The economic costs of schizophrenia: implications for public policy

The direct and indirect costs associated with schizophrenia in Australia were calculated using the incidence approach and compared with similar costings of myocardial infarction in Australia and the United States. In Australia schizophrenia affects one-twelfth as many people as does myocardial infarction, yet costs half as much. This is because the stream of costs associated with each case of schizophrenia is six times the stream of costs associated with myocardial infarction. To illustrate the utility of this costing approach, the information was used to estimate the cost-benefit ratio likely to follow the introduction of social intervention strategies. The information also showed that Australian support for research in schizophrenia is inadequate when compared with that for myocardial infarction and quite out of proportion to the cost of schizophrenia to the community

Risk of a major adverse cardiovascular event (MACE) following first-ever hospitalisation for acute gout: a Western Australian population-level linked data study.

Objectives Cardiovascular disease is the largest contributor of increased mortality in patients with gout.  Acute inflammation as seen with gout attacks may have a mechanistic role in developing Major Adverse Cardiovascular Events (MACE).  We examined the temporal relationship between admission to hospital with acute gout and MACE. Approach Linked inpatient and mortality data from the Western Australian Rheumatic Disease Epidemiology Registry were used.  We identified patients with an incident acute gout (index) hospitalisation and admission or death records due to MACE (composite of acute coronary syndrome, stroke, heart failure, cardiovascular death).  The risk of MACE during the index post-discharge period (1-30 days after index admission) and control period (365 days prior to index admission and 365 days post-discharge) was determined using a self-controlled case-series (SCCS) design.  Conditional fixed-effects Poisson regression was used to obtain incidence rate ratios (IRR).  Sensitivity analyses were performed excluding deaths and 180-day events. Results We identified 962 patients (mean age=76.2 years [SD=12.2]; 66.8% male) with incident acute gout admission and documented MACE during the control and/or index post-discharge periods.   917 (95.3%) patients experienced MACE during the control period and 114 (11.9%) during the index post-discharge period.  The rate of MACE during the control and post-discharge periods were 0.84 and 1.44 events per person-year, respectively, with an IRR=1.67 (95% CI: 1.38-2.02) for the post-discharge period compared with the control period from regression analysis.  Sensitivity analyses excluding deaths and 180-day events were IRR=1.68 (95% CI=1.29-2.20) and IRR=1.66 (95% CI=1.34-2.07) respectively. Conclusion Our self-controlled case-series study using linked administrative data found an increased risk of MACE during the 30 days after discharge for index gout hospitalisation.  This suggests a temporal association between acute inflammation and MACE

Immunohistochemical Analysis of Scarring Trachoma Indicates Infiltration by Natural Killer and Undefined CD45 Negative Cells.

INTRODUCTION: The phenotype and function of immune cells infiltrating the conjunctiva in scarring trachoma have yet to be fully characterized. We assessed tissue morphology and immunophenotype of cellular infiltrates found in trachomatous scarring compared to control participants. METHODOLOGY: Clinical assessments and conjunctival biopsy samples were obtained from 34 individuals with trachomatous scarring undergoing trichiasis surgery and 33 control subjects undergoing cataract or retinal detachment surgery. Biopsy samples were fixed in buffered formalin and embedded in paraffin wax. Hematoxylin and eosin (H&E) staining was performed for assessment of the inflammatory cell infiltrate. Immunohistochemical staining of single markers on individual sections was performed to identify cells expressing CD3 (T-cells), CD4 (helper T-cells), CD8 (suppressor/cytotoxic T-cells and Natural Killer, NK, cells), NCR1 (NK cells), CD20 (B-cells), CD45 (nucleated hematopoietic cells), CD56 (NK and T-cells), CD68 (macrophages/monocytes) and CD83 (mature dendritic cells). The degree of scarring was assessed histologically using cross-polarized light to visualize collagen fibres. PRINCIPLE FINDINGS: Scarring, regardless of clinical inflammation, was associated with increased inflammatory cell infiltrates on H&E and CD45 staining. Scarring was also associated with increased CD8+ and CD56+ cells, but not CD3+ cells, suggestive of a NK cell infiltrate. This was supported by the presence of NCR1+ cells. There was some increase in CD20+ cells, but no evidence for increased CD4+, CD68+ or CD83+ cells. Numerous CD45 negative cells were also seen in the population of infiltrating inflammatory cells in scarred conjunctiva. Disorganization of the normal collagen architecture was strongly associated with clinical scarring. CONCLUSIONS/SIGNIFICANCE: These data point to the infiltration of immune cells with a phenotype suggestive of NK cells in conjunctival trachomatous scarring. A large proportion of CD45 negative inflammatory cells were also present. Future work should seek to understand the stimuli leading to the recruitment of these cells and their role in progressive scarring

Evaluation of Nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis

Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis

A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11–17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing

Overfishing and Habitat Loss Drives Range Contraction of Iconic Marine Fishes to Near Extinction

Extinctions on land are often inferred from sparse sightings over time, but this technique is ill-suited for wide-ranging species. We develop a space-for-time approach to track the spatial contraction and drivers of decline of sawfishes. These iconic and endangered shark-like rays were once found in warm, coastal waters of 90 nations and are now presumed extinct in more than half (n = 46). Using dynamic geography theory, we predict that sawfishes are gone from at least nine additional nations. Overfishing and habitat loss have reduced spatial occupancy, leading to local extinctions in 55 of the 90 nations, which equates to 58.7% of their historical distribution. Retention bans and habitat protections are urgently necessary to secure a future for sawfishes and similar species

Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.

A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine