Although, supervised methods have shown promising results, it has intrinsic limitations in requiring ground truth depth from an external sensor. On the other hand, self-supervised depth estimation relieves the burden for collecting calibrated training data, while there is still a large performance gap between supervised and self-supervised methods. The objective of this study is to reduce the performance gap between the supervised and self-supervised approaches. The loss function of previous self-supervised methods is mainly based on a photometric error, which is indirectly computed from synthesized images using depth and pose estimates. In this paper, we argue that direct depth cue is more effective to train a depth estimation network. To obtain the direct depth cue, we employed a knowledge distillation technique, which is a teacher-student learning framework. The teacher network was trained in a self-supervised manner based on a photometric error, and its predictions were utilized to train a student network. We constructed a multi-scale dense prediction transformer with Monte Carlo dropout, and multi-scale distillation loss was proposed to train the student network based on the ensemble of stochastic estimates. Experiments were conducted on the KITTI and Make3D datasets, and our proposed method achieved the state-of-the-art accuracy in self-supervised depth estimation. Our code is publicly available at  However, due to the scale-ambiguity in the inverse projection problem, it has many additional challenges compared to other computer vision tasks which infer 2D semantic information. In this paper, we propose a novel self-supervised learning pipeline to improve the accuracy of monocular depth estimation.Recently, deep learning based visual perception algorithms have been utilized in many industry problems. Among them, depth estimation has received much attention to acquire 3D information from a monocular camera. The objective of depth estimation is to predict pixel-level distances from the camera coordinate, and it has been applied to augmented realityDepth estimation methods can be categorized into supervised and unsupervised approaches. Supervised methods require external sensor data, and 3D LiDAR points are widely utilized to generate precise supervisory signals. However, it requires expensive LiDAR sensors and external calibration work to train a depth estimation model. On the other hand, unsupervised approach can be a promising alternative to reduce the burden for collecting calibrated ground truth data. The unsupervised approach is also referred to as self-supervised depth estimation because the loss can be computed from the information obtained by the camera itself. The loss function of most unsupervised methods is mainly based on a photometric error, and it can be computed from stereo pairs and/or monocular sequential images. To compute the photometric error, an image is synthesized at a different viewpoint, and therefore, most self-supervised approaches require estimating both pixel-level distances and relative camera pose, simultaneously. Due to the complexity of the self-supervised approach, there is a large performance gap between the supervised and self-supervised methods.7. We modified the architecture of the dense prediction transformer (DPT)8 and added multi-scale prediction heads to produce depth maps at multiple scales. We refer to the proposed transformer architecture as Multi-Scale Dense Prediction Transformer (MS-DPT). To improve the reliability of the direct depth cue, we employed Monte Carlo dropout (MC-dropout)9 and generated an ensemble of Monte Carlo (MC) estimates. Finally, multi-scale distillation loss was proposed to distill the knowledge in the multi-scale version of the depth map ensemble. Figure 10 and Make3D11 datasets, and our proposed method achieved the state-of-the-art accuracy on most fundamental metrics in self-supervised depth estimation.The objective of this paper is to reduce the performance gap between the supervised and self-supervised methods. In this paper, we argue that direct depth cue is more effective to train a depth estimation module compared to the previous approach that is mainly based on a photometric error. The previous approach requires the training of depth and pose networks simultaneously, increasing the complexity of the learning process. On the other hand, the proposed method separates the procedure for obtaining the direct depth cue and the process for training a depth network. We adopted a knowledge distillation technique to generate the direct depth cue and employ it for the training of the depth network. In our proposed method, the teacher and student networks were constructed based on a transformer architecture which has shown the state-of-the-art performance in many computer vision tasks12 proposed a scale-invariant loss which has been utilized as a fundamental metric for evaluating depth estimation techniques. Fu et al.13 proposed DORN which integrates an ordinal regression layer to estimate depth maps. By introducing a spacing-increasing discretization strategy, DORN reduced the absolute relative error especially at close distances. Li et al.14 proposed another ordinal regression method called BinsFormer, and it generated adaptive bins based on a transformer architecture. Ranftl et al.8 demonstrated the effectiveness of pretraining on a large-scale dataset for improving depth estimation performance. They proposed a vision transformer architecture for dense prediction tasks and achieved the state-of-the-art performance on the KITTI dataset by incorporating pretrained parameters trained on multiple datasets.Supervised depth estimation has been studied in various aspects including network architectures and loss functions. Eigen et al.15 proposed Monodepth2 which is a self-supervised learning pipeline. By introducing a novel photometric error and auto-masking technique, it addressed the problem of depth predictions at occluded regions and moving objects. Yan et al.16 proposed CADepth-Net which contains two different attention modules for emphasizing the structure and details. Jiang et al.17 introduced a modified photometric error between a reconstructed image and the corresponding adjacent images. Chawla et al.18 proposed a depth estimation framework that employs a global positioning system as an additional supervision for pose estimation. Guizilini et al.19 and Lu et al.20 introduced novel self-supervised learning methods that jointly learn depth and optical flow. Varma et al.21 proposed MT-SfMLearner that employs the DPT8 architecture for both depth and pose networks and utilized camera intrinsic parameters as an intermediate supervision for the training of the pose network. In this work, we propose a novel self-supervised learning framework based on knowledge distillation of a transformer architecture.Recently, self-supervised depth estimation methods have received a lot of attention due to its intrinsic benefit of not requiring ground truth data. Godard et al.4 to effectively reduce the model size. Hinton et al. demonstrated that probabilistic responses of a large teacher network is beneficial to train a smaller student network. In the teacher-student learning framework, various loss functions have been proposed to distill the knowledge in intermediate feature maps22 and relationships between data samples23. Recently, knowledge distillation has been utilized to improve the accuracy of a teacher network24, and it has been successfully applied to many computer vision tasks including object detection25, segmentation26, and domain adaptation27.Knowledge distillation of deep neural networks was firstly proposed by Hinton et al.28 proposed a novel knowledge distillation method for depth estimation in edge devices. Song et al.29 proposed a method to selectively distill the knowledge in pixel-level distances from a pre-trained stereo depth network to a monocular depth network. Pilzer et al.30 introduced a cyclic pipeline that utilizes reconstructed right images computed from reconstructed left images and predicted right depth maps. In this paper, we propose a novel knowledge distillation framework for handling multi-scale depth maps generated from our teacher network.Knowledge distillation has been applied to address the problem of monocular depth estimation. Wang et al.This section presents the proposed knowledge distillation framework to address the problem of self-supervised depth estimation. We first explain the architecture of the proposed deep learning model called MS-DPT, which is employed in both teacher and student networks. Subsequently, we present the process for distilling the knowledge in the multi-scale predictions of the teacher network to train the student network.8 architecture. The DPT model was proposed for supervised depth estimation and segmentation tasks, and it consists of transformer modules. We added multi-scale prediction heads to extract feature maps at multiple scales, and Fig. H and W are the height and width of the input image. In the embedding layer, the input image is divided into p, and a learnable vector named readout token is concatenated to the tokens. A transformer block consists of layer normalization, multi-head self-attention, residual connection, and multi-layer perceptron (MLP) layer. Identical to the DPT-Large model, the hidden size D and the number of transformer blocks L were set to 1024 and 4, respectively, to utilize the pretrained parameters trained on the MIX 6 dataset8. To integrate feature representations, the outputs of the transformer blocks are fed into the decoder part consisting of reassemble blocks and multi-scale prediction heads.Our proposed model was designed by modifying the DPT31.The decoder part consists of reassemble blocks, fusion blocks, and head blocks. A reassemble block converts a token set into an image-like feature map, a fusion block doubles the spatial size of the feature map and a head block performs the downstream task. There are three operations in each reassemble block: 8, our MS-DPT contains multi-scale prediction heads to generate multi-scale depth maps as presented in Figure Different to the original DPT15. Training the teacher network requires stereo pairs and/or monocular sequential images, and we denote a pair of adjacent images as 32, and it infers the Euclidean transformation between the two viewpoints. Simultaneously, the teacher network infers the multi-scale depth map, and h for the input image h, the reconstructed image K, respectively. In (1), In our knowledge distillation framework, a MS-DPT model is trained