It was speculated that dysbiosis of gut microbiota might accelerate the toxicity of boric acid on German cockroaches.Fungicides are widely used to control diseases in soybean crops. We hypothesized that fungicides applied to healthy soybean plants compromise the plant’s physiology, affect the reproductive process and reduce crop productivity. We aimed to evaluate the photosynthetic process, pollen grain viability and yield components of soybean plants exposed to three commercial fungicides. The experiment was performed twice using soybean cultivar SYN 1378C, disease-free plants, with four treatments i) control treatment (without any fungicide application); ii) cyproconazole 150 g L-1 + difenoconazole 250 g L-1 (CPZ + DFZ; 250 mL ha-1; without adjuvant); iii) azoxystrobin 300 g Kg-1 + benzovindiflupyr 150 g Kg-1 (AZB + BZP; 200 g ha-1; Nimbus® adjuvant (Syngenta)); and iv) propiconazole 250 g L-1 + difenoconazole 250 g L-1 (PPZ + DFZ; 150 mL ha-1; without adjuvant) in both soybean pre-bloom (V8) and bloom (R1) developmental stages. The experimental design was randomized blocks with four replicates. Phytotoxicity, gas exchange and chlorophyll a fluorescence traits, pollen grain viability, pollen grain germination, flower abortion and soybean production components were evaluated. The fungicides did not affect the physiological traits, pollen grain germination and crop yield.Organophosphates cause increased oxidative susceptibility of erythrocytes and changes in erythrocyte deformability ability. We aim is to investigate the role of ethion (ETH) on erythrocyte deformability and to show whether vinpocetine (VIN) and carnosine (CAR) are protective against these changes. The study was performed on Sprague Dawley rats with an average weight of 220 ± 40 g and 4-5 months old. Six experimental groups were composed of 10 rats per group. Hematological parameters, erythrocyte deformability, % hemolysis, 2.3bisphosphoglycerate, and methemoglobin values were measured in blood samples taken after 10 days of drug application. Erythrocyte count, hemoglobin amount, hematocrit value, serum potassium level, and erythrocyte deformability decreased in the ETH group. Leukocyte, platelet count, methemoglobin amount, and % hemolysis rates increased in the ETH group. The values of the ETH + CAR and ETH + VIN groups were found to be closer to the control group. In organophosphate poisoning such as ETH, the deformability ability of erythrocytes exposed to constant oxidative stress is changing, and therefore their ability to deliver oxygen to tissues is negatively affected. VIN and CAR may have improve on erythrocyte deformability in this type of intoxication.Green mold, caused by Penicillium digitatum, is the most important citrus postharvest disease worldwide and often causes substantial economic losses to the citrus industry. The demethylation inhibitor (DMI) fungicides are highly effective against a broad range of fungal pathogens, but the DMI fungicide propiconazole has not been registered yet in China for the control of citrus green mold. In this study, baseline sensitivity of P. digitatum to propiconazole was determined. The frequency distribution of logarithms of EC50 values for 118 isolates collected from five regions in China was bimodal, and among the 118 isolates, 18 isolates were less sensitive or had low resistance to propiconazole. The mean EC50 value of the sensitive 100 isolates was 0.104 mg/L. Preventive control efficacies on Satsuma mandarin for propiconazole at 200 and 400 mg/L were 63.1 and 84.3%, respectively. The fruit treated with propiconazole at 40 and 100 mg/L produced significantly fewer conidia, and the virulence of the conidia decreas.Benfuresate (2,3-dihydro-3,3-dimethylbenzofuran-5-yl ethanesulphonate) is a widely used pre-emergence herbicide of the benzofurane group, which works through the inhibition of lipid synthesis. During embryonic development of zebrafish, benfuresate retards growth while causing internal changes in the body, including alteration of the expression of cell cycle regulators, induction of apoptosis, and suppression of the circulatory system. Acute toxicity towards benfuresate is seen across the range of 5-15 μM in a dose-dependent manner and contributes to pathological conditions and subsequent morphological changes. For embryos 120 h post fertilization (hpf), benfuresate exposure results in an array of malformations involving eye or otolith development, pericardial edema, yolk sac edema, and abnormal curvature of the spine. Mechanistically, benfuresate exposure altered the transcription levels of the proliferative pathway genes ccnd1, ccne1, cdk2, and cdk6, all of which sensitize cells to apoptosis. Benfuresate exposure also affected vascular formation, including the formation of various vessels (DA, SIVs, CA, CV) whose functions in lymphatic-blood circulation were disrupted following decreased vegfaa, vegfc, flt1, flt4, and kdrl expression. These findings provide evidence of embryo-larval toxicity due to benfuresate and highlight the perils of herbicide exposure for non-target organisms far removed from application sites, especially in aquatic environments.Over use of organophosphate pesticides including Chlorpyrifos (CPF) has led to contamination of soil and water resources, resulting in serious health problems in humans along with other non-target organisms. The current study was aimed to investigate Chlorpyrifos as well as 3, 5, 6-Trichloro-2-pyridinol (TCP) biodegradation tendency of bacterial strain Bacillus thuringiensis MB497 isolated from wheat/cotton fields of Dera Saleemabad, Mianwali, Pakistan, having a history of heavy Organophosphate pesticides application. HPLC analysis revealed almost 99% degradation of the spiked CPF (200 mg L-1) in M-9 broth, soil slurry and soil microcosm by MB497 after 9 days of incubation. Strain MB497 was also able to degrade and transform TCP (28 mg L-1), up to 90.57% after 72 h of incubation in M-9 broth. A novel compound Di-isopropyl methanephosphonate along with known products of 3, 5, 6-Trichloro-2-pyridinol (TCP), Diethyl thiophospsphate and Phosphorothioic acid were detected as metabolites of CPF by GCMS analysis. Three novel metabolites of TCP (p-Propyl phenol, 2-Ethoxy-4, 4, 5, 5-tetramethyloxazoline and 3-(2, 4, 5-Trichlorophenoxy)-1-propyne) were