Poor Recruitment Research Articles

Prediction of clinical trial enrollment rates.

Clinical trials represent a critical milestone of translational and clinical sciences. However, poor recruitment to clinical trials has been a long standing problem affecting institutions all over the world. One way to reduce the cost incurred by insufficient enrollment is to minimize initiating trials that are most likely to fall short of their enrollment goal. Hence, the ability to predict which proposed trials will meet enrollment goals prior to the start of the trial is highly beneficial. In the current study, we leveraged a data set extracted from ClinicalTrials.gov that consists of 46,724 U.S. based clinical trials from 1990 to 2020. We constructed 4,636 candidate predictors based on data collected by ClinicalTrials.gov and external sources for enrollment rate prediction using various state-of-the-art machine learning methods. Taking advantage of a nested time series cross-validation design, our models resulted in good predictive performance that is generalizable to future data and stable over time. Moreover, information content analysis revealed the study design related features to be the most informative feature type regarding enrollment. Compared to the performance of models built with all features, the performance of models built with study design related features is only marginally worse (AUC = 0.78 ± 0.03 vs. AUC = 0.76 ± 0.02). The results presented can form the basis for data-driven decision support systems to assess whether proposed clinical trials would likely meet their enrollment goal.

Randomised controlled trial of nebulised gentamicin in children with bronchiectasis.

AimFollowing trials of inhaled antibiotics in adults, this study investigates the efficacy of nebulised gentamicin to improve respiratory function in children with bronchiectasis.MethodsThis is a randomised, double‐blind, placebo‐controlled, crossover trial of 12‐week nebulised placebo/gentamicin, 6‐week washout, 12‐week gentamicin/placebo. Participants were children (5–15 years) with bronchiectasis, chronic infection (any pathogen), and able to perform spirometry from a hospital bronchiectasis clinic. Primary outcomes were change in forced expiratory volume in 1 s (FEV1) and hospitalisation days. Secondary outcomes included sputum bacterial density, sputum inflammatory markers, additional antibiotics and symptom severity. Analyses were on an intention‐to‐treat basis.ResultsFifteen children (mean 11.7‐years‐old) completed the study. There was no significant change in mean FEV1 (56%/55%, P = 0.38) or annual rate of hospital admissions (1.1/0, P = 0.12) between gentamicin and placebo, respectively. However, Haemophilus influenzae sputum growth (27% vs. 80%, P = 0.002) and bacterial density (2.4 log10 cfu/mL lower P < 0.001) improved with gentamicin. Sputum inflammatory markers interleukin‐1β (P < 0.001), interleukin‐8 (P < 0.001) and tumour necrosis factor‐α (P = 0.003) were lower with gentamicin. Poor recruitment limited study power and treatment adherence was challenging for this cohort.ConclusionsIn this crossover study of nebulised gentamicin in children with bronchiectasis, there was a reduction in sputum bacterial density and inflammation. However, there were no major improvements in clinical outcomes and adherence was a challenge.

Low Recruitment in a Double-Blind, Placebo-Controlled Trial of Ocrelizumab for Autoimmune Encephalitis: A Case Series and Review of Lessons Learned.

IntroductionObservational data suggest that B-cell-depleting therapies are effective for antibody-mediated autoimmune encephalitis. However, randomized controlled trials are needed. Here, we report challenges encountered in a randomized, placebo-controlled trial of ocrelizumab for autoimmune encephalitis that failed to meet recruitment goals.MethodsThis was a single-center, 12-month, randomized, double-blind, placebo-controlled trial. Patients with autoimmune encephalitis were randomized in 1:1 fashion to placebo or ocrelizumab infusion after receiving first-line immunotherapy. The primary endpoint of the study was clinical worsening, defined as a perceived decline by the patient or clinician or a decrease in the Lawton and Brody Instrumental Activities of Daily Living Scale (IADL), along with either worsening on the Texas Functional Living Scale (TFLS) or hospitalization for symptoms of encephalitis.ResultsAmong 16 eligible patients, only three enrolled in the study, which closed due to poor recruitment. Two participants were randomized to the ocrelizumab arm and one to the placebo arm. The single patient in the placebo arm (NMDAR+) met the primary endpoint at 12 weeks and received open-label ocrelizumab with improvement. In the ocrelizumab arm, one participant (NMDAR+) demonstrated marked improvement, and the second (LGI1+) remained clinically stable. There were no serious adverse events associated with ocrelizumab.ConclusionClinical trial recruitment for autoimmune encephalitis is challenging, and our trial did not meet recruitment goals. Large, multicenter clinical trials are still needed, and careful attention must be given to study design, endpoints, and patient selection. Instrumented functional rating scales will be valuable outcome measures for future studies.Trial RegistrationClinicalTrials.gov identifier: NCT03835728.

