Search

Background: Melioidosis, a life-threatening infection caused by the gram negative bacterium Burkholderia pseudomallei, can involve almost any organ. Bone and joint infections (BJI) are a recognised, but incompletely defined, manifestation of melioidosis that are associated with significant morbidity and mortality in resource-limited settings. Methodology/principal findings: We identified all individuals with BJI due to B. pseudomallei managed at Cairns Hospital in tropical Australia between January 1998 and June 2023. The patients' demographics, their clinical findings and their treatment were correlated with their subsequent course. Of 477 culture-confirmed cases of melioidosis managed at the hospital during the study period, 39 (8%) had confirmed BJI; predisposing risk factors for melioidosis were present in 37/39 (95%). However, in multivariable analysis only diabetes mellitus was independently associated with the presence of BJI (odds ratio (95% confidence interval): 4.04 (1.81–9.00), p = 0.001). BJI was frequently only one component of multi-organ involvement: 29/39 (74%) had infection involving other organs and bacteraemia was present in 31/39 (79%). Of the 39 individuals with BJI, 14 (36%) had osteomyelitis, 8 (20%) had septic arthritis and 17 (44%) had both osteomyelitis and septic arthritis; in 32/39 (83%) the lower limb was involved. Surgery was performed in 30/39 (77%). Readmission after the initial hospitalisation was necessary in 11/39 (28%), 5/39 (13%) had disease recrudescence and 3/39 (8%) had relapse; 4/39 (10%) developed pathological fractures. ICU admission was necessary in 11/39 (28%) but all 11 of these patients survived. Only 1/39 (3%) died, 138 days after admission, due to his significant underlying comorbidity. Conclusions: The case-fatality rate from melioidosis BJI in Australia's well-resourced health system is very low. However, recrudescence, relapse and orthopaedic complications are relatively common and emphasise the importance of collaborative multidisciplinary care that includes early surgical review, aggressive source control, prolonged antibiotic therapy, and thorough, extended follow-up. Author summary: Bone and joint infections (BJI) are a recognised and life-threatening manifestation of melioidosis but frequently only one component of multi-organ involvement. Almost all patients with BJI due to Burkholderia pseudomallei have risk factors that predispose them to developing melioidosis, but diabetes appears to be the most closely associated with BJI. The vasculopathy, neuropathy, structural deformity and decreased immunity that is seen in many individuals with diabetes increases their risk of lower limb infection and these factors–combined with greater exposure to B. pseudomallei in the soil and surface water–might explain the lower limb predominance that is seen in many series of melioidosis-related BJI. Patients require early multimodal imaging, appropriate microbiological sampling, early surgical review, prompt source control and an adequate duration of antibiotic therapy–and, in many cases, critical care support–to ensure optimal outcomes. Collaborative, multidisciplinary care reduces the case-fatality rate of melioidosis BJI, but recrudescence, relapse and orthopaedic complications are common in survivors and therefore extended patient follow up is essential. [ABSTRACT FROM AUTHOR]

