Background: Myopia is a global public health problem affecting quality of life and work productivity. Data is scarce regarding the effects of near work on myopia. Providing a larger meta-analysis with life-long perspective, including adults and occupational exposure seemed needed. Methods: We searched PubMed, Cochrane Library, Embase and Science Direct for studies reporting myopia prevalence in near work. Myopia was defined as a mean spherical equivalent ≤ −0.50 diopter. We performed a meta-analysis using random-effects model on myopia prevalence, myopia progression per year, and odds ratio (OR) of myopia in near work, completed by subgroup analyses and meta-regressions on patients’ characteristics, type of work in adults, geographic zones, time and characteristics of near work. Results: We included 78 studies, representing a total of 254,037 participants, aged from 6 to 39 years. The global prevalence of myopia in near work was 35% (95% CI: 30 to 41%), with a prevalence of 31% (95% CI: 26 to 37%) in children and 46% (95% CI: 30 to 62%) in adults. Myopia progression was −0.39 diopters per year (−0.53 to −0.24 D/year), ranging from −0.44 (−0.57 to −0.31) in children to −0.25 D/year (−0.56 to 0.06) in adults. The odds of myopia in workers exposed vs. non-exposed to near work were increased by 26% (18 to 34%), by 31% (21 to 42%) in children and 21% (6 to 35%) in adults. Prevalence of myopia was higher in adults compared to children . Conclusions: Near work conditions, including occupational exposure in adults, could be associated with myopia. Targeted prevention should be implemented in the workplace. Myopia is the most common type of refractive error  and consThe primary aim of the present study was to conduct a systematic review and meta-analysis to determine the global prevalence of myopia relative to occupation (including education). The secondary outcomes were to assess the effects of near work on myopia, through a meta-analysis on myopia progression and odds ratio of myopia in exposed patients to near work vs. those not exposed to near work, to determine the dose-response relationships between myopia and near work and to examine the influence of the occupation-related near work and socio-demographic variables.The Population-Intervention-Comparison-Outcome (PICO) question was formulated as follows: Do adults and children (P) exposed to near work either from their occupation or their educational activities (I) compared to adults and children that are not exposed to near work (C) have a different prevalence of myopia (O)? The present research was carried out in accordance with the PRISMA Guidelines. We reviewed all cohort studies involving myopia in near work. Specifically, the inclusion criteria for the search strategy were cross-sectional and cohort studies , without a case-study design. We used the following keywords: “myopia” or “short-sight” for myopia, and “near work”, “display” or “users” for near work. A display is hereafter defined as a computer output surface and projecting mechanism that shows text and images onto a screen, using a cathode ray tube, liquid crystal display, light-emitting diode, gas plasma, or other image projection technology. To be included, articles needed to describe the outcomes of interest of the present research, i.e., the number of workers with myopia, myopia progression, or odds ratio for myopia. The following databases were searched up until 30 May 2022: PubMed, Cochrane Library, Science Direct and Embase. The search was not limited to a specific time period. In addition, reference lists of all publications meeting the inclusion criteria were manually searched to identify any further studies not found through electronic research on the databases stated above. Articles written in Chinese or Japanese language were excluded. The search strategy is described in We used the Scottish Intercollegiate Guidelines Network (SIGN) for cohort studies to evaluate the risk of bias of the included articles . Not desThe collected data included first author’s name, publication year, study design, country, aims and outcomes, sample size, characteristics of individuals , myopia outcomes , use of cycloplegia or not for the diagnosis of myopia and characteristics of near work .2). Heterogeneity was considered low for I2 < 25%, modest for 25 < I2 < 50%, and high for I2 > 50%. The robustness of our results was assessed by conducting a sensitivity analysis after exclusion of studies that were not evenly distributed around the funnel plot. When sample size was sufficient, meta-regressions were used to study the relationships between our outcome variables  and clinically relevant parameters such as characteristics of individuals , type of occupation for adults, continents, time periods , duration and characteristics of near work . Results were expressed as regression coefficients and 95% CI. All p values were two-tailed. Statistical significance was defined by a p value < 0.05. Statistical analysis was conducted using Stata software .Baseline characteristics were summarized for each study and reported as mean ± standard-deviation (SD) for continuous variables, and number (%) for categorical variables. Due to the observational nature of the included studies, we chose to using random-effect models for the present meta-analysis (DerSimonian and Laird approach) ,25 to asAn initial search produced retrieved 9617 articles . RemovalUsing the SIGN checklist, overall quality of the 78 included studies was good, with a mean score of 72.2 ± 8.5%, ranging from 40.0 ,85 to 86Age of participants ranged from 6 [male ranged from 24% [Population sizes ranged from 40 ,68,71,76d from 6  to 39 yed from 6 ,66,71,85from 24% ,80,83,91from 24% ,70,87,92from 24% ,88,89,90from 24% ,85, milifrom 24% ,57, univfrom 24% ,87,88,97from 24% ,94,99. Afrom 24% ,85,87,88from 24% ,75,90,94from 24% ,87,90,94from 24% ,79,85,97from 24% ,95,95,99prevalence of myopia in 61 studies with a cross-sectional design [relating myopia  with near work exposure  in prospective case-control designs [The main outcome was the l design ,90,92,94 designs ,93,95,97Myopia prevalence was described in 72 studies [myopia progression per year in 17 studies [odds ratio for myopia in 22 studies [ studies ,95,95,97 studies ,93,95,97 studies ,88,89,93 studies ,68,69,71 studies ,93. The autorefractometry for the diagnosis of myopia aiming to calculate the refractive error based on spherical equivalent (SE = sphere + cylinder/2). Most studies used cycloplegia, except 16 studies, mostly on adults [axial length [All studies used n adults ,78,79,88l length ,92,93,94l length ,97. Studl length ,42,44,45l length ,84,88,92duration of exposure to near work, ranging from few weeks [Twenty-six studies reported the ew weeks  to 23 yeew weeks . Twenty studies ,81,85,95Only 18 studies reported the global week duration of near work ,85,86,90Seven studies quantified the exposure to near work in Diopter-hours per week ,75,84,952 > 90%). Those results are presented in Within the 74 studies reporting a prevalence ,69,70,71p < 0.001), with heterogeneous results ranging from −0.05 [p = 0.119) and −0.44 D per year in children . Insufficient data precluded analysis by occupation. Stratification by geographic zones demonstrated a significant myopia progression of −0.48 D per year for Asians  but not in the other continents. Stratification by time demonstrated a myopia progression of −0.38 D per year (−0.54 to −0.21 D/year) before 2005, −0.26 D per year (−0.36 to −0.16 D/year) between 2005 and 2015, and −0.47 D per year (−0.54 to −0.40 D) after 2015 (p < 0.001). All I2 were > 90%. These results are presented in Within the 17 studies reporting a myopia progression ,57,60,61om −0.05  to −0.92om −0.05 . After sp-values were < 0.001 and all I2 were > 75% . There was a trend for a greater prevalence of myopia with the increase of indoor activity . Except a trend for a decreased prevalence of myopia in recent years, we did not find any other variables linked with prevalence of myopia , in women compared to men , and in Asia compared to Europe  and Oceania  (f myopia . p = 0.095)  . We did = 0.095) .The main findings were that near work exposure, including occupational exposure in adults, could be associated with myopia. The odds of myopia in the population exposed to near work is increased by 31% in children, and by 21% in adults. Some regions such as Asia may be more susceptible to the risk of myopia in case of near work exposure. We then discussed the factors that may contribute to this association between the risk of myopia and near work exposure.This study is the first meta-analysis that studied myopia and near work in adults. We demonstrated that occupational exposure to near work in adults is associated with a 20% increase in the odds of myopia. The increasing prevalence of myopia also implies untreatable complications that might occur even in the working-age population, such as myopic maculopathy, more frequently observed in high myopia . In addiMyopia prevalence in our study was similar to those previously reported globally  and in EFactors promoting myopia are also specific to some cultural or subcultural characteristics, such as urbanization, economy, social class, education and lifestyle ,41,113. Our meta-analyses suggest that myopia progression may be associated with the exposure to near work ,42,44,45Our study has some limitations. Several biases could have been introduced via the literature search and selection procedure. We conducted the meta-analyses on published articles only; thus potentially exposed to publication bias. We observed that a large part of the variability in out meta-analysis is secondary to between-studies heterogeneity. Conclusions from subgroup analysis and meta-regressions were also affected by this high heterogeneity. The populations investigated in our meta-analysis appear to be from varied origin, predominantly from the developed and developing countries, favouring the external validity of our results toward the population exposed to near work. One potential confounding factor could be the amount of exposure to outdoor light one is exposed to, a parameter not reported in every included study. We could hypothesize that outdoor light exposure may be inversely correlated with indoor light exposure and near work, and thus could also be associated with myopia, but our results do not support this hypothesis . MoreoveIn conclusion, near work seems to be associated with myopia, including occupational exposure in adults. The prevalence of myopia following near-work exposure was significantly higher in adults (46%) compared to children (31%). Furthermore, our results suggest that the odds of myopia in adults with occupational exposure to near work is 21% higher (95% CI: 6 to 35%) compared to the non-exposed. Considering the consequences of myopia both for employees and employers, targeted prevention strategies should be implemented in the workplace.


