Empirically supported psychological therapies have been developed for many mental health conditions. However, in most countries only a small proportion of the public benefit from these advances. The ...English Improving Access to Psychological Therapies (IAPT) program aims to bridge the gap between research and practice by training over 10,500 new psychological therapists in empirically supported treatments and deploying them in new services for the treatment of depression and anxiety disorders. Currently IAPT treats over 560,000 patients per year, obtains clinical outcome data on 98.5% of these individuals, and places this information in the public domain. Around 50% of patients treated in IAPT services recover, and two-thirds show worthwhile benefits. The clinical and economic arguments on which IAPT is based are presented, along with details of the service model, how the program was implemented, and recent findings about service organization. Limitations and future directions are outlined.
Abstract
The Improving Access to Psychological Therapies (IAPT) programme is a large-scale initiative that aims to greatly increase the availability of NICE recommended psychological treatment for ...depression and anxiety disorders within the National Health Service in England. This article describes the background to the programme, the arguments on which it is based, the therapist training scheme, the clinical service model, and a summary of progress to date. At mid-point in a national roll-out of the programme progress is generally in line with expectation, and a large number of people who would not otherwise have had the opportunity to receive evidence-based psychological treatment have accessed, and benefited from, the new IAPT services. Planned future developments and challenges for the programme are briefly described.
It is now well recognized that the body temperature of older men and women is lower than that of younger people and that their tolerance of thermal extremes is more limited. The regulation of body ...temperature does not depend on a single organ, but rather involves almost all the systems of the body, i.e. systems not exclusively dedicated to thermoregulatory functions such as the cardiovascular and respiratory systems. Since these deteriorate naturally with advancing age, the decrement in their functions resonates throughout all the bodily processes, including those that control body temperature. To the extent that the age-related changes in some of these, e.g. in the musculoskeletal system, can be slowed, or even prevented, by certain measures, e.g. fitness training, so can the decrements in thermoregulatory functions. Some deficits, however, are unavoidable, e.g. structural skin changes and metabolic alterations. These impact directly on the ability of the elderly to maintain thermal homeostasis, particularly when challenged by ambient thermal extremes. Since the maintenance of a relatively stable, optimal core temperature is one of the body's most important activities, its very survival can be threatened by these disorders. The present article describes the principal, age-associated changes in physiological functions that could affect the ability of seniors to maintain their body temperature when exposed to hot or cold environments.
Neuropeptide Y (NPY) is an endogenous peptide of the central and enteric nervous systems which has gained significant interest as a potential neuroprotective agent for treatment of neurodegenerative ...disease. Amyotrophic lateral sclerosis (ALS) is an aggressive and fatal neurodegenerative disease characterized by motor deficits and motor neuron loss. In ALS, recent evidence from ALS patients and animal models has indicated that NPY may have a role in the disease pathogenesis. Increased NPY levels were found to correlate with disease progression in ALS patients. Similarly, NPY expression is increased in the motor cortex of ALS mice by end stages of the disease. Although the functional consequence of increased NPY levels in ALS is currently unknown, NPY has been shown to exert a diverse range of neuroprotective roles in other neurodegenerative diseases; through modulation of potassium channel activity, increased production of neurotrophins, inhibition of endoplasmic reticulum stress and autophagy, reduction of excitotoxicity, oxidative stress, neuroinflammation and hyperexcitability. Several of these mechanisms and signalling pathways are heavily implicated in the pathogenesis of ALS. Therefore, in this review, we discuss possible effects of NPY and NPY‐receptor signalling in the ALS disease context, as determining NPY’s contribution to, or impact on, ALS disease mechanisms will be essential for future studies investigating the NPY system as a therapeutic strategy in this devastating disease.
Neuropeptide Y modulates a number of molecular mechanisms implicated in amyotrophic lateral sclerosis (ALS) pathogenesis. In this review, we focus on these signalling pathways and the extensive evidence from neurodegenerative and neurological disorders that implies NPY could protect against cellular dysfunction in the ALS disease context. Implications for utilising NPY as a therapeutic approach for ALS are also considered.
Soils are subject to varying degrees of direct or indirect human disturbance, constituting a major global change driver. Factoring out natural from direct and indirect human influence is not always ...straightforward, but some human activities have clear impacts. These include land‐use change, land management and land degradation (erosion, compaction, sealing and salinization). The intensity of land use also exerts a great impact on soils, and soils are also subject to indirect impacts arising from human activity, such as acid deposition (sulphur and nitrogen) and heavy metal pollution. In this critical review, we report the state‐of‐the‐art understanding of these global change pressures on soils, identify knowledge gaps and research challenges and highlight actions and policies to minimize adverse environmental impacts arising from these global change drivers. Soils are central to considerations of what constitutes sustainable intensification. Therefore, ensuring that vulnerable and high environmental value soils are considered when protecting important habitats and ecosystems, will help to reduce the pressure on land from global change drivers. To ensure that soils are protected as part of wider environmental efforts, a global soil resilience programme should be considered, to monitor, recover or sustain soil fertility and function, and to enhance the ecosystem services provided by soils. Soils cannot, and should not, be considered in isolation of the ecosystems that they underpin and vice versa. The role of soils in supporting ecosystems and natural capital needs greater recognition. The lasting legacy of the International Year of Soils in 2015 should be to put soils at the centre of policy supporting environmental protection and sustainable development.
