To determine whether an educational leaflet had any effect on seat belt use, seat preference and motor vehicle accidents rate during pregnancy in Japan.
Prospective, non-randomised control trial with a questionnaire survey.
Eight obstetric hospitals in Sapporo, Japan.
2216 pregnant women, of whom 1105 received the leaflet (intervention group) and 1111 did not (control group).
Distribution of an educational leaflet on seat belt use to women in the intervention group.
The effect of an educational leaflet on seat belt use, each pregnant woman’s seat preference and the women’s rates of motor vehicle accidents rate during their pregnancies. To evaluate the effects, the intervention group’s responses to the questionnaires were compared with those of the control group.
The proportion of subjects who always used seat belts during pregnancy was significantly higher in the intervention group (91.3%) than in the control group (86.7%; p=0.0005). Among all subjects, the percentage of women who preferred the driver’s seat was lower during pregnancy (27.0%) than before pregnancy (38.7%), and the percentage of women who preferred the rear seat was higher during pregnancy (28.8%) than before pregnancy (21.0%). These two rates did not differ between two groups. Seventy-one women (3.2%) reported experiencing a motor vehicle accident during pregnancy. The motor vehicle accident rate for the intervention group (3.3%) was similar to that for the control group (3.2%).
An educational seat belt leaflet was effective in raising the rate of consistent seat belt use during pregnancy, but it did not decrease the rate of motor vehicle accidents. The wearing of seat belts should be promoted more extensively among pregnant women to decrease rates of pregnancy-related morbidity and mortality from motor vehicle accidents.
To determine (i) the difference in the frequency of serious adverse events (SAEs) reported in trial registrations and their respective primary publications and (ii) the effect of adding SAE data from registries to a network meta-analysis (NMA) in changing the surface under the cumulative ranking (SUCRA) curve values of interventions.
Secondary analysis of primary publications from two NMAs.
We included randomised trials published in English after 2005 that were included in two NMAs of pharmacological interventions for Alzheimer’s disease and chronic obstructive pulmonary disease.
Two reviewers independently searched multiple international trial registries for registration status and abstracted data from the included study publications and ClinicalTrials.gov.
Of the 203 randomised trials included, 140 (69.0%) were registered with a trial registry and 72 (35.5%) posted results in the registry. The proportion of registered trials increased over time (38.5% in 2005 vs 78.6% in 2014). Of the publications with results posted in a trial registry, 14 (19.4%) had inconsistent reporting of overall SAEs; 7 (10.4%) studies did not report SAEs in the publication but did in the registry. In the 134 randomised trials with a prespecified primary outcome in the registry, 19 studies (9.4%) had a change in the primary outcome in the publication. Adding SAEs reported in registries to the NMAs did not affect the ranking of interventions.
We identified inconsistent reporting of SAEs in randomised trials that were included in two NMAs. Findings highlight the importance of including trial registries in the grey literature search and verifying safety data before incorporating it into NMAs.
Low back pain is one of the most common and burdensome chronic conditions worldwide. Lifestyle factors, such as excess weight, physical inactivity, poor diet and smoking, are linked to low back pain chronicity and disability. There are few high-quality randomised controlled trials that investigate the effects of targeting lifestyle risk factors in people with chronic low back pain.
The aim of this study is to determine the effectiveness of a Healthy Lifestyle Program (HeLP) for low back pain targeting weight, physical activity, diet and smoking to reduce disability in patients with chronic low back pain compared with usual care. This is a randomised controlled trial, with participants stratified by body mass index, allocated 1:1 to the HeLP intervention or usual physiotherapy care. HeLP involves three main components: (1) clinical consultations with a physiotherapist and dietitian; (2) educational resources; and (3) telephone-based health coaching support for lifestyle risk factors. The primary outcome is disability (Roland Morris Disability Questionnaire) at 26 weeks. Secondary outcomes include pain intensity, weight, quality of life and smoking status. Data will be collected at baseline, and at weeks 6, 12, 26 and 52. Patients with chronic low back pain who have at least one health risk factor (are overweight or obese, are smokers and have inadequate physical activity or fruit and vegetable consumption) will be recruited from primary or secondary care, or the community. Primary outcome data will be analysed by intention to treat using linear mixed-effects regression models. We will conduct three supplementary analyses: causal mediation analysis, complier average causal effects analysis and economic analysis.
