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Emergency care for asthma is provided by general practitioners, pulmonologists, and emergency departments (EDs). Although it is known that patients presenting to EDs with acute asthma exacerbations are a vulnerable population and that this mode of presentation is a risk marker for more severe complications, research on this population is scarce. We conducted a retrospective study on patients with asthma exacerbations who presented to the ED of the University Hospital Basel, Switzerland, during 2017-2020. Of the last 200 presentations, 100 were selected and analyzed to assess demographic information, the use of previous and ED-prescribed asthma medication, and clinical outcomes after a mean period of time of 18 months. Of these 100 asthma patients, 96 were self-presenters, and 43 had the second highest degree of acuity (emergency severity index 2). Global Initiative for Asthma (GINA) step 1 and step 3 were the most common among patients with known GINA levels, accounting for 22 and 18 patients, respectively. A total of 4 patients were undergoing treatment with oral corticosteroids at presentation, and 34 were at discharge. At presentation, 38 patients used the combination therapy of inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA), and 6 patients underwent ICS monotherapy. At discharge, 68 patients were prescribed with ICS/LABA. At entry to the ED, about one-third of patients did not use any asthma medication. In total, 10 patients were hospitalized. None of them needed invasive or non-invasive ventilation. A follow-up for the study was precluded by the majority of patients. This group of asthma patients seemed particularly vulnerable as their asthma medication at presentation was often not according to guidelines or even lacking, and almost all the patients had self-presented to the ED without any reference from a physician. The majority of patients did not give consent to the collection of any follow-up information. These medical shortcomings reflect an urgent medical need to improve care for patients at high risk of asthma exacerbations.

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Purpose: Immune imbalances in major depressive disorder (MDD) have been targeted by anti-inflammatory treatment approaches in clinical trials to increase responsiveness to therapy. However, even after several meta-analyses, no translation of evidence into clinical practice has taken place. We performed a systematic review to evaluate meta-analytic evidence of randomized controlled trials on the use of anti-inflammatory agents for MDD to summarize efficacy estimates and elucidate shortcomings. Methods: Pooled effect estimates and heterogeneity indices were primary outcomes. Characteristics of the included meta-analyses were extracted. Scientific quality of meta-analyses was assessed using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR). Results: N=20 meta-analyses met the eligibility criteria. Study characteristics like outcome scales, composition of patient populations, and add-on or monotherapy regimen varied very little for celecoxib studies, varied little for minocycline studies, and were rather variable for omega 3 fatty acids studies. R-AMSTAR scores ranged from 26 to 39 out of 44 points indicating variable quality, where a comprehensive literature search was the strongest and the consideration of scientific quality in the conclusions was the weakest domain across all meta-analyses. For minocycline and celecoxib, superiority was demonstrated with medium to large effect size with substantial heterogeneity and with large to very large effect size with negligible heterogeneity, respectively. For omega 3 fatty acids, superiority was also demonstrated with mainly small and medium effect sizes with substantial heterogeneity. However, for minocycline and omega 3 fatty acids, non-significant meta-analyses were found also. Conclusion: Even in our synthesized approach, no clear recommendations could be derived on the use of anti-inflammatory treatment for MDD due to several critical aspects like heterogeneity, diversity of patient populations, treatment regimen, and outcomes, and limited scientific quality. However, we observed clear inter-substance differences with meta-analytic evidence being strongest for celecoxib and weakest for omega 3 fatty acids.

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Dihydroartemisinin (DHA) is a derivative of artemisinin, which firstly showed higher antimalarial activity. Over the years, DHA has also been discovered to exhibit higher anticancer efficacy without adverse side effects. Although some shortcomings have been discovered during biological evaluation (such as poor aqueous solubility, short half-life, and initial burst release effect), several attempts have been developed to overcome these shortcomings. For example, appropriate delivery techniques were used to improve its anticancer efficacy. In this minireview, we focused on summarizing the anticancer mechanisms, anticancer efficacy of free DHA and in combination therapies, hybrids, and nanoparticle formulations, which will provide adequate insights for its clinical use as anticancer agents, and on the design and synthesis of DHA derivatives for the development of anticancer agents.

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The World Health Organization (WHO) aims to improve our understanding of the factors that promote healthy cognitive aging and combat dementia. Aging theories that consider individual aging trajectories are of paramount importance to meet the WHO's aim. Both the revised Scaffolding Theory of Aging and Cognition (STAC-r) and Cognitive Reserve theory (CR) offer theoretical frameworks for the mechanisms of cognitive aging and the positive influence of an engaged lifestyle. STAC-r additionally considers adverse factors, such as depression. The two theories explain different though partly overlapping aspects of cognitive aging. Currently, it is unclear where the theories agree and differ and what compensation mechanism of age-related cognitive decline might be better explained by either STAC-r, CR, or by both. This review provides an essential discussion of the similarities and differences between these prominent cognitive aging theories, their implications for intervention methods and neurodegenerative disease, and significant shortcomings that have not yet been addressed. This review will direct researchers to common insights in the field and to intervention targets and testable hypotheses for future research. Future research should investigate the potential use of STAC-r in neurodegenerative diseases and provide clarity as to what combination of factors build CR, including their relative importance and when in life they are most effective.

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The coronavirus disease 2019 (COVID-19) has spread worldwide and imposed a substantial burden on human health, the environment, and socioeconomic development, which has also accelerated the process of nucleic acid vaccine development and licensure. Nucleic acid vaccines are viral genetic sequence-based vaccines and third-generation vaccines after whole virus vaccines and recombinant subunit vaccines, including DNA vaccines and RNA vaccines. They have many unique advantages, but there are many aspects that require optimization. Therefore, the purpose of this review is to discuss the research and development processes of nucleic acid vaccines, summarize the advantages and shortcomings, and propose further optimization strategies by taking COVID-19 vaccines as an example. Hopefully, this work can make a modest contribution in promoting the construction of emergency nucleic acid vaccine platforms and in avoiding the reemergence of similar public health emergencies.

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This article reviews the use of wearable sensors for the monitoring of physical activity (PA) for different purposes, including assessment of gait and balance, prevention and/or detection of falls, recognition of various PAs, conduction and assessment of rehabilitation exercises and monitoring of neurological disease progression. The article provides in-depth information on the retrieved articles and discusses study shortcomings related to demographic factors, i.e., age, gender, healthy participants vs patients, and study conditions. It is well known that motion patterns change with age and the onset of illnesses, and that the risk of falling increases with age. Yet, studies including older persons are rare. Gender distribution was not even provided in several studies, and others included only, or a majority of, men. Another shortcoming is that none of the studies were conducted in real-life conditions. Hence, there is still important work to be done in order to increase the usefulness of wearable sensors in these areas. The article highlights flaws in how studies based on previously collected datasets report on study samples and the data collected, which makes the validity and generalizability of those studies low. Exceptions exist, such as the promising recently reported open dataset FallAllD, wherein a longitudinal study with older adults is ongoing.

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In 2002 with the passing of the Euthanasia Law, Belgium became one of the few countries worldwide to legalize euthanasia. In the 18 years since the passing of the law, much has changed. We argue that in Belgium a widening of the use of euthanasia is occurring and that this can be ethically and legally problematic. This is in part related to the fact that several legal requirements intended to operate as safeguards and procedural guarantees in reality often fail to operate as such. We focus on three kinds of safeguards or procedural guarantees: (1) the legally defined due care criteria for eligibility for euthanasia; (2) the consultation of a second (and sometimes third) physician; and (3) the reporting of euthanasia cases to the Federal Control and Evaluation Commission for Euthanasia. We will show how each of these three safeguards can exhibit shortcomings in theory and practice.

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Methodological shortcomings in prognostic modeling for patients with spinal disorders are highly common. This general commentary discusses methodological challenges related to the specific nature of this field. Five specific methodological challenges in prognostic modeling for patients with spinal disorders are presented with their potential solutions, as related to the choice of study participants, purpose of studies, limitations in measurements of outcomes and predictors, complexity of recovery predictions, and confusion of prognosis and treatment response. Large studies specifically designed for prognostic model research are needed, using standard baseline measurement sets, clearly describing participants' recruitment and accounting and correcting for measurement limitations.

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The use of wearable body sensors for health monitoring is a quickly growing field with the potential of offering a reliable means for clinical and remote health management. This includes both real-time monitoring and health trend monitoring with the aim to detect/predict health deterioration and also to act as a prevention tool. The aim of this systematic review was to provide a qualitative synthesis of studies using wearable body sensors for health monitoring. The synthesis and analysis have pointed out a number of shortcomings in prior research. Major shortcomings are demonstrated by the majority of the studies adopting an observational research design, too small sample sizes, poorly presented, and/or non-representative participant demographics (i.e., age, gender, patient/healthy). These aspects need to be considered in future research work.

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α-Amylase is an endoenzyme that catalyses the hydrolysis of internal α-l,4 glycosidic linkages in polysaccharides to produce maltose, maltotriose, and α-limit dextrins. It is widely used in the laboratorial and industrial workflow for several applications. There are several methods utilizing different techniques and substrates to assess α-amylase activity, among which the spectroscopic methods have found widespread applicability due to their ease of use and cost-effectiveness. Depending upon the reaction principle, these assays are classified into four groups: reducing sugar, enzymatic, chromogenic, and amyloclastic methods. Despite the presence of numerous methods, there is no general reliable method to assess α-amylase activity. Each method is shown to have its own merits and demerits. Many improvements have been made to make the available methods more accurate, reliable, and easy. This communication briefly discusses the basic reaction mechanisms and critically reviews the advantages and shortcomings associated with each method. Further recommendations are made for future development. © 2020 Society of Chemical Industry.

