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A cast-free approach is described to fabricate an implant-supported interim restoration by using the postoperative cone beam computed tomography (CBCT) scan to locate the placed implant. A postoperative intraoral scan was aligned to the postoperative CBCT scan through a dental implant planning software program. An attached interim abutment and implant analog complex was then scanned and superimposed on the placed implant in the postoperative CBCT scan. Once the best alignment was achieved, a virtual cast was generated, and an interim restoration with bilateral positioning wings was fabricated on the interim abutment and inserted during the second-stage surgery. This technique offers a cast-free approach to inserting an implant-supported interim restoration immediately after the second-stage surgery to guide the healing of the soft tissue that can minimize chairside time and optimize the clinical workflow.

Background Reconstruction of continuity defect of mandible is challenging, and there has been a lot of advancement in this field with variety of options for restoration. However, choice often becomes restricted in resource limited settings due to lack of trained manpower, time, infrastructure, supply of graft materials, etc. In this context, we aim to test the reliability of Kirschner wire (K-wire) with adaptation of looped-end for immediate interim reconstruction of continuity defect of mandible. Materials and method Retrospectively, medical records of 10 years data were reviewed to include 22 patients who underwent immediate interim reconstruction of mandible with K-wire with looped-end adaptation for continuity defect of mandible. Data regarding patient demographic, type and length of mandibular defect, diameter of the wire and complications were recorded. Result Among 22 patients within a follow-up period of 1–60 months (median 7.5), complications developed in 7 (31.8%) patients. Three patients (13.6%) had major complications which required interventions, and 5 patients (22.3%) with minor complications were managed conservatively. Total wire removal in our study is only 9%, which is lowest among the reported literature, migration or extrusion through bone was nil, and overall aesthetic and functional result was good in majority except few where either wire had to be removed or got deformed. Conclusion Kirschner wire (K-wire) should be considered in resource limited setting as an immediate interim reconstructive method of mandible for being cheap and widely available. Our technique of looped-end adaptation results in better stabilisation leading to less removal rate, migration or extrusion.

A university student with a background of atopy presented to her general practitioner (GP) 2 weeks following an episode of throat tightening and dizziness occurring after touching cashew nut to her lip. She took antihistamine medication immediately and went to sleep, fearing for her life. On waking, she felt astounded to be alive. Her symptoms resolved gradually over the following week. She waited 2 weeks for an appointment with her GP, who referred her to allergy clinic. Eight months later, she was still waiting for her clinic appointment, and was left fearing a future fatal reaction, having been provided with no interim treatment. Not all patients who have severe allergic reactions present to the emergency department. Living with the constant fear of anaphylaxis can be overwhelming for patients and their families, and it can negatively impact mental health. Therefore, we advise early allergy counselling and early EpiPen prescription.

The biologically oriented preparation technique (BOPT) uses a vertical tooth preparation and simultaneously a controlled rotary instrumentation of the gingival sulcus. The resulting blood clot is stabilized with the interim restoration. However, accurate transfer of the emergence profile of the interim crown to the definitive restoration is essential to maintain the gingival architecture. This technique article describes clinical and laboratory procedures to predictably transfer the emergence profile of the interim crown to duplicate the gingival architecture in the definitive restoration.

Interim imaging with computed tomography (iCT) to assess response is common during frontline chemoimmunotherapy for follicular lymphoma (FL), but there is little evidence of its utility. We retrospectively reviewed outcomes of iCT in 190 patients with biopsy-proven FL who received first-line chemoimmunotherapy from 2003-2018. Most iCTs showed partial response (PR, 83%), with a minority showing complete response (CR, 8%) or stable disease (5%). Seven patients (4%) had radiographic disease progression (PD) on iCT; on repeat biopsy, four had another malignancy identified and three had transformation to DLBCL. Only one had asymptomatic PD. The 3-year PFS of all patients was 74% (median follow up 75 months). Patients with PR on iCT had similar 3-year PFS and OS as those with CR. In conclusion, iCT has limited utility in identifying patients with asymptomatic early progression during first-line treatment. Patients with PD mid-treatment warrant biopsy to identify histologic transformation or other malignancies.

A new technique of guided implant surgery is presented. A conventional complete denture is converted into both tomographic and surgical guides and later into an interim implant-supported fixed prosthesis. A plate derived from a computed tomography scan becomes the physical link between the virtual planning and tube positioning device. Furthermore, the interim placement of mini-implants adjacent to the symphysis region stabilizes the guide throughout the guided surgery. This technique reduces treatment time and costs.

The Kuwait Association of Rheumatology members met thrice in April 2020 to quickly address and support local practitioners treating rheumatic disease in Kuwait and the Gulf region during the coronavirus disease 2019 (COVID-19) pandemic. Because patients with rheumatic and musculoskeletal disease (RMD) may need treatment modifications during the COVID-19 pandemic, we voted online for the general guidance needed by local practitioners. In this review, we have addressed patients' vulnerability with rheumatic disease and issues associated with their optimum management. Our recommendations were based on the formulation of national/international guidelines and expert consensus among KAR members in the context of the Kuwaiti healthcare system for patients with RMD. The most recent reports from the World Health Organization, the Center for Disease Control, the National Institutes of Health-National Medical Library, and the COVID-19 educational website of the United Kingdom National Health Service have been incorporated. We discuss the management of RMD in various clinical scenarios: screening protocols in an infusion clinic, medication protocols for stable patients, and care for patients with suspected or confirmed COVID infection and whether they are stable, in a disease flare or newly diagnosed. Further, we outline the conditions for the hospital admission. This guidance is for the specialist and non-specialist readership and should be considered interim as the virus is relatively new, and we rely on the experience and necessity more than evidence collection. The guidance presented should be supplemented with recent scientific evidence wherever applicable.