We study video inpainting, which aims to recover realistic textures from damaged frames. Recent progress has been made by taking other frames as references so that relevant textures can be transferred to damaged frames. However, existing video inpainting approaches neglect the ability of the model to extract information and reconstruct the content, resulting in the inability to reconstruct the textures that should be transferred accurately. In this paper, we propose a novel and effective spatial-temporal texture transformer network (STTTN) for video inpainting. STTTN consists of six closely related modules optimized for video inpainting tasks: feature similarity measure for more accurate frame pre-repair, an encoder with strong information extraction ability, embedding module for finding a correlation, coarse low-frequency feature transfer, refinement high-frequency feature transfer, and decoder with accurate content reconstruction ability. Such a design encourages joint feature learning across the input and reference frames. To demonstrate the advancedness and effectiveness of the proposed model, we conduct comprehensive ablation learning and qualitative and quantitative experiments on multiple datasets by using standard stationary masks and more realistic moving object masks. The excellent experimental results demonstrate the authenticity and reliability of the STTTN. Video inpainting involves smearing moving or stationary objects in a video frame sequence using masks. The smeared parts are filled back based on the current frame and the content information of other frames of the video, and the repaired video should have the effect that the smeared positions 'disappear'. Typical applications are video restoration  should be extracted from the reference frame? How can the information of the reference frame and the current frame be effectively extracted and used ?We put forward the spatial-temporal texture transformer network to solve these problems in video inpainting. STTTN is divided into the following six parts: (1) Make the feature similarity measure more accurate and frame pre-repair. (2) By introducing Regional Normalization (RN)  introduced into the encoder and decoder creatively stabilizes the effect of video restoration.From the results of various mask experiments on multiple datasets, STTTN achieves excellent results visually and in terms of evaluation parameters.Video Inpainting refers to smearing some fixed areas or moving objects in a video and filling the smeared areas back in a generated way. It is required as far as possible to leave no trace . Image inpainting fills the missing area in a single image. In a narrow sense, image inpainting is a subset of video inpainting. The difference between them is that video inpainting needs to integrate the temporal and spatial information acquired from all video frames and effectively transform and fill it back into the restored image. Image inpainting only needs to make use of the spatial information outside the mask of the current picture without considering the information of other frames because it is only a single picture without any temporal information. From the perspective of repair methods, video inpainting is mainly divided into two methods. One is explicit repair, that is, it acts directly on the image and repairs from the pixel level. The other is implicit inpainting, that is, it acts on image coding and inpainting from the feature level.Explicit inpainting is a network design pattern of 'graph to graph' and is directly constructed. Before the popularity of deep learning, the main image and video inpainting methods were diffusion-based and patch-based methods. The central idea of diffusion-based methods , coarse low-frequency feature transfer (CLFT), refining high-frequency feature transfer (RHFT), and decoder. Finally, we combed the whole video restoration process and explained the model's loss function more clearly through pseudo-code.We use implicit inpainting to repair the video from the feature level. To determine the defects of the previous architecture and achieve a better inpainting effect, we erase the time domain search part of the previous baseline model  to help with network training , K (attention information of memory frame), and V (representative content information of memory frame).The input to the encoder network consists of three frames . Inp, InpΔ, Ref, and RefΔ represent the input frames, input framesΔ, reference frames, and reference framesΔ, respectively. InpΔ and RefΔ consist of an RGB image, hole mask, and no-hole mask. The hole mask on the RGB image is a single-channel greyscale image, and the no-hole mask is an area other than the hole mask area. These inputs are concatenated along the channel axis to form a 5-channel image before being fed into the first layer. Ref are composed of three-channel RGB images. Given an input feature qi and kj. We calculate their similarity by dot multiplying q and kT, where T represents the transpose operation:Different from the previous operation of obtaining q, k, v through a linear transformer and then calculating attention . The previous attention mechanism converted V over different temporal domains with input frames via CLET. More specifically, we first calculate a coarse low-frequency feature transfer map P in which the i-th element Pi is calculated from the relevance Ri, j:However, doing so may transfer a large number of textures that are not useful for the input frame to the target frame, resulting in blurring of the repaired area. To improve the ability to transfer low-frequency texture features for all reference frames. we will correlate the coarse low-frequency features in pi in map P represents the most relevant position index of a frame on all reference frames with the i-th position of the input frame. The specific calculation process obtains the index corresponding to the maximum value through the second item of the return value of the torch.max function. After obtaining the most relevant position index, we extract the low-frequency texture features that should be transferred most, so we only need to take the position of the frame that needs to be transferred in the patch v of the unfolded, then we can get the texture feature map T, where each position of T contains the high-frequency texture features of the most similar position in the Ref, where ti represents the value of the i-th position of T:That is, each value We obtain a rough feature representation T for input frames, which is then used in our refinement of high-frequency feature transfer (RHFT).W is calculated from Ri, j to represent the confidence of the transferred texture features for each position in T. The specific calculation process for obtaining W is to obtain the maximum value of Ri, j through the first item of the return value of the torch.max function, where W records the specific correlation of the most relevant feature block.High-frequency detail information is also essential for video inpainting  and fuse them with high- and low-frequency features. The above operations can be expressed as the following formula:To make full use of the original image information of the input frame, we divide the features of each level into two steps. First, the low-frequency texture features Conv, Concat, and ⊙ represent the convolution (the convolution operation adopted here is consistent with the convolution operation adopted by the DNN above), the concatenation operation, and the dot product, respectively, and Fout is the feature of the spatiotemporal texture output of the input frame combined with reference frames.In the deep network, each corrupted area and uncorrupted area are increasingly difficult to distinguish, and the corresponding mask is difficult to obtain  represents the number of channels, height, and width of the feature map of this layer; and IRef is the reference video for all frames. T is the texture feature transferred from V in The first part is no different from ordinary perceptual loss . The students chose one image from the two repaired images containing STTTN each time they thought the repair was better and better; that is, each person made ten choices, for a total of 100 × 12 = 1, 200 voting choices. In To verify the effectiveness of each part of STTTN, we carried out ablation learning, which is each part of texture transformation, and loss function, where each part of texture transformation contains four sets of ablation learning and the loss function contains two sets of ablation learning.As shown in The five columns in the first row of In this paper, we proposed a novel joint spatial-temporal texture transformer network for video inpainting. Each component cooperates closely, and the repair process progresses layer by layer, making full use of the texture feature information in time and space. The model has outstanding information extraction and content reconstruction capabilities in details and contours, which are essential and suitable for video repair tasks. The excellent results of STTTN's experiments on multiple datasets in multiple scenarios fully demonstrate its superiority over other methods.However, in our exploration process, we found that STTTN has certain defects and room for further improvement. First, the first defect is also the region normalization defect, that is, color casting is prone to occur. The second defect, which is also a defect that the entire implicit inpainting architecture is prone to have, is the inconsistency in the temporal domain . Video tests appear periodically. We hope that our exploration of video inpainting can help other researchers explore further in this field and that researchers can propose more advanced models to improve the defects we have found thus far.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.PM provided the idea of the algorithm and designed the entire architecture and was responsible for the writing of the manuscript and the conduct of the experiments. TX reviewed the manuscript. Both authors read and approved the final manuscript.This research was supported by the Shaanxi Provincial Technical Innovation Guidance Special (Fund) Plan in 2020 (2020CGXNG-012).