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The association between benzodiazepine co-prescription, opioid agonist treatment and mortality: a systematic review
Full text linkBackground: Opioid agonist treatment (OAT) is the preferred treatment for opioid dependence due to benefits such as treatment retention, reduced opioid use and mortality. Benzodiazepine co-dependence is common in OAT patients and has been linked to increased mortality. Prescribing benzodiazepines during OAT has been tried to reduce the harms of extra-medical benzodiazepine use. This systematic review examines association between benzodiazepine co-prescription during OAT and mortality. Methods: We searched MEDLINE, Embase, Psych INFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Epistemonikos for reports published from database inception to June 2021. The searches were updated in February 2024. We included studies comparing mortality rates in OAT patients with and without benzodiazepine co-prescription. Two reviewers independently screened, extracted data, and assessed risk of bias from eligible studies with the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. We combined the effect estimates in meta-analyses where possible. The certainty of the pooled effect estimates was assessed using the GRADE approach. Results: We included six observational studies (N = 84,452) conducted in Sweden, Scotland, Canada, England, and the USA. Moderate-certainty evidence linked benzodiazepine prescription to higher all-cause mortality on OAT (HR 1.83; 95% CI 1.59 to 2.11). Moderate-certainty evidence associated benzodiazepine prescription with higher non-drug-induced mortality during OAT and the whole observation period (HR 1.73; 95% CI 1.33 to 2.25) and HR 2.02; 95% CI 1.29 to 3.18). Low-certainty evidence suggested an association with higher drug-induced mortality on OAT (HR 2.36; 95% CI 1.38 to 4.0). Very low-certainty evidence linked benzodiazepine prescription to higher all-cause and drug-induced mortality throughout the observation period (HR 1.49; 95% CI 1.02 to 2.18 and HR 2.19; 95% CI 0.80 to 6.0). Conclusions: There is probably an association between prescribed benzodiazepine use and higher risk of all-cause mortality (on OAT) and mortality due to non-drug-induced causes (on OAT and on and off OAT). Benzodiazepine prescription may also be associated with higher all-cause mortality (on and off OAT) and drug-induced mortality (on OAT and on and off-OAT), but this is highly uncertain due to methodological issues and possible confounding.publishedVersio
Mental Health Dynamics between Mothers and Siblings of Children with Disabilities
Full text linkWhen a child has a disability, their families face significant challenges that also impact parents' and siblings' mental health and adjustment. We examined the potential bidirectional relationships between parental mental health and sibling mental health and adjustment in families of children with a disability. Methods. We utilized baseline and 12month follow-up data from a randomized controlled trial of a brief intervention designed to enhance parent-sibling communication in families of children with a disability. The sample comprised 214 siblings aged 8-16 years and their parents (N = 203 mothers, N = 124 fathers).We estimated bivariate latent change score models to examine the longitudinal cross-domain associations between changes in parental mental health and changes in sibling mental health, and changes in parental mental health and sibling adjustment. Results. The results showed that changes in maternal mental health and sibling adjustment over the 12-month period were correlated (r = .22). The cross-domain associations between changes in maternal mental health and sibling mental health and adjustment were not statistically significant in any of the two models. However, baseline sibling mental health had nearly doubled impact on changes in maternal mental health (Β = 0.232, p = 0.061) compared to maternal health's impact on sibling mental health (Β = -0.134, p = 0.289). Models with paternal mental health data unfortunately did not run due to low paternal response rate at 12-months. Discussion. The findings suggest that whereas maternal mental health and sibling adjustment changes are correlated over time, the relationship between maternal and sibling measures does not necessarily operate bidirectionally. Future studies on family mental health dynamics should include data from fathers that may contribute to a broader understanding of these complex relationships.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Norwegian Women’s Public Health Organization [grant number 40404] and the Norwegian Research Council [grant number 321027].publishedVersio
Breastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional study
Full text linkFolate and vitamin B12 (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B12 status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0–12 months (n = 125) were recruited through public health clinics.We registered breastfeeding status and measured serum concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). The associations between infant age, breastfeeding, and biomarker concentrations were estimated in regression models. The mean (SD) age was 24 (16) weeks, and 42% were exclusively breastfed, 38% were partially breastfed, and 21% were weaned. Overall, median (IQR) folate, cobalamin, tHcy, andMMAconcentrations were 47 (35–66) nmol/L, 250 (178–368) pmol/L, 6.99 (5.69–9.27) μmol/L, and 0.35 (0.24–0.83) μmol/L, respectively. None of the infants were folate deficient, 15% were vitamin B12 deficient (6.5 μmol/L) andMMA (>0.26 μmol/L) were found in 62% and 69% of the infants, respectively. Compared to weaned, exclusively or partially breastfed infants were younger and had 46% higher tHcy concentrations (PBreastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional studyThis study was supported by Innlandet Hospital Trust Research Fund (grant number 150407 and 150392), Regional Research Fund Innlandet (grant number 286442).publishedVersio
A systematic survey of 200 systematic reviews with network meta-analysis (published 2020-2021) reveals that few reviews report structured evidence summaries
Full text linkObjectives: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general.
Study design and setting: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met prespecified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions.
Results: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with 3 (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation and 6 (23.1%) used Confidence In Network Meta-analysis. Surface Under the Cumulative Ranking Curve was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%).
Conclusion: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms; those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice.Funding: This work was supported by a PhD grant from South-Eastern Norway Regional Health Authority (grant number 2017015 ). The funding body was not involved in planning, execution, or reporting of this study.publishedVersio
Prevalence and Characteristics of Female and Male Esports Players among Norwegian Youth: A General Population Study
Full text linkElectronic sports (esports) have evolved into a major cultural phenomenon in the 21st century, mirroring traditional sports with organized, competitive play. This study investigates the prevalence of esports participation and characteristics of esports players among Norwegian adolescents. Using data from the Ungdata survey, a comprehensive web-based survey of Norwegian adolescents that includes questions on demographics, health, physical activity, social relations, and leisure activities such as gaming and esports, we analyzed responses from 70,695 students aged 16–18 years collected during 2021–2023. We conclude that about one out of twenty in the age group of 16–18 years actively engage in esports. The figure conceals significant gender differences: only 0.7% of girls, compared to 8.8% of boys, actively participate in esports. While female esports players differ noticeably from non-players on almost all indicators included in our analyses, the picture among boys reflects more similarities between esports players and other boys, than differences. Among the esports players, females almost consistently reported more negative experiences than males, including less physical socialization, lower self-rated health, higher rates of loneliness and sleeping problems, and a greater difficulty fitting in at school. Despite these negative aspects, esports players maintain close friendships similar to their non-playing peers.Prevalence and Characteristics of Female and Male Esports Players among Norwegian Youth: A General Population StudyThis research was funded by the Norwegian Ministry of Culture and Equality, and by
Innlandet Hospital Trust, project 150631.publishedVersio
MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - a Nordic Lymphoma Group study
Full text linkThe transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.This project has received funding from the European Union’s
Horizon 2020 research and innovation programme under
Marie Skłodowska-Curie grant agreement N 754299, Cancer fonden (2016/465, 19 0309Pj and 21 1561 Pj), Mats Paulssons
Stiftelse för forskning, innovation och samhällsbyggande,
Stiftelsen Stefan Paulssons cancerfond, and CREATE Health.
All financial support was granted to SE.publishedVersio
Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages
Full text linkBackground: Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear.
Methods: In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages.
Findings: We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10-3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98-2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46).