This study was approved by the Hunter New England Research Ethics Committee (Approval No 17/02/15/4.05), and the University of Newcastle Human Research Ethics Committee (Ref No H-2017-0222). Outcomes of this trial and supplementary analyses will be disseminated through publications in peer-reviewed journals and conference presentations.
The objective of this study was to investigate the association between genetic polymorphisms of N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase (GST) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) and the risk of anti-tuberculosis drug-induced liver injury (ATDILI).
Systematic review and meta-analysis.
PubMed, Embase, Web of Science and Cochrane Reviews databases were searched through April 2019.
We included case-control or cohort studies investigating an association between NAT2, CYP2E1, GST or SLCO1B1 polymorphisms and the ATDILI risk in patients with tuberculosis.
Three authors screened articles, extracted data and assessed study quality. The strength of association was evaluated for each gene using the pooled OR with a 95% CI based on the fixed-effects or random-effects model. Sensitivity analysis was performed to confirm the reliability and robustness of the results.
Fifty-four studies were included in this analysis (n=26 for CYP2E1, n=35 for NAT2, n=19 for GST, n=4 for SLCO1B1). The risk of ATDILI was significantly increased with the following genotypes: CYP2E1 RsaI/PstI c1/c1 (OR=1.39, 95% CI 1.06 to 1.83), NAT2 slow acetylator (OR=3.30, 95% CI 2.65 to 4.11) and GSTM1 null (OR=1.30, 95% CI 1.12 to 1.52). No significant association with ATDILI was found for the genetic polymorphisms of CYP2E1 DraI, GSTT1, GSTM1/GSTT1, SLCO1B1 388A>G and SLCO1B1 521T>C (p>0.05).
ATDILI is more likely to occur in patients with NAT2 slow acetylator genotype, CYP2E1 RsaI/PstI c1/c1 genotype and GSTM1 null genotype. Close monitoring may be warranted for patients with these genotypes.
Smoke-free policies have been introduced in prisons internationally. However, high rates of relapse to smoking after release from prison indicate that these policies typically result in short-term smoking cessation only. These high rates of relapse, combined with a lack of investment in relapse prevention, highlight a missed opportunity to improve the health of a population who smoke tobacco at two to six times the rate of the general population. This paper describes the rationale and design of a randomised controlled trial, testing the effectiveness of a caseworker-delivered intervention promoting smoking cessation among former smokers released from smoke-free prisons in Victoria, Australia.
The multicomponent, brief intervention consists of behavioural counselling, provision of nicotine spray and referral to Quitline and primary care to promote use of government-subsidised smoking cessation pharmacotherapy. The intervention is embedded in routine service delivery and is administered at three time points: one prerelease and two postrelease from prison. Control group participants will receive usual care. Smoking abstinence will be assessed at 1 and 3 months postrelease, and confirmed with carbon monoxide breath testing. Linkage of participant records to survey and routinely collected administrative data will provide further information on postrelease use of health services and prescribed medication.
Ethical approval has been obtained from the Corrections Victoria Research Committee, the Victorian Department of Justice Human Research Ethics Committee, the Department of Human Services External Request Evaluation Committee and the University of Melbourne Human Research Ethics Committee. Results will be submitted to major international health-focused journals. In case of success, findings will assist policymakers to implement urgently needed interventions promoting the maintenance of prison-initiated smoking abstinence after release, to reduce the health disparities experienced by this marginalised population.
The virtual multidisciplinary stroke care clinic (VMSCC) is the first nurse-led clinic developed to offer support to community-dwelling stroke survivors and caregivers, and to promote poststroke recovery. This two-arm randomised controlled trial will evaluate its effectiveness on survivors’ self-efficacy (SE), survivors’ and caregivers’ health-related quality of life (HRQoL) and cost-effectiveness on emergency admissions and length of readmission hospital stay.
A consecutive sample of 384 stroke survivor–caregiver dyads will be recruited from four hospitals. An online platform that embraces readily accessible and reliable information will be developed. Participants randomly assigned to the intervention group will receive usual care plus the VMSCC service. The service includes access to a tablet containing 30 videos demonstrating appropriate self-care strategies, communication with a registered nurse monthly through video and telephone calls and regular blood pressure monitoring. Primary outcomes include survivors’ SE in self-management and survivors’ and caregivers’ HRQoL. Secondary outcomes include survivors’ performance of self-management behaviours, depression and social participation; and caregivers’ coping strategies, satisfaction with caring and depression. Data will be collected at baseline, and at 3 and 6 months after commencing the intervention. Survivors’ and caregivers’ satisfaction with the service will be assessed at 6-month follow-up. Multivariable regressions and generalised estimating equations model will be conducted. Survivors’ emergency admissions and length of hospital stay will be evaluated during the 6-month follow-up period. Cost-effectiveness analysis will be performed on the average total cost incurred.
The results will inform stakeholders about incorporating the VMSCC service into current stroke rehabilitation service.
This protocol was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2017.660). All participants will provide written informed consent. Results will be disseminated through scientific publications, and presentations at local and international conferences.
The wide range of outcomes after stroke emphasises the need for comprehensive long-term follow-up. The aim was to evaluate how people with stroke and health professionals (HPs) perceive the use of the poststroke checklist (PSC), with a focus on feasibility and relevance.
An exploratory design with a mix of qualitative and quantitative methods.
Outpatient care at a university hospital and primary care centres in western Sweden.
Forty-six consecutive patients (median age, 70; range, 41–85; 13 women) and 10 health professionals (median age 46; range, 35–63; 7 women).
Most patients (87%) had one or more problems identified by the PSC. The most common problem areas were life after stroke (61%), cognition (56%), mood (41%) and activities of daily living (39%). Three organisational themes emerged from the focus group discussions. The perception of the content and relevance of the PSC was that common poststroke problems were covered but that unmet needs still could be missed. Identifying needs was facilitated when using the PSC as a tool for dialogue. The dialogue between the patient and HP as well as HPs stroke expertise was perceived as important. The PSC was seen as a systematic routine and a base for egalitarian follow-up, but participants stressed consideration given to each individual. Addressing identified needs and meeting patient expectations were described as challenging given available healthcare services.
The PSC is a feasible and relevant tool to support egalitarian follow-up and identify patients who could benefit from targeted poststroke interventions. Stroke expertise, room for dialogue and caring for identified needs emerged as important issues to consider when using the PSC. Nutrition, sexuality and fatigue were areas mentioned that might need to be addressed within the discussions. The PSC can facilitate patients in expressing their needs, enhancing their ability to participate in decision-making.
by Seth E. Karol, Laura J. Janke, John C. Panetta, Laura B. Ramsey, Xiangjun Cai, Monique A. Payton, David A. Jenkins, William E. Evans, Mary V. RellingIntroduction
Combination therapy for acute lymphoblastic leukemia (ALL) is highly effective but results in significant toxicity including osteonecrosis. Asparaginase is known to potentiate both the antileukemic and osteonecrosis-inducing effects of dexamethasone. The schedule of dexamethasone alters osteonecrosis risk. However, the effects of the interaction with asparaginase are unknown when dexamethasone is given on a discontinuous schedule.Methods
Using the murine model of osteonecrosis, we compared the frequency of osteonecrosis in mice receiving discontinuous dexamethasone (3.5 days/ week) with mice receiving asparaginase and discontinuous dexamethasone. We then tested the effect on antileukemic efficacy using six pediatric ALL xenografts.Results
The addition of asparaginase to discontinuous dexamethasone did not alter the rate of osteonecrosis compared to dexamethasone alone (7/35 in dexamethasone with asparaginase combination vs. 10/36 in dexamethasone alone, p = 0.62) despite increasing steady-state plasma dexamethasone levels (103.9 nM vs. 33.4 nM, p = 9.2x10-7). Combination therapy with asparaginase and dexamethasone demonstrated synergistic antileukemic effects across all six xenografts studied.Conclusions
When discontinuous dexamethasone was given, its anti-leukemic activity synergized with asparaginase but the osteonecrosis-worsening effects of asparaginase (above dexamethasone alone) were not observed. Thus, there is a favorable drug interaction (unchanged toxicity, synergistic efficacy) between discontinuous dexamethasone and asparaginase.
The treatment of chronic functional nausea or nausea due to functional dyspepsia in children is generally symptomatic. Moreover, these disorders pose a risk for worse psychosocial and health outcomes in children. Hypnotherapy (HT), by its ability to positively influence gastrointestinal and psychosocial functioning, may be an effective treatment for chronic nausea.
To test efficacy, this multicentre, parallel, randomised controlled, open label trial evaluates whether gut-directed HT is superior to standard medical treatment (SMT) for reducing nausea. The study will be conducted at eleven academic and non-academic hospitals across the Netherlands. A total of 100 children (8–18 years), fulfilling the Rome IV criteria for chronic idiopathic nausea or functional dyspepsia with prominent nausea, will be randomly allocated (1:1) to receive HT or SMT. Children allocated to the HT group will receive six sessions of HT during 3 months, while children allocated to the SMT group will receive six sessions of SMT+supportive therapy during the same period. The primary outcome will be the difference in the proportion of children with at least 50% reduction of nausea, compared with baseline at 12 months’ follow-up. Secondary outcomes include the changes in abdominal pain, dyspeptic symptoms, quality of life, anxiety, depression, school absences, parental absence of work, healthcare costs and adequate relief of symptoms, measured directly after treatment, 6 and 12 months’ follow-up. If HT proves effective for reducing nausea, it may become a new treatment strategy to treat children with chronic functional nausea or functional dyspepsia with prominent nausea.
Results of the study will be publicly disclosed to the public, without any restrictions, in peer-reviewed journal and international conferences. The study is approved by the Medical Research Ethics Committees United (MEC-U) in the Netherlands.
Many sedentary individuals are aware of the health benefits of regular physical activity and start becoming more physically active. Yet, despite good intentions, many struggle to keep up initial exercise levels and experience a decline in exercise frequency. A possible explanation is that it is hard to establish habits or routines, and that such routines—once established—might be easy to break. In this paper, we analyse whether a break in habitual/routine behaviour—induced by the Easter holidays—results in individuals exercising less after the break.
The study included a sample of 1210 members of a Danish chain of fitness centres who were gym members at least since the preceding New Year’s Day. Participants granted access to gym attendance data, which were automatically recorded when entering the gym. We use a regression discontinuity design encompassing a time period of 10 weeks prior to and 10 weeks after Easter.
We found a significant and relevant discretionary drop in exercise frequency right after the Easter holidays of 0.24 times per week (p=0.001) corresponding to a fall of 12.25% compared with the week prior to the Easter holidays. The effect was especially profound for individuals below retirement age and for individuals who had attended the gym with a higher frequency (twice a week or more) in the 6 weeks prior to the Easter break.
This information is potentially relevant for helping individuals maintain an exercise habit. Motivational support should focus on the time period after normative breaks, such as Easter or other holidays.
The literature focuses on teaching communication skills in the ‘classroom’, with less focus on how such skills are informally learnt in the healthcare workplace. We grouped healthcare work based on the cure:care continuum to explore communication approaches based on work activities. This study asks: 1) How do healthcare professionals believe they learn communication in the workplace? 2) What are the differences (if any) across the ‘type of work’ as represented by the cure:care continuum?
This qualitative study used semi-structured individual interviews.
Community care and acute hospitals in Australia (Victoria and New South Wales).
Twenty qualified healthcare professionals (medicine n=4, nursing n=3, allied health n=13) from various clinical specialties (eg, acute, rehabilitation, surgery, palliative care) participated.
Data were analysed using framework analysis, which involved the development of a thematic coding framework. Findings were mapped to participants’ descriptions of work using the cure:care continuum.
Three themes were identified that varied across the cure:care continuum: professional discourse—tying communication approaches to work activities; personal identities—the influence of personal identities on healthcare communication and role modelling—the influence of others in the socially bound context of healthcare work.
This study highlights the influence of professional, personal and social factors on the learning of healthcare communication in the workplace. Our study illuminates differences in communication practice related to work activities, as conceptualised by the cure:care continuum. The results call for further examination of the ‘nature’ of work activities and the concomitant influence on developing healthcare communication.
It is unclear whether an association exists between obesity in children/adolescents and cognitive function, and whether the latter can be altered by body mass index (BMI) standard deviation score (SDS) reductions. We aimed to determine whether an association exists between BMI SDS and cognitive function in children/adolescents with obesity engaged in an obesity intervention. Second, we sought to determine if BMI SDS reduction at 12 months was associated with improved cognitive function.
Secondary analysis of a clinical trial.
Participants (n=69) were recruited from an obesity intervention. Eligible participants (recruited June 2013 to June 2015) were aged 6–16 years, with a BMI ≥98th centile or BMI >91st centile with weight-related comorbidities.
Primary outcome measure was change in BMI SDS from baseline at 12 months. Dependent variables of cognitive functioning and school achievement were assessed at baseline and 12 months, using dependent variables of cognitive functioning (elements of Ravens Standard Progressive Matrices, Wide Range Achievement Test-fourth edition and Wechsler Intelligence Scale for Children-fourth edition).
At baseline, BMI SDS was not associated with all aspects of cognitive function tested (n=69). Reductions in BMI SDS over time did not alter cognitive function overall. However, there was a greater reduction in comprehension standard scores in participants who increased their BMI SDS (adjusted estimated difference –6.1, 95% CI –11.6 to –0.6; p=0.03).
There were no observed associations between BMI SDS and cognitive function in participants, apart from comprehension in the exploratory analyses, which may have been a random finding. Further studies need to include larger longitudinal cohorts incorporating a wider BMI range at entry to determine whether our findings persist.
by Lindsey Beall, Teresa A. Myers, John E. Kotcher, Emily K. Vraga, Edward W. Maibach
by Ekaterina N. Spirova, Igor A. Ivanov, Igor E. Kasheverov, Denis S. Kudryavtsev, Irina V. Shelukhina, Alexandra I. Garifulina, Lina V. Son, Sarah C. R. Lummis, Gonzalo R. Malca-Garcia, Rainer W. Bussmann, Lothar Hennig, Athanassios Giannis, Victor I. TsetlinSeveral novel bisbenzylisoquinoline alkaloids (BBIQAs) have recently been isolated from a Matis tribe arrow poison and shown by two-electrode voltage-clamp to inhibit mouse muscle nicotinic acetylcholine receptors (nAChR). Here, using radioligand assay with Aplysia californica AChBP and radioiodinated α-bungarotoxin ([125I]-αBgt), we show that BBIQA1, BBIQA2, and d-tubocurarine (d-TC) have similar affinities to nAChR orthosteric site. However, a competition with [125I]-αBgt for binding to the Torpedo californica muscle-type nAChR revealed that BBIQAs1, 2, and 3 are less potent (IC50s = 26.3, 8.75, and 17.0 μM) than d-TC (IC50 = 0.39 μM), while with α7 nAChR in GH4C1 cells, BBIQA1 was less potent that d-TC (IC50s = 162 μM and 7.77 μM, respectively), but BBIQA2 was similar (IC50 = 5.52 μM). In inhibiting the Ca2+ responses induced by acetylcholine in Neuro2a cells expressing the mouse adult α1β1εδ nAChR or human α7 nAChR, BBIQAs1 and 2 had similar potencies to d-TC (IC50s in the range 0.75–3.08 μM). Our data suggest that BBIQA1 and BBIQA2 can inhibit adult muscle α1β1εδ nAChR by both competitive and noncompetitive mechanisms. Further experiments on neuronal α3β2, α4β2, and α9α10 nAChRs, expressed in Xenopus laevis oocytes, showed that similar potencies for BBIQAs1, 2, and d-TC. With α3β2γ2 GABAAR currents were almost completely inhibited by d-TC at a high (100 μM) concentration, but BBIQAs1 and 2 were less potent (only 40–50% inhibition), whereas in competition with Alexa Fluor 546-α-cobratoxin for binding to α1β3γ2 GABAAR in Neuro2a cells, d-TC and these analogs had comparable affinities. Especially interesting effects of BBIQAs1 and 2 in comparison with d-TC were observed for 5-HT3AR: BBIQA1 and BBIQA2 were 5- and 87-fold less potent than d-TC (IC50 = 22.63 nM). Thus, our results reveal that these BBIQAs differ from d-TC in their potencies towards certain Cys-loop receptors, and we suggest that understanding the reasons behind this might be useful for future drug design.