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The enterovirus Coxsackievirus B3 (CVB3) is known to be a major source for the development of cardiac dysfunctions like viral myocarditis (VMC) and dilatative cardiomyopathy (DCM), but also results in bradycardia and fatal cardiac arrest. Besides clinical reports on bradycardia and sudden cardiac death, very little is known about the influence of CVB3 on the activity of human cardiac pacemaker cells. Here, we address this issue using the first human induced pluripotent stem cell (hiPSC)-derived pacemaker-like cells, in which the expression of a transgenic non-infectious variant of CVB3 can be controlled dose- and time-dependently. We found that CVB3 drastically changed hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) distribution and function in hiPSC-derived pacemaker-like tissue. In addition, using HCN4 cell expression systems, we found that HCN4 currents were decreased with altered voltage dependency of activation when CVB3 was expressed. Increased autophagosome formation and autophagosomal HCN4 insertion was observed in hiPSC-derived pacemaker-like cells under CVB3 expression as well. Individual effects of single, non-structural CVB3 proteins were analyzed and demonstrated that CVB3 proteins 2C and 3A had the most robust effect on HCN4 activity. Treatment of cells with the Rab7 inhibitor CID 106770 or the CVB3-3A inhibitor GW5074 led to the recovery of the cytoplasmatic HCN4 accumulation into a healthy appearing phenotype, indicating that malfunctioning Rab7-directed autophagosome transport is involved in the disturbed, cytoplasmatic HCN4 accumulation in CVB3-expressing human pacemaker-like cells. Summarizing, the enterovirus CVB3 inhibits human cardiac pacemaker function by reducing the pacemaker channel plasma membrane density, an effect that can be corrected by pharmacological intervention of endocytic vesicle trafficking.The online version contains supplementary material available at 10.1007/s00018-022-04435-7. Two-electrode voltage clamp (TEVC) recordings were conducted 3–4 days after injection using a Turbo Tec-10CX  amplifier. Electrophysiological data were recorded and analyzed with GePulse and Ana . Data analysis was done using OriginPro 2018 . Recording pipettes were filled with 3 M KCl and had resistances of 0.4–1.5 MΩ. Channel currents were recorded 3 days after injection at room temperature in ND96 recording solution containing (in mM): 96 NaCl, 4 KCl, 1.8 MgCl2, 1.0 mM CaCl2, and 5 mM HEPES; (pH 7.6).Preparation of cRNAs and DNA constructs encoding human HCN4 and CVB3 constructs were done as previously described , 32. HumV1⁄2), slope factor (k), and the minimum open probability  measurements were undertaken. Therefore, young (14-day-old) and matured (40-day-old) pacemaker-like cells and matured, CVB3-induced (40-day-old + 5 days of CVB3 induction) pacemaker-like cells were compared under basal conditions and under 10 μM ivabradine, a potent HCN channel blocker. The whole MEA recording was undertaken at room temperature. Young pacemaker-like cells showed a mean signal generation rate of 30.30 signals/min (± 0.576 SEM) under basal conditions and 28.85 signals/min (± 0.501 SEM) after ivabradine supplementation , which indicates that the measured shift in V1/2 was not measured due to a change in the HCN4 channel activation state.To study the electrophysiological properties of the HCN4 channel under the influence of CVB3, the channel was expressed alone or together with non-infectious CVB3 in f were analyzed in more detail. For this purpose, the HCN4 channel was coexpressed alone or with a viral protein in Xenopus oocytes. Again, the individual viral proteins were injected separately, 2 days before the electrophysiological measurements were performed. After 2 days of expression of the viral protease 2A, the oocytes were too damaged to be measured. In addition, the lifespan of the oocytes could not be prolonged even by injecting smaller amounts of cRNA. Therefore, the injection of 2A was done only one day prior recording. The coexpression of HCN4 with the viral proteins 2C and 3A resulted in dramatic reduction of the HCN4 current amplitude by about 60–70%. The viral proteins 2A, 2BC, 3C and 3AB led to mild reduction of the currents between 22 and 40%. The coexpression of the viral proteins 2B, 3B, 3CD and 3D, however, led to little or no reduction (≥ 15%) of the HCN4 current amplitude , the Beclin-1 signal increased by 15.9% (± 2.5 SEM) and the p62 signal increased by 35,0% (± 3.8 SEM) indicating general increase of autophagosome formation during CVB3 expression  [Kr blockade, which would keep the cells closer to calcium channel activation may be another possible explanation for the observed spontaneous activity of CVB3-expressing cells [enopus laevis oocytes were performed. The activity of HCN4 decreased tremendously when co-expressed with CVB3  . The phant (IKr) . Elevateng cells . To veriion Fig. a, b. Theion Fig. a, b.. Fuion Fig. c.. TheseAs cytoplasmatic HCN4 localization and autophagy were found enhanced in CVB3-expressing cells, it raised the hypothesis that aberrant vesicular trafficking might be involved in the observed cytoplasmatic accumulation. As the cardiac Kv7.1 has previously been shown to be increasingly transported to the cell membrane via enhanced SGK1 and Rab11 activation during CVB3-2A expression, a viral disturbance of another Rab-dependent transport pathway for HCN4 might explain decreased membrane insertion and cytoplasmatic accumulation . As the Summarizing, CVB3 expression inhibits human cardiac pacemaker function by reducing the pace maker channel plasma membrane density. This process depends on RAB7 and the CVB3 effect can be corrected by pharmacological intervention of endocytic vesicle trafficking Fig. c. PotentSupplementary file1 (AVI 29912 kb)Supplementary file2 (AVI 30500 kb)Below is the link to the electronic supplementary material.


As co-factor in many enzymatic reactions, Mg2+ is essential for protein synthesis, energy production, and DNA stability. Disturbances in intracellular Mg2+ concentrations, therefore, unequivocally result in delayed cell growth and metabolic defects. To maintain physiological Mg2+ levels, all organisms rely on balanced Mg2+ influx and efflux via Mg2+ channels and transporters. This review compares the structure and the function of prokaryotic Mg2+ transporters and their eukaryotic counterparts. In prokaryotes, cellular Mg2+ homeostasis is orchestrated via the CorA, MgtA/B, MgtE, and CorB/C Mg2+ transporters. For CorA, MgtE, and CorB/C, the motifs that form the selectivity pore are conserved during evolution. These findings suggest that CNNM proteins, the vertebrate orthologues of CorB/C, also have Mg2+ transport capacity. Whereas CorA and CorB/C proteins share the gross quaternary structure and functional properties with their respective orthologues, the MgtE channel only shares the selectivity pore with SLC41 Na+/Mg2+ transporters. In eukaryotes, TRPM6 and TRPM7 Mg2+ channels provide an additional Mg2+ transport mechanism, consisting of a fusion of channel with a kinase. The unique features these TRP channels allow the integration of hormonal, cellular, and transcriptional regulatory pathways that determine their Mg2+ transport capacity. Our review demonstrates that understanding the structure and function of prokaryotic magnesiotropic proteins aids in our basic understanding of Mg2+ transport.Magnesium (Mg Thi2+ and Na+/K+-ATPases and shared in many of the MgtA homologues in various prokaryotes. In MgtB, the Thr is replaced by Ser in S. typhimurium (QSG) . Th. Th64]. 2+-ATPases have been postulated in vertebrates, the molecular identity of a MgtA/B orthologue remains obscure. Many studies reported Mg2+-dependent ATP hydrolytic activity in different organelles, such as the plasma membrane, endoplasmatic reticulum, sarcolemma, and microvesicles found in heart, muscle, and brain . T. T83]. T sapiens . The domar range . Additiolug Fig. A, which the pore , 87. Theproteins , 88, 89.r gating , 83, 86.C. elegans, which is the eukaryotic homologue of MgtE [6GN and P(D/A)X4PX6D X4PX6D motifs, allow to proteins to potentially function as monomers or dimers to facilitate Mg2+ transport, similarly to the prokaryotic MgtE proteins [Archaea, choanoflagellates, and metazoa, while uni- and multicellular algae and (cyano)bacteria share contain only one PX6GN and P(D/A)X4PX6D motif. In addition, the MgtE orthologues in Archaea and metazoa do not contain the CBS domains and the structure of the SLC41 family deviates considerably from the MgtE proteins  in humans, mouse, and  of MgtE . Interes of MgtE . The ideproteins . The douiporters –94. TakeXenopus laevis oocytes demonstrated Mg2+ elicited currents upon mouse SLC41A1 overexpression, yet other divalent cations, such as Zn2+, Fe2+ and Cu2+ were also transported [S. typhimurium MM281 strain, which is deficient in corA, mgtA, and mgtCB, displayed superior growth in Mg2+ depleted conditions compared to the those with empty pUC18 plasmids [2+ using the fluorescent-sensitive probe Mag-Fura-2. Moreover, Mg2+ extrusion was abrogated upon Na+ removal, suggesting a Na+/Mg2+ exchange function to facilitate Mg2+ extrusion [+-dependent Mg2+ transport has been observed [+-independent Mg2+ uptake and extrusion using the stable isotope 25Mg2+[2+ homeostasis. Knock-down of slc41a1 in zebrafish larvae decreased the Mg2+ content and induced a transcriptional response of genes involved in Mg2+ homeostasis [Slc41a3 expression was increased in kidneys of mice fed with low-Mg2+ diets and Slc41a3−/− mice displayed hypomagnesaemia and increased intestinal Mg2+ absorption [2+ homeostasis remains to be elucidated. While SLC41A1 and -A2 are located at the plasma membrane, SLC41A3 is predominantly found in the mitochondria [2+ transport and systemic Mg2+ homeostasis.Electrophysiological studies in nsported . Transfoplasmids . Expressxtrusion . Also foobserved , 96, yetobserved . In contpe 25Mg2+, leavingeostasis . Slc41a3sorption , 100. Yechondria , 94, 98.2+ influx and efflux, three other genes were identified in S. typhimurium; corB, corC, corD 21, a structure that is poorly characterised in terms of distribution among species and function [Methanoculleus thermophilus CorB (MtCorB) and bacterium Tepidiphilus thermophilus (TtCorB) in liposomes showed transport of Mg2+ [2+ extrusion when cells were exposed to Na+, which was prevented when Na+ was removed from the buffer. Mutational analysis of the Thermus parvatiensi CorC orthologue indicated that residue Asn94 (N94) might be important for Na+ sensitivity. Indeed, mutagenesis of this residue showed decreased efflux compared to wild type when overexpressed in HEK293 cells, being indicative that CorB/C might work as a Na+/Mg2+ antiporter [Although CorA was initially thought to be involved in both MgorD Fig. . These lsistance . While Ch 28Mg2+ . These tfunction , 102. Th of Mg2+ . Express2+ transporter in metazoa. Electrophysiological studies in X. laevis oocytes suggested that CNNM2 acts indeed as a Mg2+ exchanger [2+ probe MagnesiumGreen demonstrated Mg2+ extrusion upon CNNM2 overexpression [2+ and Zn2+-sensitive Na+ currents, which were ablated when a patient-derived CNNM2 mutant was used [2+-sensitive probe Mag-Fura-2 and failed to demonstrate changes in intracellular Mg2+ levels upon overexpression [25Mg2+ could not detect Na+-dependent Mg2+ transport in HEK293 cells [2+ sensor role for CNNM proteins was hypothesised. However, the IC50 value for MgATP binding of CNNM2 and CNNM4 are estimated to be approximately 160 and 45 μmol/L, respectively [2+ in the physiological situation.The vertebrate orthologues of CorB were first identified in mouse, and named ancient conserved domain protein (ACDP) 1–4, which later were renamed as Cyclin M(CNNM)1–4 , 104. Eaxchanger . Additiopression . Howeverwas used . In addipression . Moreove93 cells . Consequectively , 111. It2+. In contrast, studies using the stable isotope 25Mg2+ are superior in investigating Mg2+ fluxes, but do not provide information on intracellular Mg2+ concentrations. In addition, only overexpression studies have been performed that may not reflect the physiological situations. Recently, interaction partners have been identified that can modulate CNNM function. Cell-specific expression of these proteins could exert different effects based on the model used. For instance, phosphatase of regenerating liver (PRL)1–3 are proto-oncogenic proteins that can bind to CNNM proteins and are postulated to inhibit CNNM-mediated Mg2+ efflux [2+ levels [25Mg2+ uptake upon overexpression [2+ channel transient receptor potential receptor type 7 (TRPM7) in vivo and vitro.