The effectiveness of a self-reported questionnaire on masticatory function in health examinations.

Periodontal diseases have been reported to be lifestyle-related and associated with metabolic syndrome (MetS). The introduction of dental checkups in a health checkup program may create a synergistic effect and aid the prevention of MetS. In Japan, a chewing function questionnaire has now been introduced into the national health checkup program. The purpose of this study was to investigate whether the questionnaire reflects dental and oral conditions and whether it helps improve general and oral health. A total of 6599 subjects who underwent health checkups or guidance specified by the National Health Insurance of Japan for two consecutive years were included. A single comprehensive question to evaluate masticatory function was asked. Medical and dental examinations and insurance data were collected and used for analysis. In terms of masticatory function during chewing, 82.3% of subjects experienced no problems, 17.3% experienced some difficulty, and 0.4% experienced severe problems. There was a significant relationship between the questionnaire response and dental examinations results for several items of examination. The overall dental consultation rate after health screening was 42.3%. Improvement in periodontal disease was achieved in those who reported some problems with chewing function. Improvement in blood pressure was also observed in those who reported some problem with chewing function and subsequently had a dental consultation. The results of this study indicate that questionnaires on masticatory function reflect the status of dental and oral health. In addition, the results suggested that questionnaire results are potentially linked to improvement in dental and oral health status, and improvement in MetS.

Screening of aspiration pneumonia using the modified Mallampati classification tool in older adults.

Pneumonia is a major cause of morbidity and mortality in older adults. In the aging society, screening methods for predicting aspiration pneumonia are crucial for its prevention. Changes in the oropharyngeal morphology and hyoid bone position may increase the risk of aspiration pneumonia. This multicenter study aimed to investigate a simple and effective screening method for predicting dysphagia and aspiration pneumonia. Overall, 191 older adults (aged 65 years or older) were randomly sampled using the simple random sampling technique. Oropharyngeal morphology was assessed using the modified Mallampati classification, which reflects the size of the tongue in the oropharyngeal cavity. The hyoid position was measured as the distance between the menton and laryngeal prominence to evaluate aging-related changes in the muscles of the laryngopharynx. Dysphagia was assessed using the repetitive saliva swallowing test (RSST), which measures the number of swallowing movements in 30 seconds; dysphasia is defined as less than 3 swallowing movements in 30 seconds. The aspiration signs were assessed based on history of choking or coughing reflex during eating or drinking and medical history of pneumonia. The study findings revealed that the modified Mallampati classification was significantly correlated with a medical history of pneumonia. A higher incidence of pneumonia was evident in the lower Mallampati classification, which shows the smaller size of the tongue base in the oropharyngeal cavity. The results of this study suggest that the modified Mallampati classification may be a possible screening method to predict the occurrence of pneumonia.

Precursor Radiographic Findings in Patients With Medication-Related Osteonecrosis of the Jaw.

BACKGROUND: Oral surgical treatment, such as tooth extraction, has been identified as a risk factor for the onset of medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may already be latent, and its manifestation may be triggered by extraction. PURPOSE: The purpose of this study was to examine the association between pre-extraction imaging and MRONJ. STUDY DESIGN, SETTING, SAMPLE: We performed a multicenter case-control analysis of patients receiving antiresorptive agents (ARAs) who underwent extraction between 2012 and 2016. We enrolled patients who had undergone tooth extraction in the setting of ARA exposure. PREDICTOR VARIABLES: The predictor variables comprised preoperative radiographic findings associated with MRONJ stage 0. These findings included alveolar bone loss, thickening or obscuring of the periodontal ligament, and osteosclerosis involving the alveolar bone. They were coded as present or absent before tooth extraction. MAIN OUTCOME VARIABLE: The primary outcome variable was MRONJ status coded as present or absent. COVARIATES: Sex, age, underlying diseases necessitating the administration of ARA, the type of ARA used, corticosteroid use, extraction region, and wound closure were analyzed. ANALYSES: Mann-Whitney U test, χ2 test, Fisher's exact test for univariate analysis, and multiple logistic regression analysis were performed. P values < .05 were significant. RESULTS: The subjects consisted of 26 patients and 110 controls (male: 8/36, female: 18/74). The mean ages of the MRONJ group and the control group were 77.0 ± 11.9 and 63.0 ± 15.8, respectively (P value = .001). The prevalence of osteosclerosis was significantly higher in the MRONJ group than in the control group (14/72, 53.9%/29.3%, P < .01). Multivariate analysis identified osteosclerosis (odds ratio: 8.4, 95% confidence interval: 2.133.9, P < .01) as a significant independent predictor associated with the development of MRONJ after extraction. CONCLUSION AND RELEVANCE: These findings suggest that a precursor to MRONJ is highly likely to be present in patients with osteosclerosis at the time of extraction. The majority of patients who developed MRONJ after extraction had imaging findings that suggested infection in the surrounding alveolar bone.

