The impact of a health promotion program on toddlers' socio-emotional development: a cluster randomized study.

BACKGROUND: The first 3 years of life are a critical period for the development of socio-emotional skills, highlighting the importance of socio-emotional development in early childhood. This study aimed to evaluate the effectiveness of a health promotion intervention program on the socio-emotional development of children aged 12 to 42 months during the COVID-19 pandemic. METHODS: A total of 344 children from 15 childcare centers participated in this study, with six centers in the intervention group and nine in the control group. Childcare teachers in the intervention group received a 6-month training program aimed at promoting healthy lifestyles, including topics such as diet, sleep, physical activity, and sedentary behavior. Sociodemographic and anthropometric measures were assessed at baseline, and socio-emotional development was assessed using the Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) at baseline and post-intervention. RESULTS: After the intervention, a significant difference in socio-emotional development was observed between children with mothers of varying education levels. Specifically, children whose mothers had lower education levels demonstrated significantly greater socio-emotional development (B = 19.000, p = 0.028) compared to the control group. In contrast, there was no significant difference in socio-emotional development among children with mothers from higher education levels. CONCLUSION: These findings suggest that intervention programs for childcare teachers can effectively promote healthy socio-emotional development in children from socioeconomically disadvantaged backgrounds. Future intervention programs should consider tailoring their approaches to target disadvantaged populations. TRIAL REGISTRATION: This cluster randomized controlled trial was registered in the Clinical Trials database/platform on 09/09/2019 (number NCT04082247).

Assessment of calcinosis in Portuguese patients with systemic sclerosis - a multicenter study.

INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

Development of a Mobile App to Increase the Uptake of HIV Pre-exposure Prophylaxis Among Latino Sexual Minority Men: Qualitative Needs Assessment.

BACKGROUND: HIV disproportionally impacts Latino sexual minority men (SMM). Uptake of pre-exposure prophylaxis (PrEP), an effective biomedical intervention to prevent HIV, is low in this group compared with White SMM. Mobile health technology represents an innovative strategy to increase PrEP uptake among Latino SMM. OBJECTIVE: We aimed to describe the qualitative process leading to the development of SaludFindr, a comprehensive HIV prevention mobile app aiming to increase PrEP uptake, HIV testing, and condom use by Latino SMM. METHODS: We conducted 13 in-depth interviews with Latino SMM living in the Atlanta area to explore their main barriers and facilitators to PrEP uptake and to analyze their opinions of potential SaludFindr app functionalities. To explore potential app functions, we used HealthMindr, an existing HIV prevention app, as a template and added new proposed features intended to address the specific community needs. RESULTS: We identified general PrEP uptake barriers that, although common among non-Latino groups, had added complexities such as the influence of religion and family on stigma. Low perceived PrEP eligibility, intersectional stigma, lack of insurance, cost concerns, and misconceptions about PrEP side effects were described as general barriers. We also identified Latino-specific barriers that predominantly hinder access to existing services, including a scarcity of PrEP clinics that are prepared to provide culturally concordant services, limited availability of Spanish language information related to PrEP access, distrust of peers as credible sources of information, perceived ineligibility for low-cost services owing to undocumented status, fear of immigration authorities, and competing work obligations that prevent PrEP clinic attendance. Health care providers represented a trusted source of information, and 3 provider characteristics were identified as PrEP facilitators: familiarity with prescribing PrEP; being Latino; and being part of lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+) group or ally. The proposed app was very well accepted, with a particularly high interest in features that facilitate PrEP access, including a tailored list of clinics that meet the community needs and a private platform to seek PrEP information. Spanish language availability and free or low-cost PrEP care represented the 2 main clinic criteria that would facilitate PrEP uptake. Latino representation in clinic staff and providers; clinic perception as a safe space for undocumented patients; and LGBTQIA+ representation was listed as additional criteria. Only 8 of 47 clinics listed on the Centers for Diseases Control and Prevention PrEP locator website for the Atlanta area fulfilled at least 2 main criteria. CONCLUSIONS: This study provides further evidence of the substantial PrEP uptake barriers that Latino SMM face; exposes the urgent need to increase the number of accessible PrEP-providing clinics for Latino SMM; and proposes an innovative, community-driven, and mobile technology-based tool as a future intervention to overcome some of these barriers.

EarlyCDT Lung blood test for risk classification of solid pulmonary nodules: systematic review and economic evaluation.