Statement of problem Adjusting an interim screw-retained crown made of acrylic resin for maintenance of peri-implant soft tissues after immediate implant insertion requires accuracy and time. Assessments of these factors by using digital techniques are sparse. Purpose The purpose of this clinical study was to describe a technique to fabricate an acrylic resin interim crown by using the data acquired from a cone beam computed tomography (CBCT) scan. The 3D tomography files were converted to a standard tessellation language (STL) file format used to print or to mill the interim crown with a technique called digital immediate tooth restoration (DITR). Additionally, the chair time spent during the prosthetic phase was evaluated in comparison with a protocol in which a standard interim crown (SIC) was fabricated with an indirect-direct technique. Material and methods Patients who needed to replace a single nonrestorable tooth were treated from February to June 2018 with an immediately placed implant and an acrylic resin screw-retained interim prosthesis that was connected to the implant immediately after placement of the implant. The participants were divided into 2 groups according to the acrylic resin interim crown fabrication technique: group DITR and group SIC. The average time to finalize the prostheses was compared between the groups. The total chair time (TCT) taken for the adaptation of the interim crown was noted and distinguished in 3 different times corresponding to each phase of adaptation of the interim restoration of the interproximal contact areas (CT1), adaption of the postextractive alveolar bone walls (CT2), and adaption of the occlusal contacts (CT3). For each time, the number of changes (N-CT1, N-CT2, N-CT3, and TN) needed to complete each prosthetic phase was also marked and observed. Generalized linear mixed models and generalized linear models were used for data analysis. All the sites were definitively restored with a screw-retained crown after 6 months of healing, and the participants were provided with standard hygiene recall appointments for the next year. Results A total of 82 crowns at sites distributed across the mandible and the maxilla were included in the study. Thirty-five were restored with an SIC and 47 with a DITR interim crown. None of the implants were lost during the 18-month follow-up period. The analysis of the chair times registered for the adaptation of the interim crown to the implant healing abutment and to the neighboring teeth between the 2 groups showed a reduction if a DITR interim crown was used (average CT1 of 15 ±14 seconds, CT2 of 2 ±5 seconds, CT3 of 59 ±19 seconds, and TCT of 76 ±28 seconds for group DITR and average CT1 of 135 ±27 seconds, CT2 of 185 ±30 seconds, CT3 of 73 ±16 seconds, and TCT of 394 ±61 seconds for group SIC). The number of corrections to finalize the interim crown adaptations was lower for the group DITR (0.81 ±0.74 for N-CT1, 0.19 ±0.39 for N-CT2, and 2.81 ±0.74 for N-CT3) when compared with the number of corrections needed for the group SIC (4.37 ±0.81 for N-CT1, 5.57 ±0.77 for N-CT2, and 3.86 ±0.64 for N-CT3). Conclusions The data from CBCT scans led to interim acrylic resin crowns that needed fewer adjustments with the immediate implant placement and interim restoration approach, reducing chair time.

The COVID-19 pandemic identified an urgent need to re-evaluate the provision of spirometry for clinical monitoring. Home spirometry offers the opportunity for real-time disease evaluation without risk of nosocomial infection. To determine the utility of home spirometry in interstitial lung disease (ILD), interim data from the ongoing INJUSTIS study was evaluated. High correlation was observed between home and hospital spirometry at baseline(r=0.89) and three-months(r=0.82). Over 90% of home spirometry values were within Bland-Altman agreement limits at both time points, although frequently underestimated hospital values. Home spirometry is feasible in people with fibrotic ILD.

Background: There exist a limited number of studies demonstrating the benefit of initiating anti-retroviral agents (ARVs) for the treatment of human immunodeficiency virus (HIV) in the critical care setting. However, there are physiological, practical, and ethical arguments against making HIV testing and initiation of ARVs routine practice. Methods: A self-administered, cross-sectional survey of healthcare professionals was conducted with data collected using a questionnaire distributed to delegates of the Critical Care Society of South Africa (CCSSA) 2016 Congress, and members of the society. Results: There were 101 respondents. Eight per cent would not consider testing a critically ill patient for HIV (status previously unknown), largely because they considered this unethical. Sixty-nine per cent would consider commencing ARVs in a patient newly-diagnosed with HIV during an inter-current critical illness. The factor most likely to guide them towards this was severity of illness. In general, the greatest concerns focused around biological/medical issues. However, those clinicians who would not consider initiation of ARVs were more likely than those who would, to be concerned about psychosocial issues. Conclusion: Although the majority of clinicians would consider initiation of ARVs acutely in critically ill patients, it is apparent that the clinical decision-making around this matter is complex. Advocacy is needed to further clarify relevant ethical and legal dilemmas, and in the interim consultative and collaborative care is encouraged.

Background Following the publication of 2014 consensus statement regarding mass critical care during public health emergencies, much has been learned about surge responses and the care of overwhelming numbers of patients during the COVID-19 pandemic.1 Gaps in prior pandemic planning were identified and require modification in the midst of ongoing surge throughout the world. Methods The Task Force for Mass Critical Care (TFMCC) adopted a modified version of established rapid guideline methodologies from the World Health Organization2 and the Guidelines International Network-McMaster Guideline Development Checklist.3 With a consensus development process incorporating expert opinion to define important questions and extract evidence, TFMCC developed relevant pandemic surge suggestions in a structured manner, incorporating peer-reviewed literature, “gray” evidence from lay media sources, and anecdotal experiential evidence. Results Ten suggestions were identified regarding staffing, load-balancing, communication, and technology. Staffing models are suggested with resilience strategies to support critical care staff. Intensive care unit (ICU) surge strategies and strain indicators are suggested to enhance ICU prioritization tactics to maintain contingency level care and avoid crisis triage, with early transfer strategies to further load-balance care. We suggest intensivists and hospitalists be engaged with the incident command structure to ensure two-way communication, situational awareness, and the use of technology to support critical care delivery and families of patients in intensive care units (ICUs). Conclusions A subcommittee from the Task Force for Mass Critical Care offers interim evidence-informed operational strategies to assist hospitals and communities to plan for and respond to surge capacity demands from COVID-19.

Problem definition: Clinical trials are crucial to new drug development. This study investigates optimal patient enrollment in clinical trials with interim analyses, which are analyses of treatment responses from patients at intermediate points. Our model considers uncertainties in patient enrollment and drug treatment effectiveness. We consider the benefits of completing a trial early and the cost of accelerating a trial by maximizing the net present value of drug cumulative profit. Academic/practical relevance: Clinical trials frequently account for the largest cost in drug development, and patient enrollment is an important problem in trial management. Our study develops a dynamic program, accurately capturing the dynamics of the problem, to optimize patient enrollment while learning the treatment effectiveness of an investigated drug. Methodology: The model explicitly captures both the physical state (enrolled patients) and belief states about the effectiveness of the investigated drug and a standard treatment drug. Using Bayesian updates and dynamic programming, we establish monotonicity of the value function in state variables and characterize an optimal enrollment policy. We also introduce, for the first time, the use of backward approximate dynamic programming (ADP) for this problem class. We illustrate the findings using a clinical trial program from a leading firm. Our study performs sensitivity analyses of the input parameters on the optimal enrollment policy. Results: The value function is monotonic in cumulative patient enrollment and the average responses of treatment for the investigated drug and standard treatment drug. The optimal enrollment policy is nondecreasing in the average response from patients using the investigated drug and is nonincreasing in cumulative patient enrollment in periods between two successive interim analyses. The forward ADP algorithm (or backward ADP algorithm) exploiting the monotonicity of the value function reduced the run time from 1.5 months using the exact method to a day (or 20 minutes) within 4% of the exact method. Through an application to a leading firm’s clinical trial program, the study demonstrates that the firm can have a sizable gain of drug profit following the optimal policy that our model provides. Managerial implications: We developed a new model for improving the management of clinical trials. Our study provides insights of an optimal policy and insights into the sensitivity of value function to the dropout rate and prior probability distribution. A firm can have a sizable gain in the drug’s profit by managing its trials using the optimal policies and the properties of value function. We illustrated that firms can use the ADP algorithms to develop their patient enrollment strategies.

One of the major effects of the COVID-19 pandemic within nuclear medicine was to halt performance of lung ventilation studies, due to concern regarding spread of contaminated secretions into the ambient air. A number of variant protocols for performing lung scintigraphy emerged in the medical literature which minimized or eliminated the ventilation component, due to the persistent need to provide this critical diagnostic service without compromising the safety of staff and patients. We have summarized and reviewed these protocols, many of which are based on concepts developed earlier in the history of lung scintigraphy. It is possible that some of these interim remedies may gain traction and earn a more permanent place in the ongoing practice of nuclear medicine.

Peer reviewed: True, Funder: National Institute for Health Research (NIHR) Research for Patient Benefit (RfPB); Grant(s): Grant Reference Number: PB-PG-0815-20048, OBJECTIVE: A qualitative sub-study was carried out within a larger phase II feasibility trial, to identify and describe the burden experienced by advanced melanoma patients participating in a clinical trial and the factors affecting their capacity to cope with the burden. METHODS: Semi-structured interviews were conducted with fourteen patients with advanced melanoma recruited from National Health Service hospitals in the United Kingdom. Qualitative analysis was undertaken using a framework analysis approach. Normalisation process theory was applied to the concept of research participation burden in order to interpret and categorise findings. RESULTS: Burdens of participation were identified as arising from making sense of the trial and treatment; arranging transport, appointment and prescriptions; enacting management strategies and enduring side effects; reflecting on trial documents and treatment efficacy, and emotional and mental effects of randomisation and treatment side effects. Factors reported as influencing capacity include personal attributes and skills, physical and cognitive abilities and support network. DISCUSSION: This is the first study to highlight the substantial burden faced by patients with advanced melanoma in a clinical trial and factors that may lessen or worsen the burden. Consideration of identified burdens during trial design and execution will reduce the burden experienced by research participants.

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. On August 23, 2021, the Food and Drug Administration (FDA) approved a Biologics License Application (BLA) for use of the Pfizer-BioNTech COVID-19 vaccine, marketed as Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (1). The Pfizer-BioNTech COVID-19 vaccine is also recommended for adolescents aged 12-15 years under an Emergency Use Authorization (EUA) (1). All persons aged ≥12 years are recommended to receive 2 doses (30 μg, 0.3 mL each), administered 3 weeks apart (2,3). As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥12 years in the United States.* On October 29, 2021, FDA issued an EUA amendment for a new formulation of Pfizer-BioNTech COVID-19 vaccine for use in children aged 5-11 years, administered as 2 doses (10 μg, 0.2 mL each), 3 weeks apart (Table) (1). On November 2, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation† for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years for the prevention of COVID-19. To guide its deliberations regarding recommendations for the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework§ and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.¶ The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years under an EUA is interim and will be updated as additional information becomes available. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5-11 years, and ACIP determined benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.

Background Efficient trial designs are required to prioritise promising drugs within Phase II trials. Adaptive designs are examples of such designs, but their efficiency is reduced if there is a delay in assessing patient responses to treatment. Methods Motivated by the WIRE trial in renal cell carcinoma (NCT03741426), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design. The MASTER design recruits patients to one arm at a time, pausing recruitment to an arm when it has recruited the required number for an interim analysis. We conduct a simulation study to compare how long the three different trial designs take to evaluate a number of new treatment arms. Results The parallel multi-arm multi-stage and the MASTER design are much more efficient than separate trials. The MASTER design provides extra efficiency when there is endpoint delay, or recruitment is very quick. Conclusions We recommend the MASTER design as an efficient way of testing multiple promising cancer treatments in non-comparative Phase II trials.

Objective: To evaluate the speech outcomes after primary cleft palate repair in a single tertiary medical institution of Thailand.Materials and Methods: A prospective cohort study was performed. Patients who had cleft palate with/without cleft lip and underwent primary cleft palate repair were included. Speech assessment was performed using the Pittsburgh weighted speech score (PWSS) by a speech-language pathologist.Results: Forty patients (21 males and 19 females) who underwent primary cleft palate repair at Siriraj Hospital were included. The median age at the time of speech evaluation was 7 years. The median age at primary cleft palate surgery was 12 months. The predominant cleft palate type was Veau 3 (47.5%). Oronasal fistula occurred 40%. Two-flap palatoplasty and intravelar veloplasty were the most common procedures. Median PWSS was 7, in which the competence velopharyngeal mechanism was found 5%, borderline competence 10%, borderline incompetence 32.5%, and incompetence velopharyngeal mechanism 52.5%. Among the velopharyngeal incompetence group, articulation disorder was the most common disorder with median score of 3. Besides, the median scores for hypo/hyper-nasality, nasal emission, phonation, and facial grimace disorder were 1, 2, 0 and 0, respectively. There was no statistically significant association between velopharyngeal incompetence and cleft types, age at primary surgery, type of operation, the width of cleft palate and prevalence of postoperative oronasal fistula or otitis media effusion.Conclusion: Velopharyngeal incompetence has been commonly identified after cleft palate repair in our institute. The articulation disorder is the most common characteristic.

The American Medical Society for Sports Medicine (AMSSM) convened an expert panel to address the current evidence, knowledge gaps, and recommendations surrounding the COVID vaccination in athletes during the SARS-CoV-2 pandemic. The group held a series of meetings beginning in July 2021 and reviewed the available literature while using an iterative process and expert consensus to finalize this guidance statement. This document is intended to provide clinicians with suggestions on how to incorporate the COVID vaccination during the preparticipation physical examination for athletes in all levels of training and competition. The statement is not intended to address treatment, infection control principles, safety, ethical discussion, or public health issues related to SARS-CoV-2. The AMSSM task force acknowledges the clinical uncertainty, evolving public health objectives, and the limited data currently available to create this guidance statement.

Background: The novel coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019 and then spread worldwide rapidly. The records from World Health Organisation (WHO), Centres of Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) backup the fact that no medications have proven to be completely effective for prevention or treatment of SARS-CoV-2. The clinical trials are underway for many repurposed, investigational drugs and vaccine candidates. BioNTech and Pfizer Inc, Moderna, Gamaleya institute and University of Oxford (collaboration with AstraZeneca) announced positive results in the Phase 3 interim analyses of vaccine trials in November 2020. Twelve countries have approved Pfizer- BioNTech COVID-19 vaccine for emergency use, as of December 2020. Objectives: The objective was to summarize the repurposed/investigational drugs, their mechanism of action, and rationale for their use in COVID-19 treatment. The article also aimed to summarize the vaccine trials that are currently undergoing across the globe. Methods: In order to find the content for review, studies defining COVID-19 chronology, repurposed drugs along with their mode of action and potential vaccine trials were studied and summarized. Results and Conclusion: The article summarizes potential therapeutic candidates (repurposed and investigational agents) for SARS-CoV-2, their possible mechanism of action and discussion related to their involvement in recent clinical trials. Innovative vaccine platform technologies are also highlighted that are recently being used in the vaccine production pipeline.

Background Diffuse large B cell lymphoma is the most frequent aggressive non-Hodgkin lymphoma. Predicting response and estimating prognosis earlier makes management of this heterogeneous lymphoma more satisfying. Interim PET response is established in Hodgkin Lymphoma to tailor the therapy but results for non-Hodgkin Lymphoma is unconvincing. In the current study evaluation of interim PET and survival outcomes of 103 DLBCL patients is performed. Patients and Methods About 103 Patients with DLBCL followed up in a single center between 2009 and 2019 were enrolled the study. All patients received R-CHOP chemoimmunotherapy at first line. Interim PET was performed after at least one or more cycles. All PET scans were performed with 18F-FDG isotope as PET/CT. PET scoring results were evaluated according to the 5-Point Deauville Scoring system defined in the National Comprehensive Cancer Network clinical guidelines for iPET and eotPET. 5-P DS of scores of 1 to 3 were defined as negative scans, and scores of 4 to 5 were considered to be positive scans. Results Forty-six (44.7%) Female and 57 (55.3%) male aged between 25 and 83 (median 57) years newly diagnosed DLBCL patients were enrolled in the study. Median PFS was 21 (interquartile range 8.5-53.7) months and median OS was 33.5 (interquartile range 12.5-62.9) months for the total cohort. Positive predictive value of interim PET according to Deauville scoring system was 65.4% and negative predictive value was 77.9%. Conclusion Our study showed that according to Deauville 5 point scale (D 5PS) scoring system, interim PET-positive patients have shorter both PFS and OS than iPET-negative patients.

When the historical data of the early phase trial and the interim data of the Phase III trial are available, we should use them to give a more accurate prediction in both futility and efficacy anal...

Objective To investigate the treatment efficacy of low-level light therapy on dentin hypersensitivity. Materials and methods Following the PRISMA guideline, six electronic databases supplemented with bibliographies were searched till December 2020. Two reviewers performed the screenings independently with a reliability assessment. Studies fulfilling the pre-registered eligibility criteria were included for risk-of-bias assessment and data synthesis. Results Thirty-five articles ultimately informed this systematic review based on the eligibility criteria and underwent risk-of-bias assessment (ĸ = 0.86). Quantitative results were deduced by meta-analysis of 20 randomised controlled trials: LLLT showed favourable outcomes compared to placebos for immediate (SMD: 1.09, 95% CI: 0.47 to 1.70), interim (SMD: 1.32, 95% CI: 0.41 to 2.23), and persistent efficacies (SMD: 2.86, 95% CI: 1.98 to 3.74). However, substantial heterogeneity existed among included studies (I2: 64–95%). Regarding comparisons with other desensitising strategies, LLLT showed no significant benefits in DH alleviation over others except fluorides for interim efficacy (SMD: 0.31, 95% CI: 0.10 to 0.52) and persistent efficacy (SMD: 0.45, 95% CI: 0.03 to 0.86). Conclusions This systematic review shows that LLLT has positive immediate, interim, and persistent DH-treatment efficacies compared with placebo. No superior treatment effects of LLLT were observed except fluoride agent use. Further studies are warranted—RCTs with low risk of bias, consistent technical settings, comprehensive assessments, and long follow-up periods. Clinical relevance This systematic review bridges a critical research gap by analysing clinical evidence in the DH-alleviating efficacy of LLLT in comparison with placebo and other in-office desensitising strategies.

Psychosocial rehabilitation (PSR) interventions help individuals with schizophrenia and severe mental disorders learn/relearn skills to deal with social and occupational difficulties. Some patients cannot engage in face-to-face sessions for all intervention sessions due to factors like distance, time and cost. Hence, the study aimed to assess the effectiveness of additional contact through telephonic sessions on social and occupational functioning among persons with schizophrenia receiving face-to-face psychosocial interventions. Case records of patients in the PSR (psychosocial rehabilitation) program who received either weekly face-to-face interventions (n = 40) or a combination of monthly face to face with interim weekly telephonically delivered sessions (n = 43) were selected. Baseline and 6 months data on socio-demographic and SOFS scores were retrieved. The reasons for adding telephonic intervention were the distance from home (46.5%), financial constraints (23.3%), lack of motivation (13.9%) and lack of family support to attend sessions (16.3%). At baseline, there were no differences between the two groups in their socio-demographic profiles. There was a significant reduction in the SOFS scores at 6-months in both groups compared to baseline but no difference between the two groups. Combining regular telephonic interventions to face-to-face PSR sessions is as effective as more frequent face-to-face only interventions to those patients who cannot attend for interventions in person. Further research needs to examine the effectiveness of the adjunct telephone interventions using a more robust study design.

