In 2011, Dutch animal production sectors started recording veterinary antimicrobial consumption. These data are used by the Netherlands Veterinary Medicines Authority to create transparency in and ...define benchmark indicators for veterinary consumption of antimicrobials. This paper presents the results of sector wide consumption of antimicrobials, in the form of prescriptions or deliveries, for all pig, veal calf, and broiler farms. Data were used to calculate animal defined daily dosages per year (ADDD/Y) per pig or veal calf farm. For broiler farms, number of animal treatment days per year was calculated. Furthermore, data were used to calculate the consumption of specific antimicrobial classes per administration route per pig or veal calf farm. The distribution of antimicrobial consumption per farm varied greatly within and between farm categories. All categories, except for rosé starter farms, showed a highly right skewed distribution with a long tail. Median ADDD/Y values varied from 1.2 ADDD/Y for rosé finisher farms to 83.2 ADDD/Y for rosé starter farms, with 28.6 ADDD/Y for white veal calf farms. Median consumption in pig farms was 9.3 ADDD/Y for production pig farms and 3.0 ADDD/Y for slaughter pig farms. Median consumption in broiler farms was 20.9 ATD/Y. Regarding specific antimicrobial classes, fluoroquinolones were mainly used on veal calf farms, but in low quantities: P75 range was 0 - 0.99 ADDD/Y, and 0 - 0.04 ADDD/Y in pig farms. The P75 range for 3(rd)/4(th)-generation cephalosporins was 0 - 0.07 ADDD/Y for veal calf farms, and 0 - 0.1 ADDD/Y for pig farms. The insights obtained from these results, and the full transparency obtained by monitoring antimicrobial consumption per farm, will help reduce antimicrobial consumption and endorse antimicrobial stewardship. The wide and skewed distribution in consumption has important practical and methodological implications for benchmarking, surveillance and future analysis of trends.
The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little ...information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention.
To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder.
Meta analysis of papers indexed for PubMed, ...Embase, and the abstracts of sleep and chronobiologic societies (1990-2009).
Individuals with delayed sleep phase disorder.
Administration of melatonin.
A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval CI: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83 -41.72 min). The wake-up time and total sleep time did not change significantly.
Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder.
To curb increasing resistance rates, responsible antimicrobial use (AMU) is needed, both in human and veterinary medicine. In human healthcare, antimicrobial stewardship programmes (ASPs) have been ...implemented worldwide to improve appropriate AMU. No ASPs have been developed for and implemented in companion animal clinics yet.
The objective of the present study was to implement and evaluate the effectiveness of an ASP in 44 Dutch companion animal clinics. The objectives of the ASP were to increase awareness on AMU, to decrease total AMU whenever possible and to shift AMU towards 1st choice antimicrobials, according to Dutch guidelines on veterinary AMU.
The study was designed as a prospective, stepped-wedge, intervention study, which was performed from March 2016 until March 2018. The multifaceted intervention was developed using previous qualitative and quantitative research on current prescribing behaviour in Dutch companion animal clinics. The number of Defined Daily Doses for Animal (DDDAs) per clinic (total, 1st, 2nd and 3rd choice AMU) was used to quantify systemic AMU. Monthly AMU data were described using a mixed effect time series model with auto-regression. The effect of the ASP was modelled using a step function and a change in the (linear) time trend.
A statistically significant decrease of 15% (7%-22%) in total AMU, 15% (5%-24%) in 1st choice AMU and 26% (17%-34%) in 2nd choice AMU was attributed to participation in the ASP, on top of the already ongoing time trends. Use of 3rd choice AMs did not significantly decrease by participation in the ASP. The change in total AMU became more prominent over time, with a 16% (4%-26%) decrease in (linear) time trend per year.
This study shows that, although AMU in Dutch companion animal clinics was already decreasing and changing, AMU could be further optimised by participation in an antimicrobial stewardship programme.
Rationale
Pharmacokinetics of melatonin in children might differ from that in adults.
