The UK's Life Sciences Strategy: opportunities for clinical pharmacology.

The UK's Life Sciences Strategy provides UK clinical pharmacologists with a unique opportunity to enhance the impact of their discipline on patients and the NHS as well as the pharmaceutical industry. The full benefits of electronic prescribing systems, supported by artificial intelligence, will require clinical pharmacological expertise. Similarly, the Strategy's support for 'healthy ageing' will only be realized if clinical pharmacologists are able to use their expertise in promoting the safe and effective use of medicines in older people. Furthermore, their needs to be an active - and continuing - collaboration between clinical pharmacologists in the NHS and the pharmaceutical industry in general as well as with the discipline of pharmaceutical medicine.

Improving public health by improving clinical trial guidelines and their application.

Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research.

The Prevalence of Huntington's Disease.

BACKGROUND: Reviews of the epidemiology of Huntington's disease (HD) suggest that its worldwide prevalence varies widely. This review was undertaken to confirm these observations, to assess the extent to which differences in case-ascertainment and/or diagnosis might be responsible, and to investigate whether the prevalence pattern has changed over the past 50 years. METHODS: Eighty two relevant studies were identified from Medline and Embase, previous reviews, scrutiny of references from included and excluded studies and enquiry among those interested in the field. RESULTS: The lowest rates were among the Asians and the highest among the Caucasians. The differences are not fully explained by varying approaches to case-ascertainment or diagnosis. There was evidence of an increasing prevalence of between 15 and 20% per decade in studies from Australia, North America and Western Europe. CONCLUSIONS: The prevalence of HD varies more than tenfold between different geographical regions. This variation can in part be attributed to differences in case-ascertainment and/or diagnostic criteria, but there is consistent evidence of a lower incidence in Asian populations. There is also evidence that in Australia, North America and in Western Europe (including the United Kingdom), prevalence has increased over the past 50 plus years.

Evidence, values, and decision making.

BACKGROUND: The evidence supporting the use of new, or established, interventions may be derived from either (or both) experimental or observational study designs. Although a rigorous examination of the evidence base for clinical and cost-effectiveness is essential, it is never sufficient, and those undertaking a health technology assessment (HTA) also have to exercise judgments. METHODS: The basis for this discussion is largely from the author's experience as chairman of the national Institute for Health and Clinical Excellence (NICE). RESULTS: The judgments necessary for HTA to make are twofold. Scientific judgments relate to the interpretation of the science. Social value judgments are concerned with the ethical principles, preferences, culture, and aspirations of society. CONCLUSIONS: How scientific and social value judgments might be most appropriately captured is a challenge for all HTA agencies. Although competent HTA bodies should be able to exercise scientific judgments they have no legitimacy to impose their own social values. These must ultimately be informed by the general public.

Prevalence of adult Huntington's disease in the UK based on diagnoses recorded in general practice records.

BACKGROUND AND PURPOSE: The prevalence of Huntington's disease (HD) in the UK is uncertain. Recently, it has been suggested that the prevalence may be substantially greater than previously reported. This study was undertaken to estimate the overall UK prevalence in adults diagnosed with HD, using data from primary care. METHODS: The electronic medical records of patients aged 21 years or more, with recorded diagnoses of HD, were retrieved from the UK's General Practice Research Database. Prevalence was estimated from the number of persons with recorded diagnoses of HD, on 1 July each year, between 1990 and 2010. This number was divided by the total number of persons registered with participating general practices on that same date. These data were also used to estimate both age specific prevalence and prevalence in various regions of the UK. RESULTS: A total of 1136 patients diagnosed with HD, aged 21 years or more, were identified from the database. The estimated prevalence (expressed per 100 000 population) rose from 5.4 (95% CI 3.8 to 7.5) in 1990 to 12.3 (95% CI 11.2 to 13.5) in 2010. Although an increased prevalence was observed within every age group, the most dramatic was in older patients. Age specific prevalence was highest in the 51-60 year age range (15.8 95% CI 9.0 to 22.3). The prevalence of adult HD was lowest in the London region (5.4 (95% CI 3.0 to 8.9)) and highest in the North East of England (18.3 (95% CI 8.6 to 34.6)) and Scotland (16.1 (95% CI 10.8 to 22.9)). CONCLUSIONS: The prevalence of diagnosed HD is clearly substantially higher in the UK than suggested from previous studies. By extrapolation to the UK as a whole, it is estimated that there are more than 5700 people, aged 21 years or more, with HD. There has also been a surprising doubling of the HD population between 1990 and 2010. Many factors may have caused this increase, including more accurate diagnoses, better and more available therapies and an improved life expectancy, even with HD. There also appears to be a greater willingness to register a diagnosis of HD in patients' electronic medical records. Such a high prevalence of HD requires more ingenuity and responsiveness in its care. How to appropriately care for, and respond to, so many individuals and families coping with the exigencies of HD demands our greatest resolve and imagination.

What's happening at NICE?

