Screening for Depression in Adults: A Summary of the Evidence for the U.S. Preventive Services Task Force

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Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation

© Queen’s Printer and Controller of HMSO 2015.Background People diagnosed with cancer of the prostate, a sex gland in the pelvis, have a choice of treatment options depending on the severity of disease. For people whose cancer is at medium and low risk of spread, the main options are surgical removal of the prostate, radical prostatectomy (RP), use of external beam radiotherapy (EBRT) to destroy the cancer or delaying treatment until there are signs that the cancer is getting worse [active surveillance (AS)]. RP and radiotherapy are effective at curing the cancer but may also cause long-term urinary incontinence and sexual problems. AS, on the other hand, may be quite difficult for people to cope with as they know that the cancer is still present. Newer treatments aim to target the disease more precisely so that surrounding normal tissues can be preserved, reducing the risk of side effects but still effectively destroying the cancer. These more targeted ablative therapies include cryotherapy, high-intensity focused ultrasound (HIFU), brachytherapy, photodynamic therapy (PDT), radiofrequency interstitial tumour ablation (RITA) and laser therapy, among others. Aims This study aimed to develop clinical care pathways relevant to a UK NHS context review systematically the evidence of the clinical effectiveness and safety of each newer ablative therapy concerning primary and salvage treatment of localised prostate cancer• determine which therapies are most likely to be cost-effective for implementation in the UK NHS identify and prioritise future research needs. Methods Clinical effectiveness review We conducted two discrete systematic reviews: (a) primary ablative treatment of localised prostate cancer compared with AS, RP or EBRT (b) salvage ablative treatment for local prostate cancer relapse after primary EBRT compared with salvage RP. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service (BIOSIS), Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) databases were searched to the end of March 2013. Reference lists of all included studies were scanned and experts on our advisory panel were contacted for details of additional reports. Evidence came from randomised controlled trials (RCTs), non-randomised comparative studies (NRCSs) (if no RCT evidence was identified) and single-arm cohort studies (case series) with greater than 10 participants for the ablative procedures only. Conference abstracts or non-English-language reports were excluded. For the primary therapy systematic review, the ablative therapies considered were cryotherapy, HIFU, PDT, RITA, laser ablation and brachytherapy. The comparators were AS, RP and EBRT. For the salvage therapy systematic review, the ablative therapies considered were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. For meta-analysis, a Bayesian indirect mixed-treatment comparison was used. Cost-effectiveness The cost-effectiveness of the different treatments and their subsequent care pathways was assessed using a modified Markov individual simulation model, applied to a UK NHS setting. The perspective for the model was a health services perspective. Parameter estimates were derived from the systematic review of clinical effectiveness, a micro-costing exercise, other literature, the expert advisory group and other UK sources. The outputs of the model were costs and quality-adjusted life-years (QALYs) for each procedure, incremental costs and QALYs and incremental cost per QALY over the remaining lifetime. Both costs and QALYs were discounted at 3.5%. An elasticity analysis, together with probabilistic and deterministic sensitivity analyses, were performed to explore the uncertainty surrounding parameter estimates. Results Clinical effectiveness Cryotherapy Data from 3995 patients who received cryotherapy across 19 studies (1 RCT, 4 NRCSs and 14 case series) were included, with most studies considered to be at high risk of bias. In the short term, there was conflicting evidence relating to cancer-specific outcomes when cryotherapy was compared with either EBRT or surgery. The only finding that reached statistical significance was 1-year disease-free survival, which was worse for cryotherapy than for either EBRT or RP. However, none of the other cancer-specific outcomes, such as biochemical failure or overall survival, showed any significant differences between them. The findings in relation to cancer-specific outcomes are best regarded as inconclusive. There was evidence that the rate of urinary incontinence at 1 year was lower for people undergoing cryotherapy than for those undergoing