Estimated Mean Difference Research Articles

Thoracic ultrasound competence for ultrasound guided pleural procedures: The creation and validation of an assessment tool for use in the certification of basic thoracic ultrasound competence.

Focused thoracic ultrasound (TUS) provides an increased safety profile when undertaking invasive pleural procedures. This has led to the requirement for defined curricula, high quality teaching and robust, validated assessment tools among physicians to ensure patient safety and clinical excellence. Current UK practice is based almost exclusively on expert consensus, but assessment methods employed have been shown to have low reliability and validity and are potentially open to bias. As a result, several assessment tools have been developed, although each has its own limitations. This study aimed to develop and validate an assessment tool corresponding to those skills associated with the most basic level of practice, defined recently as an emergency level operator in the British Thoracic Society Training Standards for Thoracic Ultrasound. A total of 27 candidates were enrolled by two examiners based in Belfast and Oxford over a 10-month period between February and November 2019. Mean score of the inexperienced group was 44.3 (95% CI 39.2-49.4, range 28-54) compared with 74.9 (95% CI 72.8-77, range 64-80) in the experienced group providing an estimated mean difference of 30.7 between the two groups (95% CI 24.7-36.7; p < .001). This tool appears to discriminate between trainees with limited experience of TUS performance and those with no experience. It has the potential to form part of the assessment strategy for trainees in the United Kingdom and beyond, alongside well established assessment tools in postgraduate training.

Association between kidney function and intracerebral hematoma volume

Renal dysfunction has been reported to be associated with larger hematoma volume in intracerebral hemorrhage (ICH) due to concomitant nutritional imbalances and platelet dysfunction; however, this association remains controversial. This study analyzed the association between potential risk factors and hematoma volume in patients with ICH. This retrospective cohort study used data from 456 patients with ICH at a single comprehensive stroke center. We assessed the association of estimated glomerular filtration rate (eGFR) and Controlling Nutritional Status score with hematoma volume using multivariable non-linear regression models. The effect of the use of antithrombotic agents on hematoma volume was analyzed using outcome-adaptive double/debiased machine learning approach, considering many covariates. The median and interquartile range of age and eGFR were 64 (54–75) years and 56.1 (39.3–66.7) mL/min/1.73 m2, respectively. The multivariable non-linear regression model showed that (1) eGFR and hematoma volume had a positive linear association, which was not statistically significant, and (2) nutritional status was positively associated with hematoma volume, although not significantly. Outcome-adaptive double/debiased machine learning revealed that patients receiving antithrombotic agents did not present with significantly larger hematoma volume than those who were not receiving antithrombotic agents (estimated mean difference of hematoma volume [95% confidence interval] = 15.32 [−6.02 to 36.65]). Our analysis shows no statistically or clinically significant relationship between renal function and hematoma volume; however, nutritional status and the use of antithrombotic agents showed an increasing tendency of the degree of hematoma in patients with ICH.

Accuracy of the Australian National Sub-Acute and Non-Acute Patient Classification in predicting rehabilitation length of stay for stroke survivors who are ≥65 years of age and have lateropulsion

ABSTRACT Background Lateropulsion is a common impairment after stroke. Regardless of stroke severity, functional recovery is slower in people with lateropulsion, resulting in requirement for longer rehabilitation duration. In Australia, inpatient rehabilitation funding is determined via the Australian National Sub-Acute and Non-Acute Patient Classification (AN-SNAP). AN-SNAP class is determined using age, diagnosis, weighted Functional Independence Measure (FIM) motor score, and FIM cognitive score. Objectives To explore accuracy of the AN-SNAP to predict length of stay (LOS) for people with poststroke lateropulsion. Methods A retrospective database audit was undertaken. AN-SNAP predicted LOS for each participant was calculated based on 2019 calendar year national benchmarks. A multivariable linear regression model estimated mean differences in reported LOS and AN-SNAP predicted LOS after adjusting for lateropulsion severity (Four Point Pusher Score). A separate logistic regression model assessed whether FIM change during admission was associated with reported LOS exceeding AN-SNAP predicted LOS. Results Data were available from 1126 admissions. Reported LOS exceeding AN-SNAP predicted LOS was associated with greater lateropulsion severity on admission. Where AN-SNAP predicted LOS was longer, those with no lateropulsion on admission showed shorter reported than predicted LOS. Greater improvement in FIM during rehabilitation was associated with increased odds of reported LOS exceeding AN-SNAP predicted LOS (OR 1.02, 95%CI 1.01–1.03, p < .001). Conclusions Inclusion of a measure of poststroke lateropulsion in the AN-SNAP classification model would result in more accurate LOS predictions to inform funding. Costs of longer rehabilitation LOS may be countered by optimized long-term physical function, reducing requirement for ongoing care.