[X. laevis oocytes upon heterologous overexpression, suggesting a potential, complex regulatory mechanism of ARL15-CNNM regulation on TRPM7 channel activity.The role of CNNM proteins remains disputed and has been discussed elaborately earlier , 111. It+ efflux –114. Tra+ levels , which cpression . A recennd vitro. ARL15 re2+ homeostasis. Patients suffering dominant mutations in the CNNM2 gene present with hypomagnesaemia, seizures, and intellectual disability (HSMR) syndrome [2+ wasting, fitting with the expression of CNNM2 in the distal convoluted tubule within the nephron [Cnnm2 in murine models and knock-down in zebrafish larvae have shown to result in mild hypomagnesaemia [Cnnm2 knock out are embryonically lethal and may suffer exencephaly [Cnnm4 knock mice also develop hypomagnesaemia, which is attributed to intestinal malabsorption [2+ extrusion towards the blood compartment. Interestingly, patients suffering Jalili syndrome due to dominant mutations in the CNNM4 gene do not develop serum Mg2+ disturbances, rather defects in amelogenesis and cone-rod dystrophy [How the CNNM protein exert their function still remains to be determined, yet from a physiological point of view, it is clear for CNNM2 and CNNM4 that they are involved in systemic Mgsyndrome , 119. Pa nephron , 118. Synesaemia , 121. Panesaemia . Cnnm2 ksorption , 124. Itystrophy , 126.2+ ions, results in conformational changes, rendering the protein in closed. The CNNM protein subsequently contains cyclic nucleotide bind homology (CNBH) domains which, in contrast with the initial predictions (so their name), do not bind cyclic nucleotides, and perhaps regulate the function of CNNMs [2+/MgATP or II) functions as an adaptable regulator itself [2+ efflux [Structurally, CNNM proteins are similar to CorB/C Fig. B 101, 1. The CNNof CNNMs , 130. Itr itself , 130. Onr itself . This rer itself –114, 116+ efflux , 130. Th2+ transporting proteins SLC41 and the Mg2+ sensors CNNMs. However, as elaborately reviewed earlier[2+ in a different manner [2+ to close the MgtE channel is dependent on the presence of ATP [2+-sensitive gating of MgtE channels. Conversely, studies using a surface plasmon resonance sensorgram with immobilised, recombinant CBS domains from CNNM2 demonstrated binding of ionised Mg2+ to the CBS domains [2+. Taken together, these findings suggest that MgtE binds Mg2+ in an ATP-dependent manner, while conversely CNNMs bind ATP in a Mg2+ dependent fashion. Thirdly, only four Mg2+-bindings sites have been identified in CNNM orthologue, while MgtE contains seven. Lastly, binding of MgATP leads to “opening and closing” of the MgtE pore via the plug, while the CBS domains in CNNM adopt a “disc-like-flat” structure, which moves the DUF21 domain and closes the pore [Apart from its homology to the CorB/C proteins, it is intriguing to mention a potential evolutionary link between MgtE and CNNMs as both proteins form dimers and contain CBS domains. It is interesting to speculate that MgtE split in two different proteins during evolution; into the Mgd earlier, structud earlier, 86. Thid earlier, 129. Set manner . Patch ce of ATP . This su domains . In contthe pore , 132. Al2 into metazoan cells is via the transient receptors potential melastatin type (TRPM) 6 and 7 channels, which are non-selective divalent cation channels, permeable for among others Zn2+, Mg2+, and Ca2+ [The main entrance for Mgand Ca2+ , 134. Thand Ca2+ , 135–1372+ into metazoan cells. Cells deficient of TRPM7 have decreased intracellular Mg2+ levels and require Mg2+ supplementation when cultured in vitro.[2+ homeostasis in vivo [TRPM7 is expressed ubiquitously in the body and considered the main gateway of Mgin vitro., 139 The in vivo , 141.2+ transport, yet structurally they are very similar to the other members of the TRPM channels , amoebozoans (TRPP and TRPML), and choanoflagellates, which are the closest single cell relatives to the metazoa , suggesting that the TRP channels evolved during the origin of the eukaryotes , 143. Wiels Fig. A, facilieability .Fig. 7St2+ levels in the body [2+ and MgATP, Zn2+ and Ca2+ also directly regulate channel activity. Mg2+ is postulated to bind to the linker between the channel and kinase domain, whereas there is a Zn2+ binding motif located in the kinase domain, consisting of two histidines and cysteines [2O2 exposure, results in dissociation of Zn2+ ions from the channel with inactivation as a consequence. These cysteines may, therefore, act as sensors for oxidative stress. Closing the TRPM7 channel may prevent further cell damage, as increased cytosolic Mg2+ levels are associated with increased ROS levels [2+ influx has been implicated with neurotoxicity, while increased intracellular levels may induce Ca2+-mediated caspase activity and ultimately cell death [TRPM6 and TRPM7 are specialised channels in the TPRM family for two major reasons. The channels form homo or heterotetramer structures, which is necessary for their activation. Yet, TRPM6 homotetramers are considered inactive, inferring that TRPM7 expression is always concomitant with TRPM6 , 134. Sethe body , 154. Inysteines . OxidatiS levels –158. Furll death –161.2+ homeostasis in both prokaryotes and eukaryotes is orchestrated by the interplay of various Mg2+ channels and transporters, indicating a high degree of regulatory pathways. Although the structure of individual Mg2+ transporters have significantly changed, the motifs that form the selective pore in CorA, CorB/C, and MgtE have all been conserved in their eukaryotic counterparts. Incredibly, the overall tertiary and quaternary structure for CorA and CorB/C have been sustained in MRS2 and CNNM proteins respectively despite low amino acid identity. This demonstrates the importance of these structures for Mg2+ specific transport.MgS. cerevisiae, CorA orthologues play an important role in Mg2+ homeostasis with many paralogues/homologues present in different subcellular compartments. However, metazoa only have the CorA orthologue, Mrs2, in mitochondria and do not have an evolutionary conserved CorA-like protein at the plasma membrane. Cellular Mg2+ influx is mainly orchestrated via TRPM6 and -7 channels in these organisms, suggesting that these channels may have an evolutionary advantage compared to CorA orthologues. TRPM6 and -7 are responsive to different hormones and ligands [2+ homeostasis is still poorly understood, despite extensive research. Unravelling the function of this domain, as well as further identification of interaction partners and regulatory pathways may shine light upon the loss of CorA orthologues in favour of TRPM6 and -7 channels in metazoa.Despite these similarities, it is conspicuous that in unicellular fungi, such as  ligands , 163 whi2+ channels/transporters, a few approaches could be considered. First of all, the structures of several eukaryotic Mg2+ channels and transporters have not completely resolved, including SLC41 and MgtE proteins. To date, only predication tools (AlphaFold) have provided structural information of SLC41 proteins, but ultimately cryo-EM or X-ray crystallography is required to elucidate the overall structures. Transport characteristics, e.g. permeation or gating dynamics, could be investigated if structures are available. This would especially be valuable for SLC41 proteins, because they lack the CBS domains compared to MgtE channels. Second, extensive phylogenetic tracing would allow to determine the evolutionary link of SLC41 and MgtE proteins, which is particularly interesting as MgtE orthologues appear to be missing in various phyla, such as land plants and fungi. In addition, it would be important to examine whether MgtA/B orthologues exist in eukaryotes. MgATPases have been postulated to be present in vertebrates, but have not been identified on a genetic level. Lastly, the mode of action of several transporters is often disputed, frequently due the use of different experimental techniques and models. Transport assays using specific isotopes or fluorescent probes in models such as liposomes directly would significantly contribute to the field. These assays are also valuable to determine the difference between paralogues, e.g. the CNNM or SLC41 proteins.To gain more insights into the similarities and differences between pro- and eukaryotic Mg2+ transporting proteins in eukaryotes. For instance, Magnesium transporter 1 (MagT1) was postulated as a Mg2+ transporter in X. laevis oocytes [2+ conditions in HEK293T cells [MagT1 gene have been linked to N-glycosylation and immunodeficiency [2+ homeostasis by modulating Mg2+ channels and transporters at the membrane via glycosylation. Members of the solute carrier proteins 25 (SLC25) are mitochondrial specific antiporters of MgATP and HPO4−, that indeed transport (indirectly) Mg2+ [2+ transport has not been observed. Lastly, the proteins Non-imprinted in Prader-Willi/Angelman syndrome (NIPA) 1–4 have been postulated to be Mg2+ transporters [X. laevis oocytes, indeed show Mg2+ fluxes that can be ablated upon the introduction of patient mutations [2+ transport in mammalian cells is largely lacking. Extensive reviewing of aforementioned proteins should be performed in homologous cell systems to determine Mg2+ transport function.Of note, transporters discussed in this review may not be the only Mg oocytes . It is e3T cells . Yet, muficiency . As manyly) Mg2+ . Althougsporters . Mutatiosporters . Expressutations . Yet, ex2+ transporters in different phyla enables the understanding the origin and function of current mammalian magnesiotropic proteins. This broadens our current knowledge in Mg2+ homeostasis in health and disease.In conclusion, to study the structural relationship between Mg


Enhancing the educational experience provided by ward rounds requires an understanding of current perceptions of the educational value of rounds.This systematic review examines perceptions of education in ward rounds, educational activities in ward rounds, barriers to learning, and perceptions of simulation-based ward rounds.The 2020 PRISMA  guidelines were followed. MEDLINE (EBSCO), Cochrane, and Scopus were searched on May 29, 2022, for studies assessing learning during ward rounds. The search terms included “ward rounds,” “education,” and “trainees.” Then, the selected articles were reference searched. In total, 354 articles were retrieved. The articles were assessed for eligibility by 2 independent reviewers who screened titles, abstracts, and full-length texts. Articles addressing trainees’ education in all ward rounds were included. Articles were excluded if they were specific to certain disciplines, were reviews, were not published in scholarly journals, were published before 2015, were published in languages other than English, or did not concern human participants. Following the removal of 63 duplicates, a total of 268 articles were excluded. The risk of bias within the selected articles was also assessed via the Critical Appraisal Skills Programme checklist for qualitative research. Qualitative data were used to describe results in a narrative synthesis and in tables.A total of 23 articles were included. Perceptions of teaching in rounds were addressed by 6 studies, of which 3 showed negative perceptions among participants, 2 reported ambivalent perceptions, and 1 showed positive perceptions. Perceived barriers to teaching during rounds were assessed by 7 studies. The reported barriers included time constraints, workloads, schedules, interruptions, the service-oriented nature of rounds, the lack of feedback, hierarchies, the lack of opportunities to ask questions and be engaged in patient management, and divergent learner needs. Further, 8 studies identified types of educational activities, including observation, patient-specific teaching, and discussion. Perceptions of learning through simulated ward rounds were assessed by 8 studies, and a consensus of satisfaction was noted among learners. The interventions that were explored to improve education included using teaching frameworks, involving clinical librarians, and changing the setting of ward rounds.The main limitations of this review are the predominant use of qualitative data in the included articles and the lack of standardization for the educational compositions of ward rounds among articles, which made the articles hard to compare. In conclusion, learning opportunities in ward rounds are often missed, and trainees perceive rounds to have low educational value. It is important to recognize the barriers to education during ward rounds and address them to maximize the benefits of ward rounds. Finally, there is a need to develop plans that incorporate teaching regularly during ward rounds in the inpatient setting.PROSPERO CRD42022337736; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337736 Ward rounds are conducted by teams of health care practitioners to review, assess, and manage patients in an inpatient setting, visiting each patient in order at their bedside. Ward rounds also represent an opportunity for trainees to learn and enhance their clinical and interpersonal skills ,2. The eEnhancing the educational experience provided by ward rounds requires an understanding of current perceptions and experiences. This review examines perceptions of the educational value and content of ward rounds and the interventions that have been explored to optimize education in ward rounds.This systematic review followed the 2020 PRISMA  guidelines . This reMEDLINE (EBSCO), Cochrane, and Scopus were searched on May 29, 2022, for studies examining the educational value of ward rounds. The search terms used included “ward rounds,” “rounds,” “teaching,” “education,” “learning,” “junior,” and “trainee.” Search limiters were added to narrow the search; the limiters included publications in scholarly (peer-reviewed) journals, English-language articles, human studies, and a date of publication ranging from 2015 to the date of the search. The search was restricted to papers published from 2015 to the date of the search in order to ensure that recent trends in teaching and education in wards were identified. Articles addressing trainees’ education in all ward rounds were included. Articles were excluded if they did not relate to education during ward rounds, were specific to certain disciplines, were reviews, were not published in scholarly journals, were published before 2015, were published in languages other than English, or did not concern human participants.Two independent reviewers assessed articles for eligibility. In cases of disagreement, discussions were sufficient for reaching an agreement. No third-party review was needed to resolve discrepancies. After excluding articles, the number of remaining relevant articles was reduced by specifying search limiters. Articles were then excluded based on reading the abstracts and titles. A search of the references in the selected articles was also performed. Next, full texts were read to assess articles’ relevance to the selected topic. Afterward, reference searching was performed to identify more articles. Qualitative data on the following themes were extracted: perceptions of the educational value of ward rounds, perceived barriers to teaching and learning, types of educational activities, perceptions of simulation-based ward rounds, the impact of trainee characteristics on the educational experience provided by rounds, and interventions and solutions that were explored to improve learning during ward rounds. The participants’ views and reported outcomes were expressed as percentages.The quality of the evidence presented in the selected articles was assessed via the Oxford Centre for Evidence-Based Medicine levels of evidence . The risA total of 354 publications were retrieved. Studies were sorted by relevance. After removing duplicates, titles and abstracts were screened to assess eligibility, which resulted in the exclusion of 261 articles. The remaining 30 full-length articles were read, and 7 additional articles were excluded. Exclusion details are outlined in The themes pertaining to education in ward rounds were identified .Of the 23 included studies, 6 were cross-sectional observational studies, 4 were prospective observational studies, 2 were pre-post studies, 1 was an audit, and 1 was a randomized controlled trial. The details of the other study types can be found in A total of 6 studies assessed perceptions of teaching in rounds ,26,28,29A total of 7 studies assessed perceived barriers to teaching during rounds ,19,27-29Laskaratos et al , 2015Time constraintsWorkloadInterruptionsService-oriented nature of rounds (competing administrative tasks)Sparsity of feedbackLaskaratos et al , 2016Service-oriented nature of roundsGray and Enright , 2018Hierarchal nature of rounds (consultant-led rounds)Limited opportunities for trainees to be involved in setting management plansLimited opportunities to ask questionsKhan et al , 2021Time constraintsThe number of patients (workload)Service-oriented roundsModak and Gray , 2020Time restrictionsWorkloadSchedulesClerical dutiesHesitancy to provide feedbackConsultants’ willingness to teachTrainees’ initiative to ask for feedbackArmendariz et al , 2021Interruptions during rounds Rabinowitz et al , 2016Time restraintsLimited working hoursVariations in participants’ needsOne study addressed the impact of trainees’ characteristics on their perceptions of the educational value of rounds. Modak and Gray  found thA total of 8 studies mentioned learning activities during ward rounds ,24,28,29Perceptions of learning through simulated ward rounds were assessed by 8 studies ,20-22,25A total of 4 studies addressed different interventions that were attempted to optimize residents’ educational experiences during ward rounds ,23,26,30Daily ward rounds are conducted to assess patients’ status and progress throughout their hospital stay and devise management plans accordingly. They provide a great opportunity for trainee doctors to learn. However, the educational component of ward rounds remains an underresearched field; this review was conducted to explore the existing research on this topic.During rounds, attending physicians can highlight elements of clinical assessments, communication, management, general and evidence-based medical knowledge, and the decision-making process. They may explain rationales for selected approaches, emphasize cost-efficient options or alternatives, and tackle patient-centered approaches. They can also involve learners, answer their questions, and provide feedback ,19.This review showed that trainees’ views on the educational value of rounds are predominantly negative ,11,18. SOver the years, the educational value of teaching at the bedside has been commended, as it has been linked to increased information retention ; a betteAn article by Kim et al  compiledIt is important to recognize ward rounds as missed educational opportunities. This could be addressed by setting plans to incorporate teaching during rounds to make them more learner centered. This would involve physicians planning to engage trainees in the assessment and management of patients while also providing trainees with feedback. This can be followed up by assessing learners’ perceptions of the teaching methods used and the aspects they find most useful via anonymous surveys or quality assessment audits.One of the strengths of this review is that it sought the most recent information on teaching during ward rounds. This is because trainees’ current perspectives would not be masked by the changes in the educational content of ward rounds over time. Furthermore, this review addresses an underresearched topic in the literature and highlights this topic’s importance. This review also has limitations. The content that this review assesses, which includes perceptions, is mainly qualitative in nature, and some of the included articles derived results from a qualitative synthesis, which is suboptimal. Furthermore, there has been no aggregation or standardization for the educational composition of ward rounds, which made the articles difficult to compare. Finally, many of the interventions that have been attempted have not been studied further to adequately assess their efficacy and reliability.Despite the potential that ward rounds demonstrate for providing education, learning opportunities are often missed. In many articles , trainees perceived rounds to have low educational value. The perceived barriers to teaching during rounds were time constraints and the hierarchal structure and service-oriented nature of rounds. However, simulated ward rounds have been associated with improvements in the confidence and preparedness of learners. There is a need to develop plans that incorporate teaching regularly during ward rounds in the inpatient setting.