Background To date, health technology assessment (HTA) agencies have not been at the forefront of decision making regarding the adoption of interventions for coronavirus disease 2019 (COVID-19). Instead, policymakers have prioritised rapid action in response to the pandemic emergency, with no assessment of value for money. As COVID-19 vaccination coverage increases and healthcare systems begin to recover, HTA agencies will be expected to assess technologies for COVID-19. Objective We aimed to identify the key challenges when assessing therapeutic and diagnostic technologies for COVID-19, from the perspective of HTA agencies, and identify whether there is a case for novel HTA methods and/or processes to address them. Methods We used a mixed-methods approach, by conducting an online survey of HTA agencies, to collect data about the challenges faced when assessing or planning to assess diagnostic and therapeutic technologies for COVID-19. The online survey was followed by a ‘roundtable’ workshop of HTA agencies’ representatives to discuss the results and to elaborate on their responses. Results We received 21 completed surveys (response rate of 45%) and 11 of the respondents joined the roundtable discussion. Five themes emerged from the responses: assessing clinical effectiveness (44%), assessing cost effectiveness (19%), practical (19%), political (11%), and decision making (11%) challenges. At the roundtable, attendees elaborated on the challenges and identified two additional themes: how HTA agencies have responded to the pandemic to date, and how their role might change over time. Conclusion HTA agencies face both methodological and logistical challenges when assessing or planning to assess technologies for COVID-19. An interim best-practice HTA framework to address the key challenges would be valuable. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01097-4.

Background: To date, no studies have directly assessed potential cannabis use disorder (CUD) in medical cannabis (MC) patients pre- vs post-MC treatment. Given that MC patients use cannabis for symptom alleviation rather than intoxication, we hypothesized that MC patients would exhibit few symptoms of CUD after initiating MC treatment. Methods: As part of an ongoing observational, longitudinal study, 54 MC patients completed baseline assessments prior to initiating MC use and returned for at least one follow-up assessment after three, six, and/or twelve months of a self-selected MC treatment regimen; detailed MC treatment information was collected and quantified. All patients completed the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) at each visit. Changes in individual items scores and total scores were assessed over time, and we examined whether total CUDIT-R scores correlated with frequency of MC use, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) exposure. Further, Cronbach’s alpha analyses were conducted to provide preliminary data regarding the psychometric properties of the CUDIT-R when used among MC patients. Results: Although total CUDIT-R scores increased relative to baseline, on average, ratings fell below the ‘hazardous use’ threshold at each visit. Analyses of individual items revealed that increases in total scores were primarily attributable to increases in frequency of use and not necessarily other aspects of problematic use. Total CUDIT-R scores were not associated with number of MC uses or CBD exposure, but a significant relationship was detected between increased THC exposure and higher CUDIT-R scores. Importantly however, analyses revealed that the CUDIT-R does not appear to be an appropriate tool for identifying CUD in MC patients. Conclusions: Screening tools specifically designed to assess CUD in MC patients are needed and should distinguish between frequent use and problematic use; exposure to individual cannabinoids must also be considered.

The expansive geography of Central Alberta presents many barriers to optimal care, including limited resources and access issues. In response to the COVID-19 pandemic, primary care networks (PCNs) within Central Alberta partnered with a technology provider to rapidly implement home health monitoring (HHM) for patients with chronic diseases. In the 37 patients evaluated in phase 1 (90 days), diabetes was most common (73%), followed by hypertension (38%), chronic obstructive pulmonary disease (27%), and heart failure (11%). Overall, patients were comfortable using the HHM technology, and >60% reported improved quality of life after follow-up. Patients also made fewer visits to their family physician/emergency department compared with the pre-enrolment period. In January 2021, the HHM initiative was expanded to a larger patient cohort (phase 2; n = 500). Interim results for 90 patients from eight PCNs up to the end of May 2021 show similar findings to phase 1.

Introduction Like many teaching hospitals in Australia, after-hours computed tomography (CT) reporting at our institution is undertaken by the on-call radiology registrar. The accuracy of these reports is important as management is often initiated based on the interim findings, prior to review by the consultant radiologist. A common exception to this approach is cervical CT (CCT), as many hospital protocols recommend patients to remain in spinal precautions until the report is finalised by a consultant, although there are very few studies to support this practice. Methods The interim registrar reports for all CCTs performed after-hours over a 12-month period were retrospectively reviewed. The final consultant report was used as the gold standard to establish accuracy of the registrar report. The primary outcome was discrepancy between the provisional and final reports. Any discrepancy was classified as either an 'overcall' or 'miss'. Discrepancies were graded by the RADPEER scoring system. Results A total of 1084 after-hours CCT studies were reviewed. The number of cases positive for injury was 37 (3.4%). The total number of discrepancies was 14 (discrepancy rate 1.3%), including 4 overcalls (0.3%) and 10 misses (0.9%). The discrepancy rates for junior and senior registrars were 1.7% and 0.7% respectively. Only 5 misses (0.5%) were considered clinically significant. Conclusion Registrars reporting after-hours CCT have low rates of discrepancy with very few clinically significant misses. However, the reduced registrar sensitivity for detection of cervical injury highlights the ongoing importance of consultant review in the process of cervical spine clearance pathways.

OBJECTIVE: The coronavirus 19 (COVID-19) pandemic resulted in educational disruption of historic breadth and duration. The authors describe early studies and interim standardized assessment reports to highlight effects of educational disruption and present critical questions for neuropsychologists. METHOD: A summary of pre-pandemic and interim literature was compiled, including analyses of national and local assessment data and preliminary studies on academic gains related to remote learning, educational and school services disruption, chronic absenteeism, and child and adolescent mental and physical health during 2020-2021. Ten major themes were identified in the early reports on impacts of educational disruption. RESULTS: Preliminary information indicates prolonged educational disruption has resulted in attenuated learning gains, most remarkably for those already at risk for educational disparities: students of color, students with disabilities, English learners, and students from low-income households. There have also been increased mental and physical health challenges for some youth during the pandemic. Other literature highlights challenges such as diagnosis of learning disabilities, reliance on normative data and development of academic recovery programs. CONCLUSION: The effects of prolonged educational disruption and psychological stressors on learning and mental health should be considered in the neuropsychological evaluation of children and adolescents, especially marginalized students. Normative data collected prior to the pandemic may be insufficient for interpretation of scores, and evaluation and treatment may be delayed due to backlog and increased demand. Clinical practice considerations are presented.