RP [3% vs. 66%; odds ratio (OR) 0.02, 95% credible interval (CrI) < 0.01 to 0.34], but the size of the difference decreased with longer follow-up. There was a general trend for cryotherapy to have fewer procedural complications, apart from urinary retention. The only difference that reached statistical significance was for urethral stricture, which was less frequent after cryotherapy than after RP (1% vs. 8%; OR 0.24, 95% CrI 0.09 to 0.54). High-intensity focused ultrasound Data from 4000 patients who received HIFU across 21 studies (1 NRCS and 20 case series) were included, with all studies considered to be at high risk of bias. There was some evidence that biochemical failure rates were higher at 1 year when using HIFU than when using EBRT, and this was statistically significant. However, the difference was no longer statistically significant at 5 years. Similar findings were observed with regard to disease-free survival at 1 year, with worse outcomes for HIFU than for EBRT, which were statistically significant. The differences were no longer significant at 3 years. The biochemical result was in contrast to overall survival at 4 years, which was higher when using HIFU. There were insufficient data on any urinary incontinence, erectile dysfunction or bowel problems to draw any robust conclusions, although at 1 year HIFU had lower incontinence rates than RP (10% vs. 66%; OR 0.06, 95% CrI 0.01 to 0.48). The safety profile for HIFU was generally good, apart from a potential numerical increase in rates of urinary retention and dysuria. However, HIFU appeared to have a slightly higher incidence of urethral stricture than EBRT, and the difference was statistically significant (8% vs. 1%; OR 5.8, 95% CrI 1.2 to 24.5). Brachytherapy This review considered data from 26,129 patients who received brachytherapy across 40 studies (2 RCTs and 38 NRCSs), with most studies considered to be at high risk of bias. The data for brachytherapy were generally more robust than for other ablative therapies. In the short term, there was some evidence at 5-year follow-up that the rate of biochemical failure was lower for brachytherapy (7%) than for EBRT (13%; OR 0.46, 95% CrI 0.32 to 0.67) or RP (11%; OR 0.35, 95% CrI 0.21 to 0.56). There was also some evidence that disease-free survival was better for brachytherapy at 3-year follow-up. There was evidence that the rate of urinary incontinence up to 5 years after treatment was lower for people undergoing brachytherapy than for RP, but the size of the difference decreased with longer follow-up. There was also a trend towards lower erectile dysfunction rates for brachytherapy than for EBRT or RP and this reached statistical significance at 3 years after treatment (60% vs. 81% for EBRT and 88% for RP). There were insufficient data to draw any conclusions on bowel problems. The findings regarding procedural complications were mixed. Dysuria rates were higher for brachytherapy and this reached statistical significance when compared with RP. Urinary retention was also statistically significantly higher for brachytherapy than for EBRT. Stricture rates for brachytherapy were higher than those for EBRT, but lower than those for RP. The differences for stricture reached statistical significance when compared with RP. For rectal pain, there was evidence that rates were significantly lower for brachytherapy than for EBRT. Acute genitourinary toxicity, though rare, had statistically higher rates for brachytherapy than for EBRT, but acute gastrointestinal toxicity was lower for brachytherapy. Other ablative therapies Only two other ablative therapies were identified in the review: focal laser ablative therapy and PDT. Data were too scarce (a total of 35 participants for these two procedures) for any conclusions. Salvage therapy Data from 400 participants who were treated with salvage therapy following primary EBRT across nine case series were included. Six studies involved salvage RP, two involved salvage cryotherapy and one involved salvage HIFU. In six studies, data were not collected prospectively, and only short-term outcomes were reported. As such, all of the studies were considered as having a high risk of bias. There was no robust evidence that mortality or other cancer-specific outcomes differed between salvage cryotherapy and salvage RP in the short term. There were no data on cancer-specific outcomes for salvage HIFU. In regard to functional and quality of life outcomes, lack of data prevented any conclusions. In terms of adverse event outcomes, salvage cryotherapy had numerically fewer periprocedural complications (especially for bladder neck stenosis) than salvage HIFU or salvage RP, but there was a high level of uncertainty with this observation. Focal ablation Descriptive subgroup assessment within studies reporting the