Household transmission of COVID-19 in 2020 in New South Wales, Australia.

Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study examines factors associated with transmission among cases diagnosed with coronavirus disease 2019 (COVID-19) and their household contacts, in New South Wales (NSW), Australia, during July-October 2020. A register of all laboratory-confirmed COVID-19 cases was used to extract demographic and clinical information for cases and household contacts. Secondary attack rates (SARs) among household members were calculated and generalised estimating equations were used to estimate risks of transmission in relation to various characteristics of the primary case and the household contacts. In total, 229 households were included; they consisted of 229 primary cases and 659 close contacts. The overall household SAR was 22.5% (148/659). After adjusting for symptoms, age and sex of primary case, spouse status of household contacts and household size, the odds of secondary transmission were lower in primary cases who were asymptomatic at diagnosis than in symptomatic cases (odds ratio, OR: 0.13; 95% confidence interval (95% CI): 0.04-0.48); and higher in primary cases aged 60 years and over than in those aged 19-39 years (OR: 3.45; 95% CI: 1.53- 7.75). Being a spouse of the primary case was also associated with increased transmission compared to non-spouses (OR: 1.93; 95% CI: 1.24-3.02). After adjustments, there was no significant effect on transmission of the primary case's sex, or of the number of people in the household. This study documents demographic and clinical characteristics that increase transmission rates in households in the period prior to the introduction of SARS-CoV-2 variants. These data can be used as a baseline from which to compare household transmission in outbreaks dominated by new variants.

Shigella species epidemiology and antimicrobial susceptibility: the implications of emerging azithromycin resistance for guiding treatment, guidelines and breakpoints.

OBJECTIVES: To examine antimicrobial susceptibility patterns and predictors of resistance among Shigella isolates in New South Wales (NSW), Australia during 2013-14 with emphasis on azithromycin. METHODS: Cross-sectional analysis of all shigellosis cases (160) notified to public health authorities in NSW, Australia was performed. RESULTS: Among 160 Shigella isolates tested, 139 (86.9%) were susceptible to azithromycin, 104 (65.0%) to ciprofloxacin and 38 (23.7%) to co-trimoxazole. Ciprofloxacin resistance was 1.9 times more common in infections acquired in Australia compared with those acquired overseas, while azithromycin resistance was 8.5 times more common in males. CONCLUSIONS: We recommend ongoing reconsideration of guidelines for the treatment of shigellosis based on emerging resistance patterns. First-line therapy may need to be reconsidered based on local resistance rates due to common resistance to co-trimoxazole and ciprofloxacin. We recommend culture and susceptibility testing for suspected and proven shigellosis. Azithromycin susceptibility breakpoints for Shigella species may need to be species specific.

The influence of paramedic and patient gender on the administration of analgesics in the out-of-hospital setting.

OBJECTIVE: To determine whether analgesic administration in the out-of-hospital setting is influenced by the gender of the patient or the gender of the paramedic. METHODS: This retrospective cohort study of patient care records included adult patients (age > 15 years) with moderate to severe pain (verbal numerical rating score 4-10) treated by paramedics between January 1, 2008 and December 31, 2009. Data extracted included patient pain severity score, analgesia provided by paramedics, and gender of the treating paramedic. Data was analyzed by descriptive statistics, χ(2) test, and logistic regression. The primary outcome measures were the effect of patient and paramedic gender on analgesic administration. RESULTS: The study population comprised 42,051 patients, median age of 57 years (38-75); 50.4% were female and 51% were administered an analgesic agent. For the outcome of receiving any analgesia, neither patient gender nor paramedic gender was predictive (p = NS). In a multivariate model for the outcome of receiving any analgesia, patient gender, paramedic gender, and the interaction between patient and paramedic gender were all nonsignificant (p = NS). For the outcome of receiving opioid analgesia (i.e., morphine or fentanyl), male patients were at greater odds of receiving an opioid (OR 1.52, 95% CI 1.29-1.79, p < 0.0001). Paramedic gender was not predictive of whether an opioid was given (p = NS). CONCLUSIONS: The gender of the paramedic did not appear to influence the odds of analgesic administration. Female patients were less likely to receive opioids. Paramedic gender does not explain this finding.

Disparities in cataract surgery between Aboriginal and non-Aboriginal people in New South Wales, Australia.