BACKGROUND: EarlyCDT Lung (Oncimmune Holdings plc, Nottingham, UK) is a blood test to assess malignancy risk in people with solid pulmonary nodules. It measures the presence of seven lung cancer-associated autoantibodies. Elevated levels of these autoantibodies may indicate malignant disease. The results of the test might be used to modify the risk of malignancy estimated by existing risk calculators, including the Brock and Herder models. OBJECTIVES: The objectives were to determine the diagnostic accuracy, clinical effectiveness and cost-effectiveness of EarlyCDT Lung; and to develop a conceptual model and identify evidence requirements for a robust cost-effectiveness analysis. DATA SOURCES: MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, EconLit, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database ( NHS EED ) and the international Health Technology Assessment database were searched on 8 March 2021. REVIEW METHODS: A systematic review was performed of evidence on EarlyCDT Lung, including diagnostic accuracy, clinical effectiveness and cost-effectiveness. Study quality was assessed with the quality assessment of diagnostic accuracy studies-2 tool. Evidence on other components of the pulmonary nodule diagnostic pathway (computerised tomography surveillance, Brock risk, Herder risk, positron emission tomography-computerised tomography and biopsy) was also reviewed. When feasible, bivariate meta-analyses of diagnostic accuracy were performed. Clinical outcomes were synthesised narratively. A simulation study investigated the clinical impact of using EarlyCDT Lung. Additional reviews of cost-effectiveness studies evaluated (1) other diagnostic strategies for lung cancer and (2) screening approaches for lung cancer. A conceptual model was developed. RESULTS: A total of 47 clinical publications on EarlyCDT Lung were identified, but only five cohorts (695 patients) reported diagnostic accuracy data on patients with pulmonary nodules. All cohorts were small or at high risk of bias. EarlyCDT Lung on its own was found to have poor diagnostic accuracy, with a summary sensitivity of 20.2% (95% confidence interval 10.5% to 35.5%) and specificity of 92.2% (95% confidence interval 86.2% to 95.8%). This sensitivity was substantially lower than that estimated by the manufacturer (41.3%). No evidence on the clinical impact of EarlyCDT Lung was identified. The simulation study suggested that EarlyCDT Lung might potentially have some benefit when considering intermediate risk nodules (10-70% risk) after Herder risk analysis. Two cost-effectiveness studies on EarlyCDT Lung for pulmonary nodules were identified; none was considered suitable to inform the current decision problem. The conceptualisation process identified three core components for a future cost-effectiveness assessment of EarlyCDT Lung: (1) the features of the subpopulations and relevant heterogeneity, (2) the way EarlyCDT Lung test results affect subsequent clinical management decisions and (3) how changes in these decisions can affect outcomes. All reviewed studies linked earlier diagnosis to stage progression and stage shift to final outcomes, but evidence on these components was sparse. LIMITATIONS: The evidence on EarlyCDT Lung among patients with pulmonary nodules was very limited, preventing meta-analyses and economic analyses. CONCLUSIONS: The evidence on EarlyCDT Lung among patients with pulmonary nodules is insufficient to draw any firm conclusions as to its diagnostic accuracy or clinical or economic value. FUTURE WORK: Prospective cohort studies, in which EarlyCDT Lung is used among patients with identified pulmonary nodules, are required to support a future assessment of the clinical and economic value of this test. Studies should investigate the diagnostic accuracy and clinical impact of EarlyCDT Lung in combination with Brock and Herder risk assessments. A well-designed cost-effectiveness study is also required, integrating emerging relevant evidence with the recommendations in this report. STUDY REGISTRATION: This study is registered as PROSPERO CRD42021242248. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 49. See the NIHR Journals Library website for further project information.

People at risk of lung cancer sometimes undergo computerised tomography ( CT ) scans of their lungs. These scans may identify lung nodules that could be cancerous. Currently, CT scans of the lung nodules, or sometimes further positron emission tomography­computerised tomography ( PET-CT ) scans, are used to predict the risk that a nodule is cancerous. EarlyCDT Lung is a blood test that detects substances, called autoantibodies, associated with having cancer. If the autoantibodies are detected, the chance of a lung nodule being cancerous may be substantially increased. This test could help doctors make decisions about whether to treat immediately, carry out further tests or monitor the nodule over time to see if it grows or changes shape. This project examined the evidence on the clinical value of the EarlyCDT Lung test. We reviewed all published studies of EarlyCDT Lung and reanalysed the reported data. We found that there has been little research on EarlyCDT Lung among people with lung nodules (only five studies comprising 695 patients). This makes it difficult to draw any firm conclusions. The evidence suggests that EarlyCDT Lung may not be particularly effective at determining which lung nodules are cancerous, and may not improve diagnosis when compared with using CT and PET - CT scans. However, this is uncertain because the evidence is so limited. This project also looked for evidence on the value for money of the EarlyCDT Lung test in detecting lung cancer, and found no relevant evidence. This means that the value for money of EarlyCDT Lung is largely unknown, and there is currently no good evidence to support further analyses on this. We therefore sought to summarise the information and analyses that would be needed to support a future assessment of the value for money of EarlyCDT Lung.

Quality of Spontaneous Reports of Adverse Drug Reactions Sent to a Regional Pharmacovigilance Unit.

Spontaneous reports (SRs) of adverse drug reactions (ADRs) remain the basis of pharmacovigilance systems. The main objective of this study was to evaluate the quality of SRs received by the Pharmacovigilance Unit of Beira Interior, in Central Portugal. The second objective was to identify factors associated with complete SRs. SRs received between 1 January 2017 and 31 October 2019 were analyzed. SR information was classified as "mandatory" or "recommended" criteria. SR were then grouped into three categories (well, slightly, and poorly documented). Association between "well documented" SR and confounding variables was estimated using a multiple logistic regression model. The results showed 22.4% of SRs are "well documented", and 41.2% are "poorly documented". Most of the complete SRs correspond to non-serious ADRs (55.8%), with a negative association between complete SRs and serious ADRs (OR = 0.595, [95% CI 0.362-0.977], p = 0.040). There is also a significant association between complete SRs and e-mail notification (OR = 1.876, [95% CI 1.060-3.321], p = 0.002). The results highlight the small amount of SR documentation sent to pharmacovigilance systems. There is an association between non-serious ADRs and complete SRs. These results reinforce the need for training for notification of ADRs and that these SRs include as much information as possible for an effective drug risk management.