Prognostic value of a mandibular canal staging system for primary lesions in patients with lower gingival squamous cell carcinoma: a multicenter, retrospective study.

BACKGROUND: The Union for International Cancer Control and American Joint Committee on Cancer tumor staging system is used globally for treatment planning. As it may be insufficient for tumor staging of lower gingival carcinomas, we proposed the mandibular canal tumor staging system. In this study, we aimed to compare the two systems for such tumor staging and to identify prognostic markers. METHODS: This multicenter, retrospective study included patients with lower gingival squamous cell carcinoma who underwent radical surgery during 2001-2018. We compared survival rates (Kaplan-Meier estimator) and patient stratification according to the two systems. RESULTS: The proposed system yielded more balanced patient stratification than the existing system. Progression in the tumor grade according to the proposed system was associated with a poorer prognosis. The 5-year overall and disease-specific survival rates for the entire cohort were 74.9% and 81.8%, respectively. Independent factors affecting overall survival were tumor stage according to the proposed system, excision margins, and number of positive nodes, whereas those affecting disease-specific survival were excision margins and number of positive nodes. CONCLUSIONS: Subsite-specific tumor classification should be used for patients with oral cancer, and our results suggest that mandibular canal tumor classification may be effective for patients with lower gingival carcinoma.

Dental and oral management in the perioperative period of surgery: A scoping review.

Dental and oral management (DOM) is a long-established treatment modality. This scoping review aimed to narratively review previous studies, examine the effects of perioperative DOM, and identify the available evidence. A literature search was conducted using the PubMed electronic database for studies published between January 1, 2000, and March 8, 2022. The search yielded 43 studies, most of which were published in the last 10 years. The results of this study confirmed that improved perioperative oral hygiene is effective in preventing postoperative pneumonia. Our results also suggested that preoperative DOM is effective in preventing postoperative surgical site infections. Perioperative DOM is effective in reducing the incidence of postoperative pneumonia, SSI, and postsurgical complications. Further studies are needed to elucidate the various mechanism of DOM and to examine efficient intervention methods and timing.

Fully gapped pairing state in spin-triplet superconductor UTe2.

The recently discovered superconductor UTe2 is a promising candidate for spin-triplet superconductors, but the symmetry of the superconducting order parameter remains highly controversial. Here, we determine the superconducting gap structure by the thermal conductivity of ultraclean UTe2 single crystals. We find that the a-axis thermal conductivity divided by temperature κ/T in zero-temperature limit is vanishingly small for both magnetic field H‖a and H‖c axes up to H/Hc2 ∼ 0.2, demonstrating the absence of nodes around the a axis contrary to the previous belief. The present results, combined with the reduction of nuclear magnetic resonance Knight shift, indicate that the superconducting order parameter belongs to the isotropic Au representation with a fully gapped pairing state, analogous to the B phase of superfluid 3He. These findings reveal that UTe2 is likely to be a long-sought three-dimensional strong topological superconductor, hosting helical Majorana surface states on any crystal plane.

Prediction of patient-specific quality assurance for volumetric modulated arc therapy using radiomics-based machine learning with dose distribution.