Investigators' sense of failure thwarted transparency in clinical trials discontinued for poor recruitment

Background and ObjectiveWhen a randomized clinical trial (RCT) prematurely discontinues, it is essential that stakeholders do the right thing to ensure that lessons can be learnt and trust in clinical research is maintained. There is, however, a lack of evidence exploring this issue. This study aimed to examine clinical trial stakeholders’ practices following trial discontinuation due to poor participant recruitment and their views on implications of such discontinuation. MethodsIndividual semi-structured qualitative interviews were conducted with 49 clinical trial stakeholders from Switzerland (n = 39), Germany (n = 9) and Canada (n = 1) between August 2015 and November 2016. ResultsAfter interviews with 49 clinical trial stakeholders (75% male presenting), it was found that stakeholders were aware of the risks of premature trial discontinuation wasting limited resources, adversely impacting scientific evidence, and having negative personal and professional implications. However, barriers continue to undermine transparency regarding trial discontinuation in practice, with it being reported that most investigators of discontinued trials are failing to notify stakeholders or publishing their results. Investigators sense of failure and associated negative emotions were identified as a key reason why investigators are not more transparent following discontinuation. ConclusionThe decision to notify stakeholders and publish results of a discontinued clinical trial should not rest solely on individual investigators but come from a systemic approach. However, until health research proactively requires the dissemination of results of all clinical trials, much will rest on individual investigators being motivated to do the right thing. Support programs might be helpful for investigators involved in discontinued trials and promote transparency and learning lessons.

Incorporating environmental variability in a spatially-explicit individual-based model of European sea bass✰

The northern stock of European sea bass (Dicentrarchus labrax) is a large, high value, slow growing and late maturing fish that is an important target species for both commercial and recreational fisheries. Around the UK, scientific assessments have shown a rapid eight-year decline in spawning stock biomass since 2010 attributed to poor recruitment; this was likely driven by environmental factors and high fishing mortality. Management of the stock is informed by scientific assessments in which a population model is fitted to the available data and used to forecast the possible consequences of various catch options. However, the model currently used cannot represent the spatial distribution of the stock or any effects of environmental variability. One approach that may be used to represent the effects of spatial and temporal variation in environmental drivers is with Individual based models (IBMs). In IBMs populations are represented by their constituent individuals that interact with their environment and each other. The mechanistic nature of IBMs is often advantageous as a management tool for complex systems including fisheries. Here we add to an existing IBM to produce a spatio-temporally explicit IBM of the northern stock of sea bass in which individual fish respond to local food supply and sea surface temperature. All life stages (i.e., pelagic stages, juvenile and mature fish) are modelled and individual fish have their own realistic energy budgets driven by observed dynamic maps of phytoplankton density and sea surface temperature. The model is calibrated using Approximate Bayesian Computation (ABC). After calibration by ABC the model gives good fits to key population parameters including spawning stock biomass. The model provides a mechanistic link between observed local food supplies and sea surface temperatures and overall population dynamics. Plots of spatial biomass distribution show how the model uses the energy budget to predict spatial and temporal change in sea bass biomass distribution in response to environmental variability. Our results indicate that the IBM is a promising approach that could be used to support stock assessment with scope for testing a range of spatially and temporally explicit management scenarios in addition to testing stock responses to novel environmental change.

