Should we perform systematic biopsies in case of suspicious MRI for prostate cancer in 2020? A review of literature.

CONTEXT: Multiparametric magnetic resonance imaging (MRI) is now recommended before performing prostate biopsies, looking for suspicious lesions to perform targeted biopsies (TB). However, the association or exclusive performance of systematic biopsies (SB), criticized for its morbidity and for the detection of insignificant cancers, remains debated. OBJECTIVE: To perform a literature review to answer three questions: (1) In the presence of a suspicious MRI lesion, should we always perform SB in addition to TB? (2) Can we avoid SB when considering focal treatment? (3) Is there an increase in adverse events when associating SB with TB? SOURCES: A non-systematic literature review was carried out on Medline in April 2020 using the keywords "MRI", "PROSTATE CANCER", "SYSTEMATIC BIOPSY", "TARGETED BIOPSY", "ADVERSE EVENTS". The references of the selected articles were analyzed for additional articles. Selection of Studies published in the last five years were analyzed and retained if the available data made it possible to answer one of the three questions asked. RESULTS: In biopsy-naive patients, the added value of SB to TB for detection of significative cancer varied from +5 to+7% and was reduced to +1 to +3% in the case of a previous series of negative biopsies. For patients under active surveillance, this added value was higher, ranging from +8% to +17%. MRI has a negative predictive value of 85 to 95%, but this value drops to 55% for the detection of secondary or tertiary foci. The use of SB is necessary if focal treatment is considered. Serious complications from biopsies requiring hospitalization range from 1.4 to 6.9% and are increased by the number of previous biopsy series performed more than by the number of biopsies per series. CONCLUSION: In the presence of a suspicious MRI lesion, SB is indicated in addition to TB but can be discussed in patients with previous negative biopsies. They are necessary if focal treatment is considered to aid surgical planning. Severe complications from biopsies do not seem to increase when SB are associated to TB, but rather with the number of biopsy series performed.

What to expect from a non-suspicious prostate MRI? A review.

BACKGROUND: Many guidelines now recommend multiparametric MRI (mpMRI) prior to an initial or repeat prostate biopsy. However, clinical decision making for men with a non-suspicious mpMRI (Likert or PIRADS score 1-2) varies. OBJECTIVES: To review the most recent literature to answer three questions. (1) Should we consider systematic biopsy if mpMRI is not suspicious? (2) Are there additional predictive factors that can help decide which patient should have a biopsy? (3) Can the low visibility of some cancers be explained and what are the implications? SOURCES: A narrative review was performed in Medline databases using two searches with the terms "MRI" and "prostate cancer" and ("diagnosis" or "biopsy") and ("non-suspicious" or "negative" or "invisible"); "prostate cancer MRI visible". References of the selected articles were screened for additional articles. STUDY SELECTION: Studies published in the last 5 years in English language were assessed for eligibility and selected if data was available to answer one of the three study questions. RESULTS: Considering clinically significant cancer as ISUP grade≥2, the negative predictive value (NPV) of mpMRI in various settings and populations ranges from 76% to 99%, depending on cancer prevalence and the type of confirmatory reference test used. NPV is higher among patients with prior negative biopsy (88-96%), and lower for active surveillance patients (85-90%). The PSA density (PSAd) with a threshold of PSAd<0.15ng/ml/ml was the most studied and relevant predictive factor used in combination with mpMRI to rule out clinically significant cancer. Finally, mpMRI-invisible tumours appear to differ from a histopathological and genetic point of view, conferring clinical advantage to invisibility. LIMITATIONS: Most published data come from expert centres and results may not be reproducible in all settings. CONCLUSION: mpMRI has high diagnostic accuracy and in cases of negative mpMRI, PSA density can be used to determine which patient should have a biopsy. Growing knowledge of the mechanisms and genetics underlying MRI visibility will help develop more accurate risk calculators and biomarkers.

Screening characteristics for enrichment of individuals at higher risk for transitioning to classified SLE.

