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This is a summary of a publication about the ENSEMBLE trial of the Janssen Ad26.COV2.S vaccine against COVID-19, which was published in the New England Journal of Medicine in April 2021. The ENSEMBLE study started in September 2020 and is still ongoing. The study compared the effectiveness of the vaccine to a placebo in 43,783 adults from Latin America, South Africa, and the United States. Of those, 19,630 got a single dose of the vaccine. Compared to the placebo, the vaccine prevented: 66.9% of moderate to severe–critical COVID-19 cases after 14 days 66.1% of moderate to severe–critical COVID-19 cases after 28 days 85.4% of severe COVID-19 cases after 28 days 100% of people with severe COVID-19 from needing to go to hospital for treatment None of the vaccinated participants died from COVID-19. There were 5 people who got the placebo who died from COVID-19. The vaccine was similarly effective in people from all age groups and different countries, including South Africa, where most cases were caused by the beta variant of the virus that originated there. The people in the study who got the vaccine who went on to get COVID-19 generally had milder and fewer symptoms than those who got the placebo. In most people, the vaccine started working after about 2 weeks. After receiving the vaccine, some people experienced pain at the injection site, headache, tiredness, muscle pain, and nausea. In most cases, these were mild and went away within a few days. Serious side effects were very rare. Blood clots, seizures, and tinnitus were very rare but were more common in the people who got the vaccine than in those who got the placebo. At the time of the study, it was not clear if these were caused by the vaccine or not. ClinicalTrials.gov NCT number: NCT04505722. [ABSTRACT FROM AUTHOR]

Abstract Objective To determine whether the thickness of the rotator interval tendons is different when comparing both symptomatic and non-symptomatic sides in people with chronic shoulder pain, and to those free of pain. Furthermore, to calculate the level of association between the rotator interval tendon thicknesses and perceived shoulder pain-function. Design A cross-sectional, observational study. Method The supraspinatus, subscapularis and biceps brachii tendon thickness of sixty two patients with chronic shoulder pain were determined from standardized ultrasonography measures performed on both shoulders, whereas only the dominant arm was measured for the control subjects. Findings Supraspinatus, subscapularis and biceps brachii tendon thickness was comparable between sides in the symptomatic group and was also comparable between the symptomatic and asymptomatic participants. In addition, the correlation between the tendon thickness and shoulder pain-function was non-significant. Interpretations Tendon thickness was unaltered in people with chronic shoulder pain. These findings do not rule out the possibility that other changes in the tendon are present such as changes in the elastic properties and cell population and this should be explored in future studies. Highlights • The results suggest that non-traumatic chronic shoulder pain does not alter the thickness of the tendons. • The thickening of the tendon is possibly rather an early traumatic or mechanical loading response. • The tendon thickness cannot explain differences in pain perception. • The tendon thickness should not be used as an indicator of shoulder pain-function in chronic conditions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was twofold: (i) to assess the intrarater reliability of coracohumeral distance; (ii) to investigate the level of association between coracohumeral distance measured by ultrasonography, and pain-disability and shoulder range of movement, in patients suffering from chronic anterior shoulder pain.Methods: An observational, cross sectional study was carried out. A convenience sample comprised of 87 patients with chronic anterior shoulder pain was assessed from 3 primary care centres. Main outcomes as pain and function were measured through the shoulder pain and disability index. Furthermore, shoulder range of movement-free of pain in shoulder elevation, as well as coracohumeral distance at both 0 and 60 degrees, were collected.Results: Absence of any correlation was found between coracohumeral distance and shoulder pain and disability index at both 0 and 60 degrees of shoulder elevation. Furthermore, absence of any correlation was found between coracohumeral distance measurements and active shoulder range of movement -free of pain.Conclusions: There was poor association between coracohumeral distance and shoulder pain and function, as well as with shoulder range of movement, in patients with chronic anterior shoulder pain. Hence, clinicians should consider, not only increasing this space, but also other possibilities in their therapies, when patients with anterior shoulder pain are treated.Trial Registration: ACTRN12614000144617 . Registered: 1st March 2014. [ABSTRACT FROM AUTHOR]

Introduction: The natural course of frozen shoulder (FS) remains unclear and factors like altered central pain processing and autonomic dysfunction might play a role in the disease course and incomplete recovery in a subset of patients. Psychological factors (e.g. catastrophizing and hypervigilance) might influence pain severity and measurements in patients with chronic pain and an interrelation might be present. Methods: Patients with FS completed six questionnaires and underwent quantitative sensory testing, including tactile sensitivity (allodynia), pressure pain thresholds (hyperalgesia), temporal summation and conditioned pain modulation four times (at baseline and 3, 6 and 9 months after baseline). Results: One hundred and forty-nine patients with frozen shoulder were initially recruited and 88 completed all the follow-up measurements. Pain intensity, shoulder pain and disability, catastrophizing, hypervigilance, allodynia and hyperalgesia improved over time. Fair correlation was found between pain intensity and catastrophizing and catastrophizing and hypervigilance, while poor correlation was found between pain intensity and hypervigilance, allodynia and hyperalgesia, between catastrophizing and hyperalgesia and autonomic symptoms and between hypervigilance and hyperalgesia. Discussion: Patients with FS improve in several pain variables and psychological pain related variables over the course of 9 months. This improvement might be related to each other in a small extent, due to the presence of correlations between some of these variables. Process evaluation: Data analysis is in process. [ABSTRACT FROM AUTHOR]

The objective of this prospective study is to investigate possible scapular related risk factors for developing shoulder pain. Therefore, a 2-year follow-up study in a general community sports centre setting was conducted. A sample of convenience of 113 recreational overhead athletes (59 women and 54 men) with a mean age of 34 (17-64; SD 12) years were recruited. At baseline, visual observation for scapular dyskinesis, measured scapular protraction, upward scapular rotation and dynamic scapular control were evaluated. 22 % (n = 25) of all athletes developed shoulder pain during the 24 months following baseline assessment. The Mean Shoulder Disability Questionnaire (SDQ) score for the painful shoulders was 34.8 (6.3-62.5; SD 17.4). None of the scapular characteristics predicted the development of shoulder pain. However, the athletes that developed shoulder pain demonstrated significantly less upward scapular rotation at 45 ° (p = 0.010) and 90 ° (p = 0.016) of shoulder abduction in the frontal plane at baseline in comparison to the athletes that remained pain-free. In conclusion, although these scapular characteristics are not of predictive value for the development of shoulder pain, this study increases our understanding of the importance of a scapular upward rotation assessment among recreational overhead athletes. [ABSTRACT FROM AUTHOR]