Influence of environmental and population factors on Prince William Sound herring spawning phenology

Shifts in spawning phenology may impact the early life stages of small pelagic fishes, affecting their first-year survival and recruitment. In Prince William Sound, Pacific herring is a key forage species that once supported commercial and subsistence fisheries for many decades, but collapsed in 1993 and has yet to recover. Starting in 1980, spawn timing shifted earlier by approximately 2-4 wk over a 27 yr period, then abruptly shifted later by approximately 3 wk over the next 7 yr. We quantified the influence of 15 environmental and population-level covariates on these spawn timing shifts using generalized linear models. Earlier spawn timing was associated with higher biomass in the eastern sound and older mean age in the western sound. Across the entire sound, earlier spawning was associated with weaker downwelling, weaker meridional winds, and the positive phase of the Pacific-North American teleconnection pattern, which is characterized by warmer North Pacific waters. These results are a critical first step towards assessing how changes in spawning phenology impact first-year survival of herring offspring and potentially contribute to persistent poor recruitment that has inhibited the recovery of the Prince William Sound population.

The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.

Background:Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.Methods:Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site.Results:The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at 6 months was -3.86 (95% Confidence Intervals = -10.04 to 2.32). There were 14 serious adverse events; 6 in the clozapine arm and 8 in the placebo arm of the trial. There was little difference in the cost of care between groups.Interpretation:We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units.Trial registrationISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058

Pre-emergence processes limit seedling recruitment in two direct seeded Acacia spp.

The use of direct seeding for revegetation often results in poor recruitment outcomes. For many species, it is unclear where recruitment bottlenecks occur in the transitions between early life-history stages and how soil moisture conditions affect these bottlenecks. Thus, we asked: (1) which life-history stage transitions are most limiting to seedling recruitment? and (2) how do soil moisture levels affect recruitment? Using a field-based trial, we quantified the recruitment process from a seed to seedling for two woody Acacia species. Using a novel technique, in which seeds were confined to germination caches (small baskets), along with the use of germination bags, we assessed pre-emergence processes at regular intervals. Seeds sown directly into the soil in adjacent rows were intensively monitored to assess post-emergence processes. To investigate the effects of soil moisture on seedling recruitment, a glasshouse experiment assessed transitions between life-history stages under three different soil moisture treatments. In the field, the transition between a seed and germinated seed limited recruitment more than all other life-history stage transitions combined, with 32%–50% of seeds not germinating for the two species. Approximately one third of seeds of both species died prior to germinating, with few seeds remaining dormant. In the glasshouse trial, seed germination increased with increasing soil moisture, however, so did the extent of seed death. Our results suggest that the transition from a seed to germinated seed was the most limiting bottleneck to recruitment, mostly due to seed mortality rather than dormancy processes, with pathogen attack the most likely cause. As increased soil moisture both promoted germination but also seed mortality, understanding the optimal soil moisture thresholds that maximise germination and the transition to an established plant is essential in maximising direct seeding outcomes. Identifying the life-history stage transitions most limiting to plant recruitment may allow management to target specific bottlenecks in order to improve direct seeding outcomes.

Vestibular and auditory manifestations of migraine.

The purpose of this narrative review is to discuss current literature about vestibular migraine and other cochleovestibular symptoms related to migraine. Vestibular migraine affects 2.7% of the US population. Misdiagnosis is common. The pathophysiology is currently unknown but new research shows that calcitonin gene-related peptide, which is implicated in migraine headaches, is expressed in the audiovestibular periphery. A recent large-scale placebo-controlled trial looking at metoprolol for vestibular migraine was terminated early due to poor recruitment; however, at study completion, no differences were seen between treatment arms. Many other audiovestibular symptoms have been shown to be associated with migraine, including tinnitus, hearing loss, aural fullness, otalgia, and sinus symptoms. Migraine is also associated with risk for developing numerous otologic conditions, including Meniere's disease, vestibular loss, Benign Paroxysmal Positional Vertigo, and sudden sensorineural hearing loss. There is now some evidence that patients may experience fluctuating hearing loss and aural fullness without vertigo in association with migraine, which is called cochlear migraine. Migraine can cause a variety of audiologic and vestibular symptoms, and further research is required to understand how migraine affects the inner ear.

К вопросу о совершенствовании деятельности службы авиационной безопасности в России

Introduction: Aviation Security Service is an independent system that ensures the safety of air passengers and the airport as a whole. It has been given a free hand recently, namely, with the adoption of Federal Law No. 491-FZ Dated December 31, 2017 “On Amending the Aviation Code of the Russian Federation for ensuring aviation security”. Before the enactment, these functions were fulfilled by the police. In its activities, the police used some technical means necessary to identify the objects prohibited in circulation, but after the transfer of such powers to the Aviation Security Service, there was a process of improving and digitalizing technical devices, which contributed to improving the quality of screening air passengers, baggage and airport facilities. In its activities, the Aviation Security Service uses a highly systematic improved safety technology; a huge range of high-tech devices is used to ensure this service. But despite the improvement of technologies in the inspection system, the broadening of powers of the Aviation Security Service, there are also several shortcomings in its activities. Such are the gaps in the regulatory framework both for the Aviation Security Service itself and for interaction with the territorial Departments of Internal Affairs in transport. In addition, there is poor recruitment of personnel and corruption component in this area. Purpose: the purpose of the study is to analyze the features of aviation security in Russia and develop measures to improve the activities of the Aviation Security Service. Research methods: the methodological framework for the study is made up of the general scientific methods of cognition. To ensure the objectivity of the research, the analyzed problem is revealed by the authors as a phenomenon using a systematic approach, which allows us to reveal its mechanism in such a way that the theoretical provisions are used with maximum efficiency in practical activities. Research results and conclusions: the authors highlight the features of the activities of the Aviation Security Service in Russia during inspection measures, and also identify the main security problems at the airports.

Political Dynasty and Single Candidate in Indonesian Local Elections: Where Are The Parties?

The pragmatism of political parties is one of the causes for the proliferation of political dynasties and the massive number of single candidates in several electoral politics periods at the local level. The implementation of the 2020 local election simultaneously gave birth to many candidates who have a kinship with political officials both at the central and regional levels, both currently or who have served. Apart from the practice of dynastic politics, a single candidate's presence also adds to the problems in the democratic process at the local level. A single candidate is present as a consequence of implementing the local election system simultaneously, which opens wide the opportunity for the local election to be held even though only one pair of regional head candidates are joined, as a consequence, the empty column is presented as the opponent of the match. This article collects data through a literature study. To answer these two phenomena, the author examines them during the local election implementation. This study indicates that these two phenomena co-opt local democracy and clog the circulation of the leadership elite. Both political dynasty candidates and single candidates have enormous potential to win elections. Both phenomena are caused by poor internal recruitment and candidate selection processes.

General characteristics and reasons for the discontinuation of drug clinical trials in mainland China

BackgroundAlthough discontinuation is common in clinical trials, no study has been conducted to analyse the current situation and reasons for the suspension or discontinuation of drug clinical trials in China. This study aims to analyse the general characteristics and reasons for the discontinuation of registered clinical trials in mainland China and to identify the associated factors.MethodsWe conducted a cross-sectional observational study of discontinued trials registered in the Drug Trial Registration and Information Publication Platform before March 31, 2020. All trials with a status of terminated or stopped recorded in the platform were classified as discontinued trials and included in the analysis. The basic characteristics of the discontinued trials were recorded, reasons for trial discontinuation were recorded and divided into 4 categories as drug development strategy, trial planning, trial conduct and studied drug. Pearson’s chi-square test and fisher’s exact test were used to compare the differences in reasons for discontinuation between neoplasm trials and non-neoplasm trials, and to examine the associations of trial characteristics with different reasons related to trials discontinuation.ResultsThree hundred twelve discontinued trials were included in this study. The studied drugs were mainly chemical drugs [229 (73.4%)], and indications of the studied drugs were mainly neoplasms [77 (24.7%)]. Geographical location of the discontinued trials were mostly in northern [114 (36.5%)] and eastern [96 (30.8%)] China. Study type of the included trials was mainly bioequivalence studies [97 (31.1%)]. The most common reason for trial discontinuation was commercial or strategic decision [84 (26.9%)], followed by futility/lack of efficacy [70 (22.4%)]. The number of trial centers, sample size and whether participants had been enrolled were significantly associated with trial discontinuation (P < 0.05). Multiple center trials showed a higher rate of trial discontinuation due to trial conduct related reasons than single center trials (P < 0.05), trials with sample size > 500 showed a higher rate of trial discontinuation due to studied drug related reasons (P < 0.05), and trials enrolled participants showed a lower rate of trial discontinuation due to commercial or strategic decision and a higher rate of trial discontinuation due to studied drug related reasons than trials without enrolled participants (P < 0.05). Besides, neoplasm trials showed a higher rate of trial discontinuation due to poor recruitment and safety comparing with non-neoplasm trials (P < 0.05).ConclusionsTrial discontinuation in China mainly occurred because of commercial or strategic decision and futility/lack of efficacy of the studied drug. Clinical trials with multiple centers and a large sample size may more likely be discontinued due to trial conduct related reasons such as good clinical practice. Discontinuation due to drug safety and lack of efficacy in multiple center trials with a large sample size deserves more attention to avoid resources wastes. Full communication with regulatory authorities such as Center for Drug Evaluation and research institutes to develop a feasible protocol is important for sponsors to avoid trial discontinuation due to protocol issues.

Revealing the relationship between feeding and growth of larval redfish (Sebastes sp.) in the Gulf of St. Lawrence

Abstract Year-class strength of fish stocks is often set during the larval stage, with fast growth being a favourable factor leading to strong recruitment. Following 30 years of poor recruitment, redfish (Sebastes sp.) in the Gulf of St. Lawrence (GSL) produced unprecedentedly strong year classes in 2011–2013. The relationship between larval diet and growth that potentially drove these successful recruitment events is unknown. Gut content and otolith microstructure of redfish larvae collected from the GSL in 1999 and 2000 were analysed in order to understand the relationship between recent feeding success and growth in larval redfish, and identify feeding behaviours that are associated with fast growth. Growth was positively correlated with larval body depth (BD), which was used as a morphological proxy for growth. Prey type and size were the best explanatory variables of larval BD after obligatory first-feeding. Larvae that consumed large naupliar stages of frequently consumed copepod taxa were deeper-bodied and grew more quickly than larvae that consumed redfish's preferred prey, Calanus finmarchicus eggs. Warming GSL waters have shifted the phenology of commonly consumed prey taxa earlier in the season, which may increase the overlap between redfish and naupliar prey that drive fast growth, survival, and potentially recruitment success.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive after Treatment for Relapsed Follicular Lymphoma: Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study

IntroductionThe combination of rituximab & lenalidomide (R 2) is an established regimen for treatment of follicular lymphoma (FL), with efficacy reported in the first line and relapsed setting (Morchhauser NEJM 2018, Leonard JCO 2019). The inferior OS of patients who remain post-induction PET-CT positive (PET+ve) has also been demonstrated in both settings (Trotman Lancet Haem 2014, Lancet Oncol 2018, Ysebaert, ASH 2011). We sought to study the effect of R 2 in relapsed FL by examining its ability to convert to PET-negative (PET-ve) those patients who remain PET+ve after reinduction rituximab-chemotherapy.MethodsThis was a prospective, multicentre, Phase 2 study of patients with bulky Stage II, or Stage III-IV relapsed FL. Eligibility criteria were: at least stable disease on CT within 4-6 weeks of last cycle of re-induction rituximab-chemotherapy; ECOG ≤2; CrCL ³30mL/min; haemoglobin >80g/L, neutrophils >1.0 & platelets >75 x 10 9/L. Exclusion criteria were: histological transformation ≤12 months (mo); any interim-PET that was negative, and other malignancy ≤5 years. After enrolment pts underwent a centrally-reviewed PET within 8 weeks of D1 last cycle of re-induction rituximab-chemotherapy. Given the higher probability of further progression in the relapsed setting PET+ve was defined as a Deauville score (DS) 3-5. PET-ve patients were assigned rituximab maintenance q2mo for 2 years, and those remaining PET+ve were assigned R 2 to commence within 12 weeks. Lenalidomide schedule for R 2 pts was 10mg/d x 21 q28d, with dose modifications for tolerance, over a planned 2 years. Repeat PET scans were scheduled at 6 & 12 mo after starting R 2.The primary endpoint was the rate of conversion from postinduction PET+ve to PET-ve in evaluable patients 6 mo after commencing lenalidomide. Evaluable patients were defined as those receiving >63 days of Lenalidomide. Sample size calculations used a one-sided exact test for proportions, assuming a conversion rate of ³50% as worthy of further evaluation and ≤20% as unacceptable. Thus 16 evaluable patients were required to have 80% power with type I error of 5%. Secondary endpoints were PET conversion rates by baseline DS in the PET+ve, the toxicity & deliverability of R 2, and PFS & OS in both the PET+ve & PET-ve populations.ResultsThirty-seven patients (pts) were recruited from Nov 2013 to Jan 2021 when the study was closed due to poor recruitment attributed to competing studies. Median (med) age was 67yrs (36-83); 58% male, med 2 (range 2-11) prior therapies incl. the recent rituximab-chemotherapy; FLIPI low risk (21%), intermediate risk (12%) high risk (67%). Eighteen of 37 (48.6%) pts were postinduction PET+ve. Med follow-up was 38 mo (0.8 - 76.4): 32 mo (0.8 - 76.4) in PET+ve and 42 mo (6.7 - 73.8) in PET-neg. Of the 18 PET+ve pts one was ineligible for R 2 due to reactivation of hepatitis B; 3 were not evaluable having not received >63 doses of lenalidomide due to progressive disease (PD). Thus 14/18 (78%) PET+ve pts were evaluable, of whom 5/14 (36%; 95% CI 11% - 61%) became PET-ve at 6-mo, thus not excluding a PET conversion rate of <20%, (p=0.14). If we had obtained full recruitment both additional pts would have had to convert to PET-neg to meet the primary endpoint. PET conversion occurred in 4/6 evaluable pts with DS 3 and 1/8 with DS 5. PD occurred in 14 pts: 11/17 PET+ve and 3/19 PET-ve. Med PFS was 30.8 mo (5.7-37.6) in the PET+ve and NR (95% CI 42.3-NR) in the PET-ve, p = 0.0001. Death occurred in 11/37 (30%): 7 from lymphoma (5 PET+ve), 1 other malignancy, 2 pneumonia, 1 aspergillosis. Med OS was 68.1 mo (9.6 - NR) in PET+ve and NR (95% CI 42.3 - NR) in PET-ve (p 0.059).Of the 17 PET+ve pts starting lenalidomide, deliverability was limited by both disease progression and AEs: 3 failed to receive 3 cycles, 6 pts received 4-6, and 8 pts 7-24 cycles. Mean number of lenalidomide doses was 213 (SD 188). At least one AE was reported in 16/17 (94%), most commonly neutropenia (n=10, 59%, Gd4 24%). At least one SAE occurred in 9/17 (53%): infections 2, malignancy 2, cardiac disorders 2, musculoskeletal 2, other causes 3 pts.ConclusionThe high PET+ve rate of 49% (DS 3-5) after rituximab-chemotherapy for relapsed FL suggests the need for consolidation therapy. However, R 2 did not achieve a sufficiently high PET-conversion rate to justify further study. The inferior outcome of patients who remain PET+ve after treatment of relapse highlights the importance of investigating novel approaches in this setting. [Display omitted] DisclosuresTrotman: TAKEDA: Research Funding; beigene: Research Funding; roche: Research Funding; BMS: Research Funding; PCYC: Research Funding; JANSSEN: Research Funding. Gandhi: janssen: Research Funding; novartis: Honoraria. Butcher: WriteSource: Current Employment, Other: Medical writing for Pharma companies. Not pertinent to this abstract for which author is study Statisticiam.

Non-drug therapies for the management of chronic constipation in adults: the CapaCiTY research programme including three RCTs

Non-drug therapies for the management of chronic constipation in adults: the CapaCiTY research programme including three RCTs

Extreme pre-fire drought decreases shrub regeneration on fertile soils.

Extreme drought and increasing temperatures can decrease the resilience of plant communities to fires. Not only may extremely dry conditions during or after fires lead to higher plant mortality and poorer recruitment, but severe pre-fire droughts may reduce the seed production and belowground vigor that are essential to post-fire plant recovery, and may indirectly facilitate invasion. We studied survival, recruitment, and growth of shrubs and herbs in chaparral (shrubland) communities in Northern California after a 2015 fire that immediately followed California's extreme 3-yr drought. We followed the same protocols used to study similar, adjacent communities after a 1999 fire that did not follow a drought, and we compared the two recovery trajectories. Overall, the 2015 fire was not more severe than the 1999 fire, yet it caused higher mortality and lower growth of resprouting shrubs on fertile (sandstone) soils. In contrast, the 2015 fire did not affect the mortality or growth of resprouting shrubs on infertile (serpentine) soils, the density of shrub seedlings, or the richness or cover of native herbs differently than the 1999 fire. However, the 2015 fire facilitated a massive increase in exotic herbaceous cover, especially on fertile soils, possibly portending the early stages of a type conversion to exotic-dominated grassland. Our findings indicate that the consequences of climate change on fire-dependent communities will include effects of pre-fire as well as post-fire climate, and that resprouting shrubs are particularly likely to be sensitive to pre-fire drought.

Identifying juvenile and sub-adult movements to inform recovery strategies for a high value fishery—European bass (Dicentrarchus labrax)

Abstract The European bass (Dicentrarchus labrax) support high value commercial and recreational fisheries, however the Spawning Stock Biomass (SSB) of the northern Atlantic stock (ICES divisions 4.b–c, 7.a, and 7.d–h) has rapidly declined to an unsustainable level. The decline in SSB has been attributed to high fishing pressure combined with poor recruitment. By tracking juvenile fish their spatial ecology can be identified, and appropriate fisheries management policies designed to boost recruitment can be implemented. Using acoustic telemetry 146 sub-adult European bass (25.2–60 cm fork length) were tracked for up to 370 d across three sites in the southwest of the UK. Tagged fish were detected 2 724 548 times (Range: 166–106 393 detections per fish). Linear modelling estimated tagged fish were resident within 2.4–20.1 km of the site where they were first caught for 42.9–75.5% of the year. Some fish were however resident throughout summer and winter. Individual fish were also tracked moving up to 317 km to other coastal sites, 81% of which returned to their original capture site. Fisheries management should account for the high site fidelity displayed by juveniles and sub-adults of this species and coastal nursery sites should be considered essential habitat.

A Pilot Study on Electrical Impedance Tomography During CPAP Trial in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: The Bright Side of Non-invasive Ventilation.

Background: Different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia phenotypes were described that match with different lung compliance and level of oxygenation, thus requiring a personalized ventilator setting. The burden of so many patients and the lack of intensive care unit (ICU) beds often force physicians to choose non-invasive ventilation (NIV) as the first approach, even if no consent has still been reached to discriminate whether it is safer to choose straightforward intubation, paralysis, and protective ventilation. Under such conditions, electrical impedance tomography (EIT), a non-invasive bedside tool to monitor lung ventilation and perfusion defects, could be useful to assess the response of patients to NIV and choose rapidly the right ventilatory strategy.Objective: The rationale behind this study is that derecruitment is a more efficient measure of positive end expiratory pressure (PEEP)-dependency of patients than recruitment. We hypothesized that patients who derecruit significantly when PEEP is reduced are the ones that do not need early intubation while small end-expiratory lung volume (ΔEELV) variations after a single step of PEEP de-escalation could be predictive of NIV failure.Materials and Methods: Consecutive patients admitted to ICU with confirmed SARS-CoV-2 pneumonia ventilated in NIV were enrolled. Exclusion criteria were former intubation or NIV lasting > 72 h. A trial of continuos positive airway pressure (CPAP) 12 was applied in every patient for at least 15 min, followed by the second period of CPAP 6, either in the supine or prone position. Besides standard monitoring, ventilation of patients was assessed by EIT, and end-expiratory lung impedance (ΔEELI) (%) was calculated as the difference in EELI between CPAP12 and CPAP6. Tidal volume (Vt), Ve, respiratory rate (RR), and FiO2 were recorded, and ABGs were measured. Data were analyzed offline using the dedicated software. The decision to intubate or continue NIV was in charge of treating physicians, independently from study results. Outcomes of patients in terms of intubation rate and ICU mortality were recorded.Results: We enrolled 10 male patients, with a mean age of 67 years. Six patients (60%) were successfully treated by NIV until ICU discharge (Group S), and four patients failed NIV and were intubated and switched to MV (Group F). All these patients died in ICU. During the supine CPAP decremental trial, all patients experienced an increase in RR and Ve. ΔEELI was < 40% in Group F and > 50% in Group S. In the prone trial, ΔEELI was > 50% in all patients, while RR decreased in Group S and remained unchanged in Group F.Conclusion: ΔEELI < 40% after a single PEEP de-escalation step in supine position seems to be a good predictor of poor recruitment and CPAP failure.

Recruitment principles and strategies for supportive care research in pediatric oncology

BackgroundVariations in clinical practice contribute to negative outcomes for children with cancer. Research in this area is imperative to standardise practice, yet such research is challenging to undertake, and a significant proportion of studies fail. A common reason for failure is poor recruitment, yet little information is available to support researchers and clinicians planning such research.MethodsOur primary aim was to describe the recruitment strategies and outcomes in a tertiary children’s hospital across multiple observational supportive care studies. Secondary aims were to establish principles to improve both recruitment strategies and the reporting of recruitment. We undertook a retrospective descriptive analysis of the recruitment logs and data from three studies in pediatric oncology. The mean time to recruit one participant was calculated. Common reasons for not approaching eligible participants and reasons potential participants declined are described.ResultsOf the 235 potential candidates across all studies, 186 (79%) were approached and of these 125 (67%) provided consent, with 117 (63%) completing baseline measures. We estimated recruitment per participant required an average 98 min of experienced research nurse time. Four factors are described that influence recruitment and six principles are outlined to maximise recruitment and the generalisability of research findings.ConclusionsWe highlight the recruitment experiences across three different projects in children’s cancer supportive care research and provide a roadmap for other researchers planning to undertake clinical research in pediatrics.

Experimental seed sowing reveals seedling recruitment vulnerability to unseasonal fire.

Unseasonal fire occurrence is increasing globally, driven by climate change and other human activity. Changed timing of fire can inhibit postfire seedling recruitment through interactions with plant phenology (the timing of key processes, e.g., flower initiation, seed production, dispersal, germination), and therefore threaten the persistence of many plant species. Although empirical evidence from winter-rainfall ecosystems shows that optimal seedling recruitment is expected following summer and autumn (dry season) fires, we sought experimental evidence isolating the mechanisms of poor recruitment following unseasonal (wet season) fire. We implemented a seed-sowing experiment using nine species native to fire-prone, Mediterranean-climate woodlands in southwestern Australia to emulate the timing of postfire recruitment and test key mechanisms of fire seasonality effects. For seeds sown during months when fire is unseasonal (i.e., August-September: end of the wet winter season), seedling recruitment was reduced by up to 99% relative to seeds sown during seasonal fire months (i.e., May-June: end of the dry summer season) because of varying seed persistence, seedling emergence, and seedling survival. We found that up to 70 times more seedlings emerged when seeds were sown during seasonal fire months compared to when seeds were sown during unseasonal fire months. The few seedlings that emerged from unseasonal sowings all died with the onset of the dry season. Of the seeds that failed to germinate from unseasonal sowings, only 2% survived exposure on the soil surface over the ensuing hot and dry summer. Our experimental results demonstrate the potential for unseasonal fire to inhibit seedling recruitment via impacts on pregermination seed persistence and seedling establishment. As ongoing climate change lengthens fire seasons (i.e., unseasonal wildfires become more common) and managed fires are implemented further outside historically typical fire seasons, postfire seedling recruitment may become more vulnerable to failure, causing shifts in plant community composition towards those with fewer species solely dependent on seeds for regeneration.