Bayesian Index Models for Heterogeneous Treatment Effects on a Binary Outcome.

This paper develops a Bayesian model with a flexible link function connecting a binary treatment response to a linear combination of covariates and a treatment indicator and the interaction between the two. Generalized linear models allowing data-driven link functions are often called "single-index models" and are among popular semi-parametric modeling methods. In this paper, we focus on modeling heterogeneous treatment effects, with the goal of developing a treatment benefit index (TBI) incorporating prior information from historical data. The model makes inference on a composite moderator of treatment effects, summarizing the effect of the predictors within a single variable through a linear projection of the predictors. This treatment benefit index can be useful for stratifying patients according to their predicted treatment benefit levels and can be especially useful for precision health applications. The proposed method is applied to a COVID-19 treatment study.

Differences in Resumption of Orthopedic Surgery According to Characteristics of Surgery during COVID-19 Pandemic: National Registry Data.

Background: Healthcare services have been restricted after the coronavirus disease 2019 (COVID-19) outbreak. With the pandemic still ongoing, the patterns of orthopedic surgery might have changed. The purpose of this study was to determine whether the reduced volumes of orthopedic surgery were recovered over time. Among the trauma and elective surgery, which accounted for most orthopedic surgical procedures, we also sought to elucidate whether the changes in the volumes of orthopedic surgery differed according to the type of surgery. Methods: The volumes of orthopedic surgery were analyzed using the Health Insurance Review and Assessment Service of Korea databases. The surgical procedure codes were categorized depending on the characteristics of the procedures. The actual volumes of surgery were compared with the expected volumes to elucidate the effect of COVID-19 on surgical volumes. The expected volumes of surgery were estimated using Poisson regression models. Results: The reducing effect of COVID-19 on the volumes of orthopedic surgery weakened as COVID-19 continued. Although the total volumes of orthopedic surgery decreased by 8.5%-10.1% in the first wave, those recovered to a 2.2%-2.8% decrease from the expected volumes during the second and third waves. Among the trauma and elective surgery, open reduction and internal fixation and cruciate ligament reconstruction decreased as COVID-19 continued, while total knee arthroplasty recovered. However, the volumes of hemiarthroplasty of the hip did not decrease through the year. Conclusions: The number of orthopedic surgeries, which had decreased due to COVID-19, tended to recover over time, although the pandemic was still ongoing. However, the degree of resumption differed according to the characteristics of surgery. The findings of our study will be helpful to estimate the burden of orthopedic surgery in the era of persistent COVID-19.

Relationship Between Coronavirus Disease 2019 Vaccination Rates and Rare But Potentially Fatal Adverse Events: A Regression Discontinuity Analysis of Western Countries.

BACKGROUND: Owing to limited experience with the new vaccine platforms, discussion of vaccine safety is inevitable. However, media coverage of adverse events of special interest could influence the vaccination rate; thus, evaluating the outcomes of adverse events of special interest influencing vaccine administration is crucial. METHODS: We conducted regression discontinuity in time analysis to calculate the local average treatment effect (LATE) using datasets from Our World in Data and Johns Hopkins University Center for Systems Science and Engineering. For the United States, the United Kingdom, and Europe, the cutoff points were April 23rd and June 23rd, April 7th, and the 14th week of 2021, respectively. RESULTS: The LATE of the Advisory Committee on Immunization Practices (ACIP) meeting held on April 23rd was -0.249 for all vaccines, -0.133 (-0.189 to -0.076) for Pfizer, -0.064 (-0.115 to -0.012) for Moderna, and -0.038 (-0.047 to -0.030) for Johnson & Johnson. Discontinuities were observed for all three types of vaccines in the United States. The June 23rd meeting of the ACIP (mRNA vaccines and myocarditis) did not convene any discontinuities. Furthermore, there was no significant drop in the weekly average vaccination rates in Europe following the European Medicines Agency (EMA) statement on April 7th. Conversely, there was a significant drop in the first-dose vaccination rates in the United Kingdom related to the EMA report. The first-dose vaccination rate for all vaccines changed by -0.104 (-0.176 to -0.032). CONCLUSION: Although monitoring and reporting of adverse events of special interest are important, a careful approach towards public announcements is warranted.

COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Patients with Breast Cancer Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim.

Chemotherapy-induced febrile neutropenia (FN) is a medical emergency that causes severe adverse effects and death. Respiratory infections are one of the main causes of fever in patients with FN. We studied whether infection prevention and control (IPC) guidance for coronavirus 2019 disease reduced the incidence of FN. We reviewed female patients with breast cancer treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide with prophylactic pegfilgrastim between 2019 and 2021. IPC guidance was implemented in April 2020. There was no difference in the incidence of chemotherapy-induced neutropenia between patients with and without IPC. In patients with IPC, the incidence of FN (9.5%) was lower than that of patients without IPC (27.9%). The hospitalization duration (0.7 ± 1.5 days) and total hospital cost (279.6 ± 42.6 USD) of the IPC group were significantly lower than that of the non-IPC group (2.0 ± 3.8 days and 364.7 ± 271.6 USD, respectively). IPC guidance should be implemented to prevent FN in high-risk patients with breast cancer.

Green synthesis of multifunctional ZnO/chitosan nanocomposite film using wild Mentha pulegium extract for packaging applications.

Following the global corona virus pandemic and environmental contamination caused by chemical plastic packaging, awareness of the need for environmentally friendly biofilms and antibacterial coatings is increasing. In this study, a biodegradable hybrid film, comprising of green-synthesized zinc oxide nanoparticles (ZnO NPs) with a chitosan (CS) matrix, was fabricated using a simple casting procedure. The ZnO NPs were synthesized using wild Mentha pulegium extract, and the synthesized NPs and films were characterized using different approaches. The structural, morphological, mechanical, antibacterial, and optical properties, as well as the hydrophilicity, of the prepared samples were investigated using various techniques. Gas chromatography-mass spectrometry measurements revealed the presence of phenolic compounds in the M. pulegium extract. In addition, a strong coordination connection between Zn2+ and the chitosan matrix was confirmed, which resulted in a good dispersion of ZnO in the chitosan film. The surface of the composite films was transparent, smooth, and uniform, and the flexible bio-based hybrid films exhibited significant antibacterial and antioxidant characteristics, strong visible emission in the 480 nm region, and UV-blocking properties. The ZnO/CS films displayed a potential to extend the shelf life of fruits by up to eight days when stored at 23°C, and also acted as an acceptable barrier against oxygen and water. The biodegradable ZnO/CS film is expected to keep fruit fresher than general chemical plastic films and be used for the packaging of active ingredients.

Interchangeability for Biologics is a Legal Distinction in the USA, Not a Clinical One.

Biologics are increasingly vital medicines that significantly reduce morbidity as well as mortality, yet access continues to be an issue even in apparently wealthy countries, such as the USA. While patient access is expected to improve with the introduction of biosimilars, misperceptions in a significant part based on terminology continue to make a sustained contribution by biosimilars difficult. Patients are and will continue to suffer needlessly if biosimilars continue to be impugned. Consequently, it is increasingly urgent that semantics are clarified, and in particular, the implication that interchangeable biologics are better biosimilars dismissed. This paper distinguishes between the real differences between biologics that matter clinically to patients and discusses the actual meaning of a US Food and Drug Administration designation of interchangeability for a biosimilar product. This will help highlight where there is need for further Food and Drug Administration education and which stakeholders likely need that education the most.

A Nationwide Study on the Impact of COVID-19 Pandemic on Volume of Spine Surgery in South Korea.

OBJECTIVE: In March 2020, World Health Organization declared a global pandemic caused by a novel coronavirus (SARS-CoV-2). The disease caused by this virus is called COVID-19. Due to its high contagiousness, many changes have occurred in overall areas of our daily life including hospital use by patients. The aim of this study was to investigate the impact of COVID-19 on volume of spine surgery in South Korea using the National Health Insurance database and compare it with the volume of a homologous period before the pandemic. METHODS: Data of related to spine surgery from January 2019 to April 2021 were obtained from the National Health Insurance and Health Insurance Review and Assessment Service database. Primary outcomes were total number of patients, rate of patients per 100000 population, and total number of procedures. The number of patients by hospital size was also analyzed. RESULTS: COVID-19 outbreaks occurred in South Korea in March, August, and December of 2020. Compared to the previous year, the total number of patients who underwent spinal surgery showed a decrease for 2-3 months after the first and second outbreaks. However, it showed an increasing trend after the third outbreak. The same pattern was observed in terms of the ratio of the number of patients per 100000 population. Between 2019 and 2021, the mean number of spine surgeries per month tended to increase. Mean annual medical expenses increased over the years (p=0.001). When the number of spine surgeries was analyzed by hospital size, proportion of tertiary general hospital in 2021 increased compared to those in 2019 and 2020 (vs. 2019, p=0.012; vs. 2020, p=0.016). The proportion of general hospital was significantly decreased in 2020 compared to that in 2019 (p=0.037). CONCLUSION: After the COVID-19 outbreak, patients tended to postpone spinal surgery temporarily. The number of spinal surgeries decreased for 2-3 months after the first and second outbreaks. However, as the ability to respond to the COVID-19 pandemic at the hospital and society-wide level gradually increased, the number of spine surgeries did not decrease after the third outbreak in December 2020. In addition, the annual number of spine surgeries continued to increase. However, it should be noted that patients tend to be increasingly concentrated in tertiary hospitals for spinal surgery.

Scheduling Diagnostic Testing Kit Deliveries with the Mothership and Drone Routing Problem.

A critical component in the public health response to pandemics is the ability to determine the spread of diseases via diagnostic testing kits. Currently, diagnostic testing kits, treatments, and vaccines for the COVID-19 pandemic have been developed and are being distributed to communities worldwide, but the spread of the disease persists. In conjunction, a strong level of social distancing has been established as one of the most basic and reliable ways to mitigate disease spread. If home testing kits are safely and quickly delivered to a patient, this has the potential to significantly reduce human contact and reduce disease spread before, during, and after diagnosis. This paper proposes a diagnostic testing kit delivery scheduling approach using the Mothership and Drone Routing Problem (MDRP) with one truck and multiple drones. Due to the complexity of solving the MDRP, the problem is decomposed into 1) truck scheduling to carry the drones and 2) drone scheduling for actual delivery. The truck schedule (TS) is optimized first to minimize the total travel distance to cover patients. Then, the drone flight schedule is optimized to minimize the total delivery time. These two steps are repeated until it reaches a solution minimizing the total delivery time for all patients. Heuristic algorithms are developed to further improve the computational time of the proposed model. Experiments are made to show the benefits of the proposed approach compared to the commonly performed face-to-face diagnosis via the drive-through testing sites. The proposed solution method significantly reduced the computation time for solving the optimization model (less than 50 minutes) compared to the exact solution method that took more than 10 hours to reach a 20% optimality gap. A modified basic reproduction rate (i.e., m R 0) is used to compare the performance of the drone-based testing kit delivery method to the face-to-face diagnostic method in reducing disease spread. The results show that our proposed method (m R 0= 0.002) outperformed the face-to-face diagnostic method (m R 0= 0.0153) by reducing m R 0 by 7.5 times.

Real-Time Motion Analysis System Using Low-Cost Web Cameras and Wearable Skin Markers

COVID-19 has restricted outdoor exercise and hospital visits for rehabilitation therapy. Home-based training and rehabilitation coaching systems have emerged as a way to overcome these circumstances. Conventional optical motion-capture systems, such as VICON, have been used for measuring precise movement and providing posture feedback during exercise or rehabilitation;however, its application is limited to professional facilities because of its high cost and space requirement. To extend the applicability to home-based use, we designed wearable skin markers (WSMs) with body segment-specific patterns that can be detected by low-cost web cameras. WSMs are band-shaped and stretchable and thus can be worn like cloth, with minimal effort for placement. The body segment-specific patterns enable real-time data processing, which reduces the marker data post-processing time. A 6-degree-of-freedom (DOF) pose for each WSM is obtained by recognizing the segment-specific patterns;the 3D configuration of the contoured corners of the patterns found by triangulation is then utilized to construct the coordinates of each WSM. The WSM system was validated via three experiments. The robustness of marker recognition was evaluated by measuring the false-positive and false-negative rates of WSM. For accuracy validation, the angle estimation results were obtained for the mechanical joint of a 3-DOF gimbal and lower-limb joints of a walking human subject and compared to the reference systems. The gimbal experiment was included to evaluate the accuracy of our system in the condition with no skin movement artifact. The maximum standard deviation of the difference between WSM and the encoder was 0.9

Development and Validation of a Treatment Benefit Index to Identify Hospitalized Patients With COVID-19 Who May Benefit From Convalescent Plasma.

