Simon D. Bowler

Effectiveness of H1N1/09 monovalent and trivalent influenza vaccines against hospitalization with laboratory-confirmed H1N1/09 influenza in Australia: A test-negative case control study

We aimed to estimate the effectiveness of H1N1/09 containing influenza vaccines against hospitalization from influenza in Australia. We performed a test-negative case control study in patients hospitalized in 15 sentinel Australian hospitals between March and November 2010, comparing influenza vaccination (H1N1/09 monovalent or 2010 seasonal trivalent) in hospitalized patients with PCR-confirmed influenza compared to PCR-negative controls. Between March and November 2010, 1169 hospitalized patients were tested for suspected influenza, of which influenza vaccine status was ascertained in 165/238 patients with H1N1/09 influenza, 40/64 with seasonal influenza and 558/867 test negative controls; 24% of H1N1/09 cases, 43% of seasonal influenza cases and 54% of controls were vaccinated. VE against hospitalisation with H1N1/09 influenza after adjusting for age, medical comorbidities and pregnancy status was estimated at 49% (95% CI: 13%, 70%). Influenza vaccination was associated with a reduction in hospitalisation caused by H1N1/09 influenza in the 2010 southern hemisphere winter season.

Influenza A/H1N1_09: Australia and New Zealand's winter of discontent.

Influenza A/H1N1_09 emerged in Mexico at the end of the Northern Hemisphere winter. Within weeks, the focus shifted to the Southern Hemisphere as the introduction of the novel virus coincided with the beginning of the influenza season. Intensive public health and health services planning had occurred in Australia and New Zealand as preparation for an influenza pandemic before 2009. However, this first pandemic wave was quite different to what had been expected. Key elements of the pandemic and response are outlined from the perspective of clinicians working at the frontline of patient care. In particular, they examine why past influenza pandemics and recent history are poor predictors of the current pandemic, the discordance between potential for transmission and disease severity, the broad clinical spectrum of H1N1_09 infection, clinical and health service management issues, and the relationship between health care and government policy. Finally, they address the need for the respiratory community to show leadership in times of crisis. Lessons learned in Australia and New Zealand during 2009 have important messages for similarly resourced countries in the Northern Hemisphere in the coming months as they face their own influenza season.

Everolimus treatment of abdominal lymphangioleiomyoma in five women with sporadic lymphangioleiomyomatosis

Objective: Lymphangioleiomyomatosis (LAM) is a rare systemic disease of young women arising from mutations in the tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. This disrupts the mammalian target of rapamycin (mTOR) pathway, affecting cellular proliferation and growth. mTOR inhibitors are a promising novel therapy in LAM. The mTOR inhibitor sirolimus is reported to produce resolution of lymphatic abnormalities in LAM, but the efficiacy of the mTOR inhibitor everolimus has not been assessed. We aimed to examine the efficacy of everolimus on lymphatic abnormalities in LAM.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry

Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited.

Clinical and epidemiological profile of patients with severe H1N1/09 pandemic influenza in Australia and New Zealand: an observational cohort study

Background Pandemic influenza H1N1/09 emerged in April 2009 and spread widely in Australia and New Zealand. Although an unprecedented number of cases required intensive care, comparative community-based studies with seasonal influenza strains have not shown any significant differences in clinical symptoms or severity. Methods The authors performed active surveillance on confirmed influenza-related admissions and compared the clinical profile of patients with pandemic H1N1/09 influenza and patients with seasonal influenza at eight hospitals in Australia and one hospital in New Zealand. Results During the 1 July and 30 November 2009, 560 patients with confirmed influenza were admitted, of which 478 had H1N1/09, and 82 had other seasonal strains. Patients with H1N1/09 influenza were younger, were more likely to have fever and were more likely to be pregnant but less likely to have chronic obstructive pulmonary disease and ischaemic heart disease than patients with seasonal strains. Other clinical features and comorbidities were reported in similar proportions. Admission to intensive care was required in 22% of patients with H1N1/09 influenza and 12% in patients with other strains. Hospital mortality was 5% in patients with H1N1 influenza. Conclusions The clinical features of H1N1/09 influenza and seasonal strains were similar in hospitalised patients. A higher proportion of patients had comorbidities than had been reported in community-based studies. Although the overall mortality was similar, the authors found evidence that H1N1/09 caused severe disease in a higher proportion of hospitalised patients.

Real‐life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria

Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30–1500 IU/mL) and bodyweight (30–150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government‐subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR).