How concordant to an in-person diagnosis are provisional diagnoses established at a video telemedicine visit for patients presenting with a new clinical problem?In this diagnostic study of 2393 patients who underwent a video telemedicine consultation followed by an in-person outpatient visit for the same clinical problem in the same specialty within a 90-day window, the provisional diagnosis established over video telemedicine visit matched the in-person reference standard diagnosis in 86.9% of cases.These findings suggest that video telemedicine visits yield a high degree of diagnostic concordance to in-person visits for most new clinical concerns. This diagnostic study examines the concordance of provisional diagnoses established at a video telemedicine visit with diagnoses established at an in-person visit for patients presenting with a new clinical problem. There was a shift in patient volume from in-person to video telemedicine visits during the COVID-19 pandemic.To determine the concordance of provisional diagnoses established at a video telemedicine visit with diagnoses established at an in-person visit for patients presenting with a new clinical problem.This is a diagnostic study of patients who underwent a video telemedicine consultation followed by an in-person outpatient visit for the same clinical problem in the same specialty within a 90-day window. The provisional diagnosis made during the video telemedicine visit was compared with the reference standard diagnosis by 2 blinded, independent medical reviewers. A multivariate logistic regression model was used to determine factors significantly related to diagnostic concordance. The study was conducted at a large academic integrated multispecialty health care institution  between March 24 and June 24, 2020. Participants included Mayo Clinic patients residing in the US without age restriction. Data analysis was performed from December 2020 to June 2021.New clinical problem assessed via video telemedicine visit to home using Zoom Care Anyplace integrated into Epic.Concordance of provisional diagnoses established over video telemedicine visits compared against a reference standard diagnosis.International Statistical Classification of Diseases and Related Health Problems, Tenth Revision chapter ranged from 64.7%  for diseases of the ear and mastoid process to 96.8%  for neoplasms. Diagnostic concordance by medical specialty ranged from 77.3%  for otorhinolaryngology to 96.0% (92.1%-99.8%) for psychiatry. Specialty care was found to be significantly more likely than primary care to result in video telemedicine diagnoses concordant with a subsequent in-person visit .There were 2393 participants in the analysis. The median (IQR) age of patients was 53 (37-64) years; 1381 (57.7%) identified as female, and 1012 (42.3%) identified as male. Overall, the provisional diagnosis established over video telemedicine visit was concordant with the in-person reference standard diagnosis in 2080 of 2393 cases . Diagnostic concordance by This diagnostic study of video telemedicine visits yielded a high degree of diagnostic concordance compared with in-person visits for most new clinical concerns. Some specific clinical circumstances over video telemedicine were associated with a lower diagnostic concordance, and these patients may benefit from timely in-person follow-up. At its height in April 2020, telehealth usage was estimated to have increased 20-fold in the US.7 Large-scale, multispecialty data on the concordance of video telemedicine diagnoses with in-person visit diagnoses would help clinicians make evidence-based decisions regarding for which patients, in which clinical specialties, and for which types of clinical problems video telemedicine visits are likely to be sufficient for diagnosis.12 Before the COVID-19 pandemic, studies15 on the accuracy and concordance of video telemedicine diagnosis were limited by sample size, breadth of presenting diseases and clinical problems, representativeness of primary and specialty medical and surgical practices, and clinical practice implementation. A recent comprehensive report16 on the state of telehealth identified quantifying the diagnostic accuracy of telehealth as a critical research gap. The increase in telemedicine volume during the COVID-19 pandemic enabled our institution to rapidly gather data on video telemedicine visits on a larger scale than had previously been available.One of the principal concerns has been the limited data available regarding the accuracy with which clinicians diagnose patients’ diseases and conditions through video telemedicine visits and regarding the concordance between a video telemedicine diagnosis and that established through an in-person visit.STARD) 2015 reporting guidelines for reporting diagnostic studies were followed.The Mayo Clinic institutional review board (IRB) application was reviewed by expedited review procedures on April 8, 2020, and was determined to be exempt from the requirement for IRB approval and informed consent because the data were deidentified . The Mayo Clinic IRB approved a waiver of Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with applicable HIPAA regulations. The Standards for Reporting of Diagnostic Accuracy  were available during the telemedicine assessments. In-person visits were similarly scheduled through Epic and conducted on-site at any of the Mayo Clinic campuses. The description of applicable digital health technology and operations from patient and clinician standpoints has been previously published.18Video telemedicine was conducted using standard Zoom Mayo Clinic Care Anyplace integrated into Epic.International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code(s), day and time of the encounter, clinician type and characteristics, including years since certification, years of employment at Mayo Clinic, experience conducting telemedicine visits, and clinical department.For this study, clinicians included Mayo Clinic–employed consultant physicians  and advanced practice providers (nurse practitioners and physician assistants). Data from video telemedicine and in-person consultations for each included patient were extracted from the electronic medical record (EMR) Epic and auto-populated into a Research Data Capture (REDCap) database. These data included medical record number, patient demographics, primary diagnosis Twenty-seven trained third-year and fourth-year medical students from Mayo Clinic Alix School of Medicine familiar with Epic reviewed cases to abstract additional diagnostic data, including method of reference standard diagnosis, and make a blinded determination of the diagnostic agreement of the provisional telemedicine diagnosis and the reference standard in-person follow-up visit diagnosis. Medical reviewer training included two 1-hour virtual workshops conducted by lead study investigators describing in detail the workflow necessary to review the EMR, identify study-related data and definitions, decision-making, and data extraction. The definition of telemedicine provisional diagnosis was the diagnosis offered by the telemedicine clinician at the conclusion of the visit, taking into account the referral indication, chief concern, any diagnostic records, history acquisition, and video examination. The definition of the reference standard diagnosis was the diagnosis offered by the in-person clinician at the conclusion of the visit, taking into account the in-person history acquisition and physical examination, the results of any diagnostic testing available, and any information available in the EMR to the date of in-person visit. In instances where the reviewer determined that the provisional diagnosis was discordant with the reference standard diagnosis, the reviewer further assessed whether the diagnostic discordance carried the potential for morbidity or mortality and whether there was any actual morbidity or mortality. The medical reviewers reviewed the EMR documentation to determine how the clinicians tested their principal provisional diagnosis and probed their provisional differential diagnoses.In instances when a clinician established a diagnosis without reliance on a physical examination or any diagnostic testing, the modality of diagnosis was listed as “clinician opinion only.” In instances when clinicians documented specific positive physical examination findings consistent with or pathognomonic of a diagnosis, reviewers marked the modality of diagnosis as “physical examination.” In instances when clinicians documented in EMR the use of laboratory testing, diagnostic imaging, cardiac testing , neurological testing , or pathology , reviewers marked these accordingly. Other than the category of “clinician opinion only,” multiple other modalities of diagnosis could be listed and counted in the inventory.Each case was independently reviewed by 2 blinded medical students. In instances where the 2 reviewers’ assessments of the diagnostic concordance disagreed, the principal investigator reviewed the case in consultation with a specialist from the applicable clinical area. Medical reviewers also had an opportunity to flag any complex cases for tertiary review by the primary investigator. Finally, the primary investigator was assigned to review a random selection of 20% of cases in which the 2 medical student reviewers agreed and did not flag the case. In all applicable cases, the independent determination of the primary investigator was used as the determination of record.19 were calculated between the 2 medical student reviewers and also between the medical student reviewers and the physician reviewer to show interrater agreement. Telemedicine diagnostic concordance and the corresponding 95% CI by patients’ characteristics  as well as by clinicians’ characteristics  were estimated using binomial method. The χ2 test was used to test whether the telemedicine diagnostic concordances differed by different clinical practices. Logistic regression models with correlated data (patients’ data clustered within clinician) were used to determine patient and clinician characteristics that affected telemedicine diagnostic concordance. Generalized estimating equations method using exchangeable working correlation (to take the within-clinician correlation into account) was used to estimate the model parameters. Patient age, sex, clinician site, clinician type (nonphysician vs physician), case type , patient type (pediatric vs adult), specialty , telemedicine visit duration, clinicians’ years certified, and clinicians’ prior telemedicine experience were put in the univariate model, and the significant factors from the univariate model were verified in a multivariable model. All statistical analyses were performed using SAS statistical software version 9.4 (SAS Institute). All the hypothesis testing were 2-tailed testing, and P < .05 was chosen as the significance level. All statistical analyses were prespecified in the study protocol. Data analysis was performed from December 2020 to June 2021.Patients’ demographics and clinical characteristics along with clinicians’ characteristics were summarized in frequency (percentage), mean (SD), or median (IQR) accordingly. Prevalence-adjusted, bias-adjusted κ coefficientsThe eFigure in The overall concordance of diagnoses between video telemedicine visits and in-person visits was determined to be 86.9%  (2080 of 2393 visits). Patients