Limb presentations of invasive Group A Streptococci infection in children.

Infections with invasive Group A streptococcus can have a wide range of presentations and be life threatening if not diagnosed and managed rapidly. Limb presentations in children can be especially challenging and we present our experience to help manage such cases. There can be multiple foci of infection with seeding to avascular structures. Therefore, we advocate maintaining a high degree of clinical suspicion when assessing this group of patients, who are often critically unwell, and have varying presentation. Early and aggressive surgical intervention may be key for disease control.

A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss. PATIENTS AND METHODS: mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated. RESULTS: Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples. CONCLUSIONS: The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway. CLINICAL TRIAL NUMBER: NCT02525068.

Preoperative HBA1c and risk of postoperative complications in patients with gynaecological cancer.

BACKGROUND: HBA1c is used as an indicator for the long-term control of the glycaemic state and outcome predictors in diabetic patients. Diabetic patients have an increased risk of post-operative complications especially those related to infection. The aim of our study is to ascertain the relationship between HBA1c levels and post-operative recovery within the subspecialty of gynaecological oncology. METHOD: Prospective cohort study during the period 1 August 2012 through 31 August 2014. Preoperative measurement of HBA1c on all gynaecological oncology patients that underwent major surgery. Patient variables collected and analysed were BMI (kg/m(2)), length of stay (LOS in days), cancer stage (stage 1 through stage 4), infective complications, non-infective complications and readmission to hospital. RESULTS: A total of 300 patients were included in our study, 34 of them were known to be diabetic while 266 were presumed to be non-diabetic. Of the presumed non-diabetic cohort, 17.3 % (46/266) had impaired glucose tolerance or diabetes. Mean BMI was significantly increased in the pre-existing diabetic group (32.8 vs. 29.3 kg/m(2), p = 0.016). Infective complications were almost double the rate amongst the known diabetic women than those presumed to be non-diabetic (32.4 vs. 18.0 %, p = 0.048). Rate of re-admission to hospital due to complications was 20.6 % in the diabetic group and 4.1 % within the presumed non-diabetic group (p < 0.001). Infective complications occurred in 16.9 % of women with HBA1c <42 mmol/mol, 22.7 % of those with HBA1c of 42-47 mmol/mol, 43.5 % of patients with HBA1c 48-64 mmol/mol and 37.5 % of patients with HBA1c >64 mmol/mol. Non-infective complications were also more frequent in women with elevated HBA1c (11.1, 22.7, 26.1 and 12.5 % in those women with HBA1c <42, 42-47, 48-64 and >64 mmol/mol, respectively). Re-admission to hospital within 30 days for a complication of surgery occurred in 4.4 % of women with HBA1c <42 mmol/mol, 4.5 % of women with HBA1c measured at 42-47 mmol/mol, 30.8 % of those with HBA1c 48-64 mmol/mol and 25 % of women with HBA1c >64 mmol/mol. CONCLUSION: Preoperative measurement of HBA1c may identify patients (both diabetic and non-diabetic women) at higher risk of postoperative complications and could be used as a trigger for modification of the perioperative management of such patients.

Balloon Cell Urethral Melanoma: Differential Diagnosis and Management.

Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas) that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

Enterovirus 71 outbreak in Northern Sydney, 2013: case series and initial response.

AIM: Enteroviruses are a common cause of childhood disease which may manifest in a variety of ways. Enterovirus 71 (EV71) is a subtype of enterovirus which can cause meningoencephalomyelitis resulting in neurological sequelae including lethargy, weakness, ataxia, sleep myoclonus, urinary retention and, in severe cases, cardiorespiratory collapse due to neurogenic pulmonary oedema. EV71 was responsible for outbreaks in South East Asia in 1997-1998, in Western Australia in 1999 and in Sydney in 2000-2001. In 2013, we are experiencing another EV71 outbreak in Sydney. This study describes the discovery of a new outbreak in Sydney's Northern Beaches, the clinical findings as well as the public health response. METHODS: Thirty-seven children in total presented with presumed EV71 to the Northern Beaches Health Service from December 2012 to April 2013. Most children presented with a prodrome lasting 2-7 days prior to seeking medical attention. Sleep myoclonus was a common presenting sign occurring in 65%. Neurological signs were subtle in the majority of children and were at times missed by clinicians on a child's first presentation. Forty-six per cent of children who presented to Northern Beaches Health Service during this outbreak required a transfer to a tertiary paediatric centre for more intensive care. RESULTS: The public health investigation was important in establishing that the disease was widespread throughout the community and not as a result to exposure to a single child care setting. Identification of risk factors enabled more targeted communication to medical practitioners, child care centres and parents within the local community. CONCLUSIONS: EV71 is in Australia and all clinicians seeing children in primary, secondary and tertiary care centres need to be aware of the disease, the subtle nature of initial symptoms and the potentially devastating consequences.

Effect of rearing environment and dietary zinc oxide on the response of group-housed weaned pigs to enterotoxigenic Escherichia coli O149 challenge.

