Unknown Effectiveness Research Articles

Intersectional collaboration and the development of prevention infrastructures: a qualitative study

PurposeInvesting in prevention could be of great benefit to public health. Especially for people with health risks, such as overweight, depressive symptoms, low social-economic status or people who experience loneliness or a sedentary lifestyle. In the Netherlands, different parties are responsible for financing and organising selective and indicated preventive interventions: the government, municipalities and health insurance companies. The aim of this study was two-fold: First, to describe the transition towards a sustainable prevention infrastructure. And second, to gain insight into barriers and facilitators associated with intersectoral collaboration regarding organising prevention for high-risk groups.Design/methodology/approachA longitudinal qualitative study was conducted among collaborative networks working together to build a prevention infrastructure. During a five-year study period, 86 semi-structured interviews were held. The COM-B model was used for data analysis.FindingsBarriers to intersectoral collaboration are: unknown (cost-)effectiveness, limited incentives to invest in collaboration, lack of clarity about responsibilities, differences in priorities and organisational culture between municipalities and health insurers. Facilitators are commitment, trust, sharing knowledge between parties, meeting regularly within the network and acknowledgement of mutual responsibilities. Also, national policy interventions targeted at the development of regional prevention infrastructures facilitated collaboration.Originality/valueThis study shows that collaboration regarding prevention is becoming increasingly common. It can be concluded that the transition towards a sustainable prevention infrastructure has started. The relationship between key stakeholders, like municipalities and health insurers, is generally stronger than it was five years ago. They have a better understanding of each other’s interests and expectations.

A Novel Distributed Adaptive Controller for Multi-Agent Systems with Double-Integrator Dynamics: A Hedging-Based Approach

In this paper, we focus on designing a model reference adaptive control-based distributed control law to drive a set of agents with double-integrator dynamics in a leader–follower fashion in the presence of system anomalies such as agent-based uncertainties, unknown control effectiveness, and actuator dynamics. In particular, we introduce a novel hedging-based reference model with second-order dynamics to allow an adaptation in the presence of actuator dynamics. We show the stability of the overall closed-loop multi-agent system by utilizing the Lyapunov Stability Theory, where we analyze the stability condition by using the Linear Matrix Inequalities method to show the boundedness of the reference model and actuator states. Finally, we illustrate the efficacy of the proposed distributed adaptive controller on an undirected and connected line graph in five cases.

Superiority and cost-effectiveness of Individual Placement and Support versus standard employment support for people with alcohol and drug dependence: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial

Individual Placement and Support (IPS) is a specialist intervention to help people attain employment in the open competitive labour market. IPS has been developed in severe mental illness and other disabilities, but it is of unknown effectiveness for people with alcohol and drug dependence. The Individual Placement and Support-Alcohol and Drug (IPS-AD) is the first superiority trial to evaluate effectiveness and cost-effectiveness. IPS-AD was a pragmatic, parallel-group, multi-centre, randomised, controlled, phase 3 trial of standard employment support (treatment-as-usual [TAU]) versus IPS. IPS was offered as a single episode for up to 13 months. The study was done at seven community treatment centres for alcohol and drug dependence in England. Study participants were adults (18-65 years), who had been enrolled for at least 14 days in treatment for alcohol use disorder (AUD), opioid use disorder (OUD), or another drug use disorder (DUD; mostly cannabis and stimulants); were unemployed or economically inactive for at least six months; and wished to attain employment in the open competitive labour market. After random allocation to study interventions, the primary outcome was employment during 18-months of follow-up, analysed by mixed-effects logistic regression, using multiple imputation for the management of missing outcome data. There were two cost-effectiveness outcomes: a health outcome expressed as a quality adjusted life year (QALY) using £30,000 and £70,000 willingness-to-pay [WTP] thresholds; and additional days of employment, with a WTP threshold of £200 per day worked. The study was registered with ISRCTN (ISRCTN24159790) and is completed. Between 8 May 2018 and 30 September 2019, 2781 potentially eligible patients were identified. 812 were excluded before screening, and 1720 participants were randomly allocated to TAU or IPS. In error, nine participants were randomised to study interventions on two occasions-so data for their first randomisation was analysed (modified intention-to-treat). A further 24 participants withdrew consent for all data to be used (full-analysis set therefore 1687 participants [70.1% male; mean age 40.8 years]; TAU, n=844; IPS, n=843 [AUD, n=610; OUD, n=837; DUD, n=240]). Standard employment support was received by 559 [66.2%] of 844 participants in the TAU group. IPS was received by 804 [95.37%] of 843 participants in the IPS group. IPS was associated with an increase in attainment of employment compared with TAU (adjusted odds ratio [OR] 1.29; 95% CI 1.02-1.64; p-value 0.036). IPS was effective for the AUD and DUD groups (OR 1.48; 95% CI 1.14-1.92; p-value 0.004; OR 1.45, 95% CI 1.03-2.04, p-value 0.031, respectively), but not the OUD group. IPS returned an incremental QALY outcome gain of 0.01 (range 0.003-0.02) per participant with no evidence of cost-effectiveness at either WTP threshold-but QALY gains were cost-effective for the AUD and DUD groups at the £70,000 WTP threshold (probability 0.52 and 0.97, respectively). IPS was cost-effective for additional days of employment (probability 0.61), with effectiveness relating to the AUD group only (probability >0.99). Serious Adverse Events were reported by 39 participants (13 [1.5%] of 844 participants in the TAU group and 23 [2.7%] of 43 participants in the IPS group). There was a total of 25 deaths (1.5%; 9 in the TAU group and 16 in the IPS group)-none judged related to study interventions. In this first superiority randomised controlled trial of IPS in alcohol and drug dependence, IPS helped more people attain employment in the open competitive labour market than standard employment support. IPS was cost-effective for a QALY health outcome (£70,000 WTP threshold) for the AUD and DUD groups, and for additional days of employment for the AUD group (£200 per day worked WTP threshold). UK government Work and Health Unit.

Sustainable prevention infrastructure in the healthcare system: Developments in The Netherlands

Introduction: There is increasing attention to (disease) prevention within healthcare. However, in OECD countries only around 1% of health expenditure is spent on prevention. In the Netherlands different parties are responsible for organizing prevention. As a consequence, embedding preventive activities into the Dutch healthcare system lags behind. Especially for people with health risks, such as overweight children or frail older people. In order to move towards sustainable organized prevention, it is necessary that organizations start working together. In recent years several policy interventions have been introduced to stimulate cross-sector collaboration and the transition towards sustainable prevention infrastructure in the healthcare system. The aim of this study is to learn more form this transition.
 Who is it for? Researchers, policymakers, collaborative prevention networks.
 Methods: This longitudinal qualitative study was conducted among collaborative networks working together on integrating prevention, care and welfare to build a prevention infrastructure. Interviews were held with representatives of municipalities, health insurers, municipality health services and program managers. Two to five interviews per network were conducted during a five year study period. In total 88 semi-structured interviews were held. Networks were followed over time to gain insight into experiences with cross-sectoral collaboration. And to explore the changes in perceived barriers and facilitators associated with collaborating on implementing a prevention infrastructure.
 Key findings: Barriers for implementing a prevention infrastructure are unknown (cost-)effectiveness and differences in organization culture between municipalities and health insurers. Growing awareness of the urgency of prevention and acknowledgement of mutual responsibilities can be seen as a facilitator. As well as national policy interventions concerning a regional prevention infrastructure and a intervention-oriented approach. Preconditions for cross-sector collaboration became more specific over time, commitment and trust provide the basis, followed by low-threshold contact and having a shared goal. Clearness about legal responsibilities is important for stakeholders in order to work together to organize prevention. The discussion on appropriate funding played a major role over the years.
 Conclusions/Learning: This study shows that collaboration regarding prevention is becoming more and more common. The relationship between key stakeholders, like municipalities and health insurers, is generally more strengthened than five years ago. They have better understanding of each other’s interests and expectations. In addition, they started to consider prevention more as their mutual responsibility in recent years. It was found to be important for the government to regularly collect from stakeholders what they need, in order to continuously improve national public health policy. 
 Next steps: Policies regarding prevention infrastructure continues to evolve, in order to further stimulate collaboration between stakeholder. Developments in this area will continue to be monitored in the coming years.
 Keywords: Prevention, health policy, healthcare system, cross-sector collaboration, longitudinal qualitative research, collaborative networks.