Background: Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B virus (HBV) infection have a significant burden of hepatocellular carcinoma (HCC). The prevalence of comorbidities that increase the risk of HCC in this population is incompletely defined. Methods: This cross-sectional study was performed in remote tropical Queensland, Australia in January 2021. All individuals living with chronic HBV in the region were identified; the prevalence of relevant comorbidities was determined by reviewing medical records. Results: All 236 individuals in the cohort identified as Aboriginal and Torres Strait Islander Australians; their median (interquartile range (IQR)) age was 48 (40–62) years; 120/236 (50.9%) were female. Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV therapy and 38 (62.2%) were receiving it. However, 142/236 (60.2%) were obese, 73/236 (30.9%) were current smokers and 57/236 (24.2%) were drinking alcohol hazardously; 70/236 (29.7%) had ≥2 of these additional risk factors for HCC, only 43/236 (18.2%) had none. Among the 19 patients with confirmed cirrhosis, 9 (47%) were obese, 8 (42%) were currently—or had a history of—drinking alcohol hazardously and 5 (26.3%) were current smokers. Patients also had a median (IQR) of 3 (2–4) cardiovascular risk factors (cigarette smoking, hypertension, impaired glucose tolerance, dyslipidaemia, renal impairment/proteinuria). Only 9/236 (3.8%) did not have one of these 5 comorbidities. Conclusions: Aboriginal and Torres Strait Islander Australians living with chronic HBV in this region of remote Australia have a high engagement with HBV care and the majority of individuals eligible for antiviral therapy are receiving it. However, a significant comorbidity burden increases their risk of cirrhosis, HCC, and premature death. It is essential to integrate chronic HBV care with management of these comorbidities—rather than focusing on HBV alone—to achieve optimal health outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients with rheumatic heart disease (RHD) and congestive cardiac failure (CCF) are believed to have an increased risk of melioidosis and are thought to be more likely to die from the infection. This study was performed to confirm these findings in a region with a high incidence of all three conditions. Principal findings: Between January 1998 and December 2021 there were 392 cases of melioidosis in Far North Queensland, tropical Australia; 200/392 (51.0%) identified as an Indigenous Australian, and 337/392 (86.0%) had a confirmed predisposing comorbidity that increased risk for the infection. Overall, 46/392 (11.7%) died before hospital discharge; the case fatality rate declining during the study period (p for trend = 0.001). There were only 3/392 (0.8%) with confirmed RHD, all of whom had at least one other risk factor for melioidosis; all 3 survived to hospital discharge. Among the 200 Indigenous Australians in the cohort, 2 had confirmed RHD; not statistically greater than the prevalence of RHD in the local general Indigenous population (1.0% versus 1.2%, p = 1.0). RHD was present in only 1/193 (0.5%) cases of melioidosis diagnosed after October 2016, a period which coincided with prospective data collection. There were 26/392 (6.6%) with confirmed CCF, but all 26 had another traditional risk factor for melioidosis. Patients with CCF were more likely to also have chronic lung disease (OR (95% CI: 4.46 (1.93–10.31), p<0.001) and chronic kidney disease (odds ratio (OR) (95% confidence interval (CI): 2.98 (1.22–7.29), p = 0.01) than those who did not have CCF. Two patients with melioidosis and CCF died before hospital discharge; both were elderly (aged 81 and 91 years) and had significant comorbidity. Conclusions: In this region of tropical Australia RHD and CCF do not appear to be independent risk factors for melioidosis and have limited prognostic utility. Author summary: Melioidosis, a disease caused by Burkholderia pseudomallei, rarely develops in the absence of well-described predisposing conditions that include diabetes mellitus, hazardous alcohol intake, chronic kidney disease, chronic lung disease, malignancy, and immunosuppression. These comorbidities are also strongly linked to patients' short and long-term outcomes. In the large Darwin Prospective Melioidosis Study (DPMS) performed in Australia's Northern Territory, the presence of rheumatic heart disease (RHD) and/or congestive cardiac failure (CCF) were independently associated with pulmonary melioidosis and independently predicted death. Indeed, patients with RHD and/or CCF and melioidosis had the highest case-fatality rate in the DPMS cohort. The prevalence of RHD and/or CCF in cases of melioidosis in this study in Far North Queensland (FNQ), was similar to that seen in the Northern Territory. However, every patient had at least one other traditional risk factor for the disease. Furthermore, pulmonary involvement and mortality were not higher in patients with RHD and/or CCF. In FNQ, RHD and CCF are not independent risk factors for melioidosis and have limited prognostic utility. The high prevalence of these cardiac diseases in patients with melioidosis may be, at least partly, explained by the confounding presence of socioeconomic disadvantage that increases the incidence of all three conditions. [ABSTRACT FROM AUTHOR]

