Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV : a pragmatic, multicentre, open-label, randomised clinical trial

This trial was funded from public money by the Netherlands Organisation for Health Research and Development (ZonMW; grant number 171002208). Aardex provided support on the development of the study website. We thank all the HIV nurses and physicians from the seven HIV clinics involved in the AIMS study for their input and collaboration (Academic Medical Centre, Slotervaart hospital, and St. Lucas-Andreas hospital, all in Amsterdam; the Leiden University Medical Centre, Leiden; HAGA hospital, The Hague; Erasmus Medical Centre, Rotterdam; and Isala clinic, Zwolle), the study participants, and the Stichting HIV Monitoring (SHM) for their support in accessing the SHM database for identifying patient inclusion criteria and developing the Markov model. Finally, we thank and remember Herman Schaalma (deceased) for his contribution to the study design and grant application.Peer reviewedPostprin

Transfusion practice in the bleeding critically ill:An international online survey-The TRACE-2 survey

Background: Transfusion is very common in the intensive care unit (ICU), but practice is highly variable, as has recently been shown in non-bleeding critically ill patients practices survey. Bleeding patients in ICU require different blood products across a range of specific patient categories. We hypothesize that a large variety in transfusion practice exists in bleeding patients. Study design and methods: An international online survey was performed among physicians working in the ICU. Transfusion practice in massively and non-massively bleeding patients was examined, including transfusion ratios, thresholds, and the presence of transfusion guidelines. Results: Six hundred eleven respondents filled in the survey of which 401 could be analyzed, representing 64 countries. Among the respondents, 52% had a massive transfusion protocol (MTP) available at their ICU. In massively bleeding patients, 46% of the respondents used fixed transfusion component ratios. Of those who used fixed blood ratios, the 1:1:1 ratio (red blood cell [RBC] concentrates: plasma: platelet concentrates) was most commonly used (33%). The presence of an MTP was associated with a more frequent use of fixed ratios (p <.001). For RBC transfusion in the general non-massively bleeding ICU population, a hemoglobin (Hb) threshold of 7.0[7.0–7.3] g/dl was reported. In the general ICU population, a platelet count threshold of 50[26–50] × 109/L was applied. Discussion: Half of the centers had no massive transfusion protocol available. Transfusion practice in massively bleeding critically ill patients is highly variable and driven by the presence of an MTP. In the general non-massively bleeding ICU population restrictive transfusion triggers were chosen

Evidence for local inflammation in complex regional pain syndrome type 1.

BACKGROUND: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1) is still a matter of debate. Peripheral afferent, efferent and central mechanisms are supposed. Based on clinical signs and symptoms (e.g. oedema, local temperature changes and chronic pain) local inflammation is suspected. AIM: To determine the involvement of neuropetides, cytokines and eicosanoids as locally formed mediators of inflammation. METHODS: In this study, nine patients with proven CRPS 1 were included. Disease activity and impairment was determined by means of a Visual Analogue Scale, the McGill Pain Questionnaire, the difference in volume and temperature between involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Venous blood was sampled from and suction blisters made on the involved and uninvolved extremities for measurement of cytokines interleukin (IL)-6, II-1beta and tumour necrosis factor-alpha (TNF-alpha), the neuropetides NPY and CRGP, and prostaglandin E2RESULTS: The patients included in this study did have a moderate to serious disease activity and impairment. In plasma, no changes of mediators of inflammation were observed. In blister fluid, however, significantly higher levels of IL-6 and TNF-alpha in the involved extremity were observed in comparison with the uninvolved extremity. CONCLUSIONS: This is the first time that involvement of mediators of inflammation in CRPS 1 has been so clearly and directly demonstrated. This observation opens new approaches for the succesful use and development of immunosuppressives in CRPS 1

Mannan-binding lectin is involved in the protection against renal ischemia/ reperfusion injury by dietary restriction

Preoperative fasting and dietary restriction offer robust protection against renal ischemia/ reperfusion injury (I/RI) in mice.We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on these findings, we investigated the effect of short-term DR (30% reduction of total food intake) or three days of water only fasting on MBL in 10-12 weeks old male C57/Bl6 mice. Both dietary regimens significantly reduce the circulating levels of MBL as well as its mRNA expression in liver, the sole production site of MBL. Reconstitution of MBL abolished the protection afforded by dietary restriction, whereas in the fasting group the protection persisted. These data show that modulation of MBL is involved in the protection against renal I/RI induced by dietary restriction, and suggest that the mechanisms of protection induced by dietary restriction and fasting may be different. Copyright

