Low Recruitment Rates Research Articles

A feasibility (pilot) mixed methods study of an innovative non-pharmacological breath-based yoga and social-emotional intervention program in an at-risk youth sample in London, Canada

BackgroundVarious service provision models for youth at risk of homelessness have been researched and implemented, including access to housing and physical and mental health resources. However, even with these interventions, we remain unaware of how best to manage symptoms of depression and anxiety and the rate of drug use in these populations primarily because of a lack of feasibility data.MethodsThis paper presents the results of a mixed-methods study in London, Canada, that examined the feasibility of implementing a biopsychosocial intervention, SKY Schools, in at-risk youth aged between 16 and 25 (n = 49). The study also recorded qualitative responses about the program’s usefulness from the perspective of the service users. The SKY Schools intervention consisted of social-emotional learning combined with Sudarshan Kriya Yoga, a standardized yoga-based breathing exercise routine. The intervention program was divided into two phases: an active learning phase and a reinforcement phase. The following feasibility outcome measures were collected: (1) the number of potential participants approached per month, (2) number (proportion) who were successfully screened, (3) the proportion of screened participants who enrolled, (4) the rate of retention in the study, (5) rate of adherence to study protocol, (6) proportion of planned ratings that were completed, (7) intervention cost per case, (8) completeness of final data for analysis, (9) length of time to collect all data, (10) quality of all collected data, (11) determining if partnering community organizations were willing to conduct the study as per study protocol, (12) determining if there were any capacity issues with partners providing intervention and investigators being able to perform the tasks that they were committed to doing, (13) determining if there were any problems of entering the data into a computer, (14) preliminary data about the safety of the intervention, and (15) preliminary estimate of treatment effects.ResultsAll feasibility outcome measures were collectible. In the city of London, Canada it was feasible to conduct a pilot study in this population of youth at risk of homelessness. Foremost among the findings was a high retention rate (61.2%) and overall positive qualitative feedback with a number of potential suggestions to improve the delivery and quality of the intervention. However, we had a significantly low recruitment rate (0.27 participants per week) suggesting that multiple sites will be needed to achieve an adequate sample size for a subsequent definitive trial.ConclusionsFuture researchers may consider the findings of this feasibility study when designing a randomized control trial to further assess the efficacy and tolerability of SKY Schools.Trial registrationTrial registration: Clinicaltrials.gov, identifier NCT02749240. Registered April 22, 2016, https://clinicaltrials.gov/ct2/show/NCT02749240.

Comparison of the safetyand efficacyfor different regimens of pharmaco-prophylaxis among severely burned patients: a randomized controlled trial.

Venous thromboembolism (VTE) is a common complication in critically ill patients, including severe burn cases. Burn patients respond differently to medications due to pharmacokinetic changes. This study aims to assess the feasibility and safety of different VTE pharmaco-prophylaxis in patients admitted to the ICU with severe burns. A pilot, open-label randomized controlled trial was conducted on ICU patients with severe burns (BSA ≥ 20%). By using block randomization, patients were allocated to receive high-dose enoxaparin 30mg q12hours (E30q12), standard-dose enoxaparin 40mg q24hours (E40q24), or unfractionated heparin (UFH) 5000 Units q8hours.In this study, the primary outcomes assessed were the recruitment and consent rates, as well as bleeding or hematoma at both the donor and graft site. Additionally, secondary measures were evaluated to provide further insights. Twenty adult patients out of 114 screened were enrolled and received E30q12 (40%), E40q24 (30%), and UFH (30%). The recruitment rate was one patient per month with a 100% consent rate. Donor site bleeding occurred in one patient (16.7%) in the UFH group. On the other hand, graft site bleeding was only reported in one patient (12.5%) who received E30q12. Major bleeding happened in two patients, one in E30q12 and one in the UFH group. Five patients (25.0%) had minor bleeding;two patients (25.0%) received E30q12, two patients E40q24, and onepatient UFH. RBC transfusion was needed in four patients, two on E30q12 and two on UFH. Only one patient had VTE, while four patients died in the hospital. The study observed a low recruitment rate but a high consent rate. Furthermore, there were no major safety concerns identified with any of the three pharmacologic prophylaxis regimens that were evaluated. NCT05237726.