PURPOSE: We sought to develop machine learning models to predict the results of patient-specific quality assurance (QA) for volumetric modulated arc therapy (VMAT), which were represented by several dose-evaluation metrics-including the gamma passing rates (GPRs)-and criteria based on the radiomic features of 3D dose distribution in a phantom. METHODS: A total of 4,250 radiomic features of 3D dose distribution in a cylindrical dummy phantom for 140 arcs from 106 clinical VMAT plans were extracted. We obtained the following dose-evaluation metrics: GPRs with global and local normalization, the dose difference (DD) in 1% and 2% passing rates (DD1% and DD2%) for 10% and 50% dose threshold, and the distance-to-agreement in 1-mm and 2-mm passing rates (DTA1 mm and DTA2 mm) for 0.5%/mm and 1.0%.mm dose gradient threshold determined by measurement using a diode array in patient-specific QA. The machine learning regression models for predicting the values of the dose-evaluation metrics using the radiomic features were developed based on the elastic net (EN) and extra trees (ET) models. The feature selection and tuning of hyperparameters were performed with nested cross-validation in which four-fold cross-validation is used within the inner loop, and the performance of each model was evaluated in terms of the root mean square error (RMSE), the mean absolute error (MAE), and Spearman's rank correlation coefficient. RESULTS: The RMSE and MAE for the developed machine learning models ranged from <1% to nearly <10% depending on the dose-evaluation metric, the criteria, and dose and dose gradient thresholds used for both machine learning models. It was advantageous to focus on high dose region for predicating global GPR, DDs, and DTAs. For certain metrics and criteria, it was possible to create models applicable for patients' heterogeneity by training only with dose distributions in phantom. CONCLUSIONS: The developed machine learning models showed high performance for predicting dose-evaluation metrics especially for high dose region depending on the metric and criteria. Our results demonstrate that the radiomic features of dose distribution can be considered good indicators of the plan complexity and useful in predicting measured dose evaluation metrics.

Rapid increase in salivary IgA and broad recognition of spike protein following SARS-CoV-2 vaccination.

Saliva is a key component of mucosal immunity, which protects the oral cavity from viral infections. However, salivary immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in terms of immunoglobulin dynamics and recognition, have not been investigated sufficiently. In this study, saliva samples were collected from individuals that received SARS-CoV-2 vaccine, and immunoglobulin G (IgG), IgM, and IgA against whole spike protein and S1 protein were measured. IgA against whole spike protein increased significantly following vaccination, while IgA against S1 protein did not. Of note, the IgA response was evident two weeks after the first vaccine dose and continued to rise thereafter. On the contrary, IgG antibodies against S1 increased significantly at four weeks after vaccination. These results reveal the dynamics and recognition antigens of immunoglobulins in saliva, indicating the function of IgA in the mucosal immune system. These findings may pave the way for further studies on mucosal immune response induced by vaccination.

Suitability of Polymyxin B as a Mucosal Adjuvant for Intranasal Influenza and COVID-19 Vaccines.

Polymyxin B (PMB) is an antibiotic that exhibits mucosal adjuvanticity for ovalbumin (OVA), which enhances the immune response in the mucosal compartments of mice. Frequent breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants indicate that the IgA antibody levels elicited by the mRNA vaccines in the mucosal tissues were insufficient for the prophylaxis of this infection. It remains unknown whether PMB exhibits mucosal adjuvanticity for antigens other than OVA. This study investigated the adjuvanticity of PMB for the virus proteins, hemagglutinin (HA) of influenza A virus, and the S1 subunit and S protein of SARS-CoV-2. BALB/c mice immunized either intranasally or subcutaneously with these antigens alone or in combination with PMB were examined, and the antigen-specific antibodies were quantified. PMB substantially increased the production of antigen-specific IgA antibodies in mucosal secretions and IgG antibodies in plasma, indicating its adjuvanticity for both HA and S proteins. This study also revealed that the PMB-virus antigen complex diameter is crucial for the induction of mucosal immunity. No detrimental effects were observed on the nasal mucosa or olfactory bulb. These findings highlight the potential of PMB as a safe candidate for intranasal vaccination to induce mucosal IgA antibodies for prophylaxis against mucosally transmitted infections.

