Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group.

DICER1 syndrome is a rare genetic disorder that predisposes to a wide spectrum of tumors. Developing surveillance protocols for this syndrome is challenging because uncertainty exists about the clinical efficacy of surveillance, and appraisal of potential benefits and harms vary. In addition, there is increasing evidence that germline DICER1 pathogenic variants are associated with lower penetrance for cancer than previously assumed. To address these issues and to harmonize DICER1 syndrome surveillance programs within Europe, the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) and Clinical Guideline Working Group of the CanGene-CanVar project in the United Kingdom reviewed current surveillance strategies and evaluated additional relevant literature. Consensus was achieved for a new surveillance protocol and information leaflet that informs patients about potential symptoms of DICER1-associated tumors. The surveillance protocol comprises a minimum program and an extended version for consideration. The key recommendations of the minimum program are: annual clinical examination from birth to age 20 years, six-monthly chest X-ray and renal ultrasound from birth to age 6 years, and thyroid ultrasound every 3 years from age 8 to age 40 years. The surveillance program for consideration comprises additional surveillance procedures, and recommendations for DICER1 pathogenic variant carriers outside the ages of the surveillance interval. Patients have to be supported in choosing the surveillance program that best meets their needs. Prospective evaluation of the efficacy and patient perspectives of proposed surveillance recommendations is required to expand the evidence base for DICER1 surveillance protocols

Novel psychoactive substance use by mental health service consumers: an online survey of inpatient health professionals’ views and experiences

Purpose: There is evidence that novel psychoactive substances (NPS) are commonly used by people with severe mental illness. The aim of the study was to undertake a scoping survey to explore inpatient mental health workers' perceptions of NPS use by consumers. Design/methodology: A cross-sectional online survey of mental health professionals. Participants were opportunistically recruited through social media and professional networks. Findings: A total of 98 participants (of 175 who started the survey) were included in the analysis. All reported that some patients had used NPS prior to admission. Over 90% of participants reported observing at least one adverse event relating to NPS use in the previous month. The majority of participants reported that patients had used NPS during their inpatient admission. Three quarters were not clear if their workplace had a policy about NPS. Most wanted access to specific NPS information and training. Participants reported that they lacked the necessary knowledge and skills to manage NPS use in the patients they worked with. Research Limitations/Implications: Whilst we are cautious about the generalizability (due to methodological limitations), our findings provide useful insight into the perceptions of inpatient staff regarding the extent and impact of NPS use including concerns regarding impact on mental and physical health, as well as ease of availability and a need for specific training and guidance. Practical Implications: Mental health professionals require access to reliable and up to date information on changing trends in substance use. Local policies need to include guidance on the safe clinical management of substance use and ensure that NPS information is included. Originality/value: To the best of our knowledge this is the first survey of the perceptions of mental health staff working in inpatient mental health settings regarding NPS.The findings suggest that NPS is a common phenomenon in inpatient mental health settings, and there is a need for more research on the impact of NPS on people with mental health problems

Cause-Specific Mortality in the Unionized U.S. Trucking Industry

Background: Occupational and population-based studies have related exposure to fine particulate air pollution, and specifically particulate matter from vehicle exhausts, to cardiovascular diseases and lung cancer. Objectives: We have established a large retrospective cohort to assess mortality in the unionized U.S. trucking industry. To provide insight into mortality patterns associated with job-specific exposures, we examined rates of cause-specific mortality compared with the general U.S. population. Methods: We used records from four national trucking companies to identify 54,319 male employees employed in 1985. Cause-specific mortality was assessed through 2000 using the National Death Index. Expected numbers of all and cause-specific deaths were calculated stratifying by race, 10-year age group, and calendar period using U.S. national reference rates. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for the entire cohort and by job title. Results: As expected in a working population, we found a deficit in overall and all-cancer mortality, likely due to the healthy worker effect. In contrast, compared with the general U.S. population, we observed elevated rates for lung cancer, ischemic heart disease, and transport-related accidents. Lung cancer rates were elevated among all drivers (SMR = 1.10; 95% CI, 1.02–1.19) and dockworkers (SMR = 1.10; 95% CI, 0.94–1.30); ischemic heart disease was also elevated among these groups of workers [drivers, SMR = 1.49 (95% CI, 1.40–1.59); dockworkers, SMR = 1.32 (95% CI, 1.15–1.52)], as well as among shop workers (SMR = 1.34; 95% CI, 1.05–1.72). Conclusions: In this detailed assessment of specific job categories in the U.S. trucking industry, we found an excess of mortality due to lung cancer and ischemic heart disease, particularly among drivers

Getting patient blood management Pillar 1 right in the Asia-Pacific: a call for action

Preoperative anaemia is common in the Asia-Pacific. Iron-deficiency anaemia (IDA) is a risk factor that can be addressed under patient blood management (PBM) Pillar 1, leading to reduced morbidity and mortality. We examined PBM implementation under four different healthcare systems, identified challenges and proposed several measures. (a) Test for anaemia once patients are scheduled for surgery. (b) Inform patients about risks of preoperative anaemia and benefits of treatment. (c) Treat IDA and replenish iron stores before surgery, using intravenous iron when oral treatment is ineffective, not tolerated or rapid iron replenishment is needed; transfusion should not be the default management. (d) Harness support from multiple medical disciplines and relevant bodies to promote PBM implementation. (e) Demonstrate better outcomes and cost savings from reduced mortality and morbidity. Although PBM implementation may seem complex and daunting, it is feasible to start small. Implementing PBM Pillar 1, particularly in preoperative patients, is a sensible first step regardless of the healthcare setting

Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis.

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission

Assessing potential sources of clustering in individually randomised trials

Recent reviews have shown that while clustering is extremely common in individually randomised trials (for example, clustering within centre, therapist, or surgeon), it is rarely accounted for in the trial analysis. Our aim is to develop a general framework for assessing whether potential sources of clustering must be accounted for in the trial analysis to obtain valid type I error rates (non-ignorable clustering), with a particular focus on individually randomised trials

Improving data availability for brain image biobanking in healthy subjects: practice-based suggestions from an international multidisciplinary working group

International audienceBrain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function

Aid alignment for global health research: the role of HIROs

The lack of a mechanism that aligns financial flows for global health research towards public health priorities limits the impact of health research on health and health equity. Collaborative groups of health research funders appear to be particularly well situated to ameliorate this situation and to initiate discussion on aid alignment for global health research. One such group is the Heads of International Research Organizations (HIROs), which brings together a large number of major government and philanthropic funders of biomedical research. Surprisingly, there is hardly any information publicly available on HIROs' objectives, or on how it aims to achieve more harmonization in the field of research for health. Greater transparency on HIROs' objectives and on its current efforts towards addressing the gap between global health research needs and investments would be desirable, given the enormous potential benefits of more coordination by this group

Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships

<p>Abstract</p> <p>Background</p> <p>To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy.</p> <p>Methods</p> <p>Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies) and gabapentin (4 studies) over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures) and "change from baseline in seizure-free days over the last 28 days (SFD)". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations.</p> <p>Results</p> <p>The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25) and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27). Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg) were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg) in terms of SFD over the last 28 days.</p> <p>Conclusion</p> <p>In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.</p