Nevin Manimala

J Environ Manage. 2022 Mar 16;312:114909. doi: 10.1016/j.jenvman.2022.114909. Online ahead of print.

ABSTRACT

Floating treatment wetlands (FTWs), artificial systems constructed from buoyant mats and planted with emergent macrophytes, represent a potential retrofit to enhance the dissolved nutrient removal performance of existing retention ponds. Treatment occurs as water flows through the dense network of roots suspended in the water column, providing opportunities for pollutants to be removed via filtration, sedimentation, plant uptake, and adsorption to biofilms in the root zone. Despite several recent review articles summarizing the growing body of research on FTWs, FTW design guidance and strategies to optimize their contributions to pollutant removal from stormwater are lacking, due in part to a lack of statistical analysis on FTW performance at the field scale. A meta-analysis of eight international FTW studies was performed to investigate the influence of retention pond, catchment, and FTW design characteristics on effluent concentrations of nutrients and total suspended solids (TSS). Random forest regression, a tree-based machine learning approach, was used to model complex interactions between a suite of predictor variables to identify design strategies for both retention ponds and FTWs to enhance treatment of nutrient and sediment. Results indicate that pond design features, especially loading ratio and pond depth (which should be limited to 200:1 and 1.75 m, respectively), are most influential to effluent water quality, while the benefits of FTWs were limited to improving mitigation of phosphorus species and TSS which was primarily influenced by FTW coverage and planting density. Findings from this work inform wet retention pond and FTW design, as well as guidance on scenarios where FTW implementation is most appropriate, to improve dissolved nutrient and sediment removal in urban runoff.

PMID:35305357 | DOI:10.1016/j.jenvman.2022.114909

Lancet Neurol. 2022 Apr;21(4):329-341. doi: 10.1016/S1474-4422(22)00027-8.

ABSTRACT

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer’s disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer’s pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer’s disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer’s disease.

METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer’s disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models.

FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=-4·28 × 10^-2 [SE 0·013], p=0·0012), but not high cortical uptake in PiB-PET (β=-5·51 × 10^-3 [0·011], p=0·63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by Aβ42 in CSF (r=0·56 [0·22], p=0·011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=-0·67 [0·25], p=0·0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0·45 [0·21], p=0·035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between Aβ42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0·46 [0·22]), p=0·040) and diminished cognitive decline (r=0·67 [0·22], p=0·0020).

INTERPRETATION: Our findings in autosomal dominant Alzheimer’s disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing.

FUNDING: German Research Foundation, US National Institutes of Health.

PMID:35305339 | DOI:10.1016/S1474-4422(22)00027-8

Addict Behav. 2022 Mar 15;130:107307. doi: 10.1016/j.addbeh.2022.107307. Online ahead of print.

ABSTRACT

INTRODUCTION: Product placement in music videos is a growing promotional strategy. This study examined the impact of e-cigarette product placement and imagery in music videos on susceptibility to use e-cigarettes among young adults.

METHODS: A non-probability sample of young adults (18 to 24) in Southern California were recruited to participate in an experiment over Zoom. Participants were randomized into a treatment or a control group. The treatment group watched seven music videos with e-cigarette product placement and imagery. The control group watched the same seven music videos with all e-cigarette product placement and imagery digitally removed. Participants completed a questionnaire after watching the music videos. The focus of the analysis was on susceptibility to use e-cigarettes in the future among never users (n = 303).

RESULTS: Participants in the treatment group who had never used e-cigarettes were more likely to report intentions to try e-cigarettes in the future (OR = 1.94, 95% CI [1.08, 3.54], compared to participants in the control group. Participants in the treatment group who had never used e-cigarettes were more likely to report peer influence (OR = 1.97, 95% CI [1.19, 3.32], compared to participants in the control group. While these subitems of susceptibility to use e-cigarettes were statistically significant, the relationship between the treatment group and the composite measure of susceptibility was not.

CONCLUSION: Exposure to e-cigarette product placement in music videos may increase young adults’ intentions to try e-cigarettes in the future. Federal, state, and local tobacco control regulatory bodies should consider strategies to reduce e-cigarette product placement in music videos.

PMID:35305325 | DOI:10.1016/j.addbeh.2022.107307

Lancet. 2022 Mar 16:S0140-6736(22)00462-7. doi: 10.1016/S0140-6736(22)00462-7. Online ahead of print.

ABSTRACT

BACKGROUND: The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.

METHODS: Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases).

FINDINGS: The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54-0·58); for hospital admission and death, HR estimates were 0·41 (0·39-0·43) and 0·31 (0·26-0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85-1·42) in those younger than 10 years, decreasing to 0·25 (0·21-0·30) in 60-69-year-olds, and then increasing to 0·47 (0·40-0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32-0·68]) and unvaccinated (0·18 [0·06-0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88-1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48-0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28-0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8-11 weeks post-booster vs unvaccinated: 0·22 [0·20-0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2.

INTERPRETATION: The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.

FUNDING: Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.

PMID:35305296 | DOI:10.1016/S0140-6736(22)00462-7

Clin Oral Implants Res. 2022 Mar 19. doi: 10.1111/clr.13922. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the outcomes of bone regeneration using a customized titanium mesh scaffold to cover a bone graft for reconstruction of complex defects of the jaws.

MATERIALS AND METHODS: 19 large defects were digitally reconstructed using CT scans according to the prosthetic requirements. A titanium mesh scaffold was designed to cover the bone (autologous/bovine bone particulate) graft. At least six months after surgery, a new cone-beam CT was taken. The pre-and postoperative CT datasets were then converted into three-dimensional models and digitally aligned. The actual mesh position was compared to the virtual position to assess the reliability of the digital project. The reconstructed bone volumes (RBVs) were calculated according to the planned bone volumes (PBVs), outlining the areas under the mesh. These values were then correlated with the number of exposures, locations of atrophy, and virtually-planned bone volume.

RESULTS: The mean matching value between the planned position of the mesh and the actual one was 82 ± 13.4%. 52.3% (40% early and 60% late) exposures were observed, with 15.8% exhibiting infection. 26.3% resulted as failures. The amount of reconstructed bone volume (RBV) in respect to PBV was 65 ± 40.5%, including failures, and 88.2 ± 8.32% without considering the failures. The results of the exposure event were statistically significant (p = 0.006) in conditioning the bone volume regenerated.

CONCLUSIONS: This study obtained up to 88% of bone regeneration in 74% of the cases. The failures encountered (26%) should underline the operator’s expertise relevance in conditioning the final result.

PMID:35305283 | DOI:10.1111/clr.13922

Public Health Nurs. 2022 Mar 19. doi: 10.1111/phn.13065. Online ahead of print.

ABSTRACT

OBJECTIVES: In Canada, HIV diagnoses continue unabated, with many of these cases being identified at a late stage of infection. While current public health surveillance data does not capture timing of diagnoses, locally, we identified a number of patients concurrently diagnosed with AIDS and HIV.

DESIGN: To understand the key characteristics, presenting symptoms, and risk factors associated with an AIDS diagnosis, we undertook a prospective chart review of HIV and AIDS diagnoses in Ottawa, Canada.

SAMPLE: Sixty seven charts of persons diagnosed with HIV and AIDS between 2015 and 2021 were reviewed.

MEASUREMENTS: Data were analyzed using descriptive statistics.

RESULTS: Results show some inconsistencies regarding HIV risk factors identified in published literature compared to those for persons diagnosed with AIDS in this study. Namely, patients in this review were more likely to be male, Black (from HIV-endemic regions), and heterosexual, and were diagnosed at critical stage in infection (total average CD4+ count of 92.9 cells/mm³ ) with 44.8% of patients concurrently diagnosed with one or more AIDS-related opportunistic infections.

CONCLUSIONS: The findings can be applied to strengthen HIV screening efforts in primary care settings, particularly among patients who present with persistent symptoms or illnesses related to chronic HIV infection. Additional considerations should be made for public health nurses to provide counseling and linkage to HIV testing/prevention services for patients at the time of an STI or Tuberculosis diagnosis and to increase AIDS-specific data collection.

PMID:35305282 | DOI:10.1111/phn.13065

Med Phys. 2022 Mar 19. doi: 10.1002/mp.15604. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in modeling small-field block apertures in proton pencil beam scanning. Furthermore, we evaluate the suitability of MCsquare as a 2^nd check for RayStation MC.

METHODS: We have enhanced MCsquare to model block apertures. To test the accuracy of both RayStation MC and the newly enhanced MCsquare, we compare the dose predictions of each to in-water dose measurements obtained using diode detectors and radiochromic film. Nine brass apertures with openings of 1, 2, 3, 4, and 5 cm and either 2 cm or 4 cm thickness were used in the irradiation of a water phantom. Two measurement setups were used, one with a range shifter and 119.7 MeV proton beam energy and the other with no range shifter and 147 MeV proton beam energy. To further test the validity of RayStation MC and MCsquare in modeling block apertures and to evaluate MCsquare as a 2^nd check tool, ten small-field (average target volume 8.3 cm³ ) patient treatment plans were calculated by each dose engine followed by a statistical comparison.

RESULTS: Comparing to the absolute dose measurements in water, RayStation MC differed by 1.2% ± 1.0% while MCsquare differed by -1.8% ± 3.7% in the plateau region of a pristine Bragg peak. Compared to the in-water film measurements, RayStation MC and MCsquare both performed well with an average 2D-3D gamma passing rate of 99.4% and 99.7% (3%/3mm) respectively. A t-test comparing the agreement with the film measurements between RayStation MC and MCsquare suggested that the relative spatial dose distributions calculated by MCsquare and RayStation MC were statistically indistinguishable. Directly comparing the dose calculations between MCsquare and RayStation MC over ten patients resulted in an average 3D-3D gamma passing rates of 98.5% (3%/3mm) and 94.1% (2%/2mm) respectively.

CONCLUSION: The validity of RayStation MC algorithm for use with patient-specific apertures has been expanded to include small apertures. MCsquare has been enhanced to model apertures and was found to be an adequate 2^nd check of RayStation MC in this scenario. This article is protected by copyright. All rights reserved.

PMID:35305269 | DOI:10.1002/mp.15604

Rheumatol Ther. 2022 Mar 19. doi: 10.1007/s40744-022-00434-z. Online ahead of print.

ABSTRACT

BACKGROUND: Psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are chronic immune-mediated inflammatory diseases (IMIDs) associated with cardiovascular (CV) disease. High-sensitivity C-reactive protein (hsCRP) and, more recently, the neutrophil-lymphocyte ratio (NLR) are important inflammatory biomarkers predictive of CV disease and CV disease-associated mortality. Here, we report the effect of interleukin (IL)-17A inhibition with secukinumab on CV risk parameters in patients with psoriasis, PsA, and axSpA over 1 year of treatment.

METHODS: This was a post hoc analysis of pooled data from phase 3/4 secukinumab studies in psoriasis, PsA, and axSpA. CV-related exclusion criteria included uncontrolled hypertension and congestive heart failure. Traditional risk factors assessed were body mass index (BMI) > 25, high fasting glucose and blood pressure (systolic and diastolic), and high cholesterol (low-density lipoproteins [LDL], total cholesterol/HDL ratio, and triglycerides). Inflammatory CV risk parameters assessed were hsCRP and NLR. Statistical analysis was descriptive. Subgroup analyses were performed in high-risk patients defined as having baseline hsCRP > 4 mg/L (patients with psoriasis) and > 10 mg/L (patients with PsA/axSpA).

RESULTS: In total, 9197 patients from 19 clinical trials (8 in psoriasis, n = 4742; 5 in PsA, n = 2475; 6 in axSpA, n = 1980) were included. All traditional CV risk parameters remained stable in secukinumab-treated patients through 1 year. Secukinumab rapidly reduced both hsCRP and the NLR compared with placebo at week 12 (psoriasis) or week 16 (PsA/axSpA) in the overall population and in high-risk patients (all P < 0.01). This reduction was maintained for at least 1 year of secukinumab therapy in all indications.

CONCLUSIONS: Secukinumab led to a rapid and sustained reduction in hsCRP and the NLR in patients with IMIDs with a high systemic inflammatory burden. Traditional CV risk factors remained stable for at least 1 year in patients with psoriasis, PsA, and axSpA. Taken together, secukinumab had a favorable effect on systemic inflammation without impact on traditional CV risk factors.

TRIALS REGISTRATION: ClinicalTrials.gov, NCT01365455, NCT01358578, NCT01406938, NCT01555125, NCT01636687, NCT02752776, NCT02074982, NCT02826603, NCT01752634, NCT01989468, NCT02294227, NCT02404350, NCT02745080, NCT01863732, NCT01649375, NCT02008916, NCT02159053, NCT02896127, NCT02696031.

PMID:35305260 | DOI:10.1007/s40744-022-00434-z

CNS Drugs. 2022 Mar 19. doi: 10.1007/s40263-022-00911-7. Online ahead of print.

ABSTRACT

BACKGROUND: Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder and during euthymia. However, the treatment potential of hypnotic agents that might be used to manage sleep disturbance in BD is not well understood. Similarly, melatonin and medications with a melatonin-receptor agonist mechanism of action may have chronotherapeutic potential for treating people with the disorder, but the impact of these substances on sleep and circadian rhythms and core symptoms in BD is unclear.

OBJECTIVE: Our aim was to conduct a systematic review and meta-analysis evaluating the current evidence for hypnotic and melatonin/melatonin-receptor agonist pharmacotherapy for symptoms of sleep disturbance, mania, and depression in patients with BD.

METHODS: AMED, Embase, MEDLINE and PsychINFO databases were searched for studies published in English from the date of inception to 31 October 2021. Studies included in this review were randomised controlled trials (RCTs) and non-controlled/non-randomised studies for BD that examined hypnotic medications selected based on a common pattern of usage for treating insomnia (i.e. chloral, clomethiazole, diphenhydramine, doxepin, doxylamine, promethazine, suvorexant, zaleplon, zolpidem, zopiclone, and eszopiclone) and melatonin and the melatonin-receptor agonist drugs ramelteon and agomelatine. Risk of bias was assessed using the RoB2 and AXIS tools. Pooled effect sizes for RCT outcomes were estimated using random-effects models.

RESULTS: A total of eleven studies (six RCTs and five experimental feasibility studies) involving 1279 participants were included. Each study examined melatonin or melatonin-receptor agonists. No studies of hypnotics were found that fulfilled the review inclusion criteria. Pilot feasibility studies suggested beneficial treatment effects for symptoms of sleep disturbance, depression, and mania. However, the pooled effect of the two available RCT studies assessing sleep quality via Pittsburgh Sleep Quality Index scores was not statistically significant (g = – 0.04 [95% CI – 0.81 to 0.73]) and neither was the pooled effect for depressive symptoms (four studies; g = – 0.10 [95% CI – 0.27 to 0.08]). Some RCT evidence suggests ramelteon might prevent relapse into depression in BD. The largest efficacy signal detected was for manic symptoms (four studies; g = – 0.44 [95% CI – 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics. In the two RCTs assessing manic symptoms during acute mania, adjunctive melatonin demonstrated superior treatment effects versus placebo.

CONCLUSIONS: There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD. Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms. Melatonin may be a promising candidate for the adjunctive treatment of bipolar mania. However, dose-finding studies and studies with larger sample sizes are needed to confirm its efficacy. We recommend parallel monitoring of sleep and circadian rhythms in future trials. Chronobiology-informed trial designs are needed to improve the quality of future studies.

PROTOCOL REGISTRATION: PROSPERO (CRD42020167528).

PMID:35305257 | DOI:10.1007/s40263-022-00911-7

CJEM. 2022 Mar 19. doi: 10.1007/s43678-022-00278-0. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic forced emergency departments (EDs) to change operations to minimize nosocomial infection risk. Many EDs cohort patients using provincial screening tools at triage. Despite cohorting, staff exposures occurred in the ‘cold zone’ due to lack of personal protective equipment (PPE) use with patients deemed low risk, resulting in staff quarantines. The cohorting strategy was perceived to lengthen time to physician initial assessment and ED length of stay times in our ED without protecting staff well enough due to varying PPE use. The objective of this study was to assess the impact of hot/cold zones for patient cohorting during a viral pandemic on ED length of stay.

METHODS: We conducted an interrupted time series analysis 3 weeks before and after the removal of hot/cold zone care space cohorting in our ED. In the before period, staff did not routinely wear full PPE to see cold zone patients. After removal, staff wore full PPE to see almost all patients. We collected data on ED length of stay, physician initial assessment times, arrival-to-room times, patient volumes, Canadian Triage Acuity Score (CTAS), admissions, staff hours of coverage, as well as proportions of patients on droplet/contact precautions and COVD-19 positive patients. The primary outcome was median ED length of stay.

RESULTS: After the removal of the hot/cold divisions, there was a decrease in the adjusted median ED length of stay by 24 min (95% CI 14; 33). PPE use increased in the after arm of the study. The interrupted time series analysis suggested a decrease in median ED length of stay after removal, although the change in slope and difference did not reach statistical significance.

CONCLUSION: Cohorted waiting areas may provide a safety benefit without operational compromise, but cohorting staff and care spaces is likely to compromise efficiency and create delays.

PMID:35305252 | DOI:10.1007/s43678-022-00278-0