Preconception care for women with type 2 diabetes mellitus: A mixed-methods study of provider knowledge and practice.

AIMS: Preconception care may decrease adverse pregnancy outcomes associated with pre-existing diabetes mellitus. Aboriginal Australians are at high risk of type 2 diabetes mellitus (T2DM), with earlier onset. We explored practitioner views on preconception care delivery for women with T2DM in the Northern Territory, where 31% of births are to Aboriginal women. METHODS: Mixed-methods study including cross-sectional survey of 156 health practitioners and 11 semi-structured interviews. RESULTS: Practitioners reported low attendance for preconception care however, 51% provided counselling on an opportunistic basis. Rural/remote practitioners were most likely to find counselling feasible. The majority (69%) utilised appropriate guidelines and addressed lifestyle modifications including smoking (81%), weight management (79%), and change medications appropriately such as ceasing ACE inhibitors (69%). Fewer (40%) prescribed the recommended dose of folate (5mg) or felt comfortable recommending delaying pregnancy to achieve optimal preconception glucose control (42%). Themes identified as barriers to care included the complexity of care setting and infrequent preconception consultations. There was a focus on motivation of women to make informed choices about conception, including birth spacing, timing and contraception. Preconception care enablers included cross-cultural communication, a multi-disciplinary care team and strong client-based relationships. CONCLUSIONS: Health practitioners are keen to provide preconception counselling and reported knowledge of evidence-based guidelines. Improvements are needed in recommending high dose folate and optimising glucose control. Cross-cultural communication and team-based care were reported as fundamental to successful preconception care in women with T2DM. Continued education and policy changes are required to support practitioners in opportunities to enhance pregnancy planning.

Associations of mortality and cardiovascular disease risks with diabetes and albuminuria in urban Indigenous Australians: the DRUID follow-up study.

AIM: To assess the relationships of diabetes and albuminuria with all-cause mortality and cardiovascular disease outcomes in a population without prior cardiovascular disease using data from the Darwin Region Urban Indigenous Diabetes (DRUID) study. METHODS: We conducted a prospective cohort study of 706 participants (aged 15-81 years, 68% women) without prior cardiovascular disease who underwent a 75-g oral glucose tolerance test. Deaths and fatal or non-fatal cardiovascular disease were determined over 7 years, and hazard ratios with 95% CIs and population attributable risks were estimated for baseline glycaemia and albuminuria. RESULTS: Compared with normoglycaemia and after adjustment for age, sex, hypertension, dyslipidaemia and smoking, known diabetes was associated with an adjusted hazard ratio of 4.8 (95% CI 1.5-14.7) for all-cause mortality and 5.6 (95% CI 2.1-15.2) for cardiovascular disease. Compared with normoalbuminuria, the respective adjusted risks for macroalbuminuria were 10.9 (95% CI 3.7-32.1) and 3.9 (95% CI 1.4-10.8). The Adjusted all-cause mortality and cardiovascular disease estimated population attributable risks for diabetes were 27% and 32%, and for albuminuria they were 32% and 21%, respectively. CONCLUSIONS: In our study population, the burden of mortality and cardiovascular disease was largely driven by diabetes and albuminuria. This finding on the influence of diabetes and albuminuria is consistent with reports in other high-risk Indigenous populations and should be better reflected in risk scores and intervention programmes.

Judicious use of prophylactic antimicrobials to reduce abdominal surgical site infections in periparturient cows: part 1 - a risk factor review.

Surgical site infections (SSI) are an uncommon, but significant, consequence of surgical interventions. There are very few studies investigating SSI risk in veterinary medicine, and even fewer in cattle, despite the fact that major surgeries are commonly conducted on livestock. Furthermore, the suboptimal conditions under which such surgeries are frequently performed on livestock could be considered an important risk factor for the development of SSIs. With increasing public concern over the contribution of veterinary-prescribed antimicrobials to the emergence of antimicrobial-resistant bacteria in people, there is widespread scrutiny and criticism of antimicrobial use in livestock production medicine systems. While the causal link between antimicrobial resistance in livestock and people is heavily debated, it is clear that the prevalence of antimicrobial resistance, in any population, is closely correlated with the antimicrobial 'consumption' within that population. As the veterinary profession explores ways of addressing the emergence and selection of antimicrobial-resistant bacteria in food-producing animals, there is a need for veterinarians and producers to carefully consider all areas of antimicrobial use, and employ an evidence-based approach in designing appropriate clinical protocols. This paper aims to review current knowledge regarding the risk factors related to abdominal SSI in periparturient cows, and to encourage practitioners to judiciously evaluate both their standard operating procedures and their use of antimicrobials in these situations. In a second paper, to be published in a subsequent issue of Veterinary Record, these principles will be used to provide specific evidence-based recommendations for antimicrobial use in bovine abdominal surgery.