Comparison of Vie Scope® and Macintosh laryngoscopes for intubation during resuscitation by paramedics wearing personal protective equipment.

BackgroundEndotracheal intubation (ETI) is still the gold standard of airway management, but in cases of sudden cardiac arrest in patients with suspected SARS-CoV-2 infection, ETI is associated with risks for both the patient and the medical personnel. We hypothesized that the Vie Scope® is more useful for endotracheal intubation of suspected or confirmed COVID-19 cardiac arrest patients than the conventional laryngoscope with Macintosh blade when operators are wearing personal protective equipment (PPE).MethodsStudy was designed as a prospective, multicenter, randomized clinical trial performed by Emergency Medical Services in Poland. Patients with suspected or confirmed COVID-19 diagnosis who needed cardiopulmonary resuscitation in prehospital setting were included. Patients under 18 years old or with criteria predictive of impossible intubation under direct laryngoscopy, were excluded.Patients were randomly allocated 1:1 to Vie Scope® versus direct laryngoscopy with a Macintosh blade. Study groups were compared on success of intubation attempts, time to intubation, glottis visualization and number of optimization maneuvers.ResultsWe enrolled 90 out-of-hospital cardiac arrest (OHCA) patients, aged 43–92 years. Compared to the VieScope® laryngoscope, use of the Macintosh laryngoscope required longer times for tracheal intubation with an estimated mean difference of −48 s (95%CI confidence interval [CI], −60.23, −35.77; p < 0.001). Moreover VieScope® improved first attempt success rate, 93.3% vs. 51.1% respectively (odds ratio [OR] = 13.39; 95%CI: 3.62, 49.58; p < 0.001).ConclusionsThe use of the Vie Scope® laryngoscope in OHCA patients improved the first attempt success rate, and reduced intubation time compared to Macintosh laryngoscope in paramedics wearing PPE for against aerosol generating procedures.Trial registration: ClinicalTrials registration number NCT04365608

Reducing levels of C-Reactive Protein: An eight-week, open-label clinical trial of three oral supplements

C-reactive protein (CRP) is a protein in the blood that increases with inflammation, and high CRP levels measured with high-sensitivity CRP (hs-CRP) tests can indicate higher risk of heart attack or stroke. Several over-the-counter oral supplements reduce CRP levels. This eight-week, open-label clinical trial investigated whether Vitamin C, ginger, or curcumin were most effective at reducing hs-CRP levels in healthy individuals with low baseline hs-CRP levels. Thirty healthy male and female participants were enrolled in one of three trial treatment arms: Vitamin C (1000 mg/day), ginger (2000 mg/day), and curcumin (1000 mg/day). hs-CRP levels were collected at baseline and after eight weeks of oral supplements. Paired t-tests were used to analyze data by age, body mass index (BMI), and baseline hs-CRP level. The primary outcome measure was mean difference between time points and 95% confidence intervals. Twenty-six people completed the study. Baseline hs-CRP levels were very low for all three intervention groups. Based on estimated mean difference, all three supplements reduced hs-CRP levels, but change at eight weeks was not statistically significant. Within the groups, ginger most consistently reduced hs-CRP levels even though the ginger group had the lowest mean baseline hs-CRP levels. Curcumin was least likely to reduce hs-CRP levels. Overall, all three interventions reduced hs-CRP levels in this group of healthy participants with low baseline levels, suggesting that these agents, which are available over-the-counter, may provide an alternative for reducing inflammation. Larger clinical trials to assess the utility of these agents are warranted.

Glymphatic system impairment in multiple sclerosis: relation with brain damage and disability.

Recent evidence has shown the existence of a CNS 'waste clearance' system, defined as the glymphatic system. Glymphatic abnormalities have been described in several neurodegenerative conditions, including Alzheimer's and Parkinson's disease. Glymphatic function has not been thoroughly explored in multiple sclerosis, where neurodegenerative processes are intermingled with inflammatory processes. We aimed to investigate glymphatic system function in multiple sclerosis and to evaluate its association with clinical disability, disease course, demyelination and neurodegeneration, quantified using different MRI techniques. In this retrospective study, we enrolled 71 multiple sclerosis patients (49 relapsing-remitting and 22 progressive multiple sclerosis) and 32 age- and sex-matched healthy control subjects. All subjects underwent neurological and MRI assessment including high-resolution T1, T2 and double inversion recovery sequences, diffusion and susceptibility weighted imaging. We calculated the diffusion along perivascular space index, a proxy for glymphatic function, cortical and deep grey matter volume, white and cortical grey matter lesion volume and normal-appearing white matter microstructural damage. Multiple sclerosis patients showed an overall lower diffusion along perivascular space index versus healthy controls (estimated mean difference: -0.09, P = 0.01). Both relapsing-remitting and progressive multiple sclerosis patients had lower diffusion along perivascular space index versus healthy controls (estimated mean difference: -0.06, P = 0.04 for relapsing-remitting and -0.19, P = 0.001 for progressive multiple sclerosis patients). Progressive multiple sclerosis patients showed lower diffusion along perivascular space index versus relapsing-remitting multiple sclerosis patients (estimated mean difference: -0.09, P = 0.03). In multiple sclerosis patients, lower diffusion along perivascular space index was associated with more severe clinical disability (r = -0.45, P = 0.001) and longer disease duration (r = -0.37, P = 0.002). Interestingly, we detected a negative association between diffusion along perivascular space index and disease duration in the first 4.13 years of the disease course (r = -0.38, P = 0.04) without any association thereafter (up to 34 years of disease duration). Lower diffusion along perivascular space index was associated with higher white (r = -0.36, P = 0.003) and cortical (r = -0.41, P = 0.001) lesion volume, more severe cortical (r = 0.30, P = 0.007) and deep (r = 0.42, P = 0.001) grey matter atrophy, reduced fractional anisotropy (r = 0.42, P = 0.001) and increased mean diffusivity (r = -0.45, P = 0.001) in the normal-appearing white matter. Our results suggest that the glymphatic system is impaired in multiple sclerosis, especially in progressive stages. Impaired glymphatic function was associated with measures of both demyelination and neurodegeneration and reflects a more severe clinical disability. These findings suggest that glymphatic impairment may be a pathological mechanism underpinning multiple sclerosis. The dynamic interplay with other pathological substrates of the disease deserves further investigation.

Impact of a Virtual Culinary Medicine Curriculum on Biometric Outcomes, Dietary Habits, and Related Psychosocial Factors among Patients with Diabetes Participating in a Food Prescription Program.

Culinary medicine is an evidence-based approach that blends the art of cooking with the science of medicine to inculcate a healthy dietary pattern. Food prescription programs are gaining popularity in the Unites States, as a means to improve access to healthy foods among patient populations. The purpose of this paper is to describe the implementation and preliminary impact of A Prescription for Healthy Living (APHL) culinary medicine curriculum on biometric and diet-related behavioral and psychosocial outcomes among patients with diabetes participating in a clinic-led food prescription (food Rx) program. We used a quasi-experimental design to assess APHL program impact on patient biometric outcome data obtained from electronic health records, including glycosylated hemoglobin (HbA1c), body mass index (BMI), and blood pressure (n = 33 patients in the APHL group, n = 75 patients in the food Rx-only group). Pre-post surveys were administered among those in the APHL group to monitor program impact on psychosocial and behavioral outcomes. Results of the outcome analysis showed significant pre-to-post reduction in HbA1c levels among participants within the APHL group (estimated mean difference = −0.96% (−1.82, −0.10), p = 0.028). Between-group changes showed a greater decrease in HbA1c among those participating in APHL as compared to food Rx-only, albeit these differences were not statistically significant. Participation in APHL demonstrated significant increases in the consumption of fruits and vegetables, fewer participants reported that cooking healthy food is difficult, increased frequency of cooking from scratch, and increased self-efficacy in meal planning and cooking (p < 0.01). In conclusion, the results of our pilot study suggest the potential positive impact of a virtually-implemented culinary medicine approach in improving health outcomes among low-income patients with type 2 diabetes, albeit studies with a larger sample size and a rigorous study design are needed.

A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer.

Purpose: The optimal frequency for cardiac monitoring of left ventricular ejection fraction (LVEF) in patients receiving trastuzumab-based therapy for early breast cancer (EBC) is unknown. We conducted a randomized controlled trial comparing 3- versus 4-monthly cardiac monitoring. Patients and Method: Patients scheduled to receive trastuzumab-containing cancer therapy for EBC with normal (>53%) baseline LVEF were randomized to undergo LVEF assessments every 3 or 4 months. The primary outcome was the change in LVEF from baseline. Secondary outcomes included the rate of cardiac dysfunction (defined as a decrease in the LVEF of ≥10 percentage points, to a value <53%), delays in or discontinuation of trastuzumab therapy, and cardiology referral. Results: Of the 200 eligible and enrolled patients, 100 (50%) were randomized to 3-monthly and 100 (50%) to 4-monthly cardiac monitoring. Of these patients, 98 and 97 respectively underwent at least one cardiac scan. The estimated mean difference in LVEF from baseline was −0.94% (one-sided 95% lower bound: −2.14), which exceeded the pre-defined non-inferiority margin of −4%. There were also no significant differences between the two study arms for any of the secondary endpoints. The rate of detection of cardiac dysfunction was 16.3% (16/98) and 12.4% (12/97) in the 3- and 4-monthly arms, respectively (95% CI: 4.0 [−5.9, 13.8]). Conclusions: Cardiac monitoring every 4 months was deemed non-inferior to that every 3 months in patients with HER2-positive EBC being treated with trastuzumab-based therapy. Given its costs and inconvenience, cardiac monitoring every 4 months should be considered standard practice. Registration: NCT02696707, 18 February 2016.

Digital stress management in cancer: Testing StressProffen in a 12-month randomized controlled trial.

Cognitive-behavioral stress management interventions are associated with improved psychological well-being for cancer survivors. The availability of, access to, and outreach of these in-person interventions are limited, however. The current study, therefore, evaluated the efficacy of StressProffen, a digital application (app)-based stress management intervention for cancer survivors, in a 12-month randomized controlled trial. Cancer survivors 1 year or less after their treatment (N = 172) were randomized to the StressProffen intervention (n = 84) or a usual-care control group (n = 88). The intervention was delivered in a simple blended care model: 1) 1 in-person introduction session, 2) 10 app-based cognitive-behavioral stress management modules, and 3) 2 follow-up phone calls. Stress (Perceived Stress Scale), anxiety and depression (Hospital Anxiety and Depression Scale), self-regulatory fatigue (Self-Regulatory Fatigue 18), and health-related quality of life (HRQOL; RAND-36) were examined at the baseline and at 6 and 12 months. Generalized linear models for repeated measures were fitted to compare effects over time. Participants were mainly female (82%), had a mean age of 52 years (standard deviation, 11.3 years; range, 20-78 years), and had a variety of cancer types (mostly breast cancer [48%]). Over the 12-month study time, the intervention group reported significantly decreased stress (P < .001), depression (P = .003), and self-regulatory fatigue (P = .002) as well as improved HRQOL (for 6 of 8 domains, P ≤ .015) in comparison with controls. The largest favored effects for the intervention group were observed at 6 months: stress (estimated mean difference [MD], -5.1; P < .001), anxiety (MD, -1.4; P = .015), depression (MD, -2.1; P < .001), self-regulatory fatigue (MD, -4.9; P < .001), and HRQOL (7 of 8 domains; P ≤ .037). Digital stress management interventions such as StressProffen have the potential to extend the outreach of psychological interventions and provide easily available and effective psychosocial support for cancer survivors.