BACKGROUND: To investigate variation in rates of cataract surgery in New South Wales, Australia by area of residence for Aboriginal and non-Aboriginal adults. DESIGN: Observational data linkage study of hospital admissions. PARTICIPANTS: Two hundred eighty-nine thousand six hundred forty-six New South Wales residents aged 30 years and over admitted to New South Wales hospitals for 444,551 cataract surgery procedures between 2001 and 2008. METHODS: Analysis of linked routinely collected hospital data using direct standardization and multilevel negative binomial regression models accounting for clustering of individuals within Statistical Local Areas. MAIN OUTCOME MEASURES: Age-standardized cataract surgery rates and adjusted rate ratios. RESULTS: Aboriginal people had lower rates of cataract procedures than non-Aboriginal people of the same age and sex, living in the same Statistical Local Area (adjusted rate ratio 0.71, 95% confidence interval 0.68-0.75). There was significant variation in cataract surgery rates across Statistical Local Areas for both Aboriginal and non-Aboriginal people, with the disparity greater in major cities and less disadvantaged areas. Rates of surgery were lower for Aboriginal than non-Aboriginal people in most Statistical Local Areas, but in a few, the rates were similar or higher for Aboriginal people. CONCLUSIONS: Aboriginal people in New South Wales received less cataract surgery than non-Aboriginal people, despite evidence of higher cataract rates. This disparity was greatest in urban and wealthier areas. Higher rates of surgery for Aboriginal people observed in some specific locations are likely to reflect the availability of public ophthalmology services, targeted services for Aboriginal people and higher demand for surgery in these populations.

Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression.

The phosphoinositide 3-kinase/Akt pathway is thought to be essential for normal insulin action and glucose metabolism in skeletal muscle and has been shown to be dysregulated in insulin resistance. However, the specific roles of and signaling pathways triggered by Akt isoforms have not been fully assessed in muscle in vivo. We overexpressed constitutively active (ca-) Akt-1 or Akt-2 constructs in muscle using in vivo electrotransfer and, after 1 wk, assessed the roles of each isoform on glucose metabolism and fiber growth. We achieved greater than 2.5-fold increases in total Ser473 phosphorylation in muscles expressing ca-Akt-1 and ca-Akt-2, respectively. Both isoforms caused hypertrophy of muscle fibers, consistent with increases in p70S6kinase phosphorylation, and a 60% increase in glycogen accumulation, although only Akt-1 increased glycogen synthase kinase-3beta phosphorylation. Akt-2, but not Akt-1, increased basal glucose uptake (by 33%, P = 0.004) and incorporation into glycogen and lipids, suggesting a specific effect on glucose transport. Consistent with this, short hairpin RNA-mediated silencing of Akt-2 caused reductions in glycogen storage and glucose uptake. Consistent with Akt-mediated insulin receptor substrate 1 (IRS-1) degradation, we observed approximately 30% reductions in IRS-1 protein in muscle overexpressing ca-Akt-1 or ca-Akt-2. Despite this, we observed no decrease in insulin-stimulated glucose uptake. Furthermore, a 68% reduction in IRS-1 levels induced using short hairpin RNAs targeting IRS-1 also did not affect glucose disposal after a glucose load. These data indicate distinct roles for Akt-1 and Akt-2 in muscle glucose metabolism and that moderate reductions in IRS-1 expression do not result in the development of insulin resistance in skeletal muscle in vivo.

Acute bidirectional manipulation of muscle glucose uptake by in vivo electrotransfer of constructs targeting glucose transporter genes.

Analysis of conventional germ-line or tissue-specific gene manipulation in vivo is potentially confounded by developmental adaptation of animal physiology. We aimed to adapt the technique of in vivo electrotransfer (IVE) to alter local gene expression in skeletal muscle of rodents as a means of investigating the role of specific proteins in glucose metabolism in vivo. We utilized a square-wave electroporator to induce intracellular electrotransfer of DNA constructs injected into rat or mouse muscles and investigated the downstream effects. In initial studies, expression of green fluorescent protein reporter was induced in 53 +/- 10% of muscle fibers peaking at 7 days, and importantly, the electrotransfer procedure itself did not impact upon the expression of stress proteins or our ability to detect a reduction in 2-deoxyglucose tracer uptake by electroporated muscle of high-fat-fed rats during hyperinsulinemic-euglycemic clamp. To demonstrate functional effects of electrotransfer of constructs targeting glucose transporters, we administered vectors encoding GLUT-1 cDNA and GLUT-4 short hairpin RNAs (shRNAs) to rodent muscles. IVE of the GLUT-1 gene resulted in a 57% increase in GLUT-1 protein, accompanied by a proportionate increase in basal 2-deoxyglucose tracer uptake into muscles of starved rats. IVE of vectors expressing two shRNAs for GLUT-4 demonstrated to reduce specific protein expression and 2-deoxyglucose tracer uptake in 3T3-L1 adipocytes into mouse muscle caused a 51% reduction in GLUT-4 protein, associated with attenuated clearance of tracer to muscle after a glucose load. These results confirm that glucose transporter expression is largely rate limiting for glucose uptake in vivo and highlight the utility of IVE for the acute manipulation of muscle gene expression in the study of the role of specific proteins in glucose metabolism.