Robust output-feedback control of fluid resuscitation with absolute stability guarantee against uncertain physiology and therapeutic responsiveness

This paper presents a robust closed-loop control approach to fluid resuscitation in patients with hemorrhagic blood loss. A unique strength of the proposed approach is its robustness against uncertain and time-varying patient physiology and therapeutic effectiveness. First, we adopted an observer-based control architecture that can fulfill set point tracking and disturbance rejection objectives. Second, we determined the control gains to achieve adequate transient response performance using the linear quadratic regulator design. Third, we determined the observer gains as a solution to a set of linear matrix inequalities so that the overall closed-loop fluid resuscitation control system is (i) robust against the variability in patient physiology and (ii) absolutely stable against unknown therapeutic effectiveness. We demonstrated the initial proof-of-concept of the proposed approach by conducting rigorous in silico testing using a large number of physiologically plausible virtual patients, while ascertaining the absolute stability via the circle criterion analysis. The results suggested that the proposed approach to closed-loop control of fluid resuscitation is a promising option to advance automation of fluid resuscitation armed with stability against a large variability in patient physiology and therapeutic effectiveness as well as adequate performance in set point tracking and disturbance rejection.

Compared to what? An analysis of comparators in trials informing the National Institute of Clinical Excellence (NICE) low back pain guideline

BackgroundLow back pain (LBP) is the leading cause of disability globally. Clinical practice guidelines (CPGs) have been developed in hopes of encouraging evidence-based care for LBP. However, poor quality of trials that underpin CPGs can lead to misleading recommendations for LBP. ObjectivesTo categorize the comparator used in trials included in the National Institute of Clinical Excellence (NICE) LBP CPG and describe the proportion and association of suboptimal comparators with NICE recommendation. MethodsWe conducted a cross-sectional analysis to describe the proportion of trials included in the NICE LBP CPG that used a suboptimal comparator. If comparators used an ineffective treatment, a treatment of unknown effectiveness, or no or minimal treatment then they were considered suboptimal. ResultsWe included 408 trials and analyzed 580 comparators used in the trials. 30.9% of the comparators used in the trials were suboptimal. Trials testing invasive treatments (32.4%) had the highest proportion of suboptimal comparators followed by non-surgical (32.3%) and pharmacological (19.0%) treatments. Trials using suboptimal treatments were less likely to have their treatment recommended (odds ratio: 0.68; 95% CI: 0.47, 0.98) for use by NICE. ConclusionThere is a concerning proportion of suboptimal comparators used in LBP trials that may be misleading CPG recommendations, funding allocation decisions, and ultimately clinical practice. Efforts to increase the use of optimal comparators in LBP trials are urgently needed to better understand what treatments should be recommended.