Objectives
This study aims to establish a dose–response relationship for melatonin in advancing dim light ...melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI).
Methods
The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (
n
= 72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL.
Results
Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (
r
s
= −0.33,
p
= 0.022) and SO (
r
s
= −0.38,
p
= 0.004), whereas clock TOA was correlated with SO shift (
r
= −0.35,
p
= 0.006) and not with DLMO shift.
Conclusions
No dose–response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05–0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime.
Recent meta‐analyses on melatonin has raised doubts as to whether melatonin is effective in treating sleep problems in people without intellectual disabilities. This is in contrast to results of ...several trials on melatonin in treating sleep problems in individuals with intellectual disabilities. To investigate the efficacy of melatonin in treating sleep problems in individuals with intellectual disabilities, we performed a meta‐analysis of placebo‐controlled randomized trials of melatonin in individuals with intellectual disabilities and sleep problems. Data were selected from articles published on PubMed, Medline, and Embase between January 1990 and July 2008. We examined the influence of melatonin on sleep latency, total sleep time, and number of wakes per night. Quality of trials was assessed using the Downs and Black checklist. Nine studies (including a total of 183 individuals with intellectual disabilities) showed that melatonin treatment decreased sleep latency by a mean of 34 minutes (p<0.001), increased total sleep time by a mean of 50 minutes (p<0.001), and significantly decreased the number of wakes per night (p<0.05). Melatonin decreases sleep latency and number of wakes per night, and increases total sleep time in individuals with intellectual disabilities.
Indonesia has a large broiler industry with extensive antimicrobial use (AMU) according to empirical evidence. However, there are no quantitative data of on-farm AMU. Quantification of AMU at farm ...level is crucial to guide interventions on antimicrobial stewardship (AMS). The objective of this study was to compare on-farm AMU monitoring methods, to assess which monitoring method is best suited to gain insight in the quantitative AMU at farm level in medium-scale Indonesian broiler farms.
AMU was calculated using four different indicators-mg/PCU (mass-based), TF
(Treatment Frequency of Used Daily Dose, dose-based), TF
(Treatment Frequency of Defined Daily Dose, dose-based), and TF
(count-based)-for the total AMU of 98 production cycles with an average length of 30 days.
Broilers were exposed to an average of 10 days of antimicrobial treatments per production cycle, whereas 60.8% of the antimicrobials belonged to the Highest Priority Critically Important Antimicrobials (HPCIAs). For each pair of indicators, the Spearman rank correlation coefficient was calculated to assess if the production cycles were ranked consistently in increasing AMU across the different indicators. The correlation varied between 0.4 and 0.8.
This study illustrates the considerable difference in the ranking of AMU between the different indicators. In a setting comparable to medium-scale broiler farms in Indonesia, where resources are scarce and there is no professional oversight, the TF
method is best suitable. Before implementing an AMU monitoring method, careful consideration of the use-indicators is paramount to achieve fair benchmarking.
A 9-month-old German shepherd dog was examined because of a chronic cough, exercise intolerance and labored breathing, as well as recurrent episodes of lethargy with anorexia. Multifocal severe ...bronchiectasis and neutrophilic bronchitis was found with thoracic computed tomography and cytology of bronchoalveolar lavage fluid, respectively. While oral azithromycin was administered, clinical signs were absent. However, stopping azithromycin lead repeatedly to presumed bacterial pneumonia within 1-2 months. With sub-antimicrobial dosed oral doxycycline (initially 1.5 mg/kg once daily for 3 months, then 0.7-0.5 mg/kg once daily for 6 months), the dog remained free from clinical signs. Bronchiectasis is characterized by marked irreversible bronchial dilation. Accumulation of intraluminal mucopurulent material and neutrophilic inflammation cause chronic cough and recurrent bacterial pneumonia. For therapy, life-long oral antibiotics are recommended. Chronic antibiotic administration, however, can select resistant bacterial strains. Though both azithromycin and doxycycline possess anti-inflammatory effects, doxycycline has these off-target properties at a sub-antimicrobial dose. In this report, a chronic sub-antimicrobial dose of doxycycline resulted in the resolution of chronic cough, exercise intolerance and labored breathing, and prevented recurrence of suspected bacterial pneumonia in the long-term in a dog with severe bronchiectasis. Beneficial effect of doxycycline is probably related to its anti-inflammatory effects rather than its antimicrobial properties.