Assessment of deep eutectic solvents toxicity in zebrafish (Danio rerio).

Deep Eutectic Systems (DES) have emerged as a "green alternative" to organic solvents and have been coined as biocompatible and biodegradable. However, the number of studies concerning the real biodegradability and biocompatibility are scarce. Thus, to study the toxicity of certain DES, two different approaches were used: i) zebrafish exposure via water, where the system (DES) was tested at potentially realistic environmental concentrations and ii) via intraperitoneal injection, where the system was tested in different concentrations, relevant to the pharmaceutical industry. These studies were performed using zebrafish, a standardized animal model often used in biomedicine and toxicological assays. The results show low toxicity according to tested concentrations (up to 73.47 µM), when the system CA:T:W, with a 2:1:3 molar ratio, was tested through exposure via water and also in the intraperitoneal injection tests with concentrations up to 6000 µM. The activity of different enzymes involved in antioxidant pathways (glutathione S-transferase, catalase, glutathione peroxidase), the total antioxidant capacity (TAC) and lipoperoxidation (MDA content) were determined suggesting low toxicity of the tested system (DES). The promising results herein presented show that DES present the potential to be used as the new class of green solvents, not only for use in the pharmaceutical industry, but also in cosmetic and chemical engineering processes without causing negative impact on living organisms.

In silico design and in vitro assessment of anti-Helicobacter pylori compounds as potential small-molecule arginase inhibitors.

Related to a variety of gastrointestinal disorders ranging from gastric ulcer to gastric adenocarcinoma, the infection caused by the gram-negative bacteria Helicobacter pylori (H. pylori) poses as a great threat to human health; hence, the search for new treatments is a global priority. The H. pylori arginase (HPA) protein has been widely studied as one of the main virulence factors of this bacterium, being involved in the prevention of nitric oxide-mediated bacterial cell death, which is a central component of innate immunity. Given the growing need for the development of new drugs capable of combating the infection by H. pylori, the present work describes the search for new HPA inhibitors, using virtual screening techniques based on molecular docking followed by the evaluation of the proposed modes of interaction at the HPA active site. In vitro studies of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), followed by cytotoxicity activity in gastric adenocarcinoma and non-cancer cells, were performed. The results highlighted compounds 6, 11, and 13 as potential inhibitors of HPA; within these compounds, the results indicated 13 presented an improved activity toward H. pylori killing, with MIC and MBC both at 64 µg/mL. Moreover, compound 13 also presented a selectivity index of 8.3, thus being more selective for gastric adenocarcinoma cells compared to the commercial drug cisplatin. Overall, the present work demonstrates the search strategy based on in silico and in vitro techniques is able to support the rational design of new anti-H. pylori drugs.

Non-invasive imaging software to assess the functional significance of coronary stenoses: a systematic review and economic evaluation.

BACKGROUND: QAngio® XA 3D/QFR® (three-dimensional/quantitative flow ratio) imaging software (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS® vFFR® (vessel fractional flow reserve) imaging software (Pie Medical Imaging BV, Maastricht, the Netherlands) are non-invasive technologies to assess the functional significance of coronary stenoses, which can be alternatives to invasive fractional flow reserve assessment. OBJECTIVES: The objectives were to determine the clinical effectiveness and cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR. METHODS: We performed a systematic review of all evidence on QAngio XA 3D/QFR and CAAS vFFR, including diagnostic accuracy, clinical effectiveness, implementation and economic analyses. We searched MEDLINE and other databases to January 2020 for studies where either technology was used and compared with fractional flow reserve in patients with intermediate stenosis. The risk of bias was assessed with quality assessment of diagnostic accuracy studies. Meta-analyses of diagnostic accuracy were performed. Clinical and implementation outcomes were synthesised narratively. A simulation study investigated the clinical impact of using QAngio XA 3D/QFR. We developed a de novo decision-analytic model to estimate the cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR relative to invasive fractional flow reserve or invasive coronary angiography alone. Scenario analyses were undertaken to explore the robustness of the results to variation in the sources of data used to populate the model and alternative assumptions. RESULTS: Thirty-nine studies (5440 patients) of QAngio XA 3D/QFR and three studies (500 patients) of CAAS vFFR were included. QAngio XA 3D/QFR had good diagnostic accuracy to predict functionally significant fractional flow reserve (≤ 0.80 cut-off point); contrast-flow quantitative flow ratio had a sensitivity of 85% (95% confidence interval 78% to 90%) and a specificity of 91% (95% confidence interval 85% to 95%). A total of 95% of quantitative flow ratio measurements were within 0.14 of the fractional flow reserve. Data on the diagnostic accuracy of CAAS vFFR were limited and a full meta-analysis was not feasible. There were very few data on clinical and implementation outcomes. The simulation found that quantitative flow ratio slightly increased the revascularisation rate when compared with fractional flow reserve, from 40.2% to 42.0%. Quantitative flow ratio and fractional flow reserve resulted in similar numbers of subsequent coronary events. The base-case cost-effectiveness results showed that the test strategy with the highest net benefit was invasive coronary angiography with confirmatory fractional flow reserve. The next best strategies were QAngio XA 3D/QFR and CAAS vFFR (without fractional flow reserve). However, the difference in net benefit between this best strategy and the next best was small, ranging from 0.007 to 0.012 quality-adjusted life-years (or equivalently £140-240) per patient diagnosed at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. LIMITATIONS: Diagnostic accuracy evidence on CAAS vFFR, and evidence on the clinical impact of QAngio XA 3D/QFR, were limited. CONCLUSIONS: Quantitative flow ratio as measured by QAngio XA 3D/QFR has good agreement and diagnostic accuracy compared with fractional flow reserve and is preferable to standard invasive coronary angiography alone. It appears to have very similar cost-effectiveness to fractional flow reserve and, therefore, pending further evidence on general clinical benefits and specific subgroups, could be a reasonable alternative. The clinical effectiveness and cost-effectiveness of CAAS vFFR are uncertain. Randomised controlled trial evidence evaluating the effect of quantitative flow ratio on clinical and patient-centred outcomes is needed. FUTURE WORK: Studies are required to assess the diagnostic accuracy and clinical feasibility of CAAS vFFR. Large ongoing randomised trials will hopefully inform the clinical value of QAngio XA 3D/QFR. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019154575. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 56. See the NIHR Journals Library website for further project information.