Deep learning-based detection and classification of multi-leaf collimator modeling errors in volumetric modulated radiation therapy.

PURPOSE: The purpose of this study was to create and evaluate deep learning-based models to detect and classify errors of multi-leaf collimator (MLC) modeling parameters in volumetric modulated radiation therapy (VMAT), namely the transmission factor (TF) and the dosimetric leaf gap (DLG). METHODS: A total of 33 clinical VMAT plans for prostate and head-and-neck cancer were used, assuming a cylindrical and homogeneous phantom, and error plans were created by altering the original value of the TF and the DLG by ± 10, 20, and 30% in the treatment planning system (TPS). The Gaussian filters of σ = 0.5 $\sigma = 0.5$ and 1.0 were applied to the planar dose maps of the error-free plan to mimic the measurement dose map, and thus dose difference maps between the error-free and error plans were obtained. We evaluated 3 deep learning-based models, created to perform the following detections/classifications: (1) error-free versus TF error, (2) error-free versus DLG error, and (3) TF versus DLG error. Models to classify the sign of the errors were also created and evaluated. A gamma analysis was performed for comparison. RESULTS: The detection and classification of TF and DLG error were feasible for σ = 0.5 $\sigma = 0.5$ ; however, a considerable reduction of accuracy was observed for σ = 1.0 $\sigma = 1.0$ depending on the magnitude of error and treatment site. The sign of errors was detectable by the specifically trained models for σ = 0.5 $\sigma = 0.5$ and 1.0. The gamma analysis could not detect errors. CONCLUSIONS: We demonstrated that the deep learning-based models could feasibly detect and classify TF and DLG errors in VMAT dose distributions, depending on the magnitude of the error, treatment site, and the degree of mimicked measurement doses.

Superconducting spin reorientation in spin-triplet multiple superconducting phases of UTe2.

Superconducting (SC) state has spin and orbital degrees of freedom, and spin-triplet superconductivity shows multiple SC phases because of the presence of these degrees of freedom. However, the observation of spin-direction rotation occurring inside the SC state (SC spin rotation) has hardly been reported. Uranium ditelluride, a recently found topological superconductor, exhibits various SC phases under pressure: SC state at ambient pressure (SC1), high-temperature SC state above 0.5 gigapascal (SC2), and low-temperature SC state above 0.5 gigapascal (SC3). We performed nuclear magnetic resonance (NMR) and ac susceptibility measurements on a single-crystal uranium ditelluride. The b axis spin susceptibility remains unchanged in SC2, unlike in SC1, and decreases below the SC2-SC3 transition with spin modulation. These unique properties in SC3 arise from the coexistence of two SC order parameters. Our NMR results confirm spin-triplet superconductivity with SC spin parallel to b axis in SC2 and unveil the remaining of spin degrees of freedom in SC uranium ditelluride.

Verification of Qfix Encompass™ couch modeling using the Acuros XB algorithm and HypeArc™ using a high-spatial-resolution two-dimensional diode array.