Objectives In 2018, the World Health Organisation (WHO) reported that almost 10 million people worldwide had tuberculosis (TB). The majority of the TB cases were concentrated in South East Asian Region (SEAR) countries. To curb this burden, the WHO has set interim targets to reduce TB incidence by 50% and mortality by 75% by 2025 (interim targets of the ‘End TB’ strategy). Hence, this study was conducted to determine the progress of SEAR countries towards reaching these interim targets for TB incidence and mortality. Methods Secondary data analysis was performed using information from the WHO Global Health Observatory and Global Health Estimates for all SEAR countries. ARIMA modelling was used to forecast TB incidence and TB mortality from 2000 to 2025. Joinpoint regression was performed to determine the average annual percent change. Results Based on the current trend, we estimated that the incidence and mortality of TB in SEAR countries will decline to 3.7 million (4.37 million in 2018) and 495,280 (650,979 in 2016) by 2025, respectively. Projected age-standardised TB incidence showed a significant decline in only four SEAR countries, with the maximal decline in Myanmar (47.3%) followed by India (23.4%) compared with 2015 estimates. Age-standardised TB mortality showed a declining trend in six SEAR countries, with the maximum decline found in Myanmar (60.3%) followed by Thailand (39.0%). Conclusions Current study findings show that it is highly unlikely for most SEAR countries to achieve the WHO recommended interim End TB targets of 50% reduction in incidence and 75% reduction in mortality by 2025.

Boarding schools, by definition, house students in residence either on campus or close by in residential facilities - where the sleep environment is likely to differ from their home environment. For boarders, being in the boarding environment occurs alongside a convergence of psychosocial and physiological factors likely to impact adolescent sleep. This paper comprises a review of the literature on sleep and boarding students in the Australian context. We also propose recommendations aligned with the scientific evidence base that can be used to promote healthy sleep in Australian boarding school students, focusing on staff training and sleep knowledge, daily routines, sleeping arrangements, and student mental health and wellbeing. It must be noted that these recommendations should be considered interim recommendations until further research is performed in the area. Further, we suggest the development of standardised practice guidelines, to ensure that student sleep is supported appropriately within the Australian boarding context.

Background The Interim Federal Health Program (IFHP) provides health care coverage to refugees and refugee claimants, yet remains underused by providers. The objective of this study was to assess Canadian paediatricians’ current understanding and utilization of the IFHP, and perceived barriers to utilization. Methods A one-time survey was administered via the Canadian Paediatric Surveillance Program in February 2020. In addition to descriptive statistics, multinomial logistic regressions were built to examine paediatrician use of the IFHP, and characteristics associated with registration and use. Results Of the 2,753 physicians surveyed, there were 1,006 respondents (general paediatricians and subspecialists). 52.2% of respondents had provided care to IFHP-eligible patients in the previous 6 months. Of those participants, only 26.4% were registered IFHP providers, and just 16% could identify 80% or more of IFHP-covered services. Knowledge of 80% or more of IFHP-covered services was associated with registration status (adjusted odds ratio [aOR] 1.92; 95%CI 1.09 to 3.37). Among those who knew they were not registered, 70.2% indicated they did not know they had to register. aOR demonstrated that those with fewer years of practice had higher odds of not knowing that they had to register (aOR 1.22; 95%CI 1.01 to 1.49). Conclusions We demonstrate that IFHP is poorly utilized by paediatric providers, with low registration rates and poor understanding of IFHP-covered supplemental services, even among those who have recently provided care to IFHP-eligible patients. Efforts to improve registration and knowledge of IFHP are essential to improving access to health care for refugee children and youth.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barre syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public.

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.

Objective To study the use of video visits for male infertility care prior to the COVID-19 pandemic Methods We reviewed video visits for male infertility patients completed at a tertiary academic center in southeast Michigan. These patients had follow-up after an initial in-person evaluation. We designed this retrospective case series to describe the diagnostic categories seen through telehealth, management steps completed during video visits, and to understand whether additional in-person care was required within 90 days of video visits. In addition, we estimated time and cost savings for patients attributed to video visits. Results Most men seen during video visits had an endocrinologic (29%) or anatomic (21%) cause for their infertility. 73% of video visits involved reviewing results; 30% included counseling regarding assistive reproductive technologies; and 25% of video visits resulted in prescribing hormonally active medications. The two patients (3%) who were seen in clinic after their video visit underwent a varicocelectomy in the interim. No patients required an unplanned in-person visit. From a patient perspective, video visits were estimated to save a median of 97 minutes (IQR 64-250) of travel per visit. Median cost savings per patient— by avoiding travel and taking time off work for a clinic visit—were estimated to range from $149 (half day off) to $252 (full day off). Conclusion Video visits for established male infertility patients were used to manage different causes of infertility while saving patients time and money. Telehealth for established patients did not trigger additional in-person evaluations.

Background Many people with spinal cord injury (SCI) have limited access to tailored, readily available exercise resources. As a result, exercise remains an underutilized treatment strategy for improving health and function in people with SCI. The purpose of this study is to test the effectiveness of two remotely delivered exercise programs for people with SCI. Methods The Spinal Cord Injury Program in Exercise (SCIPE) study is a three-arm adaptive randomized controlled trial examining two 8-week teleexercise interventions: Movement-to-Music (M2M) and Standard Exercise Training (SET), compared to Attention Control (AC) in 327 adults with SCI. The primary outcome is change in physical activity level at post 8-week intervention. The study contains two interim analyses. The first interim analysis will assess feasibility metrics of the protocol after 36 participants complete the 8-week intervention period. The second interim analysis will examine two effectiveness comparisons: SET vs. AC and M2M vs AC, after 165 participants complete the intervention period. Early termination of the intervention arm(s) will take place when non-significant findings are found in the corresponding intervention(s). Incorporation of such interim analysis enhances trial efficiency by dropping the intervention(s) that deemed ineffective. It provides ethical benefits and allows allocation of additional resources to explore the effective intervention(s). Discussion Delivery of teleexercise programs may be an effective strategy for addressing transportation barrier to exercise resources and increasing physical activity level and quality of life in people with SCI. Trial registration ClinicalTrials.gov Identifier NCT03925077. Registered trial name: Spinal Cord Injury Program in Exercise (SCIPE). Registered on April 23rd, 2019.

Delayed treatment effects have been commonly observed in clinical trials, which bring more challenges to the interim decision making particularly in adaptive designs setting. An improper interim an...