Cryptococcal infections are an important cause of morbidity and mortality in tropical Australia. This retrospective audit was conducted to characterise the aetiology, temporospatial epidemiology, and clinical course of 49 cryptococcal infections in Far North Queensland between 1 January 1999 and 31 December 2019. Cryptococcus gattii was identified in 15/32 (47%) in whom it was possible to speciate the organism. Among these 15 patients, 13 (87%) had a rural residential address, 10 (67%) were Indigenous Australians and 11 (73%) presented during the May-November dry season. When compared to the 17 patients with Cryptococcus neoformans infection, patients with C. gattii were less likely to be immunocompromised (0/15 versus 8/17 (47%), p = 0.003). Neurosurgery was necessary in 5/15 C. gattii cases and 3/17 (18%) C. neoformans cases (p = 0.42). Outcomes were generally good with 42/49 (86%) cases—and 14/15 (93%) with C. gattii infection—surviving to hospital discharge. These positive outcomes are likely to be explained by the development of standardised treatment guidelines during the study period, low rates of comorbidity in the patients with C. gattii infection and access to liposomal amphotericin and neurosurgical support in the well-resourced Australian healthcare system. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of central nervous system (CNS) infections in tropical Australia is incompletely defined. Methods: A retrospective study of all individuals in Far North Queensland, tropical Australia, who were diagnosed with a CNS infection between January 1, 2000, and December 31, 2019. The microbiological aetiology of the infection was correlated with patients' demographic characteristics and their clinical course. Results: There were 725 cases of CNS infection during the study period, meningitis (77.4%) was the most common, followed by brain abscess (11.6%), encephalitis (9.9%) and spinal infection (1.1%). Infants (24.3%, p<0.0001) and Aboriginal and Torres Strait Islander Australians (175/666 local residents, 26.3%, p<0.0001) were over-represented in the cohort. A pathogen was identified in 513 cases (70.8%); this was viral in 299 (41.2%), bacterial in 175 (24.1%) and fungal in 35 (4.8%). Cryptococcal meningitis (24 cases) was diagnosed as frequently as pneumococcal meningitis (24 cases). There were only 2 CNS infections with a S. pneumoniae serotype in the 13-valent pneumococcal vaccine after its addition to the National Immunisation schedule in 2011. Tropical pathogens–including Cryptococcus species (9/84, 11%), Mycobacterium tuberculosis (7/84, 8%) and Burkholderia pseudomallei (5/84, 6%)–were among the most common causes of brain abscess. However, arboviral CNS infections were rare, with only one locally acquired case—a dengue infection in 2009—diagnosed in the entire study period. Intensive Care Unit admission was necessary in 14.3%; the overall case fatality rate was 4.4%. Conclusion: Tropical pathogens cause CNS infections as commonly as traditional bacterial pathogens in this region of tropical Australia. However, despite being highlighted in the national consensus guidelines, arboviruses were identified very rarely. Prompt access to sophisticated diagnostic and supportive care in Australia's well-resourced public health system is likely to have contributed to the cohort's low case-fatality rate. [ABSTRACT FROM AUTHOR]

Background: There is growing recognition of the contribution of the social determinants of health to the burden of many infectious diseases. However, the relationship between socioeconomic status and the incidence and outcome of melioidosis is incompletely defined. Methods: All residents of Far North Queensland, tropical Australia with culture-proven melioidosis between January 1998 and December 2020 were eligible for the study. Their demographics, comorbidities and socioeconomic status were correlated with their clinical course. Socioeconomic status was determined using the Socio-Economic Indexes for Areas (SEIFA) Index of Relative Socio-economic Disadvantage score, a measure of socioeconomic disadvantage developed by the Australian Bureau of Statistics. Socioeconomic disadvantage was defined as residence in a region with a SEIFA score in the lowest decile in Australia. Results: 321 eligible individuals were diagnosed with melioidosis during the study period, 174 (54.2%) identified as Indigenous Australians; 223/321 (69.5%) were bacteraemic, 85/321 (26.5%) required Intensive Care Unit (ICU) admission and 37/321 (11.5%) died. 156/321 (48.6%) were socioeconomically disadvantaged, compared with 56603/269002 (21.0%) of the local general population (p<0.001). Socioeconomically disadvantaged patients were younger, more likely to be female, Indigenous, diabetic or have renal disease. They were also more likely to die prior to hospital discharge (26/156 (16.7%) versus 11/165 (6.7%), p = 0.002) and to die at a younger age (median (IQR) age: 50 (38–68) versus 65 (59–81) years, p = 0.02). In multivariate analysis that included age, Indigenous status, the presence of bacteraemia, ICU admission and the year of hospitalisation, only socioeconomic disadvantage (odds ratio (OR) (95% confidence interval (CI)): 2.49 (1.16–5.35), p = 0.02) and ICU admission (OR (95% CI): 4.79 (2.33–9.86), p<0.001) were independently associated with death. Conclusion: Melioidosis is disease of socioeconomic disadvantage. A more holistic approach to the delivery of healthcare which addresses the social determinants of health is necessary to reduce the burden of this life-threatening disease. Author summary: The social determinants of health—the circumstances in which people grow, live, work, and age, and the systems put in place to deal with illness—have a profound effect on how, when, and even if patients access healthcare, and yet they are generally under-appreciated by practicing clinicians whose training emphasises the biomedical model of healthcare. In this region of tropical Australia patients diagnosed with melioidosis were more likely to live in a socioeconomically disadvantaged region. Socioeconomically disadvantaged individuals with melioidosis were also more likely to die from their infection and to die at a younger age. It was notable that socioeconomic disadvantage had a greater independent association with in-hospital death than age, Indigenous status, the presence of bacteraemia or any of the comorbidities that classically predispose individuals to melioidosis. A more holistic approach to the delivery of healthcare—which addresses the social determinants of health—is necessary if we are to reduce the burden of melioidosis and the many other health conditions that disproportionately affect the most disadvantaged members of our society. [ABSTRACT FROM AUTHOR]