as a teacher network by following the self-supervised learning pipeline proposed in Monodepth2h and the corresponding reconstructed image 33 and L1-norm as follows:15, we compute the minimum photometric error among multiple adjacent images to handle occluded regions as (15 and compute the scaled mask h as (34 to produce smooth depth maps when the corresponding input regions have similar color intensities. The edge-aware smoothness loss is computed as follows:The photometric error between an input ale h as .4\documefined as .6\docume8. Moreover, we employ MC-dropout9 to generate multiple stochastic depth estimates from the teacher network. At each scale h, the averaged depth map is computed from MC estimates, and it is utilized to distill the knowledge in the teacher network to the student network. Although the sampling of multiple depth estimates causes computational complexity, it is conducted only in the training phase. The effectiveness of the multi-scale prediction head in MS-DPT and the ensemble of MC estimates is analyzed in experimental results.In the proposed method, the accuracy of the teacher network directly affects the accuracy of the student network. To improve the accuracy of the teacher network, we utilized the pretrained parameter of DPT which was trained on the mixing dataset MIX 6i-th MC estimate for the depth prediction at scale h is denoted by h is denoted by M is the number of MC estimates.For the training of the student network, multiple MC estimates are inferred by the teacher network. The puted as .7\documeh. The loss between the depth estimates at scale h are measured based on the scale-invariant loss proposed by Eigen et al.12 as (n is the number of valid pixels, and i. We aim to transfer the knowledge of the teacher network by distilling the information contained in the multi-scale depth maps, and the effectiveness of the proposed method is demonstrated in experimental results.To distill the knowledge in the multi-scale averaged depth map https://github.com/ji-min-song/KD-of-MS-DPT. Transfer learning was conducted for the encoder part of MS-DPT by using the pretrained parameters of DPT which was trained on the MIX6 dataset. The use of the pretrained parameters significantly reduced the training time and improved the validation accuracy. The teacher network was trained by using a self-supervised loss function, which is mainly based on the photometric error. On the other hand, the student network was trained in a supervised manner by using a direct depth cue inferred by the teacher network. The training of the teacher and student networks took about 20 hours and 16 hours, respectively.Experiments were conducted on the hardware environment which includes AMD Ryzen9 5950X 16-Core, 32GB DDR4 RAM, and RTX 3090 GPU. The proposed algorithm was implemented by using Pytorch, and the code and trained model are available at d are predicted and ground truth depth. Accuracy metrics are measured based on the three threshold values, and more details about the evaluation measures can be found in the previous work12.The performance of the proposed method was analyzed based on 6 error metrics and 3 accuracy metrics, which are utilized in evaluating depth estimation algorithms. Silog and AbsRel indicate the scale-invariant error and absolute relative error between estimated depth maps and the corresponding ground truth data. SqRel, RMSE, iRMSE and 12. The Eigen split is composed of 39,810 monocular triplets for training, 4424 for validation, and 697 for evaluation.This section presents experimental results of the proposed method on the KITTI dataset. The KITTI benchmark provides datasets and leaderboards for the development and evaluation of visual recognition algorithms for autonomous driving. The depth prediction task provides RGB images along with their corresponding LiDAR points and extrinsic parameters between camera and LiDAR sensors. We adopted the standard experiment setting for the depth prediction task proposed by Eigen et al.35 et al. proposed another type of ground truth data which were interpolated by using a convolutional neural network, and it is referred to as the improved KITTI dataset. The performance of supervised depth estimation algorithms was improved by utilizing the improved KITTI dataset. Although self-supervised methods do not employ ground truth data in the training process, some algorithms were evaluated on the original KITTI dataset while others were evaluated on the improved KITTI dataset. Therefore, we compared our proposed algorithm with previous self-supervised depth estimation methods on both the original and improved KITTI datasets. Table 16 showed lower AbsRel in the original KITTI dataset, our algorithm demonstrated lower Silog in the official KITTI benchmark as presented in Table 16 as shown in Table 15.In the depth prediction task, there exist two types of ground truth data, referred to as the original and improved KITTI datasets. Raw LiDAR projections contain insufficient number of valid points to train a depth estimation algorithm. Therefore, the KITTI benchmark provides ground truth depth maps generated from 11 consecutive frames, and it is called the original KITTI dataset. On the other hand, Uhrig16, which achieved the second-best performance on the KITTI leaderboard. Figure 16 and MS-DPT. The error maps were visualized in log scale, and blue and red colors indicate small and large errors, respectively. As shown in Fig. The KITTI benchmark provides an online test server to compare the performance of depth estimation algorithms. In the test benchmark, previous algorithms are evaluated based on four error metrics, and their rankings are determined by Silog. Table 15, the following experimental results demonstrated that our proposed MS-DPT model is more effective for knowledge distillation.This section presents ablation studies to analyze the performance of the teacher and student networks. First, experiments were conducted to demonstrate the effectiveness of the MS-DPT architecture and the ensemble of its MC estimates. Table We conducted experiments to demonstrate the effectiveness of knowledge distillation in self-supervised depth estimation, and experimental results are summarized in Table 16. Depth estimation networks trained on the KITTI dataset were evaluated on the Make3D dataset to analyze the generalization performance of the deep learning models.This section presents experimental results on the Make3D dataset to demonstrate the generalization performance of the proposed method. The Make3D dataset contains 400 training images and 134 test samples. The dataset consists of high-resolution RGB images with the size of 227215 and CADepth-Net16. Table We evaluated the proposed student model which was trained on the KITTI dataset. This process involved median scaling and 2This paper proposes a self-supervised depth estimation algorithm based on knowledge distillation. We proposed the MS-DPT model which incorporates multi-scale depth prediction heads onto the previous dense prediction transformer. Moreover, we employed MC-dropout to generate an ensemble of MC estimates for improving the reliability of the teacher network. The student network was trained in a supervised manner based on the multi-scale distillation loss by using depth predictions obtained from the teacher network. To demonstrate the effectiveness of the proposed method, experiments were conducted on the KITTI and Make3D datasets. The proposed method achieved the state-of-the-art performance for self-supervised depth estimation on the KITTI dataset. Furthermore, the proposed method demonstrated better generalization performance on the Make3D dataset compared to previous algorithms, reducing the gap between the performance of supervised and self-supervised methods.


The transurethral resection of bladder tumors followed by intravesical Bacillus Calmette-Guerin (BCG) instillations represents the standard treatment for high-risk and selected intermediate-risk non-muscle invasive bladder cancer (NMIBC) patients. We hypothesized that intravesical BCG might be protective against symptomatic SARS-CoV-2 infection, especially in those patients who experienced systemic adverse events during BCG treatment. We tested our hypothesis in a large multicenter cohort of NMIBC patients treated with adjuvant intravesical BCG in the year preceding the first and second waves of the SARS-CoV-2 pandemic at two tertiary urological centers in Northern Italy.p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study’s primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study’s secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection ( The emergence of a novel coronavirus in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly turned into a dramatic global pandemic.However, the recent advent of effective vaccines against SARS-CoV-2 seems to have mitigated the effects of the pandemic.Bacillus Calmette-Guerin (BCG) is a vaccine that was developed in 1921 to provide immunity against tuberculosis, a bacterial infection that primarily affects the lungs. The vaccine is produced by attenuating a strain of Mycobacterium bovis, which is a bacterium closely related to the one that causes tuberculosis. The attenuated bacteria used in BCG are weakened to the point that they cannot cause disease, but are still able to stimulate the immune system to produce a response against tuberculosis [Since its introduction, BCG has become one of the most widely used vaccines worldwide, especially in countries with high tuberculosis rates. One of the remarkable benefits of the BCG vaccine is that it not only protects against tuberculosis, but also against other infectious diseases. This has been observed since the beginning of the last century, when studies showed that BCG vaccination was associated with a significant reduction in infant mortality rates .The reason for this more general protection has yet to be fully understood, but it is believed that the immune response triggered by the BCG vaccine provides a level of non-specific protection against other infectious agents. This is thought to occur because the BCG vaccine induces a robust activation of the immune system, leading to the production of cytokines and other immune mediators that enhance the ability of the immune system to combat a wide range of pathogens .In summary, the BCG vaccine has been shown to be highly effective in preventing tuberculosis, and also provides a level of non-specific protection against other infectious diseases. This has made the BCG vaccine a valuable tool in public health, particularly in regions with highly prevalent infectious diseases .Indeed, evidence from the beginning of the last century demonstrates that BCG vaccination could reduce infant mortality by up to 50%, not only as a direct consequence of the induced immune response against Mycobacterium tuberculosis, but also due to more general protection against unrelated infectious agents .Since then, the cross-reactivity of BCG has been further investigated.BCG has been shown to reduce the level of yellow fever vaccine viremia after vaccination through the induction of cytokine responses, with a crucial role for IL-1B . MoreoveBased on these considerations and on the observation that an inverse correlation between BCG vaccination coverage and SARS-CoV-2-associated morbidity and mortality has been reported in countries such as Japan , severalIntravesical BCG represents the standard treatment for high-risk and selected intermediate-risk non-muscle invasive bladder cancer (NMIBC) patients . UnfortuTherefore, we hypothesized that intravesical BCG might be protective against symptomatic SARS-CoV-2 infection, especially in those patients who experienced systemic adverse events during BCG treatment. We tested our hypothesis in a large multicenter cohort of NMIBC patients treated with adjuvant intravesical BCG in the year preceding the first and second waves of the SARS-CoV-2 pandemic at two tertiary urological centers in Northern Italy.