Patients' Perspectives on Transforming Clinical Trial Participation: Large Online Vignette-based Survey.

BACKGROUND: Patients' participation is crucial to the success of randomized controlled trials (RCTs). However, recruiting and retaining patients in trials remain a challenge. OBJECTIVE: This study aims to describe patients' preferences for the organization of RCTs (visits on- site or remotely) and evaluate the potential impact of fulfilling preferences on their willingness to participate in a clinical trial. METHODS: This was a vignette-based survey. Vignettes were case scenarios of real clinical trials assessing pharmacological treatments. These RCTs evaluated 6 prevalent chronic diseases (ie, osteoporosis, osteoarthritis, asthma, cardiovascular diseases, diabetes, and endometriosis). Each vignette described (1) the RCT and characteristics of the treatment tested (ie, doses, administration routes) and (2) the trial procedures and different options (on-site or remotely) for how the trial was organized for informed consent, follow-up visits, and communication of results when the trial was completed. We recruited 628 participants from ComPaRe (www.compare.aphp.fr), a French e-cohort of patients with chronic diseases. The outcomes were the participants' preferences for the way the trial was organized (on-site or remotely) and their willingness to participate in the trial. RESULTS: Of the 628 participants who answered the vignettes, 491 (78.2%) were female (median age 55 years), with different chronic diseases ranging from endometriosis in 59 of 491 (12%) patients to asthma in 133 of 628 (21.2%) patients. In addition, 38 (6.1%) participants wanted to provide informed consent and all trial visits on-site, 176 (28%) wished to participate in the trial entirely remotely, and 414 (65.9%) wanted to combine remote-based and hospital-based visits. Considering the trial as a whole, when the trial was organized in a way that the patients preferred, the median (Q1-Q3) likelihood of participation in the trial was 90% (80-100) versus 60% (30-80) if the trial followed the patients' nonpreferred model. Furthermore, 256 (40.8%) patients responded to open-ended questions expressing their experience with trial participation and visits to the hospital and providing suggestions for improvement. The patients emphasized the need to personalize the way a trial is organized according to each patient's needs and conditions. CONCLUSIONS: There was a significant diversity in the participants' preferences. Most participants preferred hybrid organization involving both on-site and remote visits. Participants were more likely to participate in a trial organized according to their preferences.

Risk of bias in observational studies using routinely collected data of comparative effectiveness research: a meta-research study.

BACKGROUND: To assess the completeness of reporting, research transparency practices, and risk of selection and immortal bias in observational studies using routinely collected data for comparative effectiveness research. METHOD: We performed a meta-research study by searching PubMed for comparative effectiveness observational studies evaluating therapeutic interventions using routinely collected data published in high impact factor journals from 01/06/2018 to 30/06/2020. We assessed the reporting of the study design (i.e., eligibility, treatment assignment, and the start of follow-up). The risk of selection bias and immortal time bias was determined by assessing if the time of eligibility, the treatment assignment, and the start of follow-up were synchronized to mimic the randomization following the target trial emulation framework. RESULT: Seventy-seven articles were identified. Most studies evaluated pharmacological treatments (69%) with a median sample size of 24,000 individuals. In total, 20% of articles inadequately reported essential information of the study design. One-third of the articles (n = 25, 33%) raised some concerns because of unclear reporting (n = 6, 8%) or were at high risk of selection bias and/or immortal time bias (n = 19, 25%). Only five articles (25%) described a solution to mitigate these biases. Six articles (31%) discussed these biases in the limitations section. CONCLUSION: Reporting of essential information of study design in observational studies remained suboptimal. Selection bias and immortal time bias were common methodological issues that researchers and physicians should be aware of when interpreting the results of observational studies using routinely collected data.

The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence.

BACKGROUND: Participation in randomized controlled trials (RCTs) may be quite demanding and could represent an important burden for patients. We aimed to explore this research burden (i.e., the psychological, physical, and financial burdens) experienced by patients through their participation in a RCT. METHODS: We conducted a systematic review of qualitative studies exploring adult patients' experiences with RCT participation. We searched MEDLINE (PubMed), CINAHL, PSYCHINFO, and Embase (search date March 2018) for eligible reports. Qualitative data coding and indexing were assisted by NVivo. The quality of reports was assessed by using the Critical Appraisal Skills Program (CASP) tool. RESULTS: We included 45 qualitative studies that involved 1732 RCT participants. Important psychological burdens were identified at every stage of the trial process. Participants reported feeling anxiety and being afraid of "being a 'guinea pig'" and described undergoing randomization and allocation to a placebo as particularly difficult resulting in disappointment, anger, and depression. Patients' follow-up and trial closure were also responsible for a wide range of psychological, physical, and financial burdens. Furthermore, factors related to burdensome impacts and consequences were discerned. These factors involved trial information, poorly organized and too-demanding follow-up, and lack of appropriate management when the patient's participation ended. Trial participation was also associated with beneficial effects such as the satisfaction of feeling "useful," gaining "a sense of control," and receiving special attention. CONCLUSIONS: Our finding provides a detailed description of research burden across the whole RCT process. Many of the burdens described could be anticipated, and some avoided in a movement toward minimally disruptive clinical research. Such an approach could improve trial recruitment and retention. REVIEW REGISTRATION: PROSPERO CRD42018098994.