OBJECTIVE: Further prospective study is needed to elucidate the etiology and natural history of systemic lupus erythematosus development. The clinical complexity of this heterogeneous disease makes study design challenging. Our objective was to ascertain useful screening factors for identifying at-risk individuals for follow-up rheumatologic assessment or inclusion in prospective studies. METHODS: We attempted to re-contact 3823 subjects with a family history of systemic lupus erythematosus, who did not meet American College of Rheumatology systemic lupus erythematosus classification at a baseline study visit; 436 agreed to follow-up participation an average of 6.3 years after baseline. In total, 56 of these individuals had transitioned to classified systemic lupus erythematosus (≥ 4 cumulative American College of Rheumatology criteria, verified by medical record review) by the time of follow up. Generalized estimating equations assessed associations between our dichotomous outcome of transitioning to systemic lupus erythematosus with baseline characteristics, including ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score, and number of American College of Rheumatology criteria. We analyzed predictive accuracy of characteristics on transitioning. RESULTS: ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus, and greater number of American College of Rheumatology criteria at baseline were each associated with transitioning to systemic lupus erythematosus classification. Being ANA positive and having confirmed immunologic criteria at baseline had the highest positive predictive value and specificity for transitioning to systemic lupus erythematosus. American College of Rheumatology Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus had a better positive predictive value, negative predictive value, sensitivity, and specificity than ANA positivity. CONCLUSION: Given limited resources, identifying individuals for follow up based on the systemic lupus erythematosus portion of the Connective Tissue Disease Screening questionnaire could be an efficient way to identify family members at highest risk of disease transition.

Less than 7 hours of sleep per night is associated with transitioning to systemic lupus erythematosus.

Background The role of sleep in the etiology of systemic lupus erythematosus (SLE) has not been well studied. We examined whether sleep duration was associated with subsequent transitioning to SLE in individuals at risk for SLE. Methods Four hundred and thirty-six relatives of SLE patients who did not have SLE themselves at baseline were evaluated again an average of 6.3 (± 3.9) years later. Fifty-six individuals transitioned to SLE (≥ 4 cumulative American College of Rheumatology (ACR) criteria). Sleep duration, medication use and medical history were assessed by questionnaire; ACR criteria were confirmed by medical record review. Vitamin D was measured by ELISA. Generalized estimating equations, accounting for correlation within families, assessed associations between baseline sleep and the outcome of transitioning to SLE. Results Reporting sleeping less than 7 hours per night at baseline was more common in those who subsequently transitioned than those who did not transition to SLE (55% versus 32%, p = 0.0005; OR: 2.8, 95% CI 1.6-4.9). Those who transitioned to SLE were more likely to sleep less than 7 hours per night than those who did not transition to SLE adjusting for age, sex and race (OR: 2.8, 95% CI 1.6-5.1). This association remained after individual adjustment for conditions and early symptoms that could affect sleep, including prednisone use, vitamin D deficiency and number of ACR criteria (OR: 2.0, 95% CI 1.1-4.2). Conclusion Lack of sleep may be associated with transitioning to SLE, independent of early clinical manifestations of SLE that may influence sleep duration. Further evaluation of sleeping patterns and biomarkers in at-risk individuals is warranted.

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation.

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002-2003 and 2011-2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

BACKGROUND/OBJECTIVES: Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition. METHODS: Our analysis was conducted using a prebirth observational cohort of 1079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age. RESULTS: Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (ß=0.58, 95% confidence interval (CI) 0.07-1.1, P<0.05) and FM (ß=20.74; 95% CI 1.49-40.0; P<0.05) but no difference in FFM. CONCLUSIONS: Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Smoking is not associated with autoantibody production in systemic lupus erythematosus patients, unaffected first-degree relatives, nor healthy controls.