®, D-20354 Hamburg, Germany; 2 × 108–3 × 109 CFU) (study group) and those treated with intravesical chemotherapy, this latter group serving as the control. The choice to select the control group among the bladder cancer population was made to minimize the risk of selection bias and retrieve as homogeneous a study population as possible . According to international guidelines and recommendations, intravesical BCG was administered to high-risk and some intermediate-risk patients. In addition, intravesical adjuvant chemotherapy was administered in case of intermediate-risk disease, while single postoperative instillation of chemotherapy was given to low-risk patients.We report results from a multicenter observational review board-approved study (00174/2020). Consecutive patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were included in the study. Enrolled patients were divided into two groups based on the received intravesical treatment regimen: those treated with intravesical BCG .A phone interview was conducted among the study population between May 2020 and September 2020 . Patients were asked to answer an ad hoc survey regarding SARS-CoV-2 infection previously built by the Infectious Disease Team .A serology test to highlight the presence of direct antibodies against COVID-19  was offered to all patients who tested negative (molecular test) or had never tested for SARS-CoV-2 infection.Due to the occurrence of a second wave (greater than the first) of disease spread in Italy during autumn and winter 2020, all patients were again reached by phone and their profile of exposure to SARS-CoV-2 was updated.The study was conducted in three different steps:Patients who did not answer the survey were excluded from the study.The study’s primary endpoint was the evaluation of SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study’s secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) among the study groups.p < 0.05 was considered statistically significant.Absolute numbers and proportions were used to describe categorical variables, while median and interquartile ranges (IQR) were used for continuous variables. Chi-square, Fisher exact and Kruskal–Wallis tests were used when appropriate to compare the populations. Logistic regression models were built to evaluate the predictive role of intravesical BCG in preventing SARS-CoV-2 disease and infection. Statistical analyses were performed using STATA 16 . All tests were two-sided, and Patients’ baseline characteristics are listed in Overall, 506 patients with NMIBC treated with adjuvant intravesical therapy were included in the study. Of these, 340 (67%) received intravesical BCG while 166 (33%) were treated with intravesical chemotherapy. Among the 340 patients treated with BCG, 165 (49%) experienced BCG-related adverse events .The most-frequently reported adverse events were symptoms of cystitis, fever/general malaise and hematuria. Serious adverse events, possible expression of BCG dissemination, such as arthritis and high-grade persistent fever occurred in 19 (6%) and 14 (4%) patients, respectively.Among the patients treated with BCG, 185 (54%) reported symptoms consistent with possible SARS-CoV-2 infection (mainly flu-like symptoms and fever); however, this was confirmed with a positive molecular test in only 8 patients (2%). Similarly, 73 patients (44%) treated with intravesical chemotherapy experienced SARS-CoV-2-like symptoms and a SARS-CoV-2 infection was confirmed in 4 (2%) of them .p = 0.6).Overall, 320 patients (67%) underwent a serology test to highlight the presence of direct antibodies against SARS-CoV-2. Of these, 214 were treated with BCG and 104 with intravesical chemotherapy. A positive serology test was found in 15 patients (7%) of the BCG group and in 9 patients (9%) of the chemotherapy group (p = 0.9) nor with a positive serology test .Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection  [The ACTIVATE-2 study was a multicenter, double-blind trial that randomized 301 volunteers aged >50 to receive vaccination with BCG versus placebo. The primary end points were the incidence of COVID-19 and the presence of anti–SARS-CoV-2 antibodies. At 6 months, individuals vaccinated with BCG showed a lower incidence of COVID-19  .In contrast, in a unicentric randomized phase II clinical trial, Dos Anjos et al. did not find a statistically significant lower rate of incidence of COVID-19 positivity in healthcare workers revaccinated with M. bovis BCG Moscow .Similarly, a Dutch multicentric randomized trial compared the number of days of unplanned absenteeism for any reason during the COVID-19 pandemic in healthcare workers randomized to receive BCG vaccination or placebo. Again, no protective role of BCG vaccination emerged .A third randomized double-blind placebo-controlled trial enrolling healthcare workers found that BCG vaccination did not have a protective role against COVID19 infection or symptoms .Lastly, the protective role of the genetically modified BCG vaccine VPM1002 was evaluated in a phase III randomized double-blind placebo-controlled multicenter clinical trial. VPM1002 is a modified BCG vaccine with improved immunogenicity and safety profile. However, although the authors reported a lower number of days with severe RTI in the elderly vaccinated with VPM1002, they did not find a statistically significant difference between groups .It should be considered the cited trials only focused on the role of BCG vaccination. The urological community has been using intravesical BCG as standard adjuvant treatment for patients with high-risk NMIBC since 1970 . DespiteMoreover, intravesical BCG stimulates the humoral immune response by increasing IgG levels against tuberculin and mycobacterial heat shock proteins ,31. FinaPatients treated with intravesical BCG showed a lower fatality rate  in a small retrospective Chilean study. However, the results are limited by the weak study design .Contrastingly, Karabay et al. compared the incidence of SARS-CoV-2 infection in bladder cancer patients treated with or without intravesical BCG; in this study, no differences emerged between groups .Finally, no evidence of BCG’s protective effect was shown in a recent retrospective study that included 2803 patients treated with intravesical BCG in an Italian region .In recent years, several vaccines targeting the SARS-CoV-2 virus have been developed . AlthougIn this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 infection and disease could not be demonstrated. However, we found that patients treated with intravesical BCG for NMIBC harbor the same risk of contracting the SARS-CoV-2 infection and developing symptomatic disease as patients who did not receive intravesical immunotherapy. These findings were also confirmed in the subgroup of patients who experienced severe BCG-related adverse events due to a hematogenous BCG dissemination. These findings may be used to guide decision-making regarding ongoing and future trials aiming to explore the role of BCG in the prevention of SARS-CoV-2 infection.Despite the novelty and significance of our study, it is important to note that it is not without limitations. Perhaps the most significant of these limitations is the inherent observational nature of the study design, which prevents us from drawing causal conclusions about the relationships we observe between intravesical BCG and SARS-CoV-2.Another limitation of our study is related to the testing for SARS-CoV-2. First, we were not able to test all included patients for SARS-CoV-2, as the choice to undergo a serology test was left to the discretion of the patients. This introduces a potential selection bias. Furthermore, it is important to note that the serology tests were performed after the so-called “first wave” of the pandemic. As a result, it is possible that a higher number of patients may have contracted SARS-CoV-2 in an asymptomatic form during the second and third waves of the pandemic, with a possible impact on the results of the study. This temporal limitation may have led to an underestimation of the true prevalence of SARS-CoV-2 infection in the studied population, which could affect the accuracy of our findings.Despite these limitations, our study provides valuable insights into the potential role of intravesical BCG and the risk of SARS-CoV-2 infection. However, it is important to acknowledge these limitations and the need for additional studies to further elucidate the relationship between these variables and SARS-CoV-2 infection.In this multicenter observational trial, which aimed to investigate the potential protective effect of intravesical BCG against SARS-CoV-2, the data did not demonstrate a significant protective effect. While the results are not definitive, they suggest that intravesical BCG is unlikely to be a reliable strategy for preventing SARS-CoV-2 infection.These results may have implications for decision-making regarding ongoing trials and future studies that might explore the adjunctive role of BCG in enhancing the immune response to COVID-19 vaccination. However, it is important to note that additional studies are needed to fully elucidate the potential of BCG and other agents in this regard.