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The molecular mechanisms underlying the directional neuron-to-epithelial cell transport of herpesvirus particles during infection are poorly understood. To study the role of the viral glycoprotein D (gD) in the directional spread of herpes simplex virus (HSV) and pseudorabies virus (PRV) infection, a culture system consisting of sympathetic neurons or epithelial cells in different compartments was employed. We discovered that PRV infection could spread efficiently from neurons to cells and back to neurons in the absence of gD, the viral ligand required for entry of extracellular particles. Unexpectedly, PRV infection can also spread transneuronally via axo-axonal contacts. We show that this form of interaxonal spread between neurons is gD independent and is not mediated by extracellular virions. We also found that unlike PRV gD, HSV-1 gD is required for neuron-to-cell spread of infection. Neither of the host cell gD receptors (HVEM and nectin-1) is required in target primary fibroblasts for neuron-to-cell spread of HSV-1 or PRV infection. [ABSTRACT FROM AUTHOR]

Aim: To synthesize the evidence considering effects of pre-operative patient expectations on the post-operative outcomes in patients with total shoulder arthroplasty., Methods: PubMed, Web of Science and Cochrane were searched for relevant studies. Studies before 2000 were excluded. Studies examining effects of pre-operative patient expectations on post-operative outcome in adults who had undergone total shoulder arthroplasty were included if at least one of the following treatment outcomes should have been measured: shoulder function, range of motion, shoulder pain, activities of daily living, muscle strength, patient satisfaction, or quality of life. After screening 875 studies four studies were included. Relevant data was extracted in a standardized way. Quality assessment was performed through QUIPS and EBRO methods. Both were performed by two independent reviewers., Results: All 4 studies had a high risk of bias and level of evidence B. Moderate evidence was found regarding the absence of an association between greater pre-operative patient expectations and numerous outcome measures. All other associations yielded conflicting or preliminary evidence., Discussion: Informing patients about what can be expected can be of great importance. Evidence lacking. To confirm or reject the findings of this systematic review, future research should focus on high-quality research with validated research protocols., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Massive irreparable rotator cuff tears can cause significant shoulder pain and disability. Treatment options include physiotherapy or surgery, with a lack of research comparing treatment options. For physiotherapy there is uncertainty about which patients will have a successful or unsuccessful response to treatment and a lack of consensus on what constitutes the best physiotherapy programme. With these significant gaps in the research, it is challenging for clinicians seeing patients with massive irreparable rotator cuff tears to advise on what is their best treatment pathway., Methods: A three round Delphi study was conducted with expert shoulder physiotherapists and orthopaedic surgeons to gain consensus on the important factors associated with response to physiotherapy in this patient population. Round 1 was an information-gathering round to identify predictors of response to physiotherapy in patients with massive irreparable rotator cuff tears. Rounds 2 and 3 were consensus-seeking rounds on the importance and modifiability of the predictors. Consensus criteria were determined a priori using median, interquartile range, percentage agreement and Kendall's Coefficient of Concordance., Results: Participants were recruited April-October, 2023. 88 experts participated in Round 1 and of these, 70 completed Round 3 (79.54%). In Round 1, content analysis of 344 statements identified 45 predictors. In Round 2, 29 predictors reached consensus as important and 2 additional predictors were identified. In Round 3, of the 31 predictors from Round 2, 22 reached consensus as important and 12 of these reached consensus as modifiable by physiotherapists. Both patient factors and clinician factors from a broad range of domains reached consensus: biomechanical, psychological, social, co-morbidities, communication / healthcare interactions and pain., Conclusions: The results of this Delphi study suggest that clinicians assessing patients with massive irreparable rotator cuff tears should assess across all these domains and target the modifiable factors with interventions. Particular emphasis should be placed on optimising modifiable clinician factors including therapeutic alliance, comprehensive explanation of the condition and collaborative and realistic goal-setting. These in turn may influence modifiable patient factors including patient expectations, engagement with the physiotherapy programme, motivation and self-efficacy thus creating the ideal environment to intervene on a biomechanical level with exercises., (© 2024. The Author(s).)

Background: This study aimed to support the end-of-shelf life specification (2.5 × 10 10 virus particles [vp]) for the standard Ad26.COV2.S dose (5 × 10 10 vp)., Methods: This randomized, double-blind Phase 3 study evaluated immunogenicity, reactogenicity, and safety of several Ad26.COV2.S dose levels (range 1.25 to 9 × 10 10 vp) in 1593 adults between June 2021 and July 2023., Results: Spike-binding antibody responses 28 days post-dose 1 were non-inferior for the 9 × 10 10 vp, but not the 2.5 × 10 10 vp group when compared with the standard dose. Non-inferiority was demonstrated in terms of spike-binding antibody responses 14 days post-dose 2 for each dose level, including the lowest dose level of 1.25 × 10 10 vp, compared to 28 days after one dose and 14 days after two doses of the standard dose. Spike-binding antibody levels correlated well with virus neutralizing titers. There was no impact of pre-existing Ad26.COV2.S neutralizing titers on immunogenicity at any dose level. All dose levels were well tolerated., Conclusions: This study highlights the challenges associated with conducting clinical studies in a rapidly evolving environment and underscores the importance of platform data that can guide initial vaccine specifications such as shelf life during accelerated vaccine development. The present study supports the end-of-shelf life specifications for the approved Ad26.COV2.S dose, and could provide useful information in future vaccine developments using adenovirus vector vaccines.

