Geographical Variation In Medication and Health Resource Use In Multiple Sclerosis.

BACKGROUND: Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care. METHODS: Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied. RESULTS: Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied. CONCLUSIONS: Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

Poststroke Care Pathways and Spasticity Treatment: A Retrospective Study in Alberta.

BACKGROUND: Limited evidence exists regarding care pathways for stroke survivors who do and do not receive poststroke spasticity (PSS) treatment. METHODS: Administrative data was used to identify adults who experienced a stroke and sought acute care between 2012 and 2017 in Alberta, Canada. Pathways of stroke care within the health care system were determined among those who initiated PSS treatment (PSS treatment group: outpatient pharmacy dispensation of an anti-spastic medication, focal chemo-denervation injection, or a spasticity tertiary clinic visit) and those who did not (non-PSS treatment group). Time from the stroke event until spasticity treatment initiation, and setting where treatment was initiated were reported. Descriptive statistics were performed. RESULTS: Health care settings within the pathways of stroke care that the PSS (n = 1,079) and non-PSS (n = 22,922) treatment groups encountered were the emergency department (86 and 84%), acute inpatient care (80 and 69%), inpatient rehabilitation (40 and 12%), and long-term care (19 and 13%), respectively. PSS treatment was initiated a median of 291 (interquartile range 625) days after the stroke event, and most often in the community when patients were residing at home (45%), followed by "other" settings (22%), inpatient rehabilitation (18%), long-term care (11%), and acute inpatient care (4%). CONCLUSIONS: To our knowledge, this is the first population based cohort study describing pathways of care among adults with stroke who subsequently did or did not initiate spasticity treatment. Areas for improvement in care may include strategies for earlier identification and treatment of PSS.

Disease-modifying therapy use and health resource utilisation associated with multiple sclerosis over time: A retrospective cohort study from Alberta, Canada.

BACKGROUND: Estimating multiple sclerosis (MS) prevalence and incidence, and assessing the utilisation of disease-modifying therapies (DMTs) and healthcare resources over time is critical to understanding the evolution of disease burden and impacts of therapies upon the healthcare system. METHODS: A retrospective population-based study was used to determine MS prevalence and incidence (2003-2019), and describe utilisation of DMTs (2009-2019) and healthcare resources (1998-2019) among people living with MS (pwMS) using administrative data in Alberta. RESULTS: Prevalence increased from 259 (95% confidence interval [CI]: 253-265) to 310 (95% CI: 304, 315) cases per 100,000 population, and incidence decreased from 21.2 (95% CI: 19.6-22.8) to 12.7 (95% CI: 11.7-13.8) cases per 100,000 population. The proportion of pwMS who received ≥1 DMT dispensation increased (24% to 31% annually); use of older platform injection therapies decreased, and newer oral-based, induction, and highly-effective therapies increased. The proportion of pwMS who had at least one MS-related physician, ambulatory, or tertiary clinic visits increased, and emergency department visits and hospitalizations decreased. CONCLUSIONS: Alberta has one of the highest rates of MS globally. The proportion of pwMS who received DMTs and had outpatient visits increased, while acute care visits decreased over time. The landscape of MS care appears to be rapidly evolving in response to changes in disease burden and new highly-effective therapies.

Incidence and prevalence, and medication use among adults living with dermatomyositis: an Alberta, Canada population-based cohort study.

Dermatomyositis is a rare disease characterized by progressive muscle weakness and skin rashes. Estimates of incidence and prevalence are fundamental measures in epidemiology, but few studies have been conducted on dermatomyositis. To address this knowledge gap, we conducted a population-based study to determine the contemporary incidence (between 2013 and 2019) and prevalence (2019) of adults living with dermatomyositis using administrative health data in Alberta, Canada. We also described disease-related medication use, as there are very few approved medications for the treatment of dermatomyositis, and no Canadian therapeutic guidelines. The average age- and sex-standardized annual incidence of dermatomyositis was 2.8-3.0 cases per 100,000 adults, and prevalence was 28.6 cases per 100,000 adults, which is greater than reported in other cohorts. Dermatomyositis-related medication use decreased from 73% in the first year to 46% in the eighth year after diagnosis. Glucocorticoids were the most commonly used drug class, often taken concurrently with various immunomodulatory agents; this medication use aligns with empirically-based recommendations and the few therapeutic guidelines for dermatomyositis. Considering that Alberta may have one of the highest rates of dermatomyositis among adults, further research on the burden of disease is warranted for planning within the health care system.

