Lower Termination Rate Research Articles

Global Disparities in the Characteristics and Outcomes of Leukemia Clinical Trials: A Cross-Sectional Study of the ClinicalTrials.gov Database.

Most clinical trials are conducted exclusively in high-income countries (HICs), with only a small fraction involving centers from low-middle income countries (LMICs). However, studies evaluating the global distribution of clinical trials in leukemia are limited. Therefore, we sought to assess the present state of leukemia clinical trials that involve centers from LMICs and to compare those with trials conducted exclusively in HICs. We searched ClinicalTrials.gov to identify leukemia trials initiated between 2000 and 2020. In this cross-sectional study, the search strategy was developed by a medical librarian using controlled vocabulary and free-text terms. Data abstraction was independently executed by two reviewers. Trials were defined to be LMIC trials if they included centers from LMICs according to the World Bank Atlas country's income level classification for 2022-2023. Conversely, if a trial included centers from HICs only, the study was classified as a HIC trial. Of 3,345 leukemia-related clinical trials identified, only 160 (4.8%) included centers from LMICs. Compared with HIC trials, LMIC trials had lower termination rates (12.5% v 27.5%; P < .001) and were more likely randomized (52.5% v 18.2%; P < .001), larger (sample sizes >50 patients: 69.0% v 33.6%; P < .001), multicenter (81.9% v 47.9%; P < .001), and later phase (phase III: 36.2% v 8.98%; P < .001; phase IV: 6.25% v 2.17%; P < .001). There was an increase in the proportion of randomized and diseased-focused clinical trials within the trials that involved LMIC centers between 2000-2005 and 2010-2015 (57.1% v 47.1% and 85.7% v 52.9%; P = .013 and 0.014, respectively). We found a marked underrepresentation of LMICs in leukemia clinical trials reflecting limited access to novel leukemia therapies in LMICs.

Analyzing determinants of premature trial discontinuation in leukemia clinical trials

Clinical trials are crucial for improving patient outcomes. Although a significant number of trials are discontinued prematurely, our understanding of factors influencing early termination is limited. We conducted a comprehensive search of ClinicalTrials.gov to identify leukemia trials from 2000 to 2020, followed by data abstraction performed by two independent reviewers. Among 3522 leukemia clinical trials identified, 28.4% were terminated prematurely. Slow accrual was the leading cause of termination 38.2%. The termination rate increased significantly from 17.0% between 2000 and 2005 to 30.9% between 2010 and 2015 (p < .001). Large trials had a lower termination rate than small trials (p < .001). Academic-sponsored trials had the highest termination rates compared to other sponsors’ trials (p < .001). Early-phase trials showed higher termination rates compared to late-phase (p < .001). Other significant factors included a sequential assignment, single-center, and non-randomized trials (p < .001). Much of leukemia trials are terminated prematurely, with slow accrual being the most common reason for early termination.

Management of High-Residue Cover Crops in a Conservation Tillage Organic Vegetable On-Farm Setting

A three year on-farm conservation-tillage experiment was initiated in fall of 2008 at Randle Farm LLC, located in Auburn, AL. Our objective was to evaluate and demonstrate implementation of tenable conservation vegetable production practices using high amounts of cover crop residues that reduce soil erosion, improve soil productivity and quality, reduce energy costs, and promote farm profitability. Cereal rye, crimson clover, and a rye and crimson clover mixture were evaluated as cover crops; these were terminated using either a prototype two-stage roller/crimper alone or followed by an application of 2.5 L a.i. ha−1 45% cinnamon (Cinnamomum verum L.) oil (cinnamaldehyde, eugenol, eugenol acetate,)/45% clove oil (eugenol, acetyl eugenol, caryophyllene) mixture in the spring prior to crop establishment. A winter fallow conventional tillage system was included for comparison. Watermelons, cantaloupes, and okra then were transplanted into each cover crop and termination treatment combination in mid-May, utilizing a modified transplanter equipped with a custom fitted subsoiling shank and row cleaners to alleviate soil compaction and facilitate transplanting. In all years, all cover crop treatments exceeded 4000 kg ha−1and in 2009 and 2011, exceeded 6000 kg ha−1. At 21 days after termination in 2010 when the slowest termination occurred, higher termination rates were obtained for cereal rye (95% to 96%) followed by lower termination rates for the clover/rye mixture (83% to 85%); the lowest termination rates were obtained for crimson clover (66% to 68%). Commercially available cinnamon/clove oil solution provided little cover crop termination above that provided by a roller crimper alone. Volumetric soil moisture content for rolled/crimped cover crops was consistently higher compared to the conventional system, indicating that flattened and desiccated cover crop residue provided water conservation. In 2010 and 2011, yields for cantaloupe, okra, and watermelons were consistently higher for the conventional system compared with no-till system with cover crops likely due to weed cultivation limitations and insect pressure. Future studies need to focus on weed control and integrated pest management.

Neural tube defect diagnosis and outcomes at a tertiary South African hospital with intensive case ascertainment.

Neural tube defects (NTDs) are an important category of birth defect, but surveillance remains inadequate in South Africa. To assess the identification of NTDs at a tertiary hospital using a range of prenatal, perinatal and postnatal data sources, and to estimate the impact of prenatal diagnosis and birth prevalence for the referral area. Cases of anencephaly, encephalocele and spina bifida (SB) in a 6-year period were retrospectively identified from 5 data sources covering prenatal, perinatal and postnatal care. These were cross-correlated to avoid duplicate entries and to determine the contribution of different data sources. Details of prenatal diagnosis and termination of pregnancy (TOP) were obtained for 10 years, and birth prevalence over 2 years. During a 6-year period 195 NTDs were identified at a Western Cape Province tertiary hospital. These included 59 (30%) cases of anencephaly, 28 (14%) of encephalocele and 108 (55%) of SB. The majority of NTDs (71%) were detected prenatally, although SB was less commonly diagnosed prenatally than cranial defects (56% v. 88%; p&lt;0.001). Of SB cases ascertained pre- or postnatally, 57% of patients were born alive and 50% discharged alive, but 72% of survivors had not been diagnosed prenatally. Women receiving prenatal diagnosis of any type of NTD before 24 weeks' gestation were nearly always offered TOP, and the majority accepted termination after non-directive counselling. For SB, later prenatal diagnosis was associated with much lower termination rates because the option was less often offered (51% v. 100%; p&lt;0.001), and perhaps less often accepted (57% v. 78%; p=0.06). The estimated NTD birth prevalence for the referral area was 0.76 - 0.80 per 1 000 live births, but perhaps up to 1.18 per 1 000 when considering under-referral of lethal cranial lesions from rural areas. A substantial number of NTDs can be ascertained from a tertiary hospital environment if multiple data sources are used, even though adding data from the Perinatal Problem Identification Program for outlying health facilities increases detection of lethal defects. Hospital-based surveillance can be considered, especially for SB. Prenatal diagnosis was fairly common and pregnancy termination was often offered and accepted if detected before 24 weeks' gestation. A regional prenatal ultrasound programme, predominantly based in primary care but with ready access to a tertiary centre, can be quite effective, although limited or delayed access to prenatal diagnosis must be addressed.

Does Disease Severity Contribute to Disparity in Outcome Amongst Ethnic Groups in Patients with Hypoplastic Left Heart syndrome in New Zealand?

