Biomedical subjects

Niels G Becker

Publications and source records attributed to Niels G Becker.

15 recordsLinked to original sources

PubMed2007

An analysis for a cross-over cohort study with an application to the study of triggers of Menière's disease.

When studying the effect of a transient exposure on the risk of a rare illness, for time and cost effectiveness it is desirable to follow a cohort of individuals who are 'prone' to the illness over an observation period. In this paper, we present a method of analysis for data arising from such a study. The proposed method can be used to estimate the relative risk of an exposure triggering the illness and the distribution of the time delay from exposure to the onset of illness. The model is extended to include covariate effects and to the situation where there are two types of exposure. For the two types of exposures situation, a model to handle a possible synergism of the exposures is proposed. Finally, the method is applied to study the potential triggers of attacks of Menière's disease.

Acute Disease↗

PubMed2007

The waiting time for inter-country spread of pandemic influenza.

BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.

Disease Outbreaks↗

PubMed2006

Low-level fluoroquinolone resistance among Campylobacter jejuni isolates in Australia.

BACKGROUND: Ciprofloxacin-resistant Campylobacter jejuni isolates obtained from infected patients in Australia have not been detected in studies of isolates from specific geographic areas. The Australian government has prohibited the use of fluoroquinolone in food-producing animals. To assess the impact of this policy, we have examined the antimicrobial susceptibility of isolates from 5 Australian states. METHODS: We conducted a period-prevalence survey of the susceptibility of C. jejuni isolates to 10 antimicrobial agents. C. jejuni isolates obtained from 585 patients from 5 Australian states (Queensland, South Australia, Tasmania, Victoria, and Western Australia) were identified by means of notifiable disease databases and were systematically selected from September 2001 to August 2002. RESULTS: Among locally acquired infections, only 2% of isolates (range, 0%-8% in different states) were resistant to ciprofloxacin. The locally acquired isolates also exhibited resistance to sulfisoxazole (55%), ampicillin (46%), roxithromycin (38%), tetracycline (7%), nalidixic acid (6%), chloramphenicol (3%), erythromycin (3%), gentamicin (2%), and kanamycin (0.2%). Treatment with antimicrobial agents in the 4 weeks before onset was not associated with ciprofloxacin resistance. CONCLUSIONS: The very low level of ciprofloxacin resistance in C. jejuni isolates likely reflects the success of Australia's policy of restricting use of fluoroquinolones in food-producing animals.

Australia↗

PubMed2006

Estimating vaccine effects from studies of outbreaks in household pairs.

The traditional way to measure efficacy of a vaccine, with respect to reduced susceptibility and reduced infectivity once infected, is to look at relative attack rates. Although straightforward to apply, such measures do not take disease transmission into account, with the consequence that they can depend strongly on the community setting, the duration of the study period, the way participants are recruited into the study and the virulence of the infection. Sometimes they give a very misleading assessment of the vaccine, as we illustrate by examples. Here measures of vaccine efficacy are considered that avoid these defects, and estimation procedures are presented for studies based on outbreaks in household pairs. Such studies enable estimation of vaccine effects on susceptibility, infectivity and transmission. We propose that the vaccine efficacy measures be estimated, without making any assumptions about the nature of the vaccine response, by consistent estimates of bounds for the measures.

Disease Outbreaks↗

PubMed2006

Control of transmission with two types of infection.

The effectiveness of a vaccination strategy to control transmission of an infectious disease depends on the way vaccine doses are distributed to individuals in a community of households. Here we show that this dependence is more complicated when acquisition and severity of illness are determined by the size of the infecting dose, as is thought to be the case for measles and varicella. Two alternative formulations for the way vaccination changes an individual's susceptibility and infectivity show that vaccination coverage, the nature of the vaccine response and the distribution of household size also have a big impact on which strategy is more effective. These judgements are made by comparing the post-vaccination reproduction numbers corresponding to different vaccination strategies.

Communicable Diseases↗

PubMed2006

Prevalence of heart failure and systolic ventricular dysfunction in older Australians: the Canberra Heart Study.

OBJECTIVE: To estimate the prevalence of heart failure (HF) and left ventricular (LV) systolic dysfunction in a population-based sample of older Australians. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey of 2000 randomly selected residents of Canberra, aged 60-86 years, conducted between February 2002 and June 2003. Participants were assessed by history, physical examination by a cardiologist, and echocardiography. MAIN OUTCOME MEASURES: Age- and sex-specific prevalence rates of clinical HF and LV systolic dysfunction (defined as LV ejection fraction < or = 50%). RESULTS: Of 1846 people eligible for our study, 1388 (75%) agreed to participate and 1275 completed all investigations (mean age, 69.4 years; 50% men). In the study sample, 72 subjects (5.6%; 95% CI, 4.4%-7.1%) had clinical HF that had been previously diagnosed and was confirmed by our assessment. A further 0.6% (95% CI, 0.3%-1.2%) had undiagnosed clinical HF (ie, evidence of structural heart disease and symptoms/signs of cardiac insufficiency without a previous diagnosis of clinical HF). Thus, the overall prevalence of clinical HF in the sample was 6.3% (95% CI, 5.0%-7.7%). Clinical HF increased in prevalence with advancing age (a 4.4-fold increase from the 60-64-years age group to the 80-86-years age group; P < 0.0001). Of the 75 subjects (5.9%; 95% CI, 4.7%-7.3%) with LV systolic dysfunction, 44 (59%) were in the preclinical stage of disease. CONCLUSION: Diagnosed HF cases represent the "tip of the iceberg" for the national burden of HF and LV systolic dysfunction. Clinically identifiable HF cases can remain undiagnosed, and the majority of people with LV systolic dysfunction are in a preclinical stage of the disease.

Age Factors↗

PubMed2006

Population-based detection of systolic and diastolic dysfunction with amino-terminal pro-B-type natriuretic peptide.

BACKGROUND: There is limited information regarding the clinical utility of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) for the detection of left ventricular (LV) dysfunction in the community. We evaluated predictors of circulating NT-proBNP levels and determined the utility of NT-proBNP to detect systolic and diastolic LV dysfunction in older adults. METHODS: A population-based sample of 1229 older adults (mean age 69.4 years, 50.1% women) underwent echocardiographic assessment of cardiac structure and function and measurement of circulating NT-proBNP levels. RESULTS: Predictors of NT-proBNP included age, female sex, body mass index, and cardiorenal parameters (diastolic dysfunction [DD] severity; LV mass and left atrial volume; right ventricular overload; decreasing ejection fraction [EF] and creatinine clearance). The performance of NT-proBNP to detect any degree of LV dysfunction, including mild DD, was poor (area under the curve 0.56-0.66). In contrast, the performance of NT-proBNP for the detection of EF < or = 40% and moderate-severe DD was strong with area under the curve of > 0.90 regardless of age and sex; history of hypertension, diabetes, coronary artery disease; or body mass category. The ability of NT-proBNP to detect EF < or = 40% and/or moderate-severe DD was optimized by using age/sex-specific limits. Of "false-positive" tests, 88% (124/141) were explained after considering cardiorenal determinants of NT-proBNP levels. CONCLUSIONS: Amino-terminal pro-B-type natriuretic peptide is a suboptimal marker of mild LV dysfunction, but performs strongly as a marker of EF < or = 40% and/or moderate-severe DD in the community. Most subjects with a positive NT-proBNP test, using age/sex-specific cutoffs, had prognostically significant abnormalities of cardiac structure or function.

Aged↗

PubMed2006

Air travel and the risk of deep vein thrombosis.

BACKGROUND: The magnitude of the risk of venous thromboembolism (VTE) following air travel has been difficult to resolve due to a lack of adequate data. We determine the association more precisely by using a large dataset and an improved method of analysis. METHOD: Data on air-travel history for each of 5,196 patients hospitalised for VTE in Western Australia from 1981 to 1999 is analysed using a log-linear regression model for the probability that a flight triggers VTE and for the baseline hazard rate for VTE hospitalisation. RESULTS: The risk of VTE being triggered on the day of an international flight relative to a flight-free day is 29.8 (95% CI 22.4-37.3). Evidence that this relative risk depends on age is weak (p = 0.06), but the absolute risk clearly depends on age. The annual relative risk for an individual taking one international flight, compared with an individual of the same age taking no flight, is estimated to be 1.079. The estimated median time from flight to hospital admission is 4.7 days (95% CI 3.8-5.6) and the estimated 95th percentile is 13.3 (95% CI 10.3-16.8). CONCLUSIONS: Evidence for an association between international air travel and VTE hospitalisation is strong and passengers should be advised on ways to minimise risk during long flights. While 29.8 is a large relative risk, it must be remembered that the baseline risk is very small and the relative risk applies only to the unobserved triggering of a deep vein thrombosis episode on the day of travel; the consequent hospitalisation occurs on one of numerous ensuing days.

Aviation↗

PubMed2005

Analysis of a potential trigger of an acute illness.

Sometimes certain short-term risk exposures are postulated to act as a trigger for the onset of a specific acute illness. When the incidence of the illness is low it is desirable to investigate this possible association using only data on cases detected during a specific observation period. Here we propose an analysis for such a study based on a model expressed in terms of the probability that the exposure triggers the illness and a random delay from a triggered illness until its diagnosis. Both the natural hazard rate for the illness and the probability that the exposure triggers the illness are assumed to be small and possibly dependent on age and covariates such as sex and duration or severity of the exposure. The method of analysis is illustrated with a study of the association between long flights and hospitalization for venous thromboembolism.

Acute Disease↗

PubMed2005

Controlling emerging infectious diseases like SARS.

To control emerging infectious diseases like SARS, it is necessary to resort to basic control measures that limit exposures to infectious individuals. These measures include isolating cases at diagnosis, quarantining household members and tracing contacts of diagnosed cases, providing the community with advice on how to reduce exposures, and closing schools. To justify such intervention it is important to understand how well each of these measures helps to limit transmission. In this paper, we determine the effect of a number of different interventions on the effective reproduction number and estimate requirements to achieve elimination of the infectious disease. We find that the strategy of tracing and quarantining contacts of diagnosed cases can be very successful in reducing transmission.

Australia↗

PubMed2005

Monitoring measles elimination in Victoria.

OBJECTIVES: To weigh the evidence from outbreak data that Victoria has achieved, and is maintaining, elimination of measles. To identify age groups that measles vaccination has not protected adequately. METHODS: Data on observed measles outbreaks in Victoria since the start of 1998 are used to estimate the reproduction number of cases, and the probability that it is maintained below unity, its threshold value for elimination. The relative susceptibility to measles is estimated as a function of age, with confidence intervals. RESULTS: Seventeen measles introductions led to secondary cases, while 22 were single-case introductions. From these, the probability that the reproduction number for cases exceeds unity is estimated to be 0.044, or less, depending on assumptions made. There is no evidence that the reproduction number increased over time. Those aged between 19 and 32 years were most susceptible, followed by those in the first and second year of life. CONCLUSIONS: The data provide strong evidence that Victoria has maintained elimination of measles over the period 1998 to mid-2003. There is scope to improve the immunisation coverage. It is not clear how much outbreak intervention is contributing to the success in achieving apparent elimination. IMPLICATIONS: To prevent importations from causing a major epidemic of measles, Victoria must maintain its immunisation coverage and outbreak control at current levels, or better. It is important to monitor the control of measles even when elimination is achieved.

Adolescent↗

PubMed2004

The effect of transient exposures on the risk of an acute illness with low hazard rate.

There are many situations where intermittent short-term exposures of a certain kind are thought to temporarily enhance the risk of onset of an adverse health event (illness). When the hazard rate of the illness is small it is desirable to investigate this possible association using only data on cases occurring in a finite observation period. Here we extend a method for such an analysis by allowing the baseline hazard for the illness to depend on the increasing age over the observation period and using age at the times of exposure, a time dependent variable, as a covariate in the effect of the transient exposure. The method is illustrated with a study of the possible association of long-haul air travel and hospitalization for venous thromboembolism over an observation period of 19 years. It is demonstrated that allowing for aging over the observation period can avoid bias in the estimated effect size when the baseline hazard for the illness increases with age and exposures occur irregularly over time.

Adolescent↗

PubMed2004

Does ambient temperature affect foodborne disease?

BACKGROUND: Foodborne illness is a significant public health issue in most countries, including Australia. We examined the association between temperature and salmonellosis notifications, and compared these associations for 5 Australian cities. METHODS: Log-linear models describing monthly salmonellosis notifications in terms of calendar time and monthly average temperatures were fitted over the period 1991 to 2001 for each city. We used a negative binomial chance model to accommodate overdispersion in the counts. RESULTS: The long-term trend showed an increase in salmonellosis notifications in each of the 5 cities. There was a positive association between monthly salmonellosis notifications and mean monthly temperature of the previous month in every city. Seasonal patterns in salmonellosis notifications were fully explained by changes in temperature. DISCUSSION: The strength of the association, the consistency across 5 cities, and a plausible biologic pathway suggest that higher ambient temperatures are a cause of higher salmonellosis notifications. The lag of 1 month suggests that temperature might be more influential earlier in the production process rather than at the food preparation stage. This knowledge can help to guide policy on food preparation and distribution. It also suggests a basis for an early warning system for increased risk from salmonellosis, and raises yet another possible health problem with global warming.

Australia↗

PubMed2003

Age-specific back-projection of HIV diagnosis data.

A method for reconstructing the HIV infection curve from data on both HIV and AIDS diagnoses is enhanced by using age as a covariate and by using the diagnosis data to estimate parameters that were previously assumed known. Maximum likelihood estimation is used for parameters of the induction distribution. Each of the set of parameters that specify the baseline rate of infection over time and the set of parameters giving the relative susceptibility over age are estimated by maximizing the likelihood subject to a smoothness requirement. We find that estimating the extra parameters is feasible, producing estimates with good precision. Including age as a covariate gives 90 per cent confidence intervals for the HIV incidence curve that are about 20 per cent narrower than those obtained when age data are not used.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Estimating vaccine effects on transmission of infection from household outbreak data.

This article is concerned with a method for making inferences about various measures of vaccine efficacy. These measures describe reductions in susceptibility and in the potential to transmit infection. The method uses data on household outbreaks; it is based on a model that allows for transmission of infection both from within a household and from the outside. The use of household data is motivated by the hope that these are informative about vaccine-induced reduction of the potential to transmit infection, as household outbreaks contain some information about the possible source of infection. For illustration, the method is applied to observed data on household outbreaks of smallpox. These data are of the form needed and the number of households is of a size that can be managed in a vaccine trial. It is found that vaccine effects, such as the mean reduction in susceptibility and the mean reduction in the potential to infect others, per infectious contact, can be estimated with precision. However, a more specific parameter reflecting the reduction in infectivity for individuals partially responding to vaccination is not estimated well in the application. An evaluation of the method using artificial data shows that this parameter can be estimated with greater precision when we have outbreak data on a large number of small households.

Biometry↗