identified after 72 h. Based on these metabolites, new/amended metabolic pathways for CPF and TCP degradation in these bacteria has been suggested.Plant viral diseases, known as „plant cancer”, with high contagiosity can substantially reduce crop quality and yield. To identify potential anti-tobacco mosaic virus (TMV) agents with different mechanisms, a series of novel α-aminophosphonate derivatives containing a chalcone moiety were designed and synthesized. Bioassay results revealed that some target compounds exhibited improved curative activity against TMV in vivo, and the EC50 value of compound B3 was 356.7 mg L-1. The activities of the defensive enzymes POD and CAT from tobacco leaves treated with B3 and B17 showed that these target compounds could improve the photosynthetic ability of the leaves and activate plant host resistance against TMV infection. The binding constant between B3 and TMV Coat Protein (CP) (2.51 × 108 M-1), calculated by the fluorescence titration experiment and docking results, revealed that B3 has a strong interaction with TMV CP. Further docking analysis revealed that B3 was embedded between two layers of the TMV CP, which was consistent with the 21 binding mode of TMV CP and B3 determined by the binding affinity experiment. The TEM morphological study of TMV treated with B3 and B17 indicated that this series of target compounds may trigger the disassembly of TMV by interacting directly with TMV CP. This study provides new insight for the discovery of antiviral compounds with two different mechanisms of action.Flixweed (Descurainia sophia L.) is widely distributed in winter wheat (Triticum aestivum L.) fields in the North China Plain and has evolved resistance to herbicides, including the acetolactate synthase (ALS) inhibitor florasulam. However, the florasulam resistance status of flixweed in the North China Plain is poorly understood, which hinders the integrated management of this weed in winter wheat production systems. Thus, 45 flixweed populations were collected in wheat fields in these areas, and their sensitivity to florasulam and ALS-inhibitor-resistant mutation diversity were assessed. Meanwhile, alternative herbicides/herbicide mixtures for the control of florasulam-resistant flixweed were screened and evaluated under greenhouse and field conditions. Of the populations, 30 showed florasulam resistance (RRR and RR), 9 had a high risk of evolving florasulam resistance (R?) and 6 were susceptible. These populations had 5.3 to 345.1-fold resistance to florasulam, and 4 ALS resistance mutations (P197H, P197S, P197T and W574L) were observed. The subsequent herbicide sensitivity assay showed that the SD-06 population (with ALS1 P197T and ALS2 W574L mutations) exhibited cross-resistance to all ALS inhibitors tested, but was sensitive to MCPA-Na, fluroxypyr, carfentrazone-ethyl and bipyrazone. Meanwhile, the other HN-07 population with non-target-site resistance (NTSR) also showed resistance to all tested ALS inhibitors, and it was „R?” to MCPA-Na while sensitive to fluroxypyr, carfentrazone-ethyl and bipyrazone. The field experiments were conducted at the research farm where the SD-06 population was collected, and the results suggested that florasulam at 3.75-4.5 g ai ha-1 had little efficacy (0.6-12.1%), whereas MCPA-Na + carfentrazone-ethyl (87.1-91.2%) and bipyrazone+fluroxypyr (90.1-97.8%) controlled the resistant flixweed.Cantharidin (CTD) is a natural toxin with effective toxicity to lepidopteran pests. Nevertheless, little information is available on whether pests develop resistance to CTD. After being exposed to CTD (50 mg/L to 90 mg/L) or 10 generations, the resistance ratio of laboratory selected cantharidin-resistant Mythimna separata (Cantharidin-SEL) strain was only elevated 1.95-fold. Meanwhile, the developmental time for M. separata was prolonged (delayed1.65 in males and 1.84 days in females). The reported CTD target, the serine/threonine phosphatases (PSPs), have not been shown significant activity variation during the whole process of CTD-treatment. The activity of detoxification enzymes (cytochrome monooxygenase P450, glutathione-S-transferase (GST) and carboxylesterase) were affected by CTD selection, but this change was not mathematically significant. More importantly, no obvious cross-resistance with other commonly used insecticides was observed in the M. separata population treated with CTD for 10 generations (resistance ratios were all lower 2.5). Overall, M. separata is unlikely to produce target-site insensitivity resistance, metabolic resistance to CTD. Meanwhile, cantharidin-SEL is not prone to develop cross-resistance with other insecticides. These results indicate that CTD is a promising biogenetic lead compound which can be applied in the resistance management on M. separata.The fall armyworm Spodoptera frugiperda (Lepidoptera Noctuidae) is a polyphagous pest with 353 plant species as its hosts, including maize, sorghum, cotton, and rice. Azadirachtin is one of the most effective botanical insecticides. The effect of azadirachtin against S. frugiperda remains to be determined. Here we report strong growth inhibition of azadirachtin on S. frugiperda larvae under either 1.0 or 5.0 μg/g azadirachtin. To explore the relevant mechanisms, the larvae fed with normal artificial diet and with 1.0 μg/g azadirachtin exposure for 3 days were collected as samples for RNA-Seq. RNA-Seq on S. frugiperda larvae under different treatments identified a total of 24,153 unigenes, including 3494 novel genes, were identified. Among them, 1282 genes were affected by 1.0 μg/g azadirachtin exposure, with 672 up-regulated and 610 down-regulated. The impacted genes include 61 coding for detoxification enzymes (31 P450s, 7 GSTs, 11 CarEs, 7 UGTs and 5 ABC transporters), 31 for cuticle proteins, and several proteins involved in insect chitin and hormone biosynthesis. Our results indicated that azadirachtin could regulate the growth of S. frugiperda by affecting insect chitin and hormone biosynthesis pathway. The enhanced expression of detoxification enzymes might be related to detoxifying azadirachtin. These findings provided a foundation for further delineating the molecular mechanism of growth regulation induced by azadirachtin in S. frugiperda larvae.

