Moderate Benefit Research Articles

Open Versus Closed Group Treatment of Men with a History of Sexual Offenses.

Treatment programs for people with histories of sexual violence form a critical part of criminal justice service rehabilitation. Completion of these programs is often a precondition of release. Meta-analytic reviews suggest moderate benefit is associated with treatment completion, although effect sizes vary. This study examined whether commencement of open versus closed group programs was associated with treatment completion and recidivism. Participants were 426 adult men who commenced treatment between April 1, 2014, and December 31, 2017. Participants were followed-up until June 30, 2018. Programs varied by type (open versus closed), location (in-custody versus in-community) and intensity (moderate versus high). No significant differences were observed between open and closed programs for treatment completion but men who were treated in-custody were more likely to complete treatment when compared to those men who commenced treatment in the community. No significant differences were observed between open and closed programs for sexual or for any recidivism.

EXTH-15. DRUG SCREENING ON PATIENT GBM CELL CULTURES IDENTIFIES OMACETAXINE MEPESUCCINATE AS A POTENT ANTI-GLIOMA AGENT WITH THE ABILITY TO CROSS THE BLOOD-BRAIN-BARRIER

Abstract INTRODUCTION Little progress has been made in the development of effective new therapies for glioblastoma (GBM) the past decades. Fresh patient-derived GBM cell culture models have become the gold standard for GBM drug discovery and development. One of the major obstacles in identifying novel candidate drugs against GBM remains the blood-brain barrier (BBB). Therefore, it is crucial to select drugs with favourable physicochemical properties to cross BBB and reach the tumour tissue in therapeutically effective concentrations. In current drug repurposing approach, we evaluated available anti-cancer agents in our patient-derived drug screening platform against GBM. METHODS The FDA-approved Oncology Drug Set II library was tested on 45 primary GBM cell cultures. We developed a drug shortlisting pipeline combining efficacy data with pharmacodynamic and pharmacokinetic characteristics of each compound. The therapeutic efficacy of the selected agent was assessed in an orthotopic mouse PDX model, while penetration into the CNS by LC/MS/MS. RESULTS Omacetaxine mepesuccinate (OMA) was ranked as one of the most promising candidates applying our drug selection approach. In vitro, OMA revealed anti-tumour activity at IC50 values well-below reported Cmax plasma values in approximately 80% of GBM cultures. NanoString nCounter analysis, revealed DNA damage repair as the main pathway involved in OMA’s anti-tumour effect. Activation of caspase 3/7 activity and decrease of glioma cell invasiveness were also linked to its anti-tumour effect. In vivo, 1mg/kg dose of OMA was found to reach the brain tumour tissue in concentrations similar to the reported IC50 values in vitro. No adverse reactions were noted and a survival benefit was observed in a proportion of the treated mice. CONCLUSIONS At 1 mg/kg, OMA reaches the tumour brain tissue in therapeutically effective concentrations in mice while a moderate therapeutic benefit was observed. Additional in vivo experiments are ongoing investigating higher dosages of OMA and longer exposure.

Meta-Analytic Findings of the Self-Controlled Motor Learning Literature: Underpowered, Biased, and Lacking Evidential Value

The self-controlled motor learning literature consists of experiments that compare a group of learners who are provided with a choice over an aspect of their practice environment to a group who are yoked to those choices. A qualitative review of the literature suggests an unambiguous benefit from self-controlled practice. A meta-analysis was conducted on the effects of self-controlled practice on retention test performance measures with a focus on assessing and potentially correcting for selection bias in the literature, such as publication bias and p-hacking. First, a naïve random effects model was fit to the data and a moderate benefit of self-controlled practice, g = .44 (k = 52, N = 2061, 95% CI [.31, .56]), was found. Second, publication status was added to the model as a potential moderator, revealing a significant difference between published and unpublished findings, with only the former reporting a benefit of self-controlled practice. Third, to investigate and adjust for the impact of selectively reporting statistically significant results, a weight-function model was fit to the data with a one-tailed p-value cutpoint of .025. The weight-function model revealed substantial selection bias and estimated the true average effect of self- controlled practice as g = .107 (95% CI [.047, .18]). P-curve analyses were conducted on the statistically significant results published in the literature and the outcome suggested a lack of evidential value. Fourth, a suite of sensitivity analyses were conducted to evaluate the robustness of these results, all of which converged on trivially small effect estimates. Overall, our results suggest the benefit of self-controlled practice on motor learning is small and not currently distinguishable from zero.

