The preventable productivity burden of sleep apnea in Australia: a lifetime modelling study.

Obstructive sleep apnea (OSA) is a common disorder. OSA is associated with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM) and depression, among other comorbidities. We aim to determine the productivity burden of OSA in Australia using productivity-adjusted life-years (PALYs). Using life table modelling, we built a multistate Markov model to estimate the impact of moderate to severe OSA on the whole working-age Australian population in 2021 (aged 20-65 years) with OSA until retirement (aged 66 years). The model also captured the impact of OSA on CVD, T2DM, depression, and vehicle-related accidents. Data for OSA and comorbidities and Australian specific labour data, were extracted from published sources. A second cohort was then modelled to test the effect of a hypothetical intervention, assuming a 10% reduction in OSA prevalence and a 10% reduction in comorbidities in patients with OSA. The primary outcome of interest were PALYs accrued. All outcomes were discounted 5% annually. Over a lifetime, the Australian population with OSA accrued 193,713,441 years of life lived and 182,737,644 PALYs. A reduction of 10% in OSA prevalence and comorbidities would result in 45,401 extra years of life lived and 150,950 extra PALYs. This resulted in more than AU$25 billion of gained gross domestic product over the lifetime of the working population. Our study highlights the substantial burden of OSA on the Australian population and the need to tailor interventions at the population level to reduce the health and economic impacts.

Shedding of Salmonella Typhimurium in vaccinated and unvaccinated hens during early lay in field conditions: a randomised controlled trial.

BACKGROUND: Salmonella vaccination is one of the control measure that farmers can use to reduce bacterial shedding in their flocks. This study aimed to examine the efficacy of the Vaxsafe® ST (Strain STM-1) attenuated live vaccine administered as ocular and oral doses followed by an intramuscular (IM) dose in rearing, in reducing contamination by Salmonellae of both eggs and the environment in the commercial multi-age cage layer sheds. A randomised controlled trial was conducted up to 26 weeks post last vaccine on two different multi-age caged egg farms. RESULTS: No clinical symptoms were observed following IM administration of STM-1 during rearing. Following the first two STM-1 doses, both vaccinated and unvaccinated birds exhibited antibody titres below the positive cut-off value, however after IM administration of STM-1, antibody titres in the vaccinated group were above the cut-off value. Wild type Salmonella Typhimurium was not detected during the rearing of pullets. During production, the antibody titres were significantly higher in the vaccinated group at all sampling points during this trial. There was no significant difference in the prevalence of Salmonella (detected by culture and PCR method) between the vaccinated and unvaccinated groups on the egg belt and faeces in early lay. Wild-type Salmonella spp. were consistently found in dust samples. Quantitative PCR (qPCR) assay was able to differentiate between the live vaccine strain and wild type Salmonella. The load of wild-type Salmonella in shed environment was relatively low (1.3 log10 ± 0.48 CFU/m2 of surface area). CONCLUSION: Given that Salmonella Typhimurium and other serovars are able to survive/persist in the shed environment (such as in dust), regular cleaning and or removal of dust from shed is important. Use of the Vaxsafe® ST vaccine in multi-age flocks is "not an ultimate intervention" for reduction of Salmonella Typhimurium because of the complexities involved in achieving control, such as the efficacy of cleaning of sheds, the lack of resting periods between batches and the possible carry over of contamination from existing flocks. Hence implementation of more than one or several interventions strategies is essential.

Avian pathogenic Escherichia coli ΔtonB mutants are safe and protective live-attenuated vaccine candidates.