Exercise training improves cognition in chronic stroke: A 6‐month randomized controlled trial

AbstractBackgroundA stroke doubles one’s risk for dementia. Impairment in multiple domains of cognition are common following stroke. Thus, stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. We assessed whether targeted exercise training or cognitive and social enrichment activities would promote cognitive function in community‐dwelling adults with chronic stroke (i.e., &gt; 12 months since stroke event).MethodsA three‐arm parallel, single‐blinded, 6‐month randomized controlled trial with 120 adults with chronic stroke who were randomized (2:2:3) to: 1) targeted exercise training (EX; n=34)) modeled after the Fitness And Mobility Exercise (FAME) program (Eng, Top Geriatr Rehabil, 2010); 2) cognitive and social enrichment activities (Cog‐Plus; n=34); and 3) an active control group (CON; n=52). Each experimental arm was group‐based and 2x/week. The primary outcome was the ADAS‐Cog‐Plus, a global measure of cognitive performance using multidimensional item response theory to summarize scores from the 13‐item ADAS‐Cog and other standard cognitive assessments (i.e., Trail Making Test Parts A and B, Digit Span Forward and Backward, and Animal and Vegetable Fluency). Lower ADAS‐Cog‐Plus scores represent better cognitive performance; ADAS‐Cog‐Plus scores of approximately −1.0 indicate healthy cognitive performance, 0.0 indicate mild cognitive impairment, and 1.0 indicate dementia. The primary analysis using linear mixed model compared changes in ADAS‐Cog‐Plus performance from baseline to month 6, with baseline ADAS‐Cog‐Plus and Mini‐Mental State Examination scores as covariates. Two planned simple contrasts (i.e., EX vs. CON; Cog‐Plus vs. CON) were performed using the Dunnett test.ResultMean baseline Fugl‐Meyer score was 81.21 (SD=23.85; range: 6‐100) and mean baseline Montreal Cognitive Assessment score was 21.89 points out of 30. An overall attrition rate of 14% was observed (EX=6; Cog‐Plus=5; CON=6). Participants in the EX group had significantly better ADAS‐Cog Plus performance than CON at trial completion (estimated mean difference: ‐0.23; 95%CI:[‐0.43, ‐0.03]; p=.024). There was no significant difference in ADAS‐Cog Plus performance between the Cog‐Plus and CON group at trial completion (estimated mean difference: ‐0.10; 95% CI:[‐0.30, 0.10]; p=.314).ConclusionTargeted exercise training may be efficacious in improving cognition in adults with chronic stroke and should be promoted among individuals with chronic stroke.

The Influence of the In-person Residency Interview: A Prospective Study.

This prospective study investigated whether in-person interviews affected interviewer assessments of anesthesiology residency applicants at an academic medical center, and which applicant characteristics influenced interview performance. Eighteen faculty members involved in residency recruitment between November 2019 and January 2020 documented preinterview (after full application review) and postinterview scores of the applicants on a scale of 1 to 5. Faculty also reported the relative contributions of specific interview characteristics (personality, physical appearance, professional demeanor, discussion regarding academic/scholarly activity, and level of interest in the specialty) to their postinterview assessments. Mixed-effects models were used to assess whether interviews changed faculty assessment of applicants, and what the relative contributions of applicant characteristics were to faculty assessments. A total of 696 interviews were conducted with 232 applicants. The postinterview scores differed significantly from the preinterview scores (estimated mean difference, 0.09 ± 0.02; P < 0.0001). The characteristics most affecting postinterview scores were positive impressions of applicants' personalities (marginal mean change in postinterview score, 0.259; 95% confidence interval, 0.221-0.297) and negative impressions of applicants' professional demeanor (marginal mean change, -0.257; 95% confidence interval, -0.350 to -0.164). In-person interviews significantly affected residency applicants' scores. Personality and professional demeanor influenced scores more than did other characteristics examined. Further studies are needed to clarify the relevance of in-person interviews to the assessment of residency applicants.

Comparison of Donor Corneal Endothelial Cell Density Determined by Eye Banks and by a Central Image Analysis Reading Center Using the Same Image Analysis Method.