Māori/Pacific Island patients with hypoplastic left heart syndrome (HLHS) have a later diagnosis, lower termination rates and higher mortality compared to other ethnic groups in New Zealand (NZ). Our aim was to determine if HLHS disease severity contributes to these outcome differences. Patients with HLHS diagnosed on a fetal or post-natal echocardiogram in NZ 2006 - 2015 were identified via a national database and divided into sub-groups (NZ European, Māori/Pacific Islander, and Asian). A fetal echocardiography risk score was calculated based on predictors of severity. Mitral stenosis/aortic atresia, hypoplastic aortic arch, intact/restrictive atrial septum, moderate-severe tricuspid regurgitation, and moderate-severe right ventricular dysfunction were each allocated one point. There were 125 patients with HLHS. Twenty-seven (22%) were excluded due to insufficient fetal data. All 27 were terminated or still-born. Results for included cases:Tabled 1NZ EuropeanMāori/PIAsianpTotal patients (98)60 (61%)29 (30%)9 (9%)Birth state0.002Termination of pregnancy32 (53%)3 (10%)5 (56%)Stillbirth2 (3%)2 (7%)2 (22%)Livebirth26 (43%)24 (83%)2 (22%)Risk score ≥219 (32%)20 (69%)1 (11%)0.02Survival at 1 year (% live birth)16 (62%)5 (21%)0 (0%)0.009Survival at 1 year if risk score ≥25 (26%)2 (10%)0 (0%)0.49 Open table in a new tab Disparity exists in health outcomes amongst ethnic groups in patients with HLHS in NZ. More severe disease in Māori/Pacific Island patients may in part account for differences in outcome.

Detection of PLP Structure for Accurate Determination of Propagation Rate Coefficients over an Enhanced Range of PLP-SEC Conditions

The factors influencing the periodic structure in molar mass distributions (MMDs) generated in pulsed-laser polymerization (PLP) experiments are investigated to extend the range of operating conditions under which radical polymerization propagation rate coefficients (kp) can be reliably estimated. Specifically, it is shown how kp may be determined well into conditions corresponding to the so-called low and high termination rate limits. A new parameter x is introduced to provide a convenient measure of when PLP pseudostationary conditions approach the low (x ≤ 0.2) and high (x ≥ 5.0) termination rate limits. In addition, a simple transformation is proposed to detect the PLP structure obscured by the background of the distribution under limiting experimental conditions, with simulations confirming that the methodology provides an estimate of kp with reasonable accuracy. The usefulness of the technique is then demonstrated through application to several experimental distributions. The influences of chain tra...

Light Leads to Ultra-Long Polymer Chains in Water

The synthesis of controlled ultra-high-molecular-weight polymers has been challenging in living radical polymerization. In this issue of Chem , Sumerlin and coworkers report that mild UV light irradiation activates thiocarbonylthio compounds in water to form those over 1 × 10 6 Da.

Thermooxidative aging of polydicyclopentadiene in glassy state

Thermal ageing of thin films of unstabilized polydicyclopentadiene (pDCPD) at several temperatures ranging from 120 to 30°C was investigated by means of carbonyl build up by FTIR with ammonia derivatization, double bond titration, mass uptake measurement, hydroperoxides titration by iodometry and DSC coupled with sulfur dioxide treatment. In the temperature range under investigation, pDCPD is in glassy state and it oxidizes faster than common polymers oxidized at rubbery state (e.g. polydienic elastomers). Using the kinetic analysis, these results were ascribed to increased initiation rate due to catalyst residues, some possible intramolecular processes favoring propagation, or a very low termination rate of oxidation radical chains because of the control of termination reactions by macroradical diffusion.

Polymerization of Methyl Methacrylate with Lithium Triflate. A Kinetic and Structural Study

The radical photopolymerization of methyl methacrylate in the presence of lithium triflate is investigated by EPR and NMR spectroscopies in order to assess the effect of the ionic medium on the polymerization kinetics. The EPR spectra show a notorious increase in the concentration of propagating radical as result of a dramatic decrease in the average termination rate coefficient. IR spectroscopy experiments and theoretical studies confirm the formation of a complex between the lithium cation and the oxygen atom at the carbonyl position of the ester in the methyl methacrylate. The electrostatic repulsion between the complexed propagating radicals, specifically at the end of the chains, allows explaining the observed low termination rate. This strong interaction would lead to “quasi-living” polymer chains from the first steps of the polymerization.

Surface Initiation from Adsorbed Polymer Clusters: A Rapid Route to Superhydrophobic Coatings

We introduce the use of a hydroborated polyisoprene (PIP) macroinitiator for the rapid surface-initiated growth of superhydrophobic polymethylene (PM) films. Rinsing of a dip-coated PIP film on a methyl-terminated surface atop silicon or gold substrates results in robustly bound, isolated PIP clusters. After hydroboration of the internal olefins, these clusters result in extremely rapid growth of polymethylene coatings upon exposure to a diazomethane solution in diethyl ether at -17 °C. The resulting PM films achieve 6 μm thicknesses within 20 min of polymerization and become superhydrophobic with advancing and receding water contact angles of 166° and 156°, respectively, within 1 min. The PM films grown from these PIP clusters exhibit 3× greater propagation velocities, 30% lower termination rates, and more highly textured morphologies than PM films grown from hydroborated monolayers.

Ring-opening polymerization behavior of l-lactide catalyzed by aluminum alkyl catalysts

The l-lactide polymerization using trimethylaluminum (TMA), triethylaluminum (TEAL), trioctylaluminum (TOA), triisobutylaluminum (TIBA), and aluminum isopropoxide (Al(O-i-Pr)3) were studied to produce a PLA. The conversion, turnover frequency (TOF), and molecular weight of TIBA were higher than those of Al(O-i-Pr)3 with the polymerization time of 5min. In the case of 15min, the conversion of aluminum alkyls was lower than that of Al(O-i-Pr)3, but the molecular weight of PLA produced by aluminum alkyl was relatively high in comparison with the catalytic activity of Al(O-i-Pr)3. TMA, TEAL, and TIBA seemed to have lower propagation rates and much lower termination rates than Al(O-i-Pr)3.

Long-term adherence to interferon-beta treatment in a cohort of RRMS patients in Belgrade, Serbia

ObjectiveLong-term adherence to interferon-beta (IFNβ) treatment in patients with multiple sclerosis (MS) varies considerably in daily clinical practice. The aim of the present study was to assess the frequency and reasons for stopping the INFβ treatment in our relapsing-remitting (RR) MS patients’ cohort. Patients and methodAll patients with RRMS initiating treatment with IFNβ at the Clinic of neurology, CCS, in Belgrade, from January 2004 to June 2009, were included in the study. Treatment was initiated in RRMS patients with at least two relapses in the previous two years, and EDSS score at entry ≤3.5. During the follow-up, patients underwent regular detailed clinical evaluation performed by MS specialists. ResultsThe study comprised a total of 290 RRMS patients. During the 6-year follow up period (mean 3.5±2.1years), 18% of patients stopped the treatment. The main reason for treatment discontinuation was lack of efficacy (54%); 21% of patients stopped therapy because of pregnancy and only 17% because of AE. ConclusionThe frequency of treatment discontinuation in our study pointed to the low permanent termination rate reflecting good adherence to IFNβ in our RRMS patients. Our results support the notion that long-term adherence to IFNβ treatment might be significantly influenced by optimizing the benefits to be achieved from therapy, adequate patient selection and easy accessibility of MS health professionals.

Evolution of the termination rate coefficient in styrene polymerization

AbstractStyrene bulk polymerization was conducted at 70 °C with a high initiator concentration, and this ensured that the dominant chain‐stopping mechanism was the combination of free radicals. The evolution of the molecular weight distribution (MWD) of the polymer was measured via the periodic removal of samples during the course of the reaction and their analysis with gel permeation chromatography. The overall termination rate coefficient was independent of the conversion in the dilute regime, as observed from cumulative MWDs. In the middle of the conversion range, the observed trend was compatible with a translational‐diffusion‐controlled mechanism for the termination step. A bimodal distribution of the molecular weights was also found at high conversions and could be explained in terms of an increase in the free‐radical concentration and a very low termination rate coefficient. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 178–187, 2005

Prenatal diagnosis and management of sex chromosome aneuploidy: a report on 98 cases.

To analyse the management of pregnancy after prenatal diagnosis of sex chromosome aneuploidy (SCA) and the factors influencing genetic counselling and parental decision. Between 1991 and 2001, 73 non-mosaic fetal SCA were diagnosed in our centre and 25 were referred to us from outside institutions. The same geneticist carried out genetic counselling. The outcome of pregnancies and the termination trend over time were determined according to the type of SCA. Clinical parental data were analysed in order to assess whether they influenced genetic counselling. 45,X was diagnosed in 41 fetuses. The main indication for karyotyping was abnormal ultrasound (83%). The termination rate was 93%. Sex chromosome polysomies (SCP) including 47,XXY, 47,XXX, and 47,XYY were diagnosed in 31, 16, and 10 fetuses respectively. The main indication for karyotyping was advanced maternal age (60%). The termination rate was 32, 25, and 20% respectively. The difference between the termination rate for local cases (25%) and referred cases (33%) was not significant. The termination rate for pregnancies with SCP was 38% in 1991 to 1994, 34% in 1995 to 1998, and 12% in 1999 to 2001. The parents' characteristics did not influence the outcome of pregnancy. The relatively low termination rate (28%) in pregnancies where the fetus was affected by SCP and the decreasing termination trend over time in our centre suggest an improved knowledge of the pathological conditions associated with SCP, influencing genetic counselling.

Modeling of molecular weight distribution in pulsed laser free‐radical homopolymerizations

AbstractThe use of pulsed lasers to induce radical polymerization with a subsequent analysis of the polymer molecular weight distribution (MWD) through size exclusion chromatography (PLP‐SEC method) revolutionized the determination of propagation rate coefficients kp. In this paper the program package PREDICI is applied to the simulation of PLP‐SEC orginated MWDs. The comparison with SPEEDUP‐simulations from Hutchinson et al. Shows that both programs are equally well suited for the calculation of the MWD of PLP samples. The emphasis is on the study of the effects that the experimental parameters, i.e. the primary radical concentration in a specific experiment, the gradients of this radical concentration, and above all the instrumental broadening of SEC analysis, have on the measured MWD, and therewith on the kp determination via PLP experiments. By detailed consideration of a styrene bulk polymerization experiment at 70°C and ambient pressure, it is shown that the PLP‐SEC technique at primary radical concentrations between those given by the limiting cases of the low and high termination rate limits and with simulatioenous high quality of the SEC (low broadening) is very well suited for the kp determination. As the MWD of samples from PLP is influenced in a rather complex fashion by the kinetics of the polymerizing system, by the choice of the experimental parameters determining laser‐induced primary free radical concentration, and by the performance of the SEC device, it appears highly recommendable to accompany PLP studies by simulation.

Modelling of size‐exclusion chromatograms from molecular weight distribution calculations. Application to the grafting of polymers onto functionalized silica

AbstractThe objective of this paper is the modelling of the molecular weight distribution (MWD) and the polydispersity index (P. I.) of polystyrene grafted on porous silica beads prefunctionalized by a thiosilane molecule. Grafting occurs by a transfer reaction to the fixed mercapto groups. We have analysed the MWD of both grafted and ungrafted polymers by size‐exclusion chromatography (SEC). A good agreement between the experimental SEC diagrams and those calculated from the reaction rate constants is obtained with the following hypotheses: (1) the medium is a two‐phase system constituted of an interparticle phase and a porous intraparticle phase with a high local mercapto group concentration in the pores; (2) a higher transfer efficiency of the transfer agent in the pores (what could be attributed to a higher mobility of the very short chains inside the pores); (3) a lower termination rate in the pores, which results in a higher rate of polymerization than in the interparticle phase (probably due to an increase of the medium viscosity).