Targeted genetic testing is a tool to identify women at increased risk of gynaecological cancer.

This systematic review evaluates the results and quality of cost-effectiveness modeling studies that assessed targeted genetic-based screen-and-treat strategies to prevent breast and ovarian cancer.

Using MEDLINE and databases of the Centre for Reviews and Dissemination, we searched for health economic modeling evaluations of targeted genetic-based screen-and-treat strategies to prevent inheritable breast and ovarian cancer (until August 2020). The incremental cost-effectiveness ratios (ICERs) were compared. Methodological variations were addressed by evaluating the model conceptualizations, the modeling techniques, parameter estimation and uncertainty, and transparency and validation of the models. Additionally, the reporting quality of each study was assessed.

Eighteen studies met our inclusion criteria. From a payer perspective, the ICERs of (1) BRCA screening for high-risk women without cancer ranged fiations could be decreased by the development of a reference model, which may serve as a tool for validation of present and future cost-effectiveness models.

Asthma is one of the most common major noncommunicable diseases in the world and affects individuals of all ages. Medication is used to achieve and maintain quality of life (QOL) for people with asthma. Telehealth interventions offer optimized and personalized symptom monitoring with timely treatment adjustment and the potential to increase medication adherence for individuals with asthma. This study examines and synthesizes the available data on the change in the QOL for patients with asthma who use interactive telehealth interventions, and identifies the most effective telehealth modalities used for intervention in this area.

Literature searches were conducted in 5 databases in November 2018 for studies measuring a change in QOL for patients with asthma. Study QOL outcomes, where possible, were pooled in a meta-analysis.

Seventeen publications (describing 16 studies) comprising 2015 patients were included. Based on a meta-analysis, interactive telehealth interventions can improve QOL outcomes for peopat a positive change in QOL can be attributed to these interventions and provide evidence for the implementation of telehealth interventions for individuals with asthma.

There are increasing concerns about the appropriateness of generic preference-based measures to capture health benefits in the area of mental health.

The aim of this study is to estimate preference weights for a new measure, Recovering Quality of Life (ReQoL-10), to better capture the benefits of mental healthcare.

Psychometric analyses of a larger sample of mental health service users (n= 4266) using confirmatory factor analyses and item response theory were used to derive a health state classification system and inform the selection of health states for utility assessment. A valuation survey with members of the UK public representative in terms of age, sex, and region was conducted using face-to-face interviewer administered time-trade-off with props. A series of regression models were fitted to the data and the best performing model selected for the scoring algorithm.

The ReQoL-Utility Index (UI) classification system comprises 6 mental health items and 1 physical health item. Sixty-four health states were valued by 305 participants. The preferred model was a random effects model, with significant and consistent coefficients and best model fit. Estimated utilities modeled for all health states ranged from-0.195 (state worse than dead) to 1 (best possible state).

The development of the ReQoL-UI is based on a novel application of item response theory methods for generating the classification system and selecting health states for valuation. Conventional time-trade-off was used to elicit utility values that are modeled to enable the generation of QALYs for use in cost-utility analysis of mental health interventions.

The development of the ReQoL-UI is based on a novel application of item response theory methods for generating the classification system and selecting health states for valuation. Conventional time-trade-off was used to elicit utility values that are modeled to enable the generation of QALYs for use in cost-utility analysis of mental health interventions.

Health utility decrement estimates for diabetes and complications are needed for parametrization of simulation models that aim to assess the cost-utility of diabetes prevention and care strategies. This study estimates health utility decrements associated with diabetes and cardiovascular and microvascular complications from a population-based German study.

Data were obtained from the population based cross-sectional KORA (Cooperative Health Research in the Augsburg Region) health questionnaire 2016 and comprised n= 1072 individuals with type 2 diabetes and n= 7879 individuals without diabetes. Health utility was assessed through the EQ-5D-5L. We used linear regression models with interaction terms between type 2 diabetes and different cardiovascular and microvascular complications while adjusting for demographic and socio-economic factors and other comorbidities.