Understanding the Intrinsic Rectification Properties of Nanoporous Anodic Alumina by Selective Chemical Etching.

The distribution of oxygen and aluminum vacancies across the hemispherical barrier oxide layer (BOL) of nanoporous anodic alumina (NAA) relies intrinsically on the electric field-driven flow of electrolytic species and the incorporation of electrolyte impurities during the growth of anodic oxide through anodization. This phenomenon provides new opportunities to engineer BOL's inherited ionic current rectification (ICR) fingerprints. NAA's characteristic ICR signals are associated with the space charge density gradient across BOL and electric field-induced ion migration through hopping from vacancy to vacancy. In this study, we engineer the intrinsic space charge density gradient of the BOL of NAA under a range of anodizing potentials in hard and mild anodization regimes. Real-time characterization of the ICR fingerprints of NAA during selective etching of the BOL makes it possible to unravel the distribution pattern of vacancies through rectification signals as a function of etching direction and time. Our analysis demonstrates that the space charge density gradient varies across the BOL of NAA, where the magnitude and distribution of the space charge density gradient are revealed to be critically determined by anodizing the electrolyte, regime, and potential. This study provides a comprehensive understanding of the engineering of ion transport behavior across blind-hole NAA membranes by tuning the distribution of defects across BOL through anodization conditions. This method has the potential to be harnessed for developing nanofluidic devices with tailored ionic rectification properties for energy generation and storage and sensing applications.

Trajectory of health care resources among adults stopping or reducing treatment frequency of botulinum toxin for chronic migraine treatment in Alberta, Canada.

OBJECTIVE: Understand health resource, medication use, and cost of adults with chronic migraine who received guideline-recommended onabotulinumtoxinA (botulinum toxin) treatment frequency and then continued or reduced/stopped. BACKGROUND: Botulinum toxin may be a beneficial treatment for chronic migraine; the trajectory of health resources utilization among those with continued or reduced/stopped use is unclear. METHODS: A retrospective population-based cohort study utilizing administrative data from Alberta, Canada (2012-2020), was performed. A cohort of adults who received ≥5 botulinum toxin treatment cycles for chronic migraine over 18 months (6-month run-in; 1-year pre-index period) were grouped into those who (1) continued use (≥3 treatments/year), or (2) stopped or reduced use (stopped for 6 months then received 0 or 1-2 treatments/year, respectively) over a 1-year post-index period. Health resources and medication use were described, and pre-post costs were assessed. A second cohort that received ≥3 treatments/year immediately followed by 1 year of stopped or reduced use was considered in sensitivity analysis. RESULTS: Pre-post health resource, medication use, and costs were similar among those with continued use (n = 3336). Among those who stopped or reduced use (n = 1099; 756 stopped, 343 reduced), health resource, medication use, and costs were lower in the post- (total median per-person cost [IQR]: all-cause $4851 [$8090]; migraine-related $835 [$1915]) versus pre- (all-cause $6096 [$7207]; migraine-related $2995 [$1950]) index period (estimated cost ratios [95% CI]: total all-cause 0.86 [0.79, 0.95]; total migraine-related 0.44 [0.40, 0.48]). In the second cohort (n = 3763), return to continued use (≥3 treatments/year) occurred in up to 70.4% in those with reduced use. CONCLUSIONS: Of adults treated with botulinum toxin for chronic migraine, 75.2% had continued use, stable health resource and medication use, and costs over a 2 year period. In those that stopped/reduced use, the observed lower health resource and migraine medication use may indicate improved symptom control, but the resumption of guideline-recommended treatment intervals after reduced use was common.

Analgesic Use Among Adults with a Trauma-Related Emergency Department Visit: A Retrospective Cohort Study from Alberta, Canada.

