Non-Common-Sensical: An Inference of Guilt to Sanction Non-Compliance

The Criminal Procedure (Reform and Modernisation) Bill is currently before the New Zealand Parliament. The Bill will implement mandatory defence disclosure of the issues in dispute at a pre-trial hearing stage. This paper addresses the enforcement mechanism adopted by the Bill – an inference of guilt from non-compliance – and examines the suitability of the inference as an enforcement mechanism. It outlines the compatibility of the inference with the existing framework of evidence law in New Zealand and suggests changes to the Bill that are necessary to ensure the inference is exercised in a consistent and justifiable way

Peregrine Falcons Nest Successfully During Reconstruction of Bridge Over Ohio River

Peregrine falcons (Falco peregrinus) often nest on bridges over rivers and other waterways, resulting in the need for mitigation planning for bridge maintenance and reconstruction. However, mitigation guidelines for peregrine falcon nests during bridge reconstruction are lacking in the literature. In this paper, we describe the monitoring, spatial, and temporal buffers, nest box installation, and other methods that allowed peregrine falcons to nest successfully on the Milton-Madison (US-421) Bridge during demolition and reconstruction. Construction activities occurred over a 4-year period (2011–2014), and coordination with local road departments and contracted engineers was necessary to accommodate the falcon nest. Nonetheless, construction activities were able to progress without causing major construction expense or delays, and the nesting falcons were able to fledge 14 young during the project

Tradeoffs May Counteract Effects of Telecommunication Towers on Osprey Nesting

The number of telecommunication towers (TCTs) throughout the United States has and continues to increase exponentially. Increased TCT placement has been implicated in local population increases in platform nesting birds such as ospreys (Pandion haliaetus). However, osprey use of artificial structures can cause conflicts with humans because of economic costs and risks to human safety. Managers require better information regarding the effect of artificial nesting surfaces, such as TCTS, on osprey reproduction to make informed decisions regarding species conservation and to mitigate potential conflicts. The objective of our study was to evaluate the influence of TCTs on osprey productivity and adult nesting behaviors. From March to July 2019, we monitored 30 osprey nests located in western Kentucky, USA, on TCTs (n = 11), navigation channel markers (NCMs; n = 10), and natural surfaces (NATs; n = 9). We found no differences in nest success, productivity, or the proportion of male ospreys perched at the nest between surface types. Nests on NCMs received 1.9–2.1 times more fish than nests on NATs and TCTs, respectively. Moreover, NCMs experienced 5.4–8.0 times more disturbances per hour compared to NATs and TCTs, respectively. Our data suggest ospreys nesting on TCTs are productive contributors to local populations. We recommend deterrence of osprey nesting should be focused on locations that are unsafe for ospreys and/or pose insurmountable problems for communication infrastructure

Stopping long-acting beta2-agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids.

BACKGROUND: Poorly controlled asthma often leads to preventable exacerbations that require additional medications, as well as unscheduled hospital and clinic visits.Long-acting beta2-agonists (LABA) are commonly given to adults with asthma whose symptoms are not well controlled by inhaled corticosteroids (ICS). US and UK regulators have issued warnings for LABA in asthma, and now recommend they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". OBJECTIVES: To compare cessation of long-acting beta2-agonists (LABA) versus continued use of LABA/inhaled corticosteroids (LABA/ICS) for adults whose asthma is well controlled, and to determine whether stopping LABA:1. results in loss of asthma control or deterioration in quality of life;2. increases the likelihood of asthma attacks or 'exacerbations'; or3. increases or decreases the likelihood of serious adverse events of any cause. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews and manufacturers' trial registries (GlaxoSmithKline (GSK) and AstraZeneca). We searched all databases from their inception to April 2015, and we imposed no restriction on language of publication. SELECTION CRITERIA: We looked for parallel randomised controlled trials (RCTs) of at least eight weeks' duration, in which adults whose asthma was well controlled by any dose of ICS+LABA combination therapy were randomly assigned to (1) step-down therapy to ICS alone versus (2) continuation of ICS and LABA. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all records identified by the search strategy. We used an Excel extraction tool to manage searches, document reasons for inclusion and exclusion and extract descriptive and numerical data from trials meeting inclusion criteria.Prespecified primary outcomes were (1) exacerbations requiring oral steroids, (2) asthma control and (3) all-cause serious adverse events. MAIN RESULTS: Six randomised, double-blind studies between 12 and 24 weeks' long met the inclusion criteria. Five studies contributed data to the meta-analysis, assigning 2781 people with stable asthma to the comparison of interest. The definition of stable asthma and inclusion criteria varied across studies, and Global Initiative for Asthma (GINA) criteria were not used. Risk of bias across studies was generally low, and most evidence was rated as moderate quality.Stopping LABA might increase the number of people having exacerbations and requiring oral corticosteroids (odds ratio (OR) 1.74, 95% confidence interval (CI) 0.83 to 3.65; participants = 1257; studies = 4), although the confidence intervals did not exclude the possibility that stopping LABA was beneficial; over 17 weeks, 19 people per 1000 who continued their LABA had an exacerbation, compared with 32 per 1000 when LABA were stopped (13 more per 1000, 95% CI 3 fewer to 46 more).People who stopped LABA had worse scores on the Asthma Control Questionnaire (mean difference (MD) 0.24, 95% CI 0.13 to 0.35; participants = 645; studies = 3) and on measures of asthma-related quality of life (standardised mean difference (SMD) 0.36, 95% CI 0.15 to 0.57; participants = 359; studies = 2) than those who continued LABA, but the effects were not clinically relevant.Too few events occurred for investigators to tell whether stopping LABA has a greater effect on serious adverse events compared with continuing LABA+ICS (OR 0.82, 95% CI 0.28 to 2.42; participants = 1342; studies = 5), and no study reported exacerbations requiring an emergency department visit or hospitalisation as a separate outcome. Stopping LABA may result in fewer adverse events of any kind compared with continuing, although the effect was not statistically significant (OR 0.83, 95% CI 0.66 to 1.05; participants = 1339; studies = 5), and stopping LABA made people more likely to withdraw from participation in research studies (OR 1.95, 95% CI 1.47 to 2.58; participants = 1352; studies = 5). AUTHORS' CONCLUSIONS: This review suggests that stopping LABA in adults who have stable asthma while they are taking a combination of LABA and ICS inhalers may increase the likelihood of asthma exacerbations that require treatment with oral corticosteroids, but this is not certain. Stopping LABA may slightly reduce asthma control and quality of life, but evidence was insufficient to show whether this had an effect on important outcomes such as serious adverse events and exacerbations requiring hospital admission, and longer trials are warranted. Trialists should include patient-important outcomes such as asthma control and quality of life and should use validated measurement tools. Definitions of exacerbations should be provided

Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids.

BACKGROUND: Asthma is the most common chronic medical condition among children and is one of the most common causes of hospitalisation and medical visits. Poorly controlled asthma often leads to preventable exacerbations that require additional medications, hospital stays, or treatment in the emergency department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment for children with asthma whose symptoms are not well controlled on inhaled corticosteroids (ICS). The US Food and Drug Administration has issued a 'black box' warning for LABA in asthma, and now recommends that they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". OBJECTIVES: To compare the effect on asthma control and adverse effects of stepping down to inhaled corticosteroids (ICS)-only therapy versus continuing ICS plus LABA in children whose asthma is well controlled on combined ICS and LABA therapy. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, and also searched www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews, and manufacturers' trial registries (GlaxoSmithKline and AstraZeneca). We searched all databases from their inception to the present, and imposed no restriction on language of publication. The most recent search was done in April 2015. SELECTION CRITERIA: We looked for parallel randomised controlled trials of at least eight weeks' duration, available as published full text, abstract only, or unpublished data. We excluded studies including participants with other chronic respiratory comorbidities (for example bronchiectasis).We looked for studies in which children (18 years or younger) whose asthma was well controlled on any dose of ICS and LABA combination therapy were randomised to: a) step-down therapy to ICS alone or b) continued use of ICS and LABA.We included any dose of LABA (formoterol, salmeterol, vilanterol) and any dose of ICS (beclomethasone, budesonide, ciclesonide, mometasone, flunisolide, fluticasone propionate, fluticasone furoate, triamcinolone) delivered in a combination inhaler or in separate inhalers. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all records identified in the searches. We used a data extraction tool in Microsoft Excel to manage searches and document reasons for inclusion and exclusion, and to extract descriptive and numerical data from trials meeting the inclusion criteria.The prespecified primary outcomes were exacerbations requiring oral steroids, asthma control, and all-cause serious adverse events. MAIN RESULTS: Despite conducting extensive searches of electronic databases, trial registries and manufacturers' websites we identified no trials matching the inclusion criteria.After removing duplicates, we screened 1031 abstracts, and assessed 43 full-text articles for inclusion. We identified several adult studies, which will be summarised in a separate review (Ahmad 2014). The most common reasons for exclusion after viewing full texts were 'wrong comparison' (n = 22) and 'adult population' (n = 18).Some adult studies recruited adolescents from age 15, but none reported data separately for those under 18. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials to inform the discontinuation of LABAs in children once asthma control is achieved with ICS plus LABA. It is disappointing that such an important issue has not been studied, and a randomised double-blind trial recruiting children who are controlled on ICS plus LABA is warranted. The study should be large enough to assess children of different ages, and to measure the important safety and efficacy outcomes suggested in this review over at least six months.The only randomised evidence for stopping LABA has been conducted in adults; it will be summarised in a separate review

Pharmacogenetics of inhaled long-acting beta2-agonists in asthma:a systematic review

Background: Long-acting beta2-agonists (LABA) are recommended in asthma therapy; however, not all asthma patients respond well to LABA. We performed a systematic review on genetic variants associated with LABA response in patients with asthma. Methods: Articles published until April 2017 were searched by two authors using PubMed and EMBASE. Pharmacogenetic studies in patients with asthma and LABA response as an outcome were included. Results: In total, 33 studies were included in this systematic review; eight focused on children (n = 6051). Nineteen studies were clinical trials, while 14 were observational studies. Studies used different outcomes to define LABA response, for example, lung function measurements (FEV1, PEF, MMEF, FVC), exacerbations, quality of life, and asthma symptoms. Most studies (n = 30) focused on the ADRB2 gene, encoding the beta2-adrenergic receptor. Thirty studies (n = 14 874) addressed ADRB2 rs1042713, 7 ADRB2 rs1042714 (n = 1629), and 3 ADRB2 rs1800888 (n = 1892). The association of ADRB2 rs1042713 and rs1800888 with LABA response heterogeneity was successfully replicated. Other variants were only studied in three studies but not replicated. One study focused on the ADCY9 gene. Five studies and a meta-analysis found an increased risk of exacerbations in pediatrics using LABA carrying one or two A alleles (OR 1.52 [1.17; 1.99]). These results were not confirmed in adults. Conclusions: ADRB2 rs1042713 variant is most consistently associated with response to LABA in children but not adults. To assess the clinical value of ADRB2 rs1042713 in children with asthma using LABA, a randomized clinical trial with well-defined outcomes is needed

Inhaled steroids with and without regular salmeterol for asthma: serious adverse events.

BACKGROUND: Epidemiological evidence has suggested a link between use of beta₂-agonists and increased asthma mortality. Much debate has surrounded possible causal links for this association, and whether regular (daily) long-acting beta₂-agonists (LABAs) are safe, particularly when used in combination with inhaled corticosteroids (ICSs). This is an update of a Cochrane Review that now includes data from two large trials including 11,679 adults and 6208 children; both were mandated by the US Food and Drug Administration (FDA).  OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events (SAEs) in trials that randomised participants with chronic asthma to regular salmeterol and ICS versus the same dose of ICS. SEARCH METHODS: We identified randomised trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trials registers for unpublished trial data. We also checked FDA submissions in relation to salmeterol. The date of the most recent search was 10 October 2018. SELECTION CRITERIA: We included parallel-design randomised trials involving adults, children, or both with asthma of any severity who were randomised to treatment with regular salmeterol and ICS (in separate or combined inhalers) versus the same dose of ICS of at least 12 weeks in duration. DATA COLLECTION AND ANALYSIS: We conducted the review according to standard procedures expected by Cochrane. We obtained unpublished data on mortality and SAEs from the sponsors, from ClinicalTrials.gov, and from FDA submissions. We assessed our confidence in the evidence according to current GRADE recommendations. MAIN RESULTS: We have included in this review 41 studies (27,951 participants) in adults and adolescents, along with eight studies (8453 participants) in children. We judged that the overall risk of bias was low for all-cause events, and we obtained data on SAEs from all study authors. All except 542 adults (and none of the children) were given salmeterol and fluticasone in the same (combination) inhaler.DeathsEleven of a total of 14,233 adults taking regular salmeterol and ICS died, as did 13 of 13,718 taking regular ICS at the same dose. The pooled Peto odds ratio (OR) was 0.80 (95% confidence interval (CI) 0.36 to 1.78; participants = 27,951; studies = 41; I² = 0%; moderate-certainty evidence). In other words, for every 1000 adults treated for 25 weeks, one death occurred among those on ICS alone, and the corresponding risk among those taking salmeterol and ICS was also one death (95% CI 0 to 2 deaths).No children died, and no adults or children died of asthma, so we remain uncertain about mortality in children and about asthma mortality in any age group.Non-fatal serious adverse eventsA total of 332 adults receiving regular salmeterol with ICS experienced a non-fatal SAE of any cause, compared to 282 adults receiving regular ICS. The pooled Peto OR was 1.14 (95% CI 0.97 to 1.33; participants = 27,951; studies = 41; I² = 0%; moderate-certainty evidence). For every 1000 adults treated for 25 weeks, 21 adults on ICS alone had an SAE, and the corresponding risk for those on salmeterol and ICS was 23 adults (95% CI 20 to 27).Sixty-five of 4229 children given regular salmeterol with ICS suffered an SAE of any cause, compared to 62 of 4224 children given regular ICS. The pooled Peto OR was 1.04 (95% CI 0.73 to 1.48; participants = 8453; studies = 8; I² = 0%; moderate-certainty evidence). For every 1000 children treated for 23 weeks, 15 children on ICS alone had an SAE, and the corresponding risk for those on salmeterol and ICS was 15 children (95% CI 11 to 22).Asthma-related serious adverse eventsEighty and 67 adults in each group, respectively, experienced an asthma-related non-fatal SAE. The pooled Peto OR was 1.15 (95% CI 0.83 to 1.59; participants = 27,951; studies = 41; I² = 0%; low-certainty evidence). For every 1000 adults treated for 25 weeks, five receiving ICS alone had an asthma-related SAE, and the corresponding risk among those on salmeterol and ICS was six adults (95% CI 4 to 8).Twenty-nine children taking salmeterol and ICS and 23 children taking ICS alone reported asthma-related events. The pooled Peto OR was 1.25 (95% CI 0.72 to 2.16; participants = 8453; studies = 8; I² = 0%; moderate-certainty evidence). For every 1000 children treated for 23 weeks, five receiving an ICS alone had an asthma-related SAE, and the corresponding risk among those receiving salmeterol and ICS was seven children (95% CI 4 to 12). AUTHORS' CONCLUSIONS: We did not find a difference in the risk of death or serious adverse events in either adults or children. However, trial authors reported no asthma deaths among 27,951 adults or 8453 children randomised to regular salmeterol and ICS or ICS alone over an average of six months. Therefore, the risk of dying from asthma on either treatment was very low, but we remain uncertain about whether the risk of dying from asthma is altered by adding salmeterol to ICS.Inclusion of new trials has increased the precision of the estimates for non-fatal SAEs of any cause. We can now say that the worst-case estimate is that at least 152 adults and 139 children must be treated with combination salmeterol and ICS for six months for one additional person to be admitted to the hospital (compared to treatment with ICS alone). These possible risks still have to be weighed against the benefits experienced by people who take combination treatment.However more than 90% of prescribed treatment was taken in the new trials, so the effects observed may be different from those seen with salmeterol in combination with ICS in daily practice

State of the science 60th anniversary review

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60971/1/23643_ftp.pd