Type 2 diabetes (β = -0.028, standard error [SE]= 0.014), stroke (β = -0.070, SE= 0.010), cardiac arrhythmia (β = -0.031, SE= 0.006), heart faovascular, and microvascular conditions are associated with significant health utility decrements. Utility decrements for some conditions differ between people with and without type 2 diabetes. These results are of high relevance for the parametrization of decision analytic simulation models and applied health economic evaluations in the field of prevention and management of type 2 diabetes in Germany.

Orphan medicinal products (OMPs) often receive market authorization under conditions imposed by regulators for ongoing postauthorization surveillance (PAS) to answer questions that remain at the time of market entry. This surveillance may be provided through industry-funded registries (IFRs). Nevertheless, data in these registries may not be of sufficient quality to answer these questions and may not always be accessible for regulatory review. We propose that a mandatory independent registry is an efficient and cost-effective tool for PAS for OMPs.

Using data from the Canadian Fabry Disease Initiative, we reviewed costs per unique patient from sites participating in both the independent national registry and IFRs for Fabry disease and compared data completeness from the Canadian Fabry Disease Initiative to that in published documents from IFRs.

The costs of data collection through the independent registry were 17% to 36% (depending on site) lower than costs to collect data in the IFRs, and completeness of data collected through the independent registry was higher than that through the IFRs. Data from the independent registry were reviewed annually to guide indications for publicly funded Fabry disease therapy. Even when enrollment ceased to be a requirement to receive therapy, 77% of patients continued to enroll in the registry, suggesting the structure was acceptable to patients.

Independent registries are cost-effective and efficient tools and should be mandated by regulatory agencies as the preferred tool for PAS for OMPs. Countries with publicly funded health systems should consider investment in registry infrastructure for OMPs.

Independent registries are cost-effective and efficient tools and should be mandated by regulatory agencies as the preferred tool for PAS for OMPs. Countries with publicly funded health systems should consider investment in registry infrastructure for OMPs.

Assessment of patient-reported outcomes (PROs) in oncology is of critical importance because it provides unique information that may also predict clinical outcomes.

We conducted a systematic review of prognostic factor studies to examine the prognostic value of PROs for survival in cancer. A systematic literature search was performed in PubMed for studies published between 2013 and 2018. We considered any study, regardless of the research design, that included at least 1 PRO domain in the final multivariable prognostic model. The protocol (EPIPHANY) was published and registered in the International Prospective Register of Systematic Reviews (CRD42018099160).

Eligibility criteria selected 138 studies including 158 127 patients, of which 43 studies were randomized, controlled trials. Overall, 120 (87%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival. Lung (n= 41, 29.7%) and genitourinary (n= 27, 19.6%) cancers were most commonly investigated. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies. The EORTC QLQ-C30 questionnaire was the most frequently used measure, and its physical functioning scale (range 0-100) the most frequent independent prognostic PRO, with a pooled hazard ratio estimate of 0.88 per 10-point increase (95% CI 0.84-0.92).

There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. Further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.

There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. Further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.

Cost-effectiveness analysis (CEA) embeds an assumption at odds with most economic analysis-that of constant returns to health in the creation of happiness (utility). We aim to reconcile it with the bulk of economic theory.

We generalize the traditional CEA approach, allow diminishing returns to health, and align CEA with the rest of the health economics literature.

This simple change has far-reaching implications for the practice of CEA. First, optimal cost-effectiveness thresholds should systematically rise for more severe diseases and fall for milder ones. We provide formulae for estimating how these thresholds vary with health-related quality of life (QoL) in the sick state. Practitioners can also use our approach to account for treatment outcome uncertainty. Holding average benefits fixed, risk-averse consumers value interventions more when they reduce outcome uncertainty (’insurance value’) and/or when they provide a chance at positively skewed outcomes (’value of hope’). Finally, we provide a coheised by advocates for disabled people. Our Generalized Risk-Adjusted Cost-Effectiveness (GRACE) approach helps align HTA practice with realistic preferences for health and risk.

Patients with atrial fibrillation (AF) have rapid and irregular heart rates, increasing the risk of comorbidities and mortality. Next to formal medical care, many patients receive informal care from their social environment. The objective of this study was to examine the well-being and economic burden of providing informal care to patients with AF in the UK, Italy, and Germany.

Caregivers of patients with AF completed an online survey based on the iMTA Valuation of Informal Care Questionnaire, with questions about their caregiving situation, perceived burden of caregiving, and absence from work due to health problems resulting from caregiving. Care-related quality-of-life utilities were calculated using the Care-related Quality of Life instrument and associated tariffs. Societal costs of caregiving were calculated based on the proxy good method.

A total of 585 caregivers participated in this study. On average, caregivers provided 33 hours of informal care per week to patients (SD 29 hours). On a scale from 0 to 10, their self-rated burden was 5.4. The average Care-related Quality of Life utility was 72. Caregivers primarily indicated problems with daily activities, mental health, and physical health. Still, the vast majority of caregivers (87%) derived fulfillment from providing care. Weekly societal costs of caregiving were on average €636. Comorbidities contributed substantially to the caregiver time and burden.