Stable angina is a type of chest pain; left untreated, it can lead to heart failure, heart attack and sudden death. To avoid these outcomes, patients may require surgical intervention to open obstructed arteries, known as 'revascularisation'. Patients who might need revascularisation undergo tests to identify blocked arteries. The last line of testing is called invasive fractional flow reserve assessment. This is an invasive measurement of blood flow that involves inserting a wire into an artery after the patient has taken drugs to dilate the artery. It carries some risks and may have side effects. Non-invasive tests have been proposed to precede or replace invasive fractional flow reserve assessments. These include QAngio^® XA 3D/QFR^® (three-dimensional/quantitative flow ratio) (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS^® vFFR^® (vessel fractional flow reserve) (Pie Medical Imaging BV, Maastricht, the Netherlands) imaging software. This project investigated whether or not these technologies can provide accurate assessments of blood pressure, and if they are a reasonable use of NHS resources. A thorough review of all the literature on the technologies was performed. All data were combined and re-analysed to determine whether or not the tests accurately predict the need for revascularisation and to consider their clinical benefits. An economic analysis was conducted to investigate whether or not using either of these technologies is economically viable. The project found that QAngio XA 3D/QFR can accurately measure blood flow, may be a reasonable alternative to fractional flow reserve, pending more evidence on benefits to patients' health, and is a reasonable use of NHS resources. The current evidence for CAAS vFFR is too limited to draw any firm conclusions.

Cost-effectiveness of point-of-care creatinine testing to assess kidney function prior to contrast-enhanced computed tomography imaging.

BACKGROUND: Patients undergoing contrast-enhanced computed tomography (CECT) imaging in a non-emergency outpatient setting often lack a recent estimated Glomerular Filtration Rate measurement. This may lead to inefficiencies in the CECT pathway. The use of point-of-care (POC) creatinine tests to evaluate kidney function in these patients may provide a safe and cost-effective alternative to current practice, as these can provide results within the same CECT appointment. METHODS: A decision tree model was developed to characterise the diagnostic pathway and patient management (e.g., intravenous hydration) and link these to adverse renal events associated with intravenous contrast media. Twelve diagnostic strategies including three POC devices (i-STAT, ABL800 Flex and StatSensor), risk factor screening and laboratory testing were compared with current practice. The diagnostic accuracy of POC devices was derived from a systematic review and meta-analysis; relevant literature sources and databases informed other parameters. The cost-effective strategy from a health care perspective was identified based on highest net health benefit (NHB) which were expressed in quality-adjusted life years (QALYs) at £20,000/QALY. RESULTS: The cost-effective strategy, with a NHB of 9.98 QALYs and a probability of being cost-effective of 79.3%, was identified in our analysis to be a testing sequence involving screening all individuals for risk factors, POC testing (with i-STAT) on those screening positive, and performing a confirmatory laboratory test for individuals with a positive POC result. The incremental NHB of this strategy compared to current practice, confirmatory laboratory test, is 0.004 QALYs. Results were generally robust to scenario analysis. CONCLUSIONS: A testing sequence combining a risk factor questionnaire, POC test and confirmatory laboratory testing appears to be cost-effective compared to current practice. The cost-effectiveness of POC testing appears to be driven by reduced delays within the CECT pathway. The contribution of intravenous contrast media to acute kidney injury, and the benefits and harms of intravenous hydration remain uncertain.

