A comparison of multivariate and univariate time series approaches to modelling and forecasting emergency department demand in Western Australia

Objective: To develop multivariate vector-ARMA (VARMA) forecast models for predicting emergency department (ED) demand in Western Australia (WA) and compare them to the benchmark univariate autoregressive moving average (ARMA) and Winters’ models. Methods: Seven-year monthly WA state-wide public hospital ED presentation data from 2006/07 to 2012/13 were modelled. Graphical and VARMA modelling methods were used for descriptive analysis and model fitting. The VARMA models were compared to the benchmark univariate ARMA and Winters’ models to determine their accuracy to predict ED demand. The best models were evaluated by using error correction methods for accuracy. Results: Descriptive analysis of all the dependent variables showed an increasing pattern of ED use with seasonal trends over time. The VARMA models provided a more precise and accurate forecast with smaller confidence intervals and better measures of accuracy in predicting ED demand in WA than the ARMA and Winters’ method. Conclusion: VARMA models are a reliable forecasting method to predict ED demand for strategic planning and resource allocation. While the ARMA models are a closely competing alternative, they under-estimated future ED demand

Emerging tick-borne infections in mainland China: an increasing public health threat

Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered

Rapid increase of scrub typhus incidence in Guangzhou, southern China, 2006-2014

Background: In the last decade, scrub typhus (ST) has been emerging or re-emerging in some areas of Asia, including Guangzhou, one of the most affected endemic areas of ST in China. Methods: Based on the data on all cases reported in Guangzhou from 2006 to 2014, we characterized the epidemiological features, and identified environmental determinants for the spatial distribution of ST using a panel negative binomial model. Results: A total of 4821 scrub typhus cases were reported in Guangzhou during 2006-2014. The annual incidence increased noticeably and the increase was relatively high and rapid in rural townships and among elderly females. The majority of cases (86.8%) occurred during May-October, and farmers constituted the majority of the cases, accounting for 33.9% in urban and 61.6% in rural areas. The number of housekeeper patients had a rapid increment in both rural and urban areas during the study period. Atmospheric pressure and relative humidity with lags of 1 or 2 months, distributions of broadleaved forest and rural township were identified as determinants for the spatiotemporal distribution of scrub typhus. Conclusion: Our results indicate that surveillance and public education need to be focused on the elderly farmers in rural areas covered with broadleaf forest in southern China

Mental illness related disparities in diabetes prevalence, quality of care and outcomes: a population-based longitudinal study

<p>Abstract</p> <p>Background</p> <p>Health care disparity is a public health challenge. We compared the prevalence of diabetes, quality of care and outcomes between mental health clients (MHCs) and non-MHCs.</p> <p>Methods</p> <p>This was a population-based longitudinal study of 139,208 MHCs and 294,180 matched non-MHCs in Western Australia (WA) from 1990 to 2006, using linked data of mental health registry, electoral roll registrations, hospital admissions, emergency department attendances, deaths, and Medicare and pharmaceutical benefits claims. Diabetes was identified from hospital diagnoses, prescriptions and diabetes-specific primary care claims (17,045 MHCs, 26,626 non-MHCs). Both univariate and multivariate analyses adjusted for socio-demographic factors and case mix were performed to compare the outcome measures among MHCs, category of mental disorders and non-MHCs.</p> <p>Results</p> <p>The prevalence of diabetes was significantly higher in MHCs than in non-MHCs (crude age-sex-standardised point-prevalence of diabetes on 30 June 2006 in those aged ≥20 years, 9.3% vs 6.1%, respectively, <it>P </it>< 0.001; adjusted odds ratio (OR) 1.40, 95% CI 1.36 to 1.43). Receipt of recommended pathology tests (HbA_1c, microalbuminuria, blood lipids) was suboptimal in both groups, but was lower in MHCs (for all tests combined; adjusted OR 0.81, 95% CI 0.78 to 0.85, at one year; and adjusted rate ratio (RR) 0.86, 95% CI 0.84 to 0.88, during the study period). MHCs also had increased risks of hospitalisation for diabetes complications (adjusted RR 1.20, 95% CI 1.17 to 1.24), diabetes-related mortality (1.43, 1.35 to 1.52) and all-cause mortality (1.47, 1.42 to 1.53). The disparities were most marked for alcohol/drug disorders, schizophrenia, affective disorders, other psychoses and personality disorders.</p> <p>Conclusions</p> <p>MHCs warrant special attention for primary and secondary prevention of diabetes, especially at the primary care level.</p