Caring for a patient with AF is associated with substantial objective and subjective burden, but also provides fulfillment from being able to care for a loved one.

Caring for a patient with AF is associated with substantial objective and subjective burden, but also provides fulfillment from being able to care for a loved one.

This study aims to estimate the national impact and cost-effectiveness of the 2018 American College of Physicians (ACP) guidance statements compared to the status quo.

Survey data from the 2011-2016 National Health and Nutrition Examination were used to generate a national representative sample of individuals with diagnosed type 2 diabetes in the United States. Individuals with A1c <6.5% on antidiabetic medications are recommended to deintensify their A1c level to 7.0% to 8.0% (group 1); individuals with A1c 6.5% to 8.0% and a life expectancy of <10 years are recommended to deintensify their A1c level >8.0% (group 2); and individuals with A1c >8.0% and a life expectancy of >10 years are recommended to intensify their A1c level to 7.0% to 8.0% (group 3). We used a Markov-based simulation model to evaluate the lifetime cost-effectiveness of following the ACP recommended A1c level.

14.41 million (58.1%) persons with diagnosed type 2 diabetes would be affected by the new guidance statements. Treatment deintensification would lead to a saving of $363 600 per quality-adjusted life-year (QALY) lost for group 1 and a saving of $118 300 per QALY lost for group 2. Intensifying treatment for group 3 would lead to an additional cost of $44 600 per QALY gain. Nationally, the implementation of the guidance would add 3.2 million life-years and 1.1 million QALYs and reduce healthcare costs by $47.7 billion compared to the status quo.

Implementing the new ACP guidance statements would affect a large number of persons with type 2 diabetes nationally. The new guidance is cost-effective.

Implementing the new ACP guidance statements would affect a large number of persons with type 2 diabetes nationally. The new guidance is cost-effective.

The Depression Care for People with Cancer program (DCPC) is a cost-effective depression care model for UK patients with cancer. However, DCPC’s cost-effectiveness in the United States is unknown, particularly for patients with prostate cancer in the United States. This study evaluates the health and economic impact of providing DCPC to patients with prostate cancer.

DCPC was compared with usual care in a mathematical model that simulates depression and its outcomes in a hypothetical cohort of US patients with prostate cancer. DCPC was modeled as a sequential combination of universal depression screening, post-screening evaluations, and first-line combination therapy. Primary outcomes were lifetime direct costs of depression care, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Secondary outcomes included life expectancy, number of depression-free months and lifetime depressive episodes, duration of depressive episodes, cumulative incidence of depression, lifetime depression diagnoses/misdiagnoses, and the cumulative incidence of maintenance therapy for depression. Sensitivity analyses were used to examine uncertainty.

In the base case, DCPC dominated usual care by offering 0.11 more QALYs for $2500 less per patient (from averted misdiagnoses). DCPC also offered 5 extra depression-free months, shorter depressive episodes, and a lower chance of maintenance therapy. DCPC’s trade-offs were a higher cumulative incidence of depression and more lifetime depressive episodes. Life expectancy was identical under usual care and DCPC. Sensitivity analyses indicate that DCPC was almost always preferable to usual care.

Compared with usual care, DCPC may offer more value to US patients with prostate cancer. DCPC should be considered for inclusion in prostate cancer survivorship care guidelines.

Compared with usual care, DCPC may offer more value to US patients with prostate cancer. DCPC should be considered for inclusion in prostate cancer survivorship care guidelines.

Metamodeling can address computational challenges within decision-analytic modeling studies evaluating many strategies. This article illustrates the value of metamodeling for evaluating colorectal cancer screening strategies while accounting for colonoscopy capacity constraints.

In a traditional approach, the best screening strategy was identified from a limited subset of strategies evaluated with the validated Adenoma and Serrated pathway to Colorectal CAncer model. In a metamodeling approach, metamodels were fitted to this limited subset to evaluate all potentially plausible strategies and determine the best overall screening strategy. Approaches were compared based on the best screening strategy in life-years gained compared with no screening. Metamodel runtime and accuracy was assessed.

The metamodeling approach evaluated >40 000 strategies in <1 minute with high accuracy after 1 adaptive sampling step (mean absolute error 0.0002 life-years) using 300 samples in total (generation time 8 days). strategies compared to a traditional approach. Nevertheless, metamodel validation and identifying extrapolation beyond the support of the original decision-analytic model are critical to the interpretation of results. The screening strategies identified with metamodeling support ongoing discussions on decreasing the starting age of colorectal cancer screening.

Little is known about relationships between opioid- and gabapentinoid-use patterns and healthcare expenditures that may be affected by pain management and risk of adverse outcomes. This study examined the association between patients’ opioid and gabapentinoid prescription filling/refilling trajectories and direct medical expenditures in US Medicare.

This cross-sectional study included a 5% national sample (2011-2016) of fee-for-service beneficiaries with fibromyalgia, low back pain, neuropathy, or osteoarthritis newly initiating opioids or gabapentinoids. Using group-based multitrajectory modeling, this study identified patients’ distinct opioid and gabapentinoid (OPI-GABA) dose and duration patterns, based on standardized daily doses, within a year of initiating opioids and/or gabapentinoids. Concurrent direct medical expenditures within the same year were estimated using inverse probability of treatment weighted multivariable generalized linear regression, adjusting for sociodemographic and health statutent opioid-only users and all concurrent OPI-GABA users were associated with higher healthcare expenditures compared to opioid-only discontinuers.

