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BACKGROUND: Coronavirus 2019 disease (COVID-19) is a highly infectious disease prompting extreme containment measures, including lockdown, travel restrictions, social distancing, and stringent personal hygiene. This study investigates the depression level and coping responses toward the lockdown, referred as the movement control order (MCO) during COVID-19 pandemic in Malaysia and its impact on quality of life. METHOD: This cross-sectional study was conducted from April to May 2020. The outcomes were assessed using the Depression, Anxiety and Stress ScaleC21, Coping Orientation to Problems Experienced Inventory, and World Health Organisation Quality of LifeCBREF Scale (WHOQOL-BREF) in both English and validated Malay versions. RESULTS: Mild-to-severe depression was found in 28.2% (n = 149) of the 528 respondents. Respondents with mild-to-severe depression were significantly younger (33.09 10.08 versus 36.79 12.47 years), without partner (71.8% versus 45.6%), lived in the red zone (85.9% versus 71.0%), and had lower household income as defined in the category of B40 (51.7% versus 39.3%) compared to those without depression (all p < 0.01). The avoidant coping score was significantly higher (25.43 5.69 versus 20.78 5.65), while the religious coping score was significantly lower (5.10 2.07 versus 5.94 2.11) among those with mild-to-severe depression compared to those without depression (both p < 0.001). Respondents with mild-to-severe depression also had significantly lower mean score in each domain of WHOQOL-BREF compare to those without depression [(physical health, 13.63 2.66 versus 16.20 2.11), (psychological, 12.5 2.79 versus 16.10 2.14), (social relationships, 12.17 3.49 versus 15.28 2.93), environment (14.50 2.39 versus 16.21 2.14), all p < 0.001] after controlling for age, marital status, zone, household income, and coping scores. CONCLUSION: COVID-19 lockdown had adverse mental health effects. Our study highlighted that approximately one in three individual experienced mild-to-severe depression during the nationwide MCO. The varied impact of the pandemic on mental health could be due to different population characteristics and coping strategies used. Identifying those at higher risk to develop depression during MCO for COVID-19 pandemic could help mental healthcare service providers to plan services for those susceptible, thereby mitigating the pandemics effect on quality of life.
Depression level and coping responses toward the movement control order and its impact on quality of life in the Malaysian community during the COVID-19 pandemic: a web-based cross-sectional study
Asia and Latin America and the Caribbean (LAC), two regions with large growth potential, have become increasingly connected over the last 20 years. China has emerged not only as a top trading partner, but also as an important competitor of LAC exports. China's retreat from certain markets, due to the ongoing rebalancing process, could open new opportunities for LAC exporters but also entail some challenges. Our results show that China's rebalancing will have an overall positive effect on LAC's GDP and exports in the long run, but this effect is small and uneven across countries, leading to winners and losers. We also provide evidence that other countries, such as India, are currently trying to fill the gap left by China and could undermine LAC's competitive advantage in some export markets. In this context, reduction of trade barriers and further integration within the region and/or with the rest of the world would lead to unequivocally positive outcomes for all LAC countries. The COVID-19 shock might exacerbate the effects identified in our analysis.
China's Rebalancing: Opportunities and Challenges for LAC Exporters
Objective. To study the characteristics of asthenic syndrome and the potential for treating it in the postcovid period. Materials and methods. A continuous sampling method was used to select 129 patients (mean age 49.8 8.9 years) after COVID-19. Study patients were selected at the clinical out-patient and polyclinic facilities in Samara in the period JulyCAugust, 2020. All patients signed informed consent. The envelope method was used to randomize patients into two groups: the study group (n = 64) received ethylmethylhydroxypyridine succinate (Neurox) 1 tablet (125 mg) three times daily for four weeks; medications in the reference group (n = 65) did not include any substances of the pharmacological antihypoxant/antioxidant/nootrope groups. Three visits (V) were made: the first (V(1)) was before inclusion in the study; the second (V(2)) was at 14 days; the third (V(3)) was on day 28 from treatment initiation. The dynamics of overall status (weakness, fatigue, concentration of attention, vertigo, headache, sleep impairment) were evaluated on a visual analog scale (VAS); the subjective perception of the severity of asthenia (tiredness, physical and mental fatigue, decreased motivation and activity) was evaluated using the Multidimensional Fatigue Inventory, MFI-20); cognitive functions were assessed using the Mini Mental State Examination (MMSA); and autonomic tone was assessed using the Krd? index. Results. At the end of the study (V(3)), statistically significant changes in measures (VAS, MFI-20) were seen only in patients of the study group; the Krd? Index showed no statistically significant differences. Analysis of MMSE data revealed a decline in cognitive functions in both groups, which may be linked with pseudocognitive deficit due to asthenia. Conclusions. Our studies yielded evidence of a high incidence of asthenic syndrome after COVID-19. Neurox decreased the severity and extent of the symptoms of asthenia.