Owing to the diverse treatment outcomes after a botulinum toxin A (BoNT-A) injection to the external sphincter, this study aimed to develop a new technique: an ultrasound-guided BoNT-A external sphincter injection. This single-center prospective cohort study was conducted at a tertiary medical center in Taichung, Taiwan. From December 2020 to September 2022, 12 women were enrolled. The patients were evaluated for lower urinary tract syndrome using patient perception of bladder condition (PPBC), international prostate symptom score (IPSS), uroflowmetry, post-void residual volume (PVR), cystometry, and external sphincter electromyography. We evaluated the patients the day before surgery and 1 week after the BoNT-A injection. For the patients requiring self-catheterization, we recorded the number of times they required clean intermittent catheterization (CIC) per day before the procedure and 1 month after the procedure. The IPSS, PPBC, and PVR were significantly better after the transvaginal ultrasound-guided BoNT-A external sphincter injection. The number of times the patients required daily CIC was also reduced after the injection. Only one patient developed de novo urge urinary incontinence. Our results demonstrated that a transvaginal ultrasound-guided BoNT-A injection was efficacious and safe in the treatment of underactive bladder.  A botulinum toxin A (BoNT-A) injection is an increasingly common treatment modality for patients with voiding dysfunction. However, patient outcomes after treatment and their satisfaction with treatment vary widely. Most previous studies have focused on the physiology and pathology of the urinary bladder after the injection, such as idiopathic detrusor overactivity and overactive bladder syndrome. For decades, botulinum toxin has been shown to be effective against both conditions and to significantly improve the quality of life of patients . Relatively few studies have investigated the use of BoNT-A injection therapy to the external sphincter, and these studies sometimes reported inconsistent results. Kao et al. summarized the outcomes of subjective parameters for patients diagnosed with detrusor sphincter dyssynergia (DSD) after a sphincter BoNT-A injection, and improvements of up to 61–88% were reported in clinical manifestation. They also found that a 100-unit BoNT-A injection to the external sphincter resulted in a 79–96% improvement in the clinical or urodynamic parameters in patients with a poor relaxation of the external urethral sphincter, with a patient satisfaction rate of 47–52% . HoweverUnderactive bladder (UAB) is defined by the International Continence Society as a symptom complex characterized by a slow urinary stream, hesitancy, and straining to void, with or without a feeling of incomplete bladder emptying, sometimes with storage symptoms ,6. The dThe efficacy of a BoNT-A injection to the external sphincter has been proven in patients with UAB and DU in previous studies. Lee et al. reported a successful outcome rate of up to 59.1% after a urethral BoNT-A injection in male patients with DU based on clinical diagnosis and a videourodynamic classification . In a stThe female external sphincter is very thin. Macura et al. measured the thickness of the external sphincter from the magnetic resonance images of 23 continent volunteers and reported a thickness of 2.06 ± 0.41 mm with surrounding connective tissue ,14. ThusWe hypothesized that if BoNT-A could be accurately injected into the urethral sphincter, the treatment effect in improving lower urinary tract symptoms and patient satisfaction would be elevated. Therefore, we propose a new treatment method to accurately identify the external urethral sphincter using real-time ultrasound guidance, thereby allowing for the precise injection of BoNT-A into the external urethral sphincter. In our study, we hope to discover the optima injection dose and the injection site of the external sphincter.From December 2020 to September 2022, a total of 12 women with a mean age of 56.5 ± 16.7  years were enrolled. Details of the patient characteristics, including their age, body mass index, length of UAB history, and underlying disease before treatment, are shown in Seven patients had underactive bladder syndrome with incomplete bladder emptying and relied on CIC before the BoNT-A external sphincter injection. We averaged the post-void residual volume of patients who performed self-catheterization after attempting self-voiding one day before the treatment. The average post-void residual volume before the injection of this group was measured up to 394 mL . p = 0.002, p = 0.016, The international prostate symptom score (IPSS) was 21.83 before treatment and 13.33 after treatment, and the difference was statistically significant  developed de novo urge urinary incontinence, and this complication has also been reported in previous studies . Kuo et The female external urethral sphincter is located in the distal two-thirds of the urethra and is composed of striated muscle. At the proximal portion (the mid-urethra), a horseshoe is formed around the female urethra ., where The female external sphincter is very thin, with a thickness of only about 2 mm with surrounding connective tissue ,14. TherAccording to the hammock theory of stress urinary incontinence treatment , the endAccording to most previous studies, the BoNT-A dosage for an external sphincter injection ranges from 50 units to 200 units to treat the lower urinary tract symptoms in the patient with detrusor sphincter dyssynergia, dysfunctional voiding, Fowler’s syndrome (FS), and poor relaxation of the external urethral sphincter (PRES) . Doan etJuan et al. have demonstrated that there is variability in muscle weakness following a BoNT-A injection with the same concentration. They propose that the variation in sensitivity to chemodenervation may be related to differences in muscle-specific fibers, particularly the fast-twitch and slow-twitch muscle fibers. It is noteworthy that most of the external sphincter is comprised of slow-twitch muscle fibers. Mechanical properties in rabbit knee extensors have demonstrated that the degree of muscle paralysis following a BoNT-A injection is not uniform and may depend on a variety of physiological and biophysical factors, including the force frequency and force length of the muscle . FurtherBased on previous studies, we used a dilution ratio of 4 mL per 100 units of BoNT-A . During This study has several limitations, including the small sample size and short follow-up interval. Although patients returned to our outpatient department one month and three months after the operation and reported stable and satisfactory results, only eight patients completed all evaluations, thus the results at one and three months after the BoNT-A injection were not included in the analysis. Performing EMG during the BoNT-A injection would have been ideal for identifying the external sphincter region and monitoring therapeutic effect, but we were unable to do so due to limited hardware facilities and technical difficulties in the operating room. Furthermore, not all patients underwent cystometry and EMG, as many declined the invasive procedure during outpatient visits. Due to the limited sample size, we have not been able to statistically identify potential reasons for treatment failure. Future larger-scale studies may be able to identify patient factors that contribute to treatment failure. Additionally, our study lacked a control group. In future follow-up studies, we plan to compare the prognosis between ultrasound-guided and blind injection methods.The average length of the female external sphincter is about three centimeters, located in the distal two-thirds of the urethra. In the middle of the urethra, the muscle fiber forms a horseshoe around the female urethra, providing the highest closing pressure. We targeted the 2–4 o’clock and 8–10 o’clock directions of the external sphincter (as the red fork area) according to the distribution of the external sphincter and the hammock theory. We injected 200 units BoNT-A at 16 points of the external sphincter in order to relax the vertical direction of muscle tension.A transvaginal ultrasound-guided external sphincter injection is a safe and efficacious method to improve lower urinary tract symptoms and reduce the PVR and number of daily CIC in patients with UAB.This single-center prospective cohort study was conducted at a tertiary medical center in Taichung, Taiwan. We provided the trial protocol and related information to all of the trial participants. All subjects signed informed consent for their inclusion before they participated in the study. The study was approved by the Institutional Review Board of China Medical University Hospital (protocol number MDR-94-IRB-083).®, Allergan, Irvine, CA, USA) ultrasound-guided external sphincter injection.From December 2020 to September 2022, 12 women were enrolled. The patients were evaluated for lower urinary tract syndrome using the patients’ perception of their bladder condition, the IPSS, uroflowmetry, PVR, cystometry, and external sphincter electromyography. We evaluated the patients the day before surgery and 1 week after the BoNT-A injection. For the patients requiring self-catheterization, we recorded the number of times they required CIC per day 1 day before the procedure and 1 month after the procedure. The surgical procedure was performed by a single surgeon (ECL Chou) using a BoNT-A  was used for all statistical analyses.All comparisons of the patient outcomes were assessed using the paired sample


The youth mental health crisis in the United States continues to worsen, and research has shown poor mental health treatment engagement. Despite the need for personalized engagement strategies, there is a lack of research involving youth. Due to complex youth developmental milestones, there is a need to better understand clinical presentation and factors associated with treatment engagement to effectively identify and tailor beneficial treatments.This quality improvement investigation sought to identify subgroups of clients attending a remote intensive outpatient program (IOP) based on clinical acuity data at intake, to determine the factors associated with engagement outcomes for clients who present in complex developmental periods and with cooccurring conditions. The identification of these subgroups was used to inform programmatic decisions within this remote IOP system.Data were collected as part of ongoing quality improvement initiatives at a remote IOP for youth and young adults. Participants included clients (N=2924) discharged between July 2021 and February 2023. A latent profile analysis was conducted using 5 indicators of clinical acuity at treatment entry, and the resulting profiles were assessed for associations with demographic factors and treatment engagement outcomes.P<.001; high acuity+moderate self-harm: OR 2.85, 95% CI 1.66-4.90; P<.001; high acuity+high self-harm: OR 3.67, 95% CI 2.45-5.51; P<.001). Race was unrelated to the profile membership. Profile membership was significantly associated with treatment engagement: youth and young adults in the low-acuity and high-acuity+low–self-harm profiles attended an average of 4 fewer treatment sessions compared with youth in the high-acuity+moderate–self-harm and high-acuity+high–self-harm profiles . Individuals in the high-acuity+low–self-harm profile completed treatment at a significantly lower rate relative to the other 2 high-acuity profiles . Finally, those in the high-acuity+high–self-harm profile were significantly less likely to disengage early relative to youth in all other profiles .Among the 2924 participants, 4 profiles of clinical acuity were identified: a low-acuity profile , characterized by minimal anxiety, depression, and self-harm, and 3 high-acuity profiles defined by moderately severe depression and anxiety but differentiated by rates of self-harm . Age, gender, transgender identity, and sexual orientation were significantly associated with profile membership. Clients