A 2 × 2 factorial experiment was conducted to determine the effects of rearing environment (indoor (In) v. outdoor (Out)) and dietary zinc oxide (ZnO) supplementation (0 (-Zn) v. 3100 (+Zn) mg/kg feed) on the response of weaned pigs to a challenge infection with enterotoxigenic Escherichia coli (ETEC). Pigs from the two rearing environments were weaned onto trial diets at 4 weeks of age, moved into conventional accommodation and infected 3 days later with 109 CFU ETEC per os. Faecal ETEC shedding was determined before and after challenge. After 7 days of ETEC infection, all pigs were euthanized for gut lactic acid bacteria (LAB)-to-coliform ratio, pH and small intestine morphological measurements. Both ZnO and outdoor rearing reduced ETEC excretion, and these effects were additive. Outdoor rearing increased small intestine and colon tissue weight. ZnO increased villus height and goblet cell number in the upper small intestine, LAB-to-coliform ratio (through reduced coliforms) in the lower small intestine and proximal colon, and improved growth performance. There were interactive effects of rearing environment and ZnO supplementation on upper small intestine villus height and daily gain, as outdoor rearing conferred advantages on these variables only with ZnO dietary supplementation. Daily gains were 233, 174, 277 and 347 (s.e.m. 27.2) g/day for the In - Zn, Out - Zn, In + Zn and Out + Zn, respectively. These results suggest different, but complementary mechanisms of intestinal health and performance in outdoor-reared pigs and those offered ZnO supplemented diets. The results indicate that the benefits of ZnO to the weaned pig extend beyond suppression of ETEC and appear mediated through altered development of the small intestine mucosa.

Impact of sampling techniques on measured stormwater quality data for small streams.

Science-based sampling methodologies are needed to enhance water quality characterization for setting appropriate water quality standards, developing Total Maximum Daily Loads, and managing nonpoint source pollution. Storm event sampling, which is vital for adequate assessment of water quality in small (wadeable) streams, is typically conducted by manual grab or integrated sampling or with an automated sampler. Although it is typically assumed that samples from a single point adequately represent mean cross-sectional concentrations, especially for dissolved constituents, this assumption of well-mixed conditions has received limited evaluation. Similarly, the impact of temporal (within-storm) concentration variability is rarely considered. Therefore, this study evaluated differences in stormwater quality measured in small streams with several common sampling techniques, which in essence evaluated within-channel and within-storm concentration variability. Constituent concentrations from manual grab samples and from integrated samples were compared for 31 events, then concentrations were also compared for seven events with automated sample collection. Comparison of sampling techniques indicated varying degrees of concentration variability within channel cross sections for both dissolved and particulate constituents, which is contrary to common assumptions of substantial variability in particulate concentrations and of minimal variability in dissolved concentrations. Results also indicated the potential for substantial within-storm (temporal) concentration variability for both dissolved and particulate constituents. Thus, failing to account for potential cross-sectional and temporal concentration variability in stormwater monitoring projects can introduce additional uncertainty in measured water quality data.

Apronectomy in combination with major gynaecological procedures.

Removal of excess abdominal fat may be necessary to facilitate major gynaecological surgery for oncology patients. The aim of the study was to assess the feasibility, associated morbidity of such operation when combined with other major gynaecological procedures. This was a retrospective review of cases performed in a tertiary gynaecological oncology centre. All of the patients were diagnosed with gynaecological cancers. The results show a modest increase in operative time; however the procedure was feasible and safe with no other increased risk. This represents time saving for the patients and hospital in having two operations in one session.

Development of an observational measure of healthcare worker hand-hygiene behaviour: the hand-hygiene observation tool (HHOT).

Previous observational measures of healthcare worker (HCW) hand-hygiene behaviour (HHB) fail to provide adequate standard operating procedures (SOPs), accounts of inter-rater agreement testing or evidence of sensitivity to change. This study reports the development of an observational tool in a way that addresses these deficiencies. Observational categories were developed systematically, guided by a clinical guideline, previous measures and pilot hand-hygiene behaviour observations (HHOs). The measure, a simpler version of the Geneva tool, consists of HHOs (before and after low-risk, high-risk or unobserved contact), HHBs (soap, alcohol hand rub, no action, unknown), and type of HCW. Inter-observer agreement for each category was assessed by observation of 298 HHOs and HHBs by two independent observers on acute elderly and intensive care units. Raw agreement (%) and Kappa were 77% and 0.68 for HHB; 83% and 0.77 for HHO; and 90% and 0.77 for HCW. Inter-observer agreement for overall compliance of a group of HCWs was assessed by observation of 1191 HHOs and HHBs by two pairs of independent observers. Overall agreement was good (intraclass correlation coefficient = 0.79). Sensitivity to change was examined by autoregressive time-series modelling of longitudinal observations for 8 months on the intensive therapy unit during an Acinetobacter baumannii outbreak and subsequent strengthening of infection control measures. Sensitivity to change was demonstrated by a rise in compliance from 80 to 98% with an odds ratio of increased compliance of 7.00 (95% confidence interval: 4.02-12.2) P < 0.001.

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.