Uncertainty Analysis in Intervention Impact on Health Inequality for Resource Allocation Decisions.

Cost-effectiveness analysis, routinely used in health care to inform funding decisions, can be extended to consider impact on health inequality. Distributional cost-effectiveness analysis (DCEA) incorporates socioeconomic differences in model parameters to capture how an intervention would affect both overall population health and differences in health between population groups. In DCEA, uncertainty analysis can consider the decision uncertainty around on both impacts (i.e., the probability that an intervention will increase overall health and the probability that it will reduce inequality). Using an illustrative example assessing smoking cessation interventions (2 active interventions and a "no-intervention" arm), we demonstrate how the uncertainty analysis could be conducted in DCEA to inform policy recommendations. We perform value of information (VOI) analysis and analysis of covariance (ANCOVA) to identify what additional evidence would add most value to the level of confidence in the DCEA results. The analyses were conducted for both national and local authority-level decisions to explore whether the conclusions about decision uncertainty based on the national-level estimates could inform local policy. For the comparisons between active interventions and "no intervention," there was no uncertainty that providing the smoking cessation intervention would increase overall health but increase inequality. However, there was uncertainty in the direction of both impacts when comparing between the 2 active interventions. VOI and ANCOVA show that uncertainty in socioeconomic differences in intervention effectiveness and uptake contributes most to the uncertainty in the DCEA results. This suggests potential value of collecting additional evidence on intervention-related inequalities for this evaluation. We also found different levels of decision uncertainty between settings, implying that different types and levels of additional evidence are required for decisions in different localities.

Jointly Modelling Economics and Epidemiology to Support Public Policy Decisions for the COVID-19 Response: A Review of UK Studies.

COVID-19 in the UK has had a profound impact on population health and other socially important outcomes, including on education and the economy. Although a range of evidence has guided policy, epidemiological models have been central. It is less clear whether models to support decision making have sought to integrate COVID-19 epidemiology with a consideration of broader health, wellbeing and economic implications. We report on a rapid review of studies seeking to integrate epidemiological and economic modelling to assess the impacts of alternative policies. Overall, our results suggest that few studies have explored broader impacts of different COVID-19 policies in the UK. Three studies looked only at health, capturing impacts on individuals with and without COVID-19, with various methods used to model the latter. Four models considered health and wider impacts on individuals' economic outcomes, such as wages. However, these models made no attempt to consider the dynamic impacts on economic outcomes of others and the wider economy. The most complex analyses sought to link epidemiological and dynamic economic models. Studies compared a wide range of policies, although most were defined in general terms with minimal consideration of their granular specifications. There was minimal exploration of uncertainty, with no consideration in half the studies. Selecting appropriate models to inform decisions requires careful thought of factors relevant to the decision options under consideration such as the outcomes of interest, sectors likely to be impacted and causal pathways. In summary, better linking epidemiological and economic modelling would help to inform COVID-19 policy.

Assessment of suspected adverse drug reactions in elderly patients with diabetes mellitus based on a Portuguese spontaneous reporting database: analysis of reporting from 2008 to 2018.

BACKGROUND: Age is one of the most important risk factors in the development of diabetes mellitus and certain drug classes indicated for this condition may be associated with clinically important adverse drug reactions (ADRs). The aim of this study was to analyze the suspected ADRs in older patients with diabetes mellitus, reported to the Portuguese Pharmacovigilance System from 2008 to 2018. RESEARCH DESIGN AND METHODS: A retrospective analysis of suspected ADRs reports was performed, involving patients aged ≥65 years. RESULTS: Of a total of 751 reports collected, 439 were considered serious, 199 led to hospitalization and in 19 of them occurred a fatal outcome. Most of them were observed in females (n = 393) and involved patients belonging mainly to the age group 65-74 years (n = 405). Taking into account a total of 2134 suspected ADRs, the most frequent were hypoglycemia (2.67%) and lactic acidosis (2.62%). The drugs specifically indicated for glycemic control were the most frequently involved in ADRs. CONCLUSIONS: Most of the ADRs were reported as serious and were mainly associated to drugs in diabetes mellitus. In addition, the majority of them, such as hypoglycemia, are preventable, highlighting the importance to identify possible factors that determine this occurrence, especially in the elderly.

Listeria monocytogenes Assessment in a Ready-to-Eat Salad Shelf-Life Study Using Conventional Culture-Based Methods, Genetic Profiling, and Propidium Monoazide Quantitative PCR.