Performance of upper-room ultraviolet germicidal irradiation (UVGI) system in learning environments: Effects of ventilation rate, UV fluence rate, and UV radiating volume

• We study performance of upper-room ultraviolet germicidal irradiation (UVGI) systems. • Performance of upper-room UVGI system in a classroom varies with ventilation rate. • Non-uniform airflow pattern meaningfully influences the UVGI system performance. • UV radiating volume is more crucial for virus disinfection than UV fluence rate. • Doubling UV fluence rate from 25 to 50 μW∙cm-2 yields only moderate benefit. Previous studies show that upper-room ultraviolet germicidal irradiation (UVGI) systems can help contain infectious airborne viruses indoors. However, there has been a lack of research on the performance of an upper-room UVGI system in learning environments such as a school classroom. Since classrooms are more vulnerable to airborne transmission of diseases due to high occupancy for long hours, airborne infection characteristics are different from other occupied indoor environments (e.g., offices and residences). The objective of this study is to investigate UVGI system performance in a classroom considering detailed effects of ventilation rate, UV fluence rate, and UV radiating volume. Two analytical models, a one-zone and a two-zone material balance model, along with computational fluid dynamics (CFD) simulations, were employed to analyze viral aerosol concentrations under a representative range of classroom operating conditions. The CFD results show that increasing ventilation rate from 1.1 h –1 to 5 h –1 yields about 85% of airborne disinfection while doubling UV radiating volume results in a 60% disinfection. However, increasing UV fluence rate from 25 μW∙cm –2 to 50 μW∙cm –2 yields a moderate additional disinfection of 18%. Overall, the study results reveal that operating a UVGI system in an occupied classroom can markedly disinfect airborne viruses up to 96%, which is as effective as increasing ventilation rate more than five times. Furthermore, the results suggest that the one-zone and two-zone analytical models used in several previous studies could result in notably meaningful errors in analyzing viral aerosol concentrations, especially in occupied rooms with a highly non-uniform airflow distribution.

Third international challenge to model the medium- to long-range transport of radioxenon to four Comprehensive Nuclear-Test-Ban Treaty monitoring stations

In 2015 and 2016, atmospheric transport modeling challenges were conducted in the context of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) verification, however, with a more limited scope with respect to emission inventories, simulation period and number of relevant samples (i.e., those above the Minimum Detectable Concentration (MDC)) involved. Therefore, a more comprehensive atmospheric transport modeling challenge was organized in 2019. Stack release data of Xe-133 were provided by the Institut National des Radioéléments/IRE (Belgium) and the Canadian Nuclear Laboratories/CNL (Canada) and accounted for in the simulations over a three (mandatory) or six (optional) months period. Best estimate emissions of additional facilities (radiopharmaceutical production and nuclear research facilities, commercial reactors or relevant research reactors) of the Northern Hemisphere were included as well. Model results were compared with observed atmospheric activity concentrations at four International Monitoring System (IMS) stations located in Europe and North America with overall considerable influence of IRE and/or CNL emissions for evaluation of the participants’ runs. Participants were prompted to work with controlled and harmonized model set-ups to make runs more comparable, but also to increase diversity. It was found that using the stack emissions of IRE and CNL with daily resolution does not lead to better results than disaggregating annual emissions of these two facilities taken from the literature if an overall score for all stations covering all valid observed samples is considered. A moderate benefit of roughly 10% is visible in statistical scores for samples influenced by IRE and/or CNL to at least 50% and there can be considerable benefit for individual samples. Effects of transport errors, not properly characterized remaining emitters and long IMS sampling times (12–24 h) undoubtedly are in contrast to and reduce the benefit of high-quality IRE and CNL stack data. Complementary best estimates for remaining emitters push the scores up by 18% compared to just considering IRE and CNL emissions alone. Despite the efforts undertaken the full multi-model ensemble built is highly redundant. An ensemble based on a few arbitrary runs is sufficient to model the Xe-133 background at the stations investigated. The effective ensemble size is below five. An optimized ensemble at each station has on average slightly higher skill compared to the full ensemble. However, the improvement (maximum of 20% and minimum of 3% in RMSE) in skill is likely being too small for being exploited for an independent period.