Overcoming Barriers to Mobilizing Collective Intelligence in Research: Qualitative Study of Researchers With Experience of Collective Intelligence.

BACKGROUND: Innovative ways of planning and conducting research have emerged recently, based on the concept of collective intelligence. Collective intelligence is defined as shared intelligence emerging when people are mobilized within or outside an organization to work on a specific task that could result in more innovative outcomes than those when individuals work alone. Crowdsourcing is defined as "the act of taking a job traditionally performed by a designated agent and outsourcing it to an undefined, generally large group of people in the form of an open call." OBJECTIVE: This qualitative study aimed to identify the barriers to mobilizing collective intelligence and ways to overcome these barriers and provide good practice advice for planning and conducting collective intelligence projects across different research disciplines. METHODS: We conducted a multinational online open-ended question survey and semistructured audio-recorded interviews with a purposive sample of researchers who had experience in running collective intelligence projects. The questionnaires had an interactive component, enabling respondents to rate and comment on the advice of their fellow respondents. Data were analyzed thematically, drawing on the framework method. RESULTS: A total of 82 respondents from various research fields participated in the survey (n=65) or interview (n=17). The main barriers identified were the lack of evidence-based guidelines for implementing collective intelligence, complexity in recruiting and engaging the community, and difficulties in disseminating the results of collective intelligence projects. We drew on respondents' experience to provide tips and good practice advice for governance, planning, and conducting collective intelligence projects. Respondents particularly suggested establishing a diverse coordination team to plan and manage collective intelligence projects and setting up common rules of governance for participants in projects. In project planning, respondents provided advice on identifying research problems that could be answered by collective intelligence and identifying communities of participants. They shared tips on preparing the task and interface and organizing communication activities to recruit and engage participants. CONCLUSIONS: Mobilizing collective intelligence through crowdsourcing is an innovative method to increase research efficiency, although there are several barriers to its implementation. We present good practice advice from researchers with experience of collective intelligence across different disciplines to overcome barriers to mobilizing collective intelligence.

Meta-analysis of average costs of HIV testing and counselling and voluntary medical male circumcision across thirteen countries.

Objective: Explore facility-level average costs per client of HIV testing and counselling (HTC) and voluntary medical male circumcision (VMMC) services in 13 countries.Methods: Through a literature search we identified studies that reported facility-level costs of HTC or VMMC programmes. We requested the primary data from authors and standardised the disparate data sources to make them comparable. We then conducted descriptive statistics and a meta-analysis to assess the cost variation among facilities. All costs were converted to 2017 US dollars ($).Results: We gathered data from 14 studies across 13 countries and 772 facilities (552 HTC, 220 VMMC). The weighted average unit cost per client served was $15 (95% CI 12, 18) for HTC and $59 (95% CI 45, 74) for VMMC. On average, 38% of the mean unit cost for HTC corresponded to recurrent costs, 56% to personnel costs, and 6% to capital costs. For VMMC, 41% of the average unit cost corresponded to recurrent costs, 55% to personnel costs, and 4% to capital costs. We observed unit cost variation within and between countries, and lower costs in higher scale categories in all interventions.

Antifungal activity of sterols and dipsacus saponins isolated from Dipsacus asper roots against phytopathogenic fungi.