From 1 April 2013, the National Institute for Health and Clinical Excellence (NICE) will be re-established under the provisions of the Health and Social Care Act 2012. Although its name will change to the National Institute for Health and Care Excellence, its acronym--NICE--has been written into the face of the Act. The new NICE will continue to provide the full range of guidance and other products with which the Institute has become associated. It will, though, have enhanced responsibilities in the development of quality standards and in the introduction of value-based pricing. In addition, it will be responsible for producing guidance for social care (hence the change in its name) and associated quality standards. The changes to the structure of NICE will not change its relationship with the professions and we are confident that it will continue to be relevant to all those working in the National Health Service.

Deep learning estimation of northern hemisphere soil freeze-thaw dynamics using satellite multi-frequency microwave brightness temperature observations.

Satellite microwave sensors are well suited for monitoring landscape freeze-thaw (FT) transitions owing to the strong brightness temperature (TB) or backscatter response to changes in liquid water abundance between predominantly frozen and thawed conditions. The FT retrieval is also a sensitive climate indicator with strong biophysical importance. However, retrieval algorithms can have difficulty distinguishing the FT status of soils from that of overlying features such as snow and vegetation, while variable land conditions can also degrade performance. Here, we applied a deep learning model using a multilayer convolutional neural network driven by AMSR2 and SMAP TB records, and trained on surface (~0-5 cm depth) soil temperature FT observations. Soil FT states were classified for the local morning (6 a.m.) and evening (6 p.m.) conditions corresponding to SMAP descending and ascending orbital overpasses, mapped to a 9 km polar grid spanning a five-year (2016-2020) record and Northern Hemisphere domain. Continuous variable estimates of the probability of frozen or thawed conditions were derived using a model cost function optimized against FT observational training data. Model results derived using combined multi-frequency (1.4, 18.7, 36.5 GHz) TBs produced the highest soil FT accuracy over other models derived using only single sensor or single frequency TB inputs. Moreover, SMAP L-band (1.4 GHz) TBs provided enhanced soil FT information and performance gain over model results derived using only AMSR2 TB inputs. The resulting soil FT classification showed favorable and consistent performance against soil FT observations from ERA5 reanalysis (mean percent accuracy, MPA: 92.7%) and in situ weather stations (MPA: 91.0%). The soil FT accuracy was generally consistent between morning and afternoon predictions and across different land covers and seasons. The model also showed better FT accuracy than ERA5 against regional weather station measurements (91.0% vs. 86.1% MPA). However, model confidence was lower in complex terrain where FT spatial heterogeneity was likely beneath the effective model grain size. Our results provide a high level of precision in mapping soil FT dynamics to improve understanding of complex seasonal transitions and their influence on ecological processes and climate feedbacks, with the potential to inform Earth system model predictions.

Crossing the fourth hurdle.

The fourth hurdle, the requirement that pharmaceutical manufacturers can demonstrate that their new products represent good value for money as well as being of good quality, effective and safe, is increasingly being required by healthcare systems. In crossing this 'fourth' hurdle, companies will usually need to demonstrate that their products are more effective than relevant comparators and that the increased cost is offset by the enhanced benefits. Decision makers, however, must draw their conclusions not only on the basis of the underpinning science but also on the social values of the people they serve.

Evidence and quality, practicalities and judgments: some experience from NICE.

The National Institute for Health and Clinical Excellence (NICE) is the principal provider of information about the evidence relating to effectiveness and cost-effectiveness in healthcare in the National Health Service of England and Wales. NICE regards quality as primarily to do with effectiveness, safety and the patient experience. In this paper we comment on the quality of evidence regarding these three and speculate about the consequences of widening the range of interventions for appraisal and taking more complete account of upstream determinants of health. We also comment on the type and quality of the evidence, as well as the way in which it is used, and the values--too often hidden--that permeate both the evidence and the way in which it is used.

Modeling Terrestrial Dissolved Organic Carbon Loading to Western Arctic Rivers.

The mobilization and land-to-ocean transfer of dissolved organic carbon (DOC) in Arctic watersheds is intricately linked with the region's climate and water cycle, and furthermore at risk of changes from climate warming and associated impacts. This study quantifies model-simulated estimates of runoff, surface and active layer leachate DOC concentrations and loadings to western Arctic rivers, specifically for basins that drain into coastal waters between and including the Yukon and Mackenzie Rivers. Model validation leverages data from other field measurements, synthesis studies, and modeling efforts. The simulations effectively quantify DOC leaching in surface and subsurface runoff and broadly capture the seasonal cycle in DOC concentration and mass loadings reported from other studies that use river-based measurements. A marked east-west gradient in simulated spring and summer DOC concentrations of 24 drainage basins on the North Slope of Alaska is captured by the modeling, consistent with independent data derived from river sampling. Simulated loadings for the Mackenzie and Yukon show reasonable agreement with estimates of DOC export for annual totals and four of the six seasonal comparisons. Nearly equivalent loading occurs to rivers which drain north to the Beaufort Sea and west to the Bering and Chukchi Seas. The modeling framework provides a basis for understanding carbon export to coastal waters and for assessing impacts of hydrological cycle intensification and permafrost thaw with ongoing warming in the Arctic.