Listeriosis is almost entirely transmitted through foods contaminated with Listeria monocytogenes. Ready-to-eat foods present a particular challenge due to their long refrigerated shelf-life, not requiring any heat treatment before consumption. In this work, a shelf-life assessment of an industrially produced ready-to-eat salad was performed using conventional culture-based and molecular methods. L. monocytogenes isolates were confirmed and serogrouped using multiplex PCR, and genetic subtyping was performed by pulsed-field gel electrophoresis (PFGE). PMAxx-qPCR was used as an alternative method for L. monocytogenes quantification in foods. Salad samples were kept at 4 °C, 12 °C, and 16 °C for eight days and analysed. At 4 °C, acceptable results were obtained considering hygiene indicators, i.e., Enterobacteriaceae (ranging from 3.55 ± 0.15 log cfu/g to 5.39 ± 0.21 log cfu/g) and aerobic mesophilic colony counts (5.91 ± 0.90 log cfu/g to 9.41 ± 0.58 log cfu/g) throughout the study, but the same did not happen at 12 °C and 16 °C. L. monocytogenes culture-based quantification exhibited low numbers (<1 log cfu/g) for all temperatures. From 30 presumptive isolates, 10 (33.3%) were confirmed as L. monocytogenes with the majority belonging to serogroup IVb. PFGE subtyping showed that 7 of the 10 L. monocytogenes isolates had 100% of pulsotype similarity, suggesting a possible common contamination source. PMAxx-qPCR revealed a statistically higher L. monocytogenes quantification (>3 log cfu/g) when compared to the conventional culture-based method, suggesting viable but non-culturable forms. Taken together, results underline the need to combine conventional methods with more sensitive, specific, and rapid ones for L. monocytogenes assessment in ready-to-eat foods shelf-life studies to reduce the potential risk for consumers.

Quality Assessment of Chilled and Frozen Fish-Mini Review.

Fish is a very perishable food and therefore several storage strategies need to be employed to increase its shelf-life, guaranteeing its safety and quality from catch to consumption. Despite the advances in modern fish storage technologies, chilling and freezing are still the most common preservation methods used onboard. The present review aims to summarize strategies to increase the shelf-life of fresh (chilled) and frozen fish, as whole, gutted, or fillet, involving the assessment of different traditional cooling and freezing conditions of different fish species caught in different locations. Although there are other factors that influence the fish shelf-life, such as the fish species and the stress suffered during catch, storage time and temperature and the amount of ice are some of the most important. In addition, the way that fish is stored (whole, fillet, or gutted) also contributes to the final quality of the product. In most studies, whole chilled and frozen fish present longer shelf-life than those preserved as gutted and filleted. However, it should be noted that other factors related to the organism, capture method, and transport to the preparation/processing industry should be considered for shelf-life extension.

Assessment of Campylobacter fetus subsp. venerealis molecular diagnosis using clinical samples of bulls.

BACKGROUND: Campylobacter fetus subsp. venerealis (Cfv) is the pathogen responsible for Bovine Genital Campylobacteriosis (BGC), a venereal disease of cattle associated with impaired reproductive performance. Although several PCR assays were developed to identify this pathogen, most of them are still poorly evaluated in clinical samples. This study evaluated real-time PCR assays for Cfv detection in preputial samples of bulls (n = 308). RESULTS: The detection at the subspecies level (Cfv) compared four assays: two targeting ISCfe1 and two targeting parA gene. The detection at the species level (C. fetus) considered an assay targeting the nahE gene and a commercial kit for C. fetus identification. At the subspecies level, assays directed either to different targets (parA and ISCfe1), or to the same target (ISCfe1 or parA), showed a high percentage of disagreeing results. All samples positive at the subspecies level (n = 169) were negative in C. fetus detection assays, which strongly suggests the horizontal gene transfer of ISCfe1 and parA to other bacterial species. This was confirmed by microbiological isolation of three Campylobacter portucalensis strains responsible for false positive results. Sequences with a high level of identity with ISCfe1 and parA gene of Cfv were identified in C. portucalensis genome. CONCLUSIONS: Overall, this study reveals that PCR assays solely directed to a subspecies target originate a high rate of false positive results, due to the presence of parA and ISCfe1 homologous sequences in other bacterial species, namely of the genus Campylobacter. Although the specificity of these methods may be higher if applied to bulls from herds with clinical features of BGC or in other geographical regions, current PCR diagnosis should couple subspecies and species targets, and further research must be envisaged to identify Cfv specific molecular targets.

Point-of-care creatinine tests to assess kidney function for outpatients requiring contrast-enhanced CT imaging: systematic reviews and economic evaluation.