Aims: To develop a semimechanistic model that describes the kinetic profile and variability of antibody (Ab) concentrations following vaccination with Ad26.COV2.S at different doses and dosing intervals., Methods: Data were collected from participants randomized into 5 clinical trials receiving the Ad26.COV2.S vaccine. The model considered key elements of humoral immune response, dose proportionality and the evolutionary processes of the immune response. Interindividual variability and covariates were explored., Results: Fast and slow kinetic phases of Ab and their evolution over time were differentiated. After first and second administrations, Ab concentrations of both phases increased less than dose proportionally, indicating a saturation of B-cell production processes. Ab concentrations produced during the fast kinetic phase increased significantly after the second administration, indicating an underlying evolutive process after antigen exposures. For the slow kinetic phase, a less pronounced increase occurred after the second and third administrations but was relatively higher in subjects who had low concentrations after the first administration. Ab concentrations of the slow phase were higher in females and decreased with age. After multiple administrations, the fast phase had Ab maximum concentrations about 5 times higher than the slow phase. The limiting kinetic factors in the fast and slow phases were the elimination rates of Ab itself and Ab producing cells, respectively., Conclusion: The model appears suitable to quantitatively describe the inter- and intraindividual kinetics of the immune response and the impact of covariates after multiple administrations of a vaccine., (© 2024 British Pharmacological Society.)

Objective: Physiotherapists (PTs) play a crucial role in managing individuals with Frozen Shoulder (FS), frequently being the first healthcare professionals involved in the treatment of this condition., Aim: This study aimed to compare the beliefs, expectations, and perspectives of individuals with FS with the knowledge, skills, and strategies of PTs, highlighting similarities and differences., Method: This study adhered to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). From May 1st to August 1st, 2023, a two-part survey was conducted involving PTs and individuals diagnosed with FS. The survey focused on comparing key areas such as clinical assessment, patient education, treatment expectations, and the psychological aspects of the patient-clinician relationship., Results: A total of 501 PTs and 110 subjects with FS participated in the survey. Most PTs showed proficiency in FS pathoanatomical conditions and were also attentive to psychological aspects (88.4%), describing the pathology evolution in three or two stages (68.2%). They also highlighted the importance of patient education (89.6%) and recognized the potential benefits of a multiprofessional collaboration in managing FS (82.2%). Reassurance was reported as a priority by 32.3% of PTs. Subjects with FS expressed a preference for PTs who are both expert and empathetic (73.6%). Regarding their understanding of FS, 29.09% of subjects reported receiving a three-phase explanation, while 26.36% felt inadequately informed. Nearly half of the subjects (49.09%) anticipated being managed independently by a PT, with 93.64% prioritizing the improvement of their range of motion., Conclusion: This study revealed a general agreement between subjects with FS and PTs regarding aspects of the therapeutic relationship, patient education, pathology management, compliance and motivation strategies, and pain management preferences. However, significant differences emerged concerning the perception of physiotherapy effectiveness, primary treatment goals, subjects' priorities, and the importance of psychological assessment., (© 2024. The Author(s).)

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event identified following vaccination with some adenovirus-vectored COVID-19 vaccines, including Ad26.COV2.S. VITT is characterized by the presence of antibodies against platelet factor 4 (PF4)., Objectives: To evaluate whether PF4 antibodies were generally induced following vaccination with adenovirus type 26 (Ad26)-vectored vaccines., Methods: The study included 913 and 991 healthy participants without thromboembolic (TE) events in Ad26.COV2.S and non-COVID-19 Ad26-vectored vaccine clinical studies, respectively, and 1 participant with VITT following Ad26.COV2.S vaccination. PF4 antibody levels were measured in prevaccination and postvaccination sera. PF4 antibody positivity rates were assessed in a case-control setting in participants who developed TE events during participation in Ad26-vectored vaccine clinical studies., Results: In the 1 VITT patient, PF4 antibodies were negative before vaccination. Seroconversion for platelet-activating PF4 antibodies was observed upon Ad26.COV2.S vaccination. In participants without TE events, the PF4 antibody levels and positivity rates were similar before and after Ad26 vaccination. Ad26 vaccination did not increase PF4 antibody levels in participants who were PF4 antibody-positive at baseline (n = 47). Lastly, 1 out of 28 TE cases and 2 out of 156 non-TE controls seroconverted after Ad26.COV2.S vaccination. None of the 15 TE cases and 3 of the 77 non-TE controls seroconverted following non-COVID-19 Ad26 vaccination., Conclusion: Ad26.COV2.S and the other Ad26-vectored vaccines studied did not generally induce PF4 antibodies or increase preexisting PF4 antibody levels. Moreover, unlike VITT, TE events that occurred at any time following Ad26 vaccination were not associated with PF4 antibodies., Competing Interests: Declaration of competing interests All authors were full-time employees of Johnson & Johnson at the time of the study and may have equity or stocks in Johnson & Johnson. F.S. is a former employee of GlaxoSmithKline and holds GlaxoSmithKline equity or stocks., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: There is no established consensus for screening the spine in patients with shoulder pain. The aim of this study was to explore the role of the spine in shoulder pain and generate a set of recommendations for assessing the potential involvement of the spine in patients with shoulder pain., Methods: A modified Delphi study was conducted through use of an international shoulder physical therapist's expert panel. Three domains (clinical reasoning, history, physical examination) were evaluated using a Likert scale, with consensus defined as Aiken Validity Index ≥0.7., Results: Twenty-two physical therapists participated. Consensus was reached on a total of 30 items: clinical reasoning (n = 9), history (n = 13), and physical examination (n = 8). The statement that spinal and shoulder disorders can coexist, sometimes influencing each other and at other times remaining independent issues, along with the concept of radiating pain as an explanatory phenomenon for the spine contribution to shoulder pain, achieved the highest degree of consensus., Conclusion: International physical therapists shoulder experts reached consensus on key aspects when screening the spine in people with shoulder pain, including consideration of the distal location of symptoms relative to the shoulder, the presence or previous history of neck pain, the changes in symptoms related to neck movements, and the presence of neuropathic-like symptoms. They also acknowledged the importance of assessing active cervical or cervicothoracic movements and the usefulness of the Spurling test and symptom modification techniques applied to the spine., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802., Competing Interests: Potential conflicts of interest. A. F. had/has research grants from Pfizer, Merck, Janssen, CyanVac, VaxCo, Moderna, and BioFire Diagnostics; fees for advisory boards from GSK, ADMA Biologics, and Sanofi Pasteur; and fees for data safety monitoring board from Novavax. M. E. S. had/has grants from the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) during the conduct of the study (5UM1AI069470); grants from NIH/NIAID and Gates Foundation outside the submitted work; and grants to her institution from Merck Sharpe and Dohme, Sanofi, and Gilead outside of the submitted work. S. R. W. has received institutional funding from the NIH/NIAID; institutional grants or contracts from Sanofi Pasteur, Janssen Vaccines/Johnson & Johnson, Moderna Tx, Pfizer, Vir Biotechnology, and Worcester HIV Vaccine; has participated on data safety monitoring or advisory boards for Janssen Vaccines/Johnson & Johnson and BioNTech; and his spouse holds stock/stock options in Regeneron Pharmaceuticals. C. M. E. has received research grants from Merck and AstraZeneca; and has participated in Sanofi, Janssen, and Gilead advisory board meetings. N. R. is a paid safety consultant for ICON, CyanVac, and EMMES; served on selected advisory boards for Sanofi, Seqirus, Pfizer, and Moderna; and receives funds to their institution to conduct research from Sanofi, Lilly, Merck, Quidel, Immorna, Vaccine Company, and Pfizer. C. L. G. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies; and grants to her institution from Gilead and ViiV outside of the submitted work. K. L. K. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689); and from Novavax outside of the submitted work. J. A. G. is employed by and holds stock in AstraZeneca. E. A. H. received fees from Oxford University for time spent adjudicating end points for the AstraZeneca/Oxford SARS-CoV-2 vaccine trials conducted in the UK, South Africa, and Brazil. M. D. T. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