We modeled the Qfix Encompass™ immobilization system and further verified the calculated dose distribution of the AcurosXB (AXB) dose calculation algorithm using SRS MapCHECKⓇ (SRSMC) in the HyperArc™ (HA) clinical plan. An Encompass system with a StereoPHAN™ QA phantom was scanned by SOMATOM go.Sim and imported to an Eclipse™ treatment planning system to create a treatment plan for Encompass modeling. The Encompass modeling was performed in the StereoPHAN with a pinpoint ion chamber for 6 MV and 6 MV flattening filter free (6 MV FFF), and 2 × 2 cm2, 4 × 4 cm2, and 6 × 6 cm2 irradiation field sizes. The dose calculation algorithm used was AXB ver. 15.5 with a 1.0 mm calculation grid size. The Hounsfield unit (HU) values of the Encompass modeling were set to 400, -100, -200, and -300 for Encompass, and -400, -600, -700, and -800 for the Encompass base. We evaluated the dose distribution after Encompass modeling by SRSMC using gamma analysis in 12 patients. We adopted HU values of -200 for Encompass, -800 for Encompass base for 6 MV, and -200 for Encompass and -700 for Encompass. Base for 6 MV FFF was adopted as the HU values for the Encompass modeling based on the measurement results. The proposed Encompass modeling resulted in a mean pass rate evaluation >98% for both 6 MV and 6 MV FFF when the 1%/1 mm criterion was used, demonstrating that the proposed HU value can be adopted to calculate more accurate dose distributions.

Response to mRNA SARS-CoV-2 vaccination evaluated by B-cell receptor repertoire after tixagevimab/cilgavimab administration.

The use of anti-SARS-CoV-2 antibody products like tixagevimab/cilgavimab represents an important strategy to protect immunocompromised patients with haematological malignancies from COVID-19. Although patients who receive these agents should still be vaccinated, the use of tixagevimab/cilgavimab can mask the production of anti-spike antibody after vaccination, making it hard to assess vaccine response. We have newly established a quantification method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV-AbDab). Repeated blood samples before and after vaccination were analysed for the BCR repertoire, and BCR sequences were searched in the database. We analysed the number and percentage frequency of matched sequences. We found that the number of matched sequences increased 2 weeks after the first vaccination and quickly decreased. Meanwhile, the number of matched sequences more rapidly increased after the second vaccination. These results show that the postvaccine immune response can be assessed at the mRNA level by analysing the fluctuation in matching sequences. Finally, BCR repertoire analysis with CoV-AbDab clearly demonstrated the response to mRNA SARS-CoV-2 vaccination even after tixagevimab/cilgavimab administration in haematological malignancy patients who underwent allogeneic haematopoietic stem cell transplantation.

Chiral superconductivity in UTe2 probed by anisotropic low-energy excitations.

Chiral spin-triplet superconductivity is a topologically nontrivial pairing state with broken time-reversal symmetry, which can host Majorana quasiparticles. The heavy-fermion superconductor UTe2 exhibits peculiar properties of spin-triplet pairing, and the possible chiral state has been actively discussed. However, the symmetry and nodal structure of its order parameter in the bulk, which determine the Majorana surface states, remains controversial. Here we focus on the number and positions of superconducting gap nodes in the ground state of UTe2. Our magnetic penetration depth measurements for three field orientations in three crystals all show the power-law temperature dependence with exponents close to 2, which excludes single-component spin-triplet states. The anisotropy of low-energy quasiparticle excitations indicates multiple point nodes near the ky- and kz-axes in momentum space. These results can be consistently explained by a chiral B3u + iAu non-unitary state, providing fundamentals of the topological properties in UTe2.

Comparable efficacy and safety of COVID-19 vaccines for patients receiving tegafur-uracil as postoperative adjuvant chemotherapy.

PURPOSE: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. METHODS: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. RESULTS: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. CONCLUSIONS: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. CLINICAL TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

COVID-19 transmission in dental practice during the pandemic: A questionnaire-based survey in private dental clinics in Japan.

Background/purpose: The global coronavirus disease 2019 (COVID-19) pandemic continues to cause a significant impact on patient care due to its considerable transmissibility, morbidity, and mortality. The aim of this study was to investigate whether dental procedures performed at private dental clinics were associated with the occurrence of COVID-19 clusters and measures taken to prevent nosocomial infection of COVID-19. Materials and methods: An online questionnaire-based survey on clinical activities, infection control measures, and confirmed or probable COVID-19 cases among patients and clinical staff during the pandemic (February 2020 to September 2021) was administered to dentists at private dental clinics in Nagano prefecture, Japan. Almost all dentists engaged in dental treatment were actively implementing standard precautions. Results: Twenty-seven dental clinics provided dental care to infected patients (nine confirmed and eighteen probable), but there was no transmission from patients to staff. Ten clinics had staff who were infected, but none exhibited disease transmission from staff to patients. Conclusion: The results of this survey suggest that COVID-19 clusters might not occur in dental settings where appropriate protective measures are implemented.