Avian pathogenic Escherichia coli (APEC) cause colibacillosis, a serious respiratory disease in poultry. Most APEC strains possess TonB-dependent outer membrane transporters for the siderophores salmochelin and aerobactin, which both contribute to their capacity to cause disease. To assess the potential of iron transport deficient mutants as vaccine candidates, the tonB gene was deleted in the APEC wild type strain E956 and a Δfur (ferric uptake repressor) mutant of E956. The growth of the ΔtonB and ΔtonB/Δfur mutants was impaired in iron-restricted conditions, but not in iron-replete media. Day old chicks were exposed to aerosols of the mutants to assess their efficacy as live attenuated vaccines. At day 18, the birds were challenged with aerosols of the virulent parent strain E956. Both mutants conferred protection against colibacillosis; weight gains and lesion scores were significantly different between the vaccinated groups and an unvaccinated challenged control group. Thus mutation of iron uptake systems can be used as a platform technology to generate protective live attenuated vaccines against extraintestinal E. coli infections, and potentially a range of Gram negative pathogens of importance in veterinary medicine.

The role of WlaRG, WlaTB and WlaTC in lipooligosaccharide synthesis by Campylobacter jejuni strain 81116.

Campylobacter jejuni is a major bacterial cause of gastroenteritis world-wide. C. jejuni produces a range of glycans including lipooligosaccharide (LOS), an important virulence factor. The genetic content of the LOS synthesis locus varies between C. jejuni strains and 19 classes have been described. Three LOS synthesis genes of C. jejuni strain 81116 (NCTC 11828), wlaRG, wlaTB and wlaTC were the focus of this study. WlaRG and the remaining two proteins of interest share sequence similarity to aminotransferases and glycosyltransferases, respectively. These genes were insertionally inactivated and phenotypically characterised. Each mutant produced truncated LOS. Mutants lacking WlaRG, WlaTB and WlaTC produced LOS with reduced immunogenicity. Both the wlaRG and wlaTC mutants were non-motile and aflagellate. In vitro invasion and adhesion assays revealed that the wlaRG, wlaTB and wlaTC mutants displayed reduced adherence to chicken embryo fibroblasts. All mutants were less invasive of human cells than 81116 confirming the role of intact LOS during invasion of human cells in vitro. Here we propose the general composition for the 81116 LOS core backbone based on capillary electrophoresis-mass spectrometry.

TonB is essential for virulence in avian pathogenic Escherichia coli.

Avian pathogenic Escherichia coli (APEC) strains have multiple iron-uptake systems that facilitate adaptation to iron-restricted environments and are believed to assist in colonisation of the host. These systems include several TonB-dependent transporters of ferri-siderophores encoded by the chromosome and the large virulence plasmid common to APECs. The tonB gene of the virulent APEC strain E956 was replaced with a selectable antibiotic resistance marker using Lambda Red recombinase mutagenesis. The phenotype of the ΔtonB E956 mutant was compared to the parent strain under various culture conditions and in chickens experimentally infected via the respiratory route. The mutant was resistant to streptonigrin, impaired in its ability to adapt to growth in iron-depleted medium and had greater tolerance of oxidative stress than the parental strain. The mutant was avirulent in chickens, did not affect the growth of chicks and colonisation was mostly limited to the trachea. This study has demonstrated that TonB is essential for virulence in APEC.

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study.

Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (Abeta) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly. We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean+/-1S.D. Clinically significantly cognitive decline over 4 years was defined as > or =5-point drop on the Modified Mini Mental State Exam (3MS). Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% versus 24.7% (OR=0.79; 95% CI 0.61-1.02, p=0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR=0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat.

Are there predictors of outcome in depressed elderly nursing home residents during treatment with mirtazapine orally disintegrating tablets?