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Chaihu Shugansan is a representative prescription for soothing the liver and relieving depression in traditional Chinese medicine(TCM). Chaihu Shugansan is from Jingyue Quanshu.Chaihu Shugansan has been widely used in clinic since Ming dynasty because of its exact curative effect.Chaihu Shugansan has the effect in soothing the liver and relieving depression through multiple components, multiple ways and multiple targets.At present, the mechanism of Chaihu Shugansan has been interpreted based on its multiple effect on neurotransmitters, cytokines, neuronal injury signal pathways, neuroendocrine, oxidative stress and so on.This paper summarizes the progress of clinical studies on source, pharmacology of single herbs and effective components of Chaihu Shugansan, in aspects of cardiovascular system, neuropsychiatric system, digestive system, reproduction-related systems, analyses and summarizes relevant literatures of Chaihu Shugansan published in recent years, and discusses about current development and shortcomings of Chaihu Shugansan, so as to provide ideas for the studies in the future.Beneficial explorations will be conducted in large-sample-size, standardized, clinical and experimental mutual verification.In proteomics research technology, network pharmacology, supramolecular theory of TCM and other fields, Chaihu Shugansan and liver depression syndrome will be organically connected from the microscopic perspective.And comprehensive studies will be conduct to TCM, metabonomics, proteomics, genomics and other disciplines, in order to clarify Chaihu Shugansan prescriptions, syndromes, therapeutics and its mechanism.

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On the basis of systematic evaluation of 32 provincial capital cities and municipalities in their capacity for preventing and controlling emerging infectious diseases, focus analysis is made on Wuhan in relation to its advantages and disadvantages as follows:There has been a legal basis for epidemic prevention according to law, but it has not translated into effective action.There has been an organizational basis for responding to epidemic, but coordination mechanism has not been effectively established.The management mechanism has been complete, but the division of responsibilities among different departments has not been clear.The monitoring network has been set up, but its role of "predictive warning" has not been played.Insufficiency of public health service delivery was observed owing to lack of financial investment.In cities of China, advantages and disadvantages have been both existent in their capacity to prevent and control of emerging infectious disease.We should be vigilant in this regard. It is imperative to "fill defects, stop leaks and strengthen weakness".There is a Chinese saying:"It is not too late to mend a fold after the sheep have been stolen".

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OBJECTIVES: This paper describes and comments on contemporary legislation concerning prevention of epidemics caused by contaminated drinking water from public water supplies in the Czech Republic. METHODS: Suggestions are made for removing existing legislative shortcomings, clarifying diction of existing laws and expanding sanctions and penalties for health injury caused by providers and operators of public drinking water. RESULTS: The author reflects on improving legislation concerning the compensation of victims of contaminated water with reference to the aftermath of a local epidemic in the Dejvice District of Prague. CONCLUSION: The issues raised should be addressed since better legislation can significantly contribute to the limitation of water-borne epidemics and their consequences.

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OBJECTIVES: This article describes and comments on contemporary legal regulations concerning the supply of medicines during pandemics in terms of public procurement. METHODS: Suggestions are made for removing existing legislative shortcomings, clarifying the diction of existing laws or rendering precision to legal regulation of public procurement given purchases of medicines during periods of imminent threats of pandemics and duration of pandemics. RESULTS: The author reflects on improving legislation concerning the lack of clarity and the doubts concerning the contemporary legal order of the Czech Republic, with reference to speeding up and simplifying public procurement procedures for incident-free purchases of necessary medicines in time of pandemic crisis situation and then effectively supporting the struggle against any pandemic infection. CONCLUSION: The issues raised should be addressed since better legislation can significantly contribute to the containment of pandemics and their consequences for individual and public health.

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Access to skilled provider and emergency obstetric care is not universal across all districts in Ghana. The lived experiences of 3 stakeholder groups on maternity care shortcomings in 3 rural Ghanaian districts are examined in this study. We applied an ethnographic study approach where field data were collected between March to May 2015 in 3 rural districts of northern Ghana. Data were collected among women with recent births experiences (n = 90), health care providers (n = 16), and policy actors (n = 6). Transcripts were read through to identify similar and divergent stakeholders' views. Significant expressions and experiences of stakeholders on maternity care shortcomings were extracted and evaluated to define key themes. Four themes emerged: social/community factors, payments for health care, facility level factors, and policy level factors. The results show that traditional women's roles divest time for maternity care. Poor transport arrangements, insufficient health workforce, health funding gaps, insurance reimbursements delays, and catastrophic health expenditures on travel and drugs are attested as major barriers across all stakeholder groups in all districts studied. The discussion of the study findings suggests it is important to ascertain the scale of informal payments and their impacts on health access. Investments in health workforce and reliable ambulatory service systems could help address poor referral difficulties in rural areas of the country. Social support for community initiatives that pool funds could provide extra resources and relieve cost access-related challenges for using maternity care in rural settings in Ghana.