Postcovid-19 Asthenic Syndrome
OBJECTIVES The purpose of this study was to compare the outcome of the piezo-assisted turbinoplasty with a partial turbinectomy technique in the treatment of chronic nasal obstruction due to inferior turbinate enlargement. STUDY DESIGN This is a prospective randomized single-center study in a cohort of 100 consecutive patients which underwent external septorhinoplasty and concomitant hybrid type of turbinoplasty. METHODOLOGY Patients were randomly assigned into two groups. The first group included 50 patients who underwent piezo-assisted outfracturing of the inferior turbinates in combination with bipolar coagulation. The second group included 50 patients who underwent a treatment based on turbinate bipolar coagulation and partial resection of the inferior border of the turbinate. The severity of nasal obstruction was measured in both patient groups with a patient-related outcome questionnaire (NOSE) and objective measures (anterior rhinomanometry and acoustic rhinometry). Assessments were conducted prior to surgery and 3 months after the surgery. RESULTS There was a significant improvement in the values of the NOSE questionnaire with no relevant difference between the two study groups. Acoustic rhinometry and rhinomanometry also showed no statistically significant differences between the two study groups. No differences in postoperative healing were found, and postoperative complications were comparable low in both groups. However, the piezo-assisted procedure was quicker to perform with only minimal bleeding. CONCLUSION During septorhinoplasty, the combination of thermo-coagulation with piezo-assisted turbinoplasty was as efficient as with partial turbinectomy to establish normal nasal breathing. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Piezo-assisted Turbinoplasty Versus Partial Turbinectomy in External Septorhinoplasty: A Prospective Comparative Study in 100 Patients.
With high levels of the Delta variant of COVID-19 circulating in England during September 2021, schools are set to reopen with few school-based non-pharmaceutical interventions (NPIs). In this paper, we present simulation results obtained from the individual-based model, JO_SCPLOWUNEC_SCPLOW, for English school opening after a prior vaccination campaign using an optimistic set of assumptions about vaccine efficacy and the likelihood of prior-reinfection. We take a scenario-based approach to modelling potential interventions to assess relative changes rather than real-world forecasts. Specifically, we assess the effects of vaccinating those aged 16-17, those aged 12-17, and not vaccinating children at all relative to only vaccinating the adult population, addressing what might have happened had the UK began teenage vaccinations earlier. Vaccinating children in the 12-15 age group would have had a significant impact on the course of the epidemic, saving thousands of lives overall in these simulations. In the absence of such a vaccination campaign our simulations show there could still be a significant positive impact on the epidemic (fewer cases, fewer deaths) by continuing NPI strategies in schools. Our analysis suggests that the best results in terms of lives saved are likely derived from a combination of the now planned vaccination campaign and NPIs in schools.
Vaccinations or Non-Pharmaceutical Interventions:Safe Reopening of Schools in England
BACKGROUND: Concerns about reduced milk transfer with nipple shield (NS) use are based on evidence from studies with methodological flaws. Milk removal during breastfeeding can be impacted by infant and maternal factors other than NS use. The aim of this study was to control electric breast pump vacuum strength, pattern and duration across multiple study sessions to determine if NS use reduces milk removal from the breast. METHODS: A within-subject study with two groups of breastfeeding mothers (infants < 6 months) were recruited; Control Group (CG): no breastfeeding difficulties; Pain Group (PG) used NS for persistent nipple pain. Mothers completed three randomised 15 min pumping sessions using the Symphony vacuum curve (Medela AG); no NS, fitted NS, and a small NS. Sessions were considered valid where the applied vacuum was within 20 mmHg of the set vacuum. Milk removal was considered as pumped milk volume, and also percentage of available milk removed (PAMR), which is calculated as the pumped volume divided by the estimated milk volume stored in the breast immediately prior to pumping. RESULTS: Of 62 sessions (all: n = 31 paired sessions) a total of 11 paired sessions from both PG (n = 03) and CG (n = 08) were valid (subset) with and without a fitted NS. Only 2 small shield sessions were valid and so all small shield measurements were excluded. Both pumped volumes and PAMR were significantly lower with NS use for all data but not for subset data. (All: Volume and PAMR median: no NS: 76.5 mL, 69%, Fitted NS: 32.1 mL, 41% respectively (volume p = 0.002, PAMR p = 0.002); Subset: Volume and PAMR median: no NS: 83.8 mL, 72%; Fitted NS: 35.2 mL, 40% (volume p = 0.111 and PAMR p = 0.045). The difference in PAMR, but not volume, was statistically significant when analysed by linear mixed modelling. A decrease of 10 mmHg was associated with a 4.4% increase in PAMR (p = 0.017). CONCLUSIONS: This experimental data suggests that nipple shield use may reduce milk removal. Close clinical monitoring of breastfeeding mothers using nipple shields is warranted.