Background: The incidence of rheumatic heart disease (RHD) among Indigenous Australians remains one of the highest in the world. Many studies have highlighted the relationship between the social determinants of health and RHD, but few have used registry data to link socioeconomic disadvantage to the delivery of patient care and long-term outcomes. Methods: A retrospective study of individuals living with RHD in Far North Queensland (FNQ), Australia between 1997 and 2017. Patients were identified using the Queensland state RHD register. The Socio-Economic Indexes for Areas (SEIFA) Score–a measure of socioeconomic disadvantage–was correlated with RHD prevalence, disease severity and measures of RHD care. Results: Of the 686 individuals, 622 (90.7%) were Indigenous Australians. RHD incidence increased in the region from 4.7/100,000/year in 1997 to 49.4/100,000/year in 2017 (p<0.001). In 2017, the prevalence of RHD was 12/1000 in the Indigenous population and 2/1000 in the non-Indigenous population (p<0.001). There was an inverse correlation between an area's SEIFA score and its RHD prevalence (rho = -0.77, p = 0.005). 249 (36.2%) individuals in the cohort had 593 RHD-related hospitalisations; the number of RHD-related hospitalisations increased during the study period (p<0.001). In 2017, 293 (42.7%) patients met criteria for secondary prophylaxis, but only 73 (24.9%) had good adherence. Overall, 119/686 (17.3%) required valve surgery; the number of individuals having surgery increased over the study period (p = 0.02). During the study 39/686 (5.7%) died. Non-Indigenous patients were more likely to die than Indigenous patients (9/64 (14%) versus 30/622 (5%), p = 0.002), but Indigenous patients died at a younger age (median (IQR): 52 (35–67) versus 73 (62–77) p = 0.013). RHD-related deaths occurred at a younger age in Indigenous individuals than non-Indigenous individuals (median (IQR) age: 29 (12–58) versus 77 (64–78), p = 0.007). Conclusions: The incidence of RHD, RHD-related hospitalisations and RHD-related surgery continues to rise in FNQ. Whilst this is partly explained by increased disease recognition and improved delivery of care, the burden of RHD remains unacceptably high and is disproportionately borne by the socioeconomically disadvantaged Indigenous population. Author summary: Rheumatic heart disease (RHD), a disease of poverty and disadvantage, is almost completely preventable. It is now extremely rare in wealthy countries, but in Far North Queensland in tropical Australia, the incidence of RHD, RHD-related hospitalisations and RHD-related surgery is continuing to rise, with the burden of disease borne almost entirely by the region's Indigenous population. While the increasing incidence of RHD and its complications may be partly explained by improvements in local service delivery, the disease remains inextricably linked to socioeconomic disadvantage. In this study, not only were patients living in socioeconomically disadvantaged areas more likely to have RHD, but they were also paradoxically less likely to receive valve surgery. The current local model of care—which is centralised, medical and emphasises disease monitoring and secondary prophylaxis—appears to be having a limited impact on morbidity. Strategies must evolve—in partnership with Indigenous communities—to have a greater focus on disease prevention by addressing the personal, community and environmental factors that increase the risk of the disease. This is likely to not only reduce the incidence of RHD, but will also tend to reduce the burden of the many other diseases that result from socioeconomic disadvantage and that disproportionately affect Indigenous Australians. [ABSTRACT FROM AUTHOR]