An understanding of risks to biodiversity is needed for planning action to slow current rates of decline and secure ecosystem services for future human use. Although the IUCN Red List criteria ...provide an effective assessment protocol for species, a standard global assessment of risks to higher levels of biodiversity is currently limited. In 2008, IUCN initiated development of risk assessment criteria to support a global Red List of ecosystems. We present a new conceptual model for ecosystem risk assessment founded on a synthesis of relevant ecological theories. To support the model, we review key elements of ecosystem definition and introduce the concept of ecosystem collapse, an analogue of species extinction. The model identifies four distributional and functional symptoms of ecosystem risk as a basis for assessment criteria: A) rates of decline in ecosystem distribution; B) restricted distributions with continuing declines or threats; C) rates of environmental (abiotic) degradation; and D) rates of disruption to biotic processes. A fifth criterion, E) quantitative estimates of the risk of ecosystem collapse, enables integrated assessment of multiple processes and provides a conceptual anchor for the other criteria. We present the theoretical rationale for the construction and interpretation of each criterion. The assessment protocol and threat categories mirror those of the IUCN Red List of species. A trial of the protocol on terrestrial, subterranean, freshwater and marine ecosystems from around the world shows that its concepts are workable and its outcomes are robust, that required data are available, and that results are consistent with assessments carried out by local experts and authorities. The new protocol provides a consistent, practical and theoretically grounded framework for establishing a systematic Red List of the world's ecosystems. This will complement the Red List of species and strengthen global capacity to report on and monitor the status of biodiversity.
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Nocardia infections after ...solid organ transplantation (SOT). Nocardia infections have increased in the last two decades, likely due to improved detection and identification methods and an expanding immunocompromised population. The risk of developing nocardiosis after transplantation varies with the type of organ transplanted and the immunosuppression regimen used. Nocardia infection most commonly involves the lung. Disseminated infection can occur, with spread to the bloodstream, skin, or central nervous system. Early recognition of the infection and initial appropriate treatment is important to achieve good outcomes. Species identification and antimicrobial susceptibility testing are strongly recommended, as inter‐ and intraspecies susceptibility patterns can vary. Sulfonamide is the first‐line treatment of Nocardia infections, and combination therapy with at least two antimicrobial agents should be used initially for disseminated or severe nocardiosis. Trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis may be helpful in preventing Nocardia infection after SOT.
Summary
Background
Moderate‐to‐severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and ...depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single‐item, patient‐reported outcome (PRO) of itch severity.
Objectives
To describe the content validity and psychometric assessment (test–retest reliability, construct validity, known‐groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch.
Methods
Content validity was assessed through in‐depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test–retest reliability, construct validity, known‐groups validity and sensitivity to change in patients with moderate‐to‐severe AD.
Results
Interview participants indicated that the Peak Pruritus NRS was a relevant, clear and comprehensive assessment of itch severity. Peak Pruritus NRS scores showed large, positive correlations with existing PRO measures of itch, and weak or moderate correlations with clinician‐reported measures assessing objective signs of AD. Peak Pruritus NRS score improvements were highly correlated with improvements in other itch PROs, and moderately correlated with improvements in clinician‐reported measures assessing objective signs of AD. The most appropriate threshold for defining a clinically relevant, within‐person response was ≥ 2–4‐point change in the Peak Pruritus NRS.
Conclusions
The Peak Pruritus NRS is a well‐defined, reliable, sensitive and valid scale for evaluating worst itch intensity in adults with moderate‐to‐severe AD.
What's already known about this topic?
Moderate‐to‐severe atopic dermatitis is characterized by persistent and debilitating itch, which can greatly impair quality of life.
A validated, brief patient‐reported outcome measure is needed to quantify the intensity of itch accurately and reliably in patients with atopic dermatitis in clinical trials.
What does this study add?
The Peak Pruritus Numerical Rating Scale (NRS) is a well‐defined, reliable, fit‐for‐purpose measure to evaluate patient‐reported intensity of worst itch in the previous 24 h for adults with moderate‐to‐severe atopic dermatitis.
Clinical response is indicated by a ≥ 2–4‐point change from baseline in Peak Pruritus NRS score.
What are the clinical implications of this work?
This study provides practising clinicians and clinical trialists with a validated patient‐reported outcome measure to assess itch, a hallmark symptom of atopic dermatitis and a crucial marker of treatment benefit.
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Respond to this article
A variety of machine learning methods such as naive Bayesian, support vector machines and more recently deep neural networks are demonstrating their utility for drug discovery and development. These ...leverage the generally bigger datasets created from high-throughput screening data and allow prediction of bioactivities for targets and molecular properties with increased levels of accuracy. We have only just begun to exploit the potential of these techniques but they may already be fundamentally changing the research process for identifying new molecules and/or repurposing old drugs. The integrated application of such machine learning models for end-to-end (E2E) application is broadly relevant and has considerable implications for developing future therapies and their targeting.
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