Prehabilitative high-intensity interval training and resistance exercise in patients prior allogeneic stem cell transplantation

Physical capacity prior allogeneic stem cell transplantation (allo-HCT) has been shown as a relevant prognostic factor for survival after transplant. Therefore, we evaluated feasibility and preliminary efficacy of a high-intensity interval training (HIIT) and moderate to high-intensity resistance exercise (RE) to increase physical capacity in patient’s prior allo-HCT. In this multicentre single arm pilot study, a supervised exercise program was performed twice weekly for 4–12 weeks prior allo-HCT, depending on the individual time remaining. Outcomes were feasibility (recruitment, adherence, safety), physical capacity (cardiorespiratory fitness [VO2peak], muscle strength) and patient reported outcomes (physical functioning, fatigue). Thirty patients were intended, 16 could be included, and 14 completed post intervention assessment (75% male, 55 ± 11 years). The study was stopped early due to a low recruitment rate. Nine patients (64%) reached the initial minimum planned number of eight exercise sessions. Individual adherence was high with 92% for HIIT and 85% for RE. 87% of all performed exercise sessions were completed without complaints and VO2peak increased significantly from 20.4 to 23.4 ml/kg/min. The low recruitment rate suggests that initiation of the intervention concept immediately before allo-HCT is feasible only in a small number of patients. In particular, the timeframe directly prior allo-HCT seems too short for exercise interventions, although the exercise program was designed to improve outcomes in a very short time frame. HIIT and RE were feasible, effective and well accepted by the included patients.

The effects of dexmedetomidine on postoperative tumor recurrence and patient survival after breast cancer surgery: a feasibility study

PurposeDexmedetomidine (Dexmed) is a highly selective alpha 2 adrenoceptor (α2-AR) agonist with excellent sedation and analgesic effects and is frequently used in breast cancer surgery. However, the exact impact of Dexmed on breast cancer prognosis is still unclear. The primary objective of this pilot study was to explore study feasibility (recruitment and dropout rates) for future large-scale randomized controlled trial (RCT) to test the hypothesis that intraoperative Dexmed reduced recurrence-free survival (RFS) and overall survival (OS) in patients after breast cancer surgery.MethodsInterviews with patients were performed during the anesthetic preoperative visit for informed consent. Adult females scheduled for a mastectomy due to primary breast cancer were 1:1 randomised to saline (Group Control) or Dexmed (Group Dexmed) treatment groups. The primary outcomes were descriptions of study feasibility (recruitment and dropout rates). We also performed a preliminary analysis of RFS (time from surgery to the earliest date of recurrence/metastasis) and OS (time from surgery to the date of all-cause death) and collected data on percentages/numbers of circulating immune cells at pre- and 24 h post-operation.ResultsA total of 964 patients were screened; 40% (385/964) met the inclusion criteria, among which 39% (150/385) were enrolled and randomly assigned to either Group Control (n = 75) or Group Dexmed (n = 75). The median follow-up duration was 49 months (interquartile range (IQR): 34–58 months) for Group Control and 48 months (IQR: 33–60 months) for Group Dexmed. Five percent (5%, 8/150) patients were lost to follow-up and 1% (2/150) died. There was no significant difference in RFS and OS. The percentage/number of natural killer (NK), B and T-cell subsets and the CD4+/CD8+ ratio were similar between groups at 24 h post-operation.ConclusionThe pilot study was feasible to deliver. In a future definitive trial, the lower recruitment rate may be improved by increasing the number of anesthesiologists involved in the study. The study about the effects of Dexmed on long-term prognoses of breast cancer patients that is planned to follow this pilot study is a large-scaled randomized control study with the aim of providing evidence-based guidelines for rational use of Dexmed in patients undergoing breast cancer surgery.Trial registrationRegistered at ClinicalTrials.gov on October 20, 2016 (ID: NCT03109990).Graphical

Demographics of Palmer amaranth (Amaranthus palmeri) in annual and perennial cover crops

AbstractPalmer amaranth (Amaranthus palmeri S. Watson) is the most problematic weed of cotton (Gossypium hirsutum L.)-cropping systems in the U.S. Southeast. Heavy reliance on herbicides has selected for resistance to multiple herbicide mechanisms of action. Effective management of this weed may require the integration of cultural practices that limit germination, establishment, and growth. Cover crops have been promoted as a cultural practice that targets these processes. We conducted a 2-yr study in Georgia, USA, to measure the effects of two annual cover crops (cereal rye [Secale cereale L.] and crimson clover [Trifolium incarnatum L.]), a perennial living mulch (‘Durana®’ white clover [Trifolium repens L.]), and a bare ground control on A. palmeri population dynamics. The study was conducted in the absence of herbicides. Growth stages were integrated into a basic demographic model to evaluate differences in population trajectories. Cereal rye and living mulch treatments suppressed weed seedling recruitment (seedlings seed−1) 19.2 and 13 times and 12 and 25 times more than the bare ground control, respectively. Low recruitment was correlated positively with low light transmission (photosynthetic active radiation: above canopy photosynthetically active radiation [PAR]/below cover crop PAR) at the soil surface. Low recruitment rates were also negatively correlated with high survival rates. Greater survival rates and reduced adult plant densities resulted in greater biomass (g plant−1) and fecundity (seeds plant−1) in cereal rye and living mulch treatments in both years. The annual rate of population change (seeds seed−1) was equivalent across all treatments in the first year but was greater in the living mulch treatment in the second year. Our results highlight the potential of annual cover crops and living mulches for suppressing A. palmeri seedling recruitment and would be valuable tools as part of an integrated weed management strategy.