The purpose of this study was to evaluate agreement between eye banks (EBs) and an image analysis reading center on endothelial cell density (ECD) determinations using the same image analysis method. The Cornea Image Analysis Reading Center (CIARC) determined ECD with a single experienced analyst on EB-obtained central endothelial images from donors intended for keratoplasty from 2 eye banks, Eversight and Lions VisionGift, using the Konan center analysis method. The EBs performed ECD determination on their respective sets of images using the same analysis method with experienced eye bank technicians. The mean age of the 200 donors was 54 years (range 30-75 years). Seventy (35%) of the 200 patients were women, and 57 (29%) were diabetic. The mean ECD was 10 cells/mm2 greater by the EBs than by CIARC (P = 0.39), with 95% limits of agreement of [-304 to 323 cells/mm2]. The mean difference was not substantially changed when the difference between EBs and CIARC ECD was adjusted for sex, donor age, donor diabetes, CV, HEX, number of cells analyzed, and EBs as a random effect (estimated mean difference of 20 cells/mm2 after adjustment in a linear mixed model; P = 0.73). The EB-determined preoperative ECD was within 10% of the CIARC-determined ECD for 178 (89%) image sets, with 15 (8%) higher by >10% and 7 (3%) lower by >10%. Well-trained eye bank technicians achieve comparable results for ECD determination with an experienced image analyst from an image analysis reading center when the same image analysis method is used.

Differences in birthweight by maternal and paternal nativity status in Canada.

Parental nativity, as well as duration of residence of foreign-born parents in the host country, has been shown to be associated with size at birth. However, most studies have focused on maternal nativity status only and have not accounted for important characteristics of both parents. To explore whether maternal and paternal nativity and length of residence (LOR) are independently associated with birthweight for gestational age in a representative sample of infants in Canada. We compared mean differences in sex- and gestational age-standardised birthweight z-score by nativity status of both parents in a nationally representative sample of 130,532singleton infants born between May 2004 and May 2006 to mothers residing in Canada. We categorised parental nativity status into four groups (both parents Canada-born, mother only foreign-born, father only foreign-born and both parents foreign-born) and parents' LOR into three (both ≤10years, only one parent ≤10years and both >10years). We estimated mean differences in birthweight z-score and their 95% confidence intervals in linear regression models adjusted for parity, parents' ages, education, ethnicity and marital status of the mother. Compared with babies of Canada-born couples, those of two foreign-born parents had on average smaller birthweight z-score, -0.23 (95% CI -0.28, -0.25). However, after adjustment, the mean difference in z-score was -0.02 (95% CI -0.05, 0.00). Infants born to parents who had both resided in Canada for ≤10years had a unadjusted mean difference in z-score of -0.27 (95% CI -0.29, -0.26), compared infants whose parents were both Canada-born, but the difference became negligible (-0.02, 95% CI -0.04, 0.01) after adjustment. The birthweight differences by parental nativity or length of residence observed in our study population could be attributed to differences in the distribution of other parental characteristics that affect birthweight.

Early Versus Delayed Microdiscectomy for Chronic Sciatica Lasting 4-12 Months Secondary to Lumbar Disc Herniation: A Secondary Analysis of a Randomized Controlled Trial.

To compare the effect of delaying surgery on clinical outcome in patients with chronic sciatica secondary to lumbar disc herniation. Patients with sciatica lasting 4-12months and lumbar disc herniation at the L4-L5 or L5-S1 level were randomized to undergo microdiscectomy (early surgery) or to receive 6months of nonoperative treatment followed by surgery if needed (delayed surgery). Outcomes were leg pain, Oswestry Disability Index score (ODI), back pain, SF-36 physical component (PCS) and mental component (MCS) summary scores, employment, and satisfaction measured preoperatively and at 6weeks, 3months, 6months, and 1year after surgery. Of the 64 patients in the early surgery group, 56 underwent microdiscectomy an average of 3 ± 2weeks after enrollment. Of the 64 patients randomized to nonoperative care, 22 patients underwent delayed surgery an average of 53 ± 24weeks after enrollment. The early surgery group experienced less leg pain than the delayed surgery group, which was the primary outcome, at 6months after surgery (early surgery 2.8 ± .4 vs delayed surgery 4.8 ± .7; difference, 2.0; 95% confidence interval, .5-3.5). The overall estimated mean difference between groups significantly favored early surgery for leg pain, ODI, SF36-PCS, and back pain. The adverse event rate was similar between groups. Patients presenting with chronic sciatica treated with delayed surgery after prolonging standardized non-operative care have inferior outcomes compared to those that undergo expedited surgery.

How much of the effect of disability acquisition on mental health is mediated through employment and income? A causal mediation analysis quantifying interventional indirect effects using data from four waves of an Australian cohort study

ObjectivesThere is evidence that disability acquisition causes a decline in mental health, but few studies have examined the causal mechanisms through which the effect operates. This study used a novel...

