Acute hospital-based services used by adults during the last year of life in New South Wales, Australia: A population-based retrospective cohort study

© 2015 Goldsbury et al. Background: There is limited information about health care utilisation at the end of life for people in Australia. We describe acute hospital-based services utilisation during the last year of life for all adults (aged 18+ years) who died in a 12-month period in Australia's most populous state, New South Wales (NSW). Methods: Linked administrative health data were analysed for all adults who died in NSW in 2007 (the most recent year for which cause of death information was available for linkage for this study). The data comprised linked death records (2007), hospital admissions and emergency department (ED) presentations (2006-2007) and cancer registrations (1994-2007). Measures of hospital-based service utilisation during the last year of life included: number and length of hospital episodes, ED presentations, admission to an intensive care unit (ICU), palliative-related admissions and place of death. Factors associated with these measures were examined using multivariable logistic regression. Results: Of the 45,749 adult decedents, 82 % were admitted to hospital during their last year of life: 24 % had >3 care episodes (median 2); 35 % stayed a total of >30 days in hospital (median 17); 42 % were admitted to 2 or more different hospitals. Twelve percent of decedents spent time in an ICU with median 3 days. In the metropolitan area, 80 % of decedents presented to an ED and 18 % had >3 presentations. Overall 55 % died in a hospital or inpatient hospice. Although we could not quantify the extent and type of palliative care, 24 % had mention of "palliative care" in their records. The very elderly and those dying from diseases of the circulatory system or living in the least disadvantaged areas generally had lower hospital service use. Conclusions: These population-wide health data collections give a highly informative description of NSWhospital-based end-of-life service utilisation. Use of hospital-based services during the last year of life was common, with substantial variation across sociodemographic groups, especially defined by age, cause of death and socioeconomic classification of the decedents' place of residence. Further research is now needed to identify the contributors to these findings. Gaps in data collection were identified - particularly for palliative care and patient-reported outcomes. Addressing these gaps should facilitate improved monitoring and assessment of service use and care

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Expanding the scope of the Babler-Daubin oxidation : 1,3-oxidative transposition of secondary allylic alcohols

We report the catalytic chromium-mediated oxidation of secondary allylic alcohols to give α,β-unsaturated aldehydes with exclusive (E)-stereoselectivity. This facile procedure employs catalytic PCC (5 mol%) and periodic acid (H5IO6) as a co-oxidant. This transformation occurs specifically with aromatic substituted allyl alcohols containing both electron withdrawing and electron donating substituents as well as a range of functional groups

Health-services utilisation amongst older persons during the last year of life: A population-based study

© 2018 The Author(s). Background: Accurate population-based data regarding hospital-based care utilisation by older persons during their last year of life are important in health services planning. We investigated patterns of acute hospital-based service use at the end of life, amongst older decedents in New South Wales (NSW), Australia. Methods: Data from all persons aged ≥70 years who died in the state of NSW Australia in 2007 were included. Several measures of hospital-based service utilisation during the last year of life were assessed from retrospectively linked data comprising data for all registered deaths, cause of death, hospital care during the last year of life (NSW Admitted Patient Data Collection [APDC] and Emergency Department [ED] Data Collection [EDDC]), and the NSW Cancer Registry. Results: Amongst 34,556 decedents aged ≥70 years, 82% (n = 28,366) had ≥1 hospitalisation during the last year of life (median 2), and 21% > 3 hospitalisations. Twenty-five percent (n = 5485) of decedents attended ED during the last week of life. Overall, 21% had a hospitalisation > 30 days in the last year of life, and 7% spent > 3 months in hospital; 79% had ≥1 ED attendance, 17% > 3. Nine percent (n = 3239) spent time in an intensive care unit. Fifty-three percent (n = 18,437) died in an inpatient setting. Hospital records had referenced palliative care for a fifth (7169) of decedents. Adjusting for age group, sex, place of residence, area-level socioeconomic status, and cause of death, having > 3 hospitalisations during the last year of life was more likely for persons dying from cancer (35% versus 16% non-cancer deaths, adjusted odds ratio [aOR] 2.33), 'younger' old decedents (29% for age 70-79 and 20% for age 80-89 versus 11% for 90+, aOR 2.42 and 1.77 respectively) and males (25% versus 17% females, aOR 1.38). Patterns observed for other hospital-based service use were similar. Conclusions: This population-based study reveals high use of hospital care among older persons during their last year of life, although this decreased with increasing older age, providing important data to inform health services planning for this population, and highlighting aspects requiring further study