Introduction: Aboriginal and Torres Strait Islander Australians living in remote locations suffer disproportionately from chronic hepatitis B (CHB). Defining the temporospatial epidemiology of the disease—and assessing the ability of local clinicians to deliver optimal care—is crucial to improving patient outcomes in these settings. Methods: The demographic, laboratory and radiology findings in all patients diagnosed with CHB after 1990, and presently residing in remote Far North Queensland (FNQ), tropical Australia, were correlated with their management and clinical course. Results: Of the 602 patients, 514 (85%) identified as Aboriginal and Torres Strait Islander Australians, 417 (69%) of whom had Torres Strait Islander heritage. Among the 514 Aboriginal and Torres Strait Islander Australians, there were only 61 (12%) born after universal postnatal vaccination was introduced in 1985. Community CHB prevalence varied significantly across the region from 7/1707 (0.4%) in western Cape York to 55/806 (6.8%) in the Eastern Torres Strait Islands. Although 240/602 (40%) are engaged in care, with 65 (27%) meeting criteria for antiviral therapy, only 43 (66%) were receiving this treatment. Among 537 with complete data, 32 (6%) were cirrhotic, of whom 15 (47%) were engaged in care and 10 (33%) were receiving antiviral therapy. Only 64/251 (26%) in whom national guidelines would recommend hepatocellular carcinoma (HCC) surveillance are receiving screening, however, only 20 patients have been diagnosed with HCC since 1999. Conclusion: Vaccination has had a dramatic effect on CHB prevalence in FNQ in only a generation. However, although engagement in care is the highest in Australia, this is not translating into initiation of antiviral therapy in all those that should be receiving it, increasing their risk of developing cirrhosis and HCC. New strategies are necessary to improve the care of Indigenous Australians living with CHB to reduce the morbidity and mortality of this preventable disease. [ABSTRACT FROM AUTHOR]

Background: Indigenous Australians suffer a disproportionate burden of sepsis, however, the performance of scoring systems that predict mortality in Indigenous patients with critical illness is incompletely defined. Materials and methods: The study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis. The ability of the ANZROD, APACHE-II, APACHE-III, SAPS-II, SOFA and qSOFA scores to predict death before ICU discharge in the two populations was compared. Results: There were 442 individuals enrolled in the study, 145 (33%) identified as Indigenous. Indigenous patients were younger than non-Indigenous patients (median (interquartile range (IQR) 53 (43–60) versus 65 (52–73) years, p = 0.0001) and comorbidity was more common (118/145 (81%) versus 204/297 (69%), p = 0.005). Comorbidities that were more common in the Indigenous patients included diabetes mellitus (84/145 (58%) versus 67/297 (23%), p<0.0001), renal disease (56/145 (39%) versus 29/297 (10%), p<0.0001) and cardiovascular disease (58/145 (40%) versus 83/297 (28%), p = 0.01). The use of supportive care (including vasopressors, mechanical ventilation and renal replacement therapy) was similar in Indigenous and non-Indigenous patients, and the two populations had an overall case-fatality rate that was comparable (17/145 (12%) and 38/297 (13%) (p = 0.75)), although Indigenous patients died at a younger age (median (IQR): 54 (50–60) versus 70 (61–76) years, p = 0.0001). There was no significant difference in the ability of any the scores to predict mortality in the two populations. Conclusions: Although the crude case-fatality rates of Indigenous and non-Indigenous Australians admitted to ICU with sepsis is comparable, Indigenous patients die at a much younger age. Despite this, the ability of commonly used scoring systems to predict outcome in Indigenous Australians is similar to that of non-Indigenous Australians, supporting their use in ICUs with a significant Indigenous patient population and in clinical trials that enrol Indigenous Australians. [ABSTRACT FROM AUTHOR]

Background: Severe leptospirosis can have a case-fatality rate of over 50%, even with intensive care unit (ICU) support. Multiple strategies–including protective ventilation and early renal replacement therapy (RRT)–have been recommended to improve outcomes. However, management guidelines vary widely around the world and there is no consensus on the optimal approach. Methodology/Principal findings: All cases of leptospirosis admitted to the ICU of Cairns Hospital in tropical Australia between 1998 and 2018 were retrospectively reviewed. The patients' demographics, presentation, management and clinical course were examined. The 55 patients' median (interquartile range (IQR)) age was 47 (32–62) years and their median (IQR) APACHE III score was 67 (48–105). All 55 received appropriate antibiotic therapy, 45 (82%) within the first 6 hours. Acute kidney injury was present in 48/55 (87%), 18/55 (33%) required RRT, although this was usually not administered until traditional criteria for initiation were met. Moderate to severe acute respiratory distress syndrome developed in 37/55 (67%), 32/55 (58%) had pulmonary haemorrhage, and mechanical ventilation was required in 27/55 (49%). Vasopressor support was necessary in 34/55 (62%). Corticosteroids were prescribed in 20/55 (36%). The median (IQR) fluid balance in the initial three days of ICU care was +1493 (175–3567) ml. Only 2/55 (4%) died, both were elderly men with multiple comorbidities. Conclusion: In patients with severe leptospirosis in tropical Australia, prompt ICU support that includes early antibiotics, protective ventilation strategies, conservative fluid resuscitation, traditional thresholds for RRT initiation and corticosteroid therapy is associated with a very low case-fatality rate. Prospective studies are required to establish the relative contributions of each of these interventions to optimal patient outcomes. Author summary: Severe leptospirosis continues to carry a high mortality. To improve outcomes, several countries have developed national guidelines for the management of severe disease. However, there is substantial variation in these guidelines despite the fact that severe leptospirosis has a very similar presentation around the world. In tropical Australia, the case-fatality rate of severe leptospirosis is only 4%. This retrospective study reviewed 55 patients with leptospirosis requiring support in an Australian Intensive Care Unit (ICU) in an effort to identify the management strategies that might explain these excellent outcomes. The low case-fatality rate was associated with prompt multimodal ICU support that included early antibiotics, protective ventilation strategies, conservative fluid resuscitation, traditional thresholds for renal replacement therapy initiation and corticosteroid therapy. However prospective, multinational studies–which include the resource-poor settings that bear the greatest burden of disease–are necessary to define which of these interventions have the greatest therapeutic value. [ABSTRACT FROM AUTHOR]

