethoxazole, frequently necessitating a change in therapy or a reduction in dose. Given the side effects and low rates of oral therapy completion in our region we emphasise the importance of the prior often prolonged intensive phase intravenous therapy and using weight based trimethoprim-sulfamethoxazole dosing for eradication therapy.

New insights into disease pathogenesis in crusted (Norwegian) scabies: the skin immune response in crusted scabies.

BACKGROUND: Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may be loose, scaly and flaky or thick and adherent. OBJECTIVES: To describe crusted scabies skin pathogenesis and identify markers associated with an inappropriate immune response leading to disease progression. PATIENTS/METHODS: Serial sections from skin biopsies obtained from two patients with severe crusted scabies were examined by immunohistochemistry for cell surface markers and inflammatory and regulatory cytokines. Concurrent levels of total B- and T-cell subsets and IgE, IgA, IgM, IgG and IgG subclasses were analysed in the blood. In addition antibody levels were recorded in a further 33 patients with crusted scabies and 14 patients with ordinary scabies. RESULTS: A predomination of infiltrating CD8+ T lymphocytes in the dermis was observed compared with minimal helper T lymphocytes (CD4+) and the absence of any B cells. The proportion of T and B lymphocytes and T-cell subsets in the blood of these patients were within normal ranges, indicating a selective movement of CD8+ T cells into the dermis. Furthermore, strong staining for the inflammatory cytokine interleukin-1 beta and anti-inflammatory cytokine transforming growth factor-beta1 was observed. Elevated levels of IgE, IgG, IgG1, IgG3 and IgG4 were recorded. CONCLUSIONS: Skin-homing cytotoxic T cells contribute to an imbalanced inflammatory response in the dermis of crusted scabies lesional skin. This, in combination with the lack of B cells, is contributing to the failure of the skin immune system to mount an effective response resulting in uncontrolled growth of the parasite.

A change of heart: the new infective endocarditis prophylaxis guidelines.

New Australian guidelines for the prevention of infective endocarditis were published in July 2008. The guidelines were revised by a multidisciplinary group to reflect recent changes in international recommendations regarding antibiotic prophylaxis for infective endocarditis. The reasons for the changes are explored in this review and the implications for dental practice are discussed.

Push versus pull gastrostomy in cancer patients: A single center retrospective analysis of complications and technical success rates.

PURPOSE: To compare the technical success and complication rates of push versus pull gastrostomy tubes in cancer patients, and to examine their dependence on operator experience. MATERIALS AND METHODS: A retrospective review was performed of 304 cancer patients (170 men, 134 women; mean age 60.3±12.6 [SD], range: 19-102 years) referred for primary gastrostomy tube placement, 88 (29%) of whom had a previously unsuccessful attempt at percutaneous endoscopic gastrostomy (PEG) placement. Analyzed variables included method of insertion (push versus pull), indication for gastrostomy, technical success, operator experience, and procedure-related complications within 30 days of placement. RESULTS: Gastrostomy tubes were placed for feeding in 189 patients and palliative decompression in 115 patients. Technical success was 91%: 78% after endoscopy had previously been unsuccessful and 97% when excluding failures associated with prior endoscopy. In the first 30 days, there were 29 minor complications (17.2%) associated with push gastrostomies, and only 8 minor complications (7.5%) with pull gastrostomies (P<0.05). There was no significant difference in major complications (push gastrostomy 5.3%, pull gastrostomy 5.6%). For decompressive gastrostomy tubes, the pull technique resulted in lower rates of both minor and major complications. There was no difference in complications or technical success rates for more versus less experienced operators. CONCLUSION: Pull gastrostomy tube placement had a lower rate of complications than push gastrostomy tube placement, especially when the indication was decompression. The technical success rate was high, even after a failed attempt at endoscopic placement. Both the rates of success and complications were independent of operator experience.