Comparing environmental impacts of deep-seabed and land-based mining: A defensible framework.

The crises of climate change and biodiversity loss are interlinked and must be addressed jointly. A proposed solution for reducing reliance on fossil fuels, and thus mitigating climate change, is the transition from conventional combustion-engine to electric vehicles. This transition currently requires additional mineral resources, such as nickel and cobalt used in car batteries, presently obtained from land-based mines. Most options to meet this demand are associated with some biodiversity loss. One proposal is to mine the deep seabed, a vast, relatively pristine and mostly unexplored region of our planet. Few comparisons of environmental impacts of solely expanding land-based mining versus extending mining to the deep seabed for the additional resources exist and for biodiversity only qualitative. Here, we present a framework that facilitates a holistic comparison of relative ecosystem impacts by mining, using empirical data from relevant environmental metrics. This framework (Environmental Impact Wheel) includes a suite of physicochemical and biological components, rather than a few selected metrics, surrogates, or proxies. It is modified from the "recovery wheel" presented in the International Standards for the Practice of Ecological Restoration to address impacts rather than recovery. The wheel includes six attributes (physical condition, community composition, structural diversity, ecosystem function, external exchanges and absence of threats). Each has 3-5 sub attributes, in turn measured with several indicators. The framework includes five steps: (1) identifying geographic scope; (2) identifying relevant spatiotemporal scales; (3) selecting relevant indicators for each sub-attribute; (4) aggregating changes in indicators to scores; and (5) generating Environmental Impact Wheels for targeted comparisons. To move forward comparisons of land-based with deep seabed mining, thresholds of the indicators that reflect the range in severity of environmental impacts are needed. Indicators should be based on clearly articulated environmental goals, with objectives and targets that are specific, measurable, achievable, relevant, and time bound.

Impact of fixed-dose combination Cal/BD foam on the work productivity of patients with psoriasis: results from the 52-week randomized, double-blind, PSO-LONG trial.

BACKGROUND: Psoriasis contributes to unemployment, work impairment, missed workdays and substantial indirect costs due to lost productivity. Combination Cal/BD foam is the only topical that is approved for long-term maintenance treatment of plaque psoriasis for 52 weeks. This is the first known investigation of the effect of topical psoriasis therapy on productivity. OBJECTIVE: To examine the change in work productivity and activity impairment after 4 weeks of treatment with fixed-dose combination calcipotriol 50 µg/g/betamethasone dipropionate 0.5 mg/g (Cal/BD) foam and observe long-term changes after 52 weeks of long-term management (proactive or reactive treatment). METHODS: This is a post-hoc analysis of the PSO-LONG trial - a phase 3, randomized, double-blind, vehicle-controlled, parallel group, international multi-centre trial of treatment with combination Cal/BD foam. Work and activity impairment due to psoriasis were assessed by the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Psoriasis (WPAI:PSO) questionnaire at baseline, week 4, week 28 and week 56. The improvement in hours of work productivity was translated into monthly and annual indirect cost savings estimates for patients in Italy, Sweden, United Kingdom, Canada and Germany. RESULTS: Using fixed-dose combination Cal/BD foam for four weeks significantly reduced psoriasis-related work presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI) over 56 weeks, with significant improvements observed as early as 4 weeks after the baseline visit. The proportion of patients reporting impact on work productivity (as measured by presenteeism and TWPI) and activity impairment (as measured by both DLQI-Q7b and TAI) also decreased. CONCLUSION: Fixed-dose combination Cal/BD foam used for long-term management of psoriasis significantly reduces psoriasis-related work productivity and activity impairment which may result in substantial indirect cost savings. Clinical Trial Registration NCT02899962, EudraCT number: 2016-000556-95.

Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response.

BACKGROUND: Patients with moderate-to-severe psoriasis require long-term treatment, yet few trials compare outcomes beyond a short-term induction period. Quantitative comparisons of long-term outcomes in patients with psoriasis are limited. To our knowledge, no network meta-analysis (NMA) of such data has been performed. OBJECTIVE: To compare novel systemic therapies, both biologic and non-biologic, approved for moderate-to-severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year. METHODS: An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention-to-treat approach with non-responder imputation were used. RESULTS: Twenty-four studies reporting outcomes at 40-64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52-week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long-term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long-term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded. CONCLUSION: Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long-term active-comparator RCT data are required to better assess relative efficacy across therapies.

Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer.

BACKGROUND: Colorectal cancer screening can decrease morbidity and mortality. However, there are widespread differences in the implementation of programmes and choice of strategy. The primary objective of this study was to estimate lifelong costs and health outcomes of two of the currently most preferred methods of screening for colorectal cancer: colonoscopy and sensitive faecal immunochemical test (FIT). METHODS: A cost-effectiveness analysis of colorectal cancer screening in a Swedish population was performed using a decision analysis model, based on the design of the Screening of Swedish Colons (SCREESCO) study, and data from the published literature and registries. Lifelong cost and effects of colonoscopy once, colonoscopy every 10 years, FIT twice, FIT biennially and no screening were estimated using simulations. RESULTS: For 1000 individuals invited to screening, it was estimated that screening once with colonoscopy yielded 49 more quality-adjusted life-years (QALYs) and a cost saving of €64 800 compared with no screening. Similarly, screening twice with FIT gave 26 more QALYs and a cost saving of €17 600. When the colonoscopic screening was repeated every tenth year, 7 additional QALYs were gained at a cost of €189 400 compared with a single colonoscopy. The additional gain with biennial FIT screening was 25 QALYs at a cost of €154 300 compared with two FITs. CONCLUSION: All screening strategies were cost-effective compared with no screening. Repeated and single screening strategies with colonoscopy were more cost-effective than FIT when lifelong effects and costs were considered. However, other factors such as patient acceptability of the test and availability of human resources also have to be taken into account.

Fish Ecology and Evolution in the World's Oxygen Minimum Zones and Implications of Ocean Deoxygenation.

Oxygen minimum zones (OMZs) and oxygen limited zones (OLZs) are important oceanographic features in the Pacific, Atlantic, and Indian Ocean, and are characterized by hypoxic conditions that are physiologically challenging for demersal fish. Thickness, depth of the upper boundary, minimum oxygen levels, local temperatures, and diurnal, seasonal, and interannual oxycline variability differ regionally, with the thickest and shallowest OMZs occurring in the subtropics and tropics. Although most fish are not hypoxia-tolerant, at least 77 demersal fish species from 16 orders have evolved physiological, behavioural, and morphological adaptations that allow them to live under the severely hypoxic, hypercapnic, and at times sulphidic conditions found in OMZs. Tolerance to OMZ conditions has evolved multiple times in multiple groups with no single fish family or genus exploiting all OMZs globally. Severely hypoxic conditions in OMZs lead to decreased demersal fish diversity, but fish density trends are variable and dependent on region-specific thresholds. Some OMZ-adapted fish species are more hypoxia-tolerant than most megafaunal invertebrates and are present even when most invertebrates are excluded. Expansions and contractions of OMZs in the past have affected fish evolution and diversity. Current patterns of ocean warming are leading to ocean deoxygenation, causing the expansion and shoaling of OMZs, which is expected to decrease demersal fish diversity and alter trophic pathways on affected margins. Habitat compression is expected for hypoxia-intolerant species, causing increased susceptibility to overfishing for fisheries species. Demersal fisheries are likely to be negatively impacted overall by the expansion of OMZs in a warming world.

Lipid-lowering treatment patterns in patients with new cardiovascular events - estimates from population-based register data in Sweden.

OBJECTIVES: The aim of this study was to assess treatment patterns of lipid-lowering therapy (LLT) in patients with hyperlipidaemia or prior cardiovascular (CV) events who experience new CV events. METHODS: A retrospective population-based cohort study was conducted using Swedish medical records and registers. Patients were included in the study based on a prescription of LLT or CV event history and followed up for up to 7 years for identification of new CV events and assessment of LLT treatment patterns. Patients were stratified into three cohorts based on CV risk level. All outcomes were assessed during the year following index (the date of first new CV event). Adherence was defined as medication possession ratio (MPR) > 0.80. Persistence was defined as no gaps > 60 days in supply of drug used at index. RESULTS: Of patients with major cardiovascular disease (CVD) history (n = 6881), 49% were not on LLT at index. Corresponding data for CV risk equivalent and low/unknown CV risk patients were 37% (n = 3226) and 38% (n = 2497) respectively. MPR for patients on LLT at index was similar across cohorts (0.74-0.75). The proportions of adherent (60-63%) and persistent patients (56-57%) were also similar across cohorts. Dose escalation from dose at index was seen within all cohorts and 2-3% of patients switched to a different LLT after index while 5-6% of patients augmented treatment by adding another LLT. CONCLUSIONS: Almost 50% of patients with major CVD history were not on any LLT, indicating a potential therapeutic gap. Medication adherence and persistence among patients on LLT were suboptimal.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Cost analysis of re-exploration for bleeding after coronary artery bypass graft surgery.

BACKGROUND: Re-exploration for bleeding after cardiac surgery is an indicator of substantial haemorrhage and is associated with increased hospital resource utilization. This study aimed to analyse the costs of re-exploration and estimate the costs of haemostatic prophylaxis. METHODS: A total of 4232 patients underwent isolated, first-time, coronary artery bypass graft (CABG) surgery during 2005-8. Each patient re-explored for bleeding (n=127) was matched with two controls not requiring re-exploration (n=254). Cost analysis was based on resource utilization from completion of CABG until discharge. A mean cost per patient for re-exploration was calculated. Based on this, the net cost of prophylactic treatment with haemostatic drugs for preventing re-exploration was calculated. RESULTS: Patients undergoing re-exploration had higher exposure to clopidogrel before operation, prolonged stays in the intensive care unit, and more blood transfusions than controls. The mean incremental cost for re-exploration was €6290 [95% confidence interval (CI) €3408-€9173] per patient, of which 48% [€3001 (95% CI €249-€2147)] was due to prolonged stay, 31% [€1928 (95% CI €1710-€2147)] to the cost of surgery/anaesthesia, 20% [€1261 (95% CI €1145-€1378)] to the increased number of blood transfusions, and <2% [€100 (95% CI €39-€161)] to the cost of haemostatic drugs. A cost model, at an estimated 50% efficacy for recombinant activated clotting factor VIIa and a 50% expected risk for re-exploration without prophylaxis, demonstrated that to be cost neutral, prophylaxis of four patients needed to result in one avoided re-exploration. CONCLUSIONS: The resource utilization costs were substantially higher in patients requiring re-exploration for bleeding. From a strict cost-effectiveness perspective, clinical interventions to prevent haemorrhage might be underutilized.

Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: An analysis of health equity based on a randomised trial.

Background: We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods: We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings: We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2·20 [2·01-2·42]) in parallel with the gradient in the test uptake of the FIT × 2 screening (2·08 [1·96-2·20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1·29 [1·16-1·42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation: The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake. Funding: This work was supported by the Swedish Cancer Society under Grant 20 0719. CB and US provided economic support from the Swedish Research Council for Health, Working life, and Welfare under Grant 2020-00962.

Evolving the narrative for protecting a rapidly changing ocean, post-COVID-19.

The ocean is the linchpin supporting life on Earth, but it is in declining health due to an increasing footprint of human use and climate change. Despite notable successes in helping to protect the ocean, the scale of actions is simply not now meeting the overriding scale and nature of the ocean's problems that confront us.Moving into a post-COVID-19 world, new policy decisions will need to be made. Some, especially those developed prior to the pandemic, will require changes to their trajectories; others will emerge as a response to this global event. Reconnecting with nature, and specifically with the ocean, will take more than good intent and wishful thinking. Words, and how we express our connection to the ocean, clearly matter now more than ever before.The evolution of the ocean narrative, aimed at preserving and expanding options and opportunities for future generations and a healthier planet, is articulated around six themes: (1) all life is dependent on the ocean; (2) by harming the ocean, we harm ourselves; (3) by protecting the ocean, we protect ourselves; (4) humans, the ocean, biodiversity, and climate are inextricably linked; (5) ocean and climate action must be undertaken together; and (6) reversing ocean change needs action now.This narrative adopts a 'One Health' approach to protecting the ocean, addressing the whole Earth ocean system for better and more equitable social, cultural, economic, and environmental outcomes at its core. Speaking with one voice through a narrative that captures the latest science, concerns, and linkages to humanity is a precondition to action, by elevating humankind's understanding of our relationship with 'planet Ocean' and why it needs to become a central theme to everyone's lives. We have only one ocean, we must protect it, now. There is no 'Ocean B'.

Prevalence and healthcare costs of diabetic retinopathy: a population-based register study in Sweden.

AIMS/HYPOTHESIS: The aim of the present study was to estimate the prevalence and healthcare costs of diabetic retinopathy (DR). METHODS: This population-based study included all residents (n = 251,386) in the catchment area of the eye clinic of Linköping University Hospital, Sweden. Among patients with diabetes (n = 12,026), those with and without DR were identified through register data from both the Care Data Warehouse in Ostergötland, an administrative healthcare register, and the Swedish National Diabetes Register. Healthcare cost data were elicited by record linkage of these two registers to data for the year 2008 in the Cost Per Patient Database developed by Ostergötland County Council. RESULTS: The prevalence of any DR was 41.8% (95% CI 38.9-44.6) for patients with type 1 diabetes and 27.9% (27.1-28.7) for patients with type 2 diabetes. Sight-threatening DR was present in 12.1% (10.2-14.0) and 5.0% (4.6-5.4) of the type 1 and type 2 diabetes populations respectively. The annual average healthcare cost of any DR was euro72 (euro53-91). Stratified into background retinopathy, proliferative DR, maculopathy, and the last two conditions combined, the costs were euro26 (euro10-42), euro257 (euro155-359), euro216 (euro113-318) and euro433 (euro232-635) respectively. The annual cost for DR was euro106,000 per 100,000 inhabitants. CONCLUSIONS: This study presents new information on the prevalence and costs of DR. Approximately one-third of patients with diabetes have some form of DR. Average healthcare costs increase considerably with the severity of DR, which suggests that preventing progression of DR may lower healthcare costs.

Wetland response to sedimentation and nitrogen loading: diversification and inhibition of nitrogen-fixing microbes.

Anthropogenic inputs of nutrients and sediment simultaneously impact coastal ecosystems, such as wetlands, especially during storms. Independent and combined effects of sediment and ammonium nitrate loading on nitrogen fixation rates and diversity of microbes that fix nitrogen (diazotrophs) were tested via field manipulations in Spartina foliosa and unvegetated zones at Tijuana Estuary (California, USA). This estuary is subject to episodic nitrogen enrichment and sedimentation associated with rain-driven flooding and slope instabilities, the latter of which may worsen as the Triple Border Fence is constructed along the U.S.-Mexico border. Responses of diazotrophs were assessed over 17 days using acetylene reduction assays and genetic fingerprinting (terminal restriction fragment length polymorphism [T-RFLP]) of nifH, which codes for dinitrogenase reductase. Sulfate-reducing bacteria performed approximately 70% of nitrogen fixation in Spartina foliosa rhizospheres in the absence of nitrogen loading, based on sodium molybdate inhibitions in the laboratory. Following nutrient additions, richness (number of T-RFs [terminal restriction fragments]) and evenness (relative T-RF fluorescence) of diazotrophs in surface sediments increased, but nitrogen fixation rates decreased significantly within 17 days. These responses illustrate, within a microbial community, conformance to a more general ecological pattern of high function among assemblages of low diversity. Diazotroph community composition (T-RF profiles) and rhizosphere diversity were not affected. Pore water ammonium concentrations were higher and more persistent for 17 days in plots receiving sediment additions (1 cm deep), suggesting that recovery of diazotroph functions may be delayed by the combination of sediment and nutrient inputs. Nitrogen fixation constitutes a mechanism for rapid transfer of fixed N to S. foliosa roots and a variety of primary consumers (within 3 and 8 days, respectively), as determined via 15N2 enrichment studies with in situ microcosms of intact marsh sediment. Thus, long-term declines in nitrogen fixation rates in response to increasingly frequent nutrient loading and sedimentation may potentially alter nitrogen sources for vascular plants as well as trophic pathways in wetland ecosystems.

The long-term cost-effectiveness of fetal monitoring during labour: a comparison of cardiotocography complemented with ST analysis versus cardiotocography alone.

OBJECTIVE: To assess the cost-effectiveness of the use of cardiotocography (CTG) complemented with fetal electrocardiography and ST analysis compared with the use of CTG alone in term deliveries when a decision has been made to use fetal monitoring with a scalp electrode. DESIGN: A cost-effectiveness analysis based on a probabilistic decision model incorporating relevant strategies and lifelong outcomes. SETTING: Maternity wards in Sweden. POPULATION: Women with term fetuses after a clinical decision had been made to apply a fetal scalp electrode for internal CTG. METHODS: A decision model was used to compare the costs and effects of two different treatment strategies. Baseline estimates were derived from the literature. Discounted costs and quality-adjusted life years (QALYs) were simulated over a lifetime horizon using a probabilistic model. MAIN OUTCOME MEASURES: QALYs, incremental costs, and cost per QALY gained expressed as incremental cost-effectiveness ratio (ICER). RESULTS: The analysis found an incremental effect of 0.005 QALYs for ST analysis compared with CTG; the ST analysis strategy was also moreover associated with a euro56 decrease in costs, thus dominating the CTG strategy. The probability that ST analysis is cost-effective in comparison with CTG is high, irrespective of the willingness-to-pay value for a QALY. CONCLUSIONS: Compared with CTG alone, ST analysis is cost-effective when used in term high-risk deliveries in which there is a need for internal fetal monitoring.

Association of insomnia severity with well-being, quality of life and health care costs: A cross-sectional study in older adults with chronic pain (PainS65+).

BACKGROUND: Insomnia is one of the most common complaints in chronic pain. This study aimed to evaluate the association of insomnia with well-being, quality of life and health care costs. METHODS: The sample included 2790 older individuals (median age = 76; interquartile range [IQR] = 70-82) with chronic pain. The participants completed a postal survey assessing basic demographic data, pain intensity and frequency, height, weight, comorbidities, general well-being, quality of life and the insomnia severity index (ISI). Data on health care costs were calculated as costs per year (€ prices) and measured in terms of outpatient and inpatient care, pain drugs, total drugs and total health care costs. RESULTS: The overall fraction of clinical insomnia was 24.6% (moderate clinical insomnia: 21.9% [95% CI: 18.8-23.3]; severe clinical insomnia: 2.7% [95% CI: 1.6-3.2]). Persons who reported clinical insomnia were more likely to experience pain more frequently with higher pain intensity compared to those reported no clinically significant insomnia. Mean total health care costs were € 8469 (95% CI: €4029-€14,271) for persons with severe insomnia compared with € 4345 (95% CI: €4033-€4694) for persons with no clinically significant insomnia. An association between severe insomnia, well-being, quality of life, outpatient care, total drugs costs and total health care costs remained after controlling for age, sex, pain intensity, frequency, body mass index and comorbidities using linear regression models. CONCLUSIONS: Our results determine an independent association of insomnia with low health-related quality of life and increased health care costs in older adults with chronic pain. SIGNIFICANCE: The concurrence and the severity of insomnia among older adults with chronic pain were associated with decreased well-being and quality of life, and increased health care costs to society.