INTRODUCTION: A better understanding of current acute pain-driven analgesic practices within the emergency department (ED) and upon discharge will provide foundational information in this area, as few studies have been conducted in Canada. METHODS: Administrative data were used to identify adults with a trauma-related ED visit in the Edmonton area in 2017/2018. Characteristics of the ED visit included time from initial contact to analgesic administration, type of analgesics dispensed during and upon being discharged home directly from the ED (≤ 7 days after), and patient characteristics. RESULTS: A total of 50,950 ED visits by 40,505 adults with trauma were included. Analgesics were administered in 24.2% of visits, of which non-opioids were dispensed in 77.0% and opioids were dispensed in 49.0%. Time to analgesic initiation occurred more than 2 h after first contact. Upon discharge, 11.5% received a non-opioid and 15.2% received an opioid analgesic, among whom 18.5% received a daily dose ≥ 50 morphine milligram equivalents (MME) and 30.2% received > 7 days of supply. Three hundred and seventeen adults newly met criteria for chronic opioid use after the ED visit, among whom 43.5% received an opioid dispensation upon discharge; of these individuals, 26.8% had a daily dose ≥ 50 MME and 65.9% received > 7 days of supply. CONCLUSIONS: Findings can be used to inform optimization of analgesic pharmacotherapy practices for the treatment of acute pain, which may include reducing the time to initiation of analgesics in the ED, as well as close consideration of recommendations for acute pain management upon discharge to provide ideal patient-centered, evidence-informed care.

Intelligent Healthcare: Integration of Emerging Technologies and Internet of Things for Humanity.

Health is gold, and good health is a matter of survival for humanity. The development of the healthcare industry aligns with the development of humans throughout history. Nowadays, along with the strong growth of science and technology, the medical domain in general and the healthcare industry have achieved many breakthroughs, such as remote medical examination and treatment applications, pandemic prediction, and remote patient health monitoring. The advent of 5th generation communication networks in the early 2020s led to the Internet of Things concept. Moreover, the 6th generation communication networks (so-called 6G) expected to launch in 2030 will be the next revolution of the IoT era, and will include autonomous IoT systems and form a series of endogenous intelligent applications that serve humanity. One of the domains that receives the most attention is smart healthcare. In this study, we conduct a comprehensive survey of IoT-based technologies and solutions in the medical field. Then, we propose an all-in-one computing architecture for real-time IoHT applications and present possible solutions to achieving the proposed architecture. Finally, we discuss challenges, open issues, and future research directions. We hope that the results of this study will serve as essential guidelines for further research in the human healthcare domain.

Assessment of medical waste generation rate in Viet Nam.

This study was conducted to estimate medical wastes generation rates in Viet Nam. Within 3 years (from 2017 to 2019), total medical wastes generated daily of 1,737 health-care facilities at different levels from 19/63 provinces in Viet Nam were surveyed. The calculation was based on the median daily generation (in kg) of 6 medical waste groups and total actual patient beds in 9 health-care facility categories. Six medical waste groups were sharps, non-sharps, high-risk infectious, pathological, non-infectious hazardous, recyclable and non-recyclable wastes. Surveyed health-care facilities were categorized in central general hospitals, central specialist hospitals, provincial general hospitals, provincial specialist hospitals, district health centers, regional clinics, commune health stations, private hospitals and private clinics. The results showed that waste generation rates varied from 0.0009 to 1.619 kg/bed/day depends on type of medical wastes or health-care facilities. For no-patient-bed facilities (commune health stations and private clinics), medical waste generation rates of these two were calculated in kg/day and varied from 0.1 to 1.75 kg/day.

Association of Individual and Neighborhood Characteristics to Problematic Internet Use among Youths and Adolescents: Evidence from Vietnam.

INTRODUCTION: This study aimed to determine latent profiles from the Problematic Internet Use Questionnaire Short Form-6 (PIUQ-SF-6) score of Vietnamese youths and adolescents, which supports the diagnosis of problematic internet use among a large sample size. Moreover, it also explored factors that affect each latent profile of the PIUQ-SF-6 score among participants. METHODS: A sample of 1477 Vietnamese people, aged 14 to 24, across five provinces participated in the study. Multinomial logistic regression determined factors related to the levels of the Problematic Internet Use Questionnaire Short Form-6 (PIUQ-SF-6) after using latent profile analysis. RESULTS: Participants were divided into three profiles, including those at low, moderate, and high risk of internet addiction. The high-risk latent profile was obtained for 23.1% of adolescents, and the remaining percentages were, respectively, 40.2% and 36.7% of adolescents belonging to the moderate and low-risk groups. Moreover, factors including age, living alone, high Kessler psychological distress scale, excessive time on the internet, living in central cities, and high neighborhood disorder scores were found to be related to moderate- and high-risk internet addiction profiles. CONCLUSIONS: Factors analyzed according to individual and social characteristics further explore the reasons underlying increasing internet addiction among Vietnamese youths and inform early interventions.

Associations between parent-child relationship, self-esteem, and resilience with life satisfaction and mental wellbeing of adolescents.