use of focal ablation was limited, but suggested that cancer-specific outcomes were at least comparable with those seen in full-gland therapy studies. Urinary incontinence rates may be lower following focal ablation, but the evidence is weak in light of the poor quality and quantity of the data. Active surveillance Lack of outcome data prevented comparison of the efficacy of ablative therapies with a programme of AS, apart from the rate of erectile dysfunction at 12 months, where there was no statistically significant difference. Cost-effectiveness Assuming equal recurrence in line with the lack of statistical differences from the effectiveness review, EBRT was the least costly (£19,363 per patient) and least effective (3.63 QALYs), whereas HIFU was more costly (£19,860 per patient) and more effective (3.86 QALYs). HIFU was more effective and less costly than the other newer ablative interventions. The lifetime incremental cost per QALY for HIFU compared with EBRT was £2915. There was a 75% chance that HIFU would be considered cost-effective at a £30,000-per-QALY threshold. In a plausible best-and-worst-case analysis, the probability that HIFU would be considered cost-effective varied between 60% and 70%. Strengths and limitations The main strength of the study was the systematic approach taken to review the literature and the inclusion of a relatively large quantity of studies, giving a high total number of participants. The main limitations were the low quantity and poor quality of the data available on cancer-related outcomes and long-term adverse events of urinary incontinence, sexual and bowel dysfunction, and the changing technology over the review period. Many published studies were poorly reported or lacked sufficient detail. Inconsistency in outcome definition, measurement and reporting was also a significant problem, and much of the information available was unsuitable for meta-analysis. Another major limitation resulted from the majority of comparisons being made using case series, with few head-to-head comparisons of ablative therapies against current practice. The estimates were therefore generated using indirect comparisons. Like all analyses, they require assumptions to be made that may or may not be reasonable. Accordingly, the results should be interpreted with a large degree of caution. Despite the considerable efforts to construct a model and seek the best data available, the lack of effectiveness data had implications for the economic evaluation. The limited data meant that there was insufficient evidence to assume that there was any difference between interventions for a number of parameters, a particular issue for biochemical recurrence, which was a key parameter in the evaluation. The impact of these assumptions was explored in sensitivity analyses. Conclusions Implications for health care For primary ablative therapy, neither cryotherapy nor HIFU had sufficiently robust data to enable any definitive conclusions to be made. The effectiveness data on brachytherapy were more robust and there was some evidence that cancer-specific outcomes in the short term were either better or equivalent to either EBRT or RP, with comparable adverse effect profiles apart from a possible increased risk of dysuria and urinary retention. The findings on focal ablative therapy were mostly derived from data on focal cryotherapy, which suggested that cancer-specific outcomes were at least comparable with those of full-gland cryotherapy, and there was a suggestion that the urinary incontinence outcome may be better following focal cryotherapy than whole-gland cryotherapy. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. For salvage ablative therapy following primary EBRT, a lack of reliable and robust data prevented any meaningful conclusions from being made, in comparison with salvage RP. The findings from the review indicate that there is insufficient evidence to help inform recommendations on the use of ablative therapies in the UK NHS. Need for further research The main gaps in the evidence base are the lack of direct comparative studies of ablative therapies; the consequent lack of robust data to inform calculations of cost-effectiveness and the role of focal ablative therapies; and the lack of longer-term data on cancer control, such as overall and cancer-specific mortality. The key research recommendations, in order of importance, are as follows: 1. HIFU and brachytherapy seem the most promising newer interventions but they lack high-quality evaluation. Such evaluation should ideally be by multicentre RCT with long-term follow-up, and would include predefined assessment of cancer-specific, dysfunction and health-related quality-of-life measures. Such studies should incorporate economic evaluations and also inform economic modelling