OS06.6.A Real-World Pattern of Care Study on Glioblastoma in the Austrian Population. Final results from 2014-2020

Abstract Background The Austrian ABTR-SANO Glioblastoma Registry is the first population-based assessment of patterns of care for patients with Glioblastoma across Austrian healthcare institutions. The primary aim is to assess the real world effectiveness of administered therapies. Material and Methods Clinical data are collected via a common web-based IT platform “ABTR-SANO Net” since 2014. The database and the ongoing evaluation of clinical parameters, as well as interims analysis are provided in cooperation with a review board. First Outcome analysis, including patients from 2014-2020, was performed at the end of 2021. Results Eleven centers across Austria are involved, and the data of 1416 patients (m/f ratio: 1,35, median age: 66 years) were recently analyzed in detail. Age, extent of resection, as well as ECOG was associated with improved survival. Methylated MGMT Status also showed a moderate survival benefit. Patients with re-resection and re-radiation also exhibited improved survival, which however may be attributed to a selection bias.Second line treatment manly comprised of antiangiogenic treatment, followed by alkylated agents, re-radiation and re-surgery. Median overall survival of all patients was 344 days and clearly age dependent (best for <50 years, worse for>80 years). Conclusion This is the first population based outcome analysis of Glioblastoma in Austria. Results regarding prognostic markers and outcome are mostly comparable with international data. Robust population based data are important in order to monitor quality of health care, and to match the data with results from clinical studies.

Reduction of Cardiovascular Events and Related Healthcare Expenditures through Achieving Population-Level Targets of Dietary Salt Intake in Japan: A Simulation Model Based on the National Health and Nutrition Survey.

Reducing population dietary salt intake is expected to help prevent cardiovascular disease and thus constrain increasing national healthcare expenditures in Japan’s super-aged society. We aimed to estimate the impact of achieving global and national salt-reduction targets (8, <6, and <5 grams/day) on cardiovascular events and national healthcare spending in Japan. Using published data including mean salt intake and systolic blood pressure from the 2019 National Health and Nutrition Survey, we developed a Markov model of a closed cohort of adults aged 40–79 years in 2019 (n = 66,955,000) transitioning among six health states based on the disease course of ischemic heart disease (IHD) and stroke. If mean salt intake were to remain at 2019 levels over 10 years, cumulative incident cases in the cohort would be approximately 2.0 million for IHD and 2.6 million for stroke, costing USD 61.6 billion for IHD and USD 104.6 billion for stroke. Compared with the status quo, reducing mean salt intake towards the targets over 10 years would avert 1–3% of IHD and stroke events and save up to 2% of related national healthcare costs. Attaining dietary salt-reduction goals among adults would yield moderate health economic benefits in Japan.

Deprescribing: What About Vitamins, Minerals, and Other Nutritional Supplements?

Deprescribing: What About Vitamins, Minerals, and Other Nutritional Supplements?

Effect of Compression Therapy in the Treatment of Tibial Stress Syndrome in Military Service Members.

Tibial stress syndrome (TSS) is an overuse injury of the lower extremities. There is a high incidence rate of TSS among military recruits. Compression therapy is used to treat a wide array of musculoskeletal injuries. The purpose of this study was to investigate the use of compression therapy as a treatment for TSS in military service members. A parallel randomized study design was utilized. Military members diagnosed with TSS were assigned to either a relative rest group or compression garment group. Both groups started the study with 2 weeks of lower extremity rest followed by a graduated running program during the next 6 weeks. The compression garment group additionally wore a shin splints compression wrap during the waking hours of the first 2 weeks and during activity only for the next 6 weeks. Feelings of pain, TSS symptoms, and the ability to run 2 miles pain free were assessed at baseline, 4 weeks, and 8 weeks into the study. Feelings of pain and TSS symptoms decreased during the 8-week study in both groups (P < .05), but these changes were not significantly different between groups (P > .05). The proportion of participants who were able to run 2 miles pain free was significantly different (P < .05) between the 2 groups at the 8-week time point with the compression garment group having a significantly increased ability to complete the run without pain. Although perceptions of pain at rest were not different between groups, the functional ability of running 2 miles pain free was significantly improved in the compression garment group. These findings suggest that there is a moderate benefit to using compression therapy as an adjunct treatment for TSS, promoting a return to training for military service members.

Establishing COVID-19 trials at scale and pace: Experience from the RECOVERY trial.

The Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial was set up in March 2020 to evaluate treatments for people hospitalised with COVID-19. To maximise recruitment it was designed to fit into routine clinical care throughout the UK, and as a result it has enrolled more patients than any other COVID-19 treatment trial. RECOVERY has shown four drugs to be life-saving – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab – and a further six have been shown to be of little or no benefit. In each case, results from RECOVERY were clear enough to rapidly influence global practice. Some of the reasons for this success relate to its particular setting in the UK during the SARS-CoV-2 pandemic, but many are generalisable to other contexts. In particular, its focus on recruiting large numbers of patients to identify or rule out moderate but worthwhile benefits of treatment, and the design decisions that followed from this. Similar large streamlined trials could produce similarly clear answers about the treatment of many other common diseases.

Abstract 5555: A bispecific antibody targeting CLDN18.2 and 4-1BB induces potent anti-tumor efficacy with an extraordinary safety profile

Abstract Background: Gastric cancer is one of the most common cancers worldwide, which is estimated to have 32.1 and 13.2 cases per 100,000 individuals in males and females, respectively. Claudin-18 isoform 2 (CLDN18.2), a membrane-bound protein involved in the formation of tight junctions, has been identified to be highly expressed in various types of cancers such as gastric and pancreatic cancer. Targeting CLDN18.2 with the monoclonal antibody (mAb) Zolbetuximab has achieved moderate clinical benefit with controllable toxicity. 4-1BB is a potent stimulator of T cells and NK cells, and when activated, can improve effector and/or memory responses. However, inherent on-target related toxic effects in the liver was observed during the clinical development of the monoclonal agonist antibody Urelumab. Here, we report the discovery of a humanized bispecific antibody (biAb) anti-CLDN18.2 x 4-1BB, which activates immune cells such as T cells via CLDN18.2-mediated crosslinking of 4-1BB. This bispecific antibody induces potent anti-tumor efficacy with limited toxicity. Methods: The anti-CLDN18.2 x 4-1BB biAb was generated by the fusion of an anti-4-1BB VHH targeting the CRD4 domain for 4-1BB, to the C-terminus of an anti-CLDN18.2 mAb via a G4S linker. Binding affinity and specificity testing of each arm were studied by flow cytometry and on the Retrogenix Cell Microarray Technology platform, a human membrane/secreted protein binding array. The immunomodulatory functions were evaluated using luciferase reporter cell assays in vitro and human 4-1BB KI mouse models in vivo. Results: The CLDN18.2 antibody interacted specifically to CLDN18.2 on the Retrogenix Cell Microarray platform among over 5,500 proteins. Next, in vitro studies showed how the molecule specifically induced T cell activation and cytokine release against CLDN18.2-positive cells. More importantly, such activation was correlated to the expression level of CLDN18.2, which indicates that the molecule may preferentially recognize CLDN18.2-high-expressing cancer cells. In mouse models, the anti-CLDN18.2 x 4-1BB biAb induced superior anti-tumor efficacy compared to anti-CLDN18.2 and anti-4-1BB mAbs alone with acceptable PK attributes. Furthermore, the anti-CLDN18.2 x 4-1BB biAb induced strong immunological memory where tumors could not grow in re-challenged tumor-free mice. Finally, the CLDN18.2 x 4-1BB biAb showed a safe profile in a GLP NHP study of which no obvious signs of toxicity were observed at 50 mg/kg, 100 mg/kg or 150 mg/kg doses. Conclusion: In summary, a bispecific antibody targeting CLDN18.2 and 4-1BB was developed, which displayed potent anti-tumor efficacy with strong immunological memory and has shown good safety in NHPs. Moreover, the molecule has high selectivity to CLDN18.2. The molecule shall enter clinical trials by early 2022. Citation Format: Junying Chen, Weifeng Huang, Zhiquan Liang, Xiaoniu Miao, Shaogang Peng, Chao Wang, Tiantian Dong, Andy Tsun, Yi Luo. A bispecific antibody targeting CLDN18.2 and 4-1BB induces potent anti-tumor efficacy with an extraordinary safety profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5555.

Abstract 2894: QL401, a dual PD-L1/CD47 blocker effective against both solid and hematological malignancies with improved blood safety

Abstract Upregulation of CD47, a “Do Not Eat Me” signal, is observed in nearly all solid and hematological malignancies. Engagement of CD47 on tumor cells with SIRPα on macrophages inhibits phagocytosis of tumor cells. Anti-CD47 antibodies block the CD47 - SIRPα engagement and reactivate phagocytosis of tumor cells by macrophages. Yet the ubiquitous expression of CD47 on normal cells, including red blood cells, presents a therapeutic challenge. Systemic targeting of CD47, by either anti-CD47 monoclonal antibodies or SIRPα-Fc fusion proteins, yielded only moderate clinical benefit due to severe adverse side effects, mainly anemia. QL401 is PD-L1 x CD47 bispecific antibody engineered to reduce binding to red blood cells while retaining potent phagocytic activation of macrophages in vitro and delayed tumor growth in vivo. QL401 comprises three functional components: a PD-L1 binding Fab arm, a CD47 binding scFv arm, and a human IgG4 backbone. The PD-L1 binding arm provides both tumor targeting and blocking of PD-1 for reactivating T cells. The CD47 arm blocks the binding of SIRPα, the “Do Not Eat Me” signal, while the IgG4 Fc retains Fc gamma receptor binding to provide a phagocytic “Eat Me” signal. Therefore, QL401 is multi-functional antibody that re-actives both the innate and adaptive immune response. In preclinical efficacy studies, QL401 potently blocked SIRPα to promote phagocytosis of tumor cells with sub-nanomolar potency. In vivo efficacy studies in mouse models of solid and hematological tumors showed QL401 to be comparable or superior to PD-L1 or CD47 monoclonal antibodies alone and in combination. In vitro safety evaluation of Q401 showed significantly reduced binding and phagocytosis of red blood cells, in contrast to CD47 monoclonal antibodies. In addition, Q401 did not induce hemagglutination. In non-human primates, QL401 was well tolerated up to 100 mg/kg without reduction of red blood cells below normal range. A phase 1 dose escalation and expansion study is expected to start Q1 2022 to evaluate the safety, tolerability, and early efficacy of QL401. Citation Format: Irene Tang, Lauren Schwimmer, Shenda Gu, Wei Wei Prior, Hieu V. Tran, Allan Chan, Anna McClain, Shihao Chen, Chuanzeng Cao, Chunyan Sun, Meimei Si, Guijiang Wang. QL401, a dual PD-L1/CD47 blocker effective against both solid and hematological malignancies with improved blood safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2894.

Clonal dynamics of haematopoiesis across the human lifespan

Age-related change in human haematopoiesis causes reduced regenerative capacity1, cytopenias2, immune dysfunction3 and increased risk of blood cancer4–6, but the reason for such abrupt functional decline after 70 years of age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies of haematopoietic cells across 10 human subjects from 0 to 81 years of age. Haematopoietic stem cells or multipotent progenitors (HSC/MPPs) accumulated a mean of 17 mutations per year after birth and lost 30 base pairs per year of telomere length. Haematopoiesis in adults less than 65 years of age was massively polyclonal, with high clonal diversity and a stable population of 20,000–200,000 HSC/MPPs contributing evenly to blood production. By contrast, haematopoiesis in individuals aged over 75 showed profoundly decreased clonal diversity. In each of the older subjects, 30–60% of haematopoiesis was accounted for by 12–18 independent clones, each contributing 1–34% of blood production. Most clones had begun their expansion before the subject was 40 years old, but only 22% had known driver mutations. Genome-wide selection analysis estimated that between 1 in 34 and 1 in 12 non-synonymous mutations were drivers, accruing at constant rates throughout life, affecting more genes than identified in blood cancers. Loss of the Y chromosome conferred selective benefits in males. Simulations of haematopoiesis, with constant stem cell population size and constant acquisition of driver mutations conferring moderate fitness benefits, entirely explained the abrupt change in clonal structure in the elderly. Rapidly decreasing clonal diversity is a universal feature of haematopoiesis in aged humans, underpinned by pervasive positive selection acting on many more genes than currently identified.

Connecting Healthcare with Income Maximisation Services: A Systematic Review on the Health, Wellbeing and Financial Impacts for Families with Young Children.

Financial counselling and income-maximisation services have the potential to reduce financial hardship and its associated burdens on health and wellbeing in High Income Countries. However, referrals to financial counselling services are not systematically integrated into existing health service platforms, thus limiting our ability to identify and link families who might be experiencing financial hardship. Review evidence on this is scarce. The purpose of this study is to review “healthcare-income maximisation” models of care in high-income countries for families of children aged between 0 and 5 years experiencing financial difficulties, and their impacts on family finances and the health and wellbeing of parent(s)/caregiver(s) or children. A systematic review of the MEDLINE, EMBase, PsycInfo, CINAHL, ProQuest, Family & Society Studies Worldwide, Cochrane Library, and Informit Online databases was conducted according to the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) statement. A total of six studies (five unique samples) met inclusion criteria, which reported a total of 11,603 families exposed to a healthcare-income maximisation model. An average annual gain per person of £1661 and £1919 was reported in two studies reporting one Scottish before–after study, whereby health visitors/midwives referred 4805 clients to money advice services. In another UK before–after study, financial counsellors were attached to urban primary healthcare centres and reported an average annual gain per person of £1058. The randomized controlled trial included in the review reported no evidence of impacts on financial or non-financial outcomes, or maternal health outcomes, but did observe small to moderate effects on child health and well-being. Small to moderate benefits were seen in areas relating to child health, preschool education, parenting, child abuse, and early behavioral adjustment. There was a high level of bias in most studies, and insufficient evidence to evaluate the effectiveness of healthcare-income maximisation models of care. Rigorous (RCT-level) studies with clear evaluations are needed to assess efficacy and effectiveness.

Cribado e intervención breve en consumo de alcohol

Morbidity associated with alcohol consumption includes digestive, psychiatric, neurological, infectious disease, cancers of various types, cardiovascular disease, intentional injuries, unintentional injuries, social pathology, and family problems. The most recent evidence does not indicate that “moderate” consumption is beneficial to health. The most recent evidence indicates that “moderate” consumption is not beneficial to health. Therefore, the emphasis should be placed on avoiding risky drinking and advising patients that it would be in their best health interest to avoid alcohol or to drink alcohol at low-risk doses. The AUDIT-C is the most appropriate screening instrument. Cognitive-behavioural and motivational strategies form the basis of brief intervention. Positive information about the benefits of moderation and information about the dangers of alcohol intake should be given. In early stages of dependence, pharmacological treatment for detoxification, withdrawal and follow-up is considered. More serious cases require coordination with addiction services. In Spain, BI has proven effective and to reduce alcohol consumption by 100g/week. Community strategies are the appropriate policy framework to achieve the best results from brief intervention. They should aim to reduce the supply and availability for consumption by adopting legislative measures to limit both economic and physical accessibility. Furthermore, measures should be implemented to reduce the demand for alcohol through health education for specific risk groups.

Characterization of ASES score pain and functional improvement after anatomic total shoulder arthroplasty: a patient-centered perspective.

Interpretation of anchor-based clinical differences in the context of pain and functional change remains undefined. The purpose of this study was to characterize American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores for patients after anatomic total shoulder arthroplasty with minimum 1 year of follow-up in terms of pain and change in each functional element on the ASES. We performed a retrospective study of a prospective institutional patient database of primary anatomic total shoulder arthroplasties from 2017-2020 with baseline and 1-year postoperative ASES scores. Three clinical outcome groups were established using an anchor-based global rating of change assessment: minimal clinically important difference (MCID), moderate clinical benefit (MCB), and substantial clinical benefit (SCB). Pain and functional outcomes in each group where then characterized and compared. A total of 67 patients were analyzed in terms of demographics and clinical outcomes. Two-thirds (65%) of patients achieved the SCB, 24% achieved the MCB, and 10% achieved the MCID. Washing, reaching for a shelf, and throwing were the most common functional deficits experienced preoperatively and accounted for the largest improvement in function postoperatively. Patients in the MCID group had higher preoperative visual analog scale (VAS) pain scores (7.1 ± 3.0) than the MCB (5.8 ± 2.5) or SCB (5.8 ± 2.2) groups (P = .0612). The MCID group had the least amount of preoperative functional deficits when compared to the MCB and SCB groups (P = .041). Postoperative VAS pain scores improved by 5.1 in the SCB, 3.6 in the MCB, and 3.7 in the MCID groups. Functional change in each element of the ASES improved by 1.4/4 in the SCB, followed by 0.9/4 in the MCB group and 0.05/4 in the MCID group (P < .001). The MCID group had higher preoperative pain scores and the least amount of preoperative functional deficits when compared to the MCB and SCB groups. The MCID was realized through pain improvement only, whereas the MCB and SCB consisted of meaningful improvements in pain and function.

Cost-Effectiveness of Interventions to Improve HIV Pre-exposure Prophylaxis Initiation, Adherence, and Persistence Among Men Who Have Sex With Men.

To help achieve Ending the HIV Epidemic (EHE) goals of reducing new HIV incidence, pre-exposure prophylaxis (PrEP) use and engagement must increase despite multidimensional barriers to scale-up and limitations in funding. We investigated the cost-effectiveness of interventions spanning the PrEP continuum of care. Men who have sex with men in Atlanta, GA, a focal jurisdiction for the EHE plan. Using a network-based HIV transmission model, we simulated lifetime costs, quality-adjusted life years (QALYs), and infections averted for 8 intervention strategies using a health sector perspective. Strategies included a status quo (no interventions), 3 distinct interventions (targeting PrEP initiation, adherence, or persistence), and all possible intervention combinations. Cost-effectiveness was evaluated incrementally using a $100,000/QALY gained threshold. We performed sensitivity analyses on PrEP costs, intervention costs, and intervention coverage. Strategies averted 0.2%-4.2% new infections and gained 0.0045%-0.24% QALYs compared with the status quo. Initiation strategies achieved 20%-23% PrEP coverage (up from 15% with no interventions) and moderate clinical benefits at a high cost, while adherence strategies were relatively low cost and low benefit. Under our assumptions, the adherence and initiation combination strategy was cost-effective ($86,927/QALY gained). Sensitivity analyses showed no strategies were cost-effective when intervention costs increased by 60% and the strategy combining all 3 interventions was cost-effective when PrEP costs decreased to $1000/month. PrEP initiation interventions achieved moderate public health gains and could be cost-effective. However, substantial financial resources would be needed to improve the PrEP care continuum toward meeting EHE goals.

PD49-07 SEXUAL FUNCTION RECOVERY FOLLOWING OPEN AND ROBOTIC RADICAL PROSTATECTOMY: RESULTS OF AN ACADEMIC PENILE REHABILITATION PROGRAM

You have accessJournal of UrologyCME1 May 2022PD49-07 SEXUAL FUNCTION RECOVERY FOLLOWING OPEN AND ROBOTIC RADICAL PROSTATECTOMY: RESULTS OF AN ACADEMIC PENILE REHABILITATION PROGRAM Ugo Falagario, Michele Di Nauta, Andrea Checchia, Marco Recchia, Anna Ricapito, Nicola D'Altilia, Pasquale Annese, Gian Maria Busetto, Luigi Cormio, Giuseppe Carrieri, and Carlo Bettocchi Ugo FalagarioUgo Falagario More articles by this author , Michele Di NautaMichele Di Nauta More articles by this author , Andrea ChecchiaAndrea Checchia More articles by this author , Marco RecchiaMarco Recchia More articles by this author , Anna RicapitoAnna Ricapito More articles by this author , Nicola D'AltiliaNicola D'Altilia More articles by this author , Pasquale AnnesePasquale Annese More articles by this author , Gian Maria BusettoGian Maria Busetto More articles by this author , Luigi CormioLuigi Cormio More articles by this author , Giuseppe CarrieriGiuseppe Carrieri More articles by this author , and Carlo BettocchiCarlo Bettocchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002620.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical prostatectomy (RP) is the gold standard treatment for clinically localized prostate cancer (PCa) in patients with a life expectancy 10 yr. Notwithstanding improvements in surgical techniques, erectile dysfunction (ED) is a common sequela of RP.The aim of the present study was to evaluate the effect of early penile rehabilitation in a dedicated Penile Rehabilitation Program on both assisted and unassisted erectile function (EF) in men who developed ED after open and robotic RP. METHODS: All patients undergoing open or robotic RP and early penile rehabilitation were included in the present study. All patients were treated and followed up at a single academic institution in a dedicated Penile Rehabilitation Program. Treatment included phosphodiesterase type 5 inhibitors (PDE5Is), intracavernous injections and vacuum erection devices (VEDs). EF recovery was defined as IIEF>20. Both assisted and unassisted EF was evaluated. Data were prospectively collected and retrospectively reviewed. Kaplan Mayer curves were used to evaluate EF recovery. Ethical Committee approval has been obtained. RESULTS: a total of 397 patients were eligible. 168 (42.3%) underwent robotic RP. Unilateral and bilateral nerve sparing was performed in 38 (9.6%) and 116 (29.2%) patients respectively.A combination of PDE5I and intracavernous injections was the most frequently used first line treatment (233, 59%). VEDs were used in 52 patients in addition to PDE5I and intracavernous injections (39, 10%) or intracavernous injections (23, 6%). In patients with a preoperative IIEF>21, assisted and unassisted EF recovery rates were 78% and 36% respectively.In patients with a preoperative IIEF<16, assisted and unassisted EF recovery rates were 46% and 18% respectively. Sub analysis showed a moderate benefit of penile rehabilitation also in patients with a preoperative IIEF<16 undergoing bilateral nerve sparing RP.Intensive penile rehabilitation with PDE5I, intracavernous injections and VEDs led to the best patient perceived results. CONCLUSIONS: Intensive penile rehabilitation programs improves EF recovery in patients undergoing radical prostatectomy. Preservation of Neurovascular bundles should be attempted also in patients with preoperative ED. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e832 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ugo Falagario More articles by this author Michele Di Nauta More articles by this author Andrea Checchia More articles by this author Marco Recchia More articles by this author Anna Ricapito More articles by this author Nicola D'Altilia More articles by this author Pasquale Annese More articles by this author Gian Maria Busetto More articles by this author Luigi Cormio More articles by this author Giuseppe Carrieri More articles by this author Carlo Bettocchi More articles by this author Expand All Advertisement PDF DownloadLoading ...

Is short-course radiotherapy and total neoadjuvant therapy the new standard of care in locally advanced rectal cancer? A sensitivity analysis of the RAPIDO clinical trial

The results of the RAPIDO trial have been accepted as evidence in favour of short-course radiotherapy (SC-RT) followed by chemotherapy before total mesorectal excision in high-risk locally advanced rectal cancer. A noteworthy concern is that the RAPIDO trial did not ensure that all patients in the control arm received adjuvant chemotherapy. This may bias statistical estimates in favour of the experimental arm if adjuvant chemotherapy is active in rectal cancer. Moreover, the 5-year update revealed an increase in the risk of local relapse in the experimental arm. We carried out sensitivity analyses to determine how plausible effects of adjuvant chemotherapy, adjusted by the proportion of patients in the standard arm receiving adjuvant treatment, would have influenced the observed treatment effect estimate of the RAPIDO trial. The most plausible values for the benefit of adjuvant chemotherapy were determined by Bayesian re-analysis of a prior meta-analysis. The meta-analysis suggested that oxaliplatin/fluorouracil-based adjuvant chemotherapy may improve disease-free survival (DFS) in rectal cancer although the signal is weak [hazard ratio (HR) 0.84, 95% credible interval, 0.57-1.15]; probability of benefit (HR <1) was 91.2%. In the sensitivity analysis, the HR for disease-related treatment failure would remain <1, thus favouring total neoadjuvant therapy (TNT), on most occasions, but the null hypothesis would not have been rejected in various credible settings. For the RAPIDO data to be consistent with the null effect, a moderate benefit of adjuvant chemotherapy (HR for DFS between 0.75 and 0.80) and 70%-80% of exposed participants would suffice. The decision to make adjuvant chemotherapy optional in the standard arm may have biased the results in favour of the experimental arm, in a scenario in which TNT does not offset the increase in local recurrences after SC-RT.

The Effect of Pressotherapy on Performance and Recovery in the Management of Delayed Onset Muscle Soreness: A Systematic Review and Meta-Analysis.

Background: It has been demonstrated that pressotherapy used post-exercise (Po-E) can influence training performance, recovery, and physiological properties. This study examined the effectiveness of pressotherapy on the following parameters. Methods: The systematic review and meta-analysis were performed according to PRISMA guidelines. A literature search of MEDLINE, PubMed, EBSCO, Web of Science, SPORTDiscus, and ClinicalTrials has been completed up to March 2021. Inclusion criteria were: randomized control trials (RCTs) or cross-over studies, mean participant age between 18 and 65 years, ≥1 exercise mechanical pressotherapy intervention. The risk of bias was assessed by the Cochrane risk-of-bias tool for RCT (RoB 2.0). Results: 12 studies comprised of 322 participants were selected. The mean sample size was n = 25. Pressotherapy significantly reduced muscle soreness (Standard Mean Difference; SMD = −0.33; CI = −0.49, −0.18; p < 0.0001; I2 = 7%). Pressotherapy did not significantly affect jump height (SMD = −0.04; CI = −0.36, −0.29; p = 0.82). Pressotherapy did not significantly affect creatine kinase level 24–96 h after DOMS induction (SMD = 0.41; CI = −0.07, 0.89; p = 0.09; I2 = 63%). Conclusions: Only moderate benefits of using pressotherapy as a recovery intervention were observed (mostly for reduced muscle soreness), although, pressotherapy did not significantly influence exercise performance. Results differed between the type of exercise, study population, and applied treatment protocol. Pressotherapy should only be incorporated as an additional component of a more comprehensive recovery strategy. Study PROSPERO registration number—CRD42020189382.