Introduction There is paucity of data around the support that medical students have been provided with, need to be provided with, and would like to be provided with during the COVID-19 pandemic. This study sought to explore the effects of the COVID-19 pandemic on medical students and establish the support they require. Methods A prospective, observational, multicentre study was conducted in 2020. All medical students and interim foundation year 1 doctors were eligible to participate. Results Six hundred forty individuals participated from 32 medical schools. Participants reported a drop in their mood following the onset of the pandemic (p p p p n = 111/596, 19%) had not received the support they needed from their university by August. The most common area of support that our participants needed and had not received from their medical schools by August was support with course material (n = 58/111, 52%). ‘Clinical knowledge’ was thought to have been affected by the greatest number of participants in both May and August. Conclusion Medical students’ mental well-being has been adversely affected during the COVID-19 pandemic. Our findings have actionable implications that can better protect medical students as they acclimatise to a working environment that has been radically changed by COVID-19.

Background Wolbachia technology is a novel vector control approach that can reduce mosquito populations and the risk of mosquito-borne diseases, which has recently gained popularity amongst countries. In 2016, Singapore embarked on a multi-phased field study named Project Wolbachia – Singapore, to evaluate the use of Wolbachia technology as an Aedes aegypti mosquito population suppression tool to fight dengue. Due to the novelty of this technology in Singapore, this study aims to understand the public’s acceptance and sentiments towards the use of Wolbachia technology. Methods Several public sentiment survey approaches – including online, face-to-face in the streets, as well as door-to-door household surveys – were conducted. Results The surveys conducted prior to the first field releases and implementation of the project revealed high support for the use of Wolbachia technology in Singapore. A household perception survey conducted in the interim of the first project phase was encouraging, with the majority of the respondents being aware of the project and having no concerns with the release of male Wolbachia-carrying Aedes aegypti (Wolbachia-Aedes) mosquitoes in their neighbourhood. Conclusions The study reveal high support for the use of Wolbachia technology in Singapore and also provided invaluable insights that were used in the development of a public communications and engagement framework model, which thus helped to guide these elements in the subsequent phases and expansion of the project.

Background On 16 Jan 2021, India launched its immunization program against COVID-19. Among the first recipients were 1.59 million Health Care Workers (HCWs) and Frontline Workers (FLWs) of the Indian Armed Forces, who were administered COVISHIELD (Astra Zeneca). We present an interim analysis of vaccine effectiveness (VE) estimates till 30 May 2021. Methods The VIN-WIN cohort study was carried out on anonymized data of HCWs and FLWs of Indian Armed Forces. The existing surveillance system, enhanced for COVID-19 monitoring, was sourced for data. The cohort transitioned from Unvaccinated (UV) to Partially Vaccinated (PV) to Fully Vaccinated (FV), serving as its own internal comparison. Outcomes studied in the three groups were breakthrough infections and COVID related deaths. Incidence Rate Ratio (IRR) was used to compare outcomes among the three groups to estimate VE. Results Data of 1,595,630 individuals (mean age 27.6 years; 99% male) over 135 days was analysed. Till 30 May 21, 95.4% and 82.2% were partially and fully vaccinated. The UV, PV and FV compartments comprised 106.6, 46.7 and 58.7 million person-days respectively. The number of breakthrough cases in the UV, PV and FV groups were 10061, 1159 and 2512; while the deaths were 37, 16 and 7 respectively. Corrected VE was 91.8–94.9% against infections. Conclusion Interim results of the VIN-WIN cohort study of 1.59 million HCWs and FLWs of Indian Armed Forces showed a ∼93% reduction in COVID-19 breakthrough infections with COVISHIELD vaccination.

Background: Regulatory approval of oncology drugs is often based on interim data or surrogate endpoints. However, clinically relevant data, such as long-term overall survival and quality of life (QoL), are often reported in subsequent publications. This study evaluated the ASCO-Value Framework (ASCO-VF) net health benefit (NHB) at the time of approval and over time as further evidence arose. Methods: FDA-approved oncology drug indications from January 2006 to December 2016 were reviewed to identify clinical trials scorable using the ASCO-VF. Subsequent publications of clinical trials relevant for scoring were identified (until December 2019). Using ASCO-defined thresholds (≤40 for low and ≥45 for substantial benefit), we assessed changes in classification of benefit at 3 years postapproval. Results: Fifty-five eligible indications were included. At FDA approval, 40.0% were substantial, 10.9% were intermediate, and 49.1% were low benefit. We then identified 90 subsequent publications relevant to scoring, including primary (28.9%) and secondary endpoint updates (47.8%), safety updates (31.1%), and QoL reporting (47.8%). There was a change from initial classification of benefit in 27.3% of trials (10.9% became substantial, 9.1% became low, and 7.3% became intermediate). These changes were mainly due to updated hazard ratios (36.4%), toxicities (56.4%), new tail-of-the-curve bonus (9.1%), palliation bonus (14.5%), or QoL bonus (18.2%). Overall, at 3 years postapproval, 40.0% were substantial, 9.1% were intermediate, and 50.9% were low benefit. Conclusions: Because there were changes in classification for more than one-quarter of indications, in either direction, reassessing the ASCO-VF NHB as more evidence becomes available may be beneficial to inform clinical shared decision-making. On average, there was no overall improvement in the ASCO-VF NHB with longer follow-up and evolution of evidence.

Background and Overview Severely molar-incisor hypomineralization (MIH)–affected teeth are prone to develop early posteruptive enamel breakdown (PEB) and caries. A novel conservative interim approach for the prevention of this complication is presented. Case Description A 6-year-old boy with strong hypersensitivity and extensive brown opacities in the partially erupted mandibular permanent first molars (PFMs) was diagnosed with MIH. Constant hygiene and dietary counseling were followed by the application of luted orthodontic bands and glass ionomer sealants to protect PFMs from caries and PEB until the complete eruption of the teeth. After 36 months, the PFMs were completely erupted, with no caries and PEB, and the cooperation of the child increased. Conclusions and Practical Implications Temporary strategies are useful to preserve MIH-affected PFMs. With the methodology described, the hypersensitivity decreased and the patient reached a good degree of cooperation, making possible definitive rehabilitative considerations.