Effectiveness of Internet-Based Cognitive Behavioral Therapy for Patients With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Internet-based cognitive behavioral therapy (ICBT) is a relatively new therapy with unknown effectiveness in patients with cancer. In addition, therapist-guided and self-guided ICBT patient-specific outcomes for cancer patients remain to be explored. To explore the effects of ICBT on psychological outcomes, physical outcomes, and daily life outcomes in patients with cancer. Electronic databases such as PubMed, Web of Science, Cochrane Library, EMBASE, APA PsycINFO, ProQuest, and ClinicalTrials.gov were searched for relevant studies published from their inception to October 2022. Five GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) considerations were used to assess the quality of relevant evidence. Data analysis was performed via RevMan 5.4 (The Cochrane Collaboration, London, United Kingdom) and Stata 15.0 (StataCorp, College Station, Texas). Three thousand two hundred forty-nine participants from 20 studies were included in the meta-analysis. Statistically significant effects of ICBT were found on psychological distress, quality of life (QOL), anxiety, and depression, after the intervention. A separate analysis of follow-up data showed that ICBT had a sustainable effect on psychological distress, anxiety, and depression. Subgroup analyses showed that therapist-guided ICBT was more effective for psychological distress and QOL. Internet-based cognitive behavioral therapy can improve symptom management for patients with cancer. Internet-based cognitive behavioral therapy effectively improves psychological distress, anxiety, and depression in patients with cancer after intervention and at follow-up. Internet-based cognitive behavioral therapy improved QOL for cancer patients postintervention but not during follow-up. Internet-based cognitive behavioral therapy did not relieve fatigue or fear of recurrence in cancer patients. Therapist-guided ICBT is recommended for its superior outcomes in alleviating psychological distress and improving overall QOL in adults with cancer when compared with self-guided ICBT.

Adaptive Nonlinear Incremental Flight Control for Systems With Unknown Control Effectiveness

This article exposes that although some sensor-based nonlinear fault-tolerant control frameworks including incremental nonlinear dynamic inversion control can passively resist a wide range of actuator faults and structural damage without requiring an accurate model of the dynamic system, their stability heavily relies on a sufficient condition, which is unfortunately violated if the control direction is unknown. Consequently, it is proved in this article that no matter, which perturbation compensation technique (adaptive, disturbance observer, sliding-mode) is implemented, none of the existing nonlinear incremental control methods can guarantee closed-loop stability. Therefore, this article proposes a Nussbaum function-based adaptive incremental control framework for nonlinear dynamic systems with partially known (control direction is unknown) or even completely unknown control effectiveness. Its effectiveness is proved in the Lyapunov sense and is also verified via numerical simulations of an aircraft attitude tracking problem in the presence of sensing errors, parametric model uncertainties, structural damage, actuator faults, as well as inversed and unknown control effectiveness.

Adaptive neural-network-based distributed fault estimation for heterogeneous multi-agent systems

This contribution addresses the issue of distributed fault estimation for heterogeneous multi-agent systems which are composed of unmanned ground vehicles and unmanned aerial vehicles in the presence of actuator faults, completely unknown nonlinearities and external disturbances. Given that these two types of agents have different state dimensions and the motion of unmanned aerial vehicles in the XOY plane and Z-axis is relatively independent, the heterogeneous multi-agent systems can be divided into the XOY plane of all agents’ position subsystem and the Z-axis of unmanned aerial vehicles’ position subsystem. Then, combining the influences of completely unknown nonlinearities and external disturbances, an adaptive neural-network-based distributed fault estimation scheme is proposed to effectively estimate unknown actuation effectiveness parameters and can be applied to XOY plane and Z-axis of heterogeneous multi-agent systems separately. During the design of the observer, the neural network methodology is adopted to approximate completely unknown nonlinearities and a proper adaptive update law to estimate the 2-norm upper bound of disturbances and compensate for the influences of disturbances is designed. With output from a local agent and its neighbors, the proposed observer can be built on this agent, realizing simultaneous estimation of possible faults occurring in both the selected agent and its neighbor agents, which presents a new distributed framework. At last, simulation results are shown to illustrate the feasibility and effectiveness of the presented fault estimation algorithm.