OBJECTIVE: The objective of this paper is to examine whether smoking is associated with autoantibody production in systemic lupus erythematosus (SLE) patients, unaffected first-degree relatives (FDR) of individuals with SLE--a group at increased risk of developing SLE--or unaffected, unrelated controls. METHODS: Detailed demographic, environmental, clinical, and therapeutic information was collected by questionnaire on 1242 SLE patients, 981 FDRs, and 946 controls in the Lupus Family Registry and Repository; a blood sample was obtained. All sera were tested for multiple lupus autoantibodies by immunofluorescence and luminex bead-based assays. Generalized estimating equations, adjusting for age, gender, and ethnicity and accounting for correlation within families, were used to assess smoking status with the dichotomous outcome variables of positivity for SLE status, positivity of ANA by immunofluorescence (≥1:120), positivity for ≥1 autoantibody by the luminex assay, and positivity for each of the 11 autoantibodies. RESULTS: Current smoking was associated with being positive for ≥1 autoantibody (excluding ANA) (adjusted OR = 1.53, 95% CI 1.04-2.24) in our subjects with SLE. No association was observed in unaffected FDRs or healthy controls. Former smoking was associated with anti-Ro/SS-A60 in our unaffected FDRs. There was an increased association with anti-nRNP A seropositivity, as well as a decreased association with anti-nRNP 68 positivity, in current smokers in SLE subjects. CONCLUSIONS: No clear association between smoking status and individual autoantibodies was detected in SLE patients, unaffected FDRs, nor healthy controls within this collection. The association of smoking with SLE may therefore manifest its risk through mechanisms outside of autoantibody production, at least for the specificities tested.

Serological evidence of exposure of healthy dogs to Leptospira in Sydney, New South Wales, Australia.

In 2017, highly fatal canine leptospirosis emerged in Sydney, Australia. Based on results of microscopic agglutination testing (MAT), serovar Copenhageni appeared to be the most common causative serovar. Prior to this, no clinical cases had been reported since 1976. In a serosurvey of healthy dogs in Australian shelters in 2004, 2.4% of 431 New South Wales dogs had serological evidence of exposure to Copenhageni, the most prevalent serovar. The aim of this study was to estimate the current prevalence of Leptospira exposure and associated serovars in healthy Sydney dogs, previously unvaccinated against Leptospira. Serum samples from 411 healthy dogs in leptospirosis hotspots and neighbouring suburbs were collected before vaccination. MAT for 23 serovars was performed at the WHO Leptospirosis Reference Laboratory in Queensland, Australia. The overall seroprevalence was 4.1% (17/411) with low titres (1/50-1/200) detected. Eleven dogs were from known leptospirosis hotspots. Eight dogs were known to hunt rodents. One dog had been in contact with a leptospirosis positive dog 1 year prior. Serovar Topaz was the most prevalent serovar (n = 5) followed by serovars Australis (n = 4), Copenhageni (n = 4), Djasiman (n = 2), Cynopteri (n = 1), Javanica (n = 1), Medanensis (n = 1), and Pomona (n = 1). In conclusion, serological evidence of exposure of dogs in Sydney to Leptospira is low, but apparently has increased since 2004. Positive titres to serovars not previously reported to cause disease in dogs could be due to low virulence of those serovars or cross-reactivity with other serovars.

Antiviral therapy in cats progressively infected with feline leukaemia virus: lessons from a series of 18 consecutive cases from Australia.

BACKGROUND: It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago. METHODS: Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments. RESULTS: The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 106 to 705 × 106 copies/mL plasma; P = 0.012), but MST was reduced compared to cats not given RetroMAD1™ (426 days vs 1006 days; P = 0.049). Cats treated with raltegravir and AZT had no significant changes in FeLV viral load over time, but p27 antigen load was decreased from T0 to T3-5 months in cats treated with raltegravir (median p27 antigen level reduced from 50.2% to 42.7%; P = 0.005). All other results were not significantly affected by the treatment provided. Importantly, statistically significant and substantial associations were found between age at FeLV diagnosis and survival time (P = 0.046, R2 = 18.6) and between FeLV viral load at T0 and survival time (P = 0.004, R2 = 44.4). Younger cats, and cats with higher levels of pretreatment FeLV RNA, had reduced survival times. Cats treated with RetroMAD1™ were typically younger (median age 2.0 vs 8.0 years), likely explaining the observed reduction in MST. A significant association was found between FeLV viral load and p27 antigen load at T0 (P = 0.015, R2 = 32.9). CONCLUSIONS: Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.