Antimicrobial use (AMU) in humans and animals facilitates the emergence of antimicrobial resistance (AMR). With increasing AMR being recognised as a major global threat for public health, responsible ...AMU is strongly advocated in both human and veterinary medicine. Knowledge on factors influencing antimicrobial prescribing behaviour of companion animal veterinarians is needed to promote responsible AMU in companion animals and to improve compliance with current legislation and guidelines. The present study aimed to quantitively investigate attitudes and perceptions of companion animal veterinarians towards AMU and AMR and to identify associations with demographic characteristics as possible explanatory variables. A self-administered questionnaire was developed based upon an earlier qualitative interview study, and 1608 potential participants (i.e. practising companion animal veterinarians) were invited. The questionnaire included questions addressing general descriptives of the respondents and questions with 6-point Likert scale statements, to assess attitudes towards AMU, AMR, factors influencing antimicrobial prescribing, and possible options to support responsible AMU.
The response rate was 32% (22% when complete questionnaires considered). Categorical Principal Component Analysis (CATPCA) was conducted on 76 Likert scale questions. This resulted in a final model with 37 questions explaining 38.7% of the variance of the question scores, with three underlying dimensions (“attitudinal profiles”). Additionally, general descriptives were added to the CATPCA as possible explanatory variables. The first dimension, related to “social responsibility” was positively associated with veterinarians working in clinics dedicated to companion animals, with veterinarians working in a referral clinic, and with more experienced veterinarians. The second dimension was related to “scepticism”, which was positively associated with being a male veterinarian and with more experienced veterinarians. The third dimension was related to “risk avoidance”, especially regarding surgical procedures, and was negatively associated with veterinarians working in clinics in urban areas and with veterinarians working part-time. Antimicrobial prescribing behaviour was self-reported to be well considered, and respondents did not see economic drivers as important influencing factors. The unwillingness of owners and financial constraints were perceived as important barriers for performing further diagnostics. To improve AMU, a multifaceted approach, taking differences between companion animal veterinarians (e.g., in experience and gender) and differences in work situation (e.g., full-time versus part-time) into account, should be directed at companion animal veterinarians and owners. Moreover, a joint and comprehensive effort of several stakeholders, like veterinary nurses, guideline developers, pharmaceutical industry, and providers of diagnostics, is needed to optimise AMU in companion animals.
: We conducted this study to assess long‐term melatonin treatment course, effectiveness and safety in children with attention‐deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia ...(CSOI). This was conducted by means of a structured questionnaire for the parents. The subjects of this study consisted of participants who previously participated in a randomised clinical trial on melatonin efficacy. The response rate was 93% (94/101). The mean time to follow up was 3.7 yr. No serious adverse events or treatment related co‐morbidities were reported. Sixty‐five percent of the children still used melatonin daily and 12% occasionally. Temporal discontinuation of treatment resulted in a delay of sleep onset in 92% of the children. Nine percent of the children could discontinue melatonin completely because of improvement of sleep onset insomnia. Long‐term melatonin treatment was judged to be effective against sleep onset problems in 88% of the cases. Improvement of behaviour and mood was reported in 71% and 61% respectively. We conclude that melatonin remains an effective therapy on the long term for the treatment of CSOI in children with ADHD and has no safety concerns regarding serious adverse events or treatment related co‐morbidity. Discontinuation of melatonin treatment usually leads to a relapse of sleep onset insomnia and in resuming melatonin treatment, even after several years of treatment.
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