Management of diabetes in Indigenous communities: lessons from the Australian Aboriginal population.

Type 2 diabetes mellitus and other chronic cardio-metabolic conditions are significant contributors to the large disparities in life expectancy between Indigenous and non-Indigenous Australians. Type 2 diabetes is more prevalent from a young age among Indigenous Australians and is often preceded by a cluster of risk factors, including central obesity, dyslipidaemia, albuminuria and socio-economic disadvantage. Management of type 2 diabetes in Australian Indigenous peoples can be challenging in the setting of limited resources and socio-economic disadvantage. Key strategies to address these challenges include working in partnership with patients, communities and primary healthcare services (PHC, Aboriginal community controlled and government services) and working in a multidisciplinary team. Population prevention measures are required within and beyond the health system, commencing as early as possible in the life course.

A cohort of Indigenous Australian women and their children through pregnancy and beyond: the Gomeroi gaaynggal study.

Indigenous Australians have high rates of chronic diseases, the causes of which are complex and include social and environmental determinants. Early experiences in utero may also predispose to later-life disease development. The Gomeroi gaaynggal study was established to explore intrauterine origins of renal disease, diabetes and growth in order to inform the development of health programmes for Indigenous Australian women and children. Pregnant women are recruited from antenatal clinics in Tamworth, Newcastle and Walgett, New South Wales, Australia, by Indigenous research assistants. Measures are collected at three time points in pregnancy and from women and their children at up to eight time points in the child's first 5 years. Measures of fetal renal development and function include ultrasound and biochemical biomarkers. Dietary intake, infant feeding and anthropometric measurements are collected. Standardized procedures and validated tools are used where available. Since 2010 the study has recruited over 230 women, and retained 66 postpartum. Recruitment is ongoing, and Gomeroi gaaynggal is currently the largest Indigenous pregnancy-through-early-childhood cohort internationally. Baseline median gestational age was 39.1 weeks (31.5-43.2, n=110), median birth weight was 3180 g (910-5430 g, n=110). Over one third (39.3%) of infants were admitted to special care or neonatal nursery. Nearly half of mothers (47.5%) reported tobacco smoking during pregnancy. Results of the study will contribute to knowledge about origins of chronic disease in Indigenous Australians and nutrition and growth of women and their offspring during pregnancy and postpartum. Study strengths include employment and capacity-building of Indigenous staff and the complementary ArtsHealth programme.

Oral vaccination and protection of striped skunks (Mephitis mephitis) against rabies using ONRAB®.

Skunks are one of the most important rabies vector species in North America due to their wide geographic distribution, high susceptibility to the rabies virus, and tendency to inhabit areas around human dwellings and domestic animals. Oral vaccination is a cost-effective, socially acceptable technique often used to control rabies in terrestrial wildlife; however, control of rabies in skunks has proven especially challenging due to the lack of a vaccine effective by the oral route in this species. In this study, we examined the antibody response of captive striped skunks (Mephitis mephitis) to ONRAB(®) and tested the protection afforded by the vaccine against rabies virus. Thirty-one skunks were each offered one ONRAB(®) vaccine bait, 25 skunks were administered ONRAB(®) via direct instillation into the oral cavity (DIOC) and ten controls received no vaccine. A blood sample was collected from controls and vaccinates 6 weeks prior to treatment, and then 5 and 7 weeks post-vaccination (PV). A competitive ELISA was used to detect rabies antibody (RAb). Pre-vaccination sera for all skunks, and sera for all controls throughout the serology study, were negative for RAb. Fifty-eight percent (18/31) of skunks in the bait group and 100% (25/25) of skunks that received ONRAB(®) DIOC had detectable RAb by 7 week PV. All 10 controls succumbed to experimental rabies infection. In the group of skunks administered ONRAB(®) DIOC, 100% (23/23) survived challenge 247 days PV. Survival of skunks presented ONRAB(®) baits was 81% (25/31). In the bait group, all 18 skunks that had detectable RAb by 7 week PV survived challenge. Seven additional skunks without detectable RAb prior to week 7 PV also survived. Lack of any remarkable pathology in study animals, together with positive serology and challenge results, supports that ONRAB(®) is a safe and effective oral rabies vaccine for use in skunks.