Background: Rickettsial infections are a common cause of hospitalization in tropical settings, although early diagnosis is challenging in the rural locations where these infections are usually seen. Methods: This retrospective, clinical audit of microbiologically-confirmed cases of scrub typhus or spotted fever group (SFG) rickettsial infection between 1997 and 2016 was performed a tertiary referral hospital in tropical Australia. Clinical, laboratory and radiological findings at presentation were correlated with the patients’ subsequent clinical course. Results: There were 135 locally-acquired cases (95 scrub typhus, 37 SFG, 3 undifferentiated). There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003). Eighteen (13%) of the 135 cases required ICU admission, all of whom were adults. A greater proportion of patients with SFG infection required ICU support (8/37 (22%) compared with 10/95 (11%) scrub typhus cases), although this difference did not reach statistical significance (p = 0.10). Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02). Adults with a high admission qSOFA score (≥2) had an odds ratio (OR) of 19 (95% CI:4.8–74.5) for subsequent ICU admission (p<0.001); adults with a high NEWS2 score (≥7) had an OR of 14.3 (95% CI:4.5–45.32) for ICU admission (p<0.001). A patient’s respiratory rate at presentation had strong prognostic utility: if an adult had an admission respiratory rate <22 breaths/minute, the negative predictive value for subsequent ICU admission was 95% (95% CI 88–99). Conclusions: In the well-resourced Australian health system outcomes are excellent, but the local burden of rickettsial disease appears to be increasing and the clinical phenotype of SFG infections may be more severe than previously believed. Simple, clinical assessment on admission has prognostic utility and may be used to guide management. [ABSTRACT FROM AUTHOR]

Background: The case-fatality rate of severe leptospirosis can exceed 50%. While prompt supportive care can improve survival, predicting those at risk of developing severe disease is challenging, particularly in settings with limited diagnostic support. Methodology/Principal findings: We retrospectively identified all adults with laboratory-confirmed leptospirosis in Far North Queensland, Australia, between January 1998 and May 2016. Clinical, laboratory and radiological findings at presentation were correlated with the patients’ subsequent clinical course. Medical records were available in 402 patients; 50 (12%) had severe disease. The presence of oliguria (urine output ≤500 mL/24 hours, odds ratio (OR): 16.4, 95% confidence interval (CI): 6.9–38.8, p<0.001), abnormal auscultatory findings on respiratory examination (OR 11.2 (95% CI: 4.7–26.5, p<0.001) and hypotension (systolic blood pressure ≤100 mmHg, OR 4.3 (95% CI 1.7–10.7, p = 0.002) at presentation independently predicted severe disease. A three-point score (the SPiRO score) was devised using these three clinical variables, with one point awarded for each. A score could be calculated in 392 (98%) patients; the likelihood of severe disease rose incrementally: 8/287 (3%), 14/70 (20%), 18/26 (69%) and 9/9 (100%) for a score of 0, 1, 2 and 3 respectively (p = 0.0001). A SPiRO score <1 had a negative predictive value for severe disease of 97% (95% CI: 95–99%). Conclusions/Significance: A simple, three-point clinical score can help clinicians rapidly identify patients at risk of developing severe leptospirosis, prompting early transfer to referral centres for advanced supportive care. This inexpensive, bedside assessment requires minimal training and may have significant utility in the resource-limited settings which bear the greatest burden of disease. [ABSTRACT FROM AUTHOR]