On May 10, 2021, the Food and Drug Administration (FDA) expanded its Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; this authorization was followed by interim recommendations from the Advisory Committee on Immunization Practices (ACIP) for the vaccine among this age group (1). Using data from nonprobability-based Internet panel surveys administered by the Healthcare and Public Perceptions of Immunizations (HaPPI) Survey Collaborative, the acceptability of adolescent COVID-19 vaccination and self-reported factors increasing vaccination intent were assessed among independently recruited samples of 985 adolescents aged 13-17 years and 1,022 parents and guardians (parents) of adolescents aged 12-17 years during April 15-April 23, 2021, prior to vaccine authorization for this age group. Approximately one quarter (27.6%) of parents whose adolescents were already vaccine-eligible (i.e., aged 16-17 years) reported their adolescent had received ≥1 COVID-19 vaccine dose, similar to the proportion reported by vaccine-eligible adolescents aged 16-17 years (26.1%). However, vaccine receipt reported by parents of adolescents differed across demographic groups; parents identifying as female or Hispanic, or who had an education lower than a bachelor's degree reported the lowest adolescent COVID-19 vaccination receipt. Among parents of unvaccinated adolescents aged 12-17 years, 55.5% reported they would "definitely" or "probably" have their adolescent receive a COVID-19 vaccination. Among unvaccinated adolescents aged 13-17 years, 51.7% reported they would "definitely" or "probably" receive a COVID-19 vaccination. Obtaining more information about adolescent COVID-19 vaccine safety and efficacy, as well as school COVID-19 vaccination requirements, were the most commonly reported factors that would increase vaccination intentions among both parents and adolescents. Federal, state, and local health officials and primary care professionals were the most trusted sources of COVID-19 vaccine information among both groups. Efforts focusing on clearly communicating to the public the benefits and safety of COVID-19 vaccination for adolescents, particularly by health care professionals, could help increase confidence in adolescent COVID-19 vaccine and vaccination coverage.

After the March 2020 declaration of the COVID-19 pandemic in the United States, an analysis of provider ordering data from the federally funded Vaccines for Children program found a substantial decrease in routine pediatric vaccine ordering (1), and data from New York City and Michigan indicated sharp declines in routine childhood vaccine administration in these areas (2,3). In November 2020, CDC interim guidance stated that routine vaccination of children and adolescents should remain an essential preventive service during the COVID-19 pandemic (4,5). To further understand the impact of the pandemic on routine childhood and adolescent vaccination, vaccine administration data during March-September 2020 from 10 U.S. jurisdictions with high-performing* immunization information systems were assessed. Fewer administered doses of routine childhood and adolescent vaccines were recorded in all 10 jurisdictions during March-September 2020 compared with those recorded during the same period in 2018 and 2019. The number of vaccine doses administered substantially declined during March-May 2020, when many jurisdictions enacted stay-at-home orders. After many jurisdictions lifted these orders, the number of vaccine doses administered during June-September 2020 approached prepandemic baseline levels, but did not increase to the level that would have been necessary to catch up children who did not receive routine vaccinations on time. This lag in catch-up vaccination might pose a serious public health threat that would result in vaccine-preventable disease outbreaks, especially in schools that have reopened for in-person learning. During the past few decades, the United States has achieved a substantial reduction in the prevalence of vaccine-preventable diseases driven in large part to the ongoing administration of routinely recommended pediatric vaccines. These efforts need to continue even during the COVID-19 pandemic to reduce the morbidity and mortality from vaccine-preventable diseases. Health care providers should assess the vaccination status of all pediatric patients, including adolescents, and contact those who are behind schedule to ensure that all children are fully vaccinated.

Background External control (EC) data from completed clinical trials and electronic health records can be valuable for the design and analysis of future clinical trials. We discuss the use of EC data for early stopping decisions in randomized clinical trials (RCTs). Methods We specify interim analyses (IAs) approaches for RCTs, which allow investigators to integrate external data into early futility stopping decisions. IAs utilize predictions based on early data from the RCT, possibly combined with external data. These predictions at IAs express the probability that the trial will generate significant evidence of positive treatment effects. The trial is discontinued if this predictive probability becomes smaller than a prespecified threshold. We quantify efficiency gains and risks associated with the integration of external data into interim decisions. We then analyze a collection of glioblastoma (GBM) data sets, to investigate if the balance of efficiency gains and risks justify the integration of external data into the IAs of future GBM RCTs. Results Our analyses illustrate the importance of accounting for potential differences between the distributions of prognostic variables in the RCT and in the external data to effectively leverage external data for interim decisions. Using GBM data sets, we estimate that the integration of external data increases the probability of early stopping of ineffective experimental treatments by up to 25% compared to IAs that do not leverage external data. Additionally, we observe a reduction of the probability of early discontinuation for effective experimental treatments, which improves the RCT power. Conclusion Leveraging external data for IAs in RCTs can support early stopping decisions and reduce the number of enrolled patients when the experimental treatment is ineffective.

BackgroundIn England, demand for emergency care is increasing while there is also a staffing shortage. The Royal College of Emergency Medicine (RCEM) suggested that appointment of senior doctors as clinical educators (CEs) would enable support and development of learners in EDs and improve retention and well-being. This study aimed to evaluate the impact of CEs in ED on learners.MethodsCEs were placed in 54 NHS Acute Trust EDs for a pilot beginning July 2018 and ending October 2020. Learners from multiple disciplines working at 54 NHS Acute Trust EDs where CEs were deployed were invited to complete an online survey designed to identify the impact of CEs in July of 2019, as part of an interim service evaluation.ResultsRespondents numbered 493 from 49 of 54 study sites, including 286 (58%) medical (non-consultant) and 72 (14.6%) all other nursing, allied health professionals. 9 out of 10 learners reported having experienced a change to their learning as a result of the deployment of CEs in their department. 49.9% (246/493) reported that CEs had a positive impact on their well-being. 95% (340/358) reported an improved accessibility to undertaking clinical based assessments. 78% (281/358) perceived that access to CEs increased likelihood of passing assessments. Of those responding, 80.9% (399/493) reported they would remain/return to the same ED with a CE, and 92.5% (456/493) responded that they would prefer to go to a Trust with a CE.ConclusionsAccording to survey respondents, deployment of CEs across NHS Trusts has resulted in improvement and increased accessibility of learning and assessment opportunities for learners within ED. The impact of CEs on well-being is uncertain with half reporting improvement and the remaining half unsure. Further evaluation within the project will continue to explore the service benefit and workforce impact of the CEED intervention.

Comprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germline TP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36 years [range 3–68], median follow-up 37 months [range 2–70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnosed between annual screenings but only one cancer (colorectal adenocarcinoma) was diagnosed due to an abnormal interim blood test. Fisher’s exact test and generalized estimating equation models found no statistical associations between cancer diagnoses and any test abnormality. Four- and 8-monthly interim screening blood tests may not be of independent benefit for cancer detection in LFS, but annual cancer screening and personalized follow-up remain essential.