identified as sexually and gender-marginalized populations were more likely to be classified into high-acuity profiles than into the low-acuity profile (eg, for clients who identified as transgender, high acuity+low self-harm: odds ratio [OR] 2.07, 95% CI 1.35-3.18; This investigation represents a novel application for identifying subgroups of adolescents and young adults based on clinical acuity data at intake to identify patterns in treatment engagement outcomes. Identifying subgroups that differentially engage in treatment is a critical first step toward targeting engagement strategies for complex populations. Youth mental health crises continue to persist and grow across the United States ,2. NearlPsychological interventions can effectively address these mental health concerns, leading to reduced symptoms and improved functioning, productivity, and life span ,5. The oTreatment engagement is associated with better treatment outcomes ,11. HoweClients who drop out early are less likely to have significant improvements in depression or anxiety ,11 or toVariable-centered research on individual predictors of dropout among youth and young adults has indicated few reliable pretreatment predictors . MachineAcross health care, extensive efforts are underway to develop methods to predict individual responses to treatments and select the ideal treatment and engagement strategies for the individual, such as decision support algorithms . Within One landmark study used a large data set of adult clients receiving stepped-care treatment for depression and anxiety disorders to identify subgroups and explore whether there were differences in dropout between subgroups, as well as differences in recovery and reliable change . The autDespite the potential advantages of tailored treatment and engagement strategies, few studies have specifically assessed the profiles and differential outcomes among youth and young adults . As treaThis challenge in identifying consistent dropout predictors for youth may be partly due to the complex developmental periods spanning early adolescence to young adulthood. Youth experience a barrage of psychosocial and neurobiological changes during this time while simultaneously experiencing increasing environmental and psychosocial pressures ,28. The This quality improvement study used latent profile analysis (LPA) to identify client subgroups based on the initial symptom severity of youth and young adult clients and sought to identify differences in treatment engagement between profiles. This approach provides a data-driven model for identifying subgroups to personalize treatment and engagement strategies .Drawing from a nationwide remote telehealth IOP, this study provides a practical opportunity to assess subgroups and outcomes in a transdiagnostic IOP among youth and young adults with multiple cooccurring conditions. This addresses a research-practice gap wherein youth mental health providers commonly treat youth with many different diagnoses  and at dThe data set used in this investigation was collected as part of routine outcome monitoring undertaken at a national provider of mental health services for youth and young adults. Charlie Health delivers remote-only IOP to individuals aged 11 to 30 years with complex mental health disorders. Client outcomes are routinely collected using validated measures to meet stakeholder and accreditation requirements for ongoing program evaluation to identify opportunities for service quality improvement and to drive increases in treatment responsiveness. This study is part of an organization-wide initiative to identify effective ways to personalize the components of mental health treatment for youth with mental health needs that necessitate IOP treatment.The client population of Charlie Health typically presents with high clinical acuity, a high prevalence of cooccurring mental and behavioral health issues that impair daily functioning, and significant histories of trauma. Clients often require more intensive services than those that can be delivered in a community-based care setting, or they come from regions lacking mental health resources. Because Charlie Health is in network with both public and private insurers, there is a diverse representation of socioeconomic backgrounds. In addition, clients have widely variable experiences of treatment history before admission to Charlie Health .Weekly IOP at Charlie Health involves 9 hours of web-based group sessions paired with optional 1-hour individual or 1-hour family sessions as determined by the needs and willingness of the clients or caregivers to participate. Group sessions are 3 hours long, broken into 50-minute sessions with 10-minute breaks in between. These sessions include experiential therapy ; general therapeutic processing; and evidence-based skill-building interventions . Because of the size and reach of Charlie Health and the accessibility of web-based programming, clients can be assigned to group IOP tracks based on shared identities ; presenting issues ; and appropriate treatment . To complement the individual, family, and group sessions of the IOP, Charlie Health offers comprehensive family support programs to provide psychoeducational and support groups to caregivers and loved ones. For clients who require psychopharmacological support, a team of psychiatrists and psychiatric mental health nurse practitioners is on staff to conduct evaluations and prescribe medication as needed. In addition, clients are supported by a team of Care Experience Specialists who offer care coordination outside individual or group therapy sessions. Individual and group sessions are offered a variety of times throughout the day to meet the needs of a range of schedules and to offer a higher degree of accessibility. The average length of stay in the program is 10 to 12 weeks. The target length of stay is individually determined by the clinical staff and varies by client acuity and need.The sample for this investigation included Charlie Health clients who were discharged between July 2021 and February 2023 (N=2924) and who completed both an intake and discharge survey. The sample was selected to include multiple demographic factors associated with profile membership in the analyses. Some demographics were asked on the intake survey (race and age), and some were asked on the discharge survey . The sample included clients who were discharged following the successful completion of treatment as well as those discharged due to disengagement, insurance denial, or referral to a higher or lower level of care.This program evaluation research was reviewed and approved by the Florida State University Institutional Review Board that deemed this type of investigation “nonhuman subjects research,” given its primary purpose of program evaluation and quality improvement (STUDY00003364).As part of Charlie Health’s routine data collection procedures, data were collected from clients during the first and last IOP sessions. Clients logged into the web-based group room and were then sent to a web-based survey room, where a Charlie Health staff member provided them with a closed survey Qualtrics link to complete either an intake or discharge survey. For any client who missed their last IOP session, the discharge survey link was emailed and texted to them with a small incentive for completion. All client data were downloaded and deidentified before analyses. All clinical symptom measures in this study were collected during intake survey. The measures were presented in the same order for each client.African American or Black, Asian, Indigenous people around the world, Middle Eastern or North African, White, and other); gender ; and sexual orientation . Clients could multiselect across each question to capture intersectionalities. Clients were also asked whether they identified themselves as transgender (yes or no).Demographic data were collected by self-report on both the intake (race and age) and discharge surveys  and consisted of questions regarding race .To determine the use of high-acuity service before intake, clients were asked to self-report whether they were admitted to the emergency room (ER) or a higher level of care facility  in the 30 days before their first group therapy session at Charlie Health. If a client answered yes to either, they were asked for the reason for their admission (At no time) to 5 (All of the time). The sum score, ranging from 0 to 25, is multiplied by 4 to give a final score out of 100, with 0 being the worst outcome for well-being and 100 being the best outcome for well-being. A cutoff score of ≤50 is used to assign a screening diagnosis of depression [The World Health Organization-5 Well-Being Index (WHO-5) is a self-reported measure of well-being that consists of 5 questions on a scale of 0  to 3 (nearly every day). The total score, ranging from 0 to 21, is calculated. Scores of 5, 10, and 15 represent cutoff points for mild, moderate, and severe anxiety, respectively [The Generalized Anxiety Disorder-7 (GAD-7) is a self-reported measure of generalized anxiety symptoms that consists of 7 questions on a scale of 0  to 3 (nearly every day). The total score, ranging from 0 to 27, is calculated. PHQ-A scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively [The Patient Health Questionnaire modified for adolescents (PHQ-A) is a 9-item, self-reported measure of depressive symptoms that consists of questions on a scale of 0 , and LPA class enumeration and multinomial regressions were conducted in Mplus . The solA modified 3-step multinomial logistic regression analysis  ,48 was uLPA uses full information maximum likelihood with robust SEs by computing the parameter estimates using all available information, which is considered the best practice for data missing at random, as it avoids listwise deletion .Chi-squared analysis was used to compare profiles and assess the differences in treatment engagement outcomes. Separate analyses were performed for the 3 variables of the total number of sessions attended, treatment completion, and early disengagement.The sample included 2924 clients. Participant demographics are displayed in P=.06) indicates that the 4-profile model should be accepted. The 4-profile model was also the most conceptually parsimonious, as the 5-profile solution displayed an artificial division of 1 profile into 2 new profiles. These results collectively indicate a 4-profile solution as the best fit  consisted of individuals who were admitted to treatment reporting mild levels of depression  and anxiety  and minimal self-harm . Youth and young adults in this profile reported lesser, yet still meaningful, interference from their mental health symptoms in their daily functioning . They also endorsed psychological well-being  above the cutoff used to detect a screening diagnosis of depression  .Profile 2  included individuals who endorsed significantly higher levels of depression and anxiety and lower levels of psychological well-being  at treatment entry relative to the low-acuity profile. These youth reported moderately severe depression  and severe anxiety . In contrast to their mental health symptom severity, these youth endorsed minimal self-harm  in the last month and reported that their mental health symptoms interfered with their daily functioning for 3.06 (SD 2.62) days on average out of the last 7 days.Profile 3  reported similar levels of depression and anxiety to profiles 2 and 4, with youth who entered the treatment reporting moderately severe depression  and severe anxiety . In contrast to profiles 1 and 2, these youth endorsed self-harm about half of the days in the last month  and reported that their mental health symptoms interfered with their daily functioning about half the days in the last week . Finally, similar to profile 2, they reported low levels of psychological well-being .Profile 4  showed the most consistently poor clinical and functional outcomes across all the profiles. Similar to the individuals in profiles 2 and 3, they entered treatment reporting