Purpose: Mental wellbeing and life satisfaction play an important role in the development of adolescents, yet factors potentially influencing these states have not been sufficiently studied, especially in Vietnam. This study aims to fill the research gaps by exploring the associations of the parent-child relationship, self-esteem, and resilience on the mental wellbeing and satisfaction with life of adolescents. Methods: A cross-sectional study was conducted from June to July 2020 on 1,023 adolescents from 10 to 18 years old living in Vietnam. To assess the satisfaction with life as well as the mental wellbeing of participants, this study used the Satisfaction with life and The World Health Organization-Five Wellbeing Index scale. Results: More than 70% of participants reported having conflicts with their parents (74.6% of those conflicted with their father ad 73.9% of those conflicted with their mother), while 26.3% stated dissatisfaction with life. The mean score of mental wellbeing was 61.5 (SD = 23.0). Higher academic performance, self-esteem, resilience, encounter loneliness and isolation within own family, and having support and sharing from family members had a positive effect on life satisfaction and mental wellbeing. Female participants had higher satisfaction with life score (Coef = 0.77; 95%CI = 0.10; 1.44) but they had a lower mental wellbeing score (Coef = -6.00; 95%CI = -8.57; -3.44) than male participants. High school students had lower both satisfaction with life and mental wellbeing scores than secondary students. Conclusion: The results highlight the importance of being aware of the influence that expectations (of higher grades) and bias (toward male children) imposed by parents, teachers, and society on the mental wellbeing of youths, especially in Asian cultures. Strengthening the family bond and encouraging young people to share their feeling is also crucial to enhancing the mental health condition of adolescents.

Factors Associated with the Breast Cancer Diagnostic Interval across Five Canadian Provinces: A CanIMPACT Retrospective Cohort Study.

The cancer diagnostic process can be protracted, and it is a time of great anxiety for patients. The objective of this study was to examine inter- and intra-provincial variation in diagnostic intervals and explore factors related to the variation. This was a multi-province retrospective cohort study using linked administrative health databases. All females with a diagnosis of histologically confirmed invasive breast cancer in British Columbia (2007-2010), Manitoba (2007-2011), Ontario (2007-2010), Nova Scotia (2007-2012), and Alberta (2004-2010) were included. The start of the diagnostic interval was determined using algorithms specific to whether the patient's cancer was detected through screening. We used multivariable quantile regression analyses to assess the association between demographic, clinical and healthcare utilization factors with the diagnostic interval outcome. We found significant inter- and intra-provincial variation in the breast cancer diagnostic interval and by screen-detection status; patients who presented symptomatically had longer intervals than screen-detected patients. Interprovincial diagnostic interval variation was 17 and 16 days for screen- and symptom-detected patients, respectively, at the median, and 14 and 41 days, respectively, at the 90th percentile. There was an association of longer diagnostic intervals with increasing comorbid disease in all provinces in non-screen-detected patients but not screen-detected. Longer intervals were observed across most provinces in screen-detected patients living in rural areas. Having a regular primary care provider was not associated with a shorter diagnostic interval. Our results highlight important findings regarding the length of the breast cancer diagnostic interval, its variation within and across provinces, and its association with comorbid disease and rurality. We conclude that diagnostic processes can be context specific, and more attention should be paid to developing tailored processes so that equitable access to a timely diagnosis can be achieved.

Correction: Rapid prediction of possible inhibitors for SARS-CoV-2 main protease using docking and FPL simulations.

[This corrects the article DOI: 10.1039/D0RA06212J.].

Determinants of mental health among youths and adolescents in the digital era: Roles of cyber and traditional bullying, violence, loneliness, and environment factors.

Introduction: Although the pathogenesis of depressive disorders is not fully elucidated, untreated adolescent depression can lead to serious sequelae such as impaired academic performance and social functioning, substance use disorders, poor self-esteem, and increased risk for suicidal ideation and attempts. Literature on adolescent mental health in Vietnam is limited, despite increased international awareness of this critical issue. This study aimed to investigate the prevalence and associations of depressive symptoms in Vietnamese adolescents. Methods: A cross-sectional, self-administered survey was conducted in five provinces of Vietnam among adolescents aged 14 to 24 years. In addition to collecting participants' demographics, a structured questionnaire was developed to examine depressive symptoms, suicidal ideation, loneliness, and cyberbullying victimization. Depressive symptoms and loneliness were assessed via the PHQ-9 and UCLA Loneliness Scale, respectively. Two-tailed Chi-squared, Mann-Whitney, and Kruskal-Wallis tests were performed to examine associations between variables. Multivariate Logistic regression models were conducted to examine the associations between prior-defined variables and positive depressive symptoms. Results: Among 1,600 respondents, 31.8% of participants reported having mild-moderate or severe depressive symptoms. Participants within the moderate-severe depressive symptom group had significantly lower community cohesion scores than those of participants in normal and mild depressive symptom groups (p < 0.05). Youths living alone were more likely to have moderate-severe depressive symptoms (OR 2.16; 95% CI: 1.09-4.25). Cyberbullying had significant associations with depressive severity (OR 1.93; 95% CI 1.38-2.70). Conclusion: The findings of this study characterize various risk and protective factors for depression in Vietnamese youths and adolescents. The results highlight the importance of raising awareness and increasing access to educational resources for depression and other mental health illnesses. With the rising prevalence of depression, parents, teachers, and community leaders play a vital role in addressing mental health problems in adolescents.

The Association between Peptic Ulcer Disease and Gastric Cancer: Results from the Stomach Cancer Pooling (StoP) Project Consortium.

BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. METHODS: History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth's penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. RESULTS: History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07-4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77-1.39). CONCLUSIONS: In the pooled analysis of 11 case-control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.

Distal Hydrophobic Loop Modulates the Copper Active Site and Reaction of AA13 Polysaccharide Monooxygenases.

Polysaccharide monooxygenases (PMOs) use a type-2 copper center to activate O2 for the selective hydroxylation of one of the two C-H bonds of glycosidic linkages. Our electron paramagnetic resonance (EPR) analysis and molecular dynamics (MD) simulations suggest the unprecedented dynamic roles of the loop containing the residue G89 (G89 loop) on the active site structure and reaction cycle of starch-active PMOs (AA13 PMOs). In the Cu(II) state, the G89 loop could switch between an "open" and "closed" conformation, which is associated with the binding and dissociation of an aqueous ligand in the distal site, respectively. The conformation of the G89 loop influences the positioning of the copper center on the preferred substrate of AA13 PMOs. The dissociation of the distal ligand results in the bending of the T-shaped core of the Cu(II) active site, which could help facilitate its reduction to the active Cu(I) state. In the Cu(I) state, the G89 loop is in the "closed" conformation with a confined copper center, which could allow for efficient O2 binding. In addition, the G89 loop remains in the "closed" conformation in the Cu(II)-superoxo intermediate, which could prevent off-pathway superoxide release via exchange with the distal aqueous ligand. Finally, at the end of the reaction cycle, aqueous ligand binding to the distal site could switch the G89 loop to the "open" conformation and facilitate product release.

Magnifying Chromoendoscopy with Flexible Spectral Imaging Color Enhancement, Indigo Carmine, and Crystal Violet in Predicting the Histopathology of Colorectal Polyps: Diagnostic Value in a Scare-Setting Resource.

Background and Aims: Virtual magnifying chromoendoscopy with flexible spectral imaging color enhancement (FICE), image-enhanced endoscopy techniques, and dye-staining magnifying chromoendoscopy (with Indigo carmine and Crystal violet) have contributed to better visualization of the pit pattern and vascular structure of colorectal polyp. Therefore, magnifying chromoendoscopy is capable of predicting the histopathological results of colorectal polyp without biopsy and remains their diagnostic values over time, especially in scare-setting resources. This study compared the images of magnifying chromoendoscopy between FICE, Indigo carmine, and Crystal violet and then assessed their diagnostic values based on colorectal polyps' histopathology as a gold standard. Methods: A total of 332 polyps of 266 patients were endoscopically evaluated from June 2016 to September 2019. After identified by white light endoscopy, polyps continued to be evaluated by virtual magnifying chromoendoscopy (×50-150 times) with FICE. The capillary-vessel pattern was divided into 5 subtypes according to the number, morphology, and distribution of the fine blood vessels according to Teixeira classification. Next, they were stained with Indigo carmine 0.2% and then Crystal violet 0.05% and were classified according to Kudo's pit pattern classification. Finally, polyps were resected by endoscopy or surgery and biopsy and compared with histopathological results of either neoplastic or nonplastic polyp. Results: The number of neoplastic polyps was 278/332 with 231 adenoma polyps and 47 carcinoma polyps. Magnifying chromoendoscopy has high sensitivity and accuracy when compared with the histopathological results of colorectal polyps. The sensitivity, specificity, and accuracy of magnifying chromoendoscopy with Crystal violet are 97.2%, 72.2%, and 93.0%; with Indigo carmine are 96.0%, 72.2%, and 92.1%; and with FICE are 92.1%, 68.5%, and 88.3%. Conclusions: Among the three methods, Crystal violet has the highest sensitivity and accuracy in predicting histopathological results of colorectal polyps. FICE has shown its diagnostic value with reliable sensitivity and accuracy and should still be a reasonable endoscopic choice for physicians in scare-setting resources regardless its moderate specificity. Physicians should base on their facility and capability to determine an appropriate endoscopy technique.

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia. METHODS: This retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods. RESULTS: Among 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p < 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 [SD $68,887] versus $74,131 [SD $75,941]), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 [SD $63,428] versus $68,403 [SD $72,088]) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status. CONCLUSIONS: SGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.

Molecular docking and molecular dynamics approach to identify potential compounds in Huperzia squarrosa for treating Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is a lingering progressive neurodegenerative disorder that causes patients to lose cognitive function. The enzyme Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Monoamine oxidase A (MAO A), Beta-secretase cleavage enzyme (BACE 1) and N-methyl-D-aspartate (NMDA) receptors play an important role in the pathogenesis of Alzheimer's disease. Therefore, inhibiting enzymes is an effective method to treat Alzheimer disease. In this study, we evaluated in silico inhibitory effects of AChE, BuChE, MAO A, BACE 1 and NMDA enzyme of Huperzia squarrosa's compounds. METHODS: The three-dimensional (3D) of N-methyl-D-aspartate receptor (PDB ID: 1PBQ), enzyme ß-secretase 1 (PDB ID: 4X7I), enzyme monoamine oxidase A (PDB ID: 2Z5X), enzyme butyrylcholinesterase (PDB ID: 4BDS) and enzyme acetylcholinesterase (PDB ID: 1EVE) were retrieved from the Protein Data Bank RCSB. Molecular docking was done by Autodock vina software and molecular dynamics (MD) simulation of the ligand-protein complex with the least binding energy pose was perfomed by MOE. Lipinski Rule of Five is used to compare compounds with drug-like and non-drug-like properties. Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. RESULTS: Based on previous publication of Huperzia squarrosa, we have collected 15 compounds. In these compounds, huperzine B, huperzinine, lycoposerramine U N-oxide, 12-epilycodine N-oxide showed strongly inhibit the five AChE, BuChE, MAO A, BACE 1 and NMDA targets for Alzheimer's treatment. Lipinski rule of five and ADMET predict have shown that four above compounds have drug-likeness properties, good absorption ability and cross the blood-brain barrier, which have the most potential to become drugs for the treatment of Alzheimer's in the future. Furthermore, MD study showed that huperzine B and huperzinine have stability of the docking pose with NMDA target. CONCLUSIONS: In this study, we found two natural compounds in Huperzia squarrosa including Huperzine B and Huperzinine have drug-likeness properties, good absorption ability and cross the blood-brain barrier, which have potential to become drugs for the treatment of Alzheimer's in the future.

Isolation of indole-3-acetic acid-producing Azospirillum brasilense from Vietnamese wet rice: Co-immobilization of isolate and microalgae as a sustainable biorefinery.

Production of indole-3-acetic acid (IAA) is well documented in various studies for the bacteria that inhabit the rhizosphere of plants, but with roots of wet rice, the outstandings have been not yet elucidated. This study began with the isolation of bacteria type strain Azospirillum sp. and developed the investigation to a screening of their ability in IAA production. This screening conducted a selection of only bacteria that was capable of the production of IAA with its content of over 25 µg. mL-1 for sequencing. Of 10 isolates only one resulted from the type strain Azospirillum brasilense (A. brasilense) with a similarity of 100%. Various factors that influence A. brasilense in biosynthesizing IAA such as temperature, pH, nitrogen presence and concentration of tryptophan in the culture medium were examined. The results indicated that the culture conditions were suitable for IAA biosynthesis at pH 6.5, 30 °C, culture media with nitrogen, and 0.1% trytophan. The next survey on the role of the immobilization of this bacteria with microalgae in alginate was highlighted to its support in microalgal growth. With the co-immobilization of bacteria and microalgae, the density of Chlorella vulgaris was significantly increased during 15-day culture, inducing 2.2 times of cell content in culture batch microalgae immobilized A. brasilense higher than that free-bacteria.