Effect of nipple shield use on milk removal: a mechanistic study
How do governments take strategic actions in weaving public health and safety nets to respond to the COVID-19 pandemic? Embracing Moores strategic action framework, this study investigates how municipal governments can configure authorizing environmentoperational capacitypublic value attributes to weave public health and safety nets, in order to prevent and control the public health and safety emergency. Leveraging fuzzy-set Qualitative Comparative Analysis (fsQCA) with a sample of 323 Chinese cities, we identify a distinctive taxonomy of four equally effective configurations of urban actions in blocking COVID-19 transmission: social reassurance, proactive defence, decisive resiliency, and strengthened coercion. Overall, this study provides a novel insight of public health and safety management into battles against COVID-19 in human society.
Weaving public health and safety nets to respond the COVID-19 pandemic
In response to the COVID-19 pandemic, as with other countries across the world, the Central and State Governments of India initiated several measures to slow down the spread of the virus and to flatten the curve. One such measure was a total lockdown for several weeks across the country. A complex and unexpected outcome of the lockdown which has medical, ethical, economic, and social dimensions is related to alcohol consumption. The lockdown and consequent acute non-availability of alcohol resulted in people with alcohol dependence going into withdrawals, black marketing of alcohol, and in extreme cases suicide resulting from the alleged frustration of not having access to alcohol. The health dilemmas around this situation are biological (e.g. pushing people into risky situations-potentially fatal alcohol withdrawal, consumption of illicit or other non-consumable alcohol) and psychosocial (e.g. isolation increasing the risk of relapses, loss of control over the decision to abstain which can be detrimental to recovery, restriction of access to services for alcohol problems). The legal and rights-related dilemmas are centred around whether States have the right to impinge on individual autonomy on the grounds of public health, the capacity of the health systems to provide appropriate services to cope with those who will struggle with the unavailability of alcohol, the constitutionality of the Central government's impinging on jurisdiction of states under the guise of a health emergency caused by the pandemic, and the ability of the State to make unbiased decisions about this issue when it is highly dependent on the revenue from the sale of alcohol and associated industries. The way forward could be a pragmatic and utilitarian approach involving continued access to alcohol, while observing all physical distancing norms necessary during the pandemic, for those who want to continue drinking; and implementing innovative measures such as tele-counselling for those who wish not to return back to drinking.
COVID-19 and forced alcohol abstinence in India: The dilemmas around ethics and rights
Results from an extensive vegetation survey of 1971 boreal forest stands, encompassing a full spectrum of succession and site types in the regions of Ontario and Quebec south of James Bay, are reported. Noncentered principal component analysis plus varimax rotation (nodal component analysis) is applied to overstory and understory data in order to detect vegetational noda. The overstory data are inherently more structured (i.e., contain more distinct subgroups) than those of the understory. An exception is seen with groups in which Abies balsamea plays a prominent role. These are interpreted as stages in various successions of which only one, a Betula papyrifera to A. balsamea sequence, represents the complete transition from one canopy dominant to another. The understory noda are summarized in terms of the compositional and environmental features of stands belonging to each nodum. Relationships among the understory noda are summarized in a multidimensional scaling ordination which is derived directly from similarity values (conjunction coefficients) representing the overlap between pairs of noda. Two major environmental gradients seem to affect understory composition. These are a site moisturenutrient concentration gradient and a general fertilityproductivity gradient. Canopy composition and understory vegetation are compared by nodal conjunction between the two analyses. Groups of noda, representing wet bog forests and also upland mesic forests, show moderate to good coincidence but beyond this little canopy specificity emerges. These results indicate that overstoryunderstory coincidence is due primarily to similar site requirements. Understory species' response to an overstory succession is examined. Many abundant herbs seem indifferent to dramatic canopy change. This observation and results from nodal component analysis are discussed with respect to forest fire.
Vegetation of the Boreal Forests South of James Bay: Non\Centered Component Analysis of the Vascular Flora
Case reports of COVID-19 patients who have been discharged and subsequently report positive RT-PCR again (hereafter referred as 're-positive') do not fully describe the magnitude and significance of this issue. In order to determine the re-positive rate (proportion) and review probable causes and outcomes, we conduct a retrospective study of all 119 discharged patients in Brunei Darussalam up till April 23. Patients who were discharged are required to self-isolate at home for 14 days and undergo NP specimen collection post-discharge. Discharged patients found to be re-positive were readmitted. We reviewed the clinical and epidemiological records of all discharged patients and apply log-binomial models to obtain risk ratios for re-positive status. One in five recovered patients subsequently test positive again for SARS-CoV-2 - this risk is more than six times higher in persons aged 60 years and above. The average Ct value of re-positive patients was lower pre-discharge compared to their readmission Ct value. Out of 111 close contacts tested, none were found to be positive as a result of exposure to a re-positive patient. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon. We did not observe infectivity potential in these patients. This article is protected by copyright. All rights reserved.
Probable causes and risk factors for positive SARS-CoV-2 test in recovered patients: Evidence from Brunei Darussalam
Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMX formulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. BALB/c mice were immunized three times intramuscularly with these vaccine formulations. Injection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b+) in the draining lymph nodes consistent with a chemotactic adjuvant effect. Advax4+CMX and Advax4+ECMX induced the highest levels of IgG1 and IgG2a antibodies against rCMX and rECMX, respectively. Immunized mice challenged with Mycobacterium tuberculosis (Mtb) had increased vaccine-specific Th1 responses in the lungs together with reduced Mtb - associated alveolar damage, although only the Advax4+ECMX vaccine demonstrated significant reduction of lung bacterial load. This study confirmed Advax4+ECMX as a potential TB vaccine candidate, with potential for further optimization and clinical development.
Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with highly variable clinical outcomes. Studying the temporal dynamics of host whole blood gene expression during SARS-CoV-2 infection can elucidate the biological processes that underlie these diverse clinical phenotypes. We employed a novel pseudotemporal approach using MaSigPro to model and compare the trajectories of whole blood transcriptomic responses in patients with mild, moderate and severe COVID-19 disease. We identified 5,267 genes significantly differentially expressed (SDE) over pseudotime and between severity groups and clustered these genes together based on pseudotemporal trends. Pathway analysis of these gene clusters revealed upregulation of multiple immune, coagulation, platelet and senescence pathways with increasing disease severity and downregulation of T cell, transcriptional and cellular metabolic pathways. The gene clusters exhibited differing pseudotemporal trends. Monoamine oxidase B was the top SDE gene, upregulated in severe>moderate>mild COVID-19 disease. This work provides new insights into the diversity of the host response to SARS-CoV-2 and disease severity and highlights the utility of pseudotemporal approaches in studying evolving immune responses to infectious diseases.
Pseudotemporal whole blood transcriptional profiling of COVID-19 patients stratified by clinical severity reveals differences in immune responses and possible role of monoamine oxidase B
Antisocial behaviors cause harm, directly or indirectly, to others welfare. The novel coronavirus pandemic has increased the urgency of understanding a specific form of antisociality: behaviors that increase risk of disease transmission. Because disease transmission-linked behaviors tend to be interpreted and responded to differently than other antisocial behaviors, it is unclear whether general indices of antisociality predict contamination-relevant behaviors. In a pre-registered study using an online U.S. sample, we found that individuals reporting high levels of antisociality engage in fewer social distancing measures: they report leaving their homes more frequently (p = .024) and standing closer to others while outside (p < .001). These relationships were observed after controlling for sociodemographic variables, illness risk, and use of protective equipment. Independently, higher education and leaving home for work were also associated with reduced distancing behavior. Antisociality was not significantly associated with level of worry about the coronavirus. These findings suggest that more antisocial individuals may pose health risks to themselves and their community during the COVID-19 pandemic.
Reduced social distancing early in the COVID-19 pandemic is associated with antisocial behaviors in an online United States sample
Hospital workers have increased exposure risk of healthcare-associated infections due to the frontline nature of their work. Olfactory dysfunction is highly prevalent. The objectives for this investigation are to study the prevalence of long-lasting olfactory dysfunction associated with COVID-19 infection in hospital workers during the first pandemic wave, to identify clinical characteristics and associated symptomatology, and to analyze how many patients with COVID-19 infection had developed olfactory dysfunction during infection and maintained a reduced olfactory function for approximately 10 weeks after diagnosis. Between June and July of 2020, a cross-sectional study was carried out at the Hospital Central de la Cruz Roja San Jos and Santa Adela in Madrid, Spain. One hundred sixty-four participants were included, of which 110 were patient-facing healthcare staff and 54 were non-patient-facing healthcare staff. Participants were split into three groups, according to COVID-19 diagnosis and presence of COVID-19 related olfactory symptomatology. Participants were asked to complete a structured online questionnaire along with Sniffin Stick Olfactory Test measurements. In this study, 88 participants were confirmed for COVID-19 infection, 59 of those participants also reported olfactory symptomatology. The prevalence of COVID-19 infection was 11.35%, and the prevalence for olfactory dysfunction was 67.05%. Olfactory dysfunction associated with COVID-19 infection leads to long-lasting olfactory loss. Objective assessment with Sniffin Stick Olfactory Test points to odor identification as the most affected process. Lemon, liquorice, solvent, and rose are the odors that are worst recognized. Mint, banana, solvent, garlic, coffee, and pineapple, although they are identified, are perceived with less intensity. The findings of this study confirmed a high prevalence of SARS-CoV-2 infection among the hospital workers.
Long-Lasting Olfactory Dysfunction in Hospital Workers Due to COVID-19: Prevalence, Clinical Characteristics, and Most Affected Odorants
Acute cerebrovascular accidents (ACVIs) associated with COVID-19 coronavirus infection are one of the most talked about problems in the medical community. To date, the true incidence of stroke in patients with COVID-19 remains unclear. So far, the published literature has been limited to case reports, case series, and observational cohort studies. The article analyzes possible risk factors, especially the age of patients, pathogenetic and clinical correlations of ACVA and SARS-CoV-2 (COVID-19). A clinical case of an 82-year-old patient with ischemic stroke and COVID-19 infection is described.
[Acute cerebrovascular accidents associated with SARS-CoV-2 coronavirus infection (COVID-19)]./ Ostrye narusheniya mozgovogo krovoobrashcheniya, assotsiirovannye s koronovirusnoi infektsiei SARS-CoV-2(COVID-19)
BACKGROUND: The invasion of the red blood cells by Plasmodium falciparum merozoites involves the interplay of several proteins that are also targets for vaccine development. The proteins PfRh5-PfRipr-PfCyRPA-Pfp113 assemble into a complex at the apical end of the merozoite and are together essential for erythrocyte invasion. They have also been shown to induce neutralizing antibodies and appear to be less polymorphic than other invasion-associated proteins, making them high priority blood-stage vaccine candidates. Using available whole genome sequencing data (WGS) and new capillary sequencing data (CS), this study describes the genetic polymorphism in the Rh5 complex in P. falciparum isolates obtained from Kilifi, Kenya. METHODS: 162 samples collected in 2013 and 2014 were genotyped by capillary sequencing (CS) and re-analysed WGS from 68 culture-adapted P. falciparum samples obtained from a drug trial conducted from 2005 to 2007. The frequency of polymorphisms in the merozoite invasion proteins, PfRh5, PfRipr, PfCyRPA and PfP113 were examined and where possible polymorphisms co-occurring in the same isolates. RESULTS: From a total 70 variants, including 2 indels, 19 SNPs [27.1%] were identified by both CS and WGS, while an additional 15 [21.4%] and 36 [51.4%] SNPs were identified only by either CS or WGS, respectively. All the SNPs identified by CS were non-synonymous, whereas WGS identified 8 synonymous and 47 non-synonymous SNPs. CS identified indels in repeat regions in the p113 gene in codons 275 and 859 that were not identified in the WGS data. The minor allele frequencies of the SNPs ranged between 0.7 and 34.9% for WGS and 1.1C29.6% for CS. Collectively, 12 high frequency SNPs (> 5%) were identified: four in Rh5 codon 147, 148, 203 and 429, two in p113 at codons 7 and 267 and six in Ripr codons 190, 259, 524, 985, 1003 and 1039. CONCLUSION: This study reveals that the majority of the polymorphisms are rare variants and confirms a low level of genetic polymorphisms in all proteins within the Rh5 complex. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-021-03815-x.
The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations
Virtual fracture clinics (VFC) are advocated by new orthopaedic (British Orthopaedic Association) and National Health Service (NHS) guidelines in the United Kingdom. We discuss benefits and limitations, reviewing the literature, as well as recommendations on introducing a VFC service during the coronavirus pandemic and into the future. A narrative review identifying current literature on virtual fracture clinic outcomes when compared to traditional model fracture clinics in the UK. We identify nine relevant publications related to VFC. The Glasgow model, initiated in 2011, has become the benchmark. Clinical efficiency can be improved, reducing the number of emergency department (ED) referrals seen in VFC by 15-28% and face-to-face consultations by 65%. After review in the VFC, 33-60% of patients may be discharged. Some studies have shown no negative impact on the ED; the time to discharge was not increased. Patient satisfaction ranges from 91-97% using a VFC service, and there may be cost-saving benefits annually of 67,385 to 212,705. Non-attendance may be reduced by 75% and there are educational opportunities for trainees. However, evidence is limited; 28% of patients prefer face-to-face consultations and not all have access to internet or email (72%). We propose a pathway integrating the VFC model, whilst having senior orthopaedic decision makers available in the ED, during normal working hours, to cope with the pandemic. Beyond the pandemic, evidence suggests the Glasgow model is viable for day-to-day practice.
An analysis of virtual fracture clinics in orthopaedic trauma in the UK during the coronavirus crisis
Countries must be prepared to respond to public health threats associated with emergencies, such as natural disasters, sociopolitical conflicts, or uncontrolled disease outbreaks. Rapid vaccination of populations vulnerable to epidemic-prone vaccine-preventable diseases is a major component of emergency response. Emergency vaccination planning presents challenges, including how to predict resource needs, expand vaccine availability during global shortages, and address regulatory barriers to deliver new products. The US Centers for Disease Control and Prevention supports countries to plan, implement, and evaluate emergency vaccination response. We describe work of the Centers for Disease Control and Prevention in collaboration with global partners to support emergency vaccination against cholera, typhoid, yellow fever, and Ebola, diseases for which a new vaccine or vaccine formulation has played a major role in response. Lessons learned will help countries prepare for future emergencies. Integration of vaccination with emergency response augments global health security through reducing disease burden, saving lives, and preventing spread across international borders.
Lessons Learned from Emergency Response Vaccination Efforts for Cholera, Typhoid, Yellow Fever, and Ebola
Different dosage regimens of hydroxychloroquine were used to manage COVID-19 patients, with no information on the lungs' exposure in this population. The aim of our study was to evaluate hydroxychloroquine concentrations in the lung epithelial lining fluid (ELF) in patients infected with COVID-19. This study is a retrospective, observational, multicenter, pharmacokinetics study of hydroxychloroquine in critically ill patients. No additional interventions or additional samples compared to standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed hydroxychloroquine tablets, regardless of the dosage administered by the nasogastric tube. Blood and bronchoalveolar lavage (BAL) samples (n= 28) were collected from 22 COVID-19 patients and the total hydroxychloroquine concentrations in epithelial lining fluid were estimated. Median hydroxychloroquine plasma concentrations were of 0.09 [0.06; 0.14] mg/l and 0.07 [0.05; 0.08] mg/l for 400 mg x 1/day and 200 mg x 3/day, respectively. Median hydroxychloroquine ELF concentrations were of 3.74 [1.10; 7.26] mg/l and 1.81 [1.20; 7.25] for 400 mg x 1/day and 200 mg x 3/day, respectively. The median ratio of ELF/plasma concentrations was of 40.0 [7.3; 162.7] and 21.2 [18.4; 109.5] for 400 mg x 1/day and 200 mg x 3/day, respectively. Exposure in the ELF is likely to be underestimated due to the concentrations of plasma hydroxychloroquine. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because the lung exposure may already be high.
Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19
Estimating the unreported cases of Covid-19 in a region/country is a complicated problem. We propose a new mathematical model that, combined with a deterministic model of the total growth of cases, describes the time evolution of the unreported cases for each reported Covid-19 case. The new model considers the growth of unreported cases in plateau periods and the decrease towards the end of an epidemic wave. We combined the new model with a Gompertz-growth model, a generalized logistic model, and a susceptible-infectious-removed (SIR) model; and fitted them via Bayesian methods to data from Cuba and Spain. The combined-model fits yielded better Bayesian-Information-Criterion values than the Gompertz, logistic, and SIR models alone. This suggests the new model can achieve improved descriptions of the evolution of a Covid-19 epidemic wave.
A new model of unreported COVID-19 cases outperforms three known epidemic-growth models in describing data from Cuba and Spain

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