moderately severe depression  and severe anxiety . These youth reported engaging in self-harm nearly every day in the last month  and reported the highest levels of interference with their daily functioning . Correspondingly, they reported the lowest levels of psychological well-being .Next, we used multinomial logistic regression to assess various factors associated with latent profile membership, including both demographic history and mental health treatment characteristics, to better understand the structure of each profile (see P<.001) and high-acuity+high–self-harm  profiles had significantly higher odds of visiting an ER in the 30 days before their admission, whereas there was no significant difference in ER visit between the high-acuity+low–self-harm profile and the low-acuity profile .Relative to clients in the low-acuity profile, individuals in the high-acuity+moderate–self-harm , whereas clients in the high-acuity+moderate–self-harm  and high-acuity+high–self-harm  profiles had significantly higher odds of reporting a higher level of care admission in the month preceding admission to IOP.Clients in the high-acuity+low–self-harm profile had significantly lower odds of reporting a higher level of care stay in the 30 days before admission than the clients in the low-acuity profile . Increased age was significantly related to classification in the high-acuity+low–self-harm profile relative to the low-acuity profile . Age was not significantly associated with membership in the high-acuity+moderate–self-harm profile relative to the low-acuity profile .Age was significantly related to the likelihood of profile memberships, with increased age of the individual associated with a lower likelihood of membership in the high-acuity+high–self-harm group compared with the low-acuity profile group . Alternatively, a significantly larger proportion of clients who were identified as nonbinary were classified as having high-acuity profiles relative to those with low-acuity profiles .In terms of gender, identifying as a female individual was not related to profile membership. A significantly smaller proportion of male individuals were classified in all high-acuity profiles relative to the low-acuity profile .Transgender identification was significantly associated with profile membership in all the high-acuity profiles relative to the low-acuity profile . Identification as bisexual or pansexual was not related to profile membership in the high-acuity+low–self-harm profile relative to the low-acuity profile. However, a significantly greater proportion of clients who identified as bisexual or pansexual were classified into the high-acuity+moderate–self-harm  and high-acuity+high–self-harm profiles .Clients who identified as heterosexual were less likely to be classified in the high-acuity profiles than in the low-acuity profile Youth and young adults in the low-acuity (23.98 sessions) and high-acuity+low–self-harm (24.82 sessions) profiles attended significantly fewer treatment sessions on average relative to youth in the high-acuity+moderate–self-harm (27.44 sessions) and high-acuity+high–self-harm (27.83 sessions) profiles . Individuals in the low-acuity profile  did not differ significantly in their rates of treatment completion from any of the high-acuity profiles.Youth and young adults in the high-acuity+low–self-harm profile  completed treatment at a significantly lower rate compared with those in the high-acuity+moderate–self-harm profile  and those in the high-acuity+high–self-harm profile .Youth and young adults in the high-acuity+high–self-harm profile  were significantly less likely to disengage early from treatment than youth within the low-acuity , high-acuity+low–self-harm , and the high-acuity+moderate–self-harm  profiles  and in the number of days spent engaging in self-harm the month before intake .The low-acuity profile was notable for relatively milder depressive, anxiety, and self-harm symptoms. This reflects similarities to the low-acuity class in stratified analysis with adults, with low depression and anxiety, a long duration, and a low likelihood of chronic symptom outcomes . AlthougAlthough previous analyses have identified subgroups based on the levels of mental health acuity at intake ,21, thisOne of the key variables that differentiated clinical acuity was the number of days in the month before intake that the client self-harmed. It was unexpected that the profile representing clients who reported daily self-harm tied for the highest rates of treatment completion (66%) and had the lowest levels of early disengagement (9.8%) compared with any of the other profiles analyzed. High-acuity clients are typically the most challenging to engage and retain in treatment programs. The tailored curriculum approach used in Charlie Health considers these factors and proactively assigns clients to a type of treatment that is expected to work best for their needs. This finding suggests that the clients classified into the high-acuity+high–self-harm profile maintain high engagement with the program.Second, in line with previous research -53, clieTreatment providers have been working for decades to unlock the key to personalizing treatment engagement strategies within large care systems. Attention to treatment engagement and those who drop out of treatment is also critical for effective research and evaluation, as clients who drop out often have distinct feature outcomes from those who remain . This anIn practice, many treatment providers find it difficult to personalize treatment and engagement strategies according to the unique needs of each client, even though each distinct program is likely not equally efficacious for all. This process is further complicated when working with youth, as there is increased heterogeneity due to the varying levels of development in each age group. The value of this type of investigation lies not in the replication of these particular profiles, which may or may not translate to other populations or treatment settings, but in the systematic approach to identifying subgroups of clients based on key clinical indicators that can be applied anywhere. This inquiry details one such way to harness the outcome variables that treatment providers are already collecting into actionable targets for personalization that are unique to a specific setting and treatment population.Within this care setting and population, the findings suggest immediate implications. The high-acuity+low–self-harm group is less likely to complete treatment, suggesting that youth with this profile are candidates for additional engagement strategies. The high-acuity+high–self-harm group is less likely to disengage early, suggesting that current engagement strategies for this group are effective, and greater attention on engagement strategies can be focused on the other groups. Furthermore, the finding that the low-acuity profile attended fewer sessions but had no differences in treatment completion based on treatment goals suggests that they need fewer sessions to achieve their treatment goals. This finding can guide general expectations regarding the length of stay for clients with different acuity levels.Several considerations should be considered when determining the generalizability of the findings of this investigation. Given the heterogeneity of youth and young adult treatment populations, the 4 distinct profiles of clinical acuity at intake may not replicate fully across other treatment providers. These analyses highlight one set of indicators that could be used to understand acuity at intake, but they are by no means exhaustive. Other mental health care providers should endeavor to use their own client data in similar person-centered analyses to uncover solutions that are personalized to their given treatment population. Second, although this evaluation details the identification of discrete profiles, it does not address the application of these profiles to adjust treatment journeys accordingly. Future investigations should build on these findings by helping fine-tune the appropriate levels of support and deployment of further personalized curricula. Even within a well-defined level of care such as IOP, there exists a gradient of ancillary support services. This provides an opportunity to assess the dosage of care and its impact more precisely across different subgroups of patients entering treatment with different clinical and relational needs. Clinical outcome data were not yet available, so this study could not assess the profile association with clinical outcomes; such analysis in the future could guide treatment strategies as well as engagement strategies.In addition to these broad areas for future research, this study has several methodological limitations. All data are self-reported and so may be subject to client bias. There are limited demographic variables available, and potentially key variables for engagement, such as life stress, are not captured. In addition, the indicators have different recall periods, leading to measurement inconsistencies.This quality improvement study identified subgroups of adolescents and young adults based on clinical acuity data at intake to identify trends in treatment engagement outcomes. Identifying barriers and protective factors against disengagement is crucial in providers’ ongoing efforts to ensure that an adequate dose of mental health treatment is delivered. The profiles identified in this study showcase further personalization of treatment and engagement strategies across a complex population and represent a novel application of distilling salient tailoring variables around which to build additional resources and support.


Strategies to align youth and parent expectations with the goal of improving satisfaction could be utilized as a strategy to improve partnerships in diabetes care management.Patient engagement in the process of developing a diabetes treatment plan is associated with person-centered care and improved treatment outcomes. The objective of the present study was to evaluate the self-reported patient and parent-centered satisfaction and well-being outcomes associated with the three treatment strategies utilized in a comparative effectiveness trial of technology-enhanced blood glucose monitoring and family-centered goal setting. We evaluated data from 97 adolescent-parent pairs at baseline and 6-months during the randomized intervention. Measures included: Problem Areas in Diabetes (PAID) child and parent scales, pediatric diabetes-related quality of life, sleep quality, and satisfaction with diabetes management. Inclusion criteria were 1) ages 12-18 years, 2) a T1D diagnosis for at least six months and 3) parent/caregiver participation. Longitudinal changes in survey responses were measured at 6 months from baseline. Differences between and within participant groups were evaluated using ANOVA. The average age of youth participants was 14.8 ± 1.6 years with half of the participants being female (49.5%). The predominant ethnicity/race was Non-Hispanic (89.9%) and white (85.9%). We found that youth perceived 1) greater of diabetes-related communication when using a meter capable of transmitting data electronically, 2) increased engagement with diabetes self-management when using family-centered goal setting, and 3) worse sleep quality when using both strategies together . Throughout the study, scores for self-reported satisfaction with diabetes management were higher in youth than parents. This suggests that patients and parents have different goals and expectations regarding their diabetes care management and care delivery. Our data suggest that youth with diabetes value communication  The vast majority of adolescents with type 1 diabetes (T1D) have glycosylated hemoglobin (HbA1c) values above the recommended range, indicating suboptimal glycemic control . It is wDiabetes management is associated with substantial burdens, necessitating ongoing assessment and treatment of mental health and diabetes-related distress during routine diabetes