Take-home Message Research Articles

A Primer on How to Critically Read an Observational Study on Adverse Medical Outcomes Associated With Long-Term Antidepressant Drug Use

Whether long-term antidepressant use predisposes to or protects against adverse medical outcomes is unclear. In this context, a recent retrospective cohort study found that, for example, at a 10-year follow-up, selective serotonin reuptake inhibitors lowered the risk of diabetes mellitus and hypertension but raised the risk of cerebrovascular disease, cardiovascular mortality, and all-cause mortality. The findings of this study were widely and uncritically covered in the lay and medical media with potential to adversely impact opinions about antidepressant treatment among patients, caregivers, and health care professionals. This article critically evaluates the study with a view to discuss its limitations and, more importantly, to arm the reader with skills to critically appraise other, similar studies. Concepts explained include confounding by indication, regression, and approaches to deal with confounding. Problems with the study identified and explained are incomplete adjustment for confounding, failure to correct for multiple hypothesis testing, the use of backward stepwise regression as a method of analysis, failure to consider reverse causation, and failure to remove death by suicide from analyses of all-cause mortality. Other limitations of the study are also discussed. A take-home message is that it is well established that depression is associated with substantial disability and risk of suicide and that antidepressant drugs treat depression and prevent relapse and recurrence; in contrast, no causal role for antidepressants in long-term adverse medical outcomes is established. Therefore, known long-term benefits with antidepressants must be weighed against unproven predispositions to long-term medical adverse effects in shared decision-making processes.

Comparison of Clinical and Radiographic Outcomes According to the Presence or Absence of a Posterior Draw Force during Graft Fixation in Anterior Cruciate Ligament Reconstruction.

Background and Objectives: A reduction forced toward the posterior side during graft fixation may help to lessen anterior tibial translation after ACL reconstruction. The purpose was to compare the clinical and radiological outcomes of graft fixation when a posterior draw was used and when it was not used during anterior cruciate ligament (ACL) reconstruction surgery. Materials and Methods: Of 110 patients who had undergone primary arthroscopic ACL reconstruction between January 2017 and August 2020, in all, 76 patients had been operated on without a posterior draw (non-draw group), and 34 patients had received surgery with a posterior draw (draw group). The results of the Lachman test and the pivot-shift test, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) indexes, the Lysholm scores, the International Knee Documentation Committee (IKDC) subjective scores, and side-to-side difference (STSD) on stress radiography were compared between the two groups. Results: The postoperative WOMAC indexes, Lysholm scores, and IKDC subjective scores were similar across both groups. Postoperative STSD (2.4 ± 2.2 for the non-draw group vs. 2.0 ± 2.2 for the draw group; p = 0.319) and change in STSD (3.5 ± 3.5 for preoperative STSD vs. 4.3 ± 4.4 for postoperative STSD; p = 0.295) were not superior in the draw group. Conclusions: The take-home message is that graft fixation with a posterior draw during ACL reconstruction did not result in significantly better postoperative stability. The postoperative clinical outcomes were similar between both groups.

LW-1 MY LIFE WORK : MY RESEARCH WORK FOCUSING ON TUMOR-ASSOCIATED ENDOTHELIAL CELLS ALONG WITH VEGF FOR 30 YEARS

Abstract When I was a medical student, I happened to see the typical histopathology of glioblatoma (GBM) containing expanding necrosis surrounded by enormous glomerulous microvasculature with endothelial proliferation resembling glomeruli in the kidney. It looks like tumor cells starving out due to lack of blood supply with accelerating growth. Since then, I have been fascinated by tumor angiogenesis that might be an attractive therapeutic target.In 1989, vascular endothelial growth factor (VEGF) and vascular permeability factor (VPF) turned out to be identical. In 1992, VEGF expression was distributed surrounding necrosis area in GBM. In 1993, anti-tumor effect of monoclonal antibody for VEGF via inhibition of angiogenesis on various tumor models including glioma was verified in vivo. In 1996, VEGF was found to inhibit the functional maturation of dendritic cells, suggesting that therapeutic blockade of VEGF may improve prospect for immunotherapy as well as inhibition of angiogenesis. Those findings made me excited with visionary idea that combination therapy of anti-VEGF therapy and dendritic cell-based immunotherapy might be a potential therapeutic approach for GBM. Currently, I am dedicated in clinical study of dendritic cell-based immunotherapy and bevacizumab for GBM.Since graduating from medical school and discovery of VEGF in the same era, my clinic and research have been supported by serendipity of a vast of experiences and many people. I would give take-home message to next generation that originality and creativity were cultivated in real-world, and that serendipity and integration were precious for development of basic and clinical research.

