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Public health issues related to chronic pain management and the risks of opioid misuse and abuse remain a challenge for practitioners. Data on the prevalence of disorders related to the use of prescribed opioids in patients suffering from chronic pain remains rather patchy, in particular because of the absence of a gold standard for their clinical assessment. We estimated the prevalence of prescription opioid misuse (POM), using a specific and validated opioid misuse scale (POMI-5F scale), in adults with chronic non-cancer pain. Nine-hundred-fifty-one (951) patients with opioids prescription and followed-up in pain clinics and addictology centers for chronic non-cancer pain (CNCP) completed the survey interview. The results suggest that 44.4% of participants have POM, accompanied by overuse (42.5%), use of opioids for effects other than analgesia (30.9%), withdrawal syndrome (65.7%), and craving (6.9%). The motivations cited for POM, apart from pain relief, were to calm down, relax and improve mood. POM was shown to be related to male sex (OR 1.52), young age (OR 2.21) and the presence of nociplastic pain (OR 1.62) of severe intensity (OR 2.31), codeine use (OR 1.72) and co-prescription of benzodiazepines (OR 1.59). Finally, despite the presence of three subgroups of misusers, no factor was associated with the intensity of misuse, reinforcing the view that distinguishing between strong and weak opioids is not appropriate in the context of use disorder. Almost half of patients with CNCP misuse their prescribed opioid. Practitioners should be attentive of profiles of patients at risk of POM, such as young, male patients suffering from severe nociplastic pain, receiving prescription for codeine and a co-prescription for benzodiazepine. We encourage French-speaking practitioners to use the POMI-5F scale to assess the presence of POM in their patients receiving opioid-based therapy.Clinical Trial Registrationclinicaltrials.gov, identifier NCT03195374

Abstract Background Returning to work after long-term sick leave can be challenging, particularly in small- and medium-sized enterprises (SMEs) where support may be limited. Recognizing the responsibilities and challenges of SME employers, a web-based intervention (hereafter the SME tool) has been developed. The SME tool aims to enhance the employer’s intention and ability to support the sick-listed employee. Based on the Self-Determination Theory, it is hypothesized that this intention is enhanced by intervening in the employer’s autonomy, competences, and relatedness targeted at, e.g., communication with sick-listed employee, involvement of other stakeholders, and practical support. This is achieved by means of providing templates, communication videos, and information on legislation. This article describes the design of an effect and process evaluation of the SME tool. Methods A randomized controlled trial (RCT) with a 6-month follow-up will be conducted with a parallel-group design with two arms: an intervention group and a control group. Sick-listed employees (≤ 8 weeks) of SMEs (≤ 250 employees) at risk of long-term sick leave and their employers will be recruited and randomly allocated as a dyad (1:1). Employers randomized to the intervention group receive unlimited access to the SME tool, while those in the control group will receive care as usual. The primary outcome is the satisfaction of the employee with the return to work (RTW) support provided by their employer. Secondary outcomes include social support, work performance, and quality of work life at the employee level and self-efficacy in providing RTW support at the employer level. Outcomes will be assessed using questionnaires at baseline and 1, 3, and 6 months of follow-up. Process evaluation measures include, e.g., recruitment and use of and perceived usefulness of the SME tool. Additionally, semi-structured interviews with employers, employees, and occupational physicians will explore the interpretation of the RCT results and strategies for the national implementation of the SME tool. Discussion The SME tool is hypothesized to be valuable in addition to usual care helping employers to effectively support the RTW of their long-term sick-listed employees, by improving the employers’ intention and ability to support. Trial registration ClinicalTrials.gov, NCT06330415. Registered on February 14, 2024.

Abstract Background The burnout rates among residents urge for adequate interventions to improve resilience and prevent burnout. Peer reflection, also called group intervision sessions, is a potentially successful intervention to increase the resilience of young doctors. We aimed to gain insight into the perceived added value of intervision sessions and the prerequisite conditions to achieve this, according to residents and intervisors. Our insights might be of help to those who think of implementing intervision sessions in their institution. Methods An explorative, qualitative study was performed using focus groups and semi-structured interviews with both residents (n = 8) and intervisors (n = 6) who participated in intervision sessions in a university medical center in the Netherlands. The topic list included the perceived added value of intervision sessions and factors contributing to that. The interviews were transcribed verbatim and coded using NVivo. Thematic analysis was subsequently performed. Results According to residents and intervisors, intervision sessions contributed to personal and professional identity development; improving collegiality; and preventing burn-out. Whether these added values were experienced, depended on: (1) choices made during preparation (intervisor choice, organizational prerequisites, group composition, workload); (2) conditions of the intervision sessions (safety, depth, role of intervisor, group dynamics, pre-existent development); and (3) the hospital climate. Conclusions Intervision sessions are perceived to be of added value to the identity development of medical residents and to prevent becoming burned out. This article gives insight in conditions necessary to reach the added value of intervision sessions. Optimizing preparation, meeting prerequisite conditions, and establishing a stimulating hospital climate are regarded as key to achieve this.

Abstract Background Healthcare professionals (HCPs) are increasingly recommended to play an important role in supporting people with chronic disease in work participation. An intervention for HCPs to provide work-related support to their patients in clinical care was developed with intervention mapping (Maastricht Work-Related Support; Maastricht WRS). Action research proposes ‘combining research and practice’, which allows us to incorporate experiences of HCPs while implementing and to realize intervention’s full potential. Therefore, the aim of this study is to explore, by integrating action research into an intervention mapping approach, how experiences of HCPs with early implementation can be used to optimize the Maastricht WRS in clinical care. Methods Semi-structured interviews were held with nine HCPs (response rate 82%), involved in care for people with inflammatory arthritis, knee problems or inflammatory bowel disease. Some of them were not yet trained in the Maastricht WRS while others had received the training and were providing the Maastricht WRS. Results All participants regarded WRS an important part of clinical care. Untrained HCPs indicated a lack of knowledge and skills in providing the Maastricht WRS, and a need for tools. Trained HCPs were satisfied with the training and tools, but stressed that practical limitations hindered providing the Maastricht WRS. Action research showed that the intervention meets the needs of HCPs, but need some optimizations: (1) organizing ‘intervision’ for HCPs, (2) inform and activate patients to discuss work with their HCP, (3) update initial tools and (4) including patients’ work status in the electronic patient system. Conclusions Action research integrated into intervention mapping proved to improve the Maastricht WRS intervention. By involving HCPs, the intervention could be optimized to provide to support people with chronic diseases in clinical care in healthy and sustainable work participation.

ABSTRACTIntroduction The negative impact of medical training on trainee mental health continues to be a concern. Situated within a sociocultural milieu, Generation Z and Generation Y, defined by their highly involved parents and the widespread use of technology, currently dominate undergraduate and graduate medical education respectively. It is necessary to explore medical trainees’ generational characteristics and job-related factors related to stress, burnout, depression, and resilience. This might provide different perspectives and potential solutions to medical trainees’ mental health.Methods A cross-sectional study was conducted among medical trainees (students and residents) from two institutions in Qatar. A self-administered online survey included measures for trainees’ social media overuse, their parent’s parenting style, the educational support by the clinical teacher, job (demands, control, and support), and work-life balance and their relation with their stress, burnout, depression, and resilience. Relationships were tested with multiple linear regression analyses.Results Of the 326 medical trainees who responded, 142 (44%) trainees − 93 students and 49 residents – completed all items and were included in the analysis. Social media overuse and inability to maintain a work-life balance were associated with higher levels of stress, depression, and student burnout. Higher levels of job support were associated with lower levels of stress, depression, and resident burnout, and a higher level of resilience. Job control was associated with lower burnout levels. Parenting style was unrelated to trainees’ mental health.Discussion The two generations ‘Y’ and ‘Z’ dominating current medical training showed more stress-related complaints when there is evidence of social media overuse and failure to maintain a work-life balance, while job support counterbalances this, whereas parenting style showed no effect. Measures to enhance medical trainees’ mental health may include education about the wise use of social media, encouraging spending more quality social time, and enhancing job support and job control.

Abstract Microbes are increasingly employed as cell factories to produce biomolecules. This often involves the expression of complex heterologous biosynthesis pathways in host strains. Achieving maximal product yields and avoiding build-up of (toxic) intermediates requires balanced expression of every pathway gene. However, despite progress in metabolic modeling, the optimization of gene expression still heavily relies on trial-and-error. Here, we report an approach for in vivo, multiplexed Gene Expression Modification by LoxPsym-Cre Recombination (GEMbLeR). GEMbLeR exploits orthogonal LoxPsym sites to independently shuffle promoter and terminator modules at distinct genomic loci. This approach facilitates creation of large strain libraries, in which expression of every pathway gene ranges over 120-fold and each strain harbors a unique expression profile. When applied to the biosynthetic pathway of astaxanthin, an industrially relevant antioxidant, a single round of GEMbLeR improved pathway flux and doubled production titers. Together, this shows that GEMbLeR allows rapid and efficient gene expression optimization in heterologous biosynthetic pathways, offering possibilities for enhancing the performance of microbial cell factories.

School absenteeism and its underlying causes can have negative effects on the cognitive, psychosocial and health development of a child. Research in primary education shows high rates of sickness absence. Many stakeholders are involved in addressing school absenteeism, including primary school professionals, child and youth healthcare physicians, school attendance officers and parents. This study explores these stakeholders' perspectives, their approaches and what they envisage to be necessary in order to improve. It also aims to unveil opportunities and challenges in addressing sickness absence among primary school pupils. Qualitative research was performed with six semi-structured focus group interviews and involving 27 participants from the West-Brabant and Amsterdam regions of the Netherlands. Thematic analysis was used. The overarching theme was aiming for the child's wellbeing. Each focus group interview started with low awareness of sickness absence as a threat to this wellbeing, but awareness grew during the interviews. The participating stakeholders regarded problematic sickness absence as complex due to a wide variety of causes, and felt that each other's expertise was necessary to reduce sickness absence. Schools registered absence, but only occasionally used planned steps; they based the identification of problematic sickness on gut feeling rather than any agreed-upon criteria. To be able to systematically address sickness absence and thus improve the wellbeing of children, stakeholders felt the need for a clearly structured approach, including monitoring of sickness absence of all pupils, identifying problematic absence and promoting collaboration with other stakeholders. An approach should allow for tailoring solutions to the individual child.

India's healthcare system is, for a large part, organized around a vast network of Primary Healthcare Centres (PHCs) that form the pillar on which the public healthcare sector functions. The World Health Organization (WHO) has emphasized the important role that PHCs play in strengthening community health and the provision of healthcare. Although a few studies have assessed specific elements of services offered by PHCs, only a few have studied the patients’ perspectives on the functioning and performance of PHCs in the Indian context. A qualitative research methodology was employed to explore the opinions of 188 patients attending one of three PHCs in Bengaluru (India), using in-depth interviews and thematic analysis. Results showed that patients assessed PHC based on the nine themes that broadly can be classified into components of the center, and that of the personnel. The patients valued the behavioural aspects of the personnel during service delivery and should be configured into the PHC performance.

Illicit connections of wastewater to stormwater systems are the main drawback of separate sewer systems, as they lead to a direct discharge of untreated wastewater to the aquatic environment. Consequently, several inspection methods have been developed for detecting illicit connections. This study simultaneously applied several low- and high-tech methods for the detection of illicit connections in the same catchment (De Heuvel, the Netherlands). The methods included mesh wire screens for capturing coarse contamination, measurements of electroconductivity and temperature, sampling and quantification of Escherichia coli and extended-spectrum ß-lactamase-producing E. coli (ESBL-EC), DNA analysis via quantitative polymerase chain reaction for human-, dog-, and bird-specific fecal indicators, and distributed temperature sensing. Significant illicit connections could be identified using all methods. Nonetheless, hydraulic conditions and, predominantly, the sewage volume determine whether a misconnection can be detected by especially the low-tech methods. Using these results, the identified misconnections were repaired and biological and DNA analyses were repeated. Our results demonstrate that there were no changes in E. coli or ESBL-EC before and after mitigation, suggesting that these common markers of fecal contamination are not specific enough to evaluate the performance of mitigation efforts. However, a marked decrease in human wastewater markers (HF183) was observed. HIGHLIGHTS Wire screens and conductivity are not suited to detect illicit connections at outlets of storm sewers with large water volumes upstream.; Distributed temperature sensing (DTS) is capable of identifying all sorts of misconnections like household appliances.; HF183 Bacteroides are very effective in determining the presence of human fecal material in storm sewers.; Repeated sampling and quantitative polymerase chain reaction testing could be a prescreening method before labor-intensive DTS.;

Abstract Background Post-traumatic stress disorder (PTSD) occurs more commonly in military veterans than the general population. Whilst current therapies are effective, up to half of veterans commencing treatment do not complete it. Reconsolidation of Traumatic Memories (RTM) protocol is a novel, easy to train, talking therapy with promising findings. We examine the feasibility of undertaking an efficacy trial of RTM in veterans. Methods A parallel group, single-centre randomised controlled feasibility trial with a post-completion qualitative interview study. Sixty military veterans were randomised 2:1 to RTM (n = 35) or Trauma Focussed Cognitive Behaviour Therapy (CBT) (n = 25). We aimed to determine the rate of recruitment and retention, understand reasons for attrition, determine data quality and size of efficacy signal. We explored veterans’ perceptions of experiences of joining the trial, the research procedures and therapy, and design improvements for future veteran studies. Military veterans with a diagnosis of PTSD or complex PTSD, and clinically significant symptoms, were recruited between January 2020 and June 2021. Primary outcome was feasibility using pre-determined progression criteria alongside PTSD symptoms, with depression, recovery, and rehabilitation as secondary outcomes. Data were collected at baseline, 6, 12, and 20 weeks. Interviews (n = 15) were conducted after 20 weeks. Both therapies were delivered by trained charity sector provider therapists. Results Participants’ mean age was 53 years, the mean baseline PTSD symptoms score assessed by the Post-traumatic Stress Checklist (PCL-5) was 57 (range 0–80). Fifty had complex PTSD and 39 had experienced ≥ 4 traumas. Data were analysed at 20 weeks for feasibility outcomes (n = 60) and mental health outcomes (n = 45). Seven of eight progression criteria were met. The RTM group experienced a mean 18-point reduction on the PCL-5. TFCBT group participants experienced a mean reduction of eight points. Forty-eight percent of the RTM group no longer met diagnostic criteria for PTSD compared to 16% in the TFCBT group. All veterans reported largely positive experiences of the therapy and research procedures and ways to improve them. Conclusion RTM therapy remains a promising psychological intervention for the treatment of PTSD, including complex PTSD, in military veterans. With specific strengthening, the research protocol is fit for purpose in delivering an efficacy trial. Trial registration ISRCTN registration no 10314773 on 01.10.2019. Full trial protocol: available on request or downloadable at ISRCTN reg. no. 10314773.

Purpose The prevalence of lower urinary tract symptoms (LUTS), characterized by problems regarding storage and/or voiding of urine, is known to significantly increase with age. Effective communication between the lower urinary tract and the central nervous system (CNS) is essential for the optimal function of this system, and heavily relies on the efficient interaction between the bladder urothelium and the afferent nerve fibers situated in close proximity to the urothelium within the lamina propria. Methods We aimed to quantify aging-related differences in the expression of calcitonin gene-related peptide (CGRP, an established marker for sensory nerve fibers) in the trigonal mucosal layers of young (3–4 months) and aged (25–30 months) rats. We evaluated trigonal tissue from 3 animals per age group. Tissue was serially sectioned at 10 μm and stained for CGRP. Images were taken along the full length of the tissue. For each image we computed the total CGRP-positive area (μm2) and the median value for each animal was used for further analysis. Results Upon statistical analysis the aged rats show a significantly lower CGRP-positive area compared to young rats (P=0.0049). These results indicate that aging has a negative effect on the area of CGRP-positive signal in the trigone. Conclusions The structural and functional integrity of the sensory web in the trigonum of rats is negatively affected by the aging process, potentially leading to impaired communication between the bladder urothelium the CNS. Consequently, these perturbations in the sensory system may contribute to the pathogenesis or exacerbation LUTS.

Background: Primary healthcare in India comprises health promotion and preventive health interventions at the population level, which are rendered at dedicated centres called Primary Healthcare Centres (PHCs). The performance of PHCs is vital for overall improvement in the general health of the population, specifically in a low- and middle-income country like India. It is unknown how performance at the centre level is related to performance at the provider and patient levels. The aim of this study is to explore patterns in the performance of three PHCs with a low, medium and the high number of babies delivered. Methodology: Primary and secondary data from the three selected PHCs were collected. Two questionnaire studies were done: one on the well-being of providers (Quality of Life and Engagement), and another on PHC performance as assessed by patients using the newly developed tool ‘Questionnaire for Patient’s Perspective on Performance of Primary Healthcare Centres’. The data from the centre, provider and patient levels were compared across the three centres using ANOVA tests. Results: The new tool had high internal consistency at Cronbach’s alpha score of 0.938. It was found that the PHC with the least delivery had significantly higher PHC performance in comparison with high and medium-delivery PHCs (p

Abstract Background Mental disorders (MDs) are one of the leading causes for workforce sickness absence and disability worldwide. The burden, costs and challenges are enormous for the individuals concerned, employers and society at large. Although most MDs are characterised by a high risk of relapse after treatment or by chronic courses, interventions that link medical-psychotherapeutic approaches with work-directed components to facilitate a sustainable return to work (RTW) are rare. This protocol describes the design of a study to evaluate the (cost-)effectiveness and implementation process of a multimodal, clinical and work-directed intervention, called RTW-PIA, aimed at employees with MDs to achieve sustainable RTW in Germany. Methods The study consists of an effectiveness, a health-economic and a process evaluation, designed as a two-armed, multicentre, randomised controlled trial, conducted in German psychiatric outpatient clinics. Sick-listed employees with MDs will receive either the 18-month RTW-PIA treatment in conjunction with care as usual, or care as usual only. RTW-PIA consists of a face-to-face individual RTW support, RTW aftercare group meetings, and web-based aftercare. Assessments will be conducted at baseline and 6, 12, 18 and 24 months after completion of baseline survey. The primary outcome is the employees´ achievement of sustainable RTW, defined as reporting less than six weeks of working days missed out due to sickness absence within 12 months after first RTW. Secondary outcomes include health-related quality of life, mental functioning, RTW self-efficacy, overall job satisfaction, severity of mental illness and work ability. The health-economic evaluation will be conducted from a societal and public health care perspective, as well as from the employer’s perspective in a cost–benefit analysis. The design will be supplemented by a qualitative effect evaluation using pre- and post-interviews, and a multimethod process evaluation examining various predefined key process indicators from different stakeholder perspectives. Discussion By applying a comprehensive, multimethodological evaluation design, this study captures various facets of RTW-PIA. In case of promising results for sustainable RTW, RTW-PIA may be integrated into standard care within German psychiatric outpatient clinics. Trial registration The study was prospectively registered with the German Clinical Trials Register ( DRKS00026232 , 1 September 2021).

BackgroundWorking night shifts is associated with higher safety risks due to shift work-related fatigue. Nutrition, especially certain (macro) nutrient compositions, has been suggested to reduce fatigue, however, results of studies are contradictory. This could be explained by differences in the time interval investigated between the consumption of a meal and measurement of cognitive performance. Therefore, this observational study investigated the association between macronutrient intake and objective alertness at different time intervals during the night shift in nurses.Methods128 nurses, aged 20–61 years, completed an alertness test (Psychomotor Vigilance Task) during the night shift and a 24-h dietary recall after the night shift. This was repeated three times, always on the first night shift in a night shift series. The associations between macronutrient intake 0 to 1, 1 to 2, and 2 to 3 h before the PVT with alertness during the night shift were analyzed through Linear Mixed Models. The basic model was adjusted for age and gender and the adjusted model additionally for BMI, start time of PVT and energy and caffeine intake during the relevant time interval.ResultsProtein intake was not associated with objective alertness levels, while fat and carbohydrates intake had opposite associations with objective alertness levels over similar time intervals. Fat intake up to 1 h prior to the PVT was borderline associated with a longer median reaction time (RT) (ß = 9.00 ms/10 g fat, 95% CI: −0.21, 18.20), while a higher carbohydrate intake up to 1 h prior to the PVT was borderline associated with shorter median RTs (ß = −3.89, 95% CI: −7.85, 0.06). A higher fat intake 2 to 3 h prior to the PVT was associated with less lapses (log transformed ß = −0.16; 95% CI: −0.31, −0.02), while a higher carbohydrate intake 2 to 3 h prior to the PVT was associated with more lapses (ß = 0.06, 95% CI: 0.01, 0.12).ConclusionOur results contribute to understanding the association between macronutrient intake, as part of a mixed meal, and alertness levels. Conflicting results from previous studies may probably be due to time differences between macronutrient intake and alertness testing.