Leopard Panthera pardus density and survival in an ecosystem with depressed abundance of prey and dominant competitors

The leopard Panthera pardus is in range-wide decline, and many populations are highly threatened. Prey depletion is a major cause of global carnivore declines, but the response of leopard survival and density to this threat is unclear: by reducing the density of a dominant competitor (the lion Panthera leo) prey depletion could create both costs and benefits for subordinate competitors. We used capture-recapture models fitted to data from a 7-year camera-trap study in Kafue National Park, Zambia, to obtain baseline estimates of leopard population density and sex-specific apparent survival rates. Kafue is affected by prey depletion, and densities of large herbivores preferred by lions have declined more than the densities of smaller herbivores preferred by leopards. Lion density is consequently low. Estimates of leopard density were comparable to ecosystems with more intensive protection and favourable prey densities. However, our study site is located in an area with good ecological conditions and high levels of protection relative to other portions of the ecosystem, so extrapolating our estimates across the Park or into adjacent Game Management Areas would not be valid. Our results show that leopard density and survival within north-central Kafue remain good despite prey depletion, perhaps because (1) prey depletion has had weaker effects on preferred leopard prey compared to larger prey preferred by lions, and (2) the density of dominant competitors is consequently low. Our results show that the effects of prey depletion can be more complex than uniform decline of all large carnivore species, and warrant further investigation

Habitat shifts in response to predation risk are constrained by competition within a grazing guild

Predators can affect prey not only by killing them, but also by causing them to alter their behavior, including patterns of habitat selection. Prey can reduce the risk of predation by moving to habitats where predators are less likely to detect them, less likely to attack, or less likely to succeed. The interaction of such responses to risk with other ecological processes remains relatively unstudied, but in some cases, changes in habitat use to avoid predation may be constrained by competition: larger, dominant competitors should respond freely to predation risk, but the responses of smaller, subordinate competitors may be constrained by the responses of dominant competitors. For large grazing herbivores, an alternative hypothesis proposes that smaller prey species are vulnerable to more predators, and thus should respond more strongly to predation risk. Here, we tested these two hypotheses with 775 observations of habitat selection by four species of obligate grazers (zebra, wildebeest, puku and oribi) in the immediate presence or absence of four large carnivores (lion, spotted hyena, African wild dog and cheetah) in three ecosystems (Greater Liuwa, Greater Kafue and Luangwa Valley). Patterns of predation within this set were described by observation of 1,105 kills. Our results support the hypothesis that responses to predation risk are strongest for larger, dominant competitors. Even though zebras were killed least often, they showed the strongest shift into cover when carnivores were present. Wildebeest, puku and oribi showed weaker habitat shifts, even though they were more frequently killed. These patterns remained consistent in models that controlled for differences in the hunting mode of the predator (stalking, coursing, or intermediate) and for differences among ecosystems. There was no evidence that smaller species were subject to predation by a broader set of predators. Instead, smaller prey were killed often by smaller predators, and larger prey were killed often by larger predators. Broadly, our results show that responses to predation risk interact with interspecific competition. Accounting for such interactions should help to explain the considerable variation in the strength of responses to predation risk that has been observed

Medication administration errors for older people in long-term residential care

Background Older people in long-term residential care are at increased risk of medication errors. The purpose of this study was to evaluate a computerised barcode medication management system designed to improve drug administrations in residential and nursing homes, including comparison of error rates and staff awareness in both settings. Methods All medication administrations were recorded prospectively for 345 older residents in thirteen care homes during a 3-month period using the computerised system. Staff were surveyed to identify their awareness of administration errors prior to system introduction. Overall, 188,249 attempts to administer medication were analysed to determine the prevalence of potential medication administration errors (MAEs). Error classifications included attempts to administer medication at the wrong time, to the wrong person or discontinued medication. Analysis compared data at residential and nursing home level and care and nursing staff groups. Results Typically each resident was exposed to 206 medication administration episodes every month and received nine different drugs. Administration episodes were more numerous (p < 0.01) in nursing homes (226.7 per resident) than in residential homes (198.7). Prior to technology introduction, only 12% of staff administering drugs reported they were aware of administration errors being averted in their care home. Following technology introduction, 2,289 potential MAEs were recorded over three months. The most common MAE was attempting to give medication at the wrong time. On average each resident was exposed to 6.6 potential errors. In total, 90% of residents were exposed to at least one MAE with over half (52%) exposed to serious errors such as attempts to give medication to the wrong resident. MAEs rates were significantly lower (p < 0.01) in residential homes than nursing homes. The level of non-compliance with system alerts was low in both settings (0.075% of administrations) demonstrating virtually complete error avoidance. Conclusion Potentially inappropriate administration of medication is a serious problem in long-term residential care. A computerised barcode system can accurately and automatically detect inappropriate attempts to administer drugs to residents. This tool can reliably be used by care staff as well as nurses to improve quality of care and patient safety

Drivers of MERS-CoV Emergence in Qatar

MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. This study sought to identify and quantify possible drivers for the MERS-CoV emergence and spillover to humans. A list of potential human, animal and environmental drivers for disease emergence were identified from literature. Trends in possible drivers were analyzed from national and international databases, and through structured interviews with experts in Qatar. The discovery and exploitation of oil and gas led to a 5-fold increase in Qatar GDP coupled with a 7-fold population growth in the past 30 years. The lifestyle gradually transformed from Bedouin life to urban sedentary life, along with a sharp increase in obesity and other comorbidities. Owing to substantial governmental support, camel husbandry and competitions flourished, exacerbating the already rapidly occurring desertification that forced banning of free grazing in 2005. Consequently, camels were housed in compact barns alongside their workers. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans

Useful pharmacodynamic endpoints in children: selection, measurement, and next steps.

Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families.Pediatric Research advance online publication, 11 April 2018; doi:10.1038/pr.2018.38

Deprescribing interventions and their impact on medication adherence in community-dwelling older adults with polypharmacy: a systematic review

Background: Polypharmacy, and the associated adverse drug events such as non-adherence to prescriptions, is a common problem for elderly people living with multiple comorbidities. Deprescribing, i.e. the gradual withdrawal from medications with supervision by a healthcare professional, is regarded as a means of reducing adverse effects of multiple medications including non-adherence. This systematic review examines the evidence of deprescribing as an effective strategy for improving medication adherence amongst older, community dwelling adults. Methods: A mixed methods review was undertaken. Eight bibliographic database and two clinical trials registers were searched between May and December 2017. Results were double screened in accordance with pre-defined inclusion/exclusion criteria related to polypharmacy, deprescribing and adherence in older, community dwelling populations. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal and an a priori data collection instrument was used. For the quantitative studies, a narrative synthesis approach was taken. The qualitative data was analysed using framework analysis. Findings were integrated using a mixed methods technique. The review was performed in accordance with the PRISMA reporting statement. Results: A total of 22 original studies were included, of which 12 were RCTs. Deprescribing with adherence as an outcome measure was identified in randomised controlled trials (RCTs), observational and cohort studies from 13 countries between 1996 and 2017. There were 17 pharmacy-led interventions; others were led by General Practitioners (GP) and nurses. Four studies demonstrated an overall reduction in medications of which all studies corresponded with improved adherence. A total of thirteen studies reported improved adherence of which 5 were RCTs. Adherence was reported as a secondary outcome in all but one study. Conclusions: There is insufficient evidence to show that deprescribing improves medication adherence. Only 13 studies (of 22) reported adherence of which only 5 were randomised controlled trials. Older people are particularly susceptible to non-adherence due to multi-morbidity associated with polypharmacy. Bio-psycho-social factors including health literacy and multi-disciplinary team interventions influence adherence. The authors recommend further study into the efficacy and outcomes of medicines management interventions. A consensus on priority outcome measurements for prescribed medications is indicated

Global extent and drivers of mammal population declines in protected areas under illegal hunting pressure

Illegal hunting is a persistent problem in many protected areas, but an overview of the extent of this problem and its impact on wildlife is lacking. We reviewed 40 years (1980–2020) of global research to examine the spatial distribution of research and socio-ecological factors influencing population decline within protected areas under illegal hunting pressure. From 81 papers reporting 988 species/site combinations, 294 mammal species were reported to have been illegally hunted from 155 protected areas across 48 countries. Research in illegal hunting has increased substantially during the review period and showed biases towards strictly protected areas and the African continent. Population declines were most frequent in countries with a low human development index, particularly in strict protected areas and for species with a body mass over 100 kg. Our results provide evidence that illegal hunting is most likely to cause declines of large-bodied species in protected areas of resource-poor countries regardless of protected area conservation status. Given the growing pressures of illegal hunting, increased investments in people’s development and additional conservation efforts such as improving anti-poaching strategies and conservation resources in terms of improving funding and personnel directed at this problem are a growing priority

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Recommendations for the design of therapeutic trials for neonatal seizures

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from welldesigned clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population