The in vivo antifungal activity of crude extracts of Dipsacus asper roots was evaluated against the phytopathogenic fungi Botrytis cinerea, Colletotrichum coccodes, Blumeria graminis f. sp. hordei, Magnaporthe grisea, Phytophthora infestans, Puccinia recondita and Rhizoctonia solani using a whole-plant assay method. Ethyl acetate and acetone extracts, at 1000µg/mL, suppressed the development of tomato gray mold (TGM) and tomato late blight (TLB) by 90%. Through bioassay-guided isolation, five antifungal substances were isolated from the D. asper roots and identified as ß-sitosterol (1), campesterol (2), stigmasterol (3), cauloside A (4) and a novel dipsacus saponin, named colchiside (3-O-ß-d-xylopyranosyl-23-O-ß-d-glucopyranosyl-28-O-ß-d-(6-O-acetyl)-glucopyranosyl hederagenin) (5). Of those, cauloside A (4) displayed the greatest antifungal efficacy against rice blast, TGM and TLB. Colchiside (5) moderately suppressed the development of TLB, but exhibited little effect against the other diseases. The synergistic effects of the isolated compounds against TLB were also assessed. Synergistic and additive interactions were observed between several of the sterol compounds. This study indicated that the crude extracts of, and bioactive substances from, the roots of D. asper suppress TGM and TLB. In addition, cauloside A (4) and colchiside (5) could be used as antifungal lead compounds.

Isolation of cholinesterase and ß-secretase 1 inhibiting compounds from Lycopodiella cernua.

Three new serratene-type triterpenoids (1-3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4-12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher's method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22µM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42µM. Compound 2 showed the most potent activity with an IC50 of 0.23µM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue.

Anti-inflammatory Activity of Pyrrolizidine Alkaloids from the Leaves of Madhuca pasquieri (Dubard).

A novel pyrrolizidine alkaloids, madhumidine A (1), and two known alkaloids, lindelofidine benzoic acid ester (2) and minalobine B (3) were isolated from the leaves of Madhuca pasquieri (Dubard) H. J. LAM. The chemical structures of these alkaloids were established mainly by NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against lipopolysaccharide-induced nitric oxide production in macrophage RAW264.7 cell. In addition, the cytotoxic activity of all isolated compounds was tested against a panel of cancer cell lines.

Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells.

Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE2, butyl lucidenateD2 (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting the involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum.

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.

Ophthalmologists' and patients' perspectives on treatments for diabetic retinopathy and maculopathy in Vietnam: a descriptive qualitative study.

INTRODUCTION: Globally, diabetic retinopathy (DR) is the leading cause of blindness in working-aged adults. Early detection and treatment of DR is essential for preventing sight loss. Services must be available, accessible and acceptable to patients if we are to ensure they seek such care. OBJECTIVES: To understand patients' knowledge and attitudes towards laser versus antivascular endothelial growth factor (VEGF) injections to treat DR in Vietnam, and to identify factors Vietnamese ophthalmologists consider when making treatment decisions. METHODS: This is a descriptive qualitative study based on semi-structured interviews with 18 patients (12 from Ho Chi Minh City and 6 from Hanoi) plus individual interviews with 24 ophthalmologists working in eye clinics in these cities. Thematic analysis was used to analyse the data. RESULTS: In total, 10/24 (41.7%) ophthalmologists were female, and their median age was 41 years (range 29-69 years). The median age of patients was 56.5 years (range 28-72 years), and 7/18 (38.9%) were female. Briefly, factors that influence DR treatment decisions for ophthalmologists are medical considerations (ie, severity of disease, benefits and risks), availability (ie, treatment and resources) and patient-related factors (ie, costs and adherence). Patient's perceived barriers and facilitators to treatments were based on patient and family related factors (ie, treatment and transportation costs) and previous treatment experiences (ie, positive and negative). Recommendations by all participants included ensuring that both laser and anti-VEGF injections are widely available across the country and controlling costs for patients and the healthcare system. CONCLUSIONS: Reducing DR treatment costs, optimising treatments options, and expanding the network of clinics offering treatment outside metropolitan areas were the main issues raised by participants. These findings can help inform policy changes in Vietnam and may be generalisable to other low-resource settings.

Capturing the clinical decision-making processes of expert and novice diabetic retinal graders using a 'think-aloud' approach.

BACKGROUND: Diabetic eye screening programmes have been developed worldwide based on evidence that early detection and treatment of diabetic retinopathy are crucial to preventing sight loss. However, little is known about the decision-making processes and training needs of diabetic retinal graders, particularly in low- and middle-income countries. OBJECTIVES: To provide data for improving evidence-based diabetic retinopathy training to help novice graders process fundus images more like experts. SUBJECTS/METHODS: This is a mixed-methods qualitative study conducted in southern Vietnam and Northern Ireland. Novice diabetic retinal graders in Vietnam (n = 18) and expert graders in Northern Ireland (n = 5) were selected through a purposive sampling technique. Data were collected from 21st February to 3rd September 2019. The interviewer used neutral prompts during think-aloud sessions to encourage participants to verbalise their thought processes while grading fundus images from anonymised patients, followed by semi-structured interviews. Thematic framework analysis was used to identify themes, supported by illustrative quotes from interviews. Mann-Whitney U tests were used to compare graders' performance. RESULTS: Expert graders used a more systematic approach when grading images, considered all four images per patient and used available software tools such as red-free filters prior to making a decision on management. The most challenging features for novice graders were intra-retinal microvascular abnormalities and new vessels, which were more accurately identified by experts. CONCLUSION: Taking more time to grade fundus images and adopting a protocol-driven "checklist" approach may help novice graders to function more like experts.

Impact of targeted diabetic retinopathy training for graders in Vietnam and the implications for future diabetic retinopathy screening programmes: a diagnostic test accuracy study.

OBJECTIVES: To compare the accuracy of trained level 1 diabetic retinopathy (DR) graders (nurses, endocrinologists and one general practitioner), level 2 graders (midlevel ophthalmologists) and level 3 graders (senior ophthalmologists) in Vietnam against a reference standard from the UK and assess the impact of supplementary targeted grader training. DESIGN: Diagnostic test accuracy study. SETTING: Secondary care hospitals in Southern Vietnam. PARTICIPANTS: DR training was delivered to Vietnamese graders in February 2018 by National Health Service (NHS) UK graders. Two-field retinal images (412 patient images) were graded by 14 trained graders in Vietnam between August and October 2018 and then regraded retrospectively by an NHS-certified reference standard UK optometrist (phase I). Further DR training based on phase I results was delivered to graders in November 2019. After training, a randomised subset of images from January to October 2020 (115 patient images) was graded by six of the original cohort (phase II). The reference grader regraded all images from phase I and II retrospectively in masked fashion. PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity was calculated at the two different time points, and χ2 was used to test significance. RESULTS: In phase I, the sensitivity for detecting any DR for all grader groups in Vietnam was low (41.8-42.2%) and improved in phase II after additional training was delivered (51.3-87.2%). The greatest improvement was seen among level 1 graders (p<0.001), and the lowest improvement was observed among level 3 graders (p=0.326). There was a statistically significant improvement in sensitivity for detecting referable DR and referable diabetic macular oedema between all grader levels. The post-training values ranged from 40.0 to 61.5% (including ungradable images) and 55.6%-90.0% (excluding ungradable images). CONCLUSIONS: This study demonstrates that targeted training interventions can improve accuracy of DR grading. These findings have important implications for improving service delivery in DR screening programmes in low-resource settings.

Problems with evidence assessment in COVID-19 health policy impact evaluation: a systematic review of study design and evidence strength.

INTRODUCTION: Assessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. METHODS: We included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on 26 November 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation. RESULTS: After 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-sectional), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes. DISCUSSION: The reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigour to be actionable by policy-makers. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

Network analysis and functional estimation of the microbiome reveal the effects of cashew nut shell liquid feeding on methanogen behaviour in the rumen.

The effects of cashew nut shell liquid (CNSL) feeding on the methane (CH4 ) emission and the ruminal microbiome of Lai Sind beef cattle were investigated. Changes in the methane production and rumen microbiome by CNSL feeding were monitored by a respiration chamber and 16S rRNA gene amplicon sequencing respectively. The results demonstrated that CNSL feeding mitigated 20.2%-23.4% of the CH4 emission in vivo without apparent adverse effects on feed intake and feed digestibility. The rumen fluid analysis revealed a significant increase in the proportion of propionate in the total short-chain fatty acids. The relative abundance of methanogen (order Methanobacteriales) decreased significantly, indicating the direct inhibitory effect of CNSL on methanogens. The predicted function of the rumen microbiome indicated that carbohydrate and lipid metabolisms including propionate production were upregulated by CNSL feeding, whereas CH4 metabolism was downregulated. A network analysis revealed that methanogen changed its partner bacteria after CNSL feeding. The δ13 C of CH4 ranged from -74.2‰ to -66.6‰ with significant fluctuation by CNSL feeding, in agreement with the shift of the rumen microbiome. Our findings demonstrate that CNSL feeding can mitigate the CH4 emission from local cattle production systems in South-East Asia by modifying the rumen microbiome and its function.

Research response to coronavirus disease 2019 needed better coordination and collaboration: a living mapping of registered trials.