Modeling Study of the Effects of Ageratum conyzoides on the Transmission and Control of Citrus Huanglongbing.

Ageratum conyzoides (A. conyzoides) is commonly found or intentionally planted in citrus orchards due to its ability to provide habitat and breeding grounds for the natural enemies of citrus pests. This study aims to expand from a switching Huanglongbing model by incorporating the effects of A. conyzoides, vector preferences for settling, and pesticide application intervals on disease transmission. Additionally, we establish the basic reproduction number R0 and its calculation for a general switching compartmental epidemic model. Theoretical findings demonstrate that the basic reproduction number serves as a threshold parameter to characterize the dynamics of the models: if R0<1, the disease will disappear, whereas if R0>1, it will spread. Numerical results indicate that the recruitment rate of A. conyzoides not only affects the spread speed of Huanglongbing but also leads to paradoxical effects. Specifically, in cases of high infection rates, a low recruitment rate of A. conyzoides can result in a decrease, rather than an increase, in the basic reproduction number. Conversely, a high recruitment rate can accelerate the spread of Huanglongbing. Furthermore, we show how different vector bias and pesticide spraying periods affect the basic reproduction number.

Preliminary efficacy of an acceptance-based diabetes education (ACT-DE) programme for people with type 2 diabetes on diabetes distress and self-care behaviours: A pilot randomised controlled trial

BackgroundDiabetes distress is often characterised by aversive feelings about diabetes and avoidance of diabetes self-care, leading to suboptimal blood glucose control, diabetes complications and depression. Evidence from a recent review has indicated the potential efficacy of acceptance-based diabetic self-management programmes for improving blood glucose levels and mental health outcomes by fostering psychological flexibility. MethodsWe conducted a two-arm and assessor-blinded pilot randomised controlled trial (RCT) with 48 participants aged 18–64 with type 2 diabetes and moderate distress levels, in which we compared a 6-week acceptance and commitment therapy and diabetes education (ACT-DE) programme intervention with diabetes education. Diabetes distress (the primary outcome), self-care behaviour, self-efficacy in diabetes management, and psychological inflexibility were measured at baseline and post-intervention. Focus group interviews were conducted to explore the intervention group's perceptions of the benefits and limitations of the intervention. ResultsResults of ANCOVA test showed that the intervention group exhibited significantly greater decrease in diabetes distress (effect size [Cohen's d] = 0.65), and increase in exercise frequency (d = 1.16), and foot-care frequency (d = 0.59) than the diabetes education group. The qualitative feedback of the intervention group revealed that the learnt ACT skills can be effectively applied in self-care and highlighted the utility of some of the intervention's therapeutic components, primarily mindfulness practices, metaphors, and interactive diabetes education. The intervention was well-accepted, with an 87.5% completion rate, but caution is needed due to a low recruitment rate (28.1%) during COVID-19 pandemic peak. ConclusionThis pilot study confirmed that ACT-DE programme is an acceptable intervention for people with type 2 diabetes. It demonstrated preliminary efficacy with medium-to-large effect sizes in alleviating the participants’ diabetes distress and improving their self-care. Recruitment strategies can be improved to enhance the feasibility. Moreover, a full-scale RCT with longer-term follow-up is warranted to examine the intervention effects on diabetes distress, blood glucose control and other health outcomes.

Timing of umbilical cord occlusion, delayed vs early, in preterm babies: A randomized controlled trial (CODE-P Trial)

IntroductionOur hypothesis was that delayed cord clamping (DCC) (not earlier than 30 s; at 30–60 s) in premature neonates (born between 26.0 and 32.6 weeks of gestation), as compared with the usual early cord clamping (ECC), significantly reduces the need for blood transfusions and incidence of intraventricular haemorrhage (IVH) without an increased rate of maternal postpartum haemorrhage. Material and methodsA prospective, open-label, randomized, controlled trial was conducted at Vall d’Hebron Hospital from July 2014 to December 2018. All pregnant women at risk of impending preterm birth (≥26.0-<33.0 weeks of gestation) who were admitted to the obstetrics emergency department were evaluated for eligibility. If they met the eligibility criteria, they were invited to participate in the study and, if they agreed, they signed an informed consent. Patients were randomly assigned to one of two groups: ECC group and DCC group. ResultsOur study included a total of 57 patients: 30 in the ECC group and 27 in the DCC group. Due to a lack of funding and low recruitment rates, the study was discontinued in 2018. Maternal characteristics and obstetric outcomes were similar between both groups. The intention-to-treat analysis did not reveal any differences between groups for neonatal red blood cell transfusions, neonatal IVH or maternal postpartum haemorrhage. There were no differences for secondary outcomes. Similarly, no differences were observed in the as-treated analysis. ConclusionThe primary and secondary outcomes of our study were not achieved. Therefore, more meta-analysis and trials are needed to evaluate the appropriate timing of cord clamping in preterm birth.

A systematic review of ambulance service-based randomised controlled trials in stroke

BackgroundTreatment for stroke is time-dependent, and ambulance services play a vital role in the early recognition, assessment and transportation of stroke patients. Innovations which begin in ambulance services to expedite delivery of treatments for stroke are developing. However, research delivery in ambulance services is novel, developing and not fully understood.AimsTo synthesise literature encompassing ambulance service-based randomised controlled interventions for acute stroke with consideration to the characteristics of the type of intervention, consent modality, time intervals and issues unique to research delivery in ambulance services.Summary of reviewOnline searches of MEDLINE, EMBASE, Web of Science, CENTRAL and WHO IRCTP databases and hand searches identified 15 eligible studies from 538. Articles were heterogeneous in nature and meta-analysis was partially available as 13 studies reported key time intervals, but terminology varied. Randomised interventions were evident across all points of contact with ambulance services: identification of stroke during the call for help, higher dispatch priority assigned to stroke, on-scene assessment and clinical interventions, direct referral to comprehensive stroke centres and definitive care delivery at scene. Consent methods ranged between informed patient, waiver and proxy modalities with country-specific variation. Challenges unique to the prehospital setting comprise the geographical distribution of ambulance resources, low recruitment rates, prolonged recruitment phases, management of investigational medicinal product and incomplete datasets.ConclusionResearch opportunities exist across all points of contact between stroke patients and ambulance services, but randomisation and consent remain novel. Early collaboration and engagement between trialists and ambulance services will alleviate some of the complexities reported.Registration numberPROSPERO 2018CRD42018075803

Freshwater turtle populations as bioindicators following an oil spill: Delayed demographic changes reveal long-term impacts

Chronic, long-term impacts of oil spill disasters on wildlife often exceed short-term, highly visible mass mortalities and widespread oiling of individuals. Species with long lifespans, late maturation, and low recruitment rates are particularly vulnerable to long-term population-level impacts but can be useful as indicator species for ecosystem recovery. In 2010, one of the largest freshwater oil spills in the U.S. occurred in the Kalamazoo River, MI, when 3.2 million L of spilled oil impacted 56 km of river and associated wildlife. During cleanup and restoration efforts in 2010–2011, thousands of northern map turtles (Graptemys geographica) were captured, cleaned, and released. During 2019–2020 northern map turtles were captured to evaluate changes in the population size, demography, and size classes nine to ten years later.Population demography shifts occurred in the first few years after the spill in a species that otherwise exhibits minimal demographic fluctuation under “normal” conditions. In comparing demographic parameters at the time of the oil spill to values ∼ 10 years post-spill, a nearly 30% reduction in population size was detected, distribution of body size shifted to smaller males and females, and there was a shift in the population sex ratio between 2011 and 2019. There were also signals of failed recruitment in cohorts that would have hatched during the years immediately before and after the oil spill. These data suggest that beyond the direct mortality caused by the spill, declines in the estimated population size and shifts in the size distribution of northern map turtles are likely indicative of negative demographic impacts incurred following the 2010 oil spill and resulting cleanup.

Pain and function in patients with chronic low back pain and leg pain after Zhineng Qigong – a quasi-experimental feasibility study

BackgroundQigong includes training for body and mind, one method is Zhineng Qigong. Scientific literature on qigong for chronic low back pain (LBP) is sparse. This study aimed to investigate feasibility including evaluation of a Zhineng Qigong intervention for pain and other lumbar spine-related symptoms, disability, and health-related quality of life in patients with chronic LBP and/or leg pain.MethodsProspective interventional feasibility study without control group. Fifty-two chronic pain patients (18–75 years) with LBP and/or leg pain (Visual Analogue Scale ≥ 30) were recruited from orthopaedic clinics (spinal stenosis, spondylolisthesis, or segmental pain) and primary healthcare (chronic LBP). Patients from orthopaedic clinics were 1–6 years postoperative after lumbar spine surgery or on lumbar surgery waiting list. Patients received a 12-week training intervention with European Zhineng Qigong. The intervention consisted of face-to-face group activities in non-healthcare setting (4 weekends and 2 evenings per week), and individual Zhineng Qigong training. Main health outcomes were self-reported in a 14-day pain diary, Oswestry Disability Index (ODI), Short Form 36 version 2 (SF-36v2), and EuroQol 5 Dimensions 5 Levels (EQ-5D-5L), once directly before and once directly after the intervention.ResultsRecruitment rate was 11% and retention rate was 58%. Dropouts did not report higher pain (baseline), only 3 dropped out because of lumbar spine-related pain. Adherence was median 78 h group attendance (maximum 94 h) and 14 min daily individual training. Ability to collect outcomes was 100%. Thirty patients completed (mean 15 years symptom duration). Twenty-five had degenerative lumbar disorder, and 17 history of lumbar surgery. Results showed statistically significant (within-group) improvements in pain, ODI, all SF-36v2 scales, and EQ-5D-5L.ConclusionsDespite low recruitment rate, recruitment was sufficient. A multicentre randomized controlled trial is proposed, with efforts to increase recruitment and retention rate. After this Zhineng Qigong intervention patients with chronic LBP and/or leg pain, also patients with considerable remaining LBP/sciatica after lumbar surgery, had significantly improved in pain and function. Results support involvement of postoperative patients in a future study. The results are promising, and this intervention needs to be further evaluated to provide the most reliable evidence.Trial registrationNCT04520334. Retrospectively registered 20/08/2020.

The effects of exercise with or without dietary advice on muscle mass, muscle strength, and physical functioning among older cancer survivors: a meta-analysis of randomized controlled trials.

To evaluate the effect of exercise with or without dietary advice on muscle mass, muscle strength and physical functioning (including perceived physical functioning and physical performance) in old cancer survivors. A systematic literature search was undertaken in May 2022 by searching multiple databases. Randomized controlled trials (RCTs) that compared exercise with or without dietary advice to control group among old cancer survivors were screened. Meta-analyses were conducted to evaluate the effects of exercise with or without dietary advice on muscle mass, muscle strength, and physical functioning. Data from 21 trials were included in this study, including 16 exercise trials and 5 exercise + dietary advice studies. Regarding exercise, evidence supported its significant benefits on muscle strength among old cancer survivors, while no effect was seen on physical functioning and muscle mass. Concerning exercise combined with dietary advice, meta-analysis showed overall benefits on physical functioning, while limited study examined muscle mass and strength. As for safety and feasibility of interventions, low recruitment rate, moderate compliance, and few adverse events were reported. Exercise combined with dietary advice is a more effective approach for old cancer survivors in improving physical functioning compared with exercise alone. Future study is needed to explore the effects of exercise combined with dietary advice on combating sarcopenia. As recruitment and compliance among old cancer survivors were challenging, strategies to stimulate their motivation and promote habitual healthy behaviour are warranted. It is necessary for old cancer survivors to receive exercise and dietary support to improve physical functioning.

Community Informed Recruitment: A Promising Method to Enhance Clinical Trial Participation.

Low recruitment rates in palliative care clinical trials amongst Black and rural individuals have been attributed to lack of trust and procedural barriers. Community engagement strategies have increased clinical trial participation of under-represented populations. Describe a successful community-engaged recruitment strategy in an ongoing multi-site randomized clinical trial (RCT). Using community-based participatory research principles and input from a prior pilot study's community advisory group (CAG), we designed a novel recruitment strategy for Community Tele-Pal, a three-site, culturally based palliative care tele-consult RCT for Black and White seriously ill inpatients and their family caregivers. Local site CAGs helped design and implement a recruitment strategy in which a CAG member accompanied the study coordinators to introduce the study to eligible patients. Initially, CAG members could not accompany study coordinators in person due to pandemic restrictions. Hence, they created videos of themselves introducing the study, just as they would have done in person. We examined outcomes to date by the three recruitment methods and race. Of the 2879 patients screened, 228 were eligible and approached. Overall, the proportions of patients who consented 102 (44.7%) vs. not consented 126 (55.3%) were similar by race- White (consented= 75 [44.1%]) vs; Black (consented=27 [46.6%]). Proportionally, consent rates favored CAG-involved methods: coordinator only- 47 approached and 13 (12.7%) consented vs. coordinator/CAG video-105 approached and 60 (58.8%) consented. A novel community-enhanced recruitment strategy demonstrated the potential to increase clinical trial participation from historically under-represented populations.

A national survey of current scenario and future perspectives of cancer research in Brazil.

e18721 Background: Epidemiological and clinical cancer research are the backbone to understand tumor behavior and to develop new therapies in oncology. However, several countries including Brazil and many regions in the world have a very small participation in cancer research. Despite 625.000 new cancer cases recorded in Brazil in 2022, only 2,2% of ongoing cancer clinical trials are available in the country We conducted an online survey to describe physician engagement with research and to identify the main barriers precluding participation and conduct of clinical cancer research in the country. Methods: An anonymous online survey of 23 objective questions was sent by e-mail to members of the Latin American Cooperative Oncology Group (LACOG) and the Brazilian Society of Clinical Oncology (SBOC). The first 13 questions addressed demographic information, medical training, and previous research participation. In the second part, the main barriers to engagement and participation in clinical trials in Brazil were addressed. Continuous variables were measured by median and range. Analyses were performed using SAS statistical software (version 9.4; SAS Institute, Inc. Cary, NC). Results: 109 physicians answered the survey. Most participants were oncologists (N = 98, 89.9%), living in capital cities (N = 84, 77.1%), were from the Southeast region of Brazil (N = 63, 57.8%), worked at institutions providing exclusively private healthcare (N = 59, 54.1%). Of the 109 respondents, 83 (76.1%) reported working in research centers (as investigators or sub-investigators). Surprisingly, 31.2% of physicians recognized they invite less than 1% of their patients to participate in clinical trials, even though 98 (89.9%) considered the participation of patients in clinical trials extremely relevant. The main barriers compromising conduct of research in the country were low number of available trials proposed by pharma/Clinical Research Organizations (48.2%) and the lack of qualified human resources to staff research sites (22.9%). Other reported barriers were the lengthy regulatory approval process (42.2%), followed by lack of awareness of clinical research by patients resulting in low recruitment rates (24.1%). Of the 26 (23.8%) respondents not working with research, 25 (96.1%) reported interest in being involved, 31.8% have tried participating in research, and 62.4% reported limited knowledge of trial procedures. Conclusions: These results suggest a clear need to further engage physicians in clinical research activities in Brazil. Patient education strategies should improve the low recruitment rates and secondarily increase the number of proposed trials to the country.

Long‐term nicotine treatment of mild cognitive impairment (The MIND Study): Baseline characteristics and study progress

AbstractBackgroundCognitive decline in AD/MCI is related to loss of cholinergic neurons. However, inhibition of acetylcholine degradation has not slowed progression. Treatment directly targeting nicotinic cholinergic receptors may be more helpful. We have shown proof of concept in a 6‐month multicenter trial that transdermal nicotine provides significant improvement in attention, episodic memory, and global ratings of functioning with minimal side effects in MCI. A larger and longer (2‐year) trial is underway to determine the persistence of improvement and attenuation of cognitive decline.MethodMCI participants were randomized 1:1 to either transdermal nicotine, beginning at 3.5 mg/day, increasing to 21 mg/day or matching placebo by 5 weeks. Participants were assessed at 0, 3, 6, 12, 18, and 24 months, with a subset undergoing MRI scans at 0, 12, and 24 months, and CSF collection at 0 and 24 months. Primary cognitive outcomes included reaction time standard error change‐from‐baseline (Connors CPT) for attention and delayed word recall (Cogstate) for memory. Primary clinical outcome is the CGIC. Secondary clinical measures include behavioral/functional scales and the CDR‐SOB. An MRI substudy is examining possible neural mechanisms.ResultTo date, 663 participants were screened and 309 were randomized including 133 females (43%) and 176 males (57%). Mean age was 73.7±7.1, education 16±2.8 years. Mean MMSE was 27.4±1.8 and CDR Global was 0.5. Randomization of ethnoracial underrepresented populations (URPs) was 9.4% (Black/African‐American 4%, Asian 2%, Hispanic/Latinx 3%). Treatment/Study discontinuations were higher than expected at 29% due in part to pandemic‐related disruptions. There are 87 completers thus far. Baseline MRI scans are 59 and LPs are 37. Safety results show that treatment has been generally well tolerated with no SAEs definitively or probably tied to study participation or investigational product thus far.ConclusionIf the hypotheses are validated, this will support a novel, broadly available, and inexpensive repurposed intervention for MCI and would encourage early treatment to improve symptoms, attenuate progression of cognitive impairment, and lead to combined trials with agents that interact with Aβ, tau or other mechanisms. Low URP recruitment and higher dropout rate remain challenging and will be specifically addressed in recruitment/enrollment/retention efforts moving forward.

Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial.

Activation of the TREM-1 pathway is associated with outcome in life threatening COVID-19. Data suggest that modulation of this pathway with nangibotide, a TREM-1 modulator may improve survival in TREM-1 activated patients (identified using the biomarker sTREM-1). Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0mg/kg/h) compared to placebo. Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS. Patients were included from September 2020 to April 2022, with a pause in recruitment between January and August 2021. Primary outcome was the improvement in clinical status defined by a seven-point ordinal scale in the overall population with a planned sensitivity analysis in the subgroup of patients with a sTREM-1 level above the median value at baseline (high sTREM-1 group). Secondary endpoints included safety and all-cause 28-day and day 60 mortality. The study was registered in EudraCT (2020-001504-42) and ClinicalTrials.gov (NCT04429334). The study was stopped after 220 patients had been recruited. Of them, 219 were included in the mITT analysis. Nangibotide therapy was associated with an improved clinical status at day 28. Fifty-two (52.0%) of patients had improved in the placebo group compared to 77 (64.7%) of the nangibotide treated population, an odds ratio (95% CI) for improvement of 1.79 (1.02-3.14), p=0.043. In the high sTREM-1 population, 18 (32.7%) of placebo patients had improved by day 28 compared to 26 (48.1%) of treated patients, an odds ratio (95% CI) of 2.17 (0.96-4.90), p=0.063 was observed. In the overall population, 28 (28.0%) of placebo treated patients were not alive at the day 28 visit compared to 19 (16.0%) of nangibotide treated patients, an absolute improvement (95% CI) in all-cause mortality at day 28, adjusted for baseline clinical status of 12.1% (1.18-23.05). In the high sTREM-1 population (n=109), 23 (41.8%) of patients in the placebo group and 12 (22.2%) of patients in the nangibotide group were not alive at day 28, an adjusted absolute reduction in mortality of 19.9% (2.78-36.98). The rate of treatment emergent adverse events was similar in both placebo and nangibotide treated patients. Whilst the study was stopped early due to low recruitment rate, the ESSENTIAL study demonstrated that TREM-1 modulation with nangibotide is safe in COVID-19, and results in a consistent pattern of improved clinical status and mortality compared to placebo. The relationship between sTREM-1 and both risk of death and treatment response merits further evaluation of nangibotide using precision medicine approaches in life threatening viral pneumonitis. The study was sponsored by Inotrem SA.

(126) Long-term Functional Outcomes for Men with Priapism Secondary to Recreational Use of Intracavernosal Injectables: A Multi-center Follo- up Study

Abstract Introduction Ischemic priapism is a urologic emergency which results in permanent erectile dysfunction if not managed immediately. There is a dearth of studies evaluating long term erectile function after episodes or treatment for priapism. Objective We evaluated the functional outcomes of a larger, multi-institutional population of men with priapism due to recreational use of ICIs. Methods Men who presented with ischemic priapism due to recreational use of ICIs to Cedars-Sinai Medical Center (Los Angeles, CA), University of California at San Francisco (San Francisco, CA), and Jackson Memorial Hospital (Miami, FL) from January 2010 to December 2018 were contacted via telephone. All participants completed the five-item international index of erectile function (IIEF-5). Results A total of 19 men aged 24 – 59 (mean 47.9) were recruited from the 3 sites. Mean follow up was 77.2 months (+/− 27.6). 17 men (89%) were white; the one man was Asian (5.5%) and one man was Hispanic (5.5%). Seven men (37%) had been diagnosed with ED prior to their priapism episode however none of the men had a prescription for ICIs. Four men (21%) required no intervention at all, eleven men (58%) required phenylephrine irrigation alone, four men (21%) required distal shunting. No men required proximal shunting. None of the men had no ED, 31.6% had mild ED, 36.8% had mild-moderate ED, 26.3% had moderate ED, and 5.3% had severe ED. Mean IIEF-5 for the population was 13.4 (+/− 3.9). Strengths of our study included the large population size give the relative rarity of this condition as well as the geographic diversity of our population. Limitations include our low overall recruitment rate and lack of objective measures of erectile function prior to priapism. Conclusions Men who suffer ischemic priapism secondary to recreational use of ICIs appear to retain some erectile function following their priapism episode. Nevertheless, 100% report some level of ED. This is likely due a combination of adequate erectile function at baseline and expeditious treatment of priapism in a minimally invasive manner. Disclosure No

Physiological and morphometric characteristics of Pachycereus pringlei (S.Watson) Britton &amp; Rose seedlings applying organic manures

The establishment of Pachycereus pringlei seedlings is a scarce event; soil conditions are one of the factors attributed to its high mortality rate in the early stages of development. The use of organic manures as a substrate helps to improve the structure, porosity, and density of the soil where they live, in addition to providing nutrients that would benefit the roots, increasing the possibility of their establishment during the emergence stage. The objective of this study was to evaluate the effect of different proportions of organic manures as a sown substrate in the emergence and establishment of Pachycereus pringlei seedlings, using nine treatments of organic manures in a completely randomized experimental design with four replications. The variables measured were emergence rate (ER) and percentage (EP) and their indices, seedlings’ morphometric, and physiological characteristics in the establishment stage. The results showed that the evaluated variables in the emergence and seedling establishment phase indicate the preference for natural substrate and organic manure combinations in proportions of 50 and 30%, respectively. The analysis of variance showed significant differences regarding the morphometric and physiological variables of the stem and root of the evaluated treatments. The emergence and establishment analyses show that cardon seedlings under different organic manure treatments and controlled conditions had excellent survival results compared to the low rates of recruitment and survival reported under natural conditions. Similarly, the implementation of organic manures improved the physiological and morphometric characteristics of the cardon seedlings compared to the control treatment with the natural substrate.