The effect of nanoparticles on pulmonary fibrosis: a systematic review and Meta-analysis of preclinical studies

Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant increase in human exposure with unknown particles, and ultimately leading to an increase in acute and chronic diseases. The effect of nanoparticles on pulmonary fibrosis has been reported in vivo and in vitro studies; however, the results are inconsistent. The present systematic review and meta-analysis of animal preclinical studies was conducted to assess the effect of nanoparticles on pulmonary fibrosis. A systematic search of online databases and gray literature as well as reference lists of retrieved studies was performed up to February 2019 to identify preclinical animal studies. Studies were assessed for methodological quality using the SYstematic Review Center for Laboratory animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled standardized mean difference (SMD) estimate with corresponding 95% CI was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account conceptual heterogeneity. To assess the robustness of pooled estimates as well as heterogeneity across studies, sensitivity analysis and Cochran Q statistic (with I2 statistic) was carried out using Stata 11.0. Of 6494 retrieved studies, 85 were reviewed in depth for eligibility. 16 studies met the criteria for inclusion in this systematic review. The meta-analysis was conducted on 10 studies which had reported the mean of TGF-β in 7 days after exposure by nanoparticles jointly (exposure compared to no exposure). Findings showed that exposure to nanoparticles significantly induced pulmonary fibrosis (SMD: 4.12, 95% CI: 2.57-5.67). A statistical heterogeneity was found [P < 0.001 (Q statistics), I 2 = 83.0%] across studies. Nanoparticles were the most influencing in inducing pulmonary fibrosis in animal models. Sensitivity analysis demonstrated consistency of the results, indicating that the meta-analysis model was robust. Publication bias (using visual inspection and statistical tests) was unlikely in the association between nanoparticles and pulmonary fibrosis. We found that the nanoparticles significantly induce pulmonary fibrosis through increasing proinflammatory cytokine TGF-β and histopathological changes.

Electronic waste exposure and DNA damage: a systematic review and meta-analysis.

Inappropriate processing and disposal of electronic waste (e-waste) expose workers and surrounding populations to hazardous chemicals, including clastogens and aneugens. Recently, considerable literature hasgrown around e-waste recycling, associated chemical exposures and intermediate health outcomes, including DNA damage. Micronuclei (MN) frequency has been widely used as a biomarker to investigate DNA damage in human populations exposed to genotoxic agents. We conducted a systematic review of published studies to assess DNA damage in e-waste-exposed populations and performed a meta-analysis to evaluate the association between e-waste exposure and DNA damage. This systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement checklist. Articles published in English from January 2000 through December 2020 investigating the associations between e-waste exposure and DNA damage were retrieved from the following three major databases: MEDLINE, ProQuest, and Scopus. Studies that reported the use of MN assay as a biomarker of DNA damage were included for meta-analysis. Studies that also reported other DNA damage biomarkers such as chromosomal aberrations, comet assay biomarkers, 8-hydroxy-2'-deoxyguanosine (8-OHdG), telomere length, apoptosis rate were reported using narrative synthesis. A total of 20 publications were included in this review, of which seven studies were within the occupational setting, and the remaining 13 studies were ecological studies. The review found six biomarkers of DNA damage (micronuclei, comets assay parameters (tail length, % tailDNA, tail moment, and olive tail moment), 8-OHdG, telomere length, apoptosis rate and chromosomal aberrations) which were assessed using seven different biological matrices (buccal cells, blood, umbilical cord blood, placenta, urine and semen). Most studies showed elevated levels of DNA damage biomarkers among e-waste exposed populations than in control populations. The most commonly used biomarkers were micronuclei frequency (n=9) in peripheral blood lymphocytes or buccal cells and 8-OHdG (n=7) in urine. The results of the meta-analysis showed that electronic waste recycling has contributed toan increased risk of DNA damage measured using MN frequency with a pooled estimate of the standardized mean difference (SMD) of 2.30 (95% CI: 1.36, 3.24, p<0.001) based on 865 participants. Taken together, evidence from this systematic review with meta-analysis suggest that occupational and non-occupational exposure to e-waste processing is associated with increased risk of DNA damage measured through MN assay and other types of DNA damage biomarkers. However, more studies from other developing countries in Africa, Latin America, and South Asia are needed to confirm and increase these results' generalizability.