Modeling the combined effect of RNA-binding proteins and microRNAs in post-transcriptional regulation

Recent studies show that RNA-binding proteins (RBPs) and microRNAs (miRNAs) function in coordination with each other to control post-transcriptional regulation (PTR). Despite this, the majority of research to date has focused on the regulatory effect of individual RBPs or miRNAs. Here, we mapped both RBP and miRNA binding sites on human 3′UTRs and utilized this collection to better understand PTR. We show that the transcripts that lack competition for HuR binding are destabilized more after HuR depletion. We also confirm this finding for PUM1(2) by measuring genome-wide expression changes following the knockdown of PUM1(2) in HEK293 cells. Next, to find potential cooperative interactions, we identified the pairs of factors whose sites co-localize more often than expected by random chance. Upon examining these results for PUM1(2), we found that transcripts where the sites of PUM1(2) and its interacting miRNA form a stem-loop are more stabilized upon PUM1(2) depletion. Finally, using dinucleotide frequency and counts of regulatory sites as features in a regression model, we achieved an AU-ROC of 0.86 in predicting mRNA half-life in BEAS-2B cells. Altogether, our results suggest that future studies of PTR must consider the combined effects of RBPs and miRNAs, as well as their interactions.No sponso

The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency

Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs -/- mice. However, these observations are based on independent studies with varying genetic backgrounds. Here, we generated ku80-/-, dna-pkcs -/- and double knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their lifespan, end of life pathology and mutation frequency in liver a

Transfusion practice in the non-bleeding critically ill:an international online survey-the TRACE survey

Background Over the last decade, multiple large randomized controlled trials have studied alternative transfusion strategies in critically ill patients, demonstrating the safety of restrictive transfusion strategies. Due to the lack of international guidelines specific for the intensive care unit (ICU), we hypothesized that a large heterogeneity in transfusion practice in this patient population exists. The aims of this study were to describe the current transfusion practices and identify the knowledge gaps. Methods An online, anonymous, worldwide survey among ICU physicians was performed evaluating red blood cell, platelet and plasma transfusion practices. Furthermore, the presence of a hospital- or ICU-specific transfusion guideline was asked. Only completed surveys were analysed. Results Nine hundred forty-seven respondents filled in the survey of which 725 could be analysed. Hospital transfusion protocol available in their ICU was reported by 53% of the respondents. Only 29% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin (Hb) threshold for the general ICU population was 7 g/dL (7-7). The highest reported variation in transfusion threshold was in patients on extracorporeal membrane oxygenation or with brain injury (8 g/dL (7.0-9.0)). Platelets were transfused at a median count of 20 x 10(9) cells/L IQR (10-25) in asymptomatic patients, but at a higher count prior to invasive procedures (p &lt;0.001). In patients with an international normalized ratio (INR) &gt; 3, 43% and 57% of the respondents would consider plasma transfusion without any upcoming procedures or prior to a planned invasive procedure, respectively. Finally, doctors with base specialty in anaesthesiology transfused critically ill patients more liberally compared to internal medicine physicians. Conclusion Red blood cell transfusion practice for the general ICU population is restrictive, while for different subpopulations, higher Hb thresholds are applied. Furthermore, practice in plasma and platelet transfusion is heterogeneous, and local transfusion guidelines are lacking in the majority of the ICUs.</p

Treatment Outcome Trends for Non-Ruptured Abdominal Aortic Aneurysms:A Nationwide Prospective Cohort Study

Objective: The Dutch Surgical Aneurysm Audit (DSAA) initiative was established in 2013 to monitor and improve nationwide outcomes of aortic aneurysm surgery. The objective of this study was to examine whether outcomes of surgery for intact abdominal aortic aneurysms (iAAA) have improved over time.Methods: Patients who underwent primary repair of an iAAA by standard endovascular (EVAR) or open surgical repair (OSR) between 2014 and 2019 were selected from the DSAA for inclusion. The primary outcome was peri-operative mortality trend per year, stratified by OSR and EVAR. Secondary outcomes were trends per year in major complications, textbook outcome (TbO), and characteristics of treated patients. The trends per year were evaluated and reported in odds ratios per year.Results: In this study, 11 624 patients (74.8%) underwent EVAR and 3 908 patients (25.2%) underwent OSR. For EVAR, after adjustment for confounding factors, there was no improvement in peri-operative mortality (aOR [adjusted odds ratio] 1.06, 95% CI 0.94 – 1.20), while major complications decreased (2014: 10.1%, 2019: 7.0%; aOR 0.91, 95% CI 0.88 – 0.95) and the TbO rate increased (2014: 68.1%, 2019: 80.9%; aOR 1.13, 95% CI 1.10 – 1.16). For OSR, the peri-operative mortality decreased (2014: 6.1%, 2019: 4.6%; aOR 0.89, 95% CI 0.82 – 0.98), as well as major complications (2014: 28.6%, 2019: 23.3%; aOR 0.95, 95% CI 0.91 – 0.99). Furthermore, the proportion of TbO increased (2014: 49.1%, 2019: 58.3%; aOR 1.05, 95% CI 1.01 – 1.10). In both the EVAR and OSR group, the proportion of patients with cardiac comorbidity increased.Conclusion: Since the establishment of this nationwide quality improvement initiative (DSAA), all outcomes of iAAA repair following EVAR and OSR have improved, except for peri-operative mortality following EVAR which remained unchanged.</p

A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients

__Background:__ The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single-slice computed tomography (CT)-based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter-observer, intra-observer, and inter-software correlation are unknown. Therefore, a comparative study was performed. __Methods:__ Fifty abdominal CT scans were randomly selected from 50 different patients and independently assessed by two observers. Cross-sectional muscle area (CSMA, i.e. rectus abdominis, oblique and transverse abdominal muscles, paraspinal muscles, and the psoas muscle), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) were segmented by using standard Hounsfield unit ranges and computed for regions of interest. The inter-software, intra-observer, and inter-observer agreement for CSMA, VAT, and SAT measurements using FatSeg, OsiriX, ImageJ, and sliceOmatic were calculated using intra-class correlation coefficients (ICCs) and Bland-Altman analyses. Cohen's κ was calculated for the agreement of sarcopenia and visceral obesity assessment. The Jaccard similarity coefficient was used to compare the similarity and diversity of measurements. __Results:__ Bland-Altman analyses and ICC indicated that the CSMA, VAT, and SAT measurements between the different software programmes were highly comparable (ICC 0.979-1.000, P<0.001). All programmes adequately distinguished between the presence or absence of sarcopenia (κ=0.88-0.96 for one observer and all κ=1.00 for all comparisons of the other observer) and visceral obesity (all κ=1.00). Furthermore, excellent intra-observer (ICC 0.999-1.000, P<0.001) and inter-observer (ICC 0.998-0.999, P< 0.001) agreement for all software programmes were found. Accordingly, excellent Jaccard similarity coefficients were found for all comparisons (mean≥0.964). __Conclusions:__ FatSeg, OsiriX, ImageJ, and sliceOmatic showed an excellent agreement for CSMA, VAT, and SAT measurements on abdominal CT scans. Furthermore, excellent inter-observer and intra-observer agreement were achieved. Therefore, results of studies using these different software programmes can reliably be compared

Acute myocardial infarction incidence and hospital mortality: routinely collected national data versus linkage of national registers

Background and Objective To compare levels of and trends in incidence and hospital mortality of first acute myocardial infarction (AMI) based on routinely collected hospital morbidity data and on linked registers. Cases taken from routine hospital data are a mix of patients with recurrent and first events, and double counting occurs when cases are admitted for an event several times during 1 year. By linkage of registers, recurrent events and double counts can be excluded. Study Design and Setting In 1995 and 2000, 28,733 and 25,864 admissions for AMI were registered in the Dutch national hospital discharge register. Linkage with the population register yielded 21,565 patients with a first AMI in 1995 and 20,414 in 2000. Results In 1995 and 2000, the incidence based on the hospital register was higher than based on the linked registers in men (22% and 23% higher) and women (18% and 20% higher). In both years, hospital mortality based on the hospital register and on linked registers was similar. The decline in incidence between 1995 and 2000 was comparable whether based on standard hospital register data or linked data (18% and 20% in men, 15% and 17% in women). Similarly, the decline in hospital mortality was comparable using either approach (11% and 9% in both men and women). Conclusion Although the incidence based on routine hospital data overestimates the actual incidence of first AMI based on linked registers, hospital mortality and trends in incidence and hospital mortality are not changed by excluding recurrent events and double counts. Since trends in incidence and hospital mortality of AMI are often based on national routinely collected data, it is reassuring that our results indicate that findings from such studies are indeed valid and not biased because of recurrent events and double counts