Tag: pubmed

Int J Drug Policy. 2021 Aug 29;98:103400. doi: 10.1016/j.drugpo.2021.103400. Online ahead of print.

ABSTRACT

BACKGROUND: The Ottawa Inner City Health’s Managed Opioid Program is the first, to our knowledge, to pair injectable opioid agonist hydromorphone treatment with assisted housing for people experiencing homelessness with severe opioid use disorder (OUD) and injection drug use. We aimed to describe this program and evaluate retention, health, and social wellbeing outcomes.

METHODS: We retrospectively assessed the first cohort of clients enrolled in the Managed Opioid Program between August 2017-2018. The primary outcome was retention at 12 months. Secondary outcomes included injectable and oral opioid dose titration, non-prescribed opioid use, overdoses, connection with behavioural health services, and social well-being. Descriptive statistics were used to summarize baseline demographics and secondary outcomes. Actuarial survival analysis was used to assess retention among participants.

RESULTS: The study sample included 26 participants: median age was 36 years, 14 were female, 22 were White, eight had alcohol use disorders, 25 had stimulant use disorders, and all had a history of concurrent psychiatric illness. Retention at 12 months was 77% (95% CI 62-95). Throughout the first-year participants’ opioid treatment doses increased. The median daily dose of injectable hydromorphone was 36 mg [17-54 mg] and 156 mg [108-188 mg] at enrollment and one year respectively. The median daily dose of oral opioid treatment was 120-milligram morphine equivalents [83-180 mg morphine equivalents] and 330-milligram morphine equivalents [285-428 mg morphine equivalents] at enrollment and one year respectively. Over half had no overdoses and there were no deaths among participants who remained enrolled. At one year, 45% stopped non-prescribed opioid use, 96% connected to behavioral health services, 73% reconnected with estranged families, and 31% started work or vocational programs.

CONCLUSION: Individuals with severe OUD engaged in injectable hydromorphone treatment and housing showed high retention in care and substantive improvements in patient-centered health and social well-being outcomes.

PMID:34469781 | DOI:10.1016/j.drugpo.2021.103400

J Neurophysiol. 2021 Sep 1. doi: 10.1152/jn.00181.2021. Online ahead of print.

ABSTRACT

Huntington’s disease (HD) is a fatal, hereditary neurodegenerative disorder that predominantly affects striatal medium-sized spiny neurons and cortical pyramidal neurons (CPNs). It has been proposed that perturbations in Ca²⁺ homeostasis could play a role in CPN alterations. To test this hypothesis, we used the R6/2 mouse model of juvenile HD at different stages of disease progression; presymptomatic, early symptomatic, and late symptomatic. We combined whole-cell patch clamp recordings of layer 2/3 CPNs with two-photon laser scanning microscopy to image somatic and dendritic Ca²⁺ transients associated with evoked action potentials (APs). We found that the amplitude of AP-induced Ca²⁺ transients recorded at the somata of CPNs was significantly reduced in presymptomatic and late symptomatic R6/2 mice compared to wildtype (WT) littermates. However, reduced amplitudes were compensated by increases in decay times, so that Ca²⁺ transient areas were similar between genotypes. AP-induced Ca²⁺ transients in CPN proximal dendrites were variable and differences did not reach statistical significance, except for reduced areas in the late symptomatic group. In late symptomatic mice, a specific store-operated Ca²⁺ channel antagonist, EVP4593, reduced somatic Ca²⁺ transient amplitude similarly in WT and R6/2 CPNs. In contrast, dantrolene, a ryanodine receptor (RyR) antagonist, and nifedipine, an L-type Ca²⁺ channel blocker, significantly reduced both somatic Ca²⁺ transient amplitude and area in R6/2 but not WT CPNs. These findings demonstrate that perturbations of Ca²⁺ homeostasis and compensation occur in CPNs before and after the onset of overt symptoms, and suggest RyRs and L-type Ca²⁺ channels as potential targets for therapeutic intervention.

PMID:34469694 | DOI:10.1152/jn.00181.2021

Environ Res. 2021 Aug 29:111977. doi: 10.1016/j.envres.2021.111977. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: The neurobiological processes involved in establishing sleep regulation are vulnerable to environmental exposures as early as seven weeks of gestation. Studies have linked. in utero pesticide exposure to childhood sleep-disordered breathing. However, the impact of in utero pesticide exposure on the sleep health of adolescents remains unexplored.

MATERIALS AND METHODS: Data from 137 mother-adolescent pairs from a Mexico City cohort were analyzed. We used maternal urinary 3-phenoxybenzoic acid (3-PBA, pyrethroid metabolite) and 3, 5, 6-trichloro-2-pyridinol (TCPy, chlorpyrifos metabolite) from trimester three to estimate in utero pesticide exposure. Among adolescents, we obtained repeated measures of objectively assessed sleep duration, midpoint, and fragmentation using wrist-actigraphy devices for 7 consecutive days in 2015 and 2017. Unstratified and sex-stratified associations between maternal urinary 3-PBA and TCPy and adolescent sleep measures were examined using linear mixed models. We also examined the interactive effects of maternal pesticide exposure and offspring sex on sleep outcomes.

RESULTS: 3-PBA and TCPy were detected in 44.4% and 93% of urine samples, respectively. In adjusted models, we observed monotonic associations between TCPy with longer sleep duration and later sleep midpoint. Adjusted findings demonstrated that higher exposure to maternal TCPy was associated with longer sleep duration (p, trend = 0.01), and later sleep timing (p = 0.07). Findings from interaction tests between exposure and offspring sex were not statistically significant. Adjusted sex-stratified findings showed that the association between TCPy with duration and midpoint was evident only among female offspring; those in the highest tertile of exposure had a 59 min (95% CI: 12.2, 104.8) (p, trend = 0.004) longer sleep duration and a 0.6 h (95% CI: 0.01, 1.3) (p, trend = 0.01) later sleep midpoint. We found no significant associations between 3-PBA and sleep outcomes.

CONCLUSION: Although findings from interaction tests were not statistically significant, effect estimates demonstrated that associations between maternal pesticide exposure and longer sleep duration and later sleep timing were stronger in female offspring.

PMID:34469742 | DOI:10.1016/j.envres.2021.111977

Rural Remote Health. 2021 Sep;21(3):5865. doi: 10.22605/RRH5865. Epub 2021 Sep 1.

ABSTRACT

INTRODUCTION: In various countries, a shortage of general practitioners (GPs) and worrying health statistics on risk factors, morbidity and mortality have been observed in rural areas. However, few comparative data are available on GP activities according to their location. The aim of this study was to analyse French GP activities according to their rural or urban practice location.

METHODS: This study was ancillary to the Eléments de la COnsultation en médecine GENérale (ECOGEN) study, which was a cross-sectional, multicentre, national study conducted in 128 French general practices in 2012. Data were collected by 54 interns in training during a period of 20 working days from December 2011 to April 2012. GP practice location was classified as rural area, urban cluster or urban area. The International Classification of Primary Care (ICPC-2) was used to classify reasons for encounter, health problem assessments, and processes of care. Univariate analyses were performed for all dependent variables, then multivariable analyses for key variables, using hierarchical mixed-effect models.

RESULTS: The database included 20 613 consultations. The mean yearly number of consultations per GP was higher in rural areas (p<0.0001), with a shorter consultation length (p<0.0001). No difference was found for GP sex (p=0.41), age (p=0.87), type of fees agreement (p=0.43), and type of practice (p=0.19) according to their practice location. Urban patients were younger, and there was a lower percentage of patients over 75 years (p<0.001). GPs more frequently consulted at patients’ homes in rural areas (p<0.0001). The mean number of chronic conditions managed was higher in rural areas and urban clusters than in urban areas (p<0001). Hypertension (p<0.0001), type 2 diabetes (p=0.003), and acute bronchitis/bronchiolitis (p=0.01) were more frequently managed in rural areas than in urban clusters and areas. Health maintenance/prevention (p<0.0001) and no disease situations (p<0.0001) were less frequent in rural areas. Drug prescription was more frequent in rural areas than in urban clusters and areas (p<0.0001). Multivariable analysis confirmed the influence of a GP’s rural practice location on the consultation length (p<0.0001), the number of chronic conditions per consultation (p<0.0001) and the number of health maintenance/prevention situations (p<0.0001), and a trend towards a higher yearly number of consultations per GP (p=0.09).

CONCLUSION: French rural GPs tend to have a higher workload than urban GPs. Rural patients have more chronic conditions to be managed but are offered fewer preventive services during consultations. It is necessary to increase the GP workforce and develop cooperation with allied health professionals in rural areas.

PMID:34469693 | DOI:10.22605/RRH5865

Int Braz J Urol. 2021 Nov-Dec;47(6):1150-1159. doi: 10.1590/S1677-5538.IBJU.2021.0161.

ABSTRACT

PURPOSE: To evaluate the efficacy of intravaginal electrical stimulation (IVES) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with idiopathic overactive bladder (OAB).

MATERIALS AND METHODS: Sixty-two women with idiopathic OAB were randomized into two groups using the random numbers generator as follows: Group 1 received BT alone (n:31), and Group 2 received BT+IVES (n:31). IVES was performed for twenty minutes three days a week over a course of eight weeks for a total of 24 sessions. Patients were evaluated in terms of incontinence severity (24-hour pad test), pelvic floor muscles strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes and number of pads), symptom severity (OAB-V8), incontinence-related QoL (IIQ-7), treatment success (positive response rate), cure/improvement rate and treatment satisfaction (Likert scale).

RESULTS: A statistically significant improvement was found in all parameters for all groups at the end of the treatment compared to the baseline values except pelvic floor muscles strength in Group 1 (p < 0.05). At the end of treatment, incontinence severity, frequency of voiding, nocturia, incontinence episodes, number of pads, symptom severity, and QoL were significantly improved in Group 2 compared to Group 1 (p < 0.05). Treatment satisfaction, cure/improvement, and positive response rates were significantly higher in group 2 compared to Group 1 (p < 0.05).

