Factors affecting patient recruitment to trials:qualitative research in general practice

BACKGROUND: Patient recruitment to clinical research is often challenging and, when inadequate, can result in delayed or underpowered studies. Recruitment problems were experienced during a study of women with heavy menstrual bleeding in general practice (the MIRA trial). Although efforts were made to reduce the burden of the study for those participating, patient recruitment was still an issue. AIM: To identify the barriers and facilitators associated with patient recruitment to clinical trials, as experienced by GPs. DESIGN & SETTING: A qualitative study was performed in Dutch general practice, using semi-structured interviews. METHOD: GPs participating in the MIRA trial were selected by purposive sampling and interviewed until saturation was reached. Three independent researchers performed data coding and thematic analysis. Consensus on the identified themes was reached by discussion among the researchers. RESULTS: Sixteen GPs were interviewed. The following factors were noted to influence recruitment: the incidence of the disease under study; awareness of the study; attitude towards scientific research; perceived burden for the patient; usual care by the GP; time investment; characteristics of the GP and their practice; and patient experience of research participation. CONCLUSION: The identified barriers and facilitators associated with patient recruitment highlight the areas in which future studies can be improved. Indeed, benefits could be gained by simply ensuring that study procedures are clear, by requiring limited (time) investment from the GP, and by investing in personal communication and reminders to keep the GP motivated and interested. Placing greater importance on scientific research during the GP training programme could also serve as a means to motivate future GPs to integrate scientific research in their clinical practice

Treatment of women with heavy menstrual bleeding:Results of a prospective cohort study alongside a randomised controlled trial

OBJECTIVE: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT. STUDY DESIGN: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands. Women suffering from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future fertility desire, were eligible for this trial. Women who declined randomisation were asked to participate in the observational cohort. The outcome measure was reintervention rate at 24 months of follow-up. RESULTS: 276 women were followed in the observational cohort of which 87 women preferred an initial treatment with LNG-IUS and 189 women preferred an initial treatment with endometrial ablation. At 24 months of follow-up women in the LNG-IUS-group were more likely to receive a reintervention compared to the women in the ablation group, 28/81 (35 %) versus 25/178 (14 %) (aRR 2.42, CI 1.47-3.98, p-value 0.001). No differences in reintervention rates were found between women in the observational cohort and women in the RCT. CONCLUSIONS: Women who receive an LNG-IUS are more likely to undergo an additional intervention compared to women who receive endometrial ablation. Reintervention rates of women in the cohort and RCT population were comparable. The results of this study endorse the findings of the RCT and will contribute to shared decision making in women with heavy menstrual bleeding

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Acknowledgments: We thank all the women who participated in this trial; the participating general practitioners, gynecologists, and hospitals; the research nurses; and the staff of the Dutch Consortium for Studies in Women’s Health and Reproduction.Peer reviewedPublisher PD

Amygdala 14-3-3ζ as a Novel Modulator of Escalating Alcohol Intake in Mice

Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood. We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake. Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake. Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol. This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Women's preferences for the levonorgestrel intrauterine system versus endometrial ablation for heavy menstrual bleeding

Objectives: Women's preferences for treatment of heavy menstrual bleeding (HMB) are important in clinical decision-making. Our aim was to investigate whether women with HMB have a preference for treatment characteristics of the levonorgestrel intrauterine system (LNG-IUS) or endometrial ablation and to assess the relative importance of these characteristics. Study Design: A discrete choice experiment was performed in general practices and gynaecology outpatient clinics in the Netherlands. Women with HMB were asked to choose between hypothetical profiles containing characteristics of LNG-IUS or endometrial ablation. Characteristics included procedure performed by gynaecologist or general practitioner; reversibility of the procedure; probability of dysmenorrhea; probability of irregular bleeding; additional use of contraception; need to repeat the procedure after five years; and treatment containing hormones. Data were analysed using panel mixed logit models. The main outcome measures were the relative importance of the characteristics and willingness to make trade-offs. Results: 165 women completed the questionnaire; 36 (22%) patients were recruited from general practices and 129 (78%) patients were recruited from gynaecology outpatient clinics. The characteristic found most important was whether a treatment contains hormones. Women preferred a treatment without hormones, a treatment with the least side effects, and no need for a repeat procedure or additional contraception. Women completing the questionnaire at the gynaecology outpatient clinic differed from women in primary care in their preference for a definitive treatment to be performed by a gynaecologist. Conclusions: Whether or not a treatment contains hormones was the most important characteristic influencing patient treatment choice for HMB. Participants preferred characteristics that were mostly related to endometrial ablation, but were willing to trade-off between characteristics

Incidence and treatment of heavy menstrual bleeding in general practice

Background. Heavy menstrual bleeding (HMB) is a common problem in women of reproductive age. In 2008, the Dutch guideline for general practitioners (GPs) was revised to recommend the levonorgestrel intrauterine system (LNG-IUS) as a first-choice treatment for HMB. However, GP prescribing practices have not been studied in depth. Objectives. To investigate the incidence and initial treatment of HMB in general practice, and to identify if there were changes in prescribing practices after the revision of the national guideline in 2008. Methods. Retrospective analysis of data from the Registration Network Groningen, the Netherlands. We selected data for prescriptions and referrals related to women consulting their GP for HMB between 2004 and 2013. We calculated the incidence rates and investigated potential trends in prescribing over time, with particular attention to the prescribing of LNG-IUS. Results. Over 10 years, 881 women consulted their GP for HMB, with a mean annual incidence of 9.3 per 1000 person years (95% confidence interval: 8.5-10.2). Most women received hormonal treatment (406/881; 46%) within three months of diagnosis, but many (387/881; 44%) received no medication. The LNG-IUS was prescribed for 2.4%, but there was no significant increase in the number of prescriptions over time. Conclusion. In this cohort, most women with HMB were treated with oral hormone therapy, and few received the LNG-IUS. If patients are to benefit from the LNG-IUS, further research is needed into the reasons for this lack of change in prescribing practices