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OBJECTIVES: The aim of this study was to evaluate how frequently complex interventions are shown to be superior to routine care in general practice-based cluster-randomized controlled studies (c-RCTs) and to explore whether potential differences explain results that come out in favor of a complex intervention. STUDY DESIGN AND SETTING: We performed an unrestricted search in the Central Register of Controlled Trials, MEDLINE, and EMBASE. Included were all c-RCTs that included a patient-relevant primary outcome in a general practice setting with at least 1-year follow-up. We extracted effect sizes, P-values, intracluster correlation coefficients (ICCs), and 22 quality aspects. RESULTS: We identified 29 trials with 99 patient-relevant primary outcomes. After adjustment for multiple testing on a trial level, four outcomes (4%) in four studies (14%) remained statistically significant. Of the 11 studies that reported ICCs, in 8, the ICC was equal to or smaller than the assumed ICC. In 16 of the 17 studies with available sample size calculation, effect sizes were smaller than anticipated. CONCLUSION: More than 85% of the c-RCTs failed to demonstrate a beneficial effect on a predefined primary endpoint. All but one study were overly optimistic with regard to the expected treatment effect. This highlights the importance of weighing up the potential merit of new treatments and planning prospectively, when designing clinical studies in a general practice setting.

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The Choosing Wisely initiative (CWI), a campaign led by the American Board of Internal Medicine (ABIM) Foundation, promotes doctor-patient communication and reducing waste in healthcare. At present, many of the top 5 lists from the Choosing Wisely Initiative appear to be primarily eminence-based and influenced by self-interest. The implementation of recommendations from these lists may mean taking a step backwards to the time before evidence-based medicine. On the other hand, despite all the challenges that the Choosing Wisely initiatives are currently facing, it is difficult to deny that they also hold great potential in terms of making healthcare systems more efficient and beneficial to patients. The aim of the ongoing work in Germany and Austria is to create conditions that are necessary if CW initiatives are to evolve into a model tool that will help introduce the principles of evidence-based medicine into daily practice.

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Introduction of arsenic trioxide (ATO, As2O3) to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent's further functions has rapidly advanced so that it has entered common use in hematology and oncology. In addition, As2O3 reportedly induces DNA and chromosomal damage, inhibits DNA repair, and alters DNA methylation in mammalian cells. The compound is becoming increasingly reasonable as a treatment modality to rectify genetic blood disorders and other cancer types. Nevertheless, limitations of As2O3 typically emerged from drug resistance, adverse effects and secondary tumors, which may result in a myriad of outcomes. Though prolonged exposure to As2O3 ensues poisons and genome alternations that do not permanently change the DNA sequence, other synergistic alterations should be considered as replacement. In this review, we recollect the discovery and clinical implementation of As2O3, describe its advantages and shortcomings for leukemia and solid cancer treatment, and consider future prospects for engendering useful impacts.

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BACKGROUND: Information on the occurrence of contact allergens and irritants is crucial for the diagnosis of occupational contact dermatitis. Material Safety Data Sheets (MSDS) are important sources of information concerning exposures in the workplace. OBJECTIVE: From a medical viewpoint, to evaluate the information available from MSDSs, and to ascertain whether MSDS are easy to obtain, whether they serve their purpose, and whether they provide sufficient information regarding allergens to enable correct diagnosis. METHODS: MSDS and ingredients labelling were collected from consecutive patients and reviewed. If it was suspected that the MSDS were incomplete, the manufacturer, supplier, salesperson or workplace was contacted to gather more information. RESULTS: Twenty-five per cent (79/316) of patients provided material for the exposure assessment. One or more shortcomings were found in 18.6% (137/738) of the MSDS. The most frequent shortcoming was 'Missing R43/H317 while known contact allergen was present', which was observed in 63.1% (84/137). Other shortcomings were 'Names of preservatives not included in section 3 despite containing preservatives', in 48.9% (67/137), and 'Nothing about allergy in sections 2, 3, 11, 15 or 16 in the MSDS despite the content of allergens', in 20.4% (28/137). The information retrieved led to additional testing of 21 patients. CONCLUSION: Systematic exposure assessment is time-consuming. The main shortcomings are errors/omissions in the MSDS.

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