Periodontal disease and dental caries among Indigenous Australians living in the Northern Territory, Australia.

BACKGROUND: The aim of this study was to describe the caries experience and severity of periodontal disease in a convenience sample of Indigenous Australians living in the Northern Territory. METHODS: Data were gathered via self-reported questionnaire and dental examination by calibrated examiners. Socio-demographic characteristics were compared with data from the 2011 Australian census while prevalence of periodontal disease and dental caries was compared against weighted estimates from the National Survey of Adult Oral Health 2004-2006. In each comparison, non-overlapping 95% confidence intervals inferred a significant difference. Within-study comparisons were assessed via chi-square, t-tests and analysis of variance for differences among study participants. RESULTS: A total of 312 Indigenous Australian participants provided completed data (average age 39.5 ± 10.5 years, 174 males). Of these, 87.5% were confirmed periodontitis cases; 3.5 times that of national-level estimates. The experience of untreated caries was five times that of national estimates (mean decayed 3.0 versus 0.6). Periodontitis case status was positively associated with older age, male gender and presence of diabetes. CONCLUSIONS: Periodontal disease and untreated caries were significantly more prevalent in this sample of Indigenous Australians compared to the general Australian population. The prevalence of periodontal disease was markedly higher than that previously described for Indigenous Australians.

Diet quality of Australian breast cancer survivors: a cross-sectional analysis from the Australian Longitudinal Study on Women's Health.

BACKGROUND: Evidence supports strong associations between healthful eating patterns and maintaining a healthy weight with favourable health outcomes for breast cancer survivors (BCS). The present study aimed to evaluate the diet quality of Australian BCS and to determine whether diet quality differed between BCS and age-matched healthy controls (HC) or by geographical location. METHODS: This cross-sectional study included 281 BCS and 4069 HC from the Australian Longitudinal Study on Women's Health mid-aged cohort completing Survey 3 in 2001. Data from the Dietary Questionnaire for Epidemiological Studies food frequency questionnaire were used to calculate the Australian Recommended Food Score (ARFS), a validated summary estimate of diet quality based on adherence to the Australian dietary guidelines. RESULTS: The mean (SD) ARFS of the BCS group was 33.2 (9.4) out of a maximum of 74. Mean (SD) total ARFS and component scores of BCS did not differ from the HC group [32.9 (8.7)] and no differences were found in ARFS between urban and rural BCS. CONCLUSIONS: This is the first study dedicated exclusively to describing the diet quality of Australian BCS. Although no difference was found when comparisons were made with a HC group, there is considerable room for improvement in the diet quality of Australian BCS. Given research suggesting higher risk of chronic conditions such as obesity amongst BCS, and the recognition of optimising diet quality as a key factor in health promotion for all population groups, data from the present study suggest the need for research targeting the feasibility and impact of improving diet quality of Australian BCS.

Oral vaccination and protection of red foxes (Vulpes vulpes) against rabies using ONRAB, an adenovirus-rabies recombinant vaccine.

Twenty-seven red foxes (Vulpes vulpes) were each offered a bait containing ONRAB, a recombinant oral rabies vaccine that uses a human adenovirus vector to express the immunogenic rabies virus glycoprotein; 10 controls received no vaccine baits. Serum samples collected from all foxes before treatment, and each week post-treatment for 16 weeks, were tested for the presence of rabies virus neutralizing antibody (RVNA). In the bait group, a fox was considered a responder to vaccination if serum samples from 3 or more consecutive weeks had RVNA ≥0.5 IU/ml. Using this criterion, 79% of adult foxes (11/14) and 46% of juveniles (6/13) responded to vaccination with ONRAB. Serum RVNA of adults first tested positive (≥0.5 IU/ml) between weeks 1 and 3, about 4 weeks earlier than in juveniles. Adults also responded with higher levels of RVNA and these levels were maintained longer. Serum samples from juveniles tested positive for 1-4 consecutive weeks; in adults the range was 2-15 weeks, with almost half of adults maintaining titres above 0.5 IU/ml for 9 or more consecutive weeks. Based on the kinetics of the antibody response to ONRAB, the best time to sample sera of wild adult foxes for evidence of vaccination is 7-11 weeks following bait distribution. Thirty-four foxes (25 ONRAB, 9 controls) were challenged with vulpine street virus 547 days post-vaccination. All controls developed rabies whereas eight of 13 adult vaccinates (62%) and four of 12 juvenile vaccinates (33%) survived. All foxes classed as non-responders to vaccination developed rabies. Of foxes considered responders to vaccination, 80% of adults (8/10) and 67% of juveniles (4/6) survived challenge. The duration of immunity conferred to foxes would appear adequate for bi-annual and annual bait distribution schedules as vaccinates were challenged 1.5 years post-vaccination.

