Randomized Comparative Trials Research Articles

Comparison of adjuvant targeted and anti-PD1 immunotherapy in BRAF-mutated stage III cutaneous melanoma: Retrospective, single center cohort study.

e21558 Background: Targeted therapy (TT) and anti-PD1 immunotherapy (IT) are standard of adjuvant stage III melanoma treatment. However, no comparative prospective randomized trials (head-to-head) were conducted. Data limited to a few retrospective studies. Both treatment regimens were registered in Russia in 2019. We aimed to compare adjuvant options in Russian melanoma pts. Methods: We conducted a single-center retrospective observational study approved by the IRB. We included all pts age 18 and older (one patient, female, was 14) with BRAF-mutated stage III melanoma who were treated at the N.N.Blokhin NMRC of Oncology MoH and received adjuvant therapy between Jan 2019 and Dec 2022. The primary endpoint was RFS, the secondary endpoint - OS. Cox regression analysis was used to identify prognostic factors for RFS (including substage, thickness and ulceration of primary tumor). Results: A total of 209 pts were included, mostly BRAF V600E/K, 92 (44%) male and 117 (56%) female. Median age was 50,6 years (range: 14-81). 93 (44,4%) pts received TT, 103 (49,3%) pts received IT and 13 (6,3%) didn’t receive adjuvant therapy (observation only). The observation group wasn’t analyzed due to a small number of pts. At a median follow-up of 27 mo, median RFS was 30 mo (95% CI 23-56) in TT group and wasn’t reached in IT group; median OS wasn’t reached in both groups. There weren’t statistical differences between TT and IT groups in RFS (HR 0,84, 95% CI 0,53-1,34, p = 0,47) and OS (HR 0,59, 95% CI 0,26-1,34, p = 0,21), even though at 12 mo, the rate of RFS was higher in the TT group (91.4%) compared IT group (67%), at 18 mo – 79,5% and 63,1%, 24 mo – 68,8% and 61,1% respectively. TT group had numeric but not significant RFS benefit in most subgroups. HR values for substage, thickness and ulceration are presented in the table below. Tx+T0 pts (TT, n = 7; IT, n = 13) and unknown status of ulceration (TT, n = 7; IT, n = 16) was not presented for some pts. Conclusions: Differences between TT and IT wasn't reached at a median follow-up of 27 mo. But IT-treated pts had more and earlier recurrences than TT pts. In BRAF mutated pts, adjuvant TT might prevent early recurrences more effectively than IT. These results need to be interpreted with caution given its retrospective and non-randomized nature and potential selection biases. Additional time to follow-up and biomarker analysis was planned. [Table: see text]

Effectiveness of cyclin-dependent kinase 4 and 6 inhibitors for the treatment of hormonesensitive HER2-negative metastatic breast cancer in first-line therapy: A systematic literature review

At present, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib, ribociclib, and abemaciclib are widely used for the first-line treatment of locally advanced or metastatic breast cancer. However, direct comparisons of these treatment options in randomized studies have not been conducted.Aim of the work is to gather and analyze published data on the comparative effectiveness of CDK4/6 inhibitors in combination with aromatase inhibitors in postmenopausal patients with HR+/HER2– locally advanced or metastatic breast cancer. A systematic review of publications presenting results from original studies on the impact of CDK4/6 inhibitor therapy in combination with aromatase inhibitors on the survival of patients was performed. Nineteen studies with original data on progression-free survival and overall survival were identified. None of the studies found significant differences between different CDK4/6 inhibitors and aromatase inhibitors in terms of progression-free survival. A statistically significant superiority of ribociclib over palbociclib in terms of overall survival was observed in a single matching-adjusted indirect comparison, while seven other studies of various types (real-world data studies, matching-adjusted indirect comparisons, and meta-analyses) did not find significant differences between the investigated drugs in terms of overall survival.Currently, there is no compelling evidence of the superiority of one CDK4/6 inhibitor over others. The decision on the preference for a specific drug within the class can only be made after conducting direct randomized comparison trials, or accumulating sufficient real-world data on the use of palbociclib, ribociclib, and abemaciclib.

Clinical trial of tolerability, safety and immunogenicity of influenza inactivated split-vaccine Flu-M in children aged 6 to 17 years

Purpose. To evaluate the tolerability, safety and immunogenicity of influenza inactivated split flu vaccine Flu-M during single immunization of children aged 6 to 17 years.Materials and methods. A multicentre double-blind comparative randomised clinical trial of influenza inactivated split vaccine Flu-M for immunisation of children aged 6 to 17 years (the reference agent – Ultrix vaccine) was conducted. Children aged 12 to 17 years inclusive (300 children) were studied at stage I, and children aged 6 to 12 years (300 children) at stage II. Volunteers of each age category were randomised 1:1 into 2 groups comparable in sex and age, one was vaccinated with Flu-M vaccine and the other with Ultrix vaccine. The follow-up, including various laboratory and clinical tests, lasted for 28 days from the time of vaccination.Results. Both vaccines were well tolerated by children aged 12 to 17 years and by children aged 6 to 12 years. There were no severe or serious adverse events. By all criteria of immunogenicity evaluation, vaccine Flu-M was not inferior to the comparison vaccine Ultrix.Conclusion. Influenza inactivated split Flu-M vaccine produced by SPbNIIVS is approved for use for specific prophylaxis of influenza in children aged 6 to 17 years in the Russian Federation, the Republic of Belarus, Latin America and the Caribbean.The trial is registered at ClinicalTrials. gov (NCT 05317767).

Identifying and addressing unmet clinical needs on the use ofzanubrutinib in chronic lymphocytic leukemia: A consensus-based position paper from an ad hoc expert panel.

Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first-line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.

Grafts in Peyronie's surgery without the use of prostheses: a systematic review and meta-analysis.

Peyronie's disease (PD) is characterized by abnormal penile curvature, and various surgical methods have been developed using different graft materials. However, there is currently no universal agreement on which type of graft is the best. The objective of this review was to evaluate the available literature and identify the most effective graft material for penile curvature correction in PD. A literature search was conducted using electronic databases, including PubMed, Scopus, and the Cochrane Library. The patients, intervention, comparison, and outcome (PICO) approach was used to define the eligibility of studies. Two authors independently selected studies, evaluated them, and extracted data. Random-effect models using the DerSimonian-Laird method were used. Most studies were single-arm studies and had a high risk of bias. Buccal mucosa grafts (BMG) were found to result in the highest penile straightening rates and were associated with the least de novo erectile dysfunction. TachoSil grafts demonstrated a high success rate in straightening despite a higher mean preoperative curvature, while Tutoplast grafts had a higher incidence of postoperative erectile dysfunction. BMG had the highest percentage of postoperative penile straightening. Overall, the TachoSil graft showed the best performance when preoperative curvature is taken into account. Based on the available literature, BMG appear to be the most effective for penile curvature correction in PD, but this is offset by the requirement for low preoperative curvature. The TachoSil graft shows the best overall performance when preoperative curvature is considered. Comparative randomized clinical trials are still needed to determine graft superiority.

Shoulder vibratory exercises improves shoulder external rotation muscle strength and shoulder function: Randomized comparison trial.

Based on electromyography measurements, shoulder vibratory exercises efficiently stimulate shoulder muscles activity. Yet very few studies have supported that shoulder vibratory exercises increased shoulder muscles strength and function, and the noninferiority compared with conventional elastic resistance exercises remains unknown. This study investigated the effect of vibratory exercises versus conventional elastic resistance exercises with elastic bands on shoulder external rotation muscles strength and functional performance in young adults. 26 young adults (7 males and 19 females, with age 23.89 ± 3.02) were recruited and randomly allocated to shoulder vibratory exercises with FLEXI-BAR (FLEXI-BAR group) or conventional resistance exercises with elastic band (TheraBand group) for 3 times/week, 4 weeks totally. Shoulder external rotator muscles strength test and Underkofler softball distance throw test (USDTT) were performed before and after the training period. After 4 weeks training, shoulder external rotator muscles strength increased 22.25 ± 15.06 N (P= 0.004, effect size = 1.48) within FLEXI-BAR group and 22.81 ± 14.94 N (P= 0.007, effect size = 1.53) within TheraBand group. There were no statistically significant differences between groups in the three muscle strength tests (P> 0.65). Regarding shoulder function, FLEXI-BAR exercises increased the throw distance 0.81 ± 0.92 meters in USDTT (P= 0.041, effect size = 0.88) while TheraBand exercise did not (P= 0.284), yet there was no statistically significant between group effects (P= 0.608). These findings suggest that shoulder vibratory exercises can improve shoulder muscles strength in young adults and can be a useful alternative to the conventional elastic resistance exercises to improve the shoulder muscles strength and function. This provides therapists with more options in terms of choosing training equipment for rehabilitation programs.