Dose and duration patterns of concurrent OPI-GABA varied substantially among fee-for-service Medicare beneficiaries. Consistent opioid-only users and all concurrent OPI-GABA users were associated with higher healthcare expenditures compared to opioid-only discontinuers.

To measure access to opioid treatment programs (OTPs) and office-based buprenorphine treatment (OBBTs) at the smallest geographic unit for which the Census Bureau publishes demographic and socioeconomic data (ie, block group) and to explore disparities in access to treatment across the rural-urban and area deprivation continua across the United States.

Access to OTPs and OBBTs at the block group in 2019 was quantified using an innovative 2-step floating catchment area technique that accounts for the supply of treatment facilities relative to the population size, proximity of facilities relative to the location of population in block groups, and time as a barrier within catchments. Block groups were stratified into tertiles based on the rural-urban continuum codes (metropolitan, micropolitan, small town, or rural) and area deprivation index (least-deprived, middle-deprived, most-deprived). The Integrated Nested Laplace Approximation approach was used for statistical analysis.

Across the United States, 3329 block groups corresponding to 2 915 949 adults lacked access to OTPs within a 2-hour drive of their community and 130 block groups corresponding to 86 605 adults did not have access to OBBTs. Disparities in access to treatment were observed across the urban-rural and area deprivation continua including (1) lowest mean access score to OBBTs were found among most-deprived small towns, and (2) lower mean access score to OTPs were found among micropolitan and small towns.

The results of this study revealed disparities in access to medication-assisted treatment. The findings call for creative initiatives and local and regional policies to develop to mitigate access problems.

The results of this study revealed disparities in access to medication-assisted treatment. The findings call for creative initiatives and local and regional policies to develop to mitigate access problems.

Buprenorphine is an essential medication for the treatment of opioid use disorder (OUD), but studies show it has been underused over the last 2 decades. We sought to evaluate utilization of and spending on buprenorphine formulations in Medicaid and to evaluate the impact of key market and regulatory factors affecting availability of different formulations and generic versions.

We first identified all buprenorphine formulations approved by the Food and Drug Administration for OUD using Drugs@FDA. We then used National Drug Codes to identify each drug in the Medicaid State Drug Utilization Data and extracted annual utilization rates and spending between 2002 and 2018 by drug and according to whether a brand-name or generic version was dispensed. We compared these trends to market and regulatory factors that affected competition, which we identified through searching the Federal Register, Westlaw, PubMed, and Google News.

Brand-name buprenorphine-naloxone sublingual tablet and film formulations (Suboxone) prenorphine during the height of the opioid crisis.

To assess the cost-effectiveness of an opioid abuse-prevention program embedded in the Narcotics Information Management System („the Network System to Prevent Doctor-Shopping for Narcotics”) in South Korea.

Using a Markov model with a 1-year cycle length and 30-year time horizon, we estimated the incremental cost-utility ratio (ICUR) of implementing an opioid abuse-prevention program in patients prescribed outpatient opioids from a Korean healthcare payer’s perspective. The model has 6 health states no opioid use, therapeutic opioid use, opioid abuse, overdose, overdose death, and all-cause death. Patient characteristics, healthcare costs, and transition probabilities were estimated from national population-based data and published literature. Age- and sex-specific utilities of the general Korean population were used for the no-use state, whereas the other health-state utilities were obtained from published studies. Costs (in 2019 US dollars) included the expenses of the program, opioids, and overdoses. An annual 5% discount rate was applied to the costs and quality-adjusted life-years (QALYs). Parameter uncertainties were explored via deterministic and probabilistic sensitivity analyses.

The program was associated with 2.27 fewer overdoses per 100 000 person-years, with an ICUR of $227/QALY. The ICURs were generally robust to parameter changes, although the program’s effect on abuse reduction was the most influential parameter. Probabilistic sensitivity analysis showed that the program reached a 100% probability of cost-effectiveness at a willingness-to-pay threshold of $900/QALY.

The opioid abuse-prevention program appears to be cost-effective in South Korea. Mandatory use of the program should be considered to maximize clinical and economic benefits of the program.

The opioid abuse-prevention program appears to be cost-effective in South Korea. Mandatory use of the program should be considered to maximize clinical and economic benefits of the program.

The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature.

A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study.

The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies’ accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs.

The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.

The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.

Opioid-related medication errors (MEs) can have a significant impact on patient health and contribute to opioid misuse. The objective of this study was to estimate the incidence of and variables associated with the receipt of an opioid prescription and opioid-related MEs (omissions, duplications, or dose changes) at hospital discharge. We also determined rates of adverse drug events and risks of emergency department visits, readmissions, or death 30 days and 90 days post discharge associated with MEs.

A cohort of hospitalized patients discharged from the McGill University Health Centre between 2014 and 2016 was assembled. The impact of opioid-related MEs was assessed in a propensity score-adjusted logistic regression models. Multivariable logistic regression was used to determine characteristics associated with MEs and discharge opioid prescription.

