Gerben Keijzers

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

BACKGROUND Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each days delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each days delay). INTERPRETATION We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING F Hoffmann-La Roche.

Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial

STUDY OBJECTIVE We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter. METHODS This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion. RESULTS There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups. CONCLUSION We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered.

Long-term results of lower energy transurethral microwave thermotherapy

PURPOSE We evaluate long-term results of lower energy transurethral microwave thermotherapy (Prostasoft 2.0*) and identify pretreatment characteristics that predict a favorable outcome. MATERIALS AND METHODS Between December 1990 and December 1992, 231 patients with lower urinary tract symptoms were treated with lower energy transurethral microwave thermotherapy. Subjective and objective voiding parameters were collected from medical records and a self-administered questionnaire. Kaplan-Meier plots were constructed to assess the risk of re-treatment. RESULTS Of the patients 41% underwent invasive re-treatment within 5 years of followup and 17% were re-treated with medication. The re-treatment-free period was somewhat longer in patients with a peak flow rate greater than 10 ml. per second, a Madsen score 15 or less, a post-void residual volume 100 ml. or less and age greater than 65 years at baseline. Prostate volume did not modify the outcome. No incontinence was caused by transurethral microwave thermotherapy, 8% had recurrent urinary tract infection and 8% had retrograde ejaculation. Only 1 patient had a urethral stricture after transurethral microwave thermotherapy. CONCLUSIONS At 5 years after transurethral microwave thermotherapy 41% of the patients received instrumental treatment. Patients with a lower Madsen score and lower residual volume, and those with higher peak flow and age were somewhat better responders to lower energy transurethral microwave thermotherapy.

How would Australian hospital staff react to an avian influenza admission, or an influenza pandemic?

Objective:  To estimate the expected staff absentee rates and work attitudes in an Australian tertiary hospital workforce in two hypothetical scenarios: (i) a single admission of avian influenza; and (ii) multiple admissions of human pandemic influenza.

The effect of tertiary surveys on missed injuries in trauma: a systematic review

BackgroundTrauma tertiary surveys (TTS) are advocated to reduce the rate of missed injuries in hospitalized trauma patients. Moreover, the missed injury rate can be a quality indicator of trauma care performance. Current variation of the definition of missed injury restricts interpretation of the effect of the TTS and limits the use of missed injury for benchmarking. Only a few studies have specifically assessed the effect of the TTS on missed injury. We aimed to systematically appraise these studies using outcomes of two common definitions of missed injury rates and long-term health outcomes.MethodsA systematic review was performed. An electronic search (without language or publication restrictions) of the Cochrane Library, Medline and Ovid was used to identify studies assessing TTS with short-term measures of missed injuries and long-term health outcomes. ‘Missed injury’ was defined as either: Type I) any injury missed at primary and secondary survey and detected by the TTS; or Type II) any injury missed at primary and secondary survey and missed by the TTS, detected during hospital stay. Two authors independently selected studies. Risk of bias for observational studies was assessed using the Newcastle-Ottawa scale.ResultsTen observational studies met our inclusion criteria. None was randomized and none reported long-term health outcomes. Their risk of bias varied considerably. Nine studies assessed Type I missed injury and found an overall rate of 4.3%. A single study reported Type II missed injury with a rate of 1.5%. Three studies reported outcome data on missed injuries for both control and intervention cohorts, with two reporting an increase in Type I missed injuries (3% vs. 7%, P<0.01), and one a decrease in Type II missed injuries (2.4% vs. 1.5%, P=0.01).ConclusionsOverall Type I and Type II missed injury rates were 4.3% and 1.5%. Routine TTS performance increased Type I and reduced Type II missed injuries. However, evidence is sub-optimal: few observational studies, non-uniform outcome definitions and moderate risk of bias. Future studies should address these issues to allow for the use of missed injury rate as a quality indicator for trauma care performance and benchmarking.

Clinical diagnostic criteria for isolating patients admitted to hospital with suspected pandemic influenza.

Australian hospitals have now experienced the fi rst wave of pandemic H1N1 infl uenza during a southern hemisphere winter. Patients admitted to Australian hospitals with suspected pandemic infl uenza during this period were identifi ed by use of approved national clinical diagnostic criteria. However, the imprecise nature of clinical diagnosis limited the ability of hospitals to isolate infectious patients eff ectively before the laboratory confi rmation of infection (which typically takes a minimum of 48 h). Concern about our reliance on these criteria to isolate potentially infectious patients led us to analyse our early experience with pandemic infl uenza at the two teaching hospitals in the Gold Coast region of Queensland. We collected nasopharyngeal and throat specimens and reviewed clinical and laboratory data on all 346 patients admitted to the hospitals with acute respiratory disease during the period from May 24 to Aug 16, 2009. Pandemic H1N1 infl uenza virus RNA was detected in specimens collected from 106 of 346 patients (31%). On the basis of our experience, we compared the performance of Australian clinical diagnostic criteria with those of WHO, the US Centers for Disease Control and Prevention (CDC), and the UK Health Protection Agency (HPA; table). We make the following observations: (1) Criteria that rely on documented fever (eg, those of WHO and CDC) sacrifi ce sensitivity for specifi city. In our recent experience, 41 of 106 admitted patients (39%) with laboratory-confi rmed pandemic infl uenza did not have any tempera ture recorded above 37·8°C at any stage during their admission. Such criteria are simply not sensitive enough to support good hospital infection control practice. (2) Criteria that include a “history” of fever and respiratory symptoms rather than a documented fever (eg, those of the HPA and the Australian Government Department of Health and Ageing) are adequately sensitive to the diagnosis of pandemic infl uenza. However, the resulting lack of specifi city overwhelmed the ability of our hospitals to isolate suspected cases and resulted in cohorting of infected cases with wrongly suspected cases. (3) Age seems to be a useful criterion by which to discriminate pandemic infl uenza (H1N1) from other causes of acute respiratory disease necessitating hospital admission. Only four of 106 patients admitted with the infection were older than 65 years in our population. 80 (33%) of 240 patients admitted with acute respiratory disease not due to pandemic infl uenza were older than 65 years. Given the limitations of existing criteria, we have adopted a modifi ed approach with better sensitivity and specifi city for the purpose of isolating patients admitted to hospital during the pandemic: age less than 65 years and history suggestive of fever and cough or sore throat.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

Public use and perceptions of emergency departments: A population survey

To inform demand management strategies aimed at reducing congestion in EDs by: (i) identifying public use of EDs, decision‐making and reasons; and (ii) measuring acceptance of alternative care models.

Clinical research priorities in emergency medicine

To determine the clinical research priorities of Fellows of the Australasian College for Emergency Medicine (ACEM) in order to inform the strategic research agenda specific to multicentre clinical research.

Best-practice pain management in the emergency department: A cluster-randomised, controlled, intervention trial

We aimed to provide ‘adequate analgesia’ (which decreases the pain score by ≥2 and to <4 [0–10 scale]) and determine the effect on patient satisfaction.