Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials

Background

Recruitment of sufficient participants in an efficient manner is still widely acknowledged to be a major challenge to the mounting and completion of randomised controlled trials (RCTs). Few recruitment interventions have involved staff undertaking recruitment. This study aimed i) to understand the recruitment process from the perspective of recruiters actively recruiting RCT participants in six pragmatic RCTs, and ii) to identify opportunities for interventions to improve recruitment.

Methods

Interviews were undertaken with 72 individuals (32 doctors or RCT Chief investigators (CIs); 40 nurses/other health professionals) who were actively recruiting participants in six RCTs to explore their experiences of recruitment. The RCTs varied in scale, duration, and clinical contexts. Interviews were fully transcribed and analysed using qualitative content and thematic analytic methods derived from grounded theory. For this analysis, data were systematically extracted from each RCT and synthesised across all six RCTs to produce a detailed and nuanced understanding of the recruitment process from the perspectives of the recruiters.

Results

Recruiters readily identified organisational difficulties, fewer than expected eligible patients, and patients’ treatment preferences as the key barriers to recruitment. As they described their experiences of recruitment, several previously hidden issues related to their roles as researchers and clinicians emerged, imbued with discomfort and emotion. The synthesis across the RCTs showed that doctors were uncomfortable about aspects of patient eligibility and the effectiveness of interventions, whereas nurses were anxious about approaching potential RCT participants and conflicts between the research and their clinical responsibilities. Recruiters seemed unaware that their views contributed to recruitment difficulties. Their views were not known to RCT CIs. Training and support needs were identified for both groups of staff.

Conclusions

The synthesis showed that recruitment to these RCTs was a complex and fragile process. Clear obstacles were identified but hidden challenges related to recruiters’ roles undermined recruitment, unbeknown to RCT CIs. Qualitative research can elicit and identify the hidden challenges. Training and support are then needed for recruiters to become more comfortable with the design and principles of RCTs, so that they can engage more openly with potentially eligible participants and create a more resilient recruitment process.     

Synthesis and cardiac effects of 3,4-dihydropyrimidin-2(1H)-one-5 carboxylates

A series of 4-(substituted)-3,4-dihydropyrimidinone derivatives have been synthesized by heating 1,3 dicarbonyl compounds, urea, and aromatic aldehydes in acetic acid under microwave irradiation conditions. The cardiovascular effects of 3,4-dihydropyrimidinones were studied on isolated perfused frog heart at different dose levels and compared with the activity of digoxin. The interaction of 3,4-dihydropyrimidinones with beta-blocker and calcium channel blocker was also investigated. Compound 4d emerged as the most interesting compound in this series with potential cardiotonic activity.     

Pyrazole derivatives from azines of substituted phenacyl aryl/cyclohexyl sulfides and their antimycobacterial activity

Azines derived from substituted phenacyl aryl/cyclohexyl sulfide on treatment with excess phosphorous oxychloride in N,N-dimethylformamide have been found to yield two isomeric pyrazoles in each case. A plausible mechanism has been suggested for the formation of the products. The antimycobacterial activity of the isomeric compounds has been tested against Mycobacterium tuberculosis (MTB).     

An atom economic synthesis and antitubercular evaluation of novel spiro-cyclohexanones

The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and α-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) using agar dilution method. Two compounds, 4-(2,4-dichlorophenyl)-5-phenylpyrrolo(spiro[2.2″]acenaphthene-1″-one)spiro[3.2′]-6′-(2,4-dichlorophenylmethylidene)cyclohexanone (4i) and spiro[5.2″]acenaphthene-1″-onespiro[6.2′]-6′-(2,4-dichlorophenylmethylidene)cyclohexanone-7-(2,4-dichlorophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole (5i) display maximum activity in vitro with a MIC value of 0.40 μg/mL against MTB and were 4 and 15.6 times more potent than ethambutol and pyrazinamide, respectively.     

Larvicidal and insect growth regulator effect of α-amyrin acetate from Catharanthus Roseus Linn against the malaria vector Anopheles Stephensi Liston (Diptera: Culicidae)

Vector control is a serious concern in developing countries. Over the past two decades, phytochemicals have received progressively more attention as insecticide alternatives, and they have recently become the focus in the concept of integrated vector control. α-Amyrin acetate, the n-hexane fraction of acetone extract from the leaves of Catharanthus roseus , was evaluated for its larvicidal, pupicidal and fecundity effects as well as insect growth regulator activity against the malaria vector Anopheles stephensi Liston. The highest concentration of 1 p.p.m. produced 100% mortality in first to second instars and 94% mortality in third and fourth instars. In addition, the duration of larval instars and the total developmental time were prolonged, while female longevity and fecundity were markedly decreased. The suppression of pupation and adult emergence was probably due to its action similar to juvenile hormone analogs in combination with growth regulator activity and toxicity, which reduced the overall performance of the malaria vector An. stephensi .     

The role of mycorrhizal fungi in growth enhancement of dune plants following burial in sand

1. Burial in sand of Agropyron psammophilum and Panicum virgatum plants had a stimulating effect on carbon dioxide exchange rate, leaf area and biomass, irrespective of whether sand used for burial did or did not contain mycorrhizal fungi.
2. Plants of both A. psammophilum and P. virgatum species grown in mycorrhiza-containing sand and then buried with mycorrhiza-containing sand had the highest CO₂ exchange rate, leaf area and biomass.
3. The growth stimulation following a burial episode is probably a composite response of several factors. The major contribution of mycorrhizal fungi will possibly be the exploitation of resources in the burial deposit.     

Development of highly reliable SERS‐active photonic crystal fiber probe and its application in the detection of ovarian cancer biomarker in cyst fluid

Conventionally Surface‐enhanced Raman spectroscopy (SERS) is realized by adsorbing analytes onto nano‐roughened planar substrate coated with noble metals (silver or gold) or their colloidal nanoparticles (NPs). Nanoscale irregularities in such substrates/NPs could lead to SERS sensors with poor reproducibility and repeatability. Herein, we demonstrate a suspended core photonic crystal fiber (PCF) based SERS sensor with extremely high reproducibility and repeatability in measurement with a relative SD of only 1.5% and 4.6%, respectively, which makes it more reliable than any existing SERS sensor platforms. In addition, our platform could improve the detection sensitivity owing to the increased interaction area between the guided light and the analyte, which is incorporated into the holes that runs along the length of the PCF. Numerical calculation established the significance of the interplay between light coupling efficiency and evanescent field distribution, which could eventually determine the sensitivity and reliability of the developed SERS active‐PCF sensor. As a proof of concept, using this sensor, we demonstrated the detection of haptoglobin, a biomarker for ovarian cancer, contained within the ovarian cyst fluid, which facilitated in differentiating the stages of cancer. We envision that with necessary refinements, this platform could potentially be translated as a next‐generation highly sensitive SERS‐active opto‐fluidic biopsy needle for the detection of biomarkers in body fluids.     

Role of large hydrophobic residues in proteins

Large Hydrophobic Residues (LHR) such as phenylalanine, isoleucine, leucine, methionine and valine play an important role in protein structure and activity. We describe the role of LHR in complete set of protein sequences in 15 different species. That is the distribution of LHR in different proteins of different species is reported. It is observed that the proteins prefer to have 27% of large hydrophobic residues in total and all along the sequence. It is also observed that proteins accumulate more LHR in its active sites. A window analysis on these protein sequences shows that the 27% of LHR is more frequent at window length of 45 amino acids. The influenza virus and P. falciparum show a random distribution of LHR in its proteins compared to other model organisms.