Analysing land policy processes with stages model: Land policy cases of Ethiopia and Rwanda

Land policies are formulated with the goal of addressing land use management challenges. Therefore, a thorough investigation is required to assess effectiveness of land policy processes. The unknown land use policy effectiveness is how and where the formulation and identification of land use problems affect the throughput of policy implementation. The main objective of this paper is to assess the effectiveness of land policy processes using models of public policy analysis. The study analyses how the stages model could be useful for analysis, and in which areas the advocacy coalition framework (ACF) could enhance the analysis. For comparative insights, land policy cases of Ethiopia and Rwanda were used. Data on land policy processes in the two cases were gathered from literature and data collected from field. The analysis with the two models shows that the effectiveness of executing land use policy processes does not only rely on the conventional cycle and sequence of land use policy implementation steps (i.e. identification of the problem, formulation of the solution, execution of the solution). Instead, during the problem formulation certain dynamics occur which may prevent finding the right and only solution. The stages model is useful for analyzing manifestations as they occur along processes, and the ACF is required as a valuable model to enhance analysis by understanding the cause of manifestations. This study would impact the research method for analyzing effectiveness of land policy processes and improving practices of policy making on the basis of good land governance and public administration perspective.

Solution and Parameter Identification of a Fixed-Bed Reactor Model for Catalytic CO2 Methanation Using Physics-Informed Neural Networks

In this study, we develop physics-informed neural networks (PINNs) to solve an isothermal fixed-bed (IFB) model for catalytic CO2 methanation. The PINN includes a feed-forward artificial neural network (FF-ANN) and physics-informed constraints, such as governing equations, boundary conditions, and reaction kinetics. The most effective PINN structure consists of 5–7 hidden layers, 256 neurons per layer, and a hyperbolic tangent (tanh) activation function. The forward PINN model solves the plug-flow reactor model of the IFB, whereas the inverse PINN model reveals an unknown effectiveness factor involved in the reaction kinetics. The forward PINN shows excellent extrapolation performance with an accuracy of 88.1% when concentrations outside the training domain are predicted using only one-sixth of the entire domain. The inverse PINN model identifies an unknown effectiveness factor with an error of 0.3%, even for a small number of observation datasets (e.g., 20 sets). These results suggest that forward and inverse PINNs can be used in the solution and system identification of fixed-bed models with chemical reaction kinetics.

Willingness to Treat with Therapies of Unknown Effectiveness in Severe COVID-19: A Survey of Intensivist Physicians.

RationaleLittle is known about how physicians develop their beliefs about new treatments or update their beliefs in the face of new clinical evidence. These issues are particularly salient in the context of the coronavirus disease (COVID-19) pandemic, which created rapid demand for novel therapies in the absence of robust evidence.ObjectivesTo identify psychological traits associated with physicians’ willingness to treat with unproven therapies and willingness to update their treatment preferences in the setting of new evidence in the context of COVID-19.MethodsWe administered a longitudinal e-mail survey to United States physicians board certified in intensive care medicine in April and May 2020 (phase one) and October and November 2020 (phase two). We assessed five psychological traits potentially related to evidence uptake: need for cognition, evidence skepticism, need for closure, risk tolerance, and research engagement. We then examined the relationship between these traits and physician preferences for pharmacological treatment for a hypothetical patient with severe COVID-19 pneumonia.ResultsThere were 592 responses to the phase one survey, conducted prior to publication of trial data. At this time physicians were most willing to treat with macrolide antibiotics (50.5%), followed by antimalaria agents (36.1%), corticosteroids (24.5%), antiretroviral agents (22.6%), and angiotensin inhibitors (4.4%). Greater evidence skepticism (relative risk [RR], 1.40; 95% confidence interval [CI], 1.30–1.52; P < 0.001), greater need for closure (RR, 1.19; 95% CI, 1.06–1.34; P = 0.003), and greater risk tolerance (RR, 1.17; 95% CI, 1.08–1.26; P < 0.001) were associated with an increased willingness to treat, whereas greater need for cognition (RR, 0.85; 95% CI, 0.75–0.96, P = 0.010) and greater research engagement (RR, 0.91; 95% CI, 0.88–0.95; P < 0.0001) were associated with decreased willingness to treat. In phase two, most physicians updated their beliefs after publication of trial data about antimalarial agents and corticosteroids. Physicians with greater evidence skepticism were more likely to persist in their beliefs.ConclusionsPsychological traits associated with clinical decisions in the setting of uncertain evidence may provide insight into strategies to better align clinical practice with published evidence.