Comparison of Oral Bambuterol and Terbutaline in Elderly Patients with Chronic Reversible Airflow Obstruction

Bambuterol, a carbamate prodrug of terbutaline, is the first once-daily oral beta 2-agonist. The effect/side effect ratio of bambuterol oral solution was compared with terbutaline mixture in elderly patients with chronic reversible obstructive airways disease. The study was of a double-blind, crossover, randomized design and consisted of a 4-7-day run-in period followed by four consecutive treatment periods each of 2 weeks. The treatments were bambuterol solution 20 mg nocte (B20), 10 mg nocte (B10), terbutaline mixture 3 mg t.i.d., (T), and placebo solution (P). Patients measured daily peak expiratory flow rate (PEFR), asthma symptoms, use of inhaled beta 2-agonist, and tremor. Of 84 patients, 66 completed all periods. Mean age was 67 years (60-90), basal FEV1 1.49 L, and reversibility of FEV1 30%. Ninety-four percent of the patients used inhaled/oral steroids in constant dosage. All treatments were significantly more effective than placebo. B20 resulted in higher morning PEFR than T (306 +/- 2.9 L/min vs. 297 +/- 2.9 L/min), while B10 gave equivalent results to T. No differences were seen in the use of inhaled beta 2-agonist. Less shortness of breath was experienced during the night with B20 and during the day with B10 compared with placebo. Both B20 and T produced more tremor than B10 and P. In elderly patients with chronic reversible airways obstruction once-daily bambuterol (10-20 mg) has a better effect/side effect ratio than 3 mg terbutaline thrice daily.

Long-term treatment with azithromycin results in reduced in vitro inflammatory cytokine production in adults with cystic fibrosis

Induced transcripts ID RefSeq Symbol Description GB51383 LOC550965 probable Cytochrom P450 6a14 GB40836 LOC100576126 uncharacterized LOC100576126 GB41097 LOC724565 trypsin-7 GB41306 LOC551369 actin, clone 205-like GB42514 GB43892 LOC551401 cytosolic 10-formyltetrahydrofolate dehydrogenase GB46197 LOC726277 anaphase-promoting complex subunit CDC26-like GB50989 GB51146 LOC102655756 PDZ and LIM domain protein 7-like GB51218 LOC107964586 uncharacterized LOC107964586 GB54099

Influenza Epidemiology, Vaccine Coverage and Vaccine Effectiveness in Children Admitted to Sentinel Australian Hospitals in 2017: Results from the PAEDS-FluCAN Collaboration

BACKGROUND In 2017, Australia experienced record influenza notifications. Two surveillance programs combined to summarize the epidemiology of hospitalized influenza in children and report on vaccine effectiveness (VE) in the context of a limited nationally funded vaccination program. METHODS Subjects were prospectively recruited (April-October 2017). Case patients were children aged ≤16 years admitted to 11 hospitals with an acute respiratory illness and laboratory-confirmed influenza. Controls were hospitalized with acute respiratory illness and tested negative for influenza. VE estimates were calculated using the test-negative design. RESULTS A total of 1268 children were hospitalized with influenza: 31.5% were <2 years old, 8.3% were indigenous, and 45.1% had comorbid conditions predisposing to severe influenza. Influenza B was detected in 34.1% with influenza A/H1N1 and A/H3N2 detected in 47.2% and 52.8% of subtyped influenza A specimens. The median length of stay was 3 days (interquartile range, 1-5), 14.5% were admitted to the intensive care unit, and 15.9% received oseltamivir. Four in-hospital deaths occurred (0.3%): one was considered influenza associated. Only 17.1% of test-negative-controls were vaccinated. The VE of inactivated quadrivalent influenza vaccine for preventing hospitalized influenza was estimated at 30.3% (95% confidence interval, 2.6%-50.2%). CONCLUSIONS Significant influenza-associated morbidity was observed in 2017 in Australia. Most hospitalized children had no comorbid conditions. Vaccine coverage and antiviral use was inadequate. Influenza vaccine was protective in 2017, yet VE was lower than previous seasons. Multiple Australian states have introduced funded preschool vaccination programs in 2018. Additional efforts to promote vaccination and monitor effectiveness are required.

Impact of Opioid Therapy on Sleep and Respiratory Patterns in Adults With Advanced Cancer Receiving Palliative Care

CONTEXT In advanced cancer, abnormal sleep patterns may contribute to poor quality of life, but the impact of opioid-related sleep disorders has not been explored in detail in these patients. OBJECTIVE To document sleep and respiratory patterns in patients with cancer, receiving a range of opioids, determine factors that contribute to severity of central or obstructive apnea, and to what extent these contribute to sleep disturbance. METHODS Adults with advanced cancer admitted to a palliative care service underwent a sleep analysis by an unattended polysomnography. Total sleep time, apnea hypopnea index, central apnea index, obstructive apnea hypopnea index, arousal index, and oxygen desaturation were measured. Baseline assessment included body habitus, Mallampati score, comorbidity indices, concomitant medications, and the Berlin questionnaire. Epworth Sleepiness Scale, Stanford Sleepiness Scale, and Wu cancer fatigue scales were documented. RESULTS Twenty-eight patients were studied, including 25 receiving opioids. In the latter group, the apnea hypopnea index was mildly abnormal in six patients and severely abnormal in 10 patients. Central apnea index and obstructive apnea hypopnea index were abnormal in nine and 17 patients, respectively. There was no significant correlation between opioid dose and polysomnographic results. CONCLUSION In patients with advanced cancer receiving opioid analgesia, there was a high prevalence of respiratory disturbance, both central and obstructive, and deranged sleep patterns. Addressing sleep-disordered breathing in cancer patients has the potential to improve daytime drowsiness and quality of life.