by Amy Johnston, Shu-Ching Hsieh, Marc Carrier, Shannon E. Kelly, Zemin Bai, Becky Skidmore, George A. WellsBackground
Venous thromboembolism (VTE) is a major global cause of morbidity and mortality. Low molecular weight heparin (LMWH) and fondaparinux (FDP) are frequently used to treat and prevent VTE and have a variety of safety and practical advantages over other anticoagulants, including use in outpatient settings. These medications are commonly listed on drug formularies, which act as a gateway for health plan prescription coverage by outlining the circumstances under which patients will be covered for specific drugs and drug products. Because patient access to medications is impacted by the nature of their listing on formularies, they must be rigorously reviewed and modernized as new evidence emerges.Methods
As part of a broader drug class review team, we completed a systematic review of clinical practice guidelines to determine whether the recommendations they reported aligned with the indications listed for the coverage of LMWH and FDP in an outpatient drug formulary. Guideline quality was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool. Recommendation matrices were used to systematically compare, categorize, and summarize included recommendations.Results
Twenty-seven guidelines were included from which 168 eligible recommendations were identified. Generally, AGREE II domains were adequately addressed; however, domain five (applicability) was poorly addressed. Most recommendations were based on moderate- to low-quality/limited evidence and reported on the use of LMWHs generally; few reported on specific agents.Conclusions
Our findings contributed to the recommendation that the formulary listing for LMWH and FDP be streamlined to include coverage for specific outpatient indications. The paucity of available evidence on the comparative efficacy of specific LMWH agents against each other and FDP limited agent-specific listing recommendations, highlighting the need for high-quality comparative studies on this topic.
The aim of this study was to determine the frequency and cause of interruptions during intravenous medication administration, which factors are associated with interruptions and to what extent interruptions influence protocol compliance.
Hospital nurses are frequently interrupted during medication administration, which contributes to the occurrence of administration errors. Errors with intravenous medication are especially worrisome, given their immediate therapeutic effects. However, knowledge about the extent and type of interruptions during intravenous medication administration is limited.
Multicentre observational study.
Data were collected during two national evaluation studies (2011 ‐ 2012 & 2015 ‐ 2016). Nurses were directly observed during intravenous medication administration. An interruption was defined as a situation where a break during the administration was needed or where a nurse was distracted but could process without a break. Interruptions were categorized according to source and cause. Multilevel logistic regression analyses were conducted to assess the associations between explanatory variables and interruptions or complete protocol compliance.
In total, 2,526 intravenous medication administration processes were observed. During 291 (12%) observations, nurses were interrupted 321 times. Most interruptions were externally initiated by other nurses (19%) or patients (19%). Less interruptions occurred during the evening (odds ratio: 0.23 [95% confidence interval: 0.08–0.62]). Do‐not‐disturb vests were worn by 61 (2%) nurses. No significant association was found between being interrupted and complete protocol compliance.
An interruption occurred in every eight observed intravenous medication administration, mainly caused by other nurses or patients. One needs to consider critically which strategies effectively improve safety during the high‐risk nursing‐task of intravenous medication administration.
在两项国家评估研究过程中收集数据(2011‐2012 和 2015‐2016)。给药过程中直接对护士进行观察。中断是指在给药过程中需要休息的情况,或护士分心,但不需要休息就可以处理的情况。中断根据来源和原因进行分类。进行多级逻辑回归分析以评估解释变量与中断或完全协议遵从之间的关系。