Purification of the Escherichia-coli OGT gene-product to homogeneity and its rate of action on O6-methylguanine, O6-ethylguanine and O4-methylthymine in dodecadeoxyribnucleotides

The E.coli gene ogt encodes the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (O6-AlkG ATase). The protein coding region of the gene was cloned into a multicopy expression vector to obtain high yields of the enzyme (˜ 0.2% of total protein) which was purified to apparent homogeneity by affinity, molecular exclusion and reverse-phase chromatography. Good correlation was found between the determined and predicted amino acid compositions. The ability of the purified protein to act on O6-methylguanine (O6-MeG), O6-ethylguanine (O6-EtG) and (O4-methylthymine (O4-MeT) in self-complementary dodecadeoxyribonucleotides was compared to that of 19 kDa fragment of the related ada-protein. With both proteins the rate order was O6-MeG > O6-EtG > O4-MeT, however, the ogt protein was found to repair O6MeG, O6-EtG and (O4-MeT, 1.1, 173 and 84 times, respectively, faster than the ada protein

The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against oxidative stress but is not a determinant of virulence.

BACKGROUND: The neglected parasitic infection Chagas disease is rapidly becoming a globalised public health issue due to migration. There are only two anti-parasitic drugs available to treat this disease, benznidazole and nifurtimox. Thus it is important to identify and validate new drug targets in Trypanosoma cruzi, the causative agent. T. cruzi expresses an ER-localised ascorbate-dependent peroxidase (TcAPx). This parasite-specific enzyme has attracted interest from the perspective of targeted chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: To assess the importance of TcAPx in protecting T. cruzi from oxidative stress and to determine if it is essential for virulence, we generated null mutants by targeted gene disruption. Loss of activity was associated with increased sensitivity to exogenous hydrogen peroxide, but had no effect on susceptibility to the front-line Chagas disease drug benznidazole. This suggests that increased oxidative stress in the ER does not play a significant role in its mechanism of action. Homozygous knockouts could proceed through the entire life-cycle in vitro, although they exhibited a significant decrease in their ability to infect mammalian cells. To investigate virulence, we exploited a highly sensitive bioluminescence imaging system which allows parasites to be monitored in real-time in the chronic stage of murine infections. This showed that depletion of enzyme activity had no effect on T. cruzi replication, dissemination or tissue tropism in vivo. CONCLUSIONS/SIGNIFICANCE: TcAPx is not essential for parasite viability within the mammalian host, does not have a significant role in establishment or maintenance of chronic infections, and should therefore not be considered a priority for drug design

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Natural polymorphisms in mycobacterium tuberculosis conferring resistance to delamanid in drug-naïve patients.

Mutations in the genes of the F420 signaling pathway, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, of Mycobacterium tuberculosis (Mtb) complex can lead to delamanid resistance. We searched for such mutations among 129 Mtb strains from Asia, South-America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For ten strains with mutations, we determined the minimum inhibitory concentration (MIC) of delamanid. We found one strain from a delamanid-naïve patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical MIC to delamanid

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Respiratory Evolution Facilitated the Origin of Pterosaur Flight and Aerial Gigantism

Pterosaurs, enigmatic extinct Mesozoic reptiles, were the first vertebrates to achieve true flapping flight. Various lines of evidence provide strong support for highly efficient wing design, control, and flight capabilities. However, little is known of the pulmonary system that powered flight in pterosaurs. We investigated the structure and function of the pterosaurian breathing apparatus through a broad scale comparative study of respiratory structure and function in living and extinct archosaurs, using computer-assisted tomographic (CT) scanning of pterosaur and bird skeletal remains, cineradiographic (X-ray film) studies of the skeletal breathing pump in extant birds and alligators, and study of skeletal structure in historic fossil specimens. In this report we present various lines of skeletal evidence that indicate that pterosaurs had a highly effective flow-through respiratory system, capable of sustaining powered flight, predating the appearance of an analogous breathing system in birds by approximately seventy million years. Convergent evolution of gigantism in several Cretaceous pterosaur lineages was made possible through body density reduction by expansion of the pulmonary air sac system throughout the trunk and the distal limb girdle skeleton, highlighting the importance of respiratory adaptations in pterosaur evolution, and the dramatic effect of the release of physical constraints on morphological diversification and evolutionary radiation