Active Treatment Research Articles

DNA-sensing inflammasomes cause recurrent atherosclerotic stroke

The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies1. Risk is particularly high in patients with atherosclerosis, with more than 10% of patients experiencing early recurrent events1,2. However, despite the enormous medical burden of this clinical phenomenon, the underlying mechanisms leading to increased vascular risk and recurrent stroke are largely unknown. Here, using a novel mouse model of stroke-induced recurrent ischaemia, we show that stroke leads to activation of the AIM2 inflammasome in vulnerable atherosclerotic plaques via an increase of circulating cell-free DNA. Enhanced plaque inflammation post-stroke results in plaque destabilization and atherothrombosis, finally leading to arterioarterial embolism and recurrent stroke within days after the index stroke. We confirm key steps of plaque destabilization also after experimental myocardial infarction and in carotid artery plaque samples from patients with acute stroke. Rapid neutrophil NETosis was identified as the main source of cell-free DNA after stroke and NET–DNA as the causative agent leading to AIM2 inflammasome activation. Neutralization of cell-free DNA by DNase treatment or inhibition of inflammasome activation reduced the rate of stroke recurrence after experimental stroke. Our findings present an explanation for the high recurrence rate after incident ischaemic events in patients with atherosclerosis. The detailed mechanisms uncovered here provide clinically uncharted therapeutic targets for which we show high efficacy to prevent recurrent events. Targeting DNA-mediated inflammasome activation after remote tissue injury represents a promising avenue for further clinical development in the prevention of early recurrent events.

A Meta-Analysis of Interpersonal and Psychodynamic Psychotherapies for Posttraumatic Stress Disorder.

Established trauma-focused cognitive-behavioral therapies for posttraumatic stress disorder (PTSD) have remission rates of approximately 30%-40%. Alternatively, interpersonal psychotherapy (IPT) and psychodynamic psychotherapy (PDT) focus on disrupted attachment, mentalization, and social connection in PTSD and may help some patients. The authors conducted a meta-analysis on these interpersonal and affect-oriented approaches to treating PTSD. Building on a prior meta-analysis, the authors searched for randomized controlled trials (RCTs) comparing IPT or PDT with other established PTSD treatments or control conditions for adults diagnosed as having PTSD. Random-effects meta-analyses were conducted to assess outcome effect sizes and dropout rates. RCTs were rated via the Randomized Controlled Trial Psychotherapy Quality Rating Scale. Ten RCTs (eight of IPT) comparing IPT or PDT with control (k=7) or active treatment (k=4) conditions were identified, nine of which were of adequate quality. IPT (k=5) and PDT (k=2), when analyzed together, were superior to control conditions overall (g=-1.14, p=0.011 [as was IPT alone: g=-0.88, p=0.034]) and to waitlist (g=-1.49) and treatment-as-usual (g=-0.70) groups. Effect sizes, however, may have been inflated by outliers or publication bias. IPT (k=3) and PDT (k=1), when analyzed together, were equally efficacious compared with other active PTSD treatments (primarily exposure-based psychotherapies), as was IPT alone, and had lower dropout rates (relative risk=0.63, p=0.049 for IPT and PDT analyzed together; relative risk=0.61, p=0.098 for IPT alone). Affect-focused therapies hold promise in the treatment of PTSD. IPT has demonstrated efficacy in multiple trials, whereas the evidence base for PDT is sparse.

Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.

For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.