What’s the key for success? Translocation, growth and thermal stress mitigation in the Mediterranean coral Cladocora caespitosa (Linnaeus, 1767)

Marine heat waves (MHWs) are affecting corals populations, advocating their inclusion in restoration actions since conservation measures may be not sufficient. Cladocora caespitosa is a Mediterranean reef-building, long-living species, with low recruitment rate and high juvenile mortality, leading to the need for its inclusion in international and European legislations. The aim of this study, conducted in the southern Tyrrhenian Sea, was to test the translocation of several C. caespitosa colonies thriving on an artificial substrate intended for demolition, applying transplantation techniques. Thirty-four colonies were transplanted in May 2018, and monitored over 4 years, to check for their persistence and health status. The shaded position of the recipient site resulted adequate, considering that colony survival rates were as high as 82.4%, 70.6% and 55.9% in October 2018, January 2020 and October 2022, respectively. Colonies presented signs of suffering only after the high temperatures occurred during summer 2022, with a decreasing rate of -2.5 ± 0.4 corallite/month. To better interpret the documented survival rates, 40 fragments of C. caespitosa were reared in aquaria to test temperature and light effects on growth rates and resistance to thermal stress, simulating a MHW and exacerbating the dim-light natural conditions of the recipient site, exposing half of the fragments to complete darkness. Only bigger fragments produced new corallites, with a rate of 1.3 ± 0.3 corallites/month, like the natural growth rate obtained in the field before the thermal anomaly, highlighting the suitability of ex-situ rearing as a potential tool to supply restoration project. After 5-days at 28.5°C, all fragments survived, despite showing tissue retraction, shorter tentacles, lower responsiveness, and zooxanthellae density variation. Overall, our results highlighted a promising plasticity of C. caespitosa in the field, representing a good candidate for restoration purposes. In aquaria this adaptive potential has been tested on a single genotype and more tests are needed to assess the intraspecific variability of these responses. A first insight into the species-based siting selection was provided to ensure the success of a restoration action. Our results point out the importance of knowing life history traits and ecological optima to design proper management and restoration measures.

Population dynamics of the last leopard population of eastern Indochina in the context of improved law enforcement

Poaching, a major threat to wildlife worldwide, is pushing species toward extinction. To reduce poaching pressure and combat biodiversity loss, improved law-enforcement efforts reportedly are required; the effectiveness of which can be determined through rigorous monitoring of wildlife populations, particularly of endangered large carnivores. In the Eastern Plains Landscape of Cambodia, law-enforcement efforts increased to counter the severe threats from illegal activities; however, it is unknown if these strategies are benefiting the population of the Critically Endangered Indochinese leopard (Panthera pardus delacouri), the last large felid population of eastern Indochina. We used open population spatial capture-recapture models to estimate density, survival, per-capita recruitment, and population growth rates of leopard using data from 7 camera-trap surveys conducted over 11 years (2009–2019). We found that the population (a) declined by over 82 % (from 1.5 to 0.3 leopard/100 km2), (b) had low survival probability (0.58) and low recruitment rates (males: 0.04, females: 0.24), and (c) is expected to continue declining. An additional survey in 2021 failed to detect leopard, suggesting the species now is functionally extinct, if not fully extirpated, from the landscape. Over the study period, there was a drastic increase in human activity, with a 20-fold increase in detection frequencies of humans and a 1000-fold increase in lethal-trap encounter rate. The rise in anthropogenic pressures, particularly snaring, appeared to be the primary reason for the leopard decline, indicating the last decade of management interventions was insufficient to conserve the species, which now appears to be extirpated in all of Cambodia, Laos and Vietnam. This has implications for leopard conservation in the wider region, notably that efforts should now focus on populations within the two remaining strongholds. Our results suggest that increases in law-enforcement efforts alone are unlikely to protect wildlife in eastern Indochina; thus, additional strategies are needed to address the region's snaring crisis, including legislative reforms, community engagement, and programs that reduce demand for wildlife meat and products. Long-term studies of remaining Indochinese leopard populations coupled with timely and effective conservation actions are needed to avoid the complete demise of this subspecies.