Network meta-analysis of comparative efficacy and safety of intubation devices in children

To evaluate the comparative efficacy and safety of different intubation devices on intubation outcomes in pediatric intubation. We identified relevant studies from previous meta-analyses and literature retrieval in PubMed, EMBASE, and Cochrane Library. The primary outcome was the first-pass success (FPS), and the secondary outcome included the time to intubation (TTI) and the risk of local complications (LC). Network meta-analysis was performed using STATA 14.0. Twenty-three randomized comparative trials (RCTs) including 12 devices were included. Compared with Macintosh, Airtraq (odds ratio [OR] = 13.05, 95% confidence interval [CI] = 4.68 to 36.38), Miller (OR = 4.77, 95%CI = 1.32 to 17.22), Glidescope (OR = 2.76, 95%CrI = 1.60 to 4.75) and McGrath (OR = 4.61, 95%CI = 1.18 to 17.99) obtained higher PFS. Meanwhile, Airtraq was superior to Glidescope (OR = 0.21, 95%CI = 0.07 to 0.65) for PFS. For TTI, Canada was superior to other intubation devices, as well as CMAC was superior to TruViewEVO2, Glidescope, and StorzDCI. Airtraq lowered the risk of LC compared with Macintosh and Pentax but there was no statistical difference between Airtraq and KingVision. Airtraq may be the optimal option for FPS, Canada for TTI, and KingVision for LC in pediatric intubation.

Canal wall up versus canal wall down mastoidectomy techniques in the pediatric population with cholesteatoma: A systematic review and meta-analysis of comparative studies.

The optimal surgical management of cholesteatoma remains controversial. Within pediatric otolaryngology, one of the most vital points of contention is the selection of canal wall-up (CWU) versus canal wall-down (CWD) procedures. Pediatric cholesteatoma has high rates of recurrence (16%-54%). In adults, there is evidence that the selection of surgical techniques affects recurrence rates. This has not been shown in children. 1. To systematically review the literature on recurrent and residual cholesteatoma after CWU and CWD in children and perform a meta-analysis of the data. 2. To assess the rates of recurrent and residual cholesteatoma between CWU and CWD techniques in pediatric patients. 3. To assess hearing outcomes by evaluating postoperative differences in the air-bone gap (ABG) between CWU and CWD techniques. A systematic search of PubMed, Embase, Scopus, and Cochrane Collaboration was performed from inception to May 1st, 2020, to identify studies that compared CWU and CWD procedures for acquired cholesteatoma in children. Search records were screened in duplicate by four reviewers. Inclusion criteria consisted of comparative randomized clinical trials and observational studies assessing outcomes of CWU and CWD techniques in the pediatric population. Studies involving patients with congenital cholesteatoma were excluded. Four reviewers working independently and in duplicate systematically reviewed and extracted study data. Dichotomous variables were analyzed as risk ratios (RR), while continuous variables were compared using weighted mean differences (MD). The risk of bias was assessed using the CLARITY Scale. The outcomes were recurrence, residual disease, air-bone gap (ABG), and air conductive (AC) thresholds. After screening 1036 publications, 17 retrospective cohort studies were selected. 1333 children were included; the overall mean age was ten years (SD 7.9), and the overall mean follow-up time was 5.9 years (SD 6.6). CWU and CWD techniques were performed in 60% (796) and 40% (537) cases. We did not find differences in cholesteatoma recurrence (RR: 1.50, 95% CI 0.94; 2.40; n=544; I2 0%; Tau [2]: 0.00), or rates of residual cholesteatoma (RR 1.51, 95% CI 0.96; 2.38, n=506; I2: 0%; Tau [2]: 0.00) in patients who underwent CWU and CWD mastoidectomy. The mean air-bone gap was lower with CWU than CWD (mean difference: 7.60, 95% CI -10.65; -4.54; n=242; I2: 71%; Tau [2]: 5.98). and relevance: We show similar rates of recurrence and residual disease after either CWU or CWD tympanoplasty. Our results challenge the fundamental principle of CWD surgery as a standard technique, as there is no difference in rates of recurrence and residual disease in CWU and CWD. Moreover, audiometric results support CWU with improved hearing outcomes. PROSPERO identifier: CRD42020184029.

A CLINICAL COMPARATIVE STUDY OF ULTRASOUND-GUIDED POPLITEAL NERVE BLOCK WITH 0.5% BUPIVACAINE HYDROCHLORIDE WITH AND WITHOUT 8MG DEXAMETHASONE FOR KNEE SURGERIES

Objective: This study aimed to see how adding dexamethasone 8 mg to 0.5% bupivacaine affected the length of sensory and motor blockage of the popliteal sciatic nerve in ankle and foot surgeries.
 Methods: This prospective randomized clinical comparison trial enrolled 60 patients with American Society of Anesthesiologists (ASA) physical status grades III and IV, aged 50-80 y, scheduled for ankle and foot procedures from March 2023 to July 2023. Patients were assigned into two groups of 30 at random. 28 ml of 0.5% bupivacaine and 8 mg dexamethasone were given to Group D. Group N was given 28 ml of o.5% bupivacaine and 2 ml of NS. Here, 20 ml was used for sciatic nerve block and 10 ml for saphenous nerve block.
 Results: The mean onset of sensory block in group D was 23.2±6.8 min, while 21.7±6.9 min in group N (p 0.3999). This was not statistically significant. The onset of motor block was 22.9±7.9 in group D and 22.3±7.1 in group N, which were statistically insignificant (p 0.7581). The duration of the motor block in group D was 11.3±3.2 h, whereas it was 5.9±2.3 h in group N (p 0.0001), which was statistically significant. The length of the sensory block in group D was 14.9±3.8 h, while it was 8.3±3.4 h in group N (p 0.0001), which was also statistically significant. The VAS score in group N was significantly higher than in group D; it began 3 h after surgery and remained at 4 h, 5 h, 6 h, 8 h, 10 h, and 12 h. All 30 patients in Group N required their first rescue analgesia during the first 12 h postoperatively. In contrast, only 12 patients (40%) required their first analgesia within the first 12 h, and 18 (60%) requested their first analgesia within the second 12 h.
 Conclusion: Adding 8 mg dexamethasone to 0.5% Bupivacaine hydrochloride in ultrasound-guided popliteal and saphenous nerve blocks for ankle and foot procedures extends postoperative sensory and motor block duration.

When it comes to sedentary behaviour modification, should people be told what to do? A randomized comparison trial among home-based office workers living in Ontario, Canada.

The effects of adding choice architecture to a theory-based (Health Action Process Approach; HAPA) sedentary intervention remain unknown. To investigate whether choice architecture enhances a theory-based sedentary behaviour reduction intervention in home-based office workers. A 4-week HAPA-based intervention was conducted in London, Canada. Choice architecture was tested as an enhancement via a two (group: 'Choice of Intervention' vs. 'No Choice Intervention') by two (time: Baseline vs. Week 4) factorial repeated measure randomized comparison design. Sedentary behaviour reduction strategies focussed on obtaining a sedentary break frequency (BF) of every 30-45 min with break durations (BD) of 2-3 min. BF, BD, sitting, standing, and moving time were objectively measured (activPAL4™) at both time points. Participants (n = 148) were 44.9 ± 11.4 years old and 72.3% female. BF and total sitting time showed a time effect (P < .001), where both groups improved over the 4 weeks; there were no significant differences between groups across time. BD, standing, and moving time had a significant group by time effect where the 'No Choice' group showed significant increases in BD (P < .001), standing (P = .006), and moving time (P < .001) over the 4 weeks. Augmenting a theory-based intervention with choice architecture resulted in change in some sedentary behaviours in at home office workers. Specifically, while BF increased for all participants, the 'No Choice' group exhibited greater changes for BD, standing, and moving time compared with the 'Choice' group. Overall, these changes exceeded the intervention BF and BD goals.

Unmet Clinical Needs in the Management of Idiopathic Multicentric Castleman Disease: A Consensus-based Position Paper From an ad hoc Expert Panel.

Castleman disease describes a group of heterogeneous clinicopathological disorders now included in the tumor-like lesions with B-cell predominance of the World Health Organization classification. Managing idiopathic multicentric Castleman disease (iMCD) is challenging, because few systematic studies or comparative randomized clinical trials have been conducted. International, consensus evidence-based guidelines for iMCD were published in 2018, but gaps in the therapeutic options for difficult-to-treat patients, who do not respond to siltuximab and other conventional therapies, still exist. This article presents the results of group discussion among an ad hoc constituted Panel of Italian experts to identify and address unmet clinical needs (UCNs) in managing iMCD. Recommendations on the appropriateness of clinical decisions and proposals for new research concerning the identified UCNs were issued through formalized multiple-step procedures after a comprehensive analysis of the scientific literature. The following key UCNs were addressed: strengthening the diagnostic certainty in iMCD patients before planning first-line therapy; management of siltuximab therapy; choice and management of immune-modulating, or chemotherapy agents in patients resistant/intolerant to siltuximab therapy. While most of the conclusions reached by the Panel are consistent with the existing guidelines, some alternative therapeutic options were stressed, and the discussion contributed to bringing forth the issues that need further investigation. Hopefully, this comprehensive overview will improve the practice of iMCD and inform the design and implementation of new studies in the field.

Unmet clinical needs in the use of zanubrutinib in malignant lymphomas (Waldenström macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma): A consensus-based position paper from an ad hoc expert panel.

Zanubrutinib has been approved for the treatment of patients with different lymphoproliferative disorders, and now represents a major breakthrough in the treatment of patients resistant or relapsing after the recommended therapies. Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of the drug in approved indications is challenging, and questions are emerging on its use in earlier stages of the disorders. This article presents the results of group discussion among an ad hoc constituted panel of experts aimed at identifying and addressing unmet clinical needs (UCNs) in the use of zanubrutinib in the lymphomas which have received the approval of use, specifically Waldenström macroglubulinemia, marginal zone lymphoma and mantle cell lymphoma. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. The panel produced recommendations and proposals for new studies for the management of the identified UCNs. These recommendations are intended for use not only by expert centers but above all by not experienced hematologists as well as general practitioners.

A Systematic Review on Panchakarma-Based Ayurveda Treatment in Janu Sandhigata Vata

Janu Sandhigata Vata or knee osteoarthritis (KOA) causes chronic pain, stiffness, immobility and affects daily life. Panchakarma-based Ayurvedic treatment is popular in arthritis. The present study has done a systematic review on effectiveness and safety of panchakarma-based treatment in chronic KOA. The study searched for double-arm randomized comparative trials (RCoTs) with human subjects (age ≥ 18 years) explicitly diagnosed with KOA in fourteen electronic databases including MEDLINE, PubMed Central, Cochrane, Ayush Research Portal for indexed research and clinical trials published till September 30, 2022. At least one patient-centred primary outcome, namely pain, physical function, global improvement according to OMERACT III were eligible. Risk-of-bias analysis was done independently by the two authors using the revised Cochrane risk-of-bias tool for randomized trials. Effect size as standardized mean differences between treatments were estimated for pain and stiffness. The inclusion criteria screened 10 RCoTs. The RCoT which used manual therapies in a multimodal ayurvedic care against conventional care had overall low risk of bias. Remaining 9 RCoTs compared the treatment outcomes of different panchakarma-based treatment with and without pharmacological interventions. In 3 RCoTs, effect size on pain and stiffness were medium to large and significant (P&lt;0.01). Only 3 RCTs reported safety concerns and no serious adverse outcomes related to intervention were noted. Sudation techniques and enema therapy used as standalone or in multimodal ayurvedic care showed benefit in KOA. Future studies on the long-term efficacy and safety goals aligned to psychosomatic record of patients are required for personalized Ayurveda multimodal care.

P147 Trends in choice of first line biologic therapy for patients with Inflammatory Bowel Disease. An observational cohort study

Abstract Background Biologic therapies have revolutionised the management of Inflammatory Bowel Disease (IBD) with increasing utilisation over the last decade. The anti-Tumour Necrosis Factor-alpha (anti-TNF) agents (Infliximab (IFX) and Adalimumab (ADA)) as well as newer agents (Ustekinumab (UST) and Vedolizumab (VED)) all have well demonstrated safety and efficacy profiles in the management of IBD. The choice of an optimal first line biologic remains unclear due to lack of comparative randomised trials and real-world studies; however, certain patient and disease characteristics may influence this choice. The aims of this study were to explore temporal trends in choice of 1st-line biologic therapy and factors that influence this choice. Methods A retrospective observational cohort study of all patients with IBD that commenced induction and completed at least one maintenance dose of a biologic therapy between 1st January 2015 and 31st December 2021. Relevant patient and disease-specific factors were collected, including patient comorbidities (ischaemic heart disease, malignancy and opportunistic infections) at time of diagnosis, for each eligible patient. Factors affecting choice of biologic therapy were compared using ANOVA and c2 test. Results 280 patients were included, with 50.7% being male and median age of IBD diagnosis of 29 years. There was a progressive increase in biologic use over time, with 15 patients commencing1st biologic therapy in 2015, rising to 58 patients in 2021. UST has overtaken IFX and ADA as first line choice for Crohn’s disease (CD) since its introduction in 2018 (Figure 1). IFX has remained preferred first line therapy for ulcerative colitis (UC) over VED and ADA, with stable trend in choice over time. Factors with significant differences in choice of first line biologic therapy included age (UST for older age of commencement), IBD subtype (higher proportion of patients commencing ADA had CD, whereas higher proportion of patients commencing VED had UC), disease location (VED was preferred for colonic over ileal CD), and malignancy (UST was preferred) (Table 1). Conclusion - There has been a steady rise in the number of patients commencing biologic therapies, with an average increase of 24% per year from 2015 to 2021. - Ustekinumab has replaced anti-TNF therapy as the preferred first line biologic for Crohn’s disease; a trend likely secondary to the comparatively favourable safety profile of ustekinumab. Ustekinumab was preferred in older patients and those with history of malignancy. - Infliximab remains the preferred first line therapy for ulcerative colitis with stable trends in choice. - The presence of perianal disease was not a significant factor affecting choice.

The associations between HIV stigma and mental health symptoms, life satisfaction, and quality of life among Black sexual minority men with HIV.

With the advancement of antiretroviral therapy (ART), HIV/AIDS has become a manageable illness, similar to other chronic conditions. This study examined the associations between HIV stigma and patient-reported outcomes including mental health symptoms, life satisfaction, and quality of life among Black sexual minority men with HIV. We analyzed baseline data from a randomized comparison trial of a mobile app intervention aimed to address the social work and legal needs of Black sexual minority men with HIV in Los Angeles County. We used validated scales including the Berger HIV stigma scale, the Patient Health Questionnaire-9 & the General Anxiety Disorder-7, the Satisfaction with Life Scale, and the Ladder Scale to assess HIV stigma, depressive symptoms, anxiety, life satisfaction, and quality of life, and we conducted multivariable linear regression to examine their associations. Participants experienced HIV stigma especially about disclosure concerns (e.g., 81.9% participants indicated "I am very careful who I tell that I have HIV") and public attitudes (52.3% believed "Most people with HIV are rejected when others find out"). In the multivariable models, higher overall stigma scores were associated with higher likelihood of experiencing depression (adjusted b = 0.235, p < 0.001) and anxiety (adjusted b = 0.188, p = 0.002), and lower life satisfaction (adjusted b = -0.236, p < 0.001) and quality of life (adjusted b = -0.053, p = 0.013), adjusting for clinical characteristics including ART initiation, viral load suppression, and medication adherence. In addition, being attacked or harassed in the past year were significantly associated with lower life satisfaction and quality of life (adjusted b = -3.028, p = 0.046; adjusted b = -1.438, p = 0.002). Our findings highlight the need for focused HIV stigma reduction interventions to promote the overall well-being of Black sexual minority men with HIV. Strategies to promote the patient-reported outcomes may benefit from trauma-informed approaches.

185 BETA-BLOCKERS OR CALCIUM CHANNEL BLOCKERS IN HYPERTROPHIC CARDIOMYOPATHY

Abstract Background Guidelines recommend betablockers (BB) as first line therapy in symptomatic patients with hypertrophic cardiomyopathy (HCM). A secondary role in the therapeutic algorithm is assigned to non-dihydropyridine calcium channel blockers (ND-CCB). Since no randomized comparison trials between the two drugs have been made so far, the aim of the present analysis was to evaluate the prognostic impact of BB and ND-CCB in a cohort of patients with HCM, either obstructive or not. Methods From a cohort of 1434 patients with a diagnosis of HCM included in the French register REMY, we retrospectively analysed 601 individuals treated with BB or ND-CCB. Patients taking both BB and ND-CCB or none, patients who already had an implantable cardioverter defibrillator or a pacemaker and who had already undergone a procedure of atrial fibrillation (AF) ablation or of septal reduction therapy were excluded. Results Out of 601 HCM patients, 545 (91%) were treated with BB and 56 (9%) with ND-CCB. At 8-year follow-up no differences were observed as regard the composite endpoint of cardiovascular death, hospitalization for heart failure and hospitalization for AF (133 [24%] vs. 9 [16%] for patients taking BB or ND-CCB respectively, HR 1.84, 95% CI 0.94–3.63). Patients taking ND-CCB were less symptomatic at long-term follow-up but experienced more drug interruptions or changes. Conclusions In a real-world cohort of patients with HCM, ND-CCB therapy was not associated with a higher incidence of adverse events compared to BB therapy.

Effectiveness of eye movement exercise and diaphragmatic breathing with jogging in reducing migraine symptoms: A preliminary, randomized comparison trial.

Migraine is a multifactorial headache disorder. Maladaptive functional networks or altered circuit-related connectivity in the brain with migraine appear to perturb the effects of usual treatments. In the present preliminary trial, we aim to study the effectiveness of performing pieces of body-mind, cognitive, or network reconstruction-based training (i.e., eye movement exercise plus jogging; EME+J and diaphragmatic breathing plus jogging; DB+J) in decreasing migraine symptoms. We used a three-arm, triple-blind, non-inferiority randomized comparison design with pre-test, post-test, and follow-up measurements to assess the effectiveness of EME+J and DB+J in the brain with migraine. Participants were randomly assigned to one of the study groups to perform either 12 consecutive weeks of EME+J (n=22), DB+J (n=19), or receiving, treatment as usual, TAU (n=22). The primary outcome statistical analysis through a linear mixed model showed a significant decrease in the frequency (p=.0001), duration (p=.003), and intensity (p=.007) of migraine attacks among the interventions and measurement times. The pairwise comparisons of simple effects showed that EME+J and DB+J effectively reduced migraine symptoms at the post-test and follow-up (p<.05). Cochran's tests showed that interventions decreased the number of menses-related migraine attacks. EME+J and DB+J effectively decreased over-the-counter (OTC) drug use, refreshed wake-up mode, and improved sleep and water drinking patterns. These are the secondary outcomes that Cochran's tests showed in the interventional groups after the interventions and at 12 months of follow-up. EME+J or DB+J can be an effective and safe method with no adverse effects to decrease the symptoms of migraine attacks. Moreover, a reduction in the frequency of menstrual cycle-related attacks, OTC drug use, and improved quality of sleep and drinking water were the secondary outcomes of the post-test and a 12-month follow-up.

In search of effective therapies: the current landscape of phase II trials in patients with advanced soft tissue sarcoma.

Soft tissue sarcomas (STS) are diagnosed in 4-6 cases per 100000 people a year and are associated with an unfavorable prognosis. Around one-third of patients will develop metastatic disease that requires palliative systemic therapy. Current therapeutic options have limited activity, and new treatments are tested, mainly in phase II trials. There is high variability and no standardization of phase II designs. We aimed to analyze the current landscape of phase II studies in STS and evaluate how its statistical design can affect the results. Full-text phase II studies published in STS patients between 2005 and 2020 were identified and analyzed. We have identified 102 trials, of which 77.4% were single-arm trials, 16.7% were randomized comparative trials (RCT), and 5.9% were randomized noncomparative trials. Including multiple cohorts, 22 randomized and 128 single-arm cohorts were analyzed. Nearly 80% of trials reported full statistical bases of the design. Over 20 different primary endpoints were used, with PFS as the most common in RCT trials (81.8%) and ORR (36.7%) and 3-months progression-free survival (PFS) rate (21.9%) in single-arm trials. Overall, 27.3% of RCT and 37.5% of single-arm trials were positive. Among single-arm trials, studies using 3- or 6-month rates were more often positive than those based on ORR. There is high heterogeneity in sarcoma trial designs, mainly in primary-endpoint and hypotheses used for size calculation. There is an unmet need for standardization that will incorporate factors associated with the rarity of the disease, outcomes detected in previous trials and real-life studies, and specific characteristics of new therapeutic agents.

Virtual McKenzie extension exercises for low back and leg pain: a prospective pilot exploratory case series

ABSTRACT Introduction Current evidence supports the inclusion of directional preference exercises for a subgroup of patients with low back (LBP) and leg pain. Recent pain neuroscience strategies have suggested that cortical restructuring associated with movement activating the body map representation in the brain might account for the observed improvement with the directional preference approach. Objectives To explore whether or not a motor imagery directional preference approach would result in any changes in patients with LBP and leg pain. Methods A consecutive convenience sample of patients with LBP and leg pain were recruited at two outpatient physical therapy clinics. Measurements of LBP, leg pain, fear-avoidance beliefs (FABQ), pain catastrophizing (PCS), active lumbar flexion, and straight leg raise (SLR) were compared before and immediately after a virtual (motor imagery) directional preference exercise. Results Statistically significant differences for LBP, FABQ, PCS, active lumbar flexion, and SLR were observed, but only SLR changes met or exceeded the minimally clinically important difference (MCID). Conclusions A brief virtual motor imagery extension treatment yielded some immediate positive shifts in patients presenting to physical therapy with LBP and leg pain. Our results indicate that randomized comparison trials are needed to determine the effect of this intervention on the short- and longer-term outcomes in patients with LBP and leg pain.

A video based benchmark data set (ENDOTEST) to evaluate computer-aided polyp detection systems

Background and aims Computer-aided polyp detection (CADe) may become a standard for polyp detection during colonoscopy. Several systems are already commercially available. We report on a video-based benchmark technique for the first preclinical assessment of such systems before comparative randomized trials are to be undertaken. Additionally, we compare a commercially available CADe system with our newly developed one. Methods ENDOTEST consisted in the combination of two datasets. The validation dataset contained 48 video-snippets with 22,856 manually annotated images of which 53.2% contained polyps. The performance dataset contained 10 full-length screening colonoscopies with 230,898 manually annotated images of which 15.8% contained a polyp. Assessment parameters were accuracy for polyp detection and time delay to first polyp detection after polyp appearance (FDT). Two CADe systems were assessed: a commercial CADe system (GI-Genius, Medtronic), and a self-developed new system (ENDOMIND). The latter being a convolutional neuronal network trained on 194,983 manually labeled images extracted from colonoscopy videos recorded in mainly six different gastroenterologic practices. Results On the ENDOTEST, both CADe systems detected all polyps in at least one image. The per-frame sensitivity and specificity in full colonoscopies was 48.1% and 93.7%, respectively for GI-Genius; and 54% and 92.7%, respectively for ENDOMIND. Median FDT of ENDOMIND with 217 ms (Inter-Quartile Range(IQR)8–1533) was significantly faster than GI-Genius with 1050 ms (IQR 358–2767, p = 0.003). Conclusions Our benchmark ENDOTEST may be helpful for preclinical testing of new CADe devices. There seems to be a correlation between a shorter FDT with a higher sensitivity and a lower specificity for polyp detection.