Young drivers (18–24 years) are over-represented in sleep-related crashes (comprising one in five fatal crashes in developed countries) primarily due to decreased sleep opportunity, lower tolerance for sleep loss, and ongoing maturation of brain areas associated with driving-related decision making. Impaired driving performance is the proximal reason for most car crashes. There is still a limited body of evidence examining the effects of sleep loss on young drivers’ performance, with discrepancies in the methodologies used, and in the definition of outcomes. This study aimed to identify the direction and magnitude of the effects of sleep loss on young drivers’ performance, and to appraise the quality of current evidence via a systematic review. Based on the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) approach, 16 eligible studies were selected for review, and their findings summarised. Next, critical elements of these studies were identified, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines augmented to rate those elements. Using those criteria, the quality of individual papers was calculated and the overall body of evidence for each driving outcome were assigned a quality ranking (from ‘very low’ to ‘high-quality’). Two metrics, the standard deviation of lateral position and number of line crossings, were commonly reported outcomes (although in an overall ‘low-quality’ body of evidence), with significant impairments after sleep loss identified in 50% of studies. While speed-related outcomes and crash events (also with very low- quality evidence) both increased under chronic sleep loss, discrepant findings were reported under conditions of acute total sleep deprivation. It is crucial to obtain more reliable data about the effects of sleep loss on young drivers’ performance by using higher quality experimental designs, adopting common protocols, and the use of consistent metrics and reporting of findings based on GRADE criteria and the PRISMA statement. Key words: Young drivers, sleep loss, driving performance, PRISMA, the GRADE, systematic review. [ABSTRACT FROM AUTHOR]

Background: The epidemiology, clinical presentation and management of melioidosis vary around the world. It is essential to define the disease’s local features to optimise its management. Principal findings: Between 1998 and 2016 there were 197 cases of culture confirmed melioidosis in Far North Queensland; 154 (78%) presented in the December-April wet season. 145 (74%) patients were bacteraemic, 58 (29%) were admitted to the Intensive Care Unit and 27 (14%) died; nine (33%) of these deaths occurred within 48 hours of presentation. Pneumonia was the most frequent clinical finding, present in 101 (61%) of the 166 with available imaging. A recognised risk factor for melioidosis (diabetes, hazardous alcohol use, chronic renal disease, chronic lung disease, immunosuppression or malignancy) was present in 148 (91%) of 162 patients with complete comorbidity data. Despite representing only 9% of the region’s population, Aboriginal and Torres Strait Island (ATSI) people comprised 59% of the cases. ATSI patients were younger than non-ATSI patients (median (interquartile range): 46 (38–56) years versus 59 (43–69) years (p<0.001) and had a higher case-fatality rate (22/117 (19%) versus 5/80 (6.3%) (p = 0.01)). In the 155 patients surviving the initial intensive intravenous phase of treatment, eleven (7.1%) had disease recurrence, despite the fact that nine (82%) of these patients had received prolonged intravenous therapy. Recurrence was usually due to inadequate source control or poor adherence to oral eradication therapy. The case fatality rate declined from 12/44 (27%) in the first five years of the study to 7/76 (9%) in the last five (p = 0.009), reflecting national improvements in sepsis management. Conclusions: Melioidosis in Far North Queensland is a seasonal, opportunistic infection of patients with specific comorbidities. The ATSI population bear the greatest burden of disease. Although the case-fatality rate is declining, deaths frequently occur early after hospitalisation, reinforcing the importance of prompt, targeted therapy in high-risk patients. [ABSTRACT FROM AUTHOR]

The timing, intensity, and duration of exposure to both artificial and natural light have acute metabolic and physiological effects in mammals. Recent research in human adults suggests exposure to moderate intensity light later in the day is concurrently associated with increased body mass; however, no studies have investigated the effect of light exposure on body mass in young children. We examined objectively measured light exposure and body mass of 48 preschool-aged children at baseline, and measured their body mass again 12 months later. At baseline, moderate intensity light exposure earlier in the day was associated with increased body mass index (BMI). Increased duration of light exposure at baseline predicted increased BMI 12-months later, even after controlling for baseline sleep duration, sleep timing, BMI, and activity. The findings identify that light exposure may be a contributor to the obesogenic environment during early childhood. [ABSTRACT FROM AUTHOR]