visits . Poor glShared decision-making is a model of patient-centered care that encourages individuals or families to be actively involved in the medical decisions that impact their health. It is recognized that a personal interest and investment in the diabetes treatment plan from the adolescent with diabetes is associated with engagement with diabetes self-management and improved metabolic control of T1D , 15, 16.The objective of the present study was to evaluate the self-reported patient and parent-centered satisfaction and well-being outcomes associated with the three intervention strategies utilized in the published comparative effectiveness trial . We hypoThis study was performed at Indiana University Health, Indianapolis, IN, approved by the Indiana University Institutional Review Board, and all participants signed informed consent/assent prior to enrolling. Inclusion criteria were 1) ages 12-18 years, 2) a T1D diagnosis for at least six months and 3) parent/caregiver participation. Exclusion criteria included diagnoses of other chronic diseases except depression, asthma, and thyroid disease which, if present, were required to be controlled. We did not exclude these conditions because they are commonly present in youth with T1D and when controlled with stable doses of medications would not interfere with the intervention strategies. We excluded individuals currently using a continuous glucose monitoring system at the time of study entry because one of the intervention strategies included a technology-enhanced blood glucose meter and the duplicative systems could contribute to burn-out and/or not using the assigned intervention strategy. The complete methods and primary clinical outcomes of the parent study have been published elsewhere (1c at 6 months from baseline (the mean of 2 measures taken at the onset and the end of run-in). For evaluation of the longitudinal change in outcomes measures in individuals by treatment (patients serve as their own controls): With 90 participants, we had over 90% power to detect a HbA1c difference of 0.5 ± 0.8% from baseline to 6 months among individuals . For evaluation of treatment group differences for the 3 treatment arms: With 30 participants per group, we had 80% power to detect a HbA1c difference of 0.5 ± 0.5% .The sample size estimation for the proposed pilot study was based on change in HbAAfter the run-in period, consented patients and parents were randomized to a treatment group during the baseline visit, therefore study activities were based on the allocated group, previously published . Each stHIT-enhanced SMBG strategy - The Telcare System  allowed for real-time SMBG data monitoring for the patient, their parents, and their healthcare provider by automatically transmitting SMBG data to a secure, online, HIPAA-compliant web portal via cellular data networks. Both pre-set and free-text alerts could be sent to any cell phone in real time when SMBG was performed. If randomized into this strategy, participants were encouraged to use the Telcare blood glucose meter throughout the study, regardless of their insulin delivery mode. Regardless if the patient used the intervention strategy meter or another meter, all data were downloaded and reviewed weekly by a CDE and a CNP. Adolescents were consequently either messaged through Telcare system with care recommendations or when possible, directly contacted by phone/text message.Family-centered goal setting strategy – In addition to meeting with a health educator and a CDE, families randomized into this strategy met with a board-certified pediatric endocrinologist at the randomization visit. Using motivational interviewing, the multidisciplinary team helped the families set goals that were tailored to each family’s desires, while considering the age and stage of maturity based on that age of the participating adolescent. The goal-setting tool utilized was specifically designed for this study by a patient advisory group and is published in detail elsewhere , a HIPAA-secure database system approved by the university and healthcare system  The e system , 23; 3) e system ; 4) The e system ; and 5) Participating parents completed three questionnaires at baseline and six months: 1) Problems Areas in Diabetes (PAID) measured emotional distress and burden with the adolescent’s diabetes management ; 2) The We modeled the longitudinal changes in questionnaire responses at six months from baseline. In Statistical Package for Social Sciences version 26 (SPSS v26), we used repeated one-way ANOVA to compare the differences within and between subjects. Linear mixed effects models with random intercepts for subjects were used to model the longitudinal change in questionnaire responses at six months from baseline. The Kenward-Roger approximation was used to test within-subject differences between responses at baseline and 6 months for each intervention strategy group. A likelihood ratio test was used to measure this longitudinal change difference across the three groups. Data were assumed to be missing at random (MAR), and all analyses were conducted in R version 4.0.4 (2021-02-15). The linear mixed models were fit using the lme4 package.One hundred twenty-eight participants enrolled, and 102 families completed the run-in period and were randomized to one of three intervention strategies. Ninety participants completed both the baseline and 6 months study visits. Baseline characteristics of the participants are shown in Baseline and six-month questionnaire responses are shown in In this study, we evaluated patient-and parent-centered outcomes in participants in a comparative effectiveness trial of (1) a blood glucose meter that both shared blood glucose data among patients, their parent, and health care providers, and allowed for text-message communication (HIT-enhanced SMBG strategy); (2) a family-centered goal setting strategy; and (3) a combination of (1) and (2) . In youtYouth participants who were randomized into the HIT-enhanced SMBG strategy (meter only) perceived an improvement in diabetes-related communication during the 6-month treatment period. The lack of adequate communication between providers and patients with T1D is one of the major reported barriers for care . Some stYouth in the family-centered goal setting group reported increased engagement with diabetes self-management. Despite this perception, there were not significant improvements in either SMBG frequency or HbA1c as reported in our primary outcomes paper . This diAlthough we did not document any significant changes in PAID-Peds questionnaires reported by youth, we noted that our youth scores were low (<40) . This reIntroducing diabetes technology can be associated with diabetes-related distress and sleep-related concerns . The greStrengths of our study include the randomized-controlled prospective design and 3-month run-in period. The run-in period was designed to blunt the positive effect that participation in a research study, on its own, may have on diabetes self-care and satisfaction with care. In addition, this trial was performed in a real-world clinic-based setting and questionnaires were completed at these appointment times. The limitations include that the study was underpowered for some of the analyses comparing group differences in the primary study. There were analysis limitations based on the questionnaires chosen for this study. The PAID-Peds and Adherence in Diabetes questionnaires are validated for age groups up to 17 years and our inclusion criteria included 18-year-olds. We did not collect all the psychological variables or quality of life data in the parents, which precluded evaluation of psychosocial similarities/differences in parents and their children. Satisfaction data reflected the overall experience with the clinic visit and could not be specifically attributed to the device or data sharing aspects of the study. The Adherence in Diabetes questionnaire was validated in a sample of Danish adolescents and may not have construct validity in US adolescents. There were clinical limitations as well. Due to clinic time and resource constraints, the needed family support may have been insufficient for establishing new care routines. There was no study-related clinical psychologist or social worker to provide ongoing support during the study. Finally, some adolescents may have been in the honeymoon period after diagnosis which may have affected outcomes.via technology and perceive that communication is improved by technology. Strategies to ensure receipt of this data and interim management based on technology-driven communication should be pursued. Youth with diabetes value partnership and patient-centered goal setting, but parents may be frustrated when they do not get the results that they (parents) expect. Strategies to align youth and parent expectations with the goal of improving satisfaction could be utilized as a strategy to improve partnerships in diabetes care management. Consideration should be taken with regard to self-care strategies including sleep habits. Sleep quality may be decreased with increasing burden of diabetes care. Furthermore, next steps in this research will include implementing a shared decision-making clinical process in a virtual format in preparation for diabetes clinic visits.In conclusion, our data do not support our hypothesis that the combination of a technology-enhanced blood glucose meter along with family-centered goal setting would result in higher levels of well-being or patient satisfaction. Our data suggest that recommendations to provide added support for patient-centered strategies in the pediatric/adolescent diabetes clinic may be needed. Youth with diabetes value communication The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Indiana University Institutional Review Board. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.JH, LY, and TH: responsible for the majority of writing of manuscript. HM and XL: responsible for analysis. AH and JT: responsible for study activities and data management. AC and TH: responsible for study design. All authors contributed to the article and approved the submitted version.Funding for this work provided by: Indiana University; National Center for Advancing Translational Sciences; National Institutes of Health; Agency for Healthcare Research and Quality, Grant/Award number: 5R24HS022434-05.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. 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Purpose: The purpose of this study was to analyze choroidal and retinal vascular alterations of both the macula and midperiphery areas in patients hospitalized for COVID-19 infection complicated with pneumonia within 30 days from discharge. Methods: A total of 46 eyes of 23 subjects with a history of symptomatic COVID-19 infection and recent hospitalization for pneumonia were enrolled in this observational study. Patients had not been previously vaccinated against COVID-19. A group of patients homogenous for age and sex was enrolled as controls. Microvascular retinal and choroidal features of the enrolled patients were studied with widefield optical coherence tomography angiography (OCT-A). Perfusion parameters in terms of the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the choroidal vascularity index (CVI) on enhanced depth imaging (EDI) mode OCT scans were analyzed. Results: Our cohort of patients showed a trend of reduction in VD, significantly in the SCP VD of the superior and inferior midperiphery sectors, whereas the CVI did not show significant differences between the cases and controls. Moreover, a positive correlation between CVI and vessel density in the deep capillary plexus in the macular area (VD-DCP-MAC) was found. Conclusion: The systemic disease due to COVID-19 can also involve the retina and choroid with multiple mechanisms: ischemic and inflammatory. Our study showed changes in perfusion occurring in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to the vaccines. There is still the need to better comprise how long COVID-19 actually affects vascular changes in the eye. COVID-19 is a disease mainly characterized by respiratory system involvement that can lead to acute respiratory distress syndrome. Thrombotic complications are described in patients with a severe form of the disease ,3.The angiotensin-converting enzyme (ACE) 2 receptor seems to be the receptor that allows the entry of SARS-CoV-2 in human cells and is also expressed in some ocular structures, such as the retina, ciliary body, and choroid .SARS-CoV-2 was found in tears, conjunctiva, and the retina ,6,7,8. AWith the development of retinal multimodal imaging, it has been possible to study retinal and choroidal vasculature structures also in these types of patients in a safe and fast fashion by means of optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) scanning. Some retinal alterations have been already reported in COVID-19 patients with a severe form of the disease compared with healthy controls, including retinal vessel enlargement, tortuous vessels, and lower vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) ,14,15,16Moreover, during the active period of the disease, compared to after a recovery period and healthy controls, authors have detected increased outer plexiform layer thickness, higher peripapillary RNFL, and choroidal changes as well, including a lower choroidal vascularity index and an increased choroidal thickness .Previous studies focused on the perfusion changes of the macula and did not investigate the periphery. The aim of this observational study was to explore and quantify topographical vascular modifications, assessing and correlating perfusion parameters of the macula with those of the midperiphery by means of widefield optical coherence tomography angiography (WF-OCT-A) in such a particular cohort of patients suffering from COVID-19 without any vaccination and hospitalized for interstitial pneumonia. Choroidal changes with the choroidal vascularity index (CVI) have been investigated as well.In this cross-sectional observational study, 46 eyes of 23 subjects  with a history of symptomatic COVID-19 infection confirmed with a positive test result with real-time reverse transcription–polymerase chain reaction of a nasopharyngeal swab sample and with a history of recent (within 1 month) hospitalization at the Infectious Diseases Clinic, University G. d’Annunzio, SS Annunziata Hospital of Chieti  were enrolled at the Ophthalmology Clinic of University G. D’Annunzio, Chieti–Pescara, Italy from April 2021 to October 2022. Patient characteristics are shown in A total of 46 eyes of 23 patients homogeneous for age and sex, without COVID-19 vaccination, without history of COVID-19 infection, and with a negative COVID-19 nasopharyngeal swab sample polymerase chain reaction (PCR) result within 7 days from the examination were enrolled as control group.Exclusion criteria included (1) ocular media opacities (according to the Lens Opacities Classification System III), (2) previous ocular surgeries within 6 months, (3) evidence or history of other ocular diseases, or (4) autoimmune or other uncontrolled systemic diseases affecting the eye.This study adhered to the tenets of the Declaration of Helsinki and was approved by our Institutional Review Board of the University “G. d’Annunzio” of Chieti–Pescara (Department of Medicine and Science of Ageing), and all patients provided written informed consent for participation in this study.® HRA+OCT  and widefield swept-source OCT-A platform PLEX Elite 9000 device , respectively. Biometry for axial length calculation was assessed .All patients underwent a complete ophthalmic examination which was performed by an expert retinal specialist ophthalmologist, including best corrected visual acuity (BCVA) evaluation (measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts), Goldmann applanation tonometry, slit-lamp biomicroscopy, and indirect fundus ophthalmoscopy. In addition, spectral domain (SD)-OCT and OCT-A were performed using SpectralisOCT images were obtained using the Spectralis OCT . The acquisition protocol for SD OCT included 49 horizontal raster dense linear B-scans centered on the fovea and both horizontal and vertical B-scans centered on the fovea with enhanced depth imaging (EDI) mode, obtaining scans with an axial resolution of 7 microns in tissue.Images with poor signal strength (<25) were excluded and thus repeated until good-quality scans were obtained.CVI was measured through the application of a validated algorithm as previously described ,19,20: MMicrovascular retinal and choroidal features of enrolled patients were studied with PLEX Elite 9000 device . The latter uses a swept laser source with a central wavelength of 1050 nm (1000–1100 nm full bandwidth) and operates at 100,000 A-scans per second. It is characterized by a full width at half maximum (FWHM) axial resolution of approximately 5 μm in tissue and a lateral resolution at the retinal surface estimated at approximately 14 μm .In our study, FastTrack motion correction software was used, and poor-quality scans  were excluded and thus repeated until good-quality scans  were achieved.For each eye, 12 × 12 mm volume scans centered on the fovea were performed. All vascular retinal layers were identified and segmented in the SCP and DCP . The prohttp://rsb.info.nih.gov/jj/index.html accessed on 1 October 2022). Vessel density (VD) was defined as the percentage of the area occupied by vessels in a circular region of interest (ROI) and was calculated in the macular area  and in 3 circles of 3 mm in midperiphery .Descriptive statistics: Median and 1st and 3rd quartiles were calculated to characterize the study variables. Normal distribution was verified with the Jarque Bera test. The Mann–Whitney U test was applied to investigate whether there were significant differences between cases and controls for all visual parameters. Spearman’s rho correlation coefficient with listwise deletion was calculated to assess the relationship of the continuous parameters in cases and controls. All statistical tests were 2-sided with a significance level set at A total of 46 eyes of 23 subjects with symptomatic COVID-19 infection complicated with pneumonia and not vaccinated were enrolled. The 46 eyes of 23 age-matched patients without a history of COVID-19 infection within 7 days from enrollment were considered as the controls in the analysis.p = 0.039) and VD-SCP-I  (= 0.026) . Figure The possible involvement of the eye during COVID-19 infection has been widely described. As Li et al. recently observed, the presence itself of the ACE2 and CD147 receptors in the human eye indicates their potential role in inducing the ocular manifestation of COVID-19 infection .Several retinal alterations have been described in patients with SARS-CoV2 infection, including retinal vascular changes ,26,27. AThe aim of our study was to quantify choroidal and retinal vascular modifications of both the macula and midperiphery areas in patients hospitalized for COVID-19 complicated with pneumonia within 30 days from discharge.To our knowledge, this is the first study exploring topographically retina and choroid vasculature changes in such a cohort of patients with COVID-19 complicated with pneumonia without COVID-19 vaccination by means of the widefield imaging modality.Our choice to include nonvaccinated patients was due to the reported ocular findings in patients who underwent COVID-19 vaccination. In fact, although vaccination and subsequent boost administrations remain the main factors influencing and thus reducing the spread of the COVID-19 infection, different adverse outcomes have been reported in the literature. Previous papers have demonstrated a direct or indirect connection between COVID-19 infection and ocular complications ,30.A recent one-year retrospective review has reported a detailed description of all findings about COVID-19 vaccination and ophthalmic manifestations . Among tThus, the strength of our cohort of patients was that the analyzed final outcomes were not influenced by the possible effect of a previous COVID-19 vaccination.Moreover, all our patients, who had a period of hospitalization for pneumonia, experienced ocular surface symptoms, such as dry eye discomfort, burning, redness, and blurred vision. Such symptoms have yet to be reported both in the general population due to the increased use of face masks and as ocular manifestations of COVID-19 infection ,43,44. WIn our study mainly focusing on the occurring vascular changes, we observed a trend of a reduction in VD with a significant decrease in the SCP in the superior and inferior quadrants of midperiphery compared to controls. Some retinal diseases, such as diabetic retinopathy, retinal vein occlusions, vasculitis, etc., have an impact not only on the macula but also on the midperiphery in terms of ischemia, and some differences between the center and the midperiphery can be assessed. We wanted to observe if some midperipheral changes were present in these patients with COVID-19 and if there was some interesting correlation between macular perfusion and peripheral perfusion.Other studies focused their attention on the choroid and its modifications in these types of patients using the novel marker CVI, a robust representative of the choroid in both its vascular and stromal factor, giving new additional structural information and enriching the knowledge of COVID-19-related physiopathological ocular conditions. Abrishami et al. calculated the CVI, finding an increased CVI in patients with COVID-19 one month after recovery that returned to baseline values (at recovery) after three months .Others showed a decreased CVI during the COVID-19 disease with a reversible fashion some months after discharge, suggesting reversible and multiple mechanisms (ischemic and inflammatory) of COVID-19 on ocular perfusion ,46.Conversely, in our study, the CVI did not show significant differences between the cases and controls, while a strong positive correlation between the CVI and VD-DCP-MAC was found. Given that one of the most important advantages of the CVI is that it is not influenced by a systemic and local factor , it remains a good and specific indicator of choroid vascularization .Our study underlined that, although there was an absence of changes in the CVI, the VD measured in the superficial and deep plexus showed alterations compared to healthy subjects, thus demonstrating, on one hand, the presence of changes in perfusion in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to vaccines and, on the other hand, reinforces the role of the VD parameter as a good indicator of retinal vascular changes occurring in the eye. The systemic disease due to COVID-19 can involve also the retina and choroid with multiple mechanisms, ischemic and inflammatory, since some alterations seem to be reversible, as previously described.As Byram observed, these vascular alterations may be related both to a direct host–virus interaction or an underlying autoimmune process inducing vasculitis or inflammation . For thiThe strength of our study was that it explored vascular changes in COVID-19 patients with a previous hospitalization for COVID-19 by studying, through widefield OCT-A examination, a wider area, including both the central macular area and the retinal mid periphery.However, one of the shortcomings of this study was that other functional parameters  were not investigated. Moreover, a longer follow-up period may be interesting to see how perfusion changes behave over a long time and whether they are reversible.Further studies are needed to better comprise how long COVID-19 actually affects vascular changes in the eye. COVID-19 and retinal vascular changes are known in the literature and are still questioned if they are reversible or not. This work could add a new understanding of the pathogenesis of COVID-19 to depict a small, selected cohort of patients complicated with pneumonia similar to our sample study to observe if some vascular findings visible on OCTA could predict the prognosis of the patient.