with concordant and discordant diagnoses did not differ significantly in terms of sex, Mayo Clinic care site, or location of residence .P < .001) as well as between surgical (631 of 704 cases [89.6%]) and nonsurgical (1449 of 1689 cases [85.8%]) practice settings . After adjustment, there remained a significant difference in concordance between cases seen in specialty care and primary care  but not between surgical and nonsurgical practice settings . The patient’s age was shown to be negatively associated with diagnostic concordance. For every 10-year increase in the patients’ age, the odds of receiving a concordant diagnosis by video telemedicine decreased by 9% . Diagnostic concordance did not significantly vary between clinician types (physicians vs advanced practice providers), adult and pediatric patients, durations of the consultation, or prior video telemedicine experience of the clinician  and primary care (405 of 498 cases [81.3%])  when the clinician had been certified within the past 7 years. The diagnostic concordance was 88.4% (418 of 473 cases) for certification between 7 and 14 years before this study and was 88.6% (507 of 572 cases) for certification between 14 and 23 years. Diagnostic concordance was 84.1% (427 of 508 cases) for certification 23 years or more before this study. Differences between groups were not significant.Methods of establishing diagnoses at the in-person follow-up visit are presented in For medical specialties with more than 10 cases in the study, diagnostic concordance ranged from 77.3%  for otorhinolaryngology to 96.0%  for psychiatry and psychology. The diagnostic concordance by medical specialty is presented in ICD-10 code chapters with more than 10 cases in the study, diagnostic concordance ranged from 64.7%  for diseases of the ear and mastoid process to 96.8%  for neoplasms. The diagnostic concordance by ICD-10 chapter code are presented in For Adjusted κ agreement between medical student reviewers was strong (0.81). The adjusted κ was moderate in cases where a determination was made by the principal investigator (0.60) and a medical student reviewer (0.64) in instances of discordance between the 2 initial medical reviews. Adjusted κ was strong (0.79) between medical student reviewers and principal investigator in the 20% of cases randomly selected for oversight.Of all 2393 cases, 313 (13.1%) had video telemedicine provisional diagnoses that were not sufficiently concordant with the reference standard diagnosis established at the in-person visit. Among these cases, 166 of 313 (53.0%) were determined to have had the potential for morbidity and 36 of 166 (21.7%) had actual morbidity. Of 313 cases, 30 (9.6%) were determined to have had the potential for mortality and 3 of 30 (10.0%) had actual mortality during the 90-day interval.By 6 months after the start of data collection, 31 patients in the cohort had died. For 6 of 31 of these patients, the in-person reference standard diagnosis was not concordant with the provisional video telemedicine diagnosis. Reviewers determined that for 5 of 6 of these patients, the cause of death was unrelated to the video telemedicine consultation or the cause of death could not have been prevented if the patient had instead been seen for an in-person consultation.14 New patient cases presenting to primary care via telemedicine had a significantly lower diagnostic concordance between telemedicine and in-person visits than did those patient cases presenting first by video telemedicine to specialty clinics. The diagnostic concordance varied between medical specialties and ICD-10 codes, with oncological, transplant, and psychiatric issues having the most diagnostic concordance between video and in-person visits and otological and dermatological issues having the least diagnostic concordance.In this diagnostic study of a large data set of patients who underwent video telemedicine to home for new clinical problems or presentations at our institution during the COVID-19 pandemic, we found that there was concordance between the provisional diagnosis established during the video telemedicine visit and the diagnosis at the conclusion of a subsequent in-person follow up within 90 days. In 86.9% of cases in our study, the provisional video telemedicine diagnoses matched the reference standard in-person diagnoses. This percentage agreement is consistent with what has been reported in smaller studies that studied diagnostic accuracy of virtual visits in general medical practice.The higher diagnostic concordance between video and in-person visits associated with types of clinical problems or types of diagnoses appears to align with how each diagnosis is confirmed. In diagnoses confirmed through clinician opinion, such as many psychiatric diagnoses, there was a significantly greater concordance between video telemedicine diagnosis and in-person diagnosis. In diagnoses necessitating confirmation through traditional physical examination, neurological testing, and pathology—such as many otological and dermatological diagnoses—there was a significantly decreased concordance between video telemedicine and in-person diagnoses.15 reported that telemedicine can provide the same or similar level of diagnostic concordance as face-to-face practice, 0.75 for telemedicine vs 0.81 for face-to-face. Telemedicine diagnostic concordance was reported in the published literature to be 0.40 for rheumatological complaints,20 0.61 to 0.80 for musculoskeletal complaints,21 0.75 for dermatological complaints,22 0.88 for neurosurgical complaints,23 and 0.80 to 1.00 for psychiatric complaints,24 consistent with a trend to lower diagnostic concordance for video telemedicine visits compared with in-person visits in specialties requiring a hands-on physical examination or inspection and higher for those without. Our study highlights lower diagnostic concordance for the specialty of otolaryngology, although the 95% CIs around the point estimate were wide. This result is not surprising given the limitations of the video telemedicine to home technology without any peripheral attachments or devices . Ning et al,25 however, concluded that studies assessing quality and diagnostic concordance in otolaryngology reported adequate results with significant heterogeneity.Ohta et alOne of the most salient findings in our study was the discrepancy between video telemedicine diagnostic concordance with in-person visits in specialty care (higher concordance) and primary care (lower concordance) clinical settings. This finding was further emphasized by our individual analyses of cases that resulted in morbidity and mortality. There were some cases identified in our primary-care telemedicine program that resulted in morbidity and mortality that might have been mitigated by an initial in-person visit, an observation that was not mirrored in specialty practices.26 reported that in approximately 82% of new cases, the medical history provided sufficient information to establish an initial diagnosis of a specific disease entity that agreed with the reference standard diagnosis. The physical examination and investigations each proved useful to establish a diagnosis in only 8% and 9% of new cases, respectively.26 Peterson et al27 reported that in 76% of patients the history led to the final diagnosis, whereas the physical examination and laboratory investigations led to the final diagnosis in 12% and 11% of cases, respectively. Video telemedicine assessments afford ample opportunity for history acquisition but may pose some limits to the comprehensiveness of a traditional in-person physical examination in some specialties.Research like this study in the current digital health era is reminiscent of historical clinical studies that examined the relative contributions of history taking, physical examination, and laboratory investigation to diagnose new patients presenting to a medical outpatient clinic. Hampton et alThe size of our patient cohort, the breadth of medical and surgical practices, the use of multiple independent blinded medical reviewers, and the individualized methods we used to analyze data allowed for a high degree of confidence in the reported diagnostic concordance of telemedicine video consults. The clinical practice design of this study increases confidence that these results will be generalizable to other practices.Although the specificity with which we analyzed each case is a strength of this study compared with other large telemedicine studies, further specificity could benefit clinicians by informing on both the categories of diseases that are less accurately diagnosed over telemedicine and common telemedicine pitfalls seen in different specialties. New patients may have been seeking tertiary care at our clinic and may have already had extensive workups at outside facilities. This could limit the generalizability of the results we found in some of the specialty services, such as hematology-oncology, radiation oncology, and transplant medicine.Another limitation is the potential nonrepresentativeness of the patient group under study. The patients with video telemedicine visits for a new clinical indication for which there was a corresponding in-person visit in the same department for the same indication within 90 days are neither the complete set of video telemedicine visits nor a random sample of those visits. They are instead a potentially nonrepresentative and a nonrandom sample. As a result, the group of patients under study may not be totally representative of all patients undergoing a video telemedicine visit for a new clinical indication. The generalizability of the results should be cautiously interpreted in this context. However, we designed this clinical practice study at the height of the COVID-19 pandemic to be as pragmatic as possible. The specified eligibility criteria were both (1) a video telemedicine visit to home for a new clinical indication and (2) a follow-up visit in person in the same department for the same indication within a 90-day window. The study did exclude patients with a video visit to home who did not return for an in-person visit, who returned for another indication altogether, or who returned to a different department. It is not unreasonable to assume that patients and clinicians most satisfied with the assessment and outcome of a video telemedicine visit for a straightforward and noncomplex clinical issue during COVID-19 may have been less likely to schedule an in-person visit to follow up. We postulate that diagnostic concordance of video telemedicine visits would be higher for patients with straightforward and noncomplex clinical issues.In a large database of patients seen for new clinical problems or presentations early during the COVID-19 pandemic, we found 86.9% concordance between provisional diagnoses offered at the time of selected video telemedicine to home assessments and the subsequent in-person reference standard diagnoses determined within 90 days for these visits. These findings suggest that video telemedicine visits to home may be good adjuncts to in-person care. Primary care video telemedicine programs designed to accommodate new patients or new presenting clinical problems may benefit from a lowered threshold for timely in-person direct follow-up in patients suspected to have diseases typically confirmed by physical examination, neurological testing, or pathology.


While several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined.This study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated.p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of “Recurrence” and lower rates of “Abstinence” and “Controlled drinking” (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003).The presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (ADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment.The online version contains supplementary material available at 10.1186/s12888-022-04455-4. Alcohol dependence may develop gradually in individuals who frequently drink alcohol habitually. The mechanisms responsible for the development of dependency can involve reward drinking or relief drinking , 2. RewaAlcohol use disorder is relatively common and of significant concern among patients with severe mental disorders . SubjectRecently, neurodevelopmental disorders in adults have attracted societal attention. Adults with neurodevelopmental disorders are more likely to face social distress at home and in the workplace. They may be susceptible to substance use disorders, partly because such substances can temporarily alleviate their distress . HoweverWe performed a prognostic study examining treatment-seeking alcohol-dependent patients. To examine the influence of psychological or psychiatric burden on the course of alcohol-dependent individuals, we assessed the impacts of psychiatric comorbidities and neurodevelopmental characteristics on the courses of alcohol-dependent patients after hospital treatment. The study estimated the influences in terms of abstinence rates and drinking patterns, including controlled drinking.This study enrolled inpatients at the National Hospital Organization Kurihama Medical and Addiction Center, which is a central hospital for alcohol and addiction treatment in Japan. Patients who were admitted to the hospital for alcohol treatment between January 2014 and December 2014 were registered if they provided written informed consent after receiving a complete description of the study. The exclusion criterion was a score of ≤20 on the Mini Mental State Examination (MMSE) , indicatThis prospective study was conducted over a 12-month period following inpatient alcohol treatment. The study was approved by the Ethics Committee of the National Hospital Organization Kurihama Medical and Addiction Center. In total, 712 consecutive patients were admitted for alcohol treatment during the registration period. Some patients were excluded because they had insufficient cognitive functions, refused to continue participating in the study during the treatment process, or did not attend the alcohol treatment program. Of these, 637 patients  were qualified to participate in the study . All theAfter hospital discharge, questionnaires regarding drinking patterns were mailed to the subjects every month until 6 months and then every 2 months until 12 months after hospital discharge. The subjects were asked to complete the questionnaires and to return their responses. If a subject did not return a response, a research assistant phoned the subject and asked him or her to reply to the questionnaire. Subjects who failed to respond three times in a row were regarded as study dropouts. The response rate to the first questionnaire sent one month after discharge was 76.0%. Subjects who were re-hospitalized for the recurrence of alcohol-related problems were interviewed with regard to their drinking between discharge and re-admission, even if they had never returned any of the questionnaires. Therefore, information concerning drinking after discharge was obtained from 80.4% of the subjects.The primary outcome was the first day of drinking after hospital discharge. Abstinence was defined as continuous non-drinking from the time of hospital discharge. Loss to follow-up was handled as a censored dropout in the survival analyses. The presence or absence of drinking resumption and subsequent drinking patterns were assessed using mailed questionnaires based on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), which has been shown to be a reliable and valid self-reported screening instrument . InformaThe diagnostic criteria for alcohol dependence in the ICD-10  were checked using a non-standardized psychiatric evaluation performed by specialists skilled in alcohol treatment. The validity of the checked diagnostic criteria was previously confirmed using blood hepatic markers .Current depressive episodes and current or past manic episodes were assessed using the M.I.N.I. Current panic disorder, agoraphobia, social anxiety disorder, obsessive compulsive disorder and posttraumatic stress disorder were also assessed using the M.I.N.I. Subjects who suffered from at least one of these disorders were grouped with those who had any anxiety disorder. Current and past psychiatric disorder and current eating disorder were also assessed using the M.I.N.I. Any psychiatric disorder assessed using the M.I.N.I. was included in the estimate of overlapping psychiatric disorder. Depression and anxiety were also assessed using two self-reported measures: the Zung Self-rating Depression Scale (SDS) , and theWhile the subjects were in the hospital, autistic traits were estimated using the Autism-spectrum Quotient (AQ), which is a self-assessment of one’s personal attitude and communication skills . A scoreThe properties of ADHD were estimated using the Adult ADHD Self Report Scale (ASRS) created by the World Health Organization (WHO) . The relADHD traits were also estimated using interviews based on the Semi-Structured Assessment for the Genetics of Alcoholism-II (SSAGA-II), which is based on the DSM-IV criteria . The relKaplan-Meier survival analyses were performed to show the time courses of the abstinence rates during the study period. The subjects were classified according to the presence or absence of specific comorbid psychiatric disorders. Differences in the abstinence rates among these groups were then analyzed using both log-rank tests and the generalized Wilcoxon test. To ascertain differences in results arising from the dropout criteria, the sensitivity analyses for the abstinence rates were conducted under the assumption that all the dropouts began drinking at the time of dropout. The survival analyses were processed using JMP 13 Software (SAS Institute).t-tests were used for the comparisons. Chi-square tests were used to compare the presence or absence of ADHD characteristics among the three drinking pattern groups and to estimate the association with any comorbid psychiatric disorder. These comparisons were processed using an analysis of variance performed with SPSS 19.0 software (IBM).The average SDS and BAI scores were compared among the three drinking pattern groups. Since the average scores were for continuous variables with normal distributions, p < 0.05 was regarded as significant throughout the study.Multiple Cox proportional hazards analyses using a stepwise method were applied to examine confounding factors. The analyses regarded the duration of abstinence after hospital discharge as the targeted variable. The independent variables included the following factors: gender, age, medications at discharge, education, living status, marriage status, occupation, smoking, current depressive episodes, manic episodes, anxiety disorders, and ASRS score. The hazard ratios of the indicated factors were calculated using SPSS 19.0 software. A value of p = 0.0195, log-rank test). Subjects with any anxiety disorder also had a lower abstinence rate during the follow-up period .Overall, 16.2% of the subjects had current depressive episodes at the time of admission, while 18.4% had an anxiety disorder at admission. Subjects who reported a current depressive episode at admission had a lower abstinence rate after hospital discharge than those without current depression .Overall, 6.5% of the subjects had experienced manic episodes and were suspected of having bipolar I disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) . Subjectp = 0.124; BAI, p = 0.680) . Even when the subjects were divided into three groups , no differences among the groups were observed .The presence of autistic traits, as estimated using an AQ threshold score of 33 or greater, did not affect the abstinence rates during the follow-up period Fig.  A . When the subjects were assessed using the total ASRS score (part A and part B), subjects with a cutoff score of 35 or greater were considered to have ADHD traits. The subjects with ADHD traits had significantly lower abstinence rates after discharge than the subjects without ADHD traits .ADHD traits were estimated using the ASRS symptom checklist. Subjects with 4 or more positive ratings out of the 6 questions included in part A of the ASRS were regarded as having ADHD traits. Subjects with ADHD traits had lower abstinence rates throughout the follow-up period, compared with those without ADHD traits Fig. B . The subjects who had exhibited hyperactivity and impulsivity during childhood also had lower abstinence rates, but the difference was not significant . Sensitivity analyses performed under the assumption that all the dropout subjects began drinking at the time of dropout showed unchanged or enhanced results regarding abstinence rates according to the presence or absence of attention-deficit or hyperactivity/impulsivity , the presence of hyperactivity/impulsivity hardly affected the abstinence rates during the follow-up period .Using another method, childhood symptoms of ADHD were estimated according to a semi-structured interview based on the SSAGA-II. Subjects who had exhibited attention-deficit during childhood had a significantly lower abstinence rate during the follow-up period, especially during the latter half of the follow-up period Fig. A (p = 0.p = 0.038). The analyses were performed separately for the presence or absence of attention-deficit and hyperactivity/impulsivity. The presence of attention-deficit characteristics had a definitive effect on the drinking pattern , whereas the presence of hyperactivity/impulsivity characteristics did not .Coexisting variables comprised of baseline characteristics, psychiatric comorbidities and neurodevelopmental characteristics were examined using multivariate Cox proportional hazards analyses. The dependent variable targeted the duration of abstinence after hospital discharge. A higher total ASRS score was the sole factor associated with the risk of re-drinking after hospital treatment. Though the hazard ratio of the ASRS score was relatively low , the ASRS score was significantly correlated with the re-drinking risk after adjustments for other comorbidities   Table . The preThis was a prospective study designed to investigate the effects of neurodevelopmental disorders on the course of alcohol use disorder over a 12-month period following inpatient treatment. Subjects with ADHD traits, especially those with attention-deficit characteristics, had significantly lower abstinence rates during the follow-up period. This evidence was confirmed by both subjective self-reports using the ASRS and semi-structured interviews using the SSAGA-II. The presence of ADHD traits influenced not only the abstinence rate, but also the drinking patterns after hospital discharge. Furthermore, the presence of ADHD traits as estimated using the total ASRS score had a considerable influence on the course of alcohol-dependent individuals even after adjustments for confounding factors.A preliminary study suggested that patients with alcohol dependence and a history of childhood ADHD had a higher rate of recurrence than those without a history of ADHD . HoweverSeveral studies have reported that individuals with childhood ADHD have a greater likelihood of developing alcohol dependence as they grow older , 42. TheA high rate of comorbidity is known to exist among ADHD children and adults, and ADHD is commonly accompanied by additional diagnoses , 43. ComReportedly, ASD is not prevalent among SUD subjects , partly Previous studies have shown that alcohol-dependent patients with comorbid mood disorder or anxiety disorder have a poorer course with regard to drinking and abstinence rates , 7, 8. OThe present study had some limitations. First, the reliability of self-reports regarding drinking using mailed questionnaires is an important factor. The subjects’ answers were promised to be kept confidential and were not to be shared with concerned medical staff members. Although the accuracy of self-reports might be questioned, the reliability of self-reports made by alcohol-dependent individuals has been repeatedly reported , 55. SecThis study showed an obvious effect of ADHD, especially attention-deficit characteristics, on the drinking patterns of alcohol-dependent patients. Although ADHD is known to be related to the onset of alcohol dependence and frequently overlaps with alcohol dependence , this stAdditional file 1:Supplementary Fig. 1.Additional file 2:Supplementary Fig. 2.