Defects and lithium migration in Li₂CuO₂

Li2CuO2 is an important candidate material as a cathode in lithium ion batteries. Atomistic simulation methods are used to investigate the defect processes, electronic structure and lithium migration mechanisms in Li2CuO2. Here we show that the lithium energy of migration via the vacancy mechanism is very low, at 0.11 eV. The high lithium Frenkel energy (1.88 eV/defect) prompted the consideration of defect engineering strategies in order to increase the concentration of lithium vacancies that act as vehicles for the vacancy mediated lithium self-diffusion in Li2CuO2. It is shown that aluminium doping will significantly reduce the energy required to form a lithium vacancy from 1.88 eV to 0.97 eV for every aluminium introduced, however, it will also increase the migration energy barrier of lithium in the vicinity of the aluminium dopant to 0.22 eV. Still, the introduction of aluminium is favourable compared to the lithium Frenkel process. Other trivalent dopants considered herein require significantly higher solution energies, whereas their impact on the migration energy barrier was more pronounced. When considering the electronic structure of defective Li2CuO2, the presence of aluminium dopants results in the introduction of electronic states into the energy band gap. Therefore, doping with aluminium is an effective doping strategy to increase the concentration of lithium vacancies, with a minimal impact on the kinetics

Linking disease epidemiology and livestock productivity: the case of bovine respiratory disease in France

Concerns are growing over the impact of livestock farming on environment and public health. The livestock industry is faced with the double constraint of limiting its use of natural resources and antimicrobials while ensuring its economic sustainability. In this context, reliable methods are needed to evaluate the effect of the prevention of endemic animal diseases on the productivity of livestock production systems. In this study, an epidemiological and productivity model was used to link changes in Bovine Respiratory Disease (BRD) incidence with the productivity of the beef and dairy cattle sectors in France. Cattle production parameters significantly affected by BRD were selected through literature review. Previous field study results and national cattle performance estimates were used to infer growth performances, mortality rates and carcass quality in the cattle affected and not affected by BRD. A steady-state deterministic herd production model was used to predict the productivity of the dairy and beef sector and their defined compartments (breeding-fattening, feedlot young bulls, and feedlot veal) in case of BRD incidence reduction by 20%, 50% or 100%. Results suggested that BRD should be controlled at a priority in beef breeding farms as eradication of BRD in beef calves would increase the whole beef sector’s productivity by 4.7–5.5% while eradication in other production stages would result in lower productivity gain in their respective sectors. However, the analysis performed at compartment level showed that, in both the beef and dairy sector, young bull and veal feedlot enterprises derive more economic benefits from BRD eradication for their own compartment (increase in productivity of 8.7–12.8% for beef young bulls) than the breeding farms (increase in productivity of 5.1–6% for beef calves), which may limit the investments in BRD control

A roadmap of strain in doped anatase TiO2

Anatase titanium oxide is important for its high chemical stability and photocatalytic properties, however, the latter are plagued by its large band gap that limits its activity to only a small percentage of the solar spectrum. In that respect, straining the material can reduce its band gap increasing the photocatalytic activity of titanium oxide. We apply density functional theory with the introduction of the Hubbard + U model, to investigate the impact of stress on the electronic structure of anatase in conjunction with defect engineering by intrinsic defects (oxygen/titanium vacancies and interstitials), metallic dopants (iron, chromium) and non-metallic dopants (carbon, nitrogen). Here we show that both biaxial and uniaxial strain can reduce the band gap of undoped anatase with the use of biaxial strain being marginally more beneficial reducing the band gap up to 2.96 eV at a tensile stress of 8 GPa. Biaxial tensile stress in parallel with doping results in reduction of the band gap but also in the introduction of states deep inside the band gap mainly for interstitially doped anatase. Dopants in substitutional positions show reduced deep level traps. Chromium-doped anatase at a tensile stress of 8 GPa shows the most significant reduction of the band gap as the band gap reaches 2.4 eV

Acute and chronic kidney disease in elderly patients with hip fracture: prevalence, risk factors and outcome with development and validation of a risk prediction model for acute kidney injury

Background Hip fracture is a common injury in older people with a high rate of postoperative morbidity and mortality. This patient group is also at high risk of acute kidney injury (AKI) and chronic kidney disease (CKD), but little is known of the impact of kidney disease on outcome following hip fracture. Methods An observational cohort of consecutive patients with hip fracture in a large UK secondary care hospital. Predictive modelling of outcomes using development and validation datasets. Inclusion: all patients admitted with hip fracture with sufficient serum creatinine measurements to define acute kidney injury. Main outcome measures – development of acute kidney injury during admission; mortality (in hospital, 30-365 day and to follow-up); length of hospital stay. Results Data were available for 2848 / 2959 consecutive admissions from 2007-2011; 776 (27.2%) male. Acute kidney injury occurs in 24%; development of acute kidney injury is independently associated with male sex (OR 1.48 (1.21 to 1.80), premorbid chronic kidney disease stage 3B or worse (OR 1.52 (1.19 to 1.93)), age (OR 3.4 (2.29 to 5.2) for >85 years) and greater than one major co-morbidities (OR 1.61 (1.34 to 1.93)). Acute kidney injury of any stage is associated with an increased hazard of death, and increased length of stay (Acute kidney injury: 19.1 (IQR 13 to 31) days; no acute kidney injury 15 (11 to 23) days). A simplified predictive model containing Age, CKD stage (3B-5), two or more comorbidities, and male sex had an area under the ROC curve of 0.63 (0.60 to 0.67). Conclusions Acute kidney injury following hip fracture is common and associated with worse outcome and greater hospital length of stay. With the number of people experiencing hip fracture predicted to rise, recognition of risk factors and optimal perioperative management of acute kidney injury will become even more important

