Immunopathological investigation and genetic evolution of Avian leukosis virus Subgroup-J associated with myelocytomatosis in broiler flocks in Egypt.

BACKGROUND: Avian leukosis virus Subgroup-J (ALV-J) is a rapidly oncogenic evolving retrovirus infecting a variety of avian species; causing severe economic losses to the local poultry industry. METHODS: To investigate ALV-J, a total of 117 blood samples and 57 tissue specimens of different organs were collected for virological, and pathological identification, serological examinations, molecular characterization, and sequencing analysis. To the best of our knowledge, this is the first detailed report recorded in broiler flocks in Egypt. The present study targets the prevalence of a viral tumor disease circulating in broiler flocks in the El-Sharqia, El-Dakahliya, and Al-Qalyubiyya Egyptian governorates from 2021 to 2023 using different diagnostic techniques besides ALV-J gp85 genetic diversity determination. RESULT: We first isolated ALV-J on chicken embryo rough cell culture; showing aggregation, rounding, and degeneration. Concerning egg inoculation, embryonic death, stunting, and curling were observed. Only 79 serum samples were positive for ALV-J (67.52%) based on the ELISA test. Histopathological investigation showed tumors consist of uniform masses, usually well-differentiated myelocytes, lymphoid cells, or both in the liver, spleen, and kidneys. Immunohistochemical examination showed that the myelocytomatosis-positive signals were in the spleen, liver, and kidney. The PCR assay of ALV-J gp85 confirmed 545 base pairs with only 43 positive samples (75.4%). Two positive samples were sequenced and submitted to the Genbank with accession numbers (OR509852-OR509853). Phylogenetic analysis based on the gp85 gene showed that the ALV-J Dakahlia-2 isolate is genetically related to ALV-EGY/YA 2021.3, ALV-EGY/YA 2021.4, ALV-EGY/YA 2021.14, and ALV-EGY/YA 2021.9 with amino acid identity percentage 96%, 97%; 96%, 96%; respectively. Furthermore, ALV-J Sharqia-1 isolate is highly genetically correlated to ALV-EGY/YA 2021.14, and ALV-EGY/YA 2021.9, ALV-J isolate QL1, ALV-J isolate QL4, ALV-J isolate QL3, ALV-EGY/YA 2021.4 with amino acid identity percentage 97%, 97%; 98%, 97%, 97%, 95%; respectively. CONCLUSIONS: This study confirmed that ALV-J infection had still been prevalent in broilers in Egypt, and the genetic characteristics of the isolates are diverse.

Treatment Satisfaction Among Bahraini Patients With Psoriasis: A Single Center Cross-Sectional Study Using the PsoSat Questionnaire.

INTRODUCTION: Psoriasis has a considerable negative impact on a patient's life. However, the treatment prescribed plays a crucial role in their quality of life. Treatment satisfaction is one of the fundamental elements when it comes to patient care for psoriasis (PsO). Dermatologists, just like any other healthcare physician, seek adherence to a specific treatment, and it has been shown that satisfaction influences treatment optimization and thereby the treatment outcome. METHODS: This was an observational cross-sectional study conducted to determine patient satisfaction with therapy and treatment of psoriasis. The final psoriasis satisfaction (PsoSat) questionnaire consisted of eight affirmations concerning treatment satisfaction. Each affirmation was rated by the patient on a 5-point Likert scale (0-4), indicating poor to perfect satisfaction levels. The study involved patients visiting the outpatient department of a multi-specialty medical complex in Bahrain, or patients contacted via teledermatology, between October 2019 and February. A total of 100 patients who were willing to participate in the survey and fulfilled the inclusion criteria, were considered. RESULTS: Most of the patients (89%) were moderately to very satisfied with their ongoing therapy. One patient was not satisfied with the treatment, and 10 (10%) patients reported that they were very dissatisfied with their treatment. CONCLUSION: Since psoriasis can negatively impact a patient's quality of life, treatment satisfaction is an essential factor when it comes to patient care. Dermatologists are always on the lookout for specific treatments that provide excellent results and satisfy a patient's needs.

The effect of different orthodontic mini-implant brands and geometry on primary stability (an in vitro study).