OBJECTIVE: To explore modifiable psychosocial factors, sleep-related variables, indices of central pain processing and patients' characteristics as potential prognostic factors for pain, shoulder function, and quality of life (QoL) 1 year after rotator cuff repair. DESIGN: This observational longitudinal study included 142 patients who were undergoing rotator cuff repair. All measures took place pre-rotator cuff repair (T0), and 12 weeks (T1) and 12 months (T2) after rotator cuff repair. METHODS: Mixed-effects linear regression modeled relationships between the Western Ontario Rotator Cuff Index (WORC, model A), the Subjective Shoulder Value (SSV, model B), and EuroQol's EQ-5D-5L for QoL (model C), and potential prognostic factors over time. Factors included psychosocial variables, sleep-related indices, and proxies of central pain processing. Patients' age, sex, and body mass index complemented the analyses. RESULTS: At follow-up (T2), data from 124 participants were available for analysis. Five prognostic factors were identified for the 1-year outcome. Better expectations for symptom reduction ( P <.0001, -1.4 mm) and an increase in Douleur Neuropathique 4 score ( P = .0481, -0.9 mm) affected the evolution of WORC over time (model A). An increase in injury perception subscale consequence ( P = .0035, 0.04%) influenced the SSV trajectory (model B). In addition, when sleep quality ( P = .0011, -0.13%) and sleep efficiency ( P = .0002, 0.005%) improved, the EQ-5D-5L slope was affected (model C). CONCLUSION: Addressing cognitions, pain mechanisms and sleep behavior prior to rotator cuff repair can identify people who are at risk of a poor outcome after surgery. J Orthop Sports Phys Ther 2024;54(8):530-540. Epub 4 July 2024. doi:10.2519/jospt.2024.12398 .

Background: the pathogenesis of frozen shoulder (FS) is thought to be one of inflammation and fibrosis possibly influenced by hyperglycemia. Biomechanical changes of the shoulder joint in terms of muscle strength, scapular kinematics and proprioception might occur in FS., Objectives: to compare muscle strength, scapular kinematics, proprioception, and blood glucose levels within patients with FS and to asymptomatic individuals., Design: cross-sectional study., Method: Thirty-five patients with FS and 35 asymptomatic age and gender-matched individuals underwent physical assessment to determine muscle strength (abduction, external and internal rotation), scapular kinematics (both visually and with a plurimeter), proprioception (joint position sense), and blood glucose level., Results: Patients with FS showed a decrease in muscle strength in their affected shoulder compared to both the unaffected shoulder and asymptomatic individuals. Significant differences were found between the affected and unaffected shoulder in the FS group and between groups (FS versus controls) in scapular upward rotation (plurimeter) at 30° and 60° abduction. No difference in scapular kinematics (visual observation), proprioception, and blood glucose levels was found neither between shoulders in the FS group nor between groups., Conclusion: A clinically relevant difference in muscle strength and increase in scapular upward rotation were found in the affected shoulder of patients with FS compared to their unaffected side and controls. However, no evidence of different levels of scapular kinematics (visual observation), proprioception, and blood glucose levels in the affected shoulder compared to the unaffected shoulder or controls is lacking., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This systematic review with meta-analysis aimed to assess the effectiveness of electrophysical agents in improving pain, function, disability, range of motion, quality of life, perceived stiffness, and time to recovery in subjects with frozen shoulder (FS)., Methods: A thorough search of MEDLINE, Cochrane Library, PEDro, and EMBASE yielded 1143 articles, of which 23 randomized controlled trials were included. Risk of bias (RoB) was assessed through Cochrane Risk of Bias 2 tool. The certainty of evidence was evaluated through the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)., Results: The analysis included a total of 1073 subjects. None of the studies were judged as low RoB. Potentially clinically significant differences were observed in pain at 6 weeks and 5 months after extracorporeal shockwave therapy (ESWT), and in disability up to 3 months with laser therapy, albeit with uncertain results due to the high RoB and to the study heterogeneity. Ultrasound (US) therapy did not yield significant differences in any outcomes. The certainty of evidence was very low., Conclusions: Based on the high heterogeneity and low quality and certainty of evidence, ESWT, laser, and US cannot be recommended for FS treatment. Caution should be exercised in interpreting the findings.

COVID-19 vaccine boosters may optimize durability of protection against variants of concern (VOCs). In this randomized, double-blind, phase 2 trial, participants received 3 different dose levels of an Ad26.COV2.S booster (5 × 10 10 vp [viral particles], 2.5 × 10 10 vp, or 1 × 10 10 vp) ≥6 months post-primary vaccination with either single-dose Ad26.COV2.S (homologous boost; n = 774) or 2-dose BNT162b2 (heterologous boost; n = 758). Primary endpoints were noninferiority of neutralizing antibody responses at Day 15 post-boost versus Day 29 post-primary vaccination. Secondary endpoints included reactogenicity/safety and neutralizing antibody responses to VOCs. All primary endpoints passed prespecified hierarchical noninferiority criteria by Day 15 post-boost. Geometric mean increases in neutralizing antibody titers against the D614G reference strain ranged from 5.5 to 6.8 at Day 15 for homologous boosting and 12.6 to 22.0 for heterologous boosting. For VOCs, heterologous boosting elicited higher neutralizing antibody responses than homologous boosting. Neutralizing antibody responses were dose-dependent and durable for ≥6 months post-boost. More solicited systemic adverse events occurred following heterologous versus homologous boosting. Trial Registration:ClinicalTrials.gov Identifier: NCT04999111., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MLG, JS, VC, DH, FT, GVR, CS, SSM, OC, TK, FS, HS, and MD are employees of Janssen Pharmaceuticals or were employees at the time this work was conducted and hold shares or restricted shares in Johnson & Johnson. FS holds shares from the GSK group of companies as part of past employee remuneration., (Copyright © 2024. Published by Elsevier Ltd.)

Background: A single dose of Ad26.COV2.S is well-tolerated and effective in preventing moderate-to-severe disease outcomes due to COVID-19. We evaluated the impact of dose level, number of doses, and dose interval on immunogenicity, reactogenicity, and safety of Ad26.COV2.S in adults. Anamnestic responses were also explored., Methods: This randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18-55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 10 10 , 2.5 × 10 10 , 5 × 10 10 , and 1 × 10 11 viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 10 10 vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants., Results: All Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 10 10 vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related., Conclusion: The study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 10 10 vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Vicky Cardenas reports financial support was provided by Johnson & Johnson. Mathieu Le Gars reports financial support was provided by Johnson & Johnson. Carla Truyers reports financial support was provided by Johnson & Johnson. Javier Ruiz-Guinazu reports financial support was provided by Johnson & Johnson. Frank Struyf reports financial support was provided by Johnson & Johnson. Alicia Colfer reports financial support was provided by Johnson & Johnson. Macaya Douoguih reports financial support was provided by Johnson & Johnson. Jerald Sadoff reports financial support was provided by Johnson & Johnson. Marc Bonten reports a relationship with Shionogi, Merck, GSK and Janssen Vaccines that includes: consulting or advisory. Marc Bonten reports a relationship with Sanofi that includes: board membership. Frank Struyf reports a relationship with GSK that includes: equity or stocks. Marc Bonten reports a relationship with Johnson & Johnson, Merck, Sanofi that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity., Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease., Design, Setting, and Participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023., Main Outcomes and Measures: Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis., Results: Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity., Conclusions and Relevance: In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.

Background and Purpose: Frozen shoulder (FS) is defined as a condition characterised by functional restriction and daily and nightly pain. As in other shoulder pathologies, the manifestation of psychological factors is recognised in FS; however, from a psychological point of view, only few studies have reported its prognostic value. The aim of this systematic review is to investigate, in patients with FS, the prognostic value of psychological factors on pain, function, disability, health-related quality of life, return to work and time to recovery., Materials and Methods: This systematic review was reported following the Preferred Reporting Items for Systematic reviews and Meta-Analysis-PRISMA 2020 guideline. The authors followed the Cochrane Handbook for Systematic review of Intervention as methodological guidance. The Quality in Prognostic Studies-QUIPS tool was used to assess the risk of bias., Results: Pain-related fear and depression could be prognostic regarding patient-reported outcome measures assessing shoulder function, disability, and pain; instead, pain catastrophizing could have a prognostic value assessed by the disability of the arm shoulder and hand -DASH scale. Anxiety would appear to impact on disability and pain., Discussion and Conclusions: As widely reported in numerous musculoskeletal conditions, also in FS psychological factors influence the physical dimension such as pain, disability and function. Therefore, clinicians should be encouraged to identify these factors through a comprehensive assessment of the bio-psychological profile of each individual with FS. Perhaps, patients with FS that show such psychological prognostic factors could benefit from a comprehensive and shared approach with other dedicated professionals., (© 2023 John Wiley & Sons Ltd.)

Objectives: This study evaluated the feasibility of exercising into pain in rotator cuff related shoulder pain (RCRSP), data collection procedures, feedback from physiotherapists and patients, and clinically important changes in patient-reported outcome measures (PROMs)., Design: Unblinded non-randomised single-group study., Setting: Physiotherapy clinic in Belgium., Participants: Twelve patients with unilateral RCRSP for minimum 3 months, aged 18-65 years., Interventions: Twelve weeks of four individualised exercises, with nine physiotherapist-led sessions with pain ratings 4-7 out of 10 on a verbal Numeric Pain Rating Scale for 9 weeks and then pain ratings 0-2 for 3 weeks. Every physiotherapy session included 15 min of manual therapy. Non-supervised exercises were: 2×/week in weeks with physiotherapy session, 3×/week in weeks without physiotherapy session., Outcome Measures: Primary: adherence, where patients were considered adherent with 78% (7/9 sessions) attendance for supervised sessions and 81% (22/27 sessions) completion for non-supervised exercises, and Shoulder Pain and Disability Index (SPADI); secondary: fear-avoidance behaviour, fear of pain, physical outcomes (strength, range of motion, scapular dyskinesis); others: ultrasound (US) imaging outcomes (acromionhumeral distance, supraspinatus tendon thickness, occupation ratio), global perceived effect (GPE). PROMs were collected via online survey, except for the GPE (via closed envelope). US measures were taken after physical measures., Results: Adherence and adverse effects were analysed in patients who had the possibility to attend minimum seven supervised sessions (n=8): 88% of them adhered to supervised sessions, 50% to non-supervised exercises; none of them withdrew from the study, three of them obtained individual clinically important improvements in SPADI score above 20 points. The measurement protocol of physical and ultrasonographic outcomes took around 60 min., Conclusions: Adherence to supervised sessions was satisfactory, the adherence to non-supervised exercises must be improved. Data collection procedures were feasible to perform, but some changes are recommended., Trial Registration Number: NCT04154345., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acromiohumeral distance (AHD) and supraspinatus tendon thickness (STT) measured by ultrasound (US) can be combined in the occupation ratio (OR). Inter-rater reliability on these subacromial measures depends on the US experience of raters and on the subject status, differing between asymptomatic or patients with subacromial shoulder pain (SSP)., Objective: To evaluate inter-rater reliability between two raters with different US experience (experienced examiner and novice examiner)., Methods: In total, 20 asymptomatic subjects (controls) and 21 patients with SSP were examined on one shoulder. Inter-rater reliability was evaluated with intraclass correlation coefficient (ICC)., Results: ICC for controls was good for AHD at rest and at 60° (0.76-0.77), moderate for STT and AHD at 60° with weights (0.53-0.72), while OR was poorly reliable (below 0.44). ICC for SSP was moderate for AHD at rest and at 60°, STT, OR at rest and at 60° (0.52-0.74) and poor for AHD at 60° with weights and OR at 60° with weights (0.33-0.36). Bland-Altman plots showed systematic bias., Conclusion: Inter-rater reliability varied largely from poor to good between two examiners with different US experience. Clinicians might use the US as additional tool for detecting the subacromial structures, but a structured training including also symptomatic subjects is suggested. Researchers may further investigate the OR in matched case-control studies, and an overall agreement phase is recommended before starting the inter-rater reliability phase.

Background: Altered central pain processing (CPP) and dysautonomia might play a role in the clinical course of frozen shoulder and psychological factors, like pain catastrophizing and hypervigilance, might influence clinical variables in frozen shoulder., Objectives: To explore the clinical course of frozen shoulder regarding CPP, dysautonomia, pain catastrophizing, and hypervigilance and to explore whether longitudinal correlations between these outcomes and pain intensity were present., Design: prospective longitudinal observational study., Method: Participants with frozen shoulder were recruited at hospitals and general practitioner practices and followed for 9 months. They completed six questionnaires (about demographics, shoulder pain and disability, pain intensity, pain catastrophizing, pain hypervigilance, and autonomic symptoms) and underwent tactile sensitivity (allodynia), pressure pain thresholds (hyperalgesia), temporal summation, and conditioned pain modulation during four timeframes (3-month intervals)., Results: Initially, 149 participants with frozen shoulder were recruited and 88 completed all the measurements. An improvement from baseline to at least one follow-up measurement was found for shoulder pain and disability, pain intensity, pain catastrophizing, hypervigilance, and dysautonomia. A fair longitudinal correlation was found between pain intensity and catastrophizing and hypervigilance (r = 0.301-0.397). Poor longitudinal correlations were found between pain intensity and allodynia and hyperalgesia (r = -0.180-0.193), between pain catastrophizing and dysautonomia (r = 0.209) and between hypervigilance and hyperalgesia (r = -0.159)., Conclusion: Patients with frozen shoulder showed an early improvement that flattened with time in several pain and psychological variables over the course of 9 months. However, autonomic symptoms rather showed a late improvement over 9 months., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection., Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures., Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease., Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection., Funding: National Institutes of Health., Competing Interests: Declaration of interests YiH, CY, TCSM, RMM, HMES, BG, GEG, PBG, JGK, LC, and DF declare no conflicts of interest. AMR declares unrelated grants or contracts from NIAID, I4kids, Society to Improve Diagnosis in Medicine, Beckwith Clinical Innovation Award, CTSI COVID-19 Pilot Award; unrelated consulting fees from Pfizer; unrelated support for attending meetings/travel from IDweek (2023); and an unrelated unpaid leadership role as the medical director of Human Milk Science Institute and Biobank. MBL declares unrelated grants or contracts from NIH VTEU paid to their institution. CaAR declares unrelated grants or contracts paid to their institution from Novavax and Moderna. ChAR declares unrelated grants or contracts paid to their institution from BioFire, Inc, GSK, Merck, Micron, MedImmune, Novavax, PaxVax, Regeneron, Pfizer, Sanofi-Pasteur, Janssen, Moderna, NIH, and CDC; unrelated royalties or licenses from Meissa Vaccines, Inc; and unrelated patent interests for “RSV Live-Attenuated Vaccine Candidates with Deleted G-Protein Mucin Domains” and “Chimeric RSV, Immunogenic, Compositions, and Methods of Use”. LRB declares unrelated grants or contracts paid to their institution from NIH/Harvard Medical School and Wellcome Trust/Gates Foundation; unrelated participation on a Data Safety Monitoring Board or Advisory Board for NIAID and FDA; and unrelated involvement in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), Covid Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School. CLG declares unrelated grants or contracts paid to their institution from NIH. HEJ declares unrelated grants or contracts paid to their institution from NIH; and unrelated participation in multiple NIH-convened DSMBs. YuH declares unrelated grants or contracts paid to their institution from WHO and unrelated participation (with payment) on a Data Safety Monitoring Board or Advisory Board for WHV. BL is an employee of Moderna, Inc. IH is an employee of AstraZeneca and declares unrelated stock options held in AstraZeneca. FS is an employee of Janssen and declares unrelated stock received as compensation for past employment with GlaxoSmithKline. LMD is an employee of Novavax, Inc. KMN declares unrelated grants or contracts from Pfizer (no salary support) and NIH. PAG declares unrelated grants or contracts from NIH and patent interests for “Human monoclonal antibodies to SARS-COV-2 and use thereof”. SRW declares unrelated grants or contracts from Sanofi Pasteur, Moderna, Vir Biotechnology, Worcester HIV Vaccine, Pfizer, and Janssen Vaccines/Johnson & Johnson paid to their institution; unrelated support for attending meetings and/or travel from Sasnofi Pasteur; unrelated participation on a Data Safety Monitoring Board or Advisory Board for Janssen Vaccines/Johnson & Johnson; and that their spouse is an employee that holds stock/stock options at Regeneron Pharmaceuticals. KLK declares unrelated grants or contracts from NIAID. The CoVPN was funded by the NIH., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare disorder described after vaccination with adenoviral vector-based COVID-19 vaccines. Co-occurring thrombosis with thrombocytopenia reported after vaccination can be a proxy for identification of TTS., Methods: Descriptive database review of all cases of co-occurring (within 42 days) thrombosis with thrombocytopenia in participants in Ad26.COV2.S clinical trials or recipients of Ad26.COV2.S in real-world clinical practice. Cases were retrieved from Janssens' clinical trial and Global Medical Safety databases., Results: There were 34 cases of co-occurring thrombosis with thrombocytopenia in Ad26.COV2.S recipients (46 per 100,000 person-years) and 15 after placebo (75 per 100,000 person-years) in clinical trials. Among Ad26.COV2.S recipients, mean age at the time of the event was 63 years (range 25-85), 82 % were male, mean time-to-onset 112 days (range 8-339) post-last Ad26.COV2.S dose, 26 events occurred post-dose-1, and 7 within a 28-day risk window post-vaccination. Diagnostic certainty was evaluated using Brighton Collaboration, US Centers for Disease Control and Prevention, and European Medicines Agency Pharmacovigilance Risk Assessment Committee case definitions. One case met the highest level of diagnostic certainty for all 3 definitions. There were 355 spontaneous reports of co-occurring thrombosis with thrombocytopenia in the Global Medical Safety database, 47 % males, 85 % within 28-days after vaccination. Twenty-seven cases met the highest level of diagnostic certainty for all definitions, 21 female, 19 with cerebral venous sinus thrombosis, age-range 18-68 years. Time-to-onset was 7-14 days post-vaccination in 20 cases. There were 8 fatalities., Conclusion: TTS induced by Ad26.COV2.S is very rare. Most co-occurring thrombosis with thrombocytopenia does not constitute TTS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Frank Struyf reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Karin Hardt reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Rian Van Rampelbergh reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Georgi Shukarev reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Ajinkya Inamdar reports a relationship with Johnson & Johnson that includes: employment. Javier Ruiz-Guinazu reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Vitalija van Paassen reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Luis Anaya-Velarde reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Camellia Diba reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Marc Ceuppens reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Vicky Cardenas reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Jerald Sadoff reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Macaya Douoguih reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Gerald A. Soff reports a relationship with Johnson & Johnson that includes: board membership and funding grants. Gerald A. Soff reports a relationship with Amgen that includes: funding grants. Gerald A. Soff reports a relationship with Anthos Therapeutics Inc that includes: funding grants. Gerald A. Soff reports a relationship with Dova Pharmaceuticals that includes: board membership and funding grants. Gerald A. Soff reports a relationship with Sanofi that includes: board membership. Gerald A. Soff reports a relationship with Luzsana (HengruiUSA) iotechnology that includes: board membership., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Contradictory evidence exists regarding the clinical course of frozen shoulder (FS)., Objectives: To explore the clinical course of FS regarding disabilities, pain, range of motion (ROM), muscle strength, scapular upward rotation, and proprioception and to establish longitudinal correlations between these variables., Methods: Patients with FS were prospectively followed for 9 months at 3-month intervals. Assessment included the Disabilities of the Arm, Shoulder and Hand questionnaire; visual analogue scale for pain; an inclinometer for shoulder external rotation (ER), internal rotation (IR), flexion, and abduction ROM, and scapular upward rotation and proprioception, as well as handheld dynamometry for muscle strength in shoulder abduction, ER, and IR., Results: Initially, 149 patients (98 females; mean (SD) age 53 (9) years) were included, with 88 completing all follow-up assessments. Most variables showed early improvement in the clinical course of FS, particularly ER and IR at 90° abduction, which continued to improve from 6 to 9 months of follow-up. Associations were observed between disabilities and pain (r = 0.61), disabilities/pain and ROM (r=-0.62 to -0.59 and r=-0.47 to -0.39, respectively), disabilities/pain and muscle strength (r=-0.24 to -0.35 and r=-0.36 to -0.17, respectively), and between disabilities/pain and scapular upward rotation below shoulder level (r = 0.23 to 0.38 and r = 0.24 to 0.30, respectively). ROM correlated with muscle strength (r = 0.14 to 0.44), while both ROM and ER muscle strength correlated with scapular upward rotation below shoulder level (r=-0.37 to -0.23 and r=-0.17 to -0.12, respectively). Muscle strength correlated with scapular upward rotation above shoulder level (r = 0.28 to 0.38) and lift-off muscle strength correlated with joint repositioning (r=-0.17 to -0.15)., Conclusion: Almost all factors improved in the early phase (3-6 months) after baseline assessment, while ER and IR ROM at shoulder level continued to improve long term., Competing Interests: Conflicts of interest Nothing to declare., (Copyright © 2023 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3)., Methods: This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18-40 years) and 1005 older adults (OAs; aged 60-80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination., Results: The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation., Conclusions: Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development., Clinical Trials Registration: NCT03814590., Competing Interests: Potential conflicts of interest. D. C., M.-P. D., M. d. H., N. D. S., N. D., L. F., V. H., J. K., N. M., B. S., F. S., J. T., C. V. A., and C. Ve. are/were employees of the GSK group of companies at the time of the study conduct. C. Va. is currently an employee of the GSK group of companies. D. C., M.-P. D., M. d. H., N. D. S., N. D., B. S., F. S., and C. Ve. hold shares from the GSK group of companies as part of their past/current employee remuneration. F. S. is currently an employee of Janssen Pharmaceutical Companies of Johnson & Johnson and holds restricted shares from Johnson & Johnson as part of his employee remuneration. All current/previous employees of the GSK groups of companies declare financial and nonfinancial relationships and activities. C. P. A., E. K., I. L.-R., K. S., and C. Va. report grant/research support from the GSK group of companies to their institution for study conduct and, except for C. Va., they have no nonfinancial relationships and activities to declare. E. K. has served as consultant, in advisory boards, in speaker’s bureaus, or received travel reimbursement from Amphastar, AstraZeneca, Boehringer Ingelheim, Forest, Cipla, Chiesi, GSK, Mylan, Novartis, Sunovion, Teva, Pearl Pharmaceuticals, and Theravance. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Massive irreparable rotator cuff tears can cause significant shoulder pain, disability and reduction in quality of life. Treatment approaches can be operative or non-operative. Operative approaches include reverse total shoulder arthroplasty, arthroscopic debridement, partial rotator cuff repair, subacromial balloon spacers, superior capsule reconstruction, and tendon transfer procedures. Non-operative approaches include physiotherapy exercise programs and corticosteroid injections. There are no randomized controlled trials comparing the different treatment approaches. It is therefore challenging for clinicians to advise patients on what is their best treatment pathway. Physiotherapy exercise programs are less expensive and have lower risks for patients than surgical approaches. However, the success of physiotherapy in patients with massive irreparable rotator cuff tears is highly variable with published success rates of 32-96%. Several cohort studies have sought to identify if certain factors are predictive of success with physiotherapy. Several biomechanical factors were identified as possibly being related to a successful or unsuccessful outcome following physiotherapy, with complete tear of subscapularis demonstrating the strongest evidence. However, there were no appropriately designed prognostic studies. There has been a strong emphasis on biomechanical factors. Other domains such as psychosocial factors, which are important in similar patient populations, have not been explored. We recommend that further research is needed in this area and should include randomized controlled trials comparing treatment approaches and longitudinal prospective prognostic studies to identify predictors of treatment success.

This study investigated the intra-rater reliability of a novice ultrasound (US) examiner and the inter-rater reliability of two examiners (novice, expert) in the measures of coracohumeral distance at rest (CHD) and at 60° of elevation without (CHD60) or with weights (CHD60w), tendon thickness of the long head of the biceps (LHB) and subscapularis (SCP). Twenty-one patients with subacromial pain syndrome (SAPS) and 20 asymptomatic participants were included. Intra and inter-rater reliability were tested with intraclass-correlation-coefficient (ICC), differences between raters were analyzed with Bland-Altman plots. Intra-rater reliability for CHD, CHD60 and CHD60w was excellent (ICC = 0.97-0.98) in asymptomatic participants, and good-to-excellent (0.88-0.93) in SAPS, while intra-rater reliability for LHB and SCP was good-to-excellent in asymptomatic participants (0.88-0.97) and in SAPS (0.90-0.92). Inter-rater reliability for CHD, CHD60 and CHD60w was moderate-to-good (0.70-0.90) in asymptomatic participants and good (0.85-0.87) in SAPS, in contrast inter-rater reliability for LHB and SCP was poor in asymptomatic participants (0.10-0.46) and poor-to-moderate (0.49-0.61) in SAPS. Bland-Altman plots revealed systematic and/or proportional bias for tendons' thickness. A novice showed good-to-excellent intra-rater reliability in all US measures, whereas in comparison to an expert a novice can measure reliably CHD, CHD60 and CHD60w, but not LHB and SCP, where more training is recommended., (© 2023. The Author(s).)

Stroke is a common pathology worldwide, with an age-standardized global rate of new strokes of 150.5 per 100,000 population in 2017. Stroke causes upper motor neuron impairment leading to a spectrum of muscle weakness around the shoulder joint, changes in muscle tone, and subsequent soft tissue changes. Hemiplegic shoulder pain (HSP) is the most common pain condition in stroke patients and one of the four most common medical complications after stroke. The importance of the appropriate positioning and handling of the hemiplegic shoulder for prevention of HSP is therefore of high clinical relevance. Nevertheless, HSP remains a frequent and disabling problem after stroke, with a 1-year prevalence rate up to 39%. Furthermore, the severity of the motor impairment is one of the most important identified risk factors for HSP in literature. Spasticity is one of these motor impairments that is likely to be modifiable. After ruling out or treating other shoulder pathologies, spasticity must be assessed and treated because it could lead to a cascade of unwanted complications, including spastic HSP. In clinical practice, Botulinum toxin A (BTA) is regarded as the first-choice treatment of focal spasticity in the upper limb, as it gives the opportunity to target specifically selected muscles. It thereby provides the possibility of a unique patient tailored focal and reversible treatment for post stroke spasticity. This scoping review aims to summarize the current evidence of BTA treatment for spastic HSP. First, the clinical manifestation and outcome measures of spastic HSP will be addressed, and second the current evidence of BTA treatment of spastic HSP will be reviewed. We also go in-depth into the elements of BTA application that may optimize the therapeutic effect of BTA. Finally, future considerations for the use of BTA for spastic HSP in clinical practice and research settings will be discussed.

Background: Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose., Methods: ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing., Findings: Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36·0 (15·0-62·0) days. Vaccine efficacy was 75·2% (adjusted 95% CI 54·6-87·3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55·6%] of 3015 vs 896 [57·5%] of 1559, respectively; systemic adverse events, 1764 [58·5%] of 3015 vs 821 [52·7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity., Interpretation: A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed., Funding: Janssen Research & Development., Competing Interests: Declaration of interests KH, AV, JS, MLG, JV, TK, GS, HS, JVH, MD, and FS are employees of Johnson & Johnson and hold Johnson & Johnson stock or stock options. FS is a former employee of GlaxoSmithKline and holds shares from the GlaxoSmithKline group of companies as part of past employee remuneration. CT and IVD are employees of Johnson & Johnson. DL is an employee of Johnson & Johnson and Cytel. JR-G is an employee of Johnson & Johnson and holds Johnson & Johnson stock or stock options; he is a former employee of GlaxoSmithKline, holds GlaxoSmithKline stock or stock options, and has received funding grants from GlaxoSmithKline Vaccines. CDS has received funding grants for research from Janssen-Cilag, AbbVie, Apeiron, B.Braun, Cepheid, Eli Lilly, GlaxoSmithKline, Corat Therapeutics, Gilead, Merck Sharpe & Dohme, Roche, and ViiV Healthcare; and consulting fees, honoraria, and travel support from AbbVie, Cepheid, Formycon, Gilead, GlaxoSmithKline, Molecular Partners, Merck Sharpe & Dohme, Swedish Orphan Biovitrium, Roche, and ViiV Healthcare. SNF has received research grants to his institution from Janssen–Johnson & Johnson, Pfizer, Sanofi, GlaxoSmithKline, Merck, AstraZeneca, and Valneva (no personal fees); has received consulting fees from Janssen–Johnson & Johnson, GlaxoSmithKline, and CureVac; has received fees to his institution for participation on data safety monitoring boards or advisory boards from AstraZeneca, Medimmune, Sanofi, Pfizer, Seqirus, Sandoz, Merck, and Janssen–Johnson & Johnson; and was chair of two UK National Institute for Health and Care Excellence (NICE) sessions (expenses paid per NICE financial regulations)., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.)