BACKGROUND: Patients with low estimated glomerular filtration rates may be at higher risk of post-contrast acute kidney injury following contrast-enhanced computed tomography imaging. Point-of-care devices allow rapid measurement of estimated glomerular filtration rates for patients referred without a recent estimated glomerular filtration rate result. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of point-of-care creatinine tests for outpatients without a recent estimated glomerular filtration rate measurement who need contrast-enhanced computed tomography imaging. METHODS: Three systematic reviews of test accuracy, implementation and clinical outcomes, and economic analyses were carried out. Bibliographic databases were searched from inception to November 2018. Studies comparing the accuracy of point-of-care creatinine tests with laboratory reference tests to assess kidney function in adults in a non-emergency setting and studies reporting implementation and clinical outcomes were included. Risk of bias of diagnostic accuracy studies was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Probabilities of individuals having their estimated glomerular filtration rates correctly classified were estimated within a Bayesian framework and pooled using a fixed-effects model. A de novo probabilistic decision tree cohort model was developed to characterise the decision problem from an NHS and a Personal Social Services perspective. A range of alternative point-of-care testing approaches were considered. Scenario analyses were conducted. RESULTS: Fifty-four studies were included in the clinical reviews. Twelve studies reported diagnostic accuracy for estimated glomerular filtration rates; half were rated as being at low risk of bias, but there were applicability concerns for most. i-STAT (Abbott Point of Care, Inc., Princeton, NJ, USA) and ABL (Radiometer Ltd, Crawley, UK) devices had higher probabilities of correctly classifying individuals in the same estimated glomerular filtration rate categories as the reference laboratory test than StatSensor® devices (Nova Biomedical, Runcorn, UK). There was limited evidence for epoc® (Siemens Healthineers AG, Erlangen, Germany) and Piccolo Xpress® (Abaxis, Inc., Union City, CA, USA) devices and no studies of DRI-CHEM NX 500 (Fujifilm Corporation, Tokyo, Japan). The review of implementation and clinical outcomes included six studies showing practice variation in the management decisions when a point-of-care device indicated an abnormal estimated glomerular filtration rate. The review of cost-effectiveness evidence identified no relevant studies. The de novo decision model that was developed included a total of 14 strategies. Owing to limited data, the model included only i-STAT, ABL800 FLEX and StatSensor. In the base-case analysis, the cost-effective strategy appeared to be a three-step testing sequence involving initially screening all individuals for risk factors, point-of-care testing for those individuals with at least one risk factor, and including a final confirmatory laboratory test for individuals with a point-of-care-positive test result. Within this testing approach, the specific point-of-care device with the highest net benefit was i-STAT, although differences in net benefit with StatSensor were very small. LIMITATIONS: There was insufficient evidence for patients with estimated glomerular filtration rates < 30 ml/minute/1.73 m2, and on the full potential health impact of delayed or rescheduled computed tomography scans or the use of alternative imaging modalities. CONCLUSIONS: A three-step testing sequence combining a risk factor questionnaire with a point-of-care test and confirmatory laboratory testing appears to be a cost-effective use of NHS resources compared with current practice. The risk of contrast causing acute kidney injury to patients with an estimated glomerular filtration rate of < 30 ml/minute/1.73 m2 is uncertain. Cost-effectiveness of point-of-care testing appears largely driven by the potential of point-of-care tests to minimise delays within the current computed tomography pathway. FUTURE WORK: Studies evaluating the impact of risk-stratifying questionnaires on workflow outcomes in computed tomography patients without recent estimated glomerular filtration rate results are needed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018115818. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 39. See the NIHR Journals Library website for further project information.

Before computed tomography scans are done, a contrast agent is usually needed to improve the visibility of internal body structures. After receiving a contrast agent (through a vein), some patients' kidneys may be affected, especially if their kidneys already do not work well. A blood test can identify these patients before a computed tomography scan, to reduce the risk of kidney harm. The blood test measures creatinine, which is a marker of how well the kidneys work. Before a contrast-enhanced computed tomography scan, some patients have a recent creatinine result from an earlier blood test. Blood tests are normally done in a central laboratory, and usually take at least 1 hour. Other patients do not have a recent creatinine result, so their computed tomography scan may be delayed or rearranged. Sometimes, to avoid risking kidney harm, patients may have scans without contrast. 'Point-of-care' (handheld, tabletop or portable) devices can quickly measure creatinine (usually in patients with risk factors), often from a finger-prick blood sample. Many point-of-care devices are available but they may not be as exact as laboratory tests, so their benefit is unclear. This study reviewed all available evidence on the benefits and harms of point-of-care creatinine tests before computed tomography scans and assessed whether or not they are a cost-effective use of NHS resources. The study found that some devices [i.e. i-STAT (Abbott Point of Care, Inc., Princeton, NJ, USA) and ABL (Radiometer Ltd, Crawley, UK)] were more accurate than others [i.e. StatSensor^® (Nova Biomedical, Runcorn, UK)]. There was insufficient evidence for other devices. The study found that, for outpatients, doing a point-of-care test in patients who are at a higher risk of kidney harm (according to a questionnaire) and then confirming this with a laboratory test appeared to be a cost-effective use of NHS resources. The study found that the risk of kidney harm as a result of contrast agents appears very low. The main benefit of point-of-care testing may be to reduce needless delays or rearranged computed tomography scan appointments.

Impact of Socioeconomic Differences on Distributional Cost-effectiveness Analysis.

Public health decision makers value interventions for their effects on overall health and health inequality. Distributional cost-effectiveness analysis (DCEA) incorporates health inequality concerns into economic evaluation by accounting for how parameters, such as effectiveness, differ across population groups. A good understanding of how and when accounting for socioeconomic differences between groups affects the assessment of intervention impacts on overall health and health inequality could inform decision makers where DCEA would add most value. We interrogated 2 DCEA models of smoking and alcohol policies using first national level and then local authority level information on various socioeconomic differences in health and intervention use. Through a series of scenario analyses, we explored the impact of altering these differences on the DCEA results. When all available evidence on socioeconomic differences was incorporated, provision of a smoking cessation service was estimated to increase overall health and increase health inequality, while the screening and brief intervention for alcohol misuse was estimated to increase overall health and reduce inequality. Ignoring all or some socioeconomic differences resulted in minimal change to the estimated impact on overall health in both models; however, there were larger effects on the estimated impact on health inequality. Across the models, there were no clear patterns in how the extent and direction of socioeconomic differences in the inputs translated into the estimated impact on health inequality. Modifying use or coverage of either intervention so that each population group matched the highest level improved the impacts to a greater degree than modifying intervention effectiveness. When local level socioeconomic differences were considered, the magnitude of the impacts was altered; in some cases, the direction of impact on inequality was also altered.

Prevalence of negative self-rated health and associated factors among healthcare workers in a Southeast Brazilian city. / Prevalência e fatores associados à autoavaliação negativa de saúde entre trabalhadores da rede municipal de saúde de Diamantina, Minas Gerais.

OBJECTIVE: to investigate the prevalence of negative self-rated health and associated factors among municipal health service workers in Diamantina, MG, Brazil. METHODS: this was a cross-sectional census study using Poisson regression. RESULTS: 203 health workers took part in the study, 70.9% were female, and 57.1% were up to 38 years old; prevalence of negative self-rated health was 28.6% (95%CI22.4;34.8); in the multivariate analysis, the following were associated with the outcome: being 39 years old or more (PR=1.56 - 95%CI1.01;2.40), monthly family income >3 minimum wages (PR=0.63 - 95%CI0.41;0.97), having another paid occupation (PR=0.55 - 95%CI0.34;0.89), poor sleep quality (PR=1.99 - 95%CI1.32;2.99), diagnosis of one disease (PR=2.33 - 95%CI1.13;4.81) or multiple diseases (PR=2.63 - 95%CI1.32;5.24), suffering aggression at work (PR=1.92 - 95%CI1.29;2.85), and frequent participation in domestic activities (PR=0.55 - 95%CI0.38;0.80). CONCLUSION: prevalence of negative self-rated health was high and was associated with sociodemographic, occupational, behavioral and health situation factors.

Violência no trabalho entre trabalhadores municipais do setor saúde de Diamantina, MG, 2017 / Workplace violence among municipal health care workers in Diamantina, Minas Gerais, Brazil, 2017

Introdução: Trabalhadores do setor saúde são destaques em estudos recentes pelas proporções significativas de vivência de violência no trabalho. Objetivo: Estimar a prevalência e os fatores associados à violência entre trabalhadores da saúde. Método: Estudo de corte transversal, realizado com trabalhadores municipais de saúde. A coleta de dados ocorreu de dezembro de 2016 a março de 2017, por meio de entrevistas a trabalhadores da saúde de Diamantina (MG). Para a análise, a variável violência no trabalho foi tratada como desfecho em análises bivariada e múltiplas. Foram utilizadas técnicas de estatística descritivas e analíticas (regressão de Poisson). Resultados: Participaram da pesquisa 203 trabalhadores municipais de saúde (taxa de resposta de 79%). A prevalência de violência no trabalho foi de 40,4% no total, sendo de 47,9% entre as mulheres e de 22,0% entre os homens. Os fatores do trabalho associados à violência foram a satisfação com o trabalho, o baixo apoio e a alta demanda psicológica no trabalho. Conclusão: A prevalência evidenciada e as associações sugeridas direcionam para a necessidade de reformular e criar políticas de proteção à saúde dos trabalhadores da saúde de modo que amenize os possíveis efeitos dessa experiência na saúde do trabalhador e na qualidade do serviço prestado

Background: Health care workers stand out in recent studies as a function of high rates of workplace violence. Objective: To calculate the prevalence of workplace violence involving health care workers and associated factors. Methods: Cross-sectional study with municipal health care workers in Diamantina, Minas Gerais, Brazil. Data were collected in interviews from December 2016 through March 2017. Variable workplace violence was considered as outcome on univariate and multivariate analysis. Descriptive and analytical statistical techniques were used (Poisson regression). Results: The study population comprised 203 municipal health care workers (79% response rate). The prevalence of workplace violence was 40.4­47.9% for women and 22.0% for men. Occupational factors associated with violence were job satisfaction, support at work and psychological demands. Conclusion: The prevalence rates we found and associated factors point to the relevance of health protection policies targeting this category of workers which may contribute to mitigate the negative effects of violence on the health of workers and consequently on the quality of care delivery

Arsenic in rice and rice products in Northwestern Mexico and health risk assessment.

The aim of this study was to evaluate the health risk of arsenic exposure by consumption of rice and its products marketed in northwestern Mexico. Sixty-six national and imported rice products were purchased in markets in northwestern Mexico, an endemic arsenic region. Total and inorganic arsenic in rice samples were analysed by inductively coupled plasma atomic emission spectroscopy and the risk assessment was evaluated according to the hazard quotient (HQ) and carcinogenic risk (CR). Total and inorganic arsenic in rice samples ranged from 0.06 to 0.29 mg/kg and from 0.03 to 0.13 mg/kg, respectively, and 40% of the analysed samples exceeded FAO/WHO arsenic recommended levels. The inorganic/total arsenic ratio ranged from 15% to 65%. The HQ and CR values for total and inorganic arsenic did not exceed safety levels. Therefore, rice supply in the northwestern of Mexico appears to be safe for human consumption.