The Cup Whisperer

The Cup Whisperer

Management of Aesthetic and Functional Deficits in Frontal Bone Trauma.

Frontal bone trauma has an increasing incidence and prevalence due to the wide-scale use of personal mobility devices such as motorcycles, electric bicycles, and scooters. Usually, the patients are involved in high-velocity accidents and the resulting lesions could be life-threatening. Moreover, there are immediate and long-term aesthetic and functional deficits resulting from such pathology. The immediate complications range from local infections in the frontal sinus to infections propagating inside the central nervous system, or the presence of cerebrospinal fluid leaks and vision impairment. We review current trends and available guidelines regarding the management of cases with frontal bone trauma. Treatment options taken into consideration are a conservative attitude towards minor lesions or aggressive surgical management of complex fractures involving the anterior and posterior frontal sinus walls. We illustrate and propose different approaches in the management of cases with long-term complications after frontal bone trauma. The team attending to these patients should unite otorhinolaryngologists, neurosurgeons, ophthalmologists, and maxillofacial surgeons. Take-home message: Only such complex interdisciplinary teams of trained specialists can provide a higher standard of care for complex trauma cases and limit the possible exposure to further legal actions or even malpractice.

Comment on "Models predict planned phosphorus load reduction will make Lake Erie more toxic".

Hellweger et al. (Reports, 27 May 2022, pp. 1001) predict that phosphorus limitation will increase concentrations of cyanobacterial toxins in lakes. However, several molecular, physiological, and ecological mechanisms assumed in their models are poorly supported or contradicted by other studies. We conclude that their take-home message that phosphorus load reduction will make Lake Erie more toxic is seriously flawed.

News from around the RNA world: new avenues in RNA biology, biotechnology and therapeutics from the 2022 SIBBM meeting.

ABSTRACTSince the formalization of the Central Dogma of molecular biology, the relevance of RNA in modulating the flow of information from DNA to proteins has been clear. More recently, the discovery of a vast set of non-coding transcripts involved in crucial aspects of cellular biology has renewed the enthusiasm of the RNA community. Moreover, the remarkable impact of RNA therapies in facing the COVID19 pandemics has bolstered interest in the translational opportunities provided by this incredible molecule. For all these reasons, the Italian Society of Biophysics and Molecular Biology (SIBBM) decided to dedicate its 17th yearly meeting, held in June 2022 in Rome, to the many fascinating aspects of RNA biology. More than thirty national and international speakers covered the properties, modes of action and applications of RNA, from its role in the control of development and cell differentiation to its involvement in disease. Here, we summarize the scientific content of the conference, highlighting the take-home message of each presentation, and we stress the directions the community is currently exploring to push forward our comprehension of the RNA World 3.0.

Is ABO Compatibility Important in Islet Transplantation?