Facts, values, and Attention-Deficit Hyperactivity Disorder (ADHD): an update on the controversies

The Hastings Center, a bioethics research institute, is holding a series of 5 workshops to examine the controversies surrounding the use of medication to treat emotional and behavioral disturbances in children. These workshops bring together clinicians, researchers, scholars, and advocates with diverse perspectives and from diverse fields. Our first commentary in CAPMH, which grew out of our first workshop, explained our method and explored the controversies in general. This commentary, which grows out of our second workshop, explains why informed people can disagree about ADHD diagnosis and treatment. Based on what workshop participants said and our understanding of the literature, we make 8 points. (1) The ADHD label is based on the interpretation of a heterogeneous set of symptoms that cause impairment. (2) Because symptoms and impairments are dimensional, there is an inevitable "zone of ambiguity," which reasonable people will interpret differently. (3) Many other variables, from different systems and tools of diagnosis to different parenting styles and expectations, also help explain why behaviors associated with ADHD can be interpreted differently. (4) Because people hold competing views about the proper goals of psychiatry and parenting, some people will be more, and others less, concerned about treating children in the zone of ambiguity. (5) To recognize that nature has written no bright line between impaired and unimpaired children, and that it is the responsibility of humans to choose who should receive a diagnosis, does not diminish the significance of ADHD. (6) Once ADHD is diagnosed, the facts surrounding the most effective treatment are complicated and incomplete; contrary to some popular wisdom, behavioral treatments, alone or in combination with low doses of medication, can be effective in the long-term reduction of core ADHD symptoms and at improving many aspects of overall functioning. (7) Especially when a child occupies the zone of ambiguity, different people will emphasize different values embedded in the pharmacological and behavioral approaches. (8) Truly informed decision-making requires that parents (and to the extent they are able, children) have some sense of the complicated and incomplete facts regarding the diagnosis and treatment of ADHD

Competition and parasitism in the native White Clawed Crayfish Austropotamobius pallipes and the invasive Signal Crayfish Pacifastacus leniusculus in the UK

Many crayfish species have been introduced to novel habitats worldwide, often threatening extinction of native species. Here we investigate competitive interactions and parasite infections in the native Austropotamobius pallipes and the invasive Pacifastacus leniusculus from single and mixed species populations in theUK. We found A. pallipes individuals to be significantly smaller in mixed compared to single species populations; conversely P. leniusculus individuals were larger in mixed than in single species populations. Our data provide no support for reproductive interference as a mechanism of competitive displacement and instead suggest competitive exclusion of A. pallipes from refuges by P. leniusculus leading to differential predation. We screened 52 P. leniusculus and 12 A. pallipes for microsporidian infection using PCR. We present the first molecular confirmation of Thelohania contejeani in the native A. pallipes; in addition, we provide the first evidence for T. contejeani in the invasive P. leniusculus. Three novel parasite sequenceswere also isolated fromP. leniusculus with an overall prevalence of microsporidian infection of 38% within this species; we discuss the identity of and the similarity between these three novel sequences. We also screened a subset of fifteen P. leniusculus and three A. pallipes for Aphanomyces astaci, the causative agent of crayfish plague and for the protistan crayfish parasite Psorospermium haeckeli. We found no evidence for infection by either agent in any of the crayfish screened. The high prevalence of microsporidian parasites and occurrence of shared T. contejeani infection lead us to propose that future studies should consider the impact of these parasites on native and invasive host fitness and their potential effects upon the dynamics of native-invader systems

Recognition of COVID-19 with occupational origin: a comparison between European countries

Objectives This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. Methods A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. Results The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. Conclusions COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.This publication is based on work from COST Action CA16216 (OMEGA-NET), supported by COST (European Cooperation in Science and Technology)