Adverse effects of hydroxychloroquine and azithromycin on contractility and arrhythmogenicity revealed by human engineered cardiac tissues

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic as declared by World Health Organization (WHO). In the absence of an effective treatment, different drugs with unknown effectiveness, including antimalarial hydroxychloroquine (HCQ), with or without concurrent administration with azithromycin (AZM), have been tested for treating COVID-19 patients with developed pneumonia. However, the efficacy and safety of HCQ and/or AZM have been questioned by recent clinical reports. Direct effects of these drugs on the human heart remain very poorly defined. To better understand the mechanisms of action of HCQ +/- AZM, we employed bioengineered human ventricular cardiac tissue strip (hvCTS) and anisotropic sheet (hvCAS) assays, made with human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCMs), which have been designed for measuring cardiac contractility and electrophysiology, respectively. Our hvCTS experiments showed that AZM induced a dose-dependent negative inotropic effect which could be aggravated by HCQ; electrophysiologically, as revealed by the hvCAS platform, AZM prolonged action potentials and induced spiral wave formations. Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.

India faces a challenge with its mass vaccination efforts

India faces a challenge with its mass vaccination efforts

Case series on the safety of mRNA COVID19 vaccines in cancer patients undergoing treatment.

e14562 Background: Millions of vaccines have been administered since Emergency Use Authorization has been granted for two mRNA COVID-19 vaccines (mCV). The Center for Disease Control (CDC) and Prevention recommends that immunocompromised individuals with no contraindications to vaccines may receive an mCV. The CDC suggests that patients receiving cancer therapies should be consulted about the unknown vaccine safety profile and effectiveness. The American Society of Clinical Oncology recognizes that vaccine may reduce the risk of infection for individuals with cancer. Vaccine trials have not actively enrolled immunocompromised or patients on active cancer therapy; therefore, the potential side effects and efficacy of the mRNA vaccines in these individuals are unexplored. Per state guidelines, many patients with cancer undergoing treatment qualify for vaccination however current vaccine uptake in that population is unknown. Data in this specific high-risk population is needed to increase confidence in the vaccine. We explored adverse events (AE) to the mCV in a small cohort of patients undergoing cancer therapy. Methods: Our case series evaluated patients' tolerance to the voluntary but recommended 2 doses of the mCV while on chemotherapy (CX), checkpoint inhibitors (CPI) or tyrosine kinase inhibitors (TKI) at the George Washington University (GWU) Cancer Center in Washington DC. Patient chart review and phone interviews were conducted. Patients had independently signed up for the mCV at the GWU Hospital or through the DC Health Department. Patients were asked if they had experienced any of the commonly reported side effects listed by the CDC or others new symptoms receiving the vaccine. Results: 12 patients had voluntarily received the mCV, all patients were above the age of 65 with a mean age of 72 (66-85). ECOG performance status was 2 or above in 4 patients. 6 patients were receiving single agent CPI, 1 patient was on combination CX and CPI. 2 patients were on oral TKI for EGFR mutated lung cancer. 3 other patients were on combination CX with rituximab, ramucirumab or radiation. In the 2 patients on daily TKI, treatment was not interrupted for the mCV. In the 10 other patients, all but one patient received the mCV at least one week after the last therapy. Both mCV were tolerated without any life-threatening AE or hospitalization. Pain and swelling at the vaccine site were the most common local AE and reported in 7 patients. 6 patients reported systemic AE most commonly myalgia and headaches. Conclusions: This exploratory analysis in 12 patients with cancer undergoing treatment did not uncover any additional SE signals. Larger studies are needed to evaluate AE and efficacy and to guide recommendations for COVID19 vaccination in this patient population.

Trends and Usage Patterns of Minimally Invasive Glaucoma Surgery in the United States: IRIS® Registry Analysis 2013–2018

Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness. Retrospective analysis. Minimally invasive glaucoma surgeries and standard glaucoma surgeries recorded in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. We used the data from IRIS Registry between 2013 and 2018 (inclusive) to measure the annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device [GDD] placement) performed in the United States, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique also were conducted. Trends and sociodemographic characteristics of MIGS use in the United States. Two hundred three thousand three hundred thirty-two eyes and 232 537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD), Ninth or Tenth Revision, codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, a substantial increase in annual MIGS procedures occurred over the study period (from 7586 in 2013 to 39 677) and a smaller decrease in standard glaucoma procedures (from 16 215 to 13 701). The proportion of iStent procedures almost tripled during the study period (from 14% to 40%), and by 2017 accounted for almost half (43.7%) of all glaucoma surgeries in the United States. Twenty-one thousand twenty-five of all eyes (10.3%) underwent multiple procedures: 7638 (36.3%) on the same day and 13 387 (63.7%) on subsequent days. Endocyclophotocoagulation and iStent placement were the most common concurrent procedures (55.4% of all concurrent procedures). Trabeculectomy and GDD placement were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, endocyclophotocoagulation and goniotomy were the most common procedures performed (33.0% and 21.9%, respectively). A significant increase in MIGS use occurred over the recent 6-year period, despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS versus traditional surgical treatments for glaucoma.

What Gastroenterologists Should Know About COVID-19 Vaccines

What Gastroenterologists Should Know About COVID-19 Vaccines

Systems theory and analysis of the implementation of non pharmaceutical policies for the mitigation of the COVID-19 pandemic

We utilize systems theory in the study of the implementation of non pharmaceutical strategies for the mitigation of the COVID-19 pandemic. We present two models. The first one is a model of predictive control with receding horizon and discontinuous actions of unknown costs for the implementation of adaptive triggering policies during the disease. This model is based on a periodic assessment of the peak of the pandemic (and, thus, of the health care demand) utilizing the latest data about the transmission and recovery rate of the disease. Consequently, the model seems to be suitable for discontinuous, non-mechanical (i.e. human) actions with unknown effectiveness, like those applied in the case of COVID-19. Secondly, we consider a feedback control problem in order to contain the pandemic at the capacity of the NHS (National Health System). As input parameter we consider the value $ p $ that reflects the intensity-effectiveness of the measures applied and as output the predicted maximum of infected people to be treated by NHS. The feedback control regulates $ p $ so that the number of infected people is manageable. Based on this approach, we address the following questions: (a) the limits of improvement of this approach; (b) the effectiveness of this approach; (c) the time horizon and timing of the application.

What works in Conservation 2021 by W.J. SutherlandL.V. DicksS.O. PetrovanR.K. Smith