CONCLUSION: We conclude that BT+IVES were more effective than BT alone on both incontinence-related QoL and clinical parameters in women with idiopathic OAB.

PMID:34469668 | DOI:10.1590/S1677-5538.IBJU.2021.0161

Dermatol Ther. 2021 Sep 1:e15119. doi: 10.1111/dth.15119. Online ahead of print.

ABSTRACT

Chronic urticaria is in some cases very difficult to treat, we aimed to evaluate the effect of colchicine on chronic urticaria management. Fifty-five euthyroid patients with chronic urticaria were examined based on UQL and UAS7 questionnaires. The overall UQL-Q score after three months has not any statistical difference between groups. The overall UQL-Q score changes between groups was not statistically different. However, the UQL-Q score significantly reduces during study period in each group. In conclusion, colchicine can manage the sign and symptoms of chronic urticaria which improve the patients’ quality of life. This article is protected by copyright. All rights reserved.

PMID:34469631 | DOI:10.1111/dth.15119

J Health Organ Manag. 2021 Sep 2;ahead-of-print(ahead-of-print). doi: 10.1108/JHOM-12-2020-0479.

ABSTRACT

PURPOSE: This study examines the relationship between workplace bullying (WPB) and the turnover intentions (TIs) of nurses, both directly and indirectly, i.e. through serial mediation of psychological contract violation (PCV) and poor employee wellbeing (EWB). And that with the moderating effect of servant leadership (SL) on its final path to TIs of nurses.

DESIGN/METHODOLOGY/APPROACH: A total of 285 nurses voluntarily participated in the survey through convenient sampling from 13 different district hospitals. The authors performed partial least squares structural equation modeling (PLS-SEM) to test the study’s measurement and structural models.

FINDINGS: Overall, results indicated 62% prevalence rate of WPB and TIs of nurses had 67% variance explained by the exogenous factors. Workplace bullying was found to have direct as well as indirect relationship with TIs of nurses. For the latter, PCV and poor EWB were found to have partially mediated, both singly and serially. The moderating effect of SL on the serial mediation pathway was negative and significant.

ORIGINALITY/VALUE: Drawing on a tripartite theoretical perspective, this study illuminates the mechanism underlying WPB-TIs relationship with an advanced multivariate statistical technique in the nursing work setting in a developing country.

PMID:34469664 | DOI:10.1108/JHOM-12-2020-0479

Int J Cancer. 2021 Sep 1. doi: 10.1002/ijc.33790. Online ahead of print.

ABSTRACT

Lynch syndrome (LS), Lynch-like syndrome (LLS), and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterize and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS, and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex, and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS, and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. This study may support the development of risk-adapted surveillance policies in LS, LLS and FCCX. This article is protected by copyright. All rights reserved.

PMID:34469588 | DOI:10.1002/ijc.33790

Acta Paediatr. 2021 Sep 1. doi: 10.1111/apa.16084. Online ahead of print.

ABSTRACT

AIM: We investigated timing of survival differences and effects on morbidity for fetuses alive at maternal admission to hospital delivered at 22 to 26 weeks’ gestational age (GA).

METHODS: Data for from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006), and EPIPAGE- 2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up, and outcomes at 2-3 years of age were compared.

RESULTS: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 fetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks’ GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival.

CONCLUSION: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.

PMID:34469604 | DOI:10.1111/apa.16084

J Natl Cancer Inst. 2021 Sep 1:djab169. doi: 10.1093/jnci/djab169. Online ahead of print.

ABSTRACT

BACKGROUND: Tumors with homologous recombination (HR) deficiency (HRD) show high sensitivity to platinum salts and PARP-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown.

METHODS: Next generation sequencing, whole transcriptome sequencing and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Tumors with pathogenic/presumed pathogenic mutations in 33 genes involved in the HR pathway were considered HRD, the others HR proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI/bevacizumab versus FOLFOX/bevacizumab were analyzed with next generation sequencing. The analyses were separately conducted in microsatellite stable/proficient mismatch repair (MSS/pMMR) and microsatellite instable-high/deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided.

RESULTS: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%, p and q < 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2% P and q < 0.001) and PD-L1 positive (5.0% vs 2.4%, P and q = 0.001), enriched in all immune cell and fibroblast populations, and genomic loss of heterozygosity-high (16.2% vs 9.5%, P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared to MSS/pMMR and HRP ones (40.2 vs 23.8 months; hazard ratio = 0.66; 95% confidence interval = 0.45-0.98, P = .04). Consistent results were reported in the multivariable model (hazard ratio = 0.67; 95% confidence ratio = 0.45-1.02, P = .07). No interaction effect was evident between HR groups and treatment arm.

CONCLUSIONS: HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the HR system and immune check-point inhibitors in this subgroup is worth of clinical investigation.

PMID:34469533 | DOI:10.1093/jnci/djab169