The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: the Insulin Resistance Atherosclerosis Study (IRAS).

AIMS/HYPOTHESIS: Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activator inhibitor (PAI)-1, C-reactive protein (CRP), TNF-α, leptin and fibrinogen and the progression of metabolic clearance rate of insulin (MCRI) over time. METHODS: We studied 784 non-diabetic white, Hispanic and African-American individuals in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity, acute insulin response and MCRI were determined from frequently sampled intravenous glucose tolerance tests at baseline and at 5-year follow-up. Inflammatory and fibrinolytic proteins were measured in fasting plasma at baseline. RESULTS: MCRI had declined significantly by 29% at the 5-year follow-up. We observed a significant association between higher plasma PAI-1 levels and the decline in MCRI in multivariable-adjusted regression models (ß = -0.045 [95% CI -0.081, -0.0091]). Higher plasma CRP and leptin levels were associated with a decline in MCRI in unadjusted models, but these associations were non-significant after adjusting for BMI and waist circumference (ß = -0.016 [95% CI -0.041, 0.0083] for CRP; ß = -0.044 [95% CI -0.10, 0.011] for leptin). A higher plasma TNF-α concentration was associated with a decline in MCRI in unadjusted (ß = -0.071 [95% CI -0.14, -0.00087]) but not in multivariable-adjusted (ß = -0.056 [95% CI -0.13, 0.017]) models. Plasma fibrinogen level was not associated with the change in MCRI. CONCLUSIONS/INTERPRETATION: We identified that higher plasma PAI-1 (but not CRP, TNF-α, leptin or fibrinogen) levels independently predicted the progressive decline of insulin clearance in the multiethnic cohort of the IRAS.

Vitamin D in youth with Type 1 diabetes: prevalence of insufficiency and association with insulin resistance in the SEARCH Nutrition Ancillary Study.

AIMS: To determine the prevalence of plasma vitamin D (25-dihydroxyvitamin D) insufficiency in individuals with Type 1 diabetes and to determine the cross-sectional and longitudinal associations of plasma vitamin D with insulin resistance. METHODS: Participants from the SEARCH for Diabetes in Youth Study [n = 1426; mean age 11.2 years (sd 3.9)] had physician-diagnosed Type 1 diabetes [diabetes duration mean 10.2 months (sd 6.5)] with data available at baseline and follow-up (approximately 12 and 24 months after baseline). Insulin resistance was estimated using a validated equation. Cross-sectional and longitudinal multivariate logistic regression models were used to determine the association of plasma vitamin D with insulin resistance, adjusting for potential confounders. RESULTS: Forty-nine per cent of individuals had plasma vitamin D < 50 nmol/l and 26% were insulin resistant. In cross-sectional multivariate analyses, participants who had higher plasma vitamin D (65 nmol/l) had lower odds of prevalent insulin resistance than participants with lower plasma vitamin D (25 nmol/l) (odds ratio 0.70, 95% CI 0.57-0.85). This association was attenuated after additional adjustment for BMI z-score, which could be a confounder or a mediator (odds ratio 0.81, 95% CI 0.64-1.03). In longitudinal multivariate analyses, individuals with higher plasma vitamin D at baseline had lower odds of incident insulin resistance, but this was not significant (odds ratio 0.85, 95% CI 0.63-1.14). CONCLUSIONS: Vitamin D insufficiency is common in individuals with Type 1 diabetes and may increase risk for insulin resistance. Additional prospective studies are needed to determine the association between plasma vitamin D and insulin resistance, and to further examine the role of adiposity on this association.

Components of metabolic syndrome and 5-year change in insulin clearance - the Insulin Resistance Atherosclerosis Study.