191 DOI: https://doi.org/10.3318/BIOE.2021.12 Biology and Environment: Proceedings of the Royal Irish Academy,Vol. 121, No. 3, 191–193 (2021). © Royal Irish Academy Cite as follows: O’ Criodain, C. 2021 Book review: What works in Conservation 2021. Biology and Environment: Proceedings of the Royal Irish Academy 2021. DOI: https:// doi.org/10.3318/ BIOE.2021.12 BOOK REVIEW What works in Conservation 2021 W.J. Sutherland, L.V. Dicks, S.O. Petrovan, and R.K. Smith (eds); Cambridge, UK. Open Book Publishers (2021). https://doi.org/10.11647/OBP.0267 What works in Conservation is published annually in book form (electronic and hard copy) by the Conservation Evidence Project. This project was conceived by Professor William Sutherland and is managed by Dr Rebecca Smith, both of the Zoology Department,University of Cambridge.They are supported by sixteen other experts, most of whom are also based in that university.The aim of the project is to provide evidence for various conservation interventions at ground level. The project publishes a journal entitled Conservation Evidence. More importantly, it maintains a searchable website containing a searchable database of over 7,800 summaries of previously published scientific papers, reports, reviews or systematic reviews that document the effects of a multitude of conservation interventions. The studies can be searched by ‘category’ (the taxa or biomes that are the target of the conservation actions), habitat (which overlaps somewhat with ‘category’), threat type, country, and action type (‘land/ water management’, ‘species management’, ‘land/ water protection’,‘livelihood economic and other incentives ’, ‘law and policy’, ‘education and awareness raising’ and ‘other’).There are also over 3,000 conservation actions or interventions that are searchable using the same parameters. The information contained on the website is also available in a series of synopses, again both as paper publications and in electronic format. The key messages from the synopses are, in turn, published annually in book form, with assessments of each intervention by expert panels, and it is this publication which is under review here. The book is organised in the main by chapters according to the targeted taxa or biomes. The former includes amphibians, bats, birds, primates, subtidal benthic invertebrates,aquatic mammals,and terrestrial mammals. The latter include farmland, forest, peatland, and shrubland and heathland.There are also chapters on the management of captive­ animals, control of freshwater invasive species, natural pest control and enhancing soil fertility. Within each chapter, the material is organised according to threats and/or conservation interventions . For example, the chapter on birds—the longest in the book—consists of sections addressing measures such as habitat protection and restoration, education and awareness-raising, and special actions for declining populations. Threats from residential and commercial development, agriculture, energy productions and mining, transportation, verges and airports,power lines,biological resource use (including direct take, fisheries bycatch etc.), disturbance, habitat modification, invasive alien species, pollution , and climate change are also addressed. Each section is divided into subsections,based on the classification of threats and actions used in the IUCN Red List. For example, in the agriculture section of the birds chapter, the first subsection deals with management interventions applicable to all farming systems, while further subsections follow on arable farming, livestock farming, perennial (non-timber) crops, and aquaculture. In the first subsection alone twenty-seven different interventions are assessed, including the creation of ‘skylark plots’, set-aside and the establishment of uncultivated margins. The various interventions are then assessed as ‘beneficial’, ‘likely to be beneficial’, ‘trade-off­ between benefits and harms’, ‘unknown effectiveness (limited evidence)’,‘unlikely to be beneficial’, ‘likely to be ineffective or harmful’,or‘no evidence found (no assessment)’.The assessment is arrived at by a panel of experts scoring three factors: effectiveness (0% = no effect; 100% = always effective); certainty of the evidence (0% = no evidence; 100% = complete certainty); and harms (0% = no harms; 100% = major negative side effects to the species/ habitat of concern). Before assessing the merit of the book,it should be said that the underlying website is a very useful resource. Although critics may argue that there is a heavy bias towards Western Europe and North America in the studies,this reflects the huge ­ capacity gap between those...

Adverse effects of hydroxychloroquine and azithromycin on contractility and arrhythmogenicity revealed by human engineered cardiac tissues

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic as declared by World Health Organization (WHO). In the absence of an effective treatment, different drugs with unknown effectiveness, including antimalarial hydroxychloroquine (HCQ), with or without concurrent administration with azithromycin (AZM), have been tested for treating COVID-19 patients with developed pneumonia. However, the efficacy and safety of HCQ and/or AZM have been questioned by recent clinical reports. Direct effects of these drugs on the human heart remain very poorly defined. To better understand the mechanisms of action of HCQ +/− AZM, we employed bioengineered human ventricular cardiac tissue strip (hvCTS) and anisotropic sheet (hvCAS) assays, made with human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCMs), which have been designed for measuring cardiac contractility and electrophysiology, respectively. Our hvCTS experiments showed that AZM induced a dose-dependent negative inotropic effect which could be aggravated by HCQ; electrophysiologically, as revealed by the hvCAS platform, AZM prolonged action potentials and induced spiral wave formations. Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.