Objective: The aim of this systematic review and meta-analysis was to determine the overall effect of resistance training (RT) on measures of muscular strength in people with Parkinson’s disease (PD). Methods: Controlled trials with parallel-group-design were identified from computerized literature searching and citation tracking performed until August 2014. Two reviewers independently screened for eligibility and assessed the quality of the studies using the Cochrane risk-of-bias-tool. For each study, mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for continuous outcomes based on between-group comparisons using post-intervention data. Subgroup analysis was conducted based on differences in study design. Results: Nine studies met the inclusion criteria; all had a moderate to high risk of bias. Pooled data showed that knee extension, knee flexion and leg press strength were significantly greater in PD patients who undertook RT compared to control groups with or without interventions. Subgroups were: RT vs. control-without-intervention, RT vs. control-with-intervention, RT-with-other-form-of-exercise vs. control-without-intervention, RT-with-other-form-of-exercise vs. control-with-intervention. Pooled subgroup analysis showed that RT combined with aerobic/balance/stretching exercise resulted in significantly greater knee extension, knee flexion and leg press strength compared with no-intervention. Compared to treadmill or balance exercise it resulted in greater knee flexion, but not knee extension or leg press strength. RT alone resulted in greater knee extension and flexion strength compared to stretching, but not in greater leg press strength compared to no-intervention. Discussion: Overall, the current evidence suggests that exercise interventions that contain RT may be effective in improving muscular strength in people with PD compared with no exercise. However, depending on muscle group and/or training dose, RT may not be superior to other exercise types. Interventions which combine RT with other exercise may be most effective. Findings should be interpreted with caution due to the relatively high risk of bias of most studies. [ABSTRACT FROM AUTHOR]

Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or intrinsic (retinal) network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years) with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux). Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO) was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells mediate this circadian variation. [ABSTRACT FROM AUTHOR]

An understanding of the seasonality of infections informs public health strategies and assists clinicians in their management of patients with undifferentiated illness. The seasonality of infections is driven by a variety of environmental and human factors; however, the role of individual climatic factors has garnered much attention. This study utilises Poisson regression models to assess the seasonality of six important infections in tropical Australia and their association with climatic factors and severe weather events over a 21-year period. Melioidosis and leptospirosis showed marked wet season predominance, while more cases of rickettsial disease and cryptococcosis were seen in cooler, drier months. Staphylococcus aureus infections were not seasonal, while influenza demonstrated inter-seasonality. The climate did not significantly change during the 21 years of the study period, but the incidence of melioidosis and rickettsial disease increased considerably, highlighting the primacy of other factors-including societal inequality, and the impact of urban expansion-in the incidence of these infections. While anthropogenic climate change poses a threat to the region-and may influence the burden of these infections in the future-this study highlights the fact that, even for seasonal diseases, other factors presently have a greater effect on disease incidence. Public health strategies must also target these broader drivers of infection if they are to be effective., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Fairhead et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The case-fatality rate of severe leptospirosis can exceed 50%. While prompt supportive care can improve survival, predicting those at risk of developing severe disease is challenging, particularly in settings with limited diagnostic support., Methodology/principal Findings: We retrospectively identified all adults with laboratory-confirmed leptospirosis in Far North Queensland, Australia, between January 1998 and May 2016. Clinical, laboratory and radiological findings at presentation were correlated with the patients' subsequent clinical course. Medical records were available in 402 patients; 50 (12%) had severe disease. The presence of oliguria (urine output ≤500 mL/24 hours, odds ratio (OR): 16.4, 95% confidence interval (CI): 6.9-38.8, p<0.001), abnormal auscultatory findings on respiratory examination (OR 11.2 (95% CI: 4.7-26.5, p<0.001) and hypotension (systolic blood pressure ≤100 mmHg, OR 4.3 (95% CI 1.7-10.7, p = 0.002) at presentation independently predicted severe disease. A three-point score (the SPiRO score) was devised using these three clinical variables, with one point awarded for each. A score could be calculated in 392 (98%) patients; the likelihood of severe disease rose incrementally: 8/287 (3%), 14/70 (20%), 18/26 (69%) and 9/9 (100%) for a score of 0, 1, 2 and 3 respectively (p = 0.0001). A SPiRO score <1 had a negative predictive value for severe disease of 97% (95% CI: 95-99%)., Conclusions/significance: A simple, three-point clinical score can help clinicians rapidly identify patients at risk of developing severe leptospirosis, prompting early transfer to referral centres for advanced supportive care. This inexpensive, bedside assessment requires minimal training and may have significant utility in the resource-limited settings which bear the greatest burden of disease., Competing Interests: The authors have declared that no competing interests exist.