Conclusion: Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.This work was supported the Western Norway Regional Health Authority (912119, Northern Norway Regional Health Authority (HNF1415-18), The Research Council of Norway (Project 299230) and Trond Mohn Foundation (contract TMF2019TMT03).publishedVersio
Quantification of persistent organic pollutants in breastmilk and estimated infant intake, Norway
Full text linkPersistent organic pollutants (POPs) are environmental contaminants that can accumulate in human tissues and pose potential health risks. Despite global efforts to reduce their prevalence, follow-up studies are needed to see if the measures are successful. Since most infants in Norway are breastfed for the first 6 months of life, monitoring POP contamination in breastmilk is important for children's health and development. This study aims to evaluate the current levels of various POPs in women's breastmilk in Innlandet County, Norway. A cross-sectional study was conducted measuring concentrations of 35 different POPs, including polychlorinated biphenyls (PCBs), chlordanes (ChlDs), hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), Mirex, and brominated flame retardants in 120 breastmilk samples. The study analysed the impact of maternal age, parity, pre-pregnancy BMI, and infant age on POPs levels and compared the estimated daily intake per body weight of infants to existing health guidelines. The detected percentages for PCBs were 100%, for DDTs 98.3%, and for ChlDs 98.3%. The highest median concentration was found for ΣPCBs (26.9 ng/g lw). Maternal age, parity, and infant age were significant determinants of POP concentrations. Most infants exceeded the health-based guidance values for ΣPCB, and 6.4% percent did so for ΣHCHs. Despite lower POPs concentrations in breastmilk than in earlier studies, many breastfed infants are still exposed to levels exceeding health-based guidance values. Although the study's design had limitations, the study provides updated population-based data on POPs in breastmilk. Continued monitoring and research are necessary to understand and mitigate potential health risks associated with POPs.This study was funded by the Innland Hospital Trust Research Fund (grant number: 150407).publishedVersio
Epidemiology of overweight in under-five children in India: Insights from National Family Health Survey
Full text linkChildhood overweight is not only an immediate health concern due to its implications but also significantly increases the risk of persistent obesity and consequently CVD in the future, posing a serious threat to public health. The objective of this study was to examine the trends and associated factors of childhood overweight in India, using nationally representative data from three rounds of the National Family Health Survey (NFHS). For the primary analysis, we used data from 199 375 children aged 0-59 months from fifth round of the NFHS (NFHS-5). Overweight was defined as BMI-for-age Z (BMI Z) score > +2 sd above the WHO growth standards median. We compared the prevalence estimates of childhood overweight with third round of the third round of NFHS and fourth round of the NFHS. Potential risk factors were identified through multiple logistic regression analyses. The prevalence of overweight increased from 1·9 % in third round of NFHS to 4·0 % in NFHS-5, a trend seen across most states and union territories, with the Northeast region showing the highest prevalence. The BMI Z-score distributions from the latest two surveys indicated that the increase in overweight was substantially larger than the decrease in underweight. The consistent upward trend in the prevalence across different demographic groups raises important public health concerns. While undernutrition rates have remained relatively stable, there has been a noticeable rise in the incidence of overweight during the same time frame. The increasing trend of overweight among children in India calls for immediate action.publishedVersio
Is smokeless tobacco a healthier option in patients with AUD? A follow-up study during treatment
Full text linkIntroduction: Smoking is negatively related to mental health, but there is a paucity of research on the relationship between the use of smokeless tobacco, such as snus, and mental health outcomes, especially in people with alcohol use disorders (AUD). The aim of the present study was to examine the development of mental distress and quality of life (QoL) among AUD patients in treatment who did or did not use snus.
Method: The study included 128 AUD patients (27% female) from three rehabilitation clinics in Eastern Norway who were interviewed at admission, at 6 weeks, and after 6 months. Patients were asked about their mental health-related problems, alcohol, and substance use, QoL, and physical activity. Information about tobacco use was gathered with the questions "Do you smoke cigarettes?" and "Do you use snus?", with follow-up questions "How often?".
Result: There were 39 current snus users (31%), of which 20 were also current smokers (dual users). Seventy-five patients (59%) were smokers only, and only 14 (11%) patients were abstainers. Those who used snus only had a lower severity of dependence score than the other groups (p < 0.05). The dual use group reported lower QoL than the no tobacco use group. In a regression model adjusted for sex and age, smokers and dual users, but not users of snus, had higher levels of mental distress and poorer QoL compared to nontobacco users (p < 0.05). There were no differences between tobacco groups at follow-ups.
Conclusion: In this study, among AUD patients, snus users reported QoL and mental distress close to that of non-smokers, indicating a lower problem load among snus users compared to smokers.
Implications: Previous studies have shown conflicting results regarding the potential harm reduction effect of snus use among patients with AUD who smoke regarding their tobacco use, quality of life and mental health problems. This study suggests that snus use could also be a viable alternative to smoking for patients with addictions.The study was funded under the FRIPRO program of the Norwegian Research Council, and the funding body did not take part in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.publishedVersio