Background: In orthodontic procedures, mini-implants are routinely used as temporary anchorage devices. Early failure is primarily attributed to a variety of issues, which are mostly connected to the quality and geometry of the screw that lead to insufficient primary stability. Objectives: To evaluate the primary stability of different sizes and brands of orthodontic mini-implants by optimizing the insertion torque value (ITV) and to clear out which one has the greatest primary stability among the most widely used mini-implants by orthodontists. Methods: Eighty-two self-drilling mini-implants from three different brands with different sizes were used (Optimus Ortho System (Osteonic made in Korea), Smart anchor (GNI made in Korea) (1.4 × 6, 1.6 × 8 and 1.8 × 10mm) and Morelli (made in Brazil) (1.5 × 6, 1.5 × 8 and 1.5 × 10mm), made from (Ti 6Al 4V). All were drilled at a 60° angle on Sixty artificial bone blocks made from polyurethane foam with a digital torque meter device (Orthonia, Jeil made in Korea), pullout strength (tensile force) was measured with a universal testing machine to find out the best brand and size in the mean of primary stability. Data were analyzed using SPSS Version 25 and JMP Pro Version 16 software using the One-way ANOVA test, the Post hoc and Tukey HCD tests. Results: There were significant differences between the pullout strength of different sizes for the GNI and OSTEONIC brands, while for the MORELLI brand there were no significant differences between the three different sizes considering ITV (10Ncm) whereas for ITV (20Ncm) there was a significant difference between the different sizes for the pullout of all three brands. GNI was the best brand for all the selected sizes with ITV (10Ncm) and size 1.4 × 6 for ITV (20Ncm), whereas OSTEONIC sizes 1.6 × 8 and 1.8 × 10 were the best for ITV (20Ncm) in term of primary stability. Conclusion: GNI screws were demonstrated higher primary among the three widely used brands followed by OSTEONIC for size 1.6 × 8 and 1.8 × 10 while MORELLI was the least resistant to dislodgement for the two torque insertion values 10 N/cm and 20 N/cm.

A Retrospective Database Analysis to Investigate Treatment Patterns and Health Care Resource Utilisation in Patients who CYCLe AntiMuscarinics in ENgland (CYCLAMEN).

BACKGROUND: Patients with overactive bladder may cycle through different antimuscarinic medications even though there is limited evidence to support this approach. OBJECTIVE: To describe treatment patterns and the associated health care resource utilisation (HCRU) according to antimuscarinic cycling groups. DESIGN, SETTING, AND PARTICIPANTS: The CYCLe AntiMuscarinics in ENgland (CYCLAMEN) study was a retrospective observational investigation that used primary care records from the Clinical Practice Research Datalink GOLD database linked to Hospital Episode Statistics secondary care data. Eligible patients (≥18 yr) were prescribed their first antimuscarinic between January 2014 and December 2017. Patients were categorised into groups prescribed one, two, or three or more (groups 1-3) consecutive unique antimuscarinics over 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The HCRU rate and costs were calculated for the period of continuous antimuscarinic therapy (first antimuscarinic treatment episode) and the 18-mo follow-up period. Treatment sequence patterns were displayed using sunburst plots and Kaplan-Meier analysis was used to assess time on treatment. RESULTS AND LIMITATIONS: Overall, 35 369 patients were included, of whom 31 760 (89.8%) received one antimuscarinic (group 1), 3182 (9.0%) received two (group 2), and 427 (1.2%) received three or more (group 3). The most common initial antimuscarinics were solifenacin (13 628 patients, 42.9%) in group 1, and oxybutynin in group 2 (1267 patients, 39.8%) and group 3 (200 patients, 46.8%). The median duration of the first antimuscarinic treatment episode was 57 d and <20% of patients were receiving any antimuscarinic after 18 mo. The number of primary care visits and mean costs increased across groups. The reasons for cycling could not be identified in this study. CONCLUSIONS: Approximately 10% of patients underwent sequential cycling with two or more antimuscarinics. Furthermore, as the majority discontinued treatment within 18 mo, there is a need to improve the management of these patients in the clinical care setting. PATIENT SUMMARY: We investigated treatment patterns and health care use for patients with overactive bladder who were prescribed at least one antimuscarinic drug (AMD), which are drugs that reduce some of the impulses passing from the bladder to the brain. Around 10% of patients accessing primary health care in England received more than one sequential AMD. Most patients discontinued treatment, which may indicate inadequate management of their condition. Prescription of a higher number of AMDs was associated with higher health care costs.

