Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

Melioidosis-a disease of socioeconomic disadvantage.

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.

Divergent Synthesis of γ-Amino Acid and γ-Lactam Derivatives from meso-Glutaric Anhydrides.

The first divergent synthesis of both γ-amino acid and γ-lactam derivatives from meso-glutaric anhydrides is described. The organocatalytic desymmetrisation with TMSN3 relies on controlled generation of a nucleophilic ammonium azide species mediated by a polystyrene-bound base to promote efficient silylazidation. After Curtius rearrangement of the acyl azide intermediate to access the corresponding isocyanate, hydrolysis/alcoholysis provided uniformly high yields of γ-amino acids and their N-protected counterparts. The same intermediates were shown to undergo an unprecedented decarboxylation-cyclisation cascade in situ to provide synthetically useful yields of γ-lactam derivatives without using any further activating agents. Mechanistic insights invoke the intermediacy of an unconventional γ-N-carboxyanhydride (γ-NCA) in the latter process. Among the examples prepared using this transformation are 8 APIs/molecules of considerable medicinal interest.

High Rates of Premature and Potentially Preventable Death among Patients Surviving Melioidosis in Tropical Australia.

Although the in-hospital mortality of Australian patients with melioidosis continues to decline, the ensuing clinical course of survivors is poorly described. Between January 1, 1998, and January 31, 2019, 228 patients in Cairns, tropical Australia, survived their hospitalization with melioidosis; however, 52 (23%) subsequently died. Death occurred at a median of 3.8 years after discharge, with patients dying at a mean age of 59 years. Only 1/27 (4%) without predisposing conditions for melioidosis died during follow-up, versus 51/201 (25%) with these comorbidities (P = 0.01). Death during follow-up was more likely in patients with chronic lung disease (OR [95% CI]: 4.05 (1.84-8.93, P = 0.001) and chronic kidney disease (OR [95% CI]: 2.87 [1.33-6.20], P = 0.007), and was most commonly due to infection and macrovascular disease. A significant proportion of Australians surviving hospitalization with melioidosis will die soon after discharge, usually prematurely and frequently from preventable conditions. A more holistic approach is required to their care.

Bilateral pneumothoraces following acupuncture.

A 50-year-old woman was brought to the emergency department with shortness of breath and chest tightness following acupuncture to her upper back for a chronically painful left shoulder. She had symptoms of respiratory distress and chest X-ray revealed bilateral pneumothoraces. Symptoms resolved after insertion of bilateral Seldinger chest drains. She was admitted to the Cardiothoracic Surgery ward, chest drains were removed on the second and third days and the patient was discharged from hospital after 3 days. Clinicians and acupuncturists should be aware of this adverse event following acupuncture.

The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator.

Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive "pica" behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting.

Management of over-the-counter insomnia complaints in Australian community pharmacies: a standardized patient study.

OBJECTIVE: To evaluate the current management of over-the-counter (OTC) insomnia complaints in Australian community pharmacies using standardized patient methodology. METHODS: Trained standardized patients visited a sample of 100 randomly selected South East Queensland community pharmacies in June 2011. The standardized patients enacted two OTC insomnia scenarios: a direct product request (DPR) (n = 50) and a symptom-based request (SBR) (n = 50). Results of the interactions were documented immediately after each visit and evaluated using the Pharmaceutical Society of Australia's WHAT STOP GO protocol as a standard comparison. KEY FINDINGS: Of all DPRs, 30% were handled entirely by the pharmacist, 70% of staff enquired about specific symptoms and 28% investigated the cause of insomnia. No staff investigated the frequency of product use. The DPR scenario resulted in a 92% supply of the requested doxylamine product (Restavit). In the SBR scenario, 18% of requests were handled entirely by the pharmacist, 58% of staff enquired about specific symptoms and 44% investigated the cause of insomnia. Staff recommended medicated products (38%), or herbal (78%) or non-drug techniques (18%). Investigation into smoking and alcohol intake was not undertaken in DPR or SBR interactions, while questioning on caffeine intake was undertaken in 2 and 14% of cases respectively. There were no significant differences found in the handling of sleep requests by pharmacists compared to pharmacy assistants. CONCLUSION: The standardized patient methodology was a successful way to assess the community pharmacy counselling provided with OTC sleep requests and suboptimal staff responses were found when compared with recommended practice standards.