The Use of Cannabinoids for Insomnia in Daily Life: Naturalistic Study.

BackgroundInsomnia is a prevalent condition that presents itself at both the symptom and diagnostic levels. Although insomnia is one of the main reasons individuals seek medicinal cannabis, little is known about the profile of cannabinoid use or the perceived benefit of the use of cannabinoids in daily life.ObjectiveWe conducted a retrospective study of medicinal cannabis users to investigate the use profile and perceived efficacy of cannabinoids for the management of insomnia.MethodsData were collected using the Strainprint app, which allows medicinal cannabis users to log conditions and symptoms, track cannabis use, and monitor symptom severity pre- and postcannabis use. Our analyses examined 991 medicinal cannabis users with insomnia across 24,189 tracked cannabis use sessions. Sessions were analyzed, and both descriptive statistics and linear mixed-effects modeling were completed to examine use patterns and perceived efficacy.ResultsOverall, cannabinoids were perceived to be efficacious across all genders and ages, and no significant differences were found among product forms, ingestion methods, or gender groups. Although all strain categories were perceived as efficacious, predominant indica strains were found to reduce insomnia symptomology more than cannabidiol (CBD) strains (estimated mean difference 0.59, SE 0.11; 95% CI 0.36-0.81; adjusted P<.001) and predominant sativa strains (estimated mean difference 0.74, SE 0.16; 95% CI 0.43-1.06; adjusted P<.001). Indica hybrid strains also presented a greater reduction in insomnia symptomology than CBD strains (mean difference 0.52, SE 0.12; 95% CI 0.29-0.74; adjusted P<.001) and predominant sativa strains (mean difference 0.67, SE 0.16; 95% CI 0.34-1.00; adjusted P=.002).ConclusionsMedicinal cannabis users perceive a significant improvement in insomnia with cannabinoid use, and this study suggests a possible advantage with the use of predominant indica strains compared with predominant sativa strains and exclusively CBD in this population. This study emphasizes the need for randomized placebo-controlled trials assessing the efficacy and safety profile of cannabinoids for the treatment of insomnia.

Effect of deprescribing in elderly patients with type 2 diabetes: iDegLira might improve quality of life

Older people with type 2 diabetes (T2D) often have several comorbidities and take multiple drugs. This study tested a deprescribing strategy in older T2D patients, replacing a hypoglycemic therapeutic scheme with a single drug combination (iDegLira). In this 6-month, real-world, single-arm, open interventional study, we enrolled patients ≥ 75 years with T2D taking ≥ 2 medications for diabetes. Patients on a basal-bolus insulin regimen (n = 13), on a basal-insulin regimen plus oral glucose-lowering drugs (n = 9), and those on oral glucose-lowering drugs (n = 18) were switched to daily iDegLira. The primary clinical endpoint of the study was an improvement in CASP-19 and/or DTSQ score after 6 months. We also evaluated changes in glucose metabolism, depression, cognitive function, level of independence, and markers of inflammation. Thirty-five patients (12 women, mean age=81.4 y) completed the protocol. Results shown here are given as estimated mean difference (95%CI). DTSQ score improved [11.08 (7.13/15.02); p = 0.0001], whereas CASP-19 did not after 6 months of iDegLira treatment. We observed reductions in BMI [− 0.81 (− 1.27/0.35); p < 0.001], fasting glucose [− 52.07 (− 77.26/26.88); p < 0.001], HbA1c [− 0.58 (− 1.08/0.08); p < 0.05], and TNF-α [− 1.83 (− 3.12/− 0.54); p = 0.007]. Activities of daily living and cognitive function score increased [p = 0.006 and p = 0.02], whereas depression score significantly decreased [p = 0.02]. Notably, no patient reported episodes of severe hypoglycemia after initiation of iDegLira treatment. Among older patients with T2D, deprescribing using a single dose of iDegLira resulted in a greater likelihood of improving health and quality of life. Although our data indicate the effectiveness and safety of this approach, it must be confirmed in larger studies.

Definition and incidence of hypotension in intensive care unit patients, an international survey of the European Society of Intensive Care Medicine.

Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists. We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension. Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p < 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p < 0.001). An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians.