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1.
Future Virology ; 17(7):429-439, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-2032730

RESUMO

Aim: This study aimed to evaluate chemokine receptor 5 delta 32 (CCR5-δ32) mutation and HIV-1 surveillance drug-resistance mutations (SDRMs) in peripheral blood mononuclear cells of long-term non progressors (LTNPs) of HIV-1-infected individuals. Materials & methods: This research was performed on 197 treatment-naive HIV-1-infected patients. After follow-up, it was determined that 15 (7.6%) of these people were LTNPs. The PCR assay was performed to identify the CCR5 genotype and HIV-1 SDRMs. Results: One (6.7%) of the LTNPs was heterozygous (wt/δ32) for the CCR5 delta 32 (CCR5δ32). However, none of the individuals was homozygous for this mutation (δ32/δ32). Moreover, none of the LTNPs showed HIV-1 SDRMs. The CRF35-AD subtype was the most dominant subtype, with a percentage of 93.3%. Conclusion: Iranian elite controllers are negative for CCR5-delta 32 homozygous genotype and drug resistance against antiretroviral drugs.

2.
Journal of the American Academy of Dermatology ; 87(3):AB184, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-2031395

RESUMO

Objective: We evaluated mortality in patients with pemphigus compared with non-pemphigus individuals matched on age and gender, in the United States (US). Methods: This retrospective cohort study used data from the US Optum Clinformatics claims database between May 1, 2000 and December 31, 2020. Mortality was assessed during a follow-up of up to 4 years after the index date (first pemphigus diagnosis). A sensitivity analysis was conducted (end of study period, March 31, 2020) to exclude the potential impact of COVID-19 on mortality analysis. Multivariable models (comorbidities as adjustment variables) were used to assess hazard ratios (HRs). Propensity score matched (PSM) model was used to minimize comorbidities difference at baseline. Results: Overall, 1391 patients with pemphigus (ICD-9 and ICD-10 codes) were identified (mean [SD] age: 63.7 [17.9] years;females: 57.0%). During follow-up, 227 patients (16.3%) died in the pemphigus cohort, compared with 172 patients (12.4%) in the non-pemphigus cohort. Pemphigus patients had higher death rate than the non-pemphigus cohort (adjusted HR [95% CI]: 1.69 [1.37–2.09];unadjusted HR [95% CI]: 1.33 [1.09–1.63];PSM HR [95% CI]: 1.49 [1.19–1.86];P <.01 for all). Similar results were observed in the sensitivity analysis (adjusted HR [95% CI]: 1.77 [1.41–2.23];P <.01);PSM HR [95% CI]: 1.52 [1.20–1.93];P <.01]). Infections, hypertension, diabetes, hematologic abnormalities, and cardiovascular comorbidities were strongly associated with mortality in pemphigus patients. Conclusions: These results suggest that pemphigus is associated with increased mortality observed over 4 years, highlighting the need for better treatment options for these patients.

3.
Journal of the American Academy of Dermatology ; 87(3):AB83, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-2031381

RESUMO

Objective: We evaluated mortality in patients with pemphigus compared with nonpemphigus individuals matched on age and gender, in the United States (US). Methods: This retrospective cohort study used data from the US Optum Clinformatics claims database between May 1, 2000 and December 31, 2020. Mortality was assessed during a follow-up of up to 4 years after the index date (first pemphigus diagnosis). A sensitivity analysis was conducted (end of study period, March 31, 2020) to exclude the potential impact of COVID-19 on mortality analysis. Multivariable models (comorbidities as adjustment variables) were used to assess hazard ratios (HRs). Propensity score matched (PSM) model was used to minimize comorbidities difference at baseline. Results: Overall, 1391 patients with pemphigus (ICD-9 and ICD-10 codes) were identified (mean [SD] age: 63.7 [17.9] years;females: 57.0%). During follow-up, 227 patients (16.3%) died in the pemphigus cohort, compared with 172 patients (12.4%) in the nonpemphigus cohort. Pemphigus patients had higher death rate than the nonpemphigus cohort (adjusted HR [95% CI]: 1.69 [1.37–2.09];unadjusted HR [95% CI]: 1.33 [1.09–1.63];PSM HR [95% CI]: 1.49 [1.19–1.86];P <.01 for all). Similar results were observed in the sensitivity analysis (adjusted HR [95% CI]: 1.77 [1.41–2.23];P <.01);PSM HR [95% CI]: 1.52 [1.20–1.93];P <.01]). Infections, hypertension, diabetes, hematologic abnormalities, and cardiovascular comorbidities were strongly associated with mortality in pemphigus patients. Conclusions: These results suggest that pemphigus is associated with increased mortality observed over 4 years, highlighting the need for better treatment options for these patients.

4.
The Ethiopian Journal of Health Development ; 35(4):367, 2021.
Artigo em Inglês | ProQuest Central | ID: covidwho-2026938

RESUMO

Background: Anti-SARS-CoV-2 antibody tests are increasingly used for sero-epidemiological purposes to provide a better understanding of the extent of the infection in the community, and to monitor the progression of the COVID-19 epidemic. A sero-prevalence study was conducted to estimate prior infections with SARS-CoV-2 in Addis Ababa. Methods: A cross-sectional study was conducted from April 23 to 28, 2020 among 301 randomly selected residents of Addis Ababa;sub-city health offices, health facilities and health extension workers were contacted, to obtain a population profile and to conduct the random selection of study participants. Participants were selected, who had not been in direct contact with people who had contracted COVID-19, to maintain consistency among the study population. Interviews on socio demographic and behavioural risk factors, followed by serological tests were performed for SARS-CoV-2 IgM, and IgG antibodies, using the COVID-19 IgG/IgM Rapid Test Cassette. Based on the manufacturer information, the test has a sensitivity of 87·9% and specificity of 100% for lgM;and a sensitivity of 97·2% and specificity of 100% for IgG. A Polymerase chain reaction (RT-PCR) test was also done on combined nasopharyngeal and oropharengeal swabs. Findings: The unadjusted antibody-based crude SARS-CoV-2 prevalence was 7·6% and the adjusted (weighted average) SARS-CoV-2 prevalence was estimated at 8·8% (95% CI 5·5%-11·6%) for the study population. Higher sero-prevalence were observed for males (9.0%), age below 50 years (8.2%), students and unemployed (15.6%), as well as those with primary education (12.1%), educated above high school (37·9%), non- smokers (78·7%), with no history of regular alcohol (53·8%), no chat (70·8%), and no shisha use (94·7%). According to the findings, a significantly higher number of individuals had been infected in Addis Ababa as compared to what was being detected and reported by the RT-PCR test, which is suggestive of community transmission.

5.
Vaccines ; 10(8):1285, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2024368

RESUMO

Background: quadrivalent inactivated vaccine (QIV) has replaced trivalent inactivated vaccine (TIV). In Portugal, TIV is free of charge for risk groups, including older adults (≥65 years old). In its turn, QIV—which provides broader protection as it includes an additional lineage B strain—was introduced in Portugal in October 2018;only since the 2019/20 influenza season has it been provided free of charge for risk groups. This study evaluates the cost effectiveness of switching from TIV to QIV, from the National Health Service perspective, in the Portuguese elderly mainland population. Methods: A decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the incremental cost-effectiveness ratio (ICER). In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results: the high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of EUR 5,283,047, and the resulting ICER would be EUR 26,403,007/QALY, above the usual willingness-to-pay threshold. Conclusions: from the National Health Service perspective, our findings reveal that QIV is not cost effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost effective.

6.
Vaccines ; 10(8):1257, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2024363

RESUMO

In Canada, approximately 12,000 people annually are hospitalized with influenza. While vaccination is the most effective method for reducing the burden of seasonal influenza, the propagation of vaccine virus strains in eggs can result in egg adaption, resulting in reduced antigenic similarity to circulating strains and thus lower vaccine effectiveness (VE). Cell-based propagation methods avoid these alterations and therefore may be more effective than egg-propagation vaccines. We evaluated three different scenarios: (1) egg-based quadrivalent influenza vaccine (QIVe) for individuals <65 years and adjuvanted trivalent influenza vaccine (aTIV) for ≥65 years;(2) QIVe (<65 years) and high-dose QIV (HD −;QIV;≥65 years);and (3) cell-based derived QIV (QIVc;<65 years) and aTIV (≥65 years) compared with a baseline scenario of QIVe for all age groups. Modelling was performed using a dynamic age-structured SEIR model, which assessed each strain individually using data from the 2012–2019 seasons. Probabilistic sensitivity analysis assessed the robustness of the results with respect to variation in absolute VE, relative VE, number of egg-adapted seasons, and economic parameters. QIVe + aTIV was cost-saving compared with the baseline scenario (QIVe for all), and QIVe + HD − QIV was not cost-effective in the majority of simulations, reflecting the high acquisition cost of HD − QIV. Overall, while the incremental benefits may vary by influenza season, QIVc + aTIV resulted in the greatest reductions in cases, hospitalizations, and mortality, and was cost-effective (ICER < CAD 50,000) in all simulations.

7.
Systems ; 10(4):106, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2024226

RESUMO

Evaluating pharmaceutical enterprises with sustainable and high-quality development ability (SHQDA) can not only provide strategies for the pharmaceutical management department in formulating enterprise development plans, but also provide suggestions and guidance for enterprises to enhance their core competitiveness. Nevertheless, the prior research possesses several deficiencies in coping with the assessment of enterprises with SHQDA under uncertain environments to predict the psychological behavior of the evaluator and the correlation among the evaluation criteria. To conquer the aforementioned defects, we propose an integrated framework for rating pharmaceutical enterprises that incorporates regret theory, measurement alternatives and ranking based on the compromise solution (MARCOS) and Heronian mean operating within a single-value neutrosophic set (SVNS) environment. First, the single-valued neutrosophic number (SVNN) is employed to portray the assessment information of experts. Then, a novel single-valued neutrosophic score function is presented to enhance the rationality of the SVNN comparison. Next, a combined criteria weight model is constructed by synthesizing the best and worst method (BWM) and criteria importance through intercriteria correlation (CRITIC) approach to attain more reasonable and credible weight information. Furthermore, the integrated assessment framework combining regret theory-MARCOS method and Heronian mean operator is put forward to assess and select the enterprises with SHQDA under a single-valued neutrosophic setting. Ultimately, an empirical concerning the pharmaceutical enterprises assessment is presented within SVNS to illustrate the usefulness and effectiveness of the presented SVNS regret theory-MARCOS method. Thereafter, the sensitivity analysis and comparison analysis are implemented to provide evidence for the rationality and superiority of the proposed method.

8.
Sustainability ; 14(17):10773, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2024198

RESUMO

Large-scale promotions lead to a huge number of orders, and the quantity of deliveries grows sharply, which puts considerable strain on cities’ logistics and imposes high related shipping costs. To alleviate these consequences, in this paper we provide a new contingent free shipping policy with delayed delivery (DD-CFS) for an online retailer during large-scale promotions and study its CFS threshold decisions, considering consumers’ different sensitivities to delivery time delays.We start by analyzing a consumer’s purchasing decision based on consumer utility theory. Next, we establish a mathematical model to help the online retailer find the optimal CFS threshold to maximize its expected profit. Finally, we analyze the benefit of delayed delivery to the online retailer and conduct a sensitivity analysis to examine the impacts of important parameters on the online retailer’s CFS threshold decisions, profit, and the value of the delayed delivery. We find that the DD-CFS policy can lead to more profits during the large-scale promotions period compared with the traditional CFS policy. As the delayed delivery time and the consumer’s negative attitude towards delayed delivery time increase, the online retailer should reduce the low CFS threshold value. On the other hand, as the shipping fee and the consumer’s negative attitude towards the shipping fee increase, the online retailer should raise the high and low CFS threshold values.

9.
Sustainability ; 14(17):10461, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2024170

RESUMO

The Getis-Ord Gi* statistic clustering technique was used to create a hot spot exposure map using 14 potentially toxic elements (PTEs) found in urban dust samples in a semiarid city in northwest Mexico. The dust distribution and deposition in this city are influenced by the seasonal wind and rain from the North American Monsoon. The spatial clustering patterns of hot spots were used in combination with a sensitivity analysis to determine which variables most influenced the PTE hot spot exposure base map. The hot spots areas (%) were used as indicators of environmental vulnerability, and a final integrated map was selected to represent the highest vulnerability of PTEs with a 99% level of confidence. The results of the sensitivity analysis indicated that the flood zones and pervious and impervious zones were the most sensitive variables due to their weight in the spatial distribution. The hot spot areas were reduced by 60.4% by not considering these variables. The hot spot analysis resulted in an effective tool that allowed the combination of different spatial layers with specific characteristics to determine areas that present greater vulnerability to the distribution of PTEs, with impacts on public and environmental health.

10.
Sustainability ; 14(16):10387, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2024161

RESUMO

Humanity has faced unprecedented chaos in the education sector due to the inevitable sudden adoption of online mode of learning during the pandemic. The complexities associated with technology-enabled learning and assessment have different connotations in developing countries due to a lack of infrastructure and awareness. Such countries can switch over to an online mode of education more frequently in the future due to highly volatile local political and cultural situations on top of the pandemic. This study evaluates the complexities associated with technology-enabled online assessment methods in Pakistan. Technology readiness and performance for the learning assessment of students are appraised through approaching approximately one thousand students from more than one hundred public and private sector engineering universities. A screened list of assessment alternatives and their influencing factors are then prioritized using the multi-actor multi-criteria analysis (MAMCA) by considering the perceptions of national policymakers, faculty members and students. The aggregate results reveal that, among the influencing factors, ‘mental health’ received the highest weightage, and stakeholders are indifferent to associated costs despite financial challenges. Automated MCQs secured the top position in the ranking list. Sensitivity analysis incorporates some disagreements among the stakeholders, which makes this study highly beneficial for policy modeling.

11.
Mathematics ; 10(17):3155, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2023887

RESUMO

As global public health events and regional conflicts have greater influence on supply chains nowadays, supplier default in procurement becomes more and more common in practice. However, there is less research on portfolio procurement purchasing decisions in the case of fixed-term contract supplier default. This paper focuses on the optimal purchasing decision of buyers by using a combination of fixed-term contracts and spot transactions, which is a beneficial extension of the classical newsvendor model. When supplier default is not considered, the optimal purchase quantity in the fixed-term contract is first obtained, which maximizes the buyer’s expected profits. Research shows that supplier default has an important impact on the optimal purchasing decision making in portfolio procurement. The optimal purchase quantity of the buyer in the fixed-term contract decreases with the increase in the default rate of the contract supplier, which implies that the default from the contract supplier inhibits a larger purchase quantity in the fixed-term contract. In addition, it is proved that the buyer’s expected profits from portfolio procurement increases with the decrease in the contract supplier’s default rate. Finally, numerical experiments and sensitivity analysis are conducted to prove the result, and some management opinions on the optimal decision-making in portfolio procurement with fixed-term contracts and spot transactions are put forward.

12.
Applied Sciences ; 12(16):8299, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2023101

RESUMO

During pandemic times, difficulties and problems related to the health sector are evident as the number of patients coming to health centers is higher compared to normal situations. This increase in the number of patients is typical of the pandemic, due to the high level of contagion in the population. Health personnel have a higher risk of infection, due to their sharing the work of caring for positive patients, so the infection rate is much higher. Hence, it remains necessary to understand the behavior of infection of health personnel, in order to be prepared to deal with the care of patients. Accordingly, in this research, we present a method to estimate different scenarios of infection and assess the probability of occurrence, so we can estimate the infection rate of health personnel. We present a simulation of 21 possible scenarios with 100 workers and a minimum of 80% needed to guarantee patient care. The results show that it is more likely that a 50% contagion scenario will occur, with an acceptable probability of 20%.

13.
Periodica Polytechnica. Transportation Engineering ; 50(4):369-386, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2022627

RESUMO

The boarding process is the role activity to maintain the airline's efficiency in the turnaround process on the ground. One of the scenarios to optimize the boarding process is the arrangement of passengers who enter the plane based on the amount of carry-on luggage, adjusted to the selected boarding strategy. This research aims to develop an agent-based simulation model to increase the effectiveness of passengers' boarding process by applying the luggage arrangement method for an airplane with a 180-seat configuration. The simulation results showed that applying the Ascending luggage arrangement method reduced the overall boarding process performance by 6.12%, while the Descending method increased boarding performance by 2.50%, compared to the standard Random method.

14.
PLoS One ; 17(9), 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2021957

RESUMO

Introduction Using respiratory virus rapid diagnostic tests in the emergency department could allow better and faster clinical management. Point-of-care PCR instruments now provide results in less than 30 minutes. The objective of this study was to assess the impact of the use of a rapid molecular diagnostic test, the cobas® Influenza A/B & RSV Assay, during the clinical management of emergency department patients. Methods Patients (adults and children) requiring admission or suffering from an underlying condition at risk of respiratory complications were prospectively recruited in the emergency department of four hospitals in the Brussels region. Physicians’ intentions regarding admission, isolation, antibiotic, and antiviral use were collected before and after performing the rapid molecular test. Additionally, a comparison of the analytical performance of this test against antigen rapid tests and viral culture was performed as well as a time-to-result evaluation. Results Among the 293 patients recruited, 90 had a positive PCR, whereas 44 had a positive antigen test. PCR yielded a sensitivity of 100% for all targets. Antigen tests yielded sensitivities ranging from 66.7% for influenza B to 83.3% for respiratory syncytial virus (RSV). The use of PCR allowed a decrease in the overall need for isolation and treatment by limiting the isolation of negative patients and antibiotic use for positive patients. Meanwhile, antiviral treatments better targeted patients with a positive influenza PCR. Conclusion The use of a rapid influenza and RSV molecular test improves the clinical management of patients admitted to the emergency department by providing a fast and reliable result. Their additional cost compared to antigen tests should be balanced with the benefit of their analytical performance, leading to efficient reductions in the need for isolation and antibiotic use.

15.
PLoS One ; 17(8), 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-2021936

RESUMO

Introduction Several teaching methods have been used in clinical nursing teaching to increase quality and efficiency, but disagreements over their effects persist. This study will evaluate the effects of five teaching methods in clinical nursing on nursing students’ knowledge, skill scores, learning satisfaction, and patients’ satisfaction. Methods We will conduct searches in PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure Database (CNKI), China Biological literature database (CBM), Wanfang Database, and China Science and Technology Journal Database (CSTJ) up to April 2022. Relevant randomized controlled trials meeting the eligibility criteria will be included. And the study selection and data extraction will be independently screened for eligibility by two authors. The quality of evidence will be evaluated using the Cochrane risk of bias tool. Pairwise meta-analysis and network meta-analysis (NMA) will be conducted using Rev Man, Stata, and R software. Statistical analyses including homogeneity tests, sensitivity analysis, transitivity tests, consistency tests, and publication bias will be completed. Ethics and dissemination No formal research ethics approval is required. The results will be disseminated to a peer-reviewed journal for publication. Protocol registration number INPLASY2021120040.

16.
Nonlinear Dyn ; : 1-27, 2022.
Artigo em Inglês | Web of Science | ID: covidwho-2014314

RESUMO

The realistic assessments of public health intervention strategies are of great significance to effectively combat the COVID-19 epidemic and the formation of intervention policy. In this paper, an extended COVID-19 epidemic model is devised to assess the severity of the pandemic and explore effective control strategies. The model is characterized by ordinary differential equations with seven-state variables, and it incorporates some parameters associated with the interventions (i.e., media publicity, home isolation, vaccination and face-mask wearing) to investigate the impacts of these interventions on the spread of the COVID-19 epidemic. Some dynamic behaviors of the model, such as forward and backward bifurcation, are analyzed. Specifically, we calibrate the model parameters using actual COVID-19 infected data in Brazil by Markov Chain Monte Carlo algorithm such that we can study the effects of interventions on a practical case. Through a comprehensive exploration of model design and analysis, model calibration, sensitivity analysis, implementation of optimal control problems and cost-effectiveness analysis, the rationality of our model is verified, and the effective strategies to combat the epidemic in Brazil are revealed. The results show that the asymptomatic infected individuals are the main drivers of COVID-19 transmission, and rapid detection of asymptomatic infections is critical to combat the COVID-19 epidemic in Brazil. Interestingly, the effect of the vaccination rate associated with pharmaceutical intervention on the basic reproduction number is much lower than that of non-pharmaceutical interventions (NPIs). Our study also highlights the importance of media publicity. To reduce the infected individuals, the multi-pronged NPIs have considerable positive effects on controlling the outbreak of COVID-19. The infections are significantly decreased by the early implementation of media publicity complemented with home isolation and face-mask wearing strategy. When the cost of implementation is taken into account, the early implementation of media publicity complemented with a face-mask wearing strategy can significantly mitigate the second wave of the epidemic in Brazil. These results provide some management implications for controlling COVID-19.

17.
IISE Annual Conference and Expo 2022 ; 2022.
Artigo em Inglês | Scopus | ID: covidwho-2012849

RESUMO

Wearing a mask as one of the crucial non-pharmaceutical interventions has demonstrated to be effective in the battle against the COVID-19 pandemic. The implementation of face coverings for the public remains controversial and still faces some challenges. Whether or not to wear the mask could be a complex decision-making processing, involving the trade-offs between self-interest and collective interest among multiple stakeholders. In the literature, there is a lack of quantitative analysis for strategic mask-wearing decisions during the pandemic. This paper fills the gap by studying a game-theoretic model on wearing the mask considering conflicting interests. Using a susceptible-infected-susceptible (SIS) model, we consider the players as either susceptible or infectious, characterized by homogeneous preferences within the group but heterogeneous preferences between groups. Then we propose a game-theoretic framework to model how both susceptible and infectious players make their decisions. We implement one-way sensitivity analyses to examine how the equilibrium solutions are sensitive to changes in the model parameters. The proposed game model shows that susceptible player is more likely to wear face masks compared to infectious player, when the likelihood or the cost of infection is large. Decreasing the cost of wearing masks or increasing the mask efficacy could help mitigate the reluctance of mask wearing. This paper provides insights on population mask-wearing behaviors, which can support policy makers to design regulations and incentives. © 2022 IISE Annual Conference and Expo 2022. All rights reserved.

18.
IISE Annual Conference and Expo 2022 ; 2022.
Artigo em Inglês | Scopus | ID: covidwho-2012643

RESUMO

Trauma care services are a vital part of all healthcare-based networks as timely accessibility is important for citizens. Trauma care access is even more relevant when unexpected events such as the COVID-19 pandemic overload the capacity of hospitals. Research literature has highlighted that access to trauma care is not equal for all populations, especially when comparing rural and urban groups. In this research we present a decision-making model for the expansion of a trauma hospital network by considering the demand for services of rural communities. The decision-making model provides recommendations in terms of where to place additional aeromedical facilities and where to locate additional trauma hospitals. A case study is presented for the state of Texas, where a sensitivity analysis was conducted to consider changes in demand, cost, and the total number of facilities allowed in the network. The results show that the location of new facilities is sensitive to the expected service demand and the maximum number of facilities allowed in the network. © 2022 IISE Annual Conference and Expo 2022. All rights reserved.

19.
Frontiers in Genetics ; 13, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-2009857

RESUMO

Aims: The causal relationship between COVID-19 infection and stroke has not yet been fully established. This study aimed to explore this causality using two-sample Mendelian randomization (MR). Materials and Methods: Genetic variants associated with COVID-19 infection and stroke were both obtained from genome-wide association study (GWAS) summary data. The single nucleotide polymorphisms (SNPs) were selected as instrumental variables. The standard inverse variance weighted (IVW) was primarily used to assess this causality. Finally, sensitivity analysis was performed to evaluate the reliability and stability. Results: The results showed that being hospitalized due to COVID-19 had a positive effect on stroke [OR = 1.05;95% CI= (1.01, 1.10);p = 2.34 × 10−5] and ischemic stroke [OR = 1.06;95% CI= (1.02, 1.11);p = 2.28 × 10−6] analyzed by inverse variance weighted. Moreover, the results revealed that severe respiratory symptoms due to COVID-19 had a positive effect on stroke [OR = 1.04;95% CI= (1.00, 1.06);p = 0.04] and that the causal effect of severe respiratory symptoms due to COVID-19 on ischemic stroke estimated by IVW suggested a positive effect [OR = 1.06;95% CI= (1.02, 1.09);p = 0.0068], too. Conclusion: In summary, this study showed that severe COVID-19 might increase the risk of stroke, thus much more attention should be paid to patients with severe COVID-19.

20.
Annals of the Rheumatic Diseases ; 81:210-211, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-2009170

RESUMO

Background: Interleukin-6 (IL-6) is elevated in patients with active polymyalgia rheumatica (PMR) and is associated with disease activity, relapse and severity. Clinical trials with IL-6 receptor (IL-6R) inhibitors in PMR showed higher remission rates and reduced glucocorticoid (GC) use vs GC alone.1-4 Objectives: The SAPHYR study (NCT03600818) assessed the efficacy and safety of sarilumab (SAR), a fully human anti IL-6Rα monoclonal antibody, with a 14 week (wk) GC taper in patients with steroid resistant active PMR who fared on ≥7.5 mg/day prednisone or equivalent. Methods: Patients were randomized (1:1) to 52 wks of treatment with SAR 200 mg every 2 wks (Q2W) + 14 wk GC tapered regimen (SAR arm) OR placebo Q2W + 52 wk GC tapered regimen (comparator arm). The primary endpoint was the proportion of patients achieving sustained remission at wk 52, defned as disease remission by wk 12, absence of disease fare, CRP normalization from wks 12 to 52 and adherence to the per protocol GC taper from wks 12 to 52. Results: The study was terminated early due to protracted recruitment timelines during the COVID-19 pandemic, resulting in 118 of the intended 280 patients recruited between Oct 2018 and Jul 2020, and 117 were treated (SAR n=59, comparator n=58). The demographics were balanced;patients were primarily female, Caucasian, and a median age of ~70 years (Table 1). Overall, 78 patients completed the treatment (SAR n=42;comparator n=36). Primary reasons for treatment discontinuation were adverse events (AEs;SAR n=7, comparator n=4) and lack of efficacy (SAR n=4, comparator n=9). Sustained remission rate was signifcantly higher in the SAR arm vs the comparator arm (28.3% vs 10.3%;P=0.0193). Results of a sensitivity analysis excluding CRP from the sustained remission defnition was consistent with the primary analysis (31.7% vs 13.8%;P=0.0280). All sustained remission components favored SAR (Figure 1). Patients in the SAR arm were 44% less likely to have a fare after achieving clinical remission vs the comparator arm (16.7% vs 29.3%;HR 0.56;95% CI 0.35-0.90;P=0.0158). The comparator arm required more additional GCs vs the SAR arm, mainly due to PMR fare (median difference in actual and expected cumulative dose 199.5 mg vs 0.0 mg;P=0.0189). The cumulative GC toxicity index scores numerically favored SAR but the difference was not statistically signifcant. PMR activity scores improved in the SAR arm vs the comparator arm (LS mean-15.57 vs-10.27, nominal P=0.0002). Patient reported outcomes (eg, physical and mental health component scores, disability index, etc) favored SAR (Figure 1). Incidence of treatment-emergent AEs (TEAEs) was numerically higher in the SAR arm vs the comparator arm (94.9% vs 84.5%) and included neutropenia (15.3%) and arthralgia (15.3%) in the SAR arm, and insomnia (15.5%) in the comparator arm. Conversely, the frequency of serious AEs was higher in the comparator arm vs the SAR arm (20.7% vs 13.6%). No deaths were reported. Conclusion: SAR + 14 wk GC taper demonstrated signifcant efficacy vs the comparator arm in steroid refractory PMR patients, including clinically meaningful improvement in quality of life. Safety was consistent with the known safety profile of SAR.

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