A total of 1530 (43.9%) of 3486 patients were prescribed opioids, of which 13.4% (n= 205) of patients had at least 1 opioid-related ME. Rates of MEs were higher in handwritten prescriptions compared to the electronic reconciliation discharge prescription group (20.6% vs 1.2%). Computer-based prescriptions were associated with a 69% lower risk of opioid-related MEs (adjusted odds ratio 0.31, 95% confidence interval 0.14-0.65) as well as 63% lower risk of receiving an opioid prescription. Opioid-related MEs were associated with a 2.3 times increased risk of healthcare utilization in the 30 days postdischarge period (adjusted odds ratio 2.32, 95% confidence interval 1.24-4.32).

Opioid-related MEs are common in handwritten discharge prescriptions. Our findings highlight the need for computer-based prescribing platforms and careful review of medications during critical periods of care such as hospital transitions.

Opioid-related MEs are common in handwritten discharge prescriptions. Our findings highlight the need for computer-based prescribing platforms and careful review of medications during critical periods of care such as hospital transitions.

One-legged pedaling is of interest to elite cyclists and clinicians. However, muscular usage in 1-legged vs. 2-legged pedaling is not fully understood. Thus, the study was aimed to examine changes in leg muscle activation patterns between 2-legged and 1-legged pedaling.

Fifteen healthy young recreational cyclists performed both 1-legged and 2-legged pedaling trials at about 30 Watt per leg. Surface electromyography electrodes were placed on 10 major muscles of the left leg. Linear envelope electromyography data were integrated to quantify muscle activities for each crank cycle quadrant to evaluate muscle activation changes.

Overall, the prescribed constant power requirements led to reduced downstroke crank torque and extension-related muscle activities (vastus lateralis, vastus medialis, and soleus) in 1-legged pedaling. Flexion-related muscle activities (biceps femoris long head, semitendinosus, lateral gastrocnemius, medial gastrocnemius, tensor fasciae latae, and tibialis anterior) in the upstroke phase increased to compensate for the absence of contralateral leg crank torque. During the upstroke, simultaneous increases were seen in the hamstrings and uni-articular knee extensors, and in the ankle plantarflexors and dorsiflexors. At the top of the crank cycle, greater hip flexor activity stabilized the pelvis.

The observed changes in muscle activities are due to a variety of changes in mechanical aspects of the pedaling motion when pedaling with only 1 leg, including altered crank torque patterns without the contralateral leg, reduced pelvis stability, and increased knee and ankle stiffness during the upstroke.

The observed changes in muscle activities are due to a variety of changes in mechanical aspects of the pedaling motion when pedaling with only 1 leg, including altered crank torque patterns without the contralateral leg, reduced pelvis stability, and increased knee and ankle stiffness during the upstroke.

To determine which intrinsic and extrinsic exertional heat illness (EHI) risk factors exist in youth American football players and observe perceptual and physiological responses of players during events (games and practices).

Cross-sectional cohort study observing 63 youth football players, varying in position. Independent variables were league (weight-restricted (WR, n = 27) and age-restricted (AR, n = 36)) and event type. Dependent variables were anthropometrics, work-to-rest ratio, and wet bulb globe temperature. Descriptive variables included preparticipation examination and uniform configuration. A subset of 16 players participated in physiological variables (heart rate and gastrointestinal temperature). Data collection occurred on 7 AR and 8 WR nonconsecutive practices and the first 3 games of the season.

Mean values for anthropometric variables were higher (p < 0.05) in the AR league than the WR league. Work time (χ

(1,111) = 4.232; p = 0.039) and rest time (χ

(1,111) = 43.41; p < 0.001and league type. National youth football organizations need to create thorough guidelines that address EHI risk factors for local leagues to adopt.

Research on achievement goal orientations in sport has typically relied on the use of variable-centered approaches that tend to overlook population heterogeneity. In this study, we used a person-centered approach to identify subgroups of competitive tennis players according to unique combinations of achievement goal orientations and tested for subgroup differences in motivation and mental toughness.

A sample of 323 competitive tennis athletes (69.35% male) between 15 and 25 years of age (17.60 ± 2.40 years, mean ± SD) completed the 3 × 2 Achievement Goal Questionnaire for Sport, Sport Motivation Scale II, and Mental Toughness Index. Latent profile analysis was used to identify unique combinations of achievement goal orientations. Comparisons between latent subgroups on autonomous motivation, controlled motivation, and mental toughness were performed using analysis of variance.

Latent profile analysis supported 3 distinct patterns of achievement goal profiles that were primarily distinguishable based on onjunction with approach types of achievement goals.

The present study aimed to examine the link between physical activity (PA) and life satisfaction in a large international study of adolescents. We also aimed to test whether overweight and underweight perceptions act as mediators and whether age and sex acted as moderators.

For this purpose, we analyzed data from the Health Behavior in School-aged Children study, which comprises 727,865 observations from 44 nations at 4 measurement occasions.

Multilevel analyses revealed a positive link between PA and life satisfaction. In addition, underweight and overweight perceptions mediated the effect of PA on life satisfaction. We further found that age and sex acted as moderators. In older adolescents, stronger effects were found in the links between PA and life satisfaction, PA and overweight perception, and both weight perceptions and life satisfaction. In addition, in female adolescents, the link between overweight perception and life satisfaction was stronger. Conversely, the links between PA and both weight perceptions were stronger for boys.

The results suggest that weight perception explains part of the relationship between PA and life satisfaction in adolescents and that these effects vary as a function of age and sex.

The results suggest that weight perception explains part of the relationship between PA and life satisfaction in adolescents and that these effects vary as a function of age and sex.The organs affected most commonly by AL amyloidosis are the kidneys and heart, however, liver and gastrointestinal (GI) tract are also commonly affected. Symptoms of GI amyloidosis often mimic those of other GI disorders; having a keen awareness of the need to evaluate for amyloidosis is critical in avoiding delay in diagnosis and intervention. GI and liver involvement is associated with significant complications, and challenges in symptomatic management. As with all AL-related organ disease, early systemic treatment can prevent progression of tissue damage and improve outcomes.Streptomyces sp. SCSIO 03032, isolated from a deep-sea sediment sample (-3412 m) from the Indian Ocean, produces several classes of bioactive compounds including α-pyridone antibiotics (piericidins), polycyclic macrolactams (heronamides) and bisindole alkaloids (spiroindimicins, indimicins and lynamicins). Here we report the complete genome sequence of Streptomyces sp. SCSIO 03032, which consists of a 6,287,975 bp linear chromosome. The genome analysis reveals the presence of 29 putative biosynthetic gene clusters for secondary metabolites, including those for piericidins, heronamides and spiroindimicins/indimicins/lynamicins. The genome sequence suggests that Streptomyces sp. SCSIO 03032 could be a producer for novel bioactive natural products with potential applications in drug discovery.Pseudomonas sp. SXM-1, isolated from coastal sea water of Xiamen Bay, could produce extracellular pyoverdine. Here, we present the complete genome of Pseudomonas sp. SXM-1, which will facilitate the genome mining of the pyoverdine synthetase coding gene cluster. The sequenced genome, a circular chromosome, is 7,226,716 bp in length, which contains 60.78% of GC bases, 6549 proteins, 67 tRNAs, and 16 rRNA encoding genes. The structure of pyoverdine produced by Pseudomonas sp. SXM-1 was predicted by using the antiSMASH 5.1.2 tool and further characterized with mass spectroscopic method.Pyruvate is a well-known scavenger of reactive oxygen species (ROS) like hydrogen peroxide and could prevent cells from oxidative damage. A pyruvate-requiring marine bacterium, Pyruvatibacter mobilis CGMCC 1.15125T (=KCTC 42509T), was isolated from the culture broth of a photosynthetic marine microalga. Here we report the complete genome sequence of Pyruvatibacter mobilis, which contained a circular chromosome of 3,333,914 bp with a mean G + C content of 63.9%. Through genomic analysis, we revealed that strain CGMCC 1.15125T encodes genes for some antioxidants like superoxide dismutase, glutathione, rubrerythrin and globin to relieve cellular oxidative stress, while pyruvate added to the medium may reduce extracellular ROS. The genome features of P. mobilis provide further insights into the antioxidant activities of bacteria surviving in oxygen-enriched habitats.This article has been retracted please see Elsevier Policy on Article Withdrawal (https//www.elsevier.com/about/our-business/policies/article-withdrawal). This article was retracted at the request of the authors. The authors of this abstract have advised that full agreement between authors and sponsors on publication of the abstract has not been reached and they are therefore unable to publish this data at present.The global focus on nation states’ responses to the COVID-19 pandemic has rightly highlighted the importance of science and evidence as the basis for policy action. Those with a lifelong passion for evidence-based policy (EBP) have lauded Australia’s and other nations’ policy responses to COVID-19 as a breakthrough moment for the cause. This article reflects on the complexity of the public policy process, the perspectives of its various actors, and draws on Alford’s work on the Blue, Red and Purple zones to propose a more nuanced approach to advocacy for EBP in health. We contend that the pathway for translation of research evidence into routine clinical practice is relatively linear, in contrast to the more complex course for translation of evidence to public policy – much to the frustration of health researchers and EBP advocates. Cairney’s description of the characteristics of successful policy entrepreneurs offers useful guidance to advance EBP and we conclude with proposing some practical mechanisms to support it. Finally, we recommend that researchers and policy makers spend more time in the Purple zone to enable a deeper understanding of, and mutual respect for, the unique contributions made by research, policy and political actors to sound public policy.Objective The aim of this study was to report on the rates of obstetric interventions within each hospital jurisdiction in the state of Queensland, Australia. Methods This project used a whole-of-population linked dataset that included the health and cost data of all mothers who gave birth in Queensland, Australia, between 2012 and 2015 (n=186789), plus their babies (n=189909). Adjusted and unadjusted rates of obstetric interventions and non-instrumental vaginal delivery were reported within each hospital jurisdiction in Queensland. Results High rates of obstetric intervention exist in both the private and public sectors, with higher rates demonstrated in the private than public sector. Within the public sector, there is substantial variation in rates of intervention between hospital and health service jurisdictions after adjusting for confounding variables that influence the need for obstetric intervention. Conclusions Due to the high rates of obstetric interventions statewide, a deeper understanding is needed of what factors may be driving these high rates at the health service level, with a focus on the clinical necessity of the provision of Caesarean sections.