A hybrid computational model for the effects of maspin on cancer cell dynamics.

Cancer metastasis is a complex multistep process which allows cancer cells to establish new tumours in distant organs. The process of metastasis involves cell migration and invasion; it is what makes cancer a fatal disease. The efficiency of most cancer treatments depends on metastasis suppression. Maspin is a type II tumour metastasis suppressor which has multiple cellular effects. It has been described as a key regulatory protein in both the intracellular and extracellular environments. Maspin has been shown to reduce cell migration, invasion, proliferation and angiogenesis, and increase apoptosis and cell-cell adhesion in in vitro and in vivo experiments. The clinical data regarding the predictive effects of maspin expression are variable. To date, the whole cellular mechanisms that maspin uses to influence tumour cell behaviours have not been clearly defined. The diversity of the effects of maspin motivated us to develop an intelligent model to investigate its effects on cellular proliferation and migration. This paper reports a hybrid model of solid tumour growth in order to investigate the impact of maspin on the growth and evolutionary dynamics of the cancer cell. A feed-forward neural network was used to model the behaviours (proliferation, quiescence, apoptosis and/or movement) of each cell, which has been suggested as a suitable model of cell signalling pathways. Results show that maspin reduces migration by 10-40%, confirmed by published in vitro data. The model also shows a reduction in cell proliferation by 20-30% in the presence of maspin. So far, this is the first attempt to model the effect of maspin in a computational model to verify in vitro data. This will provide new insights into the tumour suppressive properties of maspin and inform the development of novel cancer therapies.

False-positive prostate cancer markers in a man with symptomatic urethral Chlamydia trachomatis infection.

Symptomatic male urethral Chlamydia trachomatis infection resulted in inflammation of the prostate, with associated increases in both prostate-specific (PSA) and prostate cancer-specific (PCA3) markers with prostate biopsies showing no evidence of malignancy.

Immune response and protection in raccoons (Procyon lotor) following consumption of baits containing ONRAB®, a human adenovirus rabies glycoprotein recombinant vaccine.

We investigated the immune response and protection conferred in raccoons (Procyon lotor) following consumption of ONRAB(®) oral rabies vaccine baits. Forty-two wild-caught, captive raccoons were each offered an ONRAB vaccine bait; 21 controls received no vaccine baits. Blood samples collected from all raccoons before treatment, and each week posttreatment for 16 wk, were assessed for the presence of rabies virus antibody. In the bait group, an individual was considered to have responded to vaccination if serum samples from three or more consecutive weeks were antibody-positive. Using this criterion, 77% (20/26) of raccoons that consumed ONRAB baits with no observed vaccine spillage (full dose) demonstrated a humoral immune response. In the group that received a partial dose (0.05-0.90 mL vaccine recovered), 50% (8/16) of raccoons responded to vaccination. Regardless of the vaccine dose received, among the 28 raccoons that responded to vaccination 18 had antibody initially detectable at week 2 and 22 remained antibody-positive for at least 10 consecutive weeks. Kinetics of the humoral immune response suggest that the best time to conduct postbaiting surveillance for evidence of vaccination would be 6-13 wk following bait deployment, with the highest antibody prevalence expected between weeks 8-10. A sub-sample of 29 raccoons (20 ONRAB, 9 controls) was challenged with raccoon rabies virus variant 350 days posttreatment. Eight of nine controls (89%) developed rabies whereas 15/20 vaccinates (75%) survived. Survival following rabies challenge was significantly higher in raccoons presented ONRAB vaccine baits.

Miniaturized ultra high field asymmetric waveform ion mobility spectrometry combined with mass spectrometry for peptide analysis.