Hospital Mental Health Admissions in Women after Unsuccessful Infertility Treatment and In Vitro Fertilization: An Australian Population-Based Cohort Study

Objective - To examine the association between in vitro fertilization (IVF) and later admission to hospital with a mental health diagnosis in women who remained childless after infertility treatment. Methods - This was a population-based cohort study using linked administrative hospital and registry data. The study population included all women commencing hospital treatment for infertility in Western Australia between the years 1982 and 2002 aged 20–44 years at treatment commencement who did not have a recorded birth by the end of follow-up (15 August 2010) and did not have a hospital mental health admission prior to the first infertility admission (n=6,567). Of these, 2,623 women had IVF and 3,944 did not. We used multivariate Cox regression modeling of mental health admissions and compared women undergoing IVF treatment with women having infertility treatment but not IVF. Results - Over an average of 17 years of follow-up, 411 women in the cohort were admitted to hospital with a mental health diagnosis; 93 who had IVF and 318 who did not. The unadjusted hazard ratio (HR) for a hospital mental health admission comparing women who had IVF with those receiving other infertility treatment was 0.50 (95% confidence interval [CI] 0.40–0.63). After adjustment for age, calendar year and socio-economic status the HR was 0.56 (95% CI 0.44–0.71). Conclusions - IVF treatment is associated with a reduced risk of hospital mental health admissions in women after unsuccessful infertility treatment. This may be explained by the healthy cohort effect

The impact of mental illness on potentially preventable hospitalisations: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Emerging evidence indicates an association between mental illness and poor quality of physical health care. To test this, we compared mental health clients (MHCs) with non-MHCs on potentially preventable hospitalisations (PPHs) as an indicator of the quality of primary care received.</p> <p>Methods</p> <p>Population-based retrospective cohort study of 139,208 MHCs and 294,180 matched non-MHCs in Western Australia from 1990 to 2006, using linked data from electoral roll registrations, mental health registry (MHR) records, hospital inpatient discharges and deaths. We used the electoral roll data as the sampling frame for both cohorts to enhance internal validity of the study, and the MHR to separate MHCs from non-MHCs. Rates of PPHs (overall and by PPH category and medical condition) were compared between MHCs, category of mental disorders and non-MHCs. Multivariate negative binomial regression analyses adjusted for socio-demographic factors, case mix and the year at the start of follow up due to dynamic nature of study cohorts.</p> <p>Results</p> <p>PPHs accounted for more than 10% of all hospital admissions in MHCs, with diabetes and its complications, adverse drug events (ADEs), chronic obstructive pulmonary disease (COPD), convulsions and epilepsy, and congestive heart failure being the most common causes. Compared with non-MHCs, MHCs with any mental disorders were more likely to experience a PPH than non-MHCs (overall adjusted rate ratio (ARR) 2.06, 95% confidence interval (CI) 2.03-2.09). ARRs of PPHs were highest for convulsions and epilepsy, nutritional deficiencies, COPD and ADEs. The ARR of a PPH was highest in MHCs with alcohol/drug disorders, affective psychoses, other psychoses and schizophrenia.</p> <p>Conclusions</p> <p>MHCs have a significantly higher rate of PPHs than non-MHCs. Improving primary and secondary prevention is warranted in MHCs, especially at the primary care level, despite there may be different thresholds for admission in people with established physical disease that is influenced by whether or not they have comorbid mental illness.</p

Distribution and Risk Factors of 2009 Pandemic Influenza A (H1N1) in Mainland China

Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level. The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China. Significant differences in incidence were found among age groups, with incidences peaking in school-age children. Overall, the epidemic spread from southeast to northwest. Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county. Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities. These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie