Bulky DNA adducts, microRNA profiles, and lipid biomarkers in Norwegian tunnel finishing workers occupationally exposed to diesel exhaust.

OBJECTIVES: This study aimed to assess the biological impact of occupational exposure to diesel exhaust (DE) including DE particles (DEP) from heavy-duty diesel-powered equipment in Norwegian tunnel finishing workers (TFW). METHODS: TFW (n=69) and referents (n=69) were investigated for bulky DNA adducts (by 32P-postlabelling) and expression of microRNAs (miRNAs) (by small RNA sequencing) in peripheral blood mononuclear cells (PBMC), as well as circulating free arachidonic acid (AA) and eicosanoid profiles in plasma (by liquid chromatography-tandem mass spectrometry). RESULTS: PBMC from TFW showed significantly higher levels of DNA adducts compared with referents. Levels of DNA adducts were also related to smoking habits. Seventeen miRNAs were significantly deregulated in TFW. Several of these miRNAs are related to carcinogenesis, apoptosis and antioxidant effects. Analysis of putative miRNA-gene targets revealed deregulation of pathways associated with cancer, alterations in lipid molecules, steroid biosynthesis and cell cycle. Plasma profiles showed higher levels of free AA and 15-hydroxyeicosatetraenoic acid, and lower levels of prostaglandin D2 and 9-hydroxyoctadecadienoic acid in TFW compared with referents. CONCLUSION: Occupational exposure to DE/DEP is associated with biological alterations in TFW potentially affecting lung homoeostasis, carcinogenesis, inflammation status and the cardiovascular system. Of particular importance is the finding that tunnel finishing work is associated with an increased level of DNA adducts formation in PBMC.

Role of the Gut Microbiota in Atopic Dermatitis: A Systematic Review.

The immune mechanisms involved in atopic dermatitis (AD) are complex and little is known about the possible role of the gut microbiota in the aetiopathogenesis of AD. A systematic review of the literature was performed according to PRISMA guidelines, and included 44 of 2,199 studies (26 observational and 18 interventional studies). Detection of gut microbiota was performed by either 16s rRNA PCR, or by culture. Observational studies were diverse regarding the age of study participants and the bacterial species investigated. Overall, the results were conflicting with regard to diversity of the gut microbiota, specific bacterial colonization, and subsequent risk of AD. Nearly half of the included interventional studies showed that an altered gut microbial colonization due to use of probiotics had a positive effect on the severity of AD. The remaining studies did not show an effect of probiotics on the severity of AD despite an alteration in the gut microbial composition. The role of the gut microbiome for the onset and severity of pre-existing AD remains controversial.

Clinician experiences of healthy lifestyle promotion and perceptions of digital interventions as complementary tools for lifestyle behavior change in primary care.

BACKGROUND: Evidence-based practice for healthy lifestyle promotion in primary health care is supported internationally by national policies and guidelines but implementation in routine primary health care has been slow. Referral to digital interventions could lead to a larger proportion of patients accessing structured interventions for healthy lifestyle promotion, but such referral might have unknown implications for clinicians with patients accessing such interventions. This qualitative study aimed to explore the perceptions of clinicians in primary care on healthy lifestyle promotion with or without digital screening and intervention. METHODS: Focus group interviews were conducted at 10 primary care clinics in Sweden with clinicians from different health professions. Transcribed interviews were analyzed using content analysis, with inspiration from a phenomenological-hermeneutic method involving naïve understanding, structural analysis and comprehensive understanding. RESULTS: Two major themes captured clinicians' perceptions on healthy lifestyle promotion: 1) the need for structured professional practice and 2) deficient professional practice as a hinder for implementation. Sub-themes in theme 1 were striving towards professionalism, which for participants meant working in a standardized fashion, with replicable routines regardless of clinic, as well as being able to monitor statistics on individual patient and group levels; and embracing the future with critical optimism, meaning expecting to develop professionally but also being concerned about the consequences of integrating digital tools into primary care, particularly regarding the importance of personal interaction between patient and provider. For theme 2, sub-themes were being in an unmanageable situation, meaning not being able to do what is perceived as best for the patient due to lack of time and resources; and following one's perception, meaning working from a gut feeling, which for our participants also meant deviating from clinical routines. CONCLUSIONS: In efforts to increase evidence-based practice and lighten the burden of clinicians in primary care, decision- and policy-makers planning the introduction of digital tools for healthy lifestyle promotion will need to explicitly define their role as complements to face-to-face encounters. Our overriding hope is that this study will contribute to maintaining meaningfulness in the patient-clinician encounter, when digital tools are added to facilitate patient behavior change of unhealthy lifestyle behaviors.

The assessment of telemedicine to support outpatient palliative care in advanced cancer.

OBJECTIVE: We aimed to examine telemedicine as a form of home and additional support for traditional outpatient care as a way to remotely monitor and manage the symptoms of patients with advanced cancer. METHOD: In total, 12 patients were monitored through monthly consultations with a multidisciplinary healthcare team and weekly web conferences. To evaluate and treat pain and other symptoms, the Edmonton Symptom Assessment System (ESAS) was applied during all remote or in-person interviews. RESULTS: During monitoring, the team contacted the patients on 305 occasions: there were 89 consultations at the hospital, 19 in-person assistances to the family (without the patient), 77 web conferences, 38 telephone calls, 80 emails, and 2 home visits. The mean monitoring time until death was 195 ± 175.1 days. Eight patients who completed the ESAS in all interviews had lower mean distress symptom scores according to web conferences than in person. SIGNIFICANCE OF RESULTS: Telemedicine allowed greater access to the healthcare system, reduced the need to employ emergency services, improved assessment/control of symptoms, and provided greater orientation and confidence in the care given by family members through early and proactive interventions. Web conferencing proved to be a good adjuvant to home monitoring of symptoms, complementing in-person assistance.

Doxorubicin concentrations in bone tumour-relevant tissues after bolus and continuous infusion: a randomized porcine microdialysis study.

PURPOSE: Doxorubicin is a widely used chemotherapeutic drug that can be administered intravenously as both a bolus infusion and a continuous infusion. The latter is believed to lower the risk of cardiotoxicity, which is a critical long-term complication of doxorubicin treatment. The local tissue concentrations of doxorubicin will be reflected in both treatment efficacy and toxicity, but very limited information is available. The aim of this study was to measure the concentration of doxorubicin after continuous and bolus infusion in tissue compartments around a typical location of a bone tumour. METHODS: Sixteen pigs (female, Danish Landrace, mean weight 77 kg) were randomized into two groups of eight. Both groups received an intravenous infusion of 150 mg doxorubicin; Group 1 received a bolus infusion (10-15 min) and Group 2 received a continuous infusion (6 h). Before infusion, microdialysis catheters were placed intravenously and in four bone tumour-relevant tissue compartments (cancellous bone, subcutaneous tissue, synovial fluid of the knee joint and muscle tissue). Sampling was done (n = 15) over 24 h, and venous blood samples were collected as a reference. RESULTS: Area under the concentration-time curve (AUC0-24 h) for plasma (total concentration) was significantly different between the two groups, while peak drug concentration (Cmax) was significantly higher in two compartments (plasma and synovial fluid of the knee joint) in Group 1 compared to Group 2. Overall, the unbound tissue concentrations were extremely low with values below 0.20 µg/mL. CONCLUSION: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion.

Screening and treating problematic substance use among patients in psychiatry - obstacles and solutions.

OBJECTIVE: In Sweden, national guidelines recommend that all staff in the healthcare system systematically screen patients for alcohol use and illicit substance use. Where hazardous use is identified, it should be addressed as soon as possible, preferably through brief interventions (BI). Results from a previous national survey showed that most clinic directors stated that they had clear guidelines for screening alcohol use and illicit substance use, but that fewer staff than expected used screening in their work. This study aims to identify obstacles and solutions to screening and brief intervention, based on survey respondents' free-text responses to open-ended questions. RESULTS: A qualitative content analysis yielded four codes: guidelines, continuing education, cooperation and resources. The codes indicated that staff would need (a) clearer routines in order to optimize compliance with the national guidelines; (b) more knowledge about how to treat patients with problematic substance use; (c) better cooperation between addiction care and psychiatry; and (d) increased resources to improve routines at their own clinic. We conclude that increased resources could contribute to better routines and cooperation, and provide increased opportunities for continuing education. This could increase guideline compliance and increase healthy behavior changes among patients in psychiatry with problematic substance use.

Problematic substance use among patients in a Swedish outpatient psychiatry setting: staff and manager perceptions of digital options for increased intervention access.

BACKGROUND: Approximately 50% of the patients who globally seek help in psychiatry have been assessed with problematic substance use or been diagnosed with substance use disorder (SUD). Given the high treatment gap for mental health care, in particular SUD, these individuals risk poorer treatment outcomes in psychiatry. Integrated treatment for psychiatric and SUD disorders has been proposed to reduce the treatment gap for SUD, but access to integrated treatment is low. Digital interventions addressing SUD in psychiatry could potentially make treatment available to patients who otherwise would not have access. In this study "digital interventions" comprise an umbrella term covering all kinds of interventions from minimal motivational app-based interventions to internet-based interventions with and without human guidance, up to remote sessions in telepsychiatry. This study aims to explore healthcare staff perceptions of referring patients to digital interventions for reducing problematic substance use, whether or not diagnosed as SUD, in the psychiatric outpatient setting. METHOD: The study was exploratory with a qualitative design. Data were collected in the Swedish outpatient psychiatry setting, via individual semi-structured interviews with managers, and focus groups with healthcare staff. An adapted form of phenomenological hermeneutical analysis was used to analyze the data. RESULTS: Three themes emerged from the analysis. The first theme was Encountering obstacles on the path to future implementation of digital interventions, with sub-themes: Lacking resources and Feeling concerned about technical solutions. The second theme was Searching for ways forward to achieve increased access to care, with sub-themes: Blended care could facilitate integrated care and Addressing variations in patients' technical skills. The third theme was Taking steps towards the future, with sub-themes: Wanting to know more about digital interventions and Formulating a vision for the future. CONCLUSIONS: The study reveals a concern that implementing digital interventions in psychiatry will create additional work or be technically challenging. The staff see significant advantages from the patient perspective, but they feel that they themselves need training in implementing digital interventions. In order to establish constructive implementation of digital interventions for SUD in psychiatry, staff attitudes and concerns need to be considered and addressed. This study was conducted within the Swedish healthcare system and the findings may not generalize to other countries with differing healthcare systems.

Piperacillin Steady State Concentrations in Target Tissues Relevant for PJI Treatment-A Randomized Porcine Microdialysis Study Comparing Continuous Infusion with Intermittent Short-Term Infusion.

(1) Introduction: Piperacillin is a common antibiotic choice in the treatment of periprosthetic joint infections (PJI) caused by Pseudomonas aeruginosa. The aim of this study was to assess and compare the time with free piperacillin concentration above the minimum inhibitory concentration (fT > MIC) at steady state in target tissues relevant for PJI treatment following continuous and intermittent short-term infusion. (2) Methods: 16 pigs were randomized to receive either continuous or intermittent short-term infusion of piperacillin. Steady state piperacillin concentrations were assessed using microdialysis in tibial cortical bone, tibial cancellous bone, synovial fluid of the knee joint, and subcutaneous tissue. MIC-targets of 4, 8, 16, and 64 mg/L were applied. Plasma samples were obtained as reference. (3) Results: Continuous infusion resulted in longer fT > MIC for MIC targets of 4 mg/L and 8 mg/L compared to intermittent short-term infusion in all compartments with the exception of tibial cortical bone. For the MIC-target of 16 mg/L, continuous infusion resulted in a longer fT > MIC in all compartments except for the bone compartments. No differences between groups were seen when applying a MIC-target of 64 mg/L. (4) Conclusions: An aggressive dosing strategy may be necessary to obtain sufficient piperacillin concentrations in all bone compartments, particularly if more aggressive targets are applied. Based on the present study, continuous infusion should be considered in the treatment of PJI.