Reduction of N-Acetylglucosaminyltransferase-I Activity Promotes Neuroblastoma Invasiveness and EGF-Stimulated Proliferation In Vitro

Aberrant N-glycosylation has been associated with progression of the pediatric cancer neuroblastoma (NB) but remains understudied. Here we investigated oligomannose N-glycans in NB by genetic editing of MGAT1 in a human NB cell line, BE(2)-C, called BE(2)-C(MGAT1−/−). Lectin binding studies confirmed that BE(2)-C(MGAT1−/−) had decreased complex and increased oligomannose N-glycans. The relevance of 2D and 3D cell cultures was demonstrated for cell morphology, cell proliferation, and cell invasion, thereby highlighting the necessity for 3D cell culture in investigating cancerous properties. Western blotting revealed that oligomannosylated EGFR had increased autophosphorylation. Proliferation was decreased in BE(2)-C(MGAT1−/−) using 2D and 3D cultures, but both cell lines had similar proliferation rates using 3D cultures without serum. Upon EGF treatment, BE(2)-C(MGAT1−/−), but not BE(2)-C, showed increased proliferation, and furthermore, the mutant proliferated much faster than BE(2)-C under 3D conditions. Cell spheroid invasiveness was greatly increased in BE(2)-C(MGAT1−/−) compared with BE(2)-C. Moreover, invasiveness was reduced in both cell lines with either EGF or RhoA activator treatment, regardless of the N-glycan population. Thus, this study further extends our earlier findings that oligomannose N-glycans enhance NB cell invasiveness, and that EGF stimulation of oligomannosylated EGFR greatly enhances cell proliferation rates, underlining the role of oligomannose N-glycans in the promotion of NB.

Neuroplasticity in Parkinson's disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, affecting millions of people and rapidly increasing over the last decades. Even though there is no intervention yet to stop the neurodegenerative pathology, many efficient treatment methods are available, including for patients with advanced PD. Neuroplasticity is a fundamental property of the human brain to adapt both to external changes and internal insults and pathological processes. In this paper we examine the current knowledge and concepts concerning changes at network level, cellular level and molecular level as parts of the neuroplastic response to protein aggregation pathology, synapse loss and neuronal loss in PD. We analyse the beneficial, compensatory effects, such as augmentation of nigral neurons efficacy, as well as negative, maladaptive effects, such as levodopa-induced dyskinesia. Effects of physical activity and different treatments on neuroplasticity are considered and the opportunity of biomarkers identification and use is discussed.

Enhanced passivity of reinforcing steel in cementitious materials with thermally-activated red mud

Red mud (RM) is a solid waste from aluminium industry that can be used as an emerging supplementary cementitious material, and it has beneficial effects on the corrosion resistance of reinforcing steel in concrete. However, the low reactivity of RM reduces the comprehensive performance of cementitious materials, thereby limiting its widespread application in concrete. In this study, RM was thermally activated and the phase transformation behavior of the thermally-activated RM (TA-RM) was studied. Additionally, the passivation behavior of steel in extract solutions and mortars containing RM with and without thermal activation was investigated using electrochemical methods, surface characterization techniques and compositional analysis. The results showed that the reactivity of RM was effectively improved by the thermal activation treatment due to the phase transformation, and the enhanced steel passivity was observed in both extract solution and mortar with TA-RM. Compared to steel exposed to extract solutions, the mortar containing TA-RM could provide an additional protection for the embedded steel by forming a compact steel-mortar interface, further improving its passivation ability.

Oculomotor nerve palsy caused by imidacloprid at initial diagnosis: A case report.

Amid the pervasive deployment of imidacloprid, the incidence of poisoning from this compound has risen markedly. Those afflicted with imidacloprid poisoning typically exhibit symptoms ranging from headaches, dizziness, nausea, and abdominal pain, to impaired consciousness and breathlessness, yet instances of ocular paralysis induced by this toxin have not previously been documented. When the pesticide spray inadvertently made contact with the patient's eyes, they were seared with a burning sensation and discomfort. Subsequent to this incident, on the second day, the individual began to experience diplopia in the right eye and found it arduous to elevate his eyelids, indicating a challenge in achieving full extension. Based on the medical history, symptoms, and signs, the patient was diagnosed with oculomotor nerve palsy caused by imidacloprid. The treatment involved intravenous dexamethasone to reduce inflammatory response in the eye tissue; oral pantoprazole enteric-coated tablets to suppress acid production and protect the stomach; Xuesaitong administered intravenously to improve blood supply to the eye and promote metabolism of toxins; vitamin C, cobamamide, and vitamin B1 for nerve nutrition and antioxidant effects; local application of tobramycin-dexamethasone eye drops for anti-inflammatory purposes; and repeated flushing of the conjunctival sac with saline. Finally, the patient improved and was discharged. After active treatment, the patient finally improved diplopia and ptosis. This report marks the first documentation of oculomotor nerve palsy induced by imidacloprid, featuring diplopia, and blepharoptosis without substantial limitation of ocular motility. Following therapeutic intervention, the patient showed marked improvement and was discharged from the hospital, providing a point of reference for the treatment of analogous cases in future clinical practice. It also serves as a reminder for the public to take appropriate precautions when using imidacloprid.

Experiences and meaningfulness of breast cancer survivorship care in improving the quality of life of immigrant women: A qualitative systematic review.

Holistic healthcare approaches tailored to people's needs can enhance quality of life. However, needs of immigrant women in breast cancer survivorship have received little attention. Language barriers can result in significant challenges to accessing healthcare and difficulty in translating information from healthcare providers into self-management. The purpose of this review was to examine the experiences and meaningfulness of breast cancer survivorship care in improving the quality of life for immigrant breast cancer survivors. A qualitative systematic review using a systematic search of peer-reviewed and non-peer-reviewed articles of empirical research was conducted. Articles about immigrant women who were diagnosed, treated, and completed their initial course of breast cancer treatment were included. Exclusion criteria were non-immigrant women, men, younger than 18 years, no breast cancer diagnosis, not currently undergoing active or advanced treatment, and not receiving palliative or end-of-life care. Thematic synthesis and qualitative systematic review included studies of survivorship care targeting breast cancer treatment and post-treatment. Articles were obtained from PubMed/MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, and Google Scholar searches, with findings configured according to the JBI methodology. Twenty studies, most of moderate-to high-quality were included. The thematic synthesis identified two overall themes regarding breast cancer survivorship care, as well as subthemes for both. The subthemes of the first theme, challenges and experiences accessing and using healthcare services, were inadequate insurance and benefits, less acculturation and decision-making, discrimination and differential treatment, and influencing sociocultural factors. The subthemes of the second theme, facilitators and barriers to accessing and using healthcare services, included ineffective knowledge and communication, lack of continuity and information, cultural and language barriers, limited access to services, and quality of care. Supporting and engaging immigrant women throughout their breast cancer journey is critical. To do so requires integrating advancements in survivorship care as a systematic approach to lead to a better quality of life and improving patient-reported outcomes.

Materials based on biodegradable polymers chitosan/gelatin: a review of potential applications.

Increased mass manufacturing and the pervasive use of plastics in many facets of daily life have had detrimental effects on the environment. As a result, these worries heighten the possibility of climate change due to the carbon dioxide emissions from burning conventional, non-biodegradable polymers. Accordingly, biodegradable gelatin and chitosan polymers are being created as a sustainable substitute for non-biodegradable polymeric materials in various applications. Chitosan is the only naturally occurring cationic alkaline polysaccharide, a well-known edible polymer derived from chitin. The biological activities of chitosan, such as its antioxidant, anticancer, and antimicrobial qualities, have recently piqued the interest of researchers. Similarly, gelatin is a naturally occurring polymer derived from the hydrolytic breakdown of collagen protein and offers various medicinal advantages owing to its unique amino acid composition. In this review, we present an overview of recent studies focusing on applying chitosan and gelatin polymers in various fields. These include using gelatin and chitosan as food packaging, antioxidants and antimicrobial properties, properties encapsulating biologically active substances, tissue engineering, microencapsulation technology, water treatment, and drug delivery. This review emphasizes the significance of investigating sustainable options for non-biodegradable plastics. It showcases the diverse uses of gelatin and chitosan polymers in tackling environmental issues and driving progress across different industries.

‘Just because I have prostate cancer doesn’t mean that I can’t do things’ – men’s experiences of the acceptability of an exercise intervention for prostate cancer during treatment

BackgroundStructured exercise has an important role in mitigating the extensive side effects caused by ongoing prostate cancer treatments, specifically androgen deprivation therapy (ADT) and radiation therapy (RT). Little is known about men’s experiences of, and preferences for, structured exercise programmes during active cancer treatment. This study aimed to inform the acceptability of a 6-month supervised intervention that emphasised increasing and varied intensities of aerobic and resistance exercise, by exploring the experiences of men who participated.MethodsIndividual semi-structured interviews were conducted with an interviewer independent of the exercise study and data was analysed using a descriptive qualitative design.ResultsTwelve prostate cancer patients were interviewed including participants who completed (n = 9) and withdrew from (n = 3) the intervention. Four main themes captured how men experienced the intervention: (1) Navigating the Unknown: Building confidence amidst vulnerability (subtheme- pushing the limits), (2) Building Trust: The credibility and approach of the exercise instructor (subtheme- appropriateness of supervised vs. independent exercise), (3) Flexibility in Delivery, (4) Finding Purpose: Exercise as a means of escapism and regaining control during treatment.ConclusionWhile an initial lack of self-confidence can be a barrier to exercise participation, exercise programmes have the potential to provide psychosocial benefits, rebuild confidence and empower men throughout their cancer treatment and into recovery. Structured exercise is acceptable during treatment including RT and can offer a form of escapism and sense of control for men navigating their cancer journey. Trust building, flexible delivery and credibility alongside a challenging exercise prescription are important facilitators of acceptability for men. Strategies to embed exercise from the point of diagnosis through ADT and RT should reflect men’s experiences of exercise during treatment.Trial registrationThe trial has been registered on ClinicalTrials.gov as of the 14th of December 2021 (NCT05156424).

Using virtual patient cohorts to uncover immune response differences in cancer and immunosuppressed COVID-19 patients.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in millions of deaths globally. Adults with immunosuppression (e.g., solid organ transplant recipients) and those undergoing active cancer treatments experience worse infections and more severe COVID-19. It is difficult to conduct clinical studies in these populations, resulting in a restricted amount of data that can be used to relate mechanisms of immune dysfunction to COVID-19 outcomes in these vulnerable groups. To study immune dynamics after infection with SARS-CoV-2 and to investigate drivers of COVID-19 severity in individuals with cancer and immunosuppression, we adapted our mathematical model of the immune response during COVID-19 and generated virtual patient cohorts of cancer and immunosuppressed patients. The cohorts of plausible patients recapitulated available longitudinal clinical data collected from patients in Montréal, Canada area hospitals. Our model predicted that both cancer and immunosuppressed virtual patients with severe COVID-19 had decreased CD8+ T cells, elevated interleukin-6 concentrations, and delayed type I interferon peaks compared to those with mild COVID-19 outcomes. Additionally, our results suggest that cancer patients experience higher viral loads (however, with no direct relation with severity), likely because of decreased initial neutrophil counts (i.e., neutropenia), a frequent toxic side effect of anti-cancer therapy. Furthermore, severe cancer and immunosuppressed virtual patients suffered a high degree of tissue damage associated with elevated neutrophils. Lastly, parameter values associated with monocyte recruitment by infected cells were found to be elevated in severe cancer and immunosuppressed patients with respect to the COVID-19 reference group. Together, our study highlights that dysfunction in type I interferon and CD8+ T cells are key drivers of immune dysregulation in COVID-19, particularly in cancer patients and immunosuppressed individuals.

Food allergy yardstick: Where does omalizumab fit?

Food allergy management has greatly evolved in the last several years, moving from passive approaches, such as strict food allergen avoidance, to more active treatments, including regulatory approval of the first specifically indicated immunotherapy product (for peanut) in 2020. In 2024, a second therapy, omalizumab, received regulatory approval for the treatment of 1 or more IgE-mediated food allergies, providing clinicians with multiple treatment options to offer patients and families. With this expanded armamentarium of food allergy treatment options, the practicing clinician requires detailed knowledge of benefits and risks of omalizumab, how omalizumab fits into the management landscape, and how to use shared decision-making to optimize therapy. This yardstick aims to provide the clinician with a review of data leading to omalizumab's food allergy indication and an evidence-based expert opinion approach regarding on how best to use this and other therapies available to optimize patient management.

Analysis of factors selectively related to herpes zoster involving peripheral sensory ganglia: Retrospective study.

Herpes zoster (HZ), resulting from the reactivation of the varicella-zoster virus, is a significant disease. This study aimed to explore the factors influencing sensory neuron involvement in HZ at different locations and its association with postherpetic neuralgia (PHN). A total of 3143 cases were retrieved from an electronic medical record system, including 2676 cases of HZ and 467 cases of PHN. Gender, age, site of onset, past surgical history, and comorbidities were analyzed using a multifactorial logistic regression model. The results revealed correlations between age, gender, comorbidities (diabetes, coronary heart disease, percutaneous coronary intervention [PCI]), and sensory neuron involvement in HZ. Specifically, older age, female gender, and comorbid conditions such as diabetes/coronary heart disease were associated with sacral dorsal root ganglion (DRG) involvement, while PCI history was associated with lumbar DRG involvement. Additionally, sensory neuron involvement at different locations by HZ was linked to PHN. Furthermore, independent risk factors for PHN included thoracic DRG involvement, older age, and comorbidities (diabetes, surgical history, malignancy). It is crucial to prevent damage to the DRG, especially in individuals with comorbidities, through activities avoidance and active treatment, to minimize the occurrence of PHN.

Bibliometric analysis of research on osteoarthritis and extracellular vesicles: Trends and frontiers

Extensive research has made significant progress in exploring the potential application of extracellular vesicles (EV) in the diagnosis and treatment of osteoarthritis (OA). However, there is current a lack of study on bibliometrics. In this study, we completed a novel bibliometric analysis of EV research in OA over the past two decades. Specifically, we identified a total of 354 relevant publications obtained between January 1, 2003 and December 31, 2022. We also provided a description of the distribution information regarding the countries or regions of publication, institutions involved, journals, authors, citations, and keywords. The primary research focuses encompassed the role of extracellular vesicles in the diagnosis of OA, delivery of active ingredients, treatment strategies, and cartilage repair. These findings highlight the latest research frontiers and emerging areas, providing valuable insights for further investigations on the application of extracellular vesicles in the context of osteoarthritis.

FASTOCH: Feasibility of Electronic Patient-Reported Outcomes in Older Patients With Cancer-A Multicenter Prospective Study.

Multiple studies have demonstrated that electronic patient-reported outcomes (ePROs) improve overall survival and quality of life in cancer care. However, there are no specific prospective data on remote ePRO monitoring in the older population, although they represent a significant proportion of patients with cancer. From February 2021 to April 2022, patients age 75 years and older under active anticancer treatment were consecutively recruited in six institutions. Remote ePRO feasibility was determined in intention-to-test (ITT) on the basis of the number of active users in the overall population. Primary failure applied to patients who had no Internet access or declined to test ePROs, while the other patients were assigned to the ITT population. Feasibility was also determined per-protocol on the basis of the number of active patients in the ITT population. Of the 473 patients included, primary failure applied to 288 patients (233 of whom had no Internet access). Among the 185 patients in ITT, 122 used ePROs, leading to a 26% feasibility in ITT and a 66% feasibility per protocol. In a multivariate analysis, the intent to test population was from a higher socioprofessional category (P = .009) and felt in better general condition in the Geriatric 8-score evaluation (P = .002). Active patients significantly differed from the inactive on their self-assessment of a better general condition (P < .001) only. Our multicenter study showed a limited feasibility rate (26%) of remote ePROs monitoring for older patients with cancer, mainly because of technology barriers. Yet, among the patients who did have Internet access, most of them indeed used ePROs (66%). Given the expected benefit of ePROs, the technology barriers therefore need to be lifted to improve cancer care in older patients.

Clinical stage IIA/B seminoma - to do or not to do: the role of retroperitoneal lymphadenectomy

About 10% of patients with seminomatous testicuar germ cell tumors are diagnosed with clinical stage II/B. The current guideline recommended treatment options include systemic chemotherapy with 3 cycles PEB or radiation therapy with 30 Gy for CS IIA and 36 Gy for CS IIB. Despite a high cure rate of 90-94% and 82-90% for CS IIA and CS IIB, respectively, both options are associated with a high rate of treatment-associated long-term toxicities. A significantly increased risk for the development of secondary malignancies, cardiovascular and metabolic disease as well as an increased for treatment-associated mortality has been proven in various studies. Primary nerve sparing retroperitoneal lymph node dissection (nsRPLND) has been evaluated in 5 prospective and retrospective clinical studies and it has emerged as a valid treatment alternative. The relapse-rate after a median follow-up of 25-33 months is in the range of 11-30%, so that 70-90% of patients are cured without being subjected to chemotherapy and potential long-term toxicities. All relapsing patients have been cured with secondary salvage chemotherapy. The frequency of significant surgery-associated complications is low with 3-13%. Therapeutic success depends on the surgical experience of the various surgeons and the chosen template, so that this type of surgical interventions should only be performed in centres of excellence with dedicated surgeons. Preoperative evaluation of the new biomarker miR371 has been shown to predict the presence of metastatic disease with an accuracy of around 100% so that this marker might be used in daily routine prior to active treatment in CS IIA/B seminomas.

A randomised, parallel-group, double-blind, placebo-controlled phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis: DAISY study design and rationale.

The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY). DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints). The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc.

The Incidence of Extreme Serum Prostate Specific Antigen Levels During the COVID-19 Pandemic

ObjectiveThe COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. Materials and MethodsThis was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. ResultsWe identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration). ConclusionsThe COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial

ObjectivesTo investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional...

Benefits of Targeted Vibration for Bone Strength and Bone Density in Postmenopausal Women with Osteopenia: A Randomized, Sham-Controlled Trial

Abstract Postmenopausal women are at increased risk of fractures due to higher bone turnover that accompanies reduced estrogen production. Vibration may be an effective intervention for maintaining bone strength and bone density. The Osteoboost Belt is a wearable, home-use device that delivers targeted vibration to the lumbar spine and hips. This randomized, sham-controlled trial evaluated the safety and effectiveness of targeted vibration on bone strength and density in postmenopausal women with osteopenia. Participants (n = 126) were randomized (1:1) to receive the Active (vibration therapy device) or Sham (inactive device) treatment for 30 minutes/day over 12 months. At baseline and 12 months, computed tomography scans of the lumbar spine were analyzed to measure finite element analysis-assessed vertebral bone compressive strength (vertebral strength) and volumetric bone mineral density (vBMD) of the L1 vertebra. The primary endpoint, the difference in percentage change of vertebral strength between the Active (-1.40%, [95% CI: -2.73, -0.08]) and Sham (-2.74% [-4.04, -1.43]) groups in the modified intent-to-treat population, did not reach statistical significance (relative benefit: +1.33% [-0.57, 3.24], P=.17). However, a statistically significant benefit of targeted vibration was observed for participants who met the prespecified per-protocol compliance criterion (averaged ≥3 treatment sessions/week): -0.48% [-2.12, 1.17]) and -2.84% [-4.21, -1.47] (n = 73, P=.028) for Active and Sham groups, respectively. Similarly, in this compliant cohort, targeted vibration provided a statistically significant benefit on vertebral bone density, with the percentage change in vBMD of -0.29% [-1.28, 0.70] and -1.97% [-2.92, -1.01] (P=.016) for the Active and Sham groups, respectively. The vibration therapy was well-tolerated, and there were no serious device-related adverse events. These results demonstrate that targeted vibration is safe and, in adherent individuals, can significantly mitigate the decline in vertebral bone strength and vertebral bone density in postmenopausal women with osteopenia.