BACKGROUND: Treatment studies of depression in residential care are limited. Reports of predictors of response are rare. In the largest nursing home prospective antidepressant trial reported, we examined predictors of response. METHODS: This was a 12-week open-label study of mirtazapine orally disintegrating tablets performed in 30 US nursing homes. Subjects were men and women aged >or=70, with a Mini Mental State Exam (MMSE) score >or=10, who had a depressive disorder that required antidepressant treatment. Mirtazapine was started at 15 mg at bedtime, and adjusted to 15-45 mg/day. A 16-item Hamilton Depression Rating Scale was used to assess depression at baseline, weeks 2, 4, 8, and 12 or early termination. RESULTS: One hundred and twenty-four patients received at least one dose of study drug and of these, 119 had at least one post-drug assessment. Mean age was 82.9 years and 72% were female. Response rates at 12 weeks were 47% on the HAMD and 54% on the CGI. Age, sex, MMSE score, medical burden, history of prior depression, and baseline HAMD severity were not significantly associated with HAMD response (>or=50% improvement) and in most cases correlations were trivial, <0.1. Advanced age, medical burden, and cognitive impairment did not predict adverse events. CONCLUSIONS: In this sample of depressed nursing home residents treated with mirtazapine orally disintegrating tablets, advanced age, medical illness, and cognitive impairment did not predict response. The findings suggest that these variables need not be viewed as obstacles to treatment.

Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.

CONTEXT: Neuropsychiatric symptoms of dementia are common and associated with poor outcomes for patients and caregivers. Although nonpharmacological interventions should be the first line of treatment, a wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms; therefore, concise, current, evidence-based recommendations are needed. OBJECTIVE: To evaluate the efficacy of pharmacological agents used in the treatment of neuropsychiatric symptoms of dementia. EVIDENCE ACQUISITION: A systematic review of English-language articles published from 1966 to July 2004 using MEDLINE, the Cochrane Database of Systematic Reviews, and a manual search of bibliographies was conducted. Inclusion criteria were double-blind, placebo-controlled, randomized controlled trials (RCTs) or meta-analyses of any drug therapy for patients with dementia that included neuropsychiatric outcomes. Trials reporting only depression outcomes were excluded. Data on the inclusion criteria, patients, methods, results, and quality of each study were independently abstracted. Twenty-nine articles met inclusion criteria. EVIDENCE SYNTHESIS: For typical antipsychotics, 2 meta-analyses and 2 RCTs were included. Generally, no difference among specific agents was found, efficacy was small at best, and adverse effects were common. Six RCTs with atypical antipsychotics were included; results showed modest, statistically significant efficacy of olanzapine and risperidone, with minimal adverse effects at lower doses. Atypical antipsychotics are associated with an increased risk of stroke. There have been no RCTs designed to directly compare the efficacy of typical and atypical antipsychotics. Five trials of antidepressants were included; results showed no efficacy for treating neuropsychiatric symptoms other than depression, with the exception of 1 study of citalopram. For mood stabilizers, 3 RCTs investigating valproate showed no efficacy. Two small RCTs of carbamazepine had conflicting results. Two meta-analyses and 6 RCTs of cholinesterase inhibitors generally showed small, although statistically significant, efficacy. Two RCTs of memantine also had conflicting results for treatment of neuropsychiatric symptoms. CONCLUSIONS: Pharmacological therapies are not particularly effective for management of neuropsychiatric symptoms of dementia. Of the agents reviewed, the atypical antipsychotics risperidone and olanzapine currently have the best evidence for efficacy. However, the effects are modest and further complicated by an increased risk of stroke. Additional trials of cholinesterase inhibitors enrolling patients with high levels of neuropsychiatric symptoms may be warranted.

Social security, age of retirement, and economic well-being: intertemporal and demographic patterns among retired-worker beneficiaries.

We examine the economic status of a sample of new recipients of social security retired-worker benefits shortly after their first receipt of benefits (1982) and 10 years later (1991). The probability that these retired-worker beneficiaries were poor or near-poor is positively and strongly associated with their acceptance of early retired-worker benefits. Early retirees, women who remained single, and women who lost their spouses experienced large declines in economic status over the decade following their first receipt of benefits. Although both women and men who first received benefits at younger ages had lower economic status than did those who became beneficiaries at older ages, this retirement age-related disadvantage increased over the decade for women but not for men.