A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients.

We previously reported that a second dose of BNT162b2 was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of BNT162b2. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID-19 mRNA vaccine (BNT162b2 [n = 15] and mRNA-1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23-71) years. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Twenty-one patients (95%) seroconverted after the third dose. None of our patients had serious adverse events, new-onset graft-versus-host disease (GVHD), or GVHD exacerbation after vaccination. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.

Presence of periodontitis may synergistically contribute to cancer progression via Treg and IL-6.

A close causal relationship has been suggested to exist between cancer and periodontitis. We hypothesized that the immune surveillance system is impaired in patients with periodontitis, which contributes to cancer development and growth. Therefore, the present study investigated the relationship between immune surveillance mechanisms and periodontitis in cancer patients. The presence or absence of periodontitis was assessed and the peripheral blood (PB) concentrations of IL-6, immunosuppressive cytokines (VEGF, TGF-ß1, and CCL22) and proportion of T regulatory cells (Treg, CD3 + CD4 + CD25 + Foxp3 +) were measured. Subjects were classified into the following four groups: non-cancer patients without periodontitis (C - P -), non-cancer patients with periodontitis (C - P +), cancer patients without periodontitis (C + P -), and cancer patients with periodontitis (C + P +). The results of a multivariate analysis showed that the PB concentration of IL-6 was significantly higher in C + than in C- and higher in C + P + than in C + P -. The PB proportion of Treg was significantly higher in C + P + than in C + P -, C - P + , and C - P -. The results of this study suggested that the presence of periodontitis and cancer synergistically increased Treg in PB, which may be one of the underlying causes of immunosuppression and immune evasion in cancer. It was also suggested that the presence of periodontal disease and/or cancer also increases IL-6 in PB, which would be associated with cancer progression. These results suggest the possibility that the presence of periodontitis might synergistically contribute to cancer progression.

Promising Efficacy of a Third Dose of mRNA SARS-CoV-2 Vaccination in Patients Treated with Anti-CD20 Antibody Who Failed 2-Dose Vaccination.

Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells, but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for the S1 protein after a third vaccination in 22 patients treated with the anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving the seroconversion rate in patients treated with the anti-CD20 antibody who failed standard two-dose vaccination.

How Many Clinical Trials Exist that Have Adopted Selective Safety Data Collection? NEJM Literature Search Results: The Possibility of Harmonizing the ICH E19 Guideline.

BACKGROUND: The selective safety data collection (SSDC) proposed in The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E19 guideline is a more selective approach to collect safety data of medicinal products with well-characterized safety profiles. There has been no systematic survey of the implementation status of SSDCs. METHODS: A literature search was conducted on clinical trials using SSDC published in The New England Journal of Medicine from February 1, 2016, to December 31, 2019. By reviewing the retrieved texts, protocols, and statistical analysis plans, we identified the method of safety data collection and evaluated whether each trial adopted SSDC. RESULTS: Of the 459 trials of medicinal products searched, 44 clinical trials adopted SSDC. The common objectives of these studies were "to study additional endpoints" (31 trials, 70.5%) and "new indications of approved drugs" (8 trials, 18.2%). Participant number was more than 1000 in 33 trials (75.0%). Most trials adopted SSDC for the entire study population throughout the trial period. Death and serious adverse events (SAEs) were recorded in all trials. Twenty-nine (66.6%) recorded death, SAE, and AE leading to drug discontinuation, which were specified in the E19 draft guideline as the data that should be collected under all circumstances. CONCLUSION: There have already been cases where SSDC was used in clinical trials for regulatory application. It is desirable that the E19 guideline will harmonize the method for implementation of SSDC, making SSDC more common as an option for clinical trial design.