Maintenance hemodialysis patients have high cumulative radiation exposure

Hemodialysis is associated with an increased risk of neoplasms which may result, at least in part, from exposure to ionizing radiation associated with frequent radiographic procedures. In order to estimate the average radiation exposure of those on hemodialysis, we conducted a retrospective study of 100 patients in a university-based dialysis unit followed for a median of 3.4 years. The number and type of radiological procedures were obtained from a central radiology database, and the cumulative effective radiation dose was calculated using standardized, procedure-specific radiation levels. The median annual radiation dose was 6.9 millisieverts (mSv) per patient-year. However, 14 patients had an annual cumulative effective radiation dose over 20mSv, the upper averaged annual limit for occupational exposure. The median total cumulative effective radiation dose per patient over the study period was 21.7mSv, in which 13 patients had a total cumulative effective radiation dose over 75mSv, a value reported to be associated with a 7% increased risk of cancer-related mortality. Two-thirds of the total cumulative effective radiation dose was due to CT scanning. The average radiation exposure was significantly associated with the cause of end-stage renal disease, history of ischemic heart disease, transplant waitlist status, number of in-patient hospital days over follow-up, and death during the study period. These results highlight the substantial exposure to ionizing radiation in hemodialysis patients

Stakeholders’ knowledge, attitudes and practices to pharmacovigilance and adverse drug reaction reporting in clinical trials: a mixed methods study

Purpose: The purpose of this study was to explore the knowledge, attitudes and practices of health professionals working in clinical trials, to pharmacovigilance and adverse drug reaction (ADR) reporting. Methods: A mixed methods study comprising an online questionnaire disseminated from September to November 2018, three semi-structured interviews and four focus groups. The qualitative components were conducted with a random sample of questionnaire participants who had provided their contact details (n = 24). The qualitative interviews were conducted at a location convenient to the participant’s place of work between October and December 2018. Results: One hundred forty-eight participants completed the questionnaire. Study coordinators/project managers represented the largest group of participants ( 28.6%, n = 38). Poor knowledge or understanding of ADR reporting was the most frequently cited barrier to ADR reporting (75%, n = 93). The most common enabler to reporting was having a clear understanding of an ADR definition (85.7%, n = 108). Focus group and interview participants described having limited staff as a barrier to reporting an ADR. They welcomed the prospect of pharmacovigilance training and indicated that face-to-face training would be preferred to provision of online training. Conclusion: This study highlights key factors that influence the reporting of ADRs in clinical trials. Although the findings are specifically related to the clinical trial environment in Ireland, they may provide a useful platform for optimising the future conduct of trials. This research suggests that ADR reporting may be improved through provision of enhanced pharmacovigilance training to clinical trial staff

Incident adverse drug reactions in geriatric inpatients : a multicentred observational study

Background: Adverse drug reactions (ADRs) are common in older adults and frequently have serious clinical and economic consequences. This study was conducted as a feasibility study for a randomized control trial (RCT) that will investigate the efficacy of a software engine to optimize medications and reduce incident (in-hospital) ADRs. This study's objectives were to (i) establish current incident ADR rates across the six sites participating in the forthcoming RCT and (ii) assess whether incident ADRs are predictable. Methods: This was a multicentre, prospective observational study involving six European hospitals. Adults aged 65 years, hospitalized with an acute illness and on pharmacological treatment for three or more conditions were eligible for inclusion. Adverse events (AEs) were captured using a trigger list of 12 common ADRs. An AE was deemed an ADR when its association with an administered drug was adjudicated as being probable/certain, according to the World Health Organization Uppsala Monitoring Centre causality assessment. The proportion of patients experiencing at least one, probable/certain, incident ADR within 14 days of enrolment/discharge was recorded. Results: A total of 644 patients were recruited, evenly split by sex and overwhelmingly of White ethnicity. Over 80% of admissions were medical. The median number of chronic conditions was five (interquartile range 4-6), with eight or more conditions present in approximately 10%. The mean number of prescribed medications was 9.9 (standard deviation 3.8), which correlated strongly with the number of conditions (r = 0.54, p < 0.0001). A total of 732 AEs were recorded in 382 patients, of which 363 were incident. The majority of events were classified as probably or possibly drug related, with heterogeneity across sites (chi(2) = 88.567, df = 20, p value < 0.001). Out of 644 patients, 139 (21.6%; 95% confidence interval 18.5-25.0%) experienced an ADR. Serum electrolyte abnormalities were the most common ADR. The ADRROP (ADR Risk in Older People) and GerontoNet ADR risk scales correctly predicted ADR occurrence in 61% and 60% of patients, respectively. Conclusion: This feasibility study established the rates of incident ADRs across the six study sites. The ADR predictive power of ADRROP and GerontoNet ADR risk scales were limited in this population

A treatment evaluator tool to monitor the real-world effectiveness of inhaled aztreonam lysine in cystic fibrosis