Miniaturized ultra high field asymmetric waveform ion mobility spectrometry (ultra-FAIMS) combined with mass spectrometry (MS) has been applied to the analysis of standard and tryptic peptides, derived from α-1-acid glycoprotein, using electrospray and nanoelectrospray ion sources. Singly and multiply charged peptide ions were separated in the gas phase using ultra-FAIMS and detected by ion trap and time-of-flight MS. The small compensation voltage (CV) window for the transmission of singly charged ions demonstrates the ability of ultra-FAIMS-MS to generate pseudo-peptide mass fingerprints that may be used to simplify spectra and identify proteins by database searching. Multiply charged ions required a higher CV for transmission, and ions with different amino acid sequences may be separated on the basis of their differential ion mobility. A partial separation of conformers was also observed for the doubly charged ion of bradykinin. Selection on the basis of charge state and differential mobility prior to tandem mass spectrometry facilitates peptide and protein identification by allowing precursor ions to be identified with greater selectivity, thus reducing spectral complexity and enhancing MS detection.

Can cause of death be predicted from the pre-necropsy information provided in coroners' cases?

AIM: To determine whether the cause of death can be accurately predicted from the pre-necropsy information available in coroners' cases, before carrying out a postmortem examination. METHODS: In this prospective study pathologists read the clinical summary provided by the Coroner's Office and formulated a predicted cause of death. An external examination was then conducted and any relevant information recorded, together with any changes to the original predicted cause of death. They then carried out a complete necropsy before recording a final cause of death, which was subsequently compared with their prediction. RESULTS: A total of 95 necropsies were included in the study. The cause of death was deemed to have been correctly predicted from the history in 62 cases (65.3%). In 33 cases (34.7%) an unexpected cause of death was found. Findings from the external examination were noteworthy in only 8 cases (8.4%), and did not alter the cause of death in any case. CONCLUSIONS: In certain circumstances an accurate cause of death may be given with confidence without the apparent need for necropsy. However, many common causes of death can present with similar or misleading scenarios. This study indicates that performing necropsies, despite seemingly predictable circumstances, is advisable if an accurate cause of death is to be recorded.

Dermatomyositis as a paraneoplastic syndrome in carcinosarcoma of uterine origin.

Paraneoplastic syndromes are a collection of disorders affecting an organ or tissue caused by cancer but occurring at a site distant from the primary or metastases. Dermatomyositis can occur in association with malignancy as a paraneoplastic phenomenon. We present a case of a patient presenting simultaneously with an advanced carcinosarcoma of the uterus and dermatomyositis. The diagnoses, pathophysiology and treatment of these two conditions are discussed and current published studies reviewed.

Kimura disease of the eyelid: a clinicopathologic study with electron microscopic observations.

A 70-year-old white man presented with a solitary eyelid nodule of 6 months' duration. Because lymphoma could not be excluded on the initial biopsy, the mass was completely excised. Histologic examination confirmed the diagnosis of Kimura disease, an uncommon chronic inflammatory condition. Peripheral eosinophilia was present. The patient did not have any other lesions of Kimura disease on follow-up examination. The clinical, radiologic, histologic, and electron microscopic findings of Kimura disease are discussed. To our knowledge, solitary involvement of the eyelid has not been reported previously. Kimura disease should be included in the differential diagnosis of an eyelid mass lesion.

Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections.

BACKGROUND: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. OBJECTIVE: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. METHODS: CSF from patients with was tested for human herpesviruses types 1-6, JC virus, enteroviruses, and Toxoplasma gondii. The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. RESULTS: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3-14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. CONCLUSIONS: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

Symptomatic cytomegalovirus infection complicating treatment of acute systemic vasculitis.

Cytomegalovirus (CMV) is usually a complication of renal/solid organ or bone marrow transplantation. We describe three cases of severe CMV in the context of vasculitis immunosuppression.

Cervical schistosomiasis and neoplasia in HIV-infected patients.

We report two HIV-positive women with schistosomiasis of the uterine cervix, a disease that is being increasingly seen in developed countries. In both cases, there were no schistosoma ova in the cervical Papanicolaou smears. Both patients underwent LLETZ procedures that revealed an absence of a granulomatous response to the schistosoma ova, a finding that should alert the pathologist to the possibility of HIV infection. The absence of ova on cervical smears of HIV-infected women with schistosomiasis is probably related to the absence of granulomatous inflammation in these patients. A diligent search should be made for schistosoma ova in the cervical biopsy of patients from endemic areas. Treatment of schistosomiasis in HIV-infected patients should be prompt and complete to prevent recurrent high-risk HPV infection.