One of the current criteria for clinical islet allotransplantation is ABO blood group compatibility between donor and recipient.1 The distribution of ABH antigens in human pancreata was first examined >40 y ago, revealing expression in acinar and vascular cells but not in islets.2 This underlined the importance of ABO matching in whole pancreas transplantation, but the situation in islet transplantation is more complicated. Although islets in situ appear to be ABH-negative,2 islets prepared for transplant are invariably contaminated with exocrine tissue including acinar cells. Furthermore, it is not known whether the islet isolation and transplantation process itself influence ABH expression. It is therefore somewhat surprising that ABH expression in islet preparations before and after transplant has not been characterized until now. In this issue of Transplantation, Verhoeff et al3 present a detailed immunohistochemical and flow cytometric survey of ABH antigen levels in human pancreatic tissue, isolated human clinical-grade islets, and islets derived from human embryonic stem cells (hESCs). After confirming that ABH antigens are present on acinar cells but not on endocrine and ductal cells in the pancreas, the authors demonstrate that islet preparations consist primarily of ABH-negative endocrine cells but are significantly contaminated with ABH-positive acinar cells. When islets were transplanted into immunodeficient rats, the endocrine component was ABH-negative at 24 wk, whereas remnant acinar tissue stained positive. Pancreatic endocrine progenitors derived from hESCs were ABH-negative and remained so after in vivo maturation following transplantation into rats, although this was not unexpected given that the hESC donor was blood group O. The human-to-immunodeficient rat islet xenograft model used in the latter part of the study does have some limitations. First, the kidney subcapsular site does not accurately reflect the clinical scenario, in which islets are transplanted intraportally.1 Subcapsular delivery co-localizes the islets with acinar tissue fragments and potentially exposes the islets to “bystander” injury and inflammation when anti-ABH antibodies attack the acinar cells. In contrast, intraportal delivery disperses islets and acinar fragments widely throughout the liver microvasculature, which probably minimizes co-localization and thus reduces the likelihood of bystander effects. Furthermore, subcapsular but not intraportal delivery shields the graft from exposure to anti-ABH IgM antibodies. Although these differences are not relevant in the immunodeficient rat model, they may well be relevant in the clinical setting. Second, the immunodeficient rat model does not allow investigation of the importance of the in vivo anti-ABH immune response to islet grafts. I have worked with one of the authors (L.J.W.) to develop a mouse model of anti-A antibody-mediated rejection of transgenic blood group A-expressing cardiac grafts.4 However, these A-transgenic donor mice are unsuitable for examining anti-A–mediated islet graft rejection because expression of the antigen is endothelial cell-restricted and absent on islets. Humanized mouse models may be more appropriate, as suggested by the authors. The take-home message of this interesting paper is that ABO matching is indeed likely to be important in islet allotransplantation—as is the case for HLA matching5—but may become less so if islet purification efficiency improves sufficiently or if hESC-derived islets are used. On the former point, the authors speculate that the restriction of surface expression of ABH antigens to acinar tissue (starkly illustrated by Figure 6A in the paper) provides an opportunity to enrich the purity of A, B, or AB islets by some form of negative selection. Although practicality at scale may be an issue, this is an intriguing proposition that is worthy of further consideration.

A Case of a 23-Year-Old Male With Leber Hereditary Optic Neuropathy With a Rare Mutation

Mitochondrial DNA(mtDNA) is responsible for encoding 13 subunits of the respiratory chain. These subunits are crucial in providing reducing equivalents for the energy-intensive intracellular processes. Leber hereditary optic neuropathy (LHON) is a mitochondrial illness that causes carcinogenesis due to oxidative stress and painless loss of central vision as a result of selective degradation of retinal ganglion cells as well as their axons. We present a case of a 23-year-old male patient who was diagnosed with subacute LHON. The mutation in our patient was found in a less commonly mutated exon sequence of MT-NDL4, which codes for NADH (nicotinamide adenine dinucleotidehydrogen, reduced) dehydrogenase subunit 4L. The MT-ND4L exon is located immediately upstream of the MTD4 exon on the human mtDNA. The take-home message is to always perform a comprehensive mitochondrial genome analysis for identifying rare mutations when LHON is suspected.

Communicate About Quality and Safety: Let's Think Outside the Box! Experience From a Cancer Center.

While the priority of caregivers in any health care establishment is patient care, they are often constrained by time and cannot fully devote themselves to projects aiming at improving the quality and safety of care. Although the culture of quality is widespread in health care establishments, the quality and safety department team must continue to improve existing procedures and develop new ones, in order to reinforce the take-home message that safety is of paramount importance. Since good communication is a key factor in the success of quality plans, the quality and safety team in our establishment is placing special emphasis on "out of the ordinary" activities that take professional carers out of their daily routines, arouse their curiosity, and increase their adherence to quality procedures. The issues addressed during these activities are based on the year-round continuous assessment of in-house procedures. Only those that have been deemed essential for safe care are focused upon. Most of the activities that are implemented have already been tried and tested in the fields of industry and aviation, and they all have a fun, collaborative, and creative component. Their impact and effect are assessed by carrying out the same assessments as those used at the beginning on the project. These innovative activities, which have received strong support from the staff, have had a positive effect on interdepartmental cooperation, on the adherence to the new methods presented, and on ensuring that information is made available to the greatest number of professionals. They have allowed the staff to acquire and consolidate new professional knowledge and have promoted good practice. This new program of activities has considerably improved the safety culture within our establishment. While the relationship between the skills of professionals and patient safety is clear to all, the message needs to be delivered in an original way that makes a lasting impression, in addition to using "standard" communication methods such as plenary meetings. The bottom line is to get as many professionals as possible fully adherent to the culture of quality, since quality is everyone's business and health care procedures are constantly evolving. Based on our experience, we provide a set of activities that can be improved and adapted according to the setting in which it is used.

Recent Advances of Telepractice for Autism Spectrum Disorders in Speech and Language Pathology.

Telepractice or teletherapy is defined as the means of service delivery via technology-based platforms that allow long-distance interventions across populations, age spans, and geographical locations. Specifically, telepractice capitalizes on communication technologies such as online modules, videoconferencing, and computerized software programs, in servicing populations with communication challenges. Notably, telepractice has emerged as a potentially effective, low-cost, and promising means of conducting and completing online assessment, diagnosis, and intervention sessions for individuals with autism spectrum disorders (ASD). Moreover, telepractice allows the inclusion of parents, caregivers, and educators as potential facilitators in supporting treatment delivery in populations with ASD. This thematic review article aims to highlight and acquaint practitioners and other stakeholders with relatively recent information regarding the advantages and disadvantages of the telepractice service delivery model in ASD. Furthermore, the emergence of the COVID-19 pandemic has impacted service delivery in the field of Health Sciences including speech and language pathology (SLP). Consequently, the need to avoid face-to-face therapy sessions, recommended to SLPs as to all health practitioners, resulted in the call for adaptation and adjustment of service telepractice. This paper attempts to answer this call by suggesting supplementing traditional diagnostic and therapy resources with training modules consisting of online materials and use of animated and specially designed programs in SLP intervention with individuals with ASD. Lastly, the paper includes a discussion of research findings in the field, a conclusion, and a take-home message.

Detecting Time Concept Competence in Children with Autism Spectrum and Attention Disorders.

The importance of time concept in human existence is “ancient history” celebrated in the biblical book Ecclesiastes. Indeed, our time-sensitive mechanisms are literally carved into our biology and neurology on a molecular level, gifting us with neural clocks. However, time in human consciousness is not the time indicated by physical clocks: time is a subjective reality in our psychological makeup due to the nature of the temporal neural mechanisms and unique properties of physical time. Nonetheless, subjective time requires anchoring to physical time which permeates our language, endeavors, and entire existence, a process hinging on time-related skills such as estimates and measures of passage and duration of time. Moreover, accurate time reading, a critical adaptive life-skill, is imperative for effective function in all societal activities. Because it embodies the complexity of the time construct, it is central to instruction of time concept in primary education. It is often measured in children by clock drawings, a cognitive integrative skill with errors pointing to neuroanatomical differences impacting the integrity of executive function. Time competence in children with atypical neurobiological development and high prevalence, as in autism spectrum disorders (ASD), and attention disorders (ADHD), is often compromised, calling for investigation of its function. This thematic review article aims to: 1) discuss the complexity of time concept and its underlying bio-neurological mechanisms, 2) elucidate difficulties children with ASD and those with ADHD exhibit in temporal development, and 3) demonstrate the use of a set of clinical tools in uncovering temporal competence and ecological executive function in two children with ASD, and a child with ADHD, using a clock drawing task and error analyses; children’s time knowledge questionnaire; a behavior rating parent questionnaire examining ecological executive function, and parent open-ended questions related to their children’s time difficulties. A discussion, directions, and a take-home message round out the article.

Antipsychotic Augmentation With N-Acetylcysteine for Patients With Schizophrenia.

N-acetylcysteine (NAC) augmentation of antipsychotic medication is one of very many antipsychotic augmentation strategies that have been studied in schizophrenia. A recent systematic review and meta-analysis of 6 randomized controlled trials (RCTs) found that NAC (median dose, 2,000 mg/d) improved several clinical outcomes at different time points with medium to large effect sizes; however, many of the significant findings in this meta-analysis are suspect because they appeared to be influenced by 2 short-term (8-week) RCTs with outlying characteristics. Important findings not influenced by the 2 outlying RCTs were significant attenuation by NAC of negative symptom (3 RCTs) and total psychopathology (2 RCTs) ratings at ≥ 24 weeks and improvement in working memory but not processing speed (3 RCTs). Of these findings, reduction in psychopathology ratings, though statistically significant, appeared too small to be clinically meaningful. Finally, a newly published, moderately large RCT of NAC (2,000 mg/d) in schizophrenia patients refractory to clozapine found that 1 year of treatment with NAC did not outperform placebo for any clinical, cognitive, or quality of life outcome. The take-home message is that it is premature to recommend the use of NAC to treat schizophrenia for any target domain in routine clinical practice and that there does not appear to be a role for NAC for any indication in clozapine-refractory schizophrenia. However, it may be worth studying whether NAC, dosed at 2,000 mg/d or higher for 6 months or longer, improves functional outcomes in schizophrenia.