Development of a health economic model to evaluate the cost-effectiveness of roxadustat in treating anemia associated with non-dialysis-dependent chronic kidney disease.

BACKGROUND: Treatment for anemia of chronic kidney disease (CKD) largely consists of erythropoiesis-stimulating agents (ESAs) with iron supplementation. Although ESAs are well-established and efficacious, their use has been associated with considerable economic and humanistic burdens. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that targets multiple causes of CKD and has a similar efficacy and safety profile to ESAs. The cost-effectiveness of this treatment, however, has yet to be investigated. OBJECTIVE: The study objective was to develop a health economic model to evaluate the cost-effectiveness of roxadustat compared with ESAs for treating anemia of non-dialysis-dependent (NDD) CKD. METHODS: A cohort-based model was developed for a hypothetical cohort of 1,000 patients with anemia of NDD CKD, incorporating eight health states, representing the hemoglobin level of each patient. The model was informed by individual patient-level data from the roxadustat global phase 3 clinical trial program. Total and incremental costs as well as quality-adjusted life-years (QALYs) associated with roxadustat versus ESAs were estimated from the perspective of the UK National Health Service. Sensitivity analyses were performed to assess the robustness of the model. Analyses exploring alternative scenarios were also conducted. RESULTS: On a per-person basis, over 1,000 simulations, roxadustat was found to be on average less costly (-£32) and more effective (+0.01 QALYs) than ESAs, with a dominant incremental cost-effectiveness ratio. The probability of cost-effectiveness at a £20,000 per QALY willingness-to-pay threshold from the UK perspective was 67%. CONCLUSION: The model developed may be a useful instrument that, alongside expert clinical opinion, can inform clinical and policy decision-making regarding treatment of anemia of NDD CKD. The model highlights the cost-effectiveness of roxadustat, as well as its potential to have a meaningful impact in reducing the burden of anemia of NDD CKD.

Vaping and Mental Health Conditions in Children: An Umbrella Review.

The e-cigarette (EC) epidemic began in the United States (US) in 2007; since 2014 EC is the most commonly used form of tobacco. However, the mental health implications of vaping are grossly unknown. The aim of this umbrella review is to provide astate-of-the-art summary of existing research concerning vaping and mental health conditions in children. Following the PRISMA Statement 2020 guidelines, a systematic search was conducted across PubMed, Cochrane Library, and Google Scholar up to April 15th, 2022 to locate relevant studies. The Joana Briggs Institute (JBI) methodology for umbrella reviews and quality appraisal tool was utilized. Six studies, pooling a total of 846,510 adolescents aged 21 years or below, were included by collating 85 primary clinical studies. Of these, 58.8% of the primary clinical studies originated in the US, with 4.7% from Canada, South Korea, and the United Kingdom each; 3.5% each from England and Taiwan; 2.4% each from Australia, France, Hawaii, Mexico, and Russia; and 1.2% each from Denmark, Greece, Hong Kong, Iceland, New Zealand, Poland, and Switzerland. Overall, significant associations were found between mental health outcomes, including depression and suicidality, among current EC users and those who had ever used EC. Compared to adolescents who had never used EC, both depression and anxiety were reportedly higher among EC users. Impulsive behaviors, reported as impulsivity, were also found to be correlated with the adoption of EC use. However, there is a lack of evidence regarding the impact of EC use on mental health outcomes in children. This umbrella review highlights the urgent need to further explore the effects of current EC use from a psychiatric and public health perspective.

Azilsartan suppresses the antiapoptotic biomarker and pro-inflammatory cytokines in rat model of cisplatin-induced retinal and optic nerve toxicity.

BACKGROUND: The local renin-angiotensin system has been discovered in the eyes; thus, this study evaluates the Azilsartan effect in the retina and optic nerve toxicity induced by Cisplatin in vivo. METHODOLOGY: Forty-eight male rats were randomly assigned into six groups of 8 animals. Group 1 was healthy control that received 0.5 mL/day of 0.5% carboxymethyl cellulose (CMC) orally (PO). Group 2 received a single dose of the 7.0 mg/kg CIS intraperitoneally with 0.5 mL/day of 0.5% CMC-PO. Groups 3 and 4 received 3.5 and 7.0 mg/kg/day of AZIL-PO, respectively. Groups 5 and 6 received 3.5 and 7.0 mg/kg/day of AZIL-PO, respectively together with a single dose of 7.0 mg/kg of CIS-IP. The ocular tissue and serum estimated the TNF-α, NF-kß, and Casp-3. A complete blood count was also measured, and the eye was sent for histological examination. RESULTS: The administration of the 3.5 mg/kg AZIL significantly (p < 0.05) reduced the ocular tissue and serum TNF-α, NF-kB, and Casp-3 levels, when given to CIS treated group, while the 7.0 mg/kg AZIL does not. Additionally, azilsartan shows no negative impact on the CBC in rats. Finally, the eye histological examination showed a significant (p < 0.05) drop in the signs of inflammation and cellular degeneration, particularly after administration of the 3.5 mg/kg AZIL to the CIS-treated group. CONCLUSION: A low dose of AZIL exerts an anti-inflammation and an anti-apoptotic effect through significant suppression of the pro-inflammatory mediators and an apoptotic biomarker by blocking the local angiotensin II type.

In-vivo inhibition of latanoprost induced iridal hyperpigmentation in rabbits- An investigational study.

Objectives: To evaluate the inhibitory effects of different concentrations of α-methyl-DL-tyrosine on latanoprost-induced iridal hyperpigmentation in rabbits. Methods: We investigated 4 groups of rabbits. Both eyes of the pink, red, and blue groups were treated with latanoprost followed by 0.5%, 1%, and 2% α-methyl-DL-tyrosine (inhibitor) in the right eyes respectively and the green group received only inhibitor. We prospectively investigated the irides, estimated quantitatively total melanin contents, and studied any histopathological changes that occurred. Results: The observers favored hyperpigmentation in the left eyes while in the right eyes they noted a decrease in pigmentation as compared to the baseline. An increase in pigmentation was noted by 93.33% of observers in the left eye of the blue group. A significant difference in the mean melanin contents was noted in the blue group (Right eye = 09.560 µg/g (±0.750), Left eye = 3.730 µg/g (±1.062). There was no evidence of stromal malignant changes, Hemorrhage, mitosis, inflammation, and atypical melanocytes in all specimens. A moderate degree of pigmentation in the left eye of the red group was noted. Mild stromal-free melanin pigment was present in all samples of pink, red and blue groups. Conclusions: The α-methyl-DL-tyrosine significantly inhibited latanoprost-induced iridal pigmentation without causing any histopathological changes at a 2% dose.

Critical success factor based resource allocation in ERP implementation: A nonlinear programming model.

This research examines how a Constrained Nonlinear programming model for ERP implementation (CNL_ERP) can facilitate Small and medium sized enterprises (SMEs) to deploy resources to address the Critical Success Factors (CSFs) in the pre-implementation phase, and to invest in them during implementation to increase the probability that the implementation will be successful. Applications of CNL_ERP in three case studies demonstrate that the average ERP implementation outcomes outperform the observed results. Using the Generalised Reduced Gradient Method, we developed an ERP implementation strategy realising resource allocation to CSFs. The strategy provides a rich picture of where to concentrate effort in the initial, intermediate and final phases, and is very helpful in enabling an SME to understand the progress of an ERP project and the resources needed. In case there are changes in resources (such as budget, team performance), the model enables SMEs to rank CSFs, and to adjust resources allocations accordingly to achieve the best ERP implementation performance.

A Rare Case Report: Five Variants of Lichen Planus in a Young Male Patient.

Lichen planus is a common dermatological condition. It is described as a chronic inflammatory mucocutaneous disease that has characteristic clinical and histopathological findings. Classical lichen planus lesions occur as purple, pruritic polygonal papules or plaques with a lace-like pattern of whitish markings on the surface. Despite the large number of variants that exist with different clinical manifestations from the classic form, histopathology features are fairly similar among the subtypes and can aid in the diagnosis. Although most cases of lichen planus are often self-limiting with spontaneous resolution expected within one to two years, early diagnosis and treatment are encouraged to control severe pruritus and painful mucosal erosion, but most importantly to minimize the potential for malignant transformation in long-standing lesions. The main objective of this paper is to report the first case of five cutaneous variants of lichen planus occurring simultaneously in a young male patient.

Prompt Detection and Management of Globe Perforation due to Retrobulbar Anaesthesia.

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Rule Similarity and Axis Symmetry Patterns in Young Patients with Bilateral Astigmatism.

OBJECTIVE: To report rule similarity and axis symmetry patterns in young subjects with bilateral astigmatism. METHODS: The cross-sectional study was conducted at Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from October 1, 2018, to March 31, 2019, and comprised diagnosed cases of bilateral astigmatism of either gender aged 15-45 years. After giving detailed ophthalmic history, all the participants underwent autorefraction followed by subjective refraction. Based on refractive status, rule similarity was categorised as isorule or anisorule, while axis symmetry was categorised as direct or mirror. Data was analysed using SPSS 20. RESULTS: Of the 204 participants, 128(62.7%) were males and 76(37.3%) were females. The overall mean age was 26.64±8.44 years. Isorule astigmatism was present in 169(82.8%) participants, while 125(61.3%) had a mirror pattern of axis symmetry. Under the mirror and direct symmetry models, the medians of absolute difference in the axis of fellow eyes were 10 and 5 degrees respectively from exact symmetry. No significant association of rule similarity or symmetry of axis was found with age or gender (p>0.05), while significant association was found between rule similarity and type of astigmatism (p<0.001). CONCLUSIONS: Bilateral astigmatism of isorule category was found in majority of the participants, while mirror symmetry of the axis was more common than direct symmetry.

The use of mono- and combination drug therapy in men and women with lower urinary tract symptoms (LUTS) in the UK: a retrospective observational study.

BACKGROUND: Combination drug therapy for lower urinary tract symptoms (LUTS) is beneficial to selected patients and recommended by guidelines. Patterns of real-world LUTS drug use, especially combination drug therapy, have not been studied extensively. Moreover, further understanding of the recent landscape is required following the introduction of the beta-3-adrenoceptor agonist mirabegron in the UK in 2013 for overactive bladder (OAB). The objective was to describe mono- and combination drug therapy use for LUTS in patients in UK clinical practice. METHODS: This was a retrospective, descriptive, observational database study using UK Clinical Practice Research Datalink GOLD and linked databases. Men and women ≥ 18 years with a first prescription for any LUTS drug from 2014 to 2016 with ≥ 12 months continuous enrollment pre- and post-index date were included. Primary endpoints were mono- or combination drug therapy use for LUTS in male and female cohorts. Secondary endpoints were description of treatment prescribed, treatment persistence and patient demographics. Data were analyzed descriptively. Sub-cohorts were defined by drugs prescribed at index date. RESULTS: 79,472 patients (61.3% male) were included, based on index treatments. Of all men, 82.5% received any benign prostatic obstruction (BPO) drug, 25.4% any OAB drug, and 7.9% any BPO drug plus any OAB drug. As either mono- or combination drug therapy, 77.1% received an alpha-blocker, 18.9% a 5-alpha reductase inhibitor, 23.9% an antimuscarinic agent, and 2.1% mirabegron. Of all women, 94.5% received any OAB drug, 6.0% duloxetine, and 0.5% any OAB drug plus duloxetine. As either mono- or combination drug therapy, 87.7% received an antimuscarinic, and 9.7% mirabegron. In men or women receiving OAB treatment, approximately 2.5% received combination drug therapy with an antimuscarinic agent and mirabegron. For OAB drug monotherapies, mirabegron had the highest persistence in both male and female cohorts. CONCLUSIONS: This study provides a better understanding of the recent landscape of LUTS drug use in UK clinical practice. It highlights potential undertreatment of storage symptoms in men with LUTS and the low use of combination OAB treatments.

Anticholinergic Burden and Associated Healthcare Resource Utilization in Older Adults with Overactive Bladder.

BACKGROUND: Bladder anticholinergics are the most widely used drugs to treat overactive bladder (OAB) but can contribute to cumulative anticholinergic burden, which may be associated with adverse outcomes. OBJECTIVE: This study aimed to evaluate the association between cumulative anticholinergic burden and healthcare resource utilization (HRU) and costs in older adults with OAB. MATERIALS AND METHODS: This was a retrospective, observational study that used data from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Participants were aged ≥ 65 years with ≥ 3 years of continuous enrolment before and ≥ 2 years after the index date (date of OAB diagnosis or first prescription for any OAB drug between 1 April 2007 and 31 December 2015). The primary endpoint was the association between cumulative anticholinergic burden (assessed using the Anticholinergic Cognitive Burden [ACB] scale during the 3-year pre-index period) and HRU (GP consultations, specialist referrals, urological tests, hospital admissions) over the 2-year post-index period. RESULTS: Data from 23,561 adults were included in the analysis. Mean (SD) ACB scores in the pre- and post-index periods were 1.0 (1.1) and 2.4 (1.7), respectively; urological drugs contributed most (58.8%) to the latter. For the primary endpoint, higher pre-index ACB scores were associated with higher post-index HRU and costs. Mean (SD) ACB scores in the post-index period were 1.2 (1.3) and 2.5 (1.7) in those treated with mirabegron (beta-3 agonist) or bladder anticholinergics, respectively. LIMITATIONS: The generalizability of the results outside the UK is unclear. CONCLUSIONS: In older adults with OAB, higher anticholinergic burden before initiating OAB drugs is associated with higher HRU and costs. When making treatment decisions in older adults, consideration should be given to assessing the existing anticholinergic burden and using OAB treatments that do not add to this burden.

Utility of teleconsultation in accessing eye care in a developing country during COVID-19 pandemic.

OBJECTIVE: To evaluate the utility of teleconsultation in the provision of eye care services during the COVID-19 lockdown. Disparities in the consultation burden of sub-specialities and socio-demographic differences in teleconsultation utilization were also assessed. METHODS: Al-Shifa Trust Eye Hospital Rawalpindi began audio and video teleconsultation using broadband telecommunication services during the lockdown. Patients' and consultations' data gathered during the first three weeks after the commencement of this programme were compared with data from the four weeks prior to lockdown. The weekly consultation ratio and overall consultation burden of sub-specialities were measured. Chi-Square tests of association determined the relationship between different variables (socioeconomic status and consultation characteristics) and consultation modality (on-site vs online). RESULTS: In total, 17507 on-site consultations (4377/week) were conducted compared to 1431 teleconsultations (477/week), which maintained 10.89% of the weekly pre-lockdown eye care services. The post-lockdown teleconsultation programme saw a relatively higher percentage of service utility among female (47.09% vs 44.71%), younger-age (31.33±19.45 vs 41.25±23.32 years) and higher-socioeconomic-status (32.21% vs 0.30%) patients compared to pre-lockdown on-site consultations. The most common indication for teleconsultation was red-eye (16.70%). While cornea and glaucoma clinics maintained most of the pre-lockdown services (30.42% and 29% respectively), the highest dropout was seen in optometric and vitreoretinal services supporting only 5.54% and 8.28% of pre-lockdown services, respectively. CONCLUSION: Digital initiatives could partially maintain eye care services during the lockdown. Focused strategies to improve teleconsultation utilization are required during the pandemic and beyond.

Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study.

Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shape-based screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness. Communicated by Ramaswamy H. Sarma.

Impact of a Pharmacist-Led Intensive Care Unit Sleep Improvement Protocol on Sleep Duration and Quality.

BACKGROUND: Sleep improvement protocols are recommended for use in the intensive care unit (ICU) despite questions regarding which interventions to include, whether sleep quality or duration will improve, and the role of pharmacists in their development and implementation. OBJECTIVE: To characterize the impact of a pharmacist-led, ICU sleep improvement protocol on sleep duration and quality as evaluated by a commercially available activity tracker and patient perception. METHODS: Critical care pharmacists from a 40-bed, mixed ICU at a large community hospital led the development and implementation of an interprofessional sleep improvement protocol. It included daily pharmacist medication review to reduce use of medications known to disrupt sleep or increase delirium and guideline-based recommendations on both environmental and nonpharmacological sleep-focused interventions. Sleep duration and quality were compared before (December 2018 to December 2019) and after (January to June 2019) protocol implementation in non-mechanically ventilated adults using both objective (total nocturnal sleep time [TST] measured by an activity tracker (Fitbit Charge 2) and subjective (patient-perceived sleep quality using the Richards-Campbell Sleep Questionnaire [RCSQ]) measures. RESULTS: Groups before (n = 48) and after (n = 29) sleep protocol implementation were well matched. After protocol implementation, patients had a longer TST (389 ± 123 vs 310 ± 147 minutes; P = 0.02) and better RCSQ-perceived sleep quality (63 ± 18 vs 42 ± 24 mm; P = 0.0003) compared with before implementation. CONCLUSION AND RELEVANCE: A sleep protocol that incorporated novel elements led to objective and subjective improvements in ICU sleep duration and quality. Application of this study may result in increased utilization of sleep protocols and pharmacist involvement.

Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus.

Design and development of an effective drug to combat the 2019 novel coronavirus remains a challenge. Therefore, it is of interest to study the binding features of 1615 FDA approved drugs with the recently known 2019-nCoV main protease structure having high sequence homology with that from SARS-CoV. We document the binding features of top 10 drugs with the target protein. We further report that Conivaptan and Azelastine are mainly involved in hydrophobic interactions with active site residues. Both drugs can maintain close proximity to the binding pocket of main protease during simulation. However, these data need further in vitro and in vivo evaluation to repurpose these two drugs against 2019-nCoV.

Characterisation of ICU sleep by a commercially available activity tracker and its agreement with patient-perceived sleep quality.

BACKGROUND: A low-cost, quantitative method to evaluate sleep in the intensive care unit (ICU) that is both feasible for routine clinical practice and reliable does not yet exist. We characterised nocturnal ICU sleep using a commercially available activity tracker and evaluated agreement between tracker-derived sleep data and patient-perceived sleep quality. PATIENTS AND METHODS: A prospective cohort study was performed in a 40-bed ICU at a community teaching hospital. An activity tracker (Fitbit Charge 2) was applied for up to 7 ICU days in English-speaking adults with an anticipated ICU stay ≥2 days and without mechanical ventilation, sleep apnoea, delirium, continuous sedation, contact isolation or recent anaesthesia. The Richards-Campbell Sleep Questionnaire (RCSQ) was administered each morning by a trained investigator. RESULTS: Available activity tracker-derived data for each ICU study night (20:00-09:00) (total sleep time (TST), number of awakenings (#AW), and time spent light sleep, deep sleep and rapid eye movement (REM) sleep) were downloaded and analysed. Across the 232 evaluated nights (76 patients), TST and RCSQ data were available for 232 (100%), #AW data for 180 (78%) and sleep stage data for 73 (31%). Agreement between TST (349±168 min) and RCSQ Score was moderate and significant (r=0.34; 95% CI 0.18 to 0.48). Agreement between #AW (median (IQR), 4 (2-9)) and RCSQ Score was negative and non-significant (r=-0.01; 95% CI -0.19 to 0.14). Agreement between time (min) spent in light (259 (182 to 328)), deep (43±29), and REM (47 (28-72)) sleep and RCSQ Score was moderate but non-significant (light (r=0.44, 95% CI -0.05 to 0.36); deep sleep (r=0.44, 95% CI -0.11 to 0.15) and REM sleep (r=0.44; 95% CI -0.21 to 0.21)). CONCLUSIONS: A Fitbit Charge 2 when applied to non-intubated adults in an ICU consistently collects TST data but not #AW or sleep stage data at night. The TST moderately correlates with patient-perceived sleep quality; a correlation between either #AW or sleep stages and sleep quality was not found.