Importance: Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact. Objective: To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics. Design, Setting, and Participants: This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants). Exposure: Receipt of CCP. Main Outcomes and Measures: World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI. Results: A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary diseases), with blood type A or AB, and at an early COVID-19 stage (low baseline WHO scores) were expected to benefit most, while those without preexisting conditions and at more advanced stages of COVID-19 could potentially be harmed. In the derivation cohort, odds ratios for worse outcome, where smaller odds ratios indicate larger benefit from CCP, were 0.69 (95% credible interval [CrI], 0.48-1.06) for B1, 0.82 (95% CrI, 0.61-1.11) for B2, and 1.58 (95% CrI, 1.14-2.17) for B3. Testing on 4 external datasets supported the validation of the derived TBIs. Conclusions and Relevance: The findings of this study suggest that the CCP TBI is a simple tool that can quantify the relative benefit from CCP treatment for an individual patient hospitalized with COVID-19 that can be used to guide treatment recommendations. The TBI precision medicine approach could be especially helpful in a pandemic.

Satisfaction Survey of Patients and Medical Staff for Telephone-Based Telemedicine During Hospital Closing Due to COVID-19 Transmission.

Introduction: Telephone-based telemedicine was temporarily permitted in Korea during the COVID-19 pandemic. The purpose of this study was to assess satisfaction with the telemedicine done during temporary hospital closing when in-person visits were not allowed due to in-hospital COVID-19 transmission. Methods: Survey questionnaires partially taken from a telehealth usability questionnaire (TUQ) were sent to 6,840 patients who used telephone-based telemedicine from February 24 to March 7, 2020. Questionnaires sent to patients and additionally created questionnaires to evaluate telemedicine were sent to medical staff (182 doctors and 138 nurses). Results: Response rates of patients and medical staff were 13.2% and 17.2%, respectively. Patients' satisfaction with telemedicine was significantly greater than medical staff's satisfaction for all five components taken from TUQ (all p = 0.000). In addition, created questionnaires showed good reliability, obtaining similar results between doctors and nurses (all p > 0.05). More than 85% of medical staff replied that telemedicine was needed in COVID-19, whereas more than 80% of them worried about incomplete assessment and communication of medical condition. Overall satisfaction with telemedicine by medical staff was 49.7%. The strength of telephone-based telemedicine was patients' convenience (53.4%). However, incomplete assessment of patients' condition (55.0%) was its weakness. Conclusion: Satisfaction with telephone-based telemedicine by patients was significantly greater than that by medical staff (doctors and nurses). Negative views for safety and inconvenience resulted in a greater proportion of dissatisfaction among medical staff. For safe application of telemedicine, medical staff insisted that developing a platform and creating guidelines should be needed.

Drinking Trajectories and Factors in Koreans.

This study aimed to explore the drinking culture in Korea by sex, age, household type, occupation, and income level to identify demographic groups with prominent drinking behaviors and factors affecting their drinking. Furthermore, we evaluated recent changes, including those due to COVID-19, in drinking behavior, using data from the Korea Welfare Panel Study from 2010 to 2020. Panel analysis was performed to reveal the effects of material deprivation, depression, and sociodemographic factors on drinking behavior. We used the AUDIT 3 scale including frequency of drinking, average amount of drinking, and frequency of excessive drinking. The two characteristics of Korean drinking are consistent with the claim of the ecological system theory that humans, as social beings, drink to facilitate social communication or promote problematic drinking when social communication is difficult. Drinking among Koreans is characterized by a pattern that alternates between social drinking and problem drinking. Our study recognizes drinking as a social problem that should be managed at social as well as national levels.