Intermittent Short-Term Infusion vs. Continuous Infusion of Piperacillin: Steady State Concentrations in Porcine Cervical Spine Tissue Evaluated by Microdialysis.

Background: Piperacillin is a central drug in the treatment of Pseudomonas aeruginosa spondylodiscitis. Intermittent short-term infusion (STI) remains standard treatment in most centres, although the application of continuous infusion (CI) has shown promising results in other clinical settings. We aimed to evaluate time above the minimal inhibitory concentration (fT > MIC) of the free fraction of piperacillin in steady state conditions in porcine cervical spine tissue following CI and STI using microdialysis with MIC targets of 4, 8, and 16 µg/mL. Methods: 16 female pigs were randomized to receive piperacillin/tazobactam as STI (4/0.5 g every 6 h) or CI (4/0.5 g as a bolus followed by 12/1.5 g) for 18 h. Microdialysis catheters were placed for sampling of piperacillin concentrations from the intervertebral disc, vertebral cancellous bone, paravertebral muscle, and adjacent subcutaneous tissue during the third dosing interval (12−18 h). Blood samples were collected as reference. Results: CI resulted in fT > MIC > 82% across all compartments and targets, except for intervertebral disc (37%) and vertebral cancellous bone (28%) at MIC = 16 µg/mL. In Group STI, >72% fT > MIC was reached for MIC = 4 µg/mL in all investigated compartments, while for MIC = 16 µg/mL only subcutaneous tissue exhibited fT > MIC > 50%. Conclusion: CI of piperacillin resulted in higher fT > MIC compared to STI infusion across the investigated tissues and targets. CI should therefore be considered in spondylodiscitis cases requiring piperacillin treatment.

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure ‒ assessment in a novel porcine model.

Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·µg/mL), mean Cmax (range: 10.6-26.0 µg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 µg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

Staff experiences of encountering and treating outpatients with substance use disorder in the psychiatric context: a qualitative study.

BACKGROUND: High comorbidity exists between mental illness and substance use disorders (SUD). Patients in psychiatry living with problematic alcohol or drug consumption can experience a sense of exclusion, where seeking help for SUD can be perceived as stigmatizing. The aim of this study is to illuminate staff experiences of encountering patients with SUD within the psychiatric outpatient context. METHODS: The study was exploratory, with a qualitative design. Interviews with outpatient psychiatry managers and focus groups with clinical staff focused on the experience of encountering patients with SUD. Data were evaluated using content analysis inspired by phenomenological-hermeneutic methodology. RESULTS: Three themes were identified and each illuminated by two sub-themes. Bridging the organizational gap included sub-themes of having an established collaboration and facing difficulties in the collaboration; Having beliefs about the patient you encounter included sub-themes of working with patients who are exposed to prejudicial thoughts and expressing prejudicial thoughts about the patient. Striving to achieve a therapeutic alliance included sub-themes of having a feeling of developing together and supporting the patient towards recovery. CONCLUSION: A life-world perspective, used to interpret results, indicated that caring for patients with SUD in psychiatry was perceived as difficult, where collaboration between psychiatry and addiction care was often experienced as problematic. Based on these findings, we believe that the current gap between the psychiatry and addiction care could be reduced to some extent by offering patients digital treatment for SUD. In this way, patients could remain under the care of their regular psychiatric clinic without having to physically visit SUD services. Thus, a virtual bridge could be established to bring psychiatry and addiction care closer to each other for the patients' benefit.

Influence of anastomoses on intestine ischemia and cefuroxime concentrations: Evaluated in the ileum and colon in a porcine model.

BACKGROUND: Anastomotic leakage is a serious complication following gastrointestinal surgery and is associated with increased morbidity and mortality. The incidence of anastomotic leakage is determined by anatomy and is reported to be between 4%-33% for colon anastomosis and 1%-3% for small intestine anastomosis. The etiology of anastomotic leakage of the intestine has been divided into three main factors: healing disturbances, communication between intra- and extra-luminal compartments, and infection. All three factors interact, and one factor will inevitably lead to the other two factors resulting in tissue ischemia, tissue necrosis, and anastomotic leakage. AIM: To evaluate ischemic metabolites and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon in a porcine model. METHODS: Eight healthy female pigs (Danish Landrace breed, weight 58-62 kg) were included in this study. Microdialysis catheters were placed for sampling of ischemic metabolites (glucose, lactate, glycerol, and pyruvate) and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon. Cefuroxime 1.5 g was administered as an intravenous infusion over 15 min. Subsequently, dialysates and blood samples were collected over 8 h and the ischemic metabolites and cefuroxime concentrations were quantified in all samples. The concentrations of glucose, lactate, glycerol and pyruvate were determined using the CMA 600 Microdialysis Analyzer with Reagent Set A (M Dialysis AB, Sweden), and the concentrations of cefuroxime and meropenem were quantified using a validated ultra-high-performance liquid chromatography assay. RESULTS: Only the colon anastomosis induced mean ischemic lactate/pyruvate ratios above 25 (ischemic cut-off) throughout the entire sampling interval, and simultaneously decreased glucose concentrations. The mean time for which cefuroxime concentrations were maintained above the clinical breakpoint minimal inhibitory concentration for Escherichia coli (8 µg/mL) ranged between 116-128 min across all the investigated compartments, and was similar between the anastomosis and non-anastomosis ileum and colon. For all pigs and in all the investigated compartments, a cefuroxime concentration of 8 µg/mL was reached within 10 min after administration. When comparing the pharmacokinetic parameters between the anastomosis and non-anastomosis sites for both ileum and colon, only colon Tmax and half-life differed between anastomosis and non-anastomosis (P < 0.03). Incomplete tissue penetrations were found in all tissues except for the non-anastomosis colon. CONCLUSION: Administering 1.5 g cefuroxime 10 min prior to intestine surgery seems sufficient, and effective concentrations are sustained for approximately 2 h. Only colon anastomosis was locally vulnerable to ischemia.

Identification and management of alcohol use and illicit substance use in outpatient psychiatric clinics in Sweden: a national survey of clinic directors and staff.

BACKGROUND: Swedish national guidelines recommend that all health care settings systematically screen patients for alcohol use and illicit substance use. When hazardous use is identified, it should immediately be addressed, preferably through brief interventions (BI). It is well known that the prevalence of alcohol use and illicit substance use among psychiatric patients is high, but it is not known to what extent screening and BI are routinely carried out in such clinics. METHODS: Two online surveys investigating the use of screening and BI for alcohol and illicit substances were constructed; one for psychiatric outpatient clinic directors and one for staff at these clinics. The main analyses were calculated as simple frequencies. In secondary analyses, we investigated the associations between substance abuse training, type of clinic and screening/BI delivery. For these analyses, the Chi square test was used. RESULTS: Most clinic directors reported that they have guidelines to screen for alcohol (93.1%) and illicit substance use (78.9%) at initial assessment. Fifty percent reported having guidelines for delivering BI when identifying hazardous alcohol use (35.9% for hazardous illicit substance use). Among staff, 66.6% reported always screening for alcohol use and 57.8% reported always screening for illicit substance use at initial assessment. Further, 36.7% reported that they usually deliver BI when identifying hazardous alcohol use (35.7% for hazardous illicit substance use). Secondary analyses indicated that staff with substance abuse training were significantly more likely to screen for alcohol use than staff without such training. Further, staff at psychosis clinics were significantly less likely to screen for both alcohol and substance use than staff at both general and specialist psychiatric clinics. CONCLUSIONS: Most clinic directors reported having clear guidelines for staff to screen for alcohol use and illicit substance use, but fewer staff members than expected indicated that these guidelines were adhered to. Providing training about substance use disorders for staff may increase use of screening for alcohol use, and psychosis clinics may need to improve their screening routines.