AIMS: Cross-sectional evidence indicates that abdominal adiposity, hypertension, dyslipidaemia and glycaemia are associated with reduced metabolic clearance rate of insulin (MCRI). Little is known about the progression of MCRI and whether components of metabolic syndrome are associated with the change in MCRI. In this study, we examined the association between components of metabolic syndrome and the 5-year change of MCRI. METHODS: At baseline and 5-year follow-up, we measured fasting plasma triglycerides (TG), high-density lipoprotein (HDL) cholesterol, blood pressure (BP), waist circumference (WC) and fasting blood glucose (FBG) in 784 non-diabetic participants in the Insulin Resistance Atherosclerosis Study. MCRI, insulin sensitivity (SI ) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. RESULTS: We observed a 29% decline of MCRI at follow-up. TG, systolic BP and WC at baseline were inversely associated with a decline of MCRI regression models adjusted for age, sex, ethnicity, smoking, alcohol consumption, energy expenditure, family history of diabetes, BMI, SI and AIR [ß = -0.057 (95% confidence interval, CI: -0.11, -0.0084) for TG, ß = -0.0019 (95% CI: -0.0035, -0.00023) for systolic BP and ß = -0.0084 (95% CI: -0.013, -0.0039) for WC; all p < 0.05]. Higher HDL cholesterol at baseline was associated with an increase in MCRI [multivariable-adjusted ß = 0.0029 (95% CI: 0.0010, 0.0048), p = 0.002]. FBG at baseline was not associated with MCRI at follow-up [multivariable-adjusted ß = 0.0014 (95% CI: -0.0026, 0.0029)]. CONCLUSIONS: MCRI declined progressively over 5 years in a non-diabetic cohort. Components of metabolic syndrome at baseline were associated with a significant change in MCRI.

Low prevalence of antimicrobial resistant organisms (methicillin resistant Staphylococcus aureus, extended beta-lactamase producing Enterobacteriaceae, and vancomycin resistant enterococci) in bulk tank milk in New South Wales, Australia.

OBJECTIVE: Estimate the presence of methicillin resistant Staphylococcus aureus (MRSA), extended beta-lactamase (ESBL) producing Enterobacteriaceae, and vancomycin resistant enterococci (VRE) in bulk tank milk in dairy herds in New South Wales (NSW), Australia. METHODS: Bulk tank milk samples (n = 80) were collected from dairy farms (n = 40, i.e. 2 per farm) in NSW during 2021. Bacteria were cultured using selective chromogenic indicator media with isolate identity confirmed using biochemical testing, Gram stain, and MALDI-TOF mass spectroscopy. Antimicrobial resistance (AMR) was confirmed using antibiotic disk diffusion. RESULTS: No samples tested positive to the targeted AMR organisms. CONCLUSION: The prevalence of MRSA, ESBL-producing Enterobacteriaceae, and VRE is low in NSW dairy herds.

A framework for evaluation of on-farm mastitis diagnostics in Australia.

Numerous culture-based diagnostics are available on the Australian and international markets for on-farm detection of bacterial pathogens in milk. Use of such diagnostics may provide an opportunity to improve the prudent use of antimicrobials in udder health management. Farms are low-resource settings in terms of diagnostic microbiology capacity. The World Health Organisation has identified criteria for the evaluation of diagnostic tests in low resource settings based on Accuracy, Sensitivity, Specificity, User-friendliness, being Rapid or Robust, Equipment-free and being Deliverable (ASSURED). Here, we review how those criteria can be interpreted in the context of microbiological diagnosis of mastitis pathogens, and how on-farm diagnostics that are currently available in Australia perform relative to ASSURED criteria. This evaluation identifies multiple trade-offs, both with regard to scientific criteria and with regards to convenience criteria. More importantly, the purpose of testing may differ between farms, and test performance should be evaluated relative to its intended use. The ability of on-farm mastitis diagnostics to inform mastitis treatment decision-making in a timely and cost-effective manner depends not just on test characteristics but also on farm-specific pathogen prevalence, and on the farm enterprise's priorities and the farm manager's potential courses of action. With most assay evaluations to date conducted in professional laboratories, there is a surprising dearth of information on how well any of the diagnostic tests perform on-farm and, indeed, of the on-farm decision-making processes that they aim to inform.

The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH Study.

OBJECTIVE: To evaluate the influence of breast-feeding on the body mass index (BMI) growth trajectory from birth through 13 years of age among offspring of diabetic pregnancies (ODP) and offspring of non-diabetic pregnancies (ONDP) participating in the Exploring Perinatal Outcomes Among Children Study. SUBJECTS: There were 94 ODP and 399 ONDP who had multiple BMI measures obtained from birth throughout childhood. A measure of breast milk-months was derived from maternal self-report to categorize breast-feeding status as adequate (≥6 breast milk-months) or low (<6 breast milk-months). Mixed linear-effects models were constructed to assess the impact of breast-feeding on the BMI growth curves during infancy (birth to 27 months) and childhood (27 months to 13 years). RESULTS: ODP who were adequately breast-fed had a slower BMI growth trajectory during childhood (P=0.047) and slower period-specific growth velocity with significant differences between 4 and 6 years of age (P=0.03) and 6 to 9 years of age (P=0.01) compared with ODP with low breast-feeding. A similar pattern was seen in the ONDP, with adequate breast-feeding associated with lower average BMI in infancy (P=0.03) and childhood (P=0.0002) and a slower growth trajectory in childhood (P=0.0002). Slower period-specific growth velocity was seen among the ONDP associated with adequate breast-feeding with significant differences between 12-26 months (P=0.02), 4-6 years (P=0.03), 6-9 years (P=0.0001) and 9-13 years of age (P<0.0001). CONCLUSION: Our study provides novel evidence that breast-feeding is associated with long-term effects on childhood BMI growth that extend beyond infancy into early and late childhood. Importantly, these effects are also present in the high-risk offspring, exposed to overnutrition during pregnancy. Breast-feeding in the early postnatal period may represent a critical opportunity to reduce the risk of childhood obesity.

Implication of European-derived adiposity loci in African Americans.

OBJECTIVE: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. METHODS: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. RESULTS: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005

Factors influencing dairy cattle farmer use of antimicrobials on farms in New South Wales, Australia.

Antimicrobial use (AMU) in the food chain is a potential driver of antimicrobial resistance. Despite Australia's strong regulation of AMU limited to veterinary prescriptions, a proportion of empirical antimicrobial treatments are administered by dairy farmers to manage common cattle health problems. This cross-sectional survey identified key influences on AMU by dairy cattle farmers within New South Wales, Australia, to detect opportunities for antimicrobial stewardship (AMS) engagement. The study identified existing relationships, resources and attitudes of the dairy farmers that could be optimised for on-farm AMS strategies. Farmers were most highly influenced by veterinary advice and clinical signs of the animal followed by the withholding period and the potential for antimicrobial resistance development. Farmers' high confidence regarding their own knowledge of antimicrobials (>90%), their high regard for veterinary advice (>90%) and high rate of veterinary health care plan use (69%) provides a strong framework to build the profile and practice of AMS on dairy farms. Positive engagement by dairy farmers (survey response of 20%), was achieved by working with the NSW Food Authority. Despite respondents reporting low reliance on formal (government and commercial) organisations for information about AMU, their engagement demonstrates an opportunity for groups with unparalleled access to dairy farmers to drive AMS. An association between frequent use of veterinary advice and respondents keeping ceftiofur on-farm requires further investigation. Quantitative and qualitative analysis of on-farm resources, decision-making, and practices is required to understand how practices relate to veterinary advice and accepted standards of appropriate AMU on dairy farms.

Seroprevalence of Coxiella burnetii in pig-hunting dogs from north Queensland, Australia.