Development and Clinical Evaluation of a Web-Based Upper Limb Home Rehabilitation System Using a Smartwatch and Machine Learning Model for Chronic Stroke Survivors: Prospective Comparative Study.

BACKGROUND: Recent advancements in wearable sensor technology have shown the feasibility of remote physical therapy at home. In particular, the current COVID-19 pandemic has revealed the need and opportunity of internet-based wearable technology in future health care systems. Previous research has shown the feasibility of human activity recognition technologies for monitoring rehabilitation activities in home environments; however, few comprehensive studies ranging from development to clinical evaluation exist. OBJECTIVE: This study aimed to (1) develop a home-based rehabilitation (HBR) system that can recognize and record the type and frequency of rehabilitation exercises conducted by the user using a smartwatch and smartphone app equipped with a machine learning (ML) algorithm and (2) evaluate the efficacy of the home-based rehabilitation system through a prospective comparative study with chronic stroke survivors. METHODS: The HBR system involves an off-the-shelf smartwatch, a smartphone, and custom-developed apps. A convolutional neural network was used to train the ML algorithm for detecting home exercises. To determine the most accurate way for detecting the type of home exercise, we compared accuracy results with the data sets of personal or total data and accelerometer, gyroscope, or accelerometer combined with gyroscope data. From March 2018 to February 2019, we conducted a clinical study with two groups of stroke survivors. In total, 17 and 6 participants were enrolled for statistical analysis in the HBR group and control group, respectively. To measure clinical outcomes, we performed the Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment of Upper Extremity, grip power test, Beck Depression Inventory, and range of motion (ROM) assessment of the shoulder joint at 0, 6, and 12 months, and at a follow-up assessment 6 weeks after retrieving the HBR system. RESULTS: The ML model created with personal data involving accelerometer combined with gyroscope data (5590/5601, 99.80%) was the most accurate compared with accelerometer (5496/5601, 98.13%) or gyroscope data (5381/5601, 96.07%). In the comparative study, the drop-out rates in the control and HBR groups were 40% (4/10) and 22% (5/22) at 12 weeks and 100% (10/10) and 45% (10/22) at 18 weeks, respectively. The HBR group (n=17) showed a significant improvement in the mean WMFT score (P=.02) and ROM of flexion (P=.004) and internal rotation (P=.001). The control group (n=6) showed a significant change only in shoulder internal rotation (P=.03). CONCLUSIONS: This study found that a home care system using a commercial smartwatch and ML model can facilitate participation in home training and improve the functional score of the WMFT and shoulder ROM of flexion and internal rotation in the treatment of patients with chronic stroke. This strategy can possibly be a cost-effective tool for the home care treatment of stroke survivors in the future. TRIAL REGISTRATION: Clinical Research Information Service KCT0004818; https://tinyurl.com/y92w978t.

Effectiveness of Penalties for Lockdown Violations During the COVID-19 Pandemic in Germany.

Objectives. To investigate whether the imposition of fines can mitigate the spread of COVID-19.Methods. We used quasi-experimental difference-in-difference models. On March 20, 2020, Bavaria introduced fines as high as €25 000 (US $28 186) against citizens in violation of the Bundesland's (federal state's) lockdown policy. Its neighboring Bundesländer (federal states), on the other hand, were slow to impose such clear restrictions. By comparing 38 Landkreise (counties) alongside Bavaria's border from March 15 to May 11 using data from the Robert Koch Institute, we produced for each Landkreis its (1) time-dependent reproduction numbers (Rt) and (2) growth rates in confirmed cases.Results. The demographics of the Landkreise were similar enough to allow for difference-in-difference analyses. Landkreise that introduced fines on March 20 reduced the Rt by a further 0.32 (95% confidence interval [CI] = -0.46, -0.18; P < .001) and decreased the growth rate in confirmed cases by an additional 6 percentage points (95% CI = -0.11, -0.02; P = .005) compared with the control group.Conclusions. Imposing fines may slow down the spread of COVID-19.Public Health Implications. Lockdowns may work better when governments introduce penalties against those who ignore them.