UK healthcare support workers and the COVID-19 pandemic: an explorative analysis of lived experiences during the COVID-19 pandemic

ABSTRACT Support workers are an underrepresented profession that receives less attention with a high degree of responsibilities. The aim of this study was to explore the lived experiences of healthcare support workers within the care sector during the COVID-19 pandemic. This is a qualitative semi-structured interview study using an interpretative phenomenology (IP) framework. Fifteen (15) support workers were interviewed while all COVID-19 restrictions from the government were still in place. We identified five main themes: (1) challenging experiences; (2) coping mechanisms; (3) emotions and behaviors arising from the COVID-19 pandemic; (4) external interest on support worker’s health; (5) take-home message from the COVID-19 pandemic. The organization selected for the research is a good representative of how care organizations operate within the UK both in terms of policies and staff selection.

Use of Human iPSC-CMs in Nonclinical Regulatory Studies for Cardiac Safety Assessment.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a human-relevant platform for cardiac function assessment. Alternative assays using hiPSC-CMs are increasingly being employed for regulatory decision-making. A retrospective review revealed steady use of hiPSC-CM-based in vitro assays in nonclinical studies of drug-induced cardiotoxicity in regulatory submissions to the U.S. Food and Drug Administration (FDA). Most of the hiPSC-CMs data were obtained in exploratory studies and submitted as supportive evidence in concordance with other nonclinical data. Some of those studies were used to inform clinical trial design. This article provides an overview of the use of hiPSC-CMs in regulatory applications to FDA, with a focus on the integration of human-relevant in vitro data into proarrhythmic and non-proarrhythmic risk assessment. By identifying the regulatory submissions including hiPSC-CMs data, we explore their utility and discuss their limitations for predicting human cardiac safety in clinical trials. An important take-home message is that regulatory acceptance of hiPSC-CMs data is dependent on both the context of use and accurate data interpretation.

ACL Research Retreat IX Summary Statement: The Pediatric Athlete, March 17-19, 2022; High Point, North Carolina.

ACL Research Retreat IX Summary Statement: The Pediatric Athlete, March 17-19, 2022; High Point, North Carolina.

Spatial and Temporal Characteristics of High-Temperature Heat Wave Disasters in Chongqing

In the background of global warming, heat wave disasters have become more frequent globally, and mountainous cities are more seriously affected by heat wave disasters due to the special features of topography and urban morphology. This paper analyzes the temporal and spatial distribution characteristics of heat wave disasters in Chongqing, a mountainous city. The results shows that heat wave disasters in Chongqing tend to increase overall and decrease locally before increasing. Significant growth in heat waves since 2010 and time series model prediction analysis shows that Chongqing will face more severe heat waves in the future. The spatial distribution of heat wave disasters varies significantly, high in the middle and low at the ends. There is a tendency for the center of heat wave disasters to shift from the south-central part of Chongqing to the northeast. In addition to the influence of atmospheric circulation and mountain topography, the causes are also positively related to urban development intensity and urbanization trends. It is necessary to develop specific control and management measures for heat waves depending on the characteristics of them. The take-home message of the study is the spatial and temporal trends of heat waves in Chongqing to provide a theoretical basis for high-temperature mitigation.

Eye emergency during wars; Take-home message for soldiers

The Article Abstract is not available.

A Take-Home Message "Fall Armyworm Management in Asia and the Pacific Region"

A Take-Home Message "Fall Armyworm Management in Asia and the Pacific Region"- Y.D. GC

A Take-Home Message: Workplace Food Waste Interventions Influence Household Pro-environmental Behaviors

Previous research on food waste interventions has mostly focused on micro-level factors related to the individuals, and largely neglected macro-level contextual factors such as work-to-home spillovers. Inspired by the multi-level framework, we present a case study of how macro-level workplace campaigns could decrease food waste in staff cafeterias, compete with micro-level factors like environmental identity, and further stimulate some employees’ food saving efforts at home. The workplace interventions combined smart bins with fortnightly informational feedback trialed in three staff cafeterias of a large hotel chain in Macau, China. Actual food waste data and self-reported behavior consistently show that the staff cafeteria receiving environmental framing with anthropomorphic cues had more reductions in food waste behaviors. A key determinant of self-reported food saving efforts at home was efforts to reduce food waste at work, which predicted beyond and above environmental identity and provided evidence for positive contextual spillover effects.