The causative agent of Q fever, Coxiella burnetii, is endemic to Queensland and is one of the most important notifiable zoonotic diseases in Australia. The reservoir species for C. burnetii are classically ruminants, including sheep, cattle and goats. There is increasing evidence of C. burnetii exposure in dogs across eastern and central Australia. The present study aimed to determine if pig-hunting dogs above the Tropic of Capricorn in Queensland had similar rates of C. burnetii exposure to previous serosurveys of companion dogs in rural north-west New South Wales. A total of 104 pig-hunting dogs had serum IgG antibody titres to phase I and phase 2 C. burnetii determined using an indirect immunofluorescence assay test. Almost one in five dogs (18.3%; 19/104; 95% confidence interval 9.6%-35.5%) were seropositive to C. burnetii, with neutered dogs more likely to test positive compared to entire dogs (P = 0.0497). Seropositivity of the sampled pig-hunting dogs was one of the highest recorded in Australia. Thirty-nine owners of the pig-hunting dogs completed a survey, revealing 12.8% (5/39) had been vaccinated against Q fever and 90% (35/39) were aware that both feral pigs and dogs could potentially be sources of C. burnetii. Our findings indicate that pig hunters should be aware of the risk of exposure to Q fever during hunts and the sentinel role their dogs may play in C. burnetii exposure.

Emerging leptospirosis in urban Sydney dogs: a case series (2017-2020).

Canine leptospirosis has not been reported in the Sydney dog population since 1976. However, between 2017 and 2020, leptospirosis was confirmed in 17 dogs, five of which were known to hunt rodents. Dogs infected between 2017 and 2019 lived within a 3 km radius in the Inner City of Sydney (n = 11). In 2020, cases emerged across a broader area of Sydney; Inner City (n = 1), Inner West (n = 3), Lower North Shore (n = 1) and Upper North Shore (n = 1). The disease was characterised by severe hepatorenal involvement resulting in an unusually high case fatality rate (88%). In conjunction with supportive clinical signs, diagnosis was confirmed by real-time PCR on whole blood (n = 1), kidney (n = 1), urine (n = 4), whole blood and urine (n = 9) or by seroconversion (n = 3). Antibody titres determined by Microscopic Agglutination Test (MAT) to Leptospira serovars were measured in 12 dogs: seven were positive for serovar Copenhageni, one was positive for serovar Hardjo, three were negative for all serovars, likely due to insufficient time for seroconversion before death and one had a low positive titre (1/50) for serovars Australis and Robinsoni. This sudden emergence of a highly fatal disease in pet dogs in Sydney has led to the introduction of Leptospira vaccination protocols for dogs living in inner Sydney using a monovalent vaccine containing serovar Copenhageni. The success of this vaccination program will require ongoing research to understand the emergence of leptospirosis in this region and the serovars involved.

Detection of Brucella spp. during a serosurvey of pig-hunting and regional pet dogs in eastern Australia.

Brucellosis is a zoonotic disease with worldwide distribution. Brucella suis serotype 1 is thought to be maintained in the Australian feral pig population, with disease prevalence higher in Queensland (Qld) than New South Wales (NSW). Pig hunting is a popular recreational activity in rural Qld and NSW, with feral pigs in these states thought to carry B. suis. Brucellosis associated with B. suis has been diagnosed in dogs engaged in pig hunting in some of these areas. A total of 431 dogs from northern Qld and north-west NSW were recruited. Two distinct cohorts of clinically healthy dogs were tested - (1) 96 dogs from central, north and far north Queensland actively engaged in pig-hunting and (2) 335 dogs from rural and remote north-west NSW that were primarily companion (non-pig hunting) animals. Serum samples were tested for antibodies to Brucella spp. using the Rose Bengal test (RBT) test followed by complement fixation testing (CFT) for RBT-positive samples. A subset of samples was retested using RBT and CFT. Seven dogs were considered seropositive for B. suis from Qld and remote NSW, including 4/96 (4.2%; 95% CI 3.5% to 4.3%) from the pig-hunting cohort and 3/335 (0.9%) from the regional pet dog cohort. The use of RBT and CFT in dogs to detect anti-Brucella antibodies requires validation. Veterinarians treating pig-hunting dogs and physicians treating pig hunters in central, north and far north Qld need to be aware of the zoonotic risk posed by B. suis to these groups.