OBJECTIVES: Researchers worldwide are actively engaging in research activities to search for preventive and therapeutic interventions against coronavirus disease 2019 (COVID-19). Our aim was to describe the planning of randomized controlled trials (RCTs) in terms of timing related to the course of the COVID-19 epidemic and research question evaluated. STUDY DESIGN AND SETTING: We performed a living mapping of RCTs registered in the WHO International Clinical Trials Registry Platform. We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered. RESULTS: By August 12, 2020, 1,568 trials for COVID-19 were registered worldwide. Overall, the median ([Q1-Q3]; range) delay between the first case recorded in each country and the first RCT registered was 47 days ([33-67]; 15-163). For the 9 countries with the highest number of trials registered, most trials were registered after the peak of the epidemic (from 100% trials in Italy to 38% in the United States). Most trials evaluated treatments (1,333 trials; 85%); only 223 (14%) evaluated preventive strategies and 12 postacute period intervention. A total of 254 trials were planned to assess different regimens of hydroxychloroquine with an expected sample size of 110,883 patients. CONCLUSION: This living mapping analysis showed that COVID-19 trials have relatively small sample size with certain redundancy in research questions. Most trials were registered when the first peak of the pandemic has passed.

Problems with Evidence Assessment in COVID-19 Health Policy Impact Evaluation: A systematic review of study design and evidence strength.

INTRODUCTION: Assessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. This study systematically reviewed the strength of evidence in the published COVID-19 policy impact evaluation literature. METHODS: We included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on November 26, 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation, assessing what impact evaluation method was used, graphical display of outcomes data, functional form for the outcomes, timing between policy and impact, concurrent changes to the outcomes, and an overall rating. RESULTS: After 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. The majority (n=23/36) of studies in our sample examined the impact of stay-at-home requirements. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-section), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 1/27 studies passed all of the above checks, and 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes. DISCUSSION: The reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigor to be actionable by policymakers. This was largely driven by the circumstances under which policies were passed making it difficult to attribute changes in COVID-19 outcomes to particular policies. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

A scoping review provided a framework for new ways of doing research through mobilizing collective intelligence.

OBJECTIVES: New forms of research involving collective intelligence (CI) of diverse individuals mobilized through crowdsourcing is successfully emerging in various fields. This scoping review aimed to describe these methods across different fields and propose a framework for implementation. STUDY DESIGN AND SETTING: We searched seven electronic databases for reports describing projects that had mobilized CI with crowdsourcing. We used content analysis to develop themes and categories of the methods. RESULTS: We identified 145 reports. CI was mobilized to generate ideas, conduct evaluations, solve problems, and create intellectual outputs. Most projects (n = 110, 76%) were open to the public without restrictions on participants' expertise. Participants contributed to projects by independent contribution (i.e., no interaction with other participants) (n = 50, 34%), collaboration (n = 41, 28%), competitions (n = 33, 23%), and playing games (n = 16, 11%). In total, 61% of articles (n = 89) reported methods to evaluate participants' contribution and decision-making process: 43% used an independent panel of experts and 18% involved end users. We identified challenges in implementation and sustainability of CI and proposed solutions. CONCLUSION: New research methods based on CI through crowdsourcing could transform clinical research. This framework facilitates the implementation of these methods.

Cytotoxic Activity of Compounds from Styrax obassia.

Cancer is a major public health burden in both developed and developing countries. Plant-derived compounds have played an important role in the development of useful anti-cancer agents. The current study was designed to evaluate the cytotoxic activity of chemical compounds from the stem bark of Styrax obassia. Seven known compounds (1-7) were isolated and identified. Compound 2 exhibited cytotoxic activity against the breast cancer cell line MCF-7 with an IC550 of 27.9 µM, followed by the human cervical cancer cell line Hela with an IC50 of 23.3 µM, and the human promyelocytic leukemia cell line HL-60 with an IC50 of 47.8 RM. Compound 7 exhibited cytotoxicity against Hela cells with an ICso of 16.8 pM, followed by MCF-7 cells with an IC50 of 53.5 µM. This is the first study to investigate the significant anti-tumor properties of isolated compounds from the stem bark of S. obassia.

Anti-inflammatory activities of compounds from twigs of Morus alba.

Five new compounds, 10-oxomornigrol F (1), (7″R)-(-)-6-(7″-hydroxy-3″,8″-dimethyl-2″,8″-octadien-1″-yl)apigenin (2), ramumorin A (3), ramumorin B (4), and (4S,7S,8R)-trihydroxyoctadeca-5Z-enoic acid (5), together with 31 known compounds (6-36), were isolated from the twigs of Morus alba (Moraceae). The chemical structures of these compounds were established using spectroscopic analyses, 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and Mosher's methods. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264.7 cells. Compounds 1, 2, 13, 17, 19, 25-28, and 32 showed inhibitory effects with IC50 values ranging from 2.2 to 5.3µg/mL. Compounds 1, 2, 17, 25, and 32 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. In addition, pretreating the cells with compound 1, 17, and 32 significantly suppressed LPS-induced expression of cyclooxygenase-2 (COX-2) protein.