Clinical experiences with MLCu250 and MLCu375 IUD

The paper summarizes the author's ten-year experience with 1446 interval insertions of the MLCu250 standard-type device, and makes comparison between the first two-year results of this and the MLCu375 IUD. The 120th month was completed by 106 MLCu250 users, and the cumulative woman-months of use (wmu) were 78,078. At the end of the second year, 976 patients were at risk in this group, representing a total of 28,097 wmu. From the initial 224 MLCu375 IUD cases, 160 (2,151 wmu) and 93 (3634 wmu) were eligible for life-table calculation at the end of the first and the second year, respectively. The overall performance was evaluated by net and gross cumulative and yearly specific rates as suggested by Tietze. These figures are detailed by the article. Based on this evaluation, two statements are made: (1) the MLCu250 standard-type device has a good overall performance and a longer life span than was previously expected; (2) the first two-year results with the MLCu375 are more favorable (lower termination rates, higher continuation) than the MLCu250.

Five years' experience of intrauterine contraception with the Nova-T and the Copper-T-200

A randomized study was performed for the comparison of two copper-releasing intrauterine contraceptive devices (IUDs), the Nova-T and the Copper-T-200, simultaneously in Denmark, Finland, and Sweden. Five years' experience demonstrated that Nova-T users had a significantly lower pregnancy rate than Copper-T-200 users. The Pearl index over 5 years was 0.8 for Nova-T users and 2.0 for Copper-T users. The performance and tolerance of the Nova-T were less affected by parity and age than was the performance of the Copper-T. Infections were treated by removal of the device and with antibiotics. The cumulative rate of removals because of infections and suspected infections was below 5 with both devices over 5 years. The copper wire in the Nova-T has a silver core which prevents corrosion-induced fragmentation of the wire. Hence, the effective lifetime of this device is more than 5 years. The results indicate that the Nova-T, which is easy to insert and remove and is associated with a low pregnancy rate and a low medical termination rate, is a real improvement over other IUDs.

Five years' experience of intrauterine contraception with the Nova-T and the Copper-T-200

A randomized study was performed for the comparison of two copper-releasing intrauterine contraceptive devices (IUDs), the Nova-T and the Copper-T-200, simultaneously in Denmark, Finland, and Sweden. Five years' experience demonstrated that Nova-T users had a significantly lower pregnancy rate than Copper-T-200 users. The Pearl index over 5 years was 0.8 for Nova-T users and 2.0 for Copper-T users. The performance and tolerance of the Nova-T were less affected by parity and age than was the performance of the Copper-T. Infections were treated by removal of the device and with antibiotics. The cumulative rate of removals because of infections and suspected infections was below 5 with both devices over 5 years. The copper wire in the Nova-T has a silver core which prevents corrosion-induced fragmentation of the wire. Hence, the effective lifetime of this device is more than 5 years. The results indicate that the Nova-T, which is easy to insert and remove and is associated with a low pregnancy rate and a low medical termination rate, is a real improvement over other IUDs.

ChemInform Abstract: OXIDATION OF HYDROCARBONS IN THE PRESENCE OF ADDED HYDROPEROXIDE. ON THE DETERMINATION OF RATE CONSTANTS BY THE HYDROPEROXIDE METHOD

Oxidation of tetralin in the presence of tert-butyl hydroperoxide and tetralyl hydroperoxide, initiated with azobisisobutyronitrile, was studied at 60°C in order to examine the complications involved in the hydroperoxide method devised by Howard and Ingold. From literature data on absolute rate constants and our rates of oxidation, cross termination rate constants and contributions of each elementary propagation and termination step were computed. It was confirmed that this method was quite useful in determining the cross propagation rate constant, but it was also demonstrated that the rate of oxidation should be measured at very low conversion and with quite high concentrations of hydroperoxide, especially when the peroxy radical derived from the added hydroperoxide has a much lower termination rate constant than that from the oxidizing substrate.