Background: Studies are required that evaluate real-world outcomes of inhaled aztreonam lysine in patients with cystic fibrosis (CF). Methods: Our treatment-evaluator tool assessed the effectiveness of inhaled aztreonam in routine practice in 117 CF patients across four time periods (6–12 (P2) and 0–6 months (P1) pre-initiation, and 0–6 (T1) and 6–12 months (T2) post-initiation). Outcomes were: changes in %-predicted forced expiratory volume in 1 s (FEV1), body-mass index (BMI), hospitalisation days and intravenous antibiotic usage. Results: Median FEV1% predicted for each 6-month period was 38.9%, 34.6%, 37.1% and 36.5%; median change was − 2.0% between P2 and P1, increasing to + 0.6% (p &lt; 0.001) between P1 and T1. Annualised hospital bed-days was reduced (p = 0.05) post-initiation, as was intravenous antibiotics days (p = 0.001). BMI increased over 6 months post-initiation (p ≤ 0.001). Conclusions: In patients with CF in routine practice, inhaled aztreonam lysine is associated with improved lung function and weight, and reduced hospitalisation and intravenous antibiotic use

Study protocol for the implementation and evaluation of the Self-harm Assessment and Management for General Hospitals programme in Ireland (SAMAGH)

Background: Previous self-harm is one of the strongest predictors of future self-harm and suicide. Increased risk of repeated self-harm and suicide exists amongst patients presenting to hospital with high-risk self-harm and major self-harm repeaters. However, so far evidence-based training in the management of self-harm for mental health professionals is limited. Within this context, we aim to develop, implement and evaluate a training programme, SAMAGH, Self-harm Assessment and Management Programme for General Hospitals in Ireland. SAMAGH aims to (a) reduce hospital-based self-harm repetition rates and (b) increase rates of mental health assessments being conducted with self-harm patients. We also aim to evaluate the training on self-harm knowledge, attitudes, and skills related outcomes of healthcare professionals involved in the training. Methods/design: The study will be conducted in three phases. First, the SAMAGH Training Programme has been developed, which comprises two parts: 1) E-learning Programme and 2) Simulation Training. Second, SAMAGH will be delivered to healthcare professionals from general hospitals in Ireland. Third, an outcome and process evaluation will be conducted using a pre-post design. The outcome evaluation will be conducted using aggregated data from the National Self-Harm Registry Ireland (NSHRI) on self-harm repetition rates from all 27 public hospitals in Ireland. Aggregated data based on the 3-year average (2016, 2017, 2018) self-harm repetition rates prior to the implementation of the SAMAGH will be used as baseline data, and NSHRI data from 6 and 12 months after the implementation of SAMAGH will be used as follow-up. For the process evaluation, questionnaires and focus groups will be administered and conducted with healthcare professionals who completed the training. Discussion: This study will contribute to the evidence base regarding the effectiveness of an evidence informed training programme that aims to reduce repeated hospital self-harm presentations and to improve compliance with self-harm assessment and management. This study is also expected to contribute to self-harm and suicide training with the possibility of being translated to other settings. Its feasibility will be evaluated through a process evaluation

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial

Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifcally on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/ critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modifed intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute diference and 95% CI −0.1% [−8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (−3.2% [−9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a signifcant interac‑ tion between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated partici‑ pants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to con‑ clude on a potential survival beneft of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these fnd‑ ings warrant further investigation in other trials and real-world studies

Implementation and evaluation of a multi-level mental health promotion intervention for the workplace (MENTUPP): study protocol for a cluster randomised controlled trial

Background Well-organised and managed workplaces can be a source of wellbeing. The construction, healthcare and information and communication technology sectors are characterised by work-related stressors (e.g. high workloads, tight deadlines) which are associated with poorer mental health and wellbeing. The MENTUPP intervention is a flexibly delivered, multi-level approach to supporting small- and medium-sized enterprises (SMEs) in creating mentally healthy workplaces. The online intervention is tailored to each sector and designed to support employees and leaders dealing with mental health difficulties (e.g. stress), clinical level anxiety and depression, and combatting mental health-related stigma. This paper presents the protocol for the cluster randomised controlled trial (cRCT) of the MENTUPP intervention in eight European countries and Australia. Methods Each intervention country will aim to recruit at least two SMEs in each of the three sectors. The design of the cRCT is based on the experiences of a pilot study and guided by a Theory of Change process that describes how the intervention is assumed to work. SMEs will be randomly assigned to the intervention or control conditions. The aim of the cRCT is to assess whether the MENTUPP intervention is effective in improving mental health and wellbeing (primary outcome) and reducing stigma, depression and suicidal behaviour (secondary outcome) in employees. The study will also involve a process and economic evaluation. Conclusions At present, there is no known multi-level, tailored, flexible and accessible workplace-based intervention for the prevention of non-clinical and clinical symptoms of depression, anxiety and burnout, and the promotion of mental wellbeing. The results of this study will provide a comprehensive overview of the implementation and effectiveness of such an intervention in a variety of contexts, languages and cultures leading to the overall goal of delivering an evidence-based intervention for mental health in the workplace

Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe