Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

A Substantial Population of Low Mass Stars in Luminous Elliptical Galaxies

The stellar initial mass function (IMF) describes the mass distribution of stars at the time of their formation and is of fundamental importance for many areas of astrophysics. The IMF is reasonably well constrained in the disk of the Milky Way but we have very little direct information on the form of the IMF in other galaxies and at earlier cosmic epochs. Here we investigate the stellar mass function in elliptical galaxies by measuring the strength of the Na I doublet and the Wing-Ford molecular FeH band in their spectra. These lines are strong in stars with masses <0.3 Msun and weak or absent in all other types of stars. We unambiguously detect both signatures, consistent with previous studies that were based on data of lower signal-to-noise ratio. The direct detection of the light of low mass stars implies that they are very abundant in elliptical galaxies, making up >80% of the total number of stars and contributing >60% of the total stellar mass. We infer that the IMF in massive star-forming galaxies in the early Universe produced many more low mass stars than the IMF in the Milky Way disk, and was probably slightly steeper than the Salpeter form in the mass range 0.1 - 1 Msun.Comment: To appear in Natur

Participation and satisfaction after spinal cord injury: results of a vocational and leisure outcome study

Study design: Survey. Objectives: Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. Design: Descriptive analysis of data from a questionnaire. Setting: Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. Subjects: A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. Main outcome measures: Changes in participation in activities; current life satisfaction; support and unmet needs. Results: Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60% of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. Conclusions: Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation

Definitions of Urinary Tract Infection in Current Research: A Systematic Review

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI

Severe childhood malaria syndromes defined by plasma proteome profiles

BACKGROUND Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Self-reported smoking cessation activities among Swiss primary care physicians

ABSTRACT: BACKGROUND: Individual counselling, pharmacotherapy, and group therapy are evidence-based interventions that help patients stop smoking. Acupuncture, hypnosis, and relaxation have no demonstrated efficacy on smoking cessation, whereas self-help material may only have a small benefit. The purpose of this study is to assess physicians' current clinical practice regarding smokers motivated to stop smoking. METHODS: The survey included 3385 Swiss primary care physicians. Self-reported use of nine smoking cessation interventions was scored. One point was given for each positive answer about practicing interventions with demonstrated efficacy, i.e. nicotine replacement therapy, bupropion, counselling, group therapy, and smoking cessation specialist. No points were given for the recommendation of acupuncture, hypnosis, relaxation, and self-help material. Multivariable logistic analysis was performed to identify factors associated with a good practice score, defined as &gt;1. RESULTS: The response rate was 55%. Respondents were predominately over the age of 40 years (88%), male (79%), and resided in urban areas (74%). Seventeen percent reported being smokers. Most of the physicians prescribed nicotine replacement therapy (84%), bupropion (65%), or provided counselling (70%). A minority of physicians recommended acupuncture (26%), hypnosis (8%), relaxation (7%), or self-help material (24%). A good practice score was obtained by 85% of respondents. Having attended a smoking cessation training program was the only significant predictor of a good practice score (odds ratio: 6.24 , 95% CI 1.95-20.04). CONCLUSION: The majority of respondents practice recommended smoking cessation interventions. However, there is room for improvement and implementing an evidence-based smoking cessation-training program could provide additional benefit

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups

Ecosystem Resilience and Threshold Response in the Galápagos Coastal Zone

Background: The Intergovernmental Panel on Climate Change (IPCC) provides a conservative estimate on rates of sea-level rise of 3.8 mm yr⁻¹ at the end of the 21st century, which may have a detrimental effect on ecologically important mangrove ecosystems. Understanding factors influencing the long-term resilience of these communities is critical but poorly understood. We investigate ecological resilience in a coastal mangrove community from the Galápagos Islands over the last 2700 years using three research questions: What are the 'fast and slow' processes operating in the coastal zone? Is there evidence for a threshold response? How can the past inform us about the resilience of the modern system?Methodology/Principal Findings: Palaeoecological methods (AMS radiocarbon dating, stable carbon isotopes (δ13C)) were used to reconstruct sedimentation rates and ecological change over the past 2,700 years at Diablas lagoon, Isabela, Galápagos. Bulk geochemical analysis was also used to determine local environmental changes, and salinity was reconstructed using a diatom transfer function. Changes in relative sea level (RSL) were estimated using a glacio-isostatic adjustment model. Non-linear behaviour was observed in the Diablas mangrove ecosystem as it responded to increased salinities following exposure to tidal inundations. A negative feedback was observed which enabled the mangrove canopy to accrete vertically, but disturbances may have opened up the canopy and contributed to an erosion of resilience over time. A combination of drier climatic conditions and a slight fall in RSL then resulted in a threshold response, from a mangrove community to a microbial mat.Conclusions/Significance: Palaeoecological records can provide important information on the nature of non-linear behaviour by identifying thresholds within ecological systems, and in outlining responses to 'fast and slow' environmental change between alternative stable